Fiskerfarrell0183
Inquiry-based components of ecology curricula can be valuable, exposing students to what it means to do science, from conceiving of a meaningful question to effectively disseminating results to an audience. Here, we describe two approaches for implementing independent, remote research for undergraduates enacted in the spring semester of 2020 at Reed College in Portland, OR, reporting case studies from an intermediate-level ecology course and an interdisciplinary environmental science course. We report on both the challenges as well as the novel opportunities for independent research projects in such a setting, the details of how projects were implemented, the tools and resources that may help facilitate such endeavors, as well as perceptions on the effectiveness of this endeavor by students. As institutes of higher education continue to operate in an online learning environment, we hope these materials help spark a discussion about how to engage in meaningful research experiences as part of coursework in the COVID-19 era and beyond.Simulation models are increasingly used by ecologists to study complex, ecosystem-scale phenomena, but integrating ecosystem simulation modeling into ecology undergraduate and graduate curricula remains rare. Engaging ecology students with ecosystem simulation models may enable students to conduct hypothesis-driven scientific inquiry while also promoting their use of systems thinking, but it remains unknown how using hands-on modeling activities in the classroom affects student learning. Here, we developed short (3-hr) teaching modules as part of the Macrosystems EDDIE (Environmental Data-Driven Inquiry & Exploration) program that engage students with hands-on ecosystem modeling in the R statistical environment. We embedded the modules into in-person ecology courses at 17 colleges and universities and assessed student perceptions of their proficiency and confidence before and after working with models. Across all 277 undergraduate and graduate students who participated in our study, completing one Macrosystems EDDIE teaching module significantly increased students' self-reported proficiency, confidence, and likely future use of simulation models, as well as their perceived knowledge of ecosystem simulation models. Further, students were significantly more likely to describe that an important benefit of ecosystem models was their "ease of use" after completing a module. Interestingly, students were significantly more likely to provide evidence of systems thinking in their assessment responses about the benefits of ecosystem models after completing a module, suggesting that these hands-on ecosystem modeling activities may increase students' awareness of how individual components interact to affect system-level dynamics. Overall, Macrosystems EDDIE modules help students gain confidence in their ability to use ecosystem models and provide a useful method for ecology educators to introduce undergraduate and graduate students to ecosystem simulation modeling using in-person, hybrid, or virtual modes of instruction.Restrictions on public gatherings in early 2020 due to the COVID-19 pandemic resulted in cancelation of in-person outreach programs offered by the Florida Master Naturalist Program and Natural Areas Training Academy, two successful University of Florida extension programs that provide natural history and resource management training to lay and professional audiences. In response, both programs rapidly transitioned to blended or 100% online educational methods to continue offering courses and maintain program operations. To assess participant responses to these changes, we used surveys and course registry data to evaluate and compare course enrollment, satisfaction, and outcomes among courses with new online formats to courses offered prior to the COVID-19 pandemic. We also examined logistical challenges and key programmatic elements that facilitated the transition of both programs to increased reliance on online education. Course participants responded favorably to classes offered online. Our results revealed an audience exists for online programming, that satisfaction with online courses was high and comparable to that measured for in-person courses, and that online approaches effectively transferred knowledge and promoted behavior change in participants. The transition to online programming required investments of time, energy, and in some cases, direct costs. However, this transition was greatly facilitated by the existence of well-defined program protocols, educational curricula, strong partnerships, and feedback mechanisms for both programs. Long-term investments in program structure, partnerships, and support systems enabled both programs to be resilient and adaptable and successfully implement online programming in response to the COVID-19 pandemic.There are many barriers to fieldwork including cost, time, and physical ability. Unfortunately, these barriers disproportionately affect minority communities and create a disparity in access to fieldwork in the natural sciences. Travel restrictions, concerns about our carbon footprint, and the global lockdown have extended this barrier to fieldwork across the community and led to increased anxiety about gaps in productivity, especially among graduate students and early-career researchers. In this paper, we discuss agent-based modeling as an open-source, accessible, and inclusive resource to substitute for lost fieldwork during COVID-19 and for future scenarios of travel restrictions such as climate change and economic downturn. We describe the benefits of Agent-Based models as a teaching and training resource for students across education levels. We discuss how and why educators and research scientists can implement them with examples from the literature on how agent-based models can be applied broadly across life science research. We aim to amplify awareness and adoption of this technique to broaden the diversity and size of the agent-based modeling community in ecology and evolutionary research. Finally, we discuss the challenges facing agent-based modeling and discuss how quantitative ecology can work in tandem with traditional field ecology to improve both methods.The current COVID-19 pandemic has forced the global higher education community to rapidly adapt to partially or fully online course offerings. For field- or laboratory-based courses in ecological curricula, this presents unique challenges. Fortunately, a diverse set of active learning techniques exists, and these techniques translate well to online settings. However, limited guidance and resources exist for developing, implementing, and evaluating active learning assignments that fulfill specific objectives of ecology-focused courses. To address these informational gaps, we (a) identify broad learning objectives across a variety of ecology-focused courses, (b) provide examples, based on our collective online teaching experience, of active learning activities that are relevant to the identified ecological learning objectives, and (c) provide guidelines for successful implementation of active learning assignments in online courses. Using The Wildlife Society's list of online higher education ecology-focused courses as a guide, we obtained syllabi from 45 ecology-focused courses, comprising a total of 321 course-specific learning objectives. We classified all course-specific learning objectives into at least one of five categories (a) Identification, (b) Application of Concepts/Hypotheses/Theories, (c) Management of Natural Resources, (d) Development of Professional Skills, or (e) Evaluation of Concepts/Practices. We then provided two examples of active learning activities for each of the five categories, along with guidance on their implementation in online settings. We suggest that, when based on sound pedagogy, active learning techniques can enhance the online student's experience by activating ecological knowledge.Quantitative skills are becoming central to the undergraduate and graduate curriculum in ecology and evolutionary biology. While previous studies acknowledge that students perceive their quantitative training to be inadequate, there is little guidance on best practices. Moreover, with the recent COVID-19 sudden transition to online learning, there is even less guidance on how to effectively teach quantitative ecology online. Here, I synthesize a prescription of pedagogical best practices for teaching quantitative ecology online based on a broad review of the literature on multiple quantitative disciplines. These best practices include the following (1) design and implement the class to meet learning goals using online strategies specifically; (2) create an open, inclusive, and welcoming online environment that promotes a sense of learning community; (3) acknowledge the diversity of talents and learning strategies; (4) use real-world examples and assessments; (5) account for gaps in knowledge; (6) emphasize the modeling cycle process; (7) focus on developing ideas rather than tools or procedures; (8) if needed, introduce computational tools thoroughly before combining them with mathematical or statistical concepts; (9) evaluate the course constantly; and (10) put your heart and soul into the class. I hope these practices help fellow instructors of quantitative ecology facing similar challenges in providing our students with the knowledge and skills needed to meet the challenges of the future.Scientific disciplines face large diversity challenges, with the fields of ecology and evolution being among the most homogeneous-specifically with respect to race and ethnicity. These problems have been recently compounded by large-scale racial unrest, highlighting some of the underlying disparities that have led to these diversity challenges, and a global pandemic, which, by moving instruction online, has created new challenges for inclusive teaching. Among the inclusive-teaching techniques that can be implemented during remote instruction are Scientist Spotlights-role-model interventions that use available online materials to highlight the work of scientists representing multiple axes of diversity. We report here on the implementation of Scientist Spotlights in two courses, both of which emphasize ecology and evolution. We conclude with sample resources and suggestions for adopters.Conferences provide an invaluable set of opportunities for professional development. Online, virtual, and distributed conferences do not necessarily mean less opportunity for growth and innovation in science but varied and novel options for communicating the scientific process. Open science and many existing tools are in place in the practice of contemporary ecology and evolution to provide latitude for a much broader scope of sharing and thus learning from conferences. A brief overview of the science supporting online conferences and a highlight of some of the open science concepts in ecology and evolution are provided here to enable better learning through better planning for online conferences.The COVID-19 pandemic has forced the transition of many traditional face-to-face classes into an online format with little time to prepare best practice guidelines. In this article, we share a case study of how we adapted a group field activity into an individual laboratory assignment that can be completed during shelter-in-place restrictions. We conclude with ideas for future applications while staying mindful of the ways in which this pandemic has highlighted the inequities of the classroom, especially at community colleges.The coronavirus disease (COVID-19) outbreak forced an emergency transition to online classes across the world with little warning or instruction for faculty and students. The goal of this research was to document how this response impacted undergraduate students studying the principles of evolution in an introductory organismal biology class over time; specifically, how their study habits for exams differed (a) one week and (b) one month after a university's decision to transition to emergency remote instruction. We asked students about the extent to which COVID-19 impacted their study habits, and we categorized students' responses using open coding. We identified a number of consistent similarities-as well as dramatic differences-in their responses as the time away from campus increased. The report that follows is a summary of the documented barriers and recommendations based on literature concerning crises and equitable practices.COVID-19 presented the world with trauma and isolation, but many people, including educators, have offered bright spots of creativity and engagement. As we confronted these issues in our own ecology classroom, we sought solutions to carry-forward the learning objectives we set for our students in January 2020, yet encourage interaction with the sensitivity that a pandemic requires. In the rapid transition to online course delivery, we opted to retain the original end-of-semester poster project in our introductory ecology course. However, we experimented with a new virtual platform where students could disseminate their work and communicate with the community. In this paper, we discuss the Mozilla Hubs virtual reality platform that we used for our event. We also collected qualitative data to share the benefits and challenges of this experience felt by the students, the instructors, and external observers.The coronavirus disease 2019 (COVID-19) pandemic introduced an abrupt change in human behavior globally. Here, we discuss unique insights the pandemic has provided into the eco-evolutionary role of pathogens in ecosystems and present data that indicates the pandemic may have fundamentally changed our learning choices. COVID-19 has indirectly affected many organisms and processes by changing the behavior of humans to avoid being infected. The pandemic also changed our learning behavior by affecting the relative importance of information and forcing teaching and learning into a framework that accommodates human behavioral measures to avoid disease transmission. Not only are these indirect effects on the environment occurring through a unique mechanistic pathway in ecology, the pandemic along with its effects on us provides a profound example of the role risk can play in the transmission of information between the at risk. Ultimately, these changes in our learning behavior led to this special issue "Taking learning online in Ecology and Evolution." The special issue was a call to the community to take learning in new directions, including online and distributed experiences. The topics examined include a significant component of DIY ecology and evolution that is experiential but done individually, opportunities to use online tools and apps to be more inclusive, student-focused strategies for teaching online, how to reinvent conferences, strategies to retain experiential learning safely, emerging forms of teaching such as citizen science, apps and podcasting, and ideas on how to accommodate ever changing constraints in the college classroom, to name a few. The collective consensus in our fields is that these times are challenging but we can continue to improve and innovate on existing developments, and more broadly and importantly, this situation may provide an opportunity to reset some of the existing practices that fail to promote an effective and inclusive learning environment.Aqueous-phase reactions within microporous Brønsted acids occur at active centers comprised of water-reactant-clustered hydronium ions, solvated within extended hydrogen-bonded water networks that tend to stabilize reactive intermediates and transition states differently. The effects of these diverse clustered and networked structures were disentangled here by measuring turnover rates of gas-phase ethanol dehydration to diethyl ether (DEE) on H-form zeolites as water pressure was increased to the point of intrapore condensation, causing protons to become solvated in larger clusters that subsequently become solvated by extended hydrogen-bonded water networks, according to in situ IR spectra. Measured first-order rate constants in ethanol quantify the stability of SN2 transition states that eliminate DEE relative to (C2H5OH)(H+)(H2O) n clusters of increasing molecularity, whose structures were respectively determined using metadynamics and ab initio molecular dynamics simulations. At low water pressures (2-10 ks and transition states disrupt their confined water networks, which manifest as different kinetic orders of inhibition at high water pressures. The confinement of water within sub-nanometer spaces influences the structures and dynamics of the complexes and extended networks formed, and in turn their ability to accommodate the evolution in polarity and hydrogen-bonding capacity as reactive intermediates become transition states in Brønsted acid-catalyzed reactions.Sensitive tumor imaging and precise tumor therapy play critical roles in the cancer combat. Herein, we build a DNA machine based on a primer exchange reaction (PER) for mRNA imaging and gene therapy. By using zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) to co-deliver the components including a primer, hairpin and strand displacing polymerase to the living cells, the PER-based DNA machine can be initiated by intracellular survivin mRNA and continuously produce Bcl-2 antisense DNA (ASD), which enables the DNA machine not only to image survivin mRNA but also to implement gene therapy. The results demonstrate that ZIF-8 NPs can protect the polymerases and nucleic acid probes from protease attack and nuclease degradation. After internalization, pH-responsive ZIF-8 NPs can efficiently release cargos from endo-lysosomes due to the protonation effect. The intracellular PER-based DNA machine has been demonstrated to be able to sensitively image survivin mRNA expression levels and selectively kill the cancer cells and has no effect on the normal cells. The PER-based DNA machine may provide a promising platform for early stage tumor diagnosis and more precise tumor therapy.Pnictogen-bond donors are attractive for use in catalysis because of deep σ holes, high multivalency, rich hypervalency, and chiral binding pockets. We here report natural product inspired epoxide-opening polyether cyclizations catalyzed by fluoroarylated Sb(v) > Sb(iii) > Bi > Sn > Ge. The distinctive characteristic found for pnictogen-bonding catalysis is the breaking of the Baldwin rules, that is selective endo cyclization into the trans-fused ladder oligomers known from the brevetoxins. Moreover, tris(3,4,5-trifluorophenyl)stibines and their hypervalent stiborane catecholates afford different anti-Baldwin stereoselectivity. Lewis (SbCl3), Brønsted (AcOH) and π acids fail to provide similar access to these forbidden rings. Like hydrogen-bonding catalysis differs from Brønsted acid catalysis, pnictogen-bonding catalysis thus emerges as the supramolecular counterpart of covalent Lewis acid catalysis.Growing experimental evidence indicates that iron-sulfur proteins play key roles in DNA repair and replication. In particular, charge transport between [Fe4S4] clusters, mediated by proteins and DNA, may convey signals to coordinate enzyme action. Human primase is a well studied [Fe4S4] protein, and its p58c domain (which contains an [Fe4S4] cluster) plays a role in the initiation of DNA replication. The Y345C mutation in p58c is linked to gastric tumors and may influence the protein-mediated charge transport. The complexity of protein-DNA systems, and the intricate electronic structure of [Fe4S4] clusters, have impeded progress into understanding functional charge transport in these systems. In this study, we built force fields to describe the high potential [Fe4S4] cluster in both oxidation states. The parameterization is compatible with AMBER force fields and enabled well-balanced molecular dynamics simulations of the p58c-RNA/DNA complex relevant to the initiation of DNA replication. Using the molecular mechanics Poisson-Boltzmann and surface area solvation method on the molecular dynamics trajectories, we find that the p58c mutation induces a modest change in the p58c-duplex binding free energy in agreement with recent experiments. Through kinetic modeling and analysis, we identify key features of the main charge transport pathways in p58c. In particular, we find that the Y345C mutation partially changes the composition and frequency of the most efficient (and potentially relevant to the biological function) charge transport pathways between the [Fe4S4] cluster and the duplex. Moreover, our approach sets the stage for a deeper understanding of functional charge transfer in [Fe4S4] protein-DNA complexes.Cationic iron complexes [Cp*(iPr2MeP)FeH2SiHR]+, generated and characterized in solution, are very efficient catalysts for the hydrosilation of terminal alkenes and internal alkynes by primary silanes at low catalyst loading (0.1 mol%) and ambient temperature. These reactions yield only the corresponding secondary silane product, even with SiH4 as the substrate. Mechanistic experiments and DFT calculations indicate that the high rate of hydrosilation is associated with an inherently low barrier for dissociative silane exchange (product release).The effect of chelate cooperativity on the binding of several ditopic anions to two tetrathiourea macrocycles has been analysed in competitive solvent mixtures (H2O DMSO 1 9 v/v). The semi-flexible receptors bind dicarboxylates with high affinity dependent on the length and flexibility of the guest. Chemical double mutant cycle (DMC) analysis allowed the chelate cooperativity effects to be measured in detail and revealed both positive and negative cooperativity effects which were dependent on guest size, flexibility and spacer interactions between guest and macrocycle. 1H NMR and crystallographic studies confirmed the macrocycle hosts are adaptable, changing conformation to match their pore size to a selected guest.Protein-protein interactions play an essential role in many biological processes, and their perturbation is a major cause of disease. The use of small molecules to modulate them is attracting increased attention, but protein interfaces generally do not have clear cavities for binding small compounds. A proposed strategy is to target interface hot-spot residues, but their identification through computational approaches usually require the complex structure, which is not often available. In this context, pyDock energy-based docking and scoring can predict hot-spots on the unbound proteins, thus not requiring the complex structure. Here, we have devised a new strategy to detect protein-protein inhibitor binding sites, based on the integration of molecular dynamics for the generation of transient cavities, and docking-based interface hot-spot prediction for the selection of the suitable cavities. This integrative approach has been validated on a test set formed by protein-protein complexes with known inhibitors for which complete structural data of unbound molecules and complexes is available. The results show that local conformational sampling with short molecular dynamics can generate transient cavities similar to the known inhibitor binding sites, and that docking simulations can identify the best cavities with similar predictive accuracy as when knowing the real interface. In a few cases, these predicted pockets are shown to be suitable for protein-ligand docking. The proposed strategy will be useful for many protein-protein complexes for which there is no available structure, as long as the the unbound proteins do not deviate dramatically from the bound conformations.The current coronavirus disease (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) has emerged as a threat to global social and economic systems. Disparity in the infection of SARS-CoV2 among host population and species is an established fact without any clear explanation. To initiate infection, viral S-protein binds to the Angiotensin-Converting Enzyme 2 (ACE2) receptor of the host cell. Our analysis of retrieved amino acid sequences deposited in data bases shows that S-proteins and ACE2 are rich in cysteine (Cys) residues, many of which are conserved in various SARS-related coronaviruses and participate in intra-molecular disulfide bonds. High-resolution protein structures of S-proteins and ACE2 receptors highlighted the probability that two of these disulfide bonds are potentially redox-active, facilitating the primal interaction between the receptor and the spike protein. Presence of redox-active disulfides in the interacting parts of S-protein, ACE2, and a ferredoxin-like fold domain in ACE2, strongly indicate the role of redox in COVID-19 pathogenesis and severity. Resistant animals lack a redox-active disulfide (Cys133-Cys141) in ACE2 sequences, further strengthening the redox hypothesis for infectivity. ACE2 is a known regulator of oxidative stress. Augmentation of cellular oxidation with aging and illness is the most likely explanation of increased vulnerability of the elderly and persons with underlying health conditions to COVID-19.Immunotherapy techniques, such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T cell therapies and cancer vaccines, have been burgeoning with great success, particularly for specific cancer types. However, side effects with fatal risks, dysfunction in tumor microenvironment and low immune response rates remain the bottlenecks in immunotherapy. Nano metal-organic frameworks (nMOFs), with an accurate structure and a narrow size distribution, are emerging as a solution to these problems. In addition to their function of temporospatial delivery, a large library of their compositions, together with flexibility in chemical interaction and inherent immune efficacy, offers opportunities for various designs of nMOFs for immunotherapy. In this review, we overview state-of-the-art research on nMOFs-based immunotherapies as well as their combination with other therapies. We demonstrate that nMOFs are predominantly customized for vaccine delivery or tumor-microenvironment modulation. Finally, a prospect of nMOFs in cancer immunotherapy will be discussed.The 2019 Coronavirus disease (COVID-19) has affected more than 200 countries. Wearing masks can effectively cut off the virus spreading route since the coronavirus is mainly spreading by respiratory droplets. However, the common surgical masks cannot be reused, resulting in the increasing economic and resource consumption around the world. Herein, we report a superhydrophobic, photo-sterilize, and reusable mask based on graphene nanosheet-embedded carbon (GNEC) film, with high-density edges of standing structured graphene nanosheets. The GNEC mask exhibits an excellent hydrophobic ability (water contact angle 157.9°) and an outstanding filtration efficiency with 100% bacterial filtration efficiency (BFE). In addition, the GNEC mask shows the prominent photo-sterilize performance, heating up to 110 °C quickly under the solar illumination. These high performances may facilitate the combat against the COVID-19 outbreaks, while the reusable masks help reducing the economic and resource consumption.
Supplementary material is available for this article at 10.1007/s12274-020-3158-1 and is accessible for authorized users.
Supplementary material is available for this article at 10.1007/s12274-020-3158-1 and is accessible for authorized users.In this work, a novel and simple bone morphogenetic protein (BMP)-2 carrier is developed, which enables localized and controlled release of BMP-2 and facilitates bone regeneration. BMP-2 is localized in the gelatin methacrylate (GelMA) micropatterns on hydrophilic semi-permeable membrane (SNM), and its controlled release is regulated by the concentration of GelMA hydrogel and BMP-2. The controlled release of BMP-2 is verified using computational analysis and quantified using fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) diffusion model. The osteogenic differentiation of osteosarcoma MG-63 cells is manipulated by localized and controlled BMP-2 release. The calcium deposits are significantly higher and the actin skeletal networks are denser in MG-63 cells cultured in the BMP-2-immobilized GelMA micropattern than in the absence of BMP-2. The proposed BMP-2 carrier is expected to not only act as a barrier membrane that can prevent invasion of connective tissue during bone regeneration, but also as a carrier capable of localizing and controlling the release of BMP-2 due to GelMA micropatterning on SNM. This approach can be extensively applied to tissue engineering, including the localization and encapsulation of cells or drugs.
Cutaneous metastases originating from pancreatic cancer are relatively rare. The most common reported site of metastasis is the umbilicus, and this manifestation is known as the Sister Mary Joseph's nodule. Non-umbilical cutaneous metastases are far less common, with only a few cases reported in the literature. Our case is the first case report, to our knowledge, on metastasis involving the labia majora and flat papules.
A 49-year-old Chinese female patient presented with a number of red, swollen papules on the vulva for 2 mo. Histological examination of the labia majora lesion revealed metastatic adenocarcinoma. The serum levels of tumor biomarkers CA199, CA242, and CA125 were significantly elevated. B-mode ultrasound-guided needle biopsy of the pancreas demonstrated moderately and poorly differentiated adenocarcinoma. The patient finally declined treatment for financial reasons and died 3 mo later.
Metastatic cutaneous lesions could indicate pancreatic cancer. Serum levels of tumor biomarkers may aid in diagnosing metastatic pancreatic adenocarcinoma.
Metastatic cutaneous lesions could indicate pancreatic cancer. Serum levels of tumor biomarkers may aid in diagnosing metastatic pancreatic adenocarcinoma.
Fistula formation is a severe adverse event related to antiangiogenetic agents such as bevacizumab and inferior mesenteric arteriovenous fistula (IMAVF) is a result of acquired factor, especially colon surgery. However, IMAVF occurs very rarely and there are few reports in patients during chemotherapy. We report a case of a patient who developed IMAVF during treatment with bevacizumab in metastatic colorectal cancer (mCRC) after colon surgery.
An 81-year-old man was diagnosed with descending colon cancer and underwent left hemicolectomy without any complications. He was definitely diagnosed with high-risk stage 2 and received tegafur-uracil plus leucovorin as adjuvant chemotherapy. Three years and 6 mo after the operation, the cancer relapsed with peritoneal dissemination. The patient underwent CyberKnife radiosurgery targeting the recurrent tumor and received chemotherapy with S-1 plus bevacizumab. At 1 year after chemotherapy, he complained of severe diarrhea, which is suspected drug-induced colitis. As diarrhea worsened despite the termination of treatment, he underwent colonoscopy and computed tomography (CT) scans that revealed edematous change from sigmoid to rectosigmoid colon. CT scans also revealed an aneurysm adjacent to the inferior mesenteric vein and multidetector CT angiography showed the IMAVF. Elective angiography confirmed the diagnosis of an IMAVF and it was successfully treated by arterial embolization. The patient resumed chemotherapy with only S-1 6 mo after embolization.
Clinicians should keep in mind the probability of severe diarrhea arose from IMAVF in mCRC patients treated with bevacizumab.
Clinicians should keep in mind the probability of severe diarrhea arose from IMAVF in mCRC patients treated with bevacizumab.
Faced with limited and inadequate treatment options for patients with advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC), researchers have turned toward, with the support of promising clinical trials, anti-PD-1/anti-PD-L1 antibody therapy. But there are also different clinical trial results. To better assess its efficacy and safety, we integrated data from 13 eligible studies for a systematic review and meta-analysis.
To comprehensively evaluate the efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in the treatment of advanced GC/GEJC patients.
PubMed, Web of Science, Cochrane Library ,and EMBASE databases were searched to identify eligible articles with outcomes including objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of anti-PD-1/anti-PD-L1 antibody therapy.
Our study encompassed a total of 13 trials totaling 1618 patients. The outcomes showed a pooled ORR and DCR of 15% (95% coverexpressing patients exhibiting a higher ORR. What is more, the clinical efficacy of anti-PD-1/PD-L1 combined with traditional chemotherapy drugs is even better, although the occurrence of AEs still causes considerate concerns.
Colonoscopy is the accepted gold standard for the detection of colorectal cancer. However, colonoscopy is less effective in preventing colon cancer in the right side compared with the left side.
To investigate the feasibility of a novel type of retroflexion colonoscope, EC-3490Ti colonoscope, for detection of proximal colon lesions.
In this prospective trial, we recruited patients who underwent colonoscopy for screening or surveillance. When the endoscopists could not grasp the whole observation of the right-side colon mucosa in the forward view (FV), insertion and withdrawal were repeatedly performed in the FV group with the EC38-i10F colonoscope while retroflexion was performed in the retroflexed view (RV) group with the EC-3490Ti colonoscope. Adenoma detection rate, the total number of adenomas per positive participant, the success rate of retroflexion, and endoscope withdrawal time were recorded and compared.
The total adenoma detection rate (39.3%
37.7%,
= 0.646) did not show any significant difference between the two groups. However, the polyp detection rate (59.6%
51.0%,
= 0.002), adenoma detection rate in the right colon (21.6%
14.4%,
= 0.012), and the total number of adenomas per positive participant (2.1
1.7,
= 0.011) reached statistical significance. Retroflexion was achieved in 91.7% of our cohort. Compared with the FV group, the withdrawal time was significantly prolonged in the RV group (586.1 ± 124.4 s
508.8 ± 129.6 s,
< 0.001). In contrast, the proportion of additional ancillary pressure decreased (27.4%
45.7%,
< 0.001), and the visual analog scale pain scores did not increase (2.7 ± 1.4
2.8 ± 1.4,
= 0.377).
Retroflexion in the proximal colon could be performed successfully and safely with the EC-3490Ti colonoscope. This maneuver could detect more adenomas effectively.
Retroflexion in the proximal colon could be performed successfully and safely with the EC-3490Ti colonoscope. This maneuver could detect more adenomas effectively.
Although Borrmann type IV (B-4) gastric cancer has a higher mortality rate and presents distant metastasis easily, especially peritoneal metastasis, when diagnosed, some B-4 patients were found to have no distant metastasis by preoperative detection and underwent curative surgery, which was defined as circumscribed B-4 in our study. In this study, we focused on the circumscribed B-4 patients without distant metastasis during surgery to identify factors related to prognosis and postoperative peritoneal cavity metastasis (PPCM), which is important for selecting an appropriate therapeutic strategy.
To identify factors related to the prognosis and PPCM of B-4 patients.
A total of 117 B-4 patients who underwent gastrectomy between January 2005 and December 2012 were included in this study. Survival analysis was performed using Kaplan-Meier analysis and Cox multivariate models. Pearson correlation analyses were performed to identify the factors related to PPCM. All statistical analyses were performed using SP independent prognostic factor for circumscribed B-4 patients. In addition, subtotal gastrectomy and postoperative chemotherapy could effectively improve prognosis and even suppress PPCM.
Colorectal cancer (CRC) is an important disease worldwide, accounting for the second highest number of cancer-related deaths and the third highest number of new cancer cases. The blood test is a simple and minimally invasive diagnostic test. However, there is currently no blood test that can accurately diagnose CRC.
To develop a comprehensive, spontaneous, minimally invasive, label-free, blood-based CRC screening technique based on Raman spectroscopy.
We used Raman spectra recorded using 184 serum samples obtained from patients undergoing colonoscopies. Patients with malignant tumor histories as well as those with cancers in organs other than the large intestine were excluded. Consequently, the specific diseases of 184 patients were CRC (12), rectal neuroendocrine tumor (2), colorectal adenoma (68), colorectal hyperplastic polyp (18), and others (84). We used the 1064-nm wavelength laser for excitation. The power of the laser was set to 200 mW.
Use of the recorded Raman spectra as training data allowed the construction of a boosted tree CRC prediction model based on machine learning. Therefore, the generalized
values for CRC, adenomas, hyperplastic polyps, and neuroendocrine tumors were 0.9982, 0.9630, 0.9962, and 0.9986, respectively.
For machine learning using Raman spectral data, a highly accurate CRC prediction model with a high
value was constructed. We are currently planning studies to demonstrate the accuracy of this model with a large amount of additional data.
For machine learning using Raman spectral data, a highly accurate CRC prediction model with a high R2 value was constructed. We are currently planning studies to demonstrate the accuracy of this model with a large amount of additional data.
Patients with right sided colorectal cancer are known to have a poorer prognosis than patients with left sided colorectal cancer, whatever the cancer stage. To this day, primary tumor resection (PTR) is still controversial in a metastatic, non resectable setting.
To explore the survival impact of PTR in patients with metastatic colorectal cancer (mCRC) depending on PTL.
We retrospectively collected data from all consecutive patients treated for mCRC at the Centre Georges Francois Leclerc Hospital. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of PTR on survival. We then evaluated the association between PTL and overall survival among patients who previously underwent or did not undergo PTR. A propensity score was performed to match cohorts.
Four hundred and sixty-six patients were included. A total of 153 (32.8%) patients had unresected synchronous mCRC and 313 (67.2%) patients had resected synchronous mCRC. The number of patients with right colic cancer, left colic cancer and rectal cancer was respectively 174 (37.3%), 203 (43.6%) and 89 (19.1%). In the multivariate analysis only PTL, PTR, resection of hepatic and or pulmonary metastases and the use of oxaliplatin, EGFR inhibitors or bevacizumab throughout treatment were associated to higher overall survival rates. Survival evaluation depending on PTR and PTL found that PTR improved the prognosis of both left and right sided mCRC. Results were confirmed by using a weighted propensity score.
In mCRC, PTR seems to confer a higher survival rate to patients whatever the PTL.
In mCRC, PTR seems to confer a higher survival rate to patients whatever the PTL.
Microangiopathic hemolytic anemia (MAHA) with thrombocytopenia and organ failure caused by tumor-associated thrombotic microangiopathy (TMA) is a life-threatening oncological emergency. Rapid diagnosis and precise distinction from other forms of TMA is crucial for appropriate therapy, which aims at treating the underlying malignancy. However, the prognosis of patients with cancer-related (CR)-MAHA is limited. To date, less than 50 patients with gastric cancer and CR-MAHA have been reported, mainly as single case reports, and detailed information on treatment strategies and outcome are scarce. We analyzed the characteristics and outcomes data of CR-MAHA patients with gastric cancer treated at our center between 2012 and 2019.
To gain knowledge about CR-MAHA and the course of disease.
We retrospectively analyzed patients using an institutional prospectively maintained database. Patients who had CR-MAHA but other cancer types or cancer of unknown primary were excluded. The basic requirements for inclusion rovement of clinical symptoms and blood values. Progression-free survival (PFS) of the whole cohort was 1.9 wk and median overall survival (OS) was 1.9 wk. For patients with chemotherapy, PFS was 9.0 wk and OS was 10.3 wk. The patient with the MSI-H tumor has been undergoing immunotherapy for more than 3 years.
The benefit of chemotherapy in CR-MAHA patients is limited. Immunotherapy for patients with MSI-H tumors may lead to long-term tumor control even in CR-MAHA patients.
The benefit of chemotherapy in CR-MAHA patients is limited. Immunotherapy for patients with MSI-H tumors may lead to long-term tumor control even in CR-MAHA patients.
Recent studies have proved the important role of many oncogenic long non-coding RNAs (lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancreatic cancer.
To evaluate the function of tumor suppressor lncRNA C9orf139 in pancreatic cancer progression and to study the underlying mechanism.
We assigned 54 patients with pancreatic ductal adenocarcinoma treated at our hospital to the patient group and 30 normal subjects undergoing physical examination to the control group. RT-qPCR was used to measure the relative expression of C9orf139 in the tissue and serum of patients, in an attempt to investigate the prognostic value of C9orf139 in pancreatic cancer patients. The luciferase reporter gene assay was performed to determine the interaction between C9orf139 and miR-663a. The biological function of C9orf139 was assessed by
assays and
subcutaneous tumor formation tests in animal models. To figure out the molecular mechanism of C9orf139 to acttial diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663a/Sox12 axis.
The exact regulation network of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thus deciphering their possible biological processes in hepatocellular carcinoma (HCC).
To find the possible mechanism of function of PD-1, PD-L1, and PD-L2 in HCC.
Based on the expression data of HCC from The Cancer Genome Atlas, the PD-1/PD-L1/PD-L2 related genes were screened by weighted correlation network analysis method and the biological processes of certain genes were enriched. Relation of PD1/PD-L1/PD-L2 with immune infiltration and checkpoints was investigated by co-expression analysis. The roles of PD-1/PD-L1/PD-L2 in determination of clinical outcome were also analyzed.
Mutations of calcium voltage-gated channel subunit alpha1 E, catenin beta 1, ryanodine receptor 2, tumor suppressor protein p53, and Titin altns of key genes influence PD-1, PD-L1, and PD-L2 expression. PD-1, PD-L1, and PD-L2 related genes participate in T cell activation, cell adhesion, and other important lymphocyte effects. The finding that PD-1/PD-L1/PD-L2 is related to immune infiltration and other immune checkpoints would expand our understanding of promising anti-PD-1 immunotherapy.
Long non-coding RNAs (lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer (GC) has not been fully elucidated.
To explore the expression level and molecular mechanism of
in GC tissues and cells, and analyze its significance in the prognosis of GC.
Real-time quantitative PCR was used to detect the expression of
in 79 pairs of GC tissues and five cell lines. The pc
plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of
on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of
on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between
and
and PI3K/Akt signaling pathway was verified by Western blot analysis.
The low expression of lncRNA
was associated with lymph node metastasis and tumor-node-metastasis stage in GC.
functional experiments demonstrated that overexpression of
inhibited GC cell progression. Mechanistic studies revealed that
regulated the expression of its nearby gene
and inhibited the activity of the PI3K/Akt signaling pathway.
These results indicate that downregulation of
significantly promotes the progression of GC cells by regulating
expression and activating the PI3K/Akt signaling pathway.
may be a novel diagnostic biomarker and effective therapeutic target for GC.
These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.
Programmed death ligand 1 (PD-L1) immunotherapy remains poorly efficacious in colorectal cancer (CRC). The recepteur d'origine nantais (RON) receptor tyrosine kinase plays an important role in regulating tumor immunity.
To identify the patterns of RON and PD-L1 expression and explore their clinical significance in CRC.
Gene expression data from the Gene Expression Omnibus database (GEO;
= 290) and patients at the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZUSM;
= 381) were analyzed to determine the prognostic value of RON and PD-L1 expression within the tumor microenvironment of CRC. HT29 cell line was treated with BMS-777607 to explore the relationship between RON activity and PD-L1 expression. Signaling pathways and protein expression perturbed by RON inhibition were evaluated by cellular immunofluorescence and Western blot.
In the GEO patient cohort, cut-off values for RON and PD-L1 expression were determined to be 7.70 and 4.3, respectively. Stratification of patiever, phosphorylation of RON upregulates PD-L1 expression, which provides a novel approach to immunotherapy in CRC.
RON, PD-L1, and their crosstalk are significant in predicting the prognostic value of CRC. Moreover, phosphorylation of RON upregulates PD-L1 expression, which provides a novel approach to immunotherapy in CRC.Pulmonary nodule detection plays an important role in lung cancer screening with low-dose computed tomography (CT) scans. It remains challenging to build nodule detection deep learning models with good generalization performance due to unbalanced positive and negative samples. In order to overcome this problem and further improve state-of-the-art nodule detection methods, we develop a novel deep 3D convolutional neural network with an Encoder-Decoder structure in conjunction with a region proposal network. Particularly, we utilize a dynamically scaled cross entropy loss to reduce the false positive rate and combat the sample imbalance problem associated with nodule detection. We adopt the squeeze-and-excitation structure to learn effective image features and utilize inter-dependency information of different feature maps. We have validated our method based on publicly available CT scans with manually labelled ground-truth obtained from LIDC/IDRI dataset and its subset LUNA16 with thinner slices. Ablation studies and experimental results have demonstrated that our method could outperform state-of-the-art nodule detection methods by a large margin.Functional connectivity (FC) analysis is an appealing tool to aid diagnosis and elucidate the neurophysiological underpinnings of autism spectrum disorder (ASD). Many machine learning methods have been developed to distinguish ASD patients from healthy controls based on FC measures and identify abnormal FC patterns of ASD. Particularly, several studies have demonstrated that deep learning models could achieve better performance for ASD diagnosis than conventional machine learning methods. Although promising classification performance has been achieved by the existing machine learning methods, they do not explicitly model heterogeneity of ASD, incapable of disentangling heterogeneous FC patterns of ASD. To achieve an improved diagnosis and a better understanding of ASD, we adopt capsule networks (CapsNets) to build classifiers for distinguishing ASD patients from healthy controls based on FC measures and stratify ASD patients into groups with distinct FC patterns. Evaluation results based on a large multi-site dataset have demonstrated that our method not only obtained better classification performance than state-of-the-art alternative machine learning methods, but also identified clinically meaningful subgroups of ASD patients based on their vectorized classification outputs of the CapsNets classification model.Psychologists who work as therapists or administrators, or who engage in forensic practice in criminal justice settings, find it daunting to transition into practice in civil cases involving personal injury, namely psychological injury from the psychological perspective. In civil cases, psychological injury arises from allegedly deliberate or negligent acts of the defendant(s) that the plaintiff contends caused psychological conditions to appear. These alleged acts are disputed in courts and other tribunals. Conditions considered in psychological injury cases include posttraumatic stress disorder, depression, chronic pain conditions, and sequelae of traumatic brain injury. This article outlines a detailed case sequence from referral through the end of expert testimony to guide the practitioner to work effectively in this field of practice. It addresses the rules and regulations that govern admissibility of expert evidence in court. The article provides ethical and professional guidance throughout, including best practices in assessment and testing, and emphasizes evidence-based forensic practice.Two case reports demonstrating the need for enhanced usage of personal protective equipment of face shield, respirator, gloves, and gown during routine radiologic evaluation who may screen negative for COVID-19 and or atypical COVID-19 symptoms. First case is of a 42-year-old woman undergoing preoperative evaluation for endometrial cancer in the outpatient setting. The second case is of a 49-year-old woman presenting with abdominal pain, nausea, and vomiting for abdominal CT imaging from the emergency department. Both cases demonstrate typical lung imaging finding of COVID-19. These cases highlight the need for additional precautions in the outpatient and emergency setting even for patients in whom COVID-19 infection is not suspected.