Meierkenny3039

e timing and development of hearing loss caused by different cancer treatment regimens.

This is an international multidisciplinary consensus report providing standardized supportive care recommendations on hearing monitoring in children undergoing potentially ototoxic cancer treatment. The recommendations are intended to improve the care of children with cancer and facilitate comparative research on the timing and development of hearing loss caused by different cancer treatment regimens.Animals evolved in environments with variable nutrient availability and one form of adaptation is the delay of reproduction in food shortage conditions. Belew et al. (2021. J. Cell Biol.https//doi.org/10.1083/jcb.202009197) report that in the nematode C. elegans, starvation-induced transcriptional quiescence in germ cells is achieved through a pathway that combines two well-known chromatin compaction mechanisms.The eukaryotic endomembrane system consists of multiple interconnected organelles. this website Rab GTPases are organelle-specific markers that give identity to these membranes by recruiting transport and trafficking proteins. During transport processes or along organelle maturation, one Rab is replaced by another, a process termed Rab cascade, which requires at its center a Rab-specific guanine nucleotide exchange factor (GEF). The endolysosomal system serves here as a prime example for a Rab cascade. Along with endosomal maturation, the endosomal Rab5 recruits and activates the Rab7-specific GEF Mon1-Ccz1, resulting in Rab7 activation on endosomes and subsequent fusion of endosomes with lysosomes. In this review, we focus on the current idea of Mon1-Ccz1 recruitment and activation in the endolysosomal and autophagic pathway. We compare identified principles to other GTPase cascades on endomembranes, highlight the importance of regulation, and evaluate in this context the strength and relevance of recent developments in in vitro analyses to understand the underlying foundation of organelle biogenesis and maturation.

The choice of anti-inflammatory prophylaxis parallel to cataract surgery is important for patient safety and successful outcome of surgery, but which regimen to choose is contested.

To determine whether a combination of prednisolone and nonsteroidal anti-inflammatory drug (NSAID) eye drops was superior in preventing increased central macular thickness (central subfield thickness [CST]) after uncomplicated cataract surgery compared with NSAID monotherapy and sub-Tenon capsule depot (dropless surgery), and to test whether preoperative initiation of eye drop treatment was superior to initiation on the day of surgery.

This investigator-driven, single-center, randomized clinical trial with masked statistical analyses enrolled patients at the Department of Ophthalmology, Rigshospitalet Glostrup, Glostrup, Denmark, from February 1, 2018, to August 15, 2019. Follow-up was completed December 18, 2019. Participants included low-risk patients undergoing phacoemulsification for age-related cataract by an experience

A significant subset of patients with stage II/III non-small cell lung cancer (NSCLC) cannot receive standard concurrent chemoradiotherapy owing to the risk of toxic effects outweighing potential benefits. Without concurrent chemotherapy, however, the efficacy of conventional radiotherapy is reduced.

To determine whether hypofractionated image-guided radiotherapy (IGRT) would improve overall survival in patients with stage II/III NSCLC who could not receive concurrent chemoradiotherapy and therefore were traditionally relegated to receiving only conventionally fractionated radiotherapy (CFRT).

This nonblinded, phase 3 randomized clinical study enrolled 103 patients and analyzed 96 patients with stage II/III NSCLC and Zubrod performance status of at least 2, with greater than 10% weight loss in the previous 6 months, and/or who were ineligible for concurrent chemoradiotherapy after oncology consultation. Enrollment occurred at multiple US institutions. Patients were enrolled from November 13, 2012, to Aubetween the 2 treatment groups.

This phase 3 randomized clinical trial found that hypofractionated IGRT (60 Gy in 15 fractions) was not superior to CFRT (60 Gy in 30 fractions) for patients with stage II/III NSCLC ineligible for concurrent chemoradiotherapy. Further studies are needed to verify equivalence between these radiotherapy regimens. Regardless, for well-selected patients with NSCLC (ie, peripheral primary tumors and limited mediastinal/hilar adenopathy), the convenience of hypofractionated radiotherapy regimens may offer an appropriate treatment option.

ClinicalTrials.gov Identifier NCT01459497.

ClinicalTrials.gov Identifier NCT01459497.

Individuals with perceived experience and expertise are invited by editorial boards to provide commentary through editorials. Female representation among editorialists is not yet defined.

To determine female representation as editorial authors in 3 high-impact general ophthalmology journals.

This cross-sectional study investigates the proportion of female authorship in editorials published between 2005 to 2009 and 2015 to 2019 in 3 journals Ophthalmology, JAMA Ophthalmology, and American Journal of Ophthalmology. Data were collected from April to June 2020.

Proportions of female first and senior (last or solo) authors between 2005 to 2009 compared with 2015 to 2019. Secondary outcome measures include representation by sex across degree types and subspecialties. Comparisons were made for all editorialists and ophthalmologist editorialists.

Of 814 editorial articles, there were 1179 (first and senior) authors identified. Women held 301 (25.5%) of these authorships, including 116 of 365 first authorshieled the rising proportion of female ophthalmologists over time, parity by sex has yet to be attained. Greater awareness of disparities and strategies to mitigate them may help equalize representation.

Rechallenge therapy with anti-epidermal growth factor receptor (EGFR) drugs has been suggested in patients with chemo-refractory RAS wild-type (WT) metastatic colorectal cancer (mCRC) after initial response to anti-EGFR-based first-line treatment. The association of treatment with cetuximab plus avelumab with overall survival (OS) may be worthy of investigation in this setting.

To assess the efficacy and safety of cetuximab rechallenge therapy plus avelumab.

This single-arm, multicenter phase 2 trial enrolled patients from August 2018 to February 2020. Eligible patients with RAS WT mCRC had a complete or partial response to first-line chemotherapy plus anti-EGFR drugs, developed acquired resistance, and failed second-line therapy. Baseline circulating tumor DNA (ctDNA) for KRAS, NRAS, BRAF, and EGFR-S492R mutation analysis was done.

Patients received avelumab (10 mg/kg every 2 weeks) and cetuximab (400 mg/m2 and, subsequently, 250 mg/m2 weekly) until disease progression or unacceptable toxic effects.

CI, 2.9-5.2 months) in RAS/BRAF WT patients compared with 3.0 months (95% CI, 2.6-3.5 months) in patients with mutated ctDNA (HR, 0.42; 95% CI, 0.23-0.75; P = .004).

The findings of this single-arm phase 2 trial suggest that cetuximab plus avelumab is an active, well tolerated rechallenge therapy in RAS WT mCRC. Plasma ctDNA analysis before treatment may allow selection of patients who could benefit.

ClinicalTrials.gov Identifier NCT04561336.

ClinicalTrials.gov Identifier NCT04561336.Cell-cell fusion is central for sexual reproduction, and generally involves gametes of different shapes and sizes. In walled fission yeast Schizosaccharomyces pombe, the fusion of h+ and h- isogametes requires the fusion focus, an actin structure that concentrates glucanase-containing vesicles for cell wall digestion. Here, we present a quantitative correlative light and electron microscopy (CLEM) tomographic dataset of the fusion site, which reveals the fusion focus ultrastructure. Unexpectedly, gametes show marked asymmetries a taut, convex plasma membrane of h- cells progressively protrudes into a more slack, wavy plasma membrane of h+ cells. Asymmetries are relaxed upon fusion, with observations of ramified fusion pores. h+ cells have a higher exo-/endocytosis ratio than h- cells, and local reduction in exocytosis strongly diminishes membrane waviness. Reciprocally, turgor pressure reduction specifically in h- cells impedes their protrusions into h+ cells and delays cell fusion. We hypothesize that asymmetric membrane conformations, due to differential turgor pressure and exocytosis/endocytosis ratios between mating types, favor cell-cell fusion.The global pandemic scenario has definitely pushed the scientific community to develop COVID-19 vaccines at unprecedented speed. Nevertheless, a worldwide vaccination campaign is still far from being achieved, making the usual precautionary measures as necessary as at the beginning of the outbreak. Many aspects of the SARS-CoV-2 infectious potential and disease severity do not solely rely on interactions at the molecular level but also on physical-chemical parameters that often involve nanoscale effects. Here the SARS-CoV-2 journey to infect a susceptible host is reviewed, focusing on the nanoscale aspects that play a role in the viral infectivity and disease progression. These nanoscale-driven interactions are essential to establish mitigation-related strategies.The fast setting of gels originating from an arrested phase separation leads to solid structures that incorporate a substantial amount of frozen-in stresses. Using a colloidal system made of particles whose interactions can accurately be tuned with temperature and exploiting Photon Correlation Imaging (PCI), an optical correlation technique blending the powers of scattering and imaging, we show that the relaxation of these internal stresses, which occurs through a cascade of microscopic restructuring events, is strongly influenced by the thermal history of the sample. By changing with a temperature jump the interparticle interactions in an already set gel, we specifically show that gels formed by a deep quench within the coexistence region store a lot of residual stress. This stress quickly relaxes when the interparticle attractions are weakened by decreasing temperature. Conversely, the relaxation of stresses accumulated in gels obtained by a shallower quench comes to a halt by a temperature jump that hardens the gel structure. The evidence we collected may provide useful hints about tempering and annealing processes in disordered solids.In the past two decades, the number of reports on the construction of uric acid (UA) sensors has increased dramatically, as it is a vital factor in the diagnosis of physiological functions and diseases. Among these sensors, cascade colorimetric detection based on peroxidase mimics has received great attention owing to the advantages of easier operation and more intuitive results. Herein, we report a simple UA detection method via the integration of urate oxidase (UOx) and PCN-222(Fe) with peroxidase-like activity, in which UOx is immobilized in PCN-222(Fe) by physical adsorption. UOx could catalyze the UA oxidation to produce H2O2, and then PCN-222(Fe) catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 to generate a blue product with a maximum absorbance at 652 nm. Under optimal conditions, the increasing absorbance at 652 nm was proportional to the UA concentration. The linear range for UA detection was 10-800 μM with a limit of detection of 3.5 μM, and the cascade system has been successfully utilised for the detection of UA in human serum samples to demonstrate the accuracy of the proposed method.