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The control of contagious or refractory diseases requires early, rapid diagnostic assays that are simple, fast, and easy-to-use. Here, easy-to-implement CRISPR/Cas12a-based diagnostic platform through Raman transducer generated by Raman enhancement effect, term as SERS-CRISPR (S-CRISPR), are described. The S-CRISPR uses high-activity noble metallic nanoscopic materials to increase the sensitivity in the detection of nucleic acids, without amplification. This amplification-free platform, which can be performed within 30-40 min of incubation time, is then used for detection of SARS-CoV-2 derived nucleic acids in RNA extracts obtained from nasopharyngeal swab specimens (n  =  112). Compared with the quantitative reverse transcription polymerase chain reaction (RT-qPCR), the sensitivity and specificity of S-CRISPR reaches 87.50% and 100%, respectively. In general, the S-CRISPR can rapidly identify the RNA of SARS-CoV-2 RNA without amplification and is a potential strategy for nucleic acid point of care test (POCT).

Messenger RNA (mRNA) coronavirus disease of 2019 (COVID-19) vaccine are known to cause minor side effects at the injection site and mild global systemic symptoms in first 24-48h. Recently published case series have reported a possible association between acute myocarditis and COVID-19 vaccination, predominantly in young males.

We report a case series of 5 young male patients with cardiovascular magnetic resonance (CMR)-confirmed acute myocarditis within 72h after receiving a dose of an mRNA-based COVID-19 vaccine.

Our case series suggests that myocarditis in this setting is characterized by myocardial edema and late gadolinium enhancement in the lateral wall of the left ventricular (LV) myocardium, reduced global LV longitudinal strain, and preserved LV ejection fraction. All patients in our series remained clinically stable during a relatively short inpatient hospital stay.

In conjunction with other recently published case series and national vaccine safety surveillance data, this case series suggests a possible association between acute myocarditis and COVID-19 vaccination in young males and highlights a potential pattern in accompanying CMR abnormalities.

In conjunction with other recently published case series and national vaccine safety surveillance data, this case series suggests a possible association between acute myocarditis and COVID-19 vaccination in young males and highlights a potential pattern in accompanying CMR abnormalities.

Protein S deficiency (PSD) is an autosomal dominant hereditary disease. In 1984, familial PSD was reported to be prone to recurrent thrombosis. Follow-up studies have shown that heterozygous protein S (PROS1) mutations increase the risk of thrombosis. More than 300 PROS1 mutations have been identified; among them, only a small number of mutations have been reported its possible mechanism to reduce plasma protein S (PS) levels. However, whether PROS1 mutations affect protein structure and why it can induce PSD remains unknown.

The clinical phenotypes of the members of a family with thrombosis were collected. Their PS activity was measured using the coagulation method, whereas their protein C and antithrombin III activities were measured using methods such as the chromogenic substrate method. The proband and her parents were screened for the responsible mutation using second-generation whole exon sequencing, and the members of the family were verified for suspected mutations using Sanger sequencing. Mutant otein. These data indicate that impaired PS translation and synthesis or possible secretion impairment is the main pathogenesis of this family with hereditary PSD and thrombophilia.

The analysis of family phenotype, gene association, and cell function tests suggest that the PROS1 Leu607Ser heterozygous mutation may be a pathogenic mutation. Serine substitution causes structural instability of the entire protein. These data indicate that impaired PS translation and synthesis or possible secretion impairment is the main pathogenesis of this family with hereditary PSD and thrombophilia.Tumor heterogeneity is a primary cause of treatment failure. However, changes in drug sensitivity over time are not well mapped in cancer. Patient-derived organoids (PDOs) may predict clinical drug responses ex vivo and offer an opportunity to evaluate novel treatment strategies in a personalized fashion. Sodium palmitate Here we have evaluated spatio-temporal functional and molecular dynamics of five PDO models established after hepatic re-resections and neoadjuvant combination chemotherapies in a patient with microsatellite stable and KRAS mutated metastatic rectal cancer. Histopathological differentiation phenotypes of the PDOs corresponded with the liver metastases, and ex vivo drug sensitivities generally reflected clinical responses and selection pressure, assessed in comparison to a reference data set of PDOs from metastatic colorectal cancers. PDOs from the initial versus the two recurrent metastatic settings showed heterogeneous cell morphologies, protein marker expression, and drug sensitivities. Exploratory analyses of a drug screen library of 33 investigational anticancer agents showed the strongest ex vivo sensitivity to the SMAC mimetic LCL161 in PDOs of recurrent disease compared to those of the initial metastasis. Functional analyses confirmed target inhibition and apoptosis induction in the LCL161 sensitive PDOs from the recurrent metastases. Gene expression analyses indicated an association between LCL161 sensitivity and tumor necrosis factor alpha signaling and RIPK1 gene expression. In conclusion, LCL161 was identified as a possible experimental therapy of a metastatic rectal cancer that relapsed after hepatic resection and standard systemic treatment.

Retinol binding protein 4 (RBP4) has been regarded as an important serological biomarker for type 2 diabetes mellitus (T2DM). Hence, the construction of a highly sensitive detection method for RBP4 is the key to early prevention and multidisciplinary intervention of T2DM. In this work, a dual-quenched electrochemiluminescence (ECL) immunosensor has been fabricated for ultrasensitive detection of RBP4 by combining zeolitic imidazolate framework-67/AuPt-supported luminol (luminol@AuPt/ZIF-67) with MnO

nanosheets-grown on carbon nanotubes (MnO

@CNTs).

AuPt/ZIF-67 hybrids with high-efficiency peroxidase-like activity could provide multipoint binding sites for luminol and antibodies and significantly boost the amplified initial signal of the ECL immunosensor. Upon glutathione/H

O

coreactants system, MnO

@CNTs composites could quench the initial signal by inhibiting mimic peroxidase activity of luminol@AuPt/ZIF-67. Moreover, the absorption spectrum of the MnO

@CNTs composites completely overlaps with the emission spectrum of luminol, which can further reduce initial signal by ECL resonance energy transfer (ECL-RET).

Benefiting from the above-mentioned properties, the designed immunoassay sensitivity exhibited excellent sensitivity and relative stability for RBP4 detection range from 0.0001 to 100ngmL

with a low detection limit of 43fgmL

. Therefore, our ECL immunosensor provides an alternative assaying strategy for early diagnosis of T2DM.

Benefiting from the above-mentioned properties, the designed immunoassay sensitivity exhibited excellent sensitivity and relative stability for RBP4 detection range from 0.0001 to 100 ng mL-1 with a low detection limit of 43 fg mL-1. Therefore, our ECL immunosensor provides an alternative assaying strategy for early diagnosis of T2DM.

After stroke, motor control is often negatively affected, leaving survivors with less muscle strength and coordination, increased tone, and abnormal synergies (coupled joint movements) in their affected upper extremity. Humeral internal and external rotation have been included in definitions of abnormal synergy but have yet to be studied in-depth.

Determine the ability to generate internal and external rotation torque under different shoulder abduction and adduction loads in persons with chronic stroke (paretic and non-paretic arm) and uninjured controls.

24 participants, 12 with impairments after stroke and 12 controls, completed this study. A robotic device controlled abduction and adduction loading to 0, 25, and 50% of maximum strength in each direction. Once established against the vertical load, each participant generated maximum internal and external rotation torque in a dual-task paradigm. Four linear mixed-effects models tested the effect of group (control, non-paretic, and paretic), load (0, 25l-tasks in paretic arms.

Common biomechanical constraints (muscle actions) explain limitations in external and internal rotation strength during adduction and abduction dual-tasks, respectively. Additional non-load-dependent effects such as increased antagonist co-activation (hypertonia) may cause the observed decreased performance in individuals with stroke. The inclusion of external rotation in flexion synergy and of internal rotation in extension synergy may be over-simplifications.

Common biomechanical constraints (muscle actions) explain limitations in external and internal rotation strength during adduction and abduction dual-tasks, respectively. Additional non-load-dependent effects such as increased antagonist co-activation (hypertonia) may cause the observed decreased performance in individuals with stroke. The inclusion of external rotation in flexion synergy and of internal rotation in extension synergy may be over-simplifications.

Quality improvement (QI) casebooks, compilations of QI experiences, are one way to share experiential knowledge that healthcare policy-makers, managers and professionals can adapt to their own contexts. However, QI casebook use, characteristics and impact are unknown. We aimed to synthesize published research on QI prevalence, development, characteristics and impact.

We conducted a scoping review by searching MEDLINE, EMBASE, CINAHL and SCOPUS from inception to 4 February 2021. We extracted data on study characteristics and casebook definitions, development, characteristics (based on the WIDER [Workgroup for Intervention Development and Evaluation Research] framework) and impact. We reported findings using summary statistics, text and tables.

We screened 2999 unique items and included five articles published in Canada from 2011 to 2020 describing three studies. Casebooks focused on promoting positive weight-related conversations with children and parents, coordinating primary care-specialist cancer manaethods for developing casebooks and to evaluate their impact. One approach is to assess how the many QI casebooks available online were developed. Casebooks should be evaluated alone or in combination with other interventions that support QI on a range of outcomes.

Future research is needed to optimize methods for developing casebooks and to evaluate their impact. One approach is to assess how the many QI casebooks available online were developed. Casebooks should be evaluated alone or in combination with other interventions that support QI on a range of outcomes.

Infertility is a common complication in obese men. Oxidative stress and testicular apoptosis play critical roles in obesity-induced spermatogenesis dysfunction. It has been reported that irisin, an exercise-induced myokine, may attenuate oxidative damage and testicular apoptosis in several diseases; however, its role in obesity-induced spermatogenesis dysfunction remains unclear. The purpose of this study was to investigate the role and underlying mechanism of irisin in obesity-induced dysfunction of spermatogenesis.

Male mice were fed a high-fat diet (HFD) for 24weeks to establish a model of obesity-induced spermatogenesis dysfunction. To explore the effects of irisin, mice were subcutaneously infused with recombinant irisin for 8weeks beginning at 16weeks after starting a HFD. To confirm the role of AMP-activated protein kinase α (AMPKα), AMPKα-deficient mice were used.

The data showed decreased serum irisin levels in obese patients, which was negatively correlated with sperm count and progressive motility.

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