Miracle-dz/UniFAR-FTUs huggingface dataset:
Worse prognosis in young patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

Abstract To determine the efficacy of neoadjuvant chemoradiotherapy (NCRT) between young and old patients with locally advanced rectal cancer (LARC) in terms of tumor response and survival outcome. LARC patients undergoing NCRT and radical surgery from 2011 to 2015 were included and divided into: young (aged ≤50 years) and old group (aged >50 years). Multivariate analyses were performed to identify risk factors for local recurrence. Least absolute shrinkage and selection operator analysis was performed to identify risk factors for overall survival. Predicting nomograms and time-indepent receiver operating characteristic curve analysis were performed to compare the models containing with/withour age groups. A total of 572 LARC patients were analyzed. The young group was associated with higher pathological TNM stage, poorly differentiated tumors, and higher rate of positive distal resection margin (P = .010; P = .019; P = .023 respectively). Young patients were associated with poorer 5-year disease-free survival and local recurrence rates (P = .023, P = .003 respectively). Cox regression analysis demonstrated that age ≤50 years (Hazard ratio = 2.994, P = .038) and higher pathological TNM stage (Hazard ratio = 3.261, P = .005) were significantly associated with increased risk for local recurrence. Least absolute shrinkage and selection operator analysis and the time-indepent receiver operating characteristic curve analysis demonstrated that including the age group were superior than that without age group. Young patients were associated with poorer disease free survival (DFS) and a higher risk for local recurrence in LARC following NCRT. The predicting model basing based on the age group had a better predictive ability. More intense adjuvant treatment could be considered to improve DFS and local control for young patients with LARC following NCRT.
A MALT1 inhibitor suppresses human myeloid DC, effector T-cell and B-cell responses and retains Th1/regulatory T-cell homeostasis

The paracaspase mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) regulates nuclear-factor-kappa-B (NF-κB) activation downstream of surface receptors with immunoreceptor tyrosine-based activation motifs (ITAMs), such as the B-cell or T-cell receptor and has thus emerged as a therapeutic target for autoimmune diseases. However, recent reports demonstrate the development of lethal autoimmune inflammation due to the excessive production of interferon gamma (IFN-ɣ) and defective differentiation of regulatory T-cells in genetically modified mice deficient in MALT1 paracaspase activity. To address this issue, we explored the effects of pharmacological MALT1 inhibition on the balance between T-effector and regulatory T-cells. Here we demonstrate that allosteric inhibition of MALT1 suppressed Th1, Th17 and Th1/Th17 effector responses, and inhibited T-cell dependent B-cell proliferation and antibody production. Allosteric MALT1 inhibition did not interfere with the suppressive function of human T-regulatory cells, although it impaired de novo differentiation of regulatory T-cells from naïve T-cells. Treatment with an allosteric MALT1 inhibitor alleviated the cytokine storm, including IFN-ɣ, in a mouse model of acute T-cell activation, and long-term treatment did not lead to an increase in IFN-ɣ producing CD4 cells or tissue inflammation. Together, our data demonstrate that the effects of allosteric inhibition of MALT1 differ from those seen in mice with proteolytically inactive MALT1, and thus we believe that MALT1 is a viable target for B and T-cell driven autoimmune diseases.
Ultra-high-field imaging reveals increased whole brain connectivity underpins cognitive strategies that attenuate pain

We investigated how the attenuation of pain with cognitive interventions affects brain connectivity using neuroimaging and a whole brain novel analysis approach. While receiving tonic cold pain, 20 healthy participants performed three different pain attenuation strategies during simultaneous collection of functional imaging data at seven tesla. Participants were asked to rate their pain after each trial. We related the trial-by-trial variability of the attenuation performance to the trial-by-trial functional connectivity strength change of brain data. Across all conditions, we found that a higher performance of pain attenuation was predominantly associated with higher functional connectivity. Of note, we observed an association between low pain and high connectivity for regions that belong to brain regions long associated with pain processing, the insular and cingulate cortices. For one of the cognitive strategies (safe place), the performance of pain attenuation was explained by diffusion tensor imaging metrics of increased white matter integrity.
COVID-19 in Healthcare Workers: A Living Systematic Review and Meta-analysis of Prevalence, Risk Factors, Clinical Characteristics, and Outcomes

Abstract Health care workers (HCW) are at the frontline response to the new coronavirus disease 2019 (COVID-19), being at a higher risk of acquiring the disease, and subsequently, exposing patients and colleagues. Searches in eight bibliographic databases were performed to systematically review the evidence on the prevalence, risk factors, clinical characteristics, and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCW. Ninety-seven studies (All published in 2020), including 230,398 HCW, met the inclusion criteria. From the screened HCW using RT-PCR and the presence of antibodies, the estimated prevalence of SARS-CoV-2 infection was 11% (95%CI; 7%-15%) and 7% (95% CI; 4%-11%), respectively. The most frequently affected personnel were the nurses (48%. 95%CI; 41%-56%), while most of the COVID-19 positive medical personnel were working in hospitalization/non-emergency wards during the screening (43%, 95%CI;28%-59%). Anosmia, fever and myalgia were identified as the only symptoms associated with HCW SARS-CoV-2 positivity. Among RT-PCR positive HCW, 40% (95%CI;17%-65%) did not show symptoms at the time of diagnosis. Finally, 5% (95%CI;3%-8%) of the COVID-19 positive HCW developed severe clinical complications, and 0.5% (95% CI; 0.02%-1.3%) died. HCW suffer a significant burden from COVID-19, with HCW working in hospitalization/non-emergency wards and nurses being the most infected personnel.
Impact of Disclosure Videos and Self-Understanding Imagined Interactions on Emotions and Homophobia

ABSTRACT Disclosure, or “coming out,” videos on YouTube are a popular part of YouTube’s global online video sharing culture. Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) coming out videos are among the most popular, as they allow for LGBTQ+ persons to share their stories with others. This study examines LGBTQ+ coming out videos and their potential to reduce prejudice through the parasocial contact hypothesis, particularly for non-LGBTQ+ persons who view these videos. Through a 2 × 2 experimental design, this study proposed a path model that explores how coming out YouTube videos and self-understanding imagined interactions helps to reduce homophobia, especially as they relate to emotional responses to the videos and stories. Results found strong effects for video admiration reducing homophobia and hatred increasing homophobia. Further, self-understanding imagined interactions reduced homophobia through admiration. Results and implications for these findings are discussed.
Pollution, Health, and the Moderating Role of Physical Activity Opportunities

Air and water pollution have detrimental effects on health, while physical activity opportunities have a positive relationship. The purpose of this study was to explore whether physical activity opportunities moderate the relationships among air and water pollution, and measures of health. Aggregate data were collected at the county level in the United States (n = 3104). Variables included the mean daily density of fine particle matter (air pollution), reported cases of health-related drinking water violations (water pollution), subjective ratings of poor or fair health (overall health), the number of physically and mentally unhealthy (physical and mental health, respectively), and the percentage of people living in close proximity to a park or recreation facility (access to physical activity). Air and water pollution have a significant positive effect on all measures of residents’ poor health, while physical activity opportunities only have a negative effect on overall health and physical health. Access to physical activity only moderates the relationship between air pollution and all health outcomes. Since physical activity behavior can be more rapidly changed than some causes of pollution, providing the resident population with better access to physical activity can represent an effective tool in environmental health policy.
Nutritional management in patients with chronic kidney disease

The global prevalence of chronic kidney disease (CKD) is increasing with the aging of populations worldwide. As kidney function declines, the accumulation of metabolic waste products and excessive electrolytes can significantly impair the health of patients with CKD. As nutritional management of patients with CKD is thought to control uremic symptoms and provide beneficial effects on the progression of kidney dysfunction, the diet of patients with CKD should be an important consideration in their care. Many guidelines recommend limiting protein intake in these patients, as high-protein diets aggravate kidney dysfunction. Excess sodium may be associated with CKD progression and all-cause mortality and, therefore, limiting salt intake is generally recommended. Low potassium is associated with muscle weakness and hypertension, whereas high potassium is associated with cardiac arrhythmia. Therefore, recent guidelines recommend adjusting dietary potassium intake on an individual basis to maintain serum potassium levels within the normal range. Appropriate dietary calcium intake is recommended to maintain calcium balance in patients with CKD G3, G4. Given the many dietary considerations for patients with CKD, effective nutritional management is challenging. Individualized strategies are needed to ensure the best outcome for patients with CKD.
Gestational Diabetes Type 2: Variation in High-Density Lipoproteins Composition and Function

Aims: Class A2 gestational diabetes mellitus (GDMA2) has short- and long-term effects on the mother and child. These may include abnormalities of placentation, damage to endothelial cells and cardiovascular disease. This research investigated the function and composition of high-density lipoproteins (HDL) among women with GDMA2 and their fetuses. Methods: Thirty pregnant women were recruited during admission for delivery. The function and expression of HDL, paraoxonase1 (PON1) and apolipoprotein A1 (APOA1) in the blood samples and the placental tissue were evaluated. The effect of HDL on migration of endothelial cells was measured in vitro. Results: Compared to normal pregnancy (NP), APOA1 in the maternal plasma of women with GDMA2 was decreased. More APOA1 and PON1 were released from HDL of women with GDMA2, compared to NP. Placental APOA1 and PON1 were decreased in GDMA2. For endothelial cells stimulated with TNFα, HDL cell migration was decreased when cells were evaluated with NP-HDL, as compared to GDMA2-HDL. Conclusions: GDMA2 affects the composition and function of HDL in plasma. Changes in HDL commonly seen in GDMA2 were observed in maternal and placental samples, but not in cord samples. These results might indicate a placental role in protecting the fetus by preserving the components and functions of HDL and require further investigation.
Diagnostic Value of High Resolution Neckultrasongraghy, Fine Needle Aspiration Cytology and BRAFV600E Mutation in Diagnosis of Malignant Thyroid Nodules

Background: Thyroid malignancy is rapidly raising, nearly 9-15% of the thyroid nodules are malignant nodules. Finding an optimal mean to diagnose malignant thyroid nodule preoperative is a challenge. Combination of molecular analysis, imaging and cytopathology may be helpful. This study aimed to evaluate the value of adding BRAFV600E analysis to nodules with suspicious ultra-sonographic criteria. Patients and methodology: 50 patients from Kasr alainy endocrine outpatient clinic with solitary or multiple thyroid nodules are included, All patients subjected to full history and examination, thyroid profile, high resolution neck High resolution neck ultrasound (U/S), Fine needle Aspiration Cytology (FNAC), U/S guided FNAC and BRAFV600E analysis on FNAC using DNA sequencing then high resolution melt curve analysis (HRMA) for confirmation. Results: The incidence of BRAFV600E mutation among papillary thyroid cancer (PTC) patients was 55.6%. it’s sensitivity 42.9%, specificity was 100% in diagnosing PTC. Sensitivity of high resolution neck ultrasonograghy in detecting malignancy was 88.2%, specificity 72.7%. Addition of ultrasonography to BRAFV600E analysis increased ultrasound sensitivity in detecting PTC preoperative to 92%. There was a positive correlation between most suspicious ultrasonography findings and presence of BRAFV600E mutation (increased AP/T diameter, Increase intra-nodular blood flow, cervical lymphadenopathy, absent or incomplete halo (all p value<0.001), irregular border p value 0.004, micro calcifications p value 0.007. Conclusion: Adding BRAF-V600E analysis to work up of suspicious thyroid nodule would increase the sensitivity of preoperative diagnosis of PTC especially in cases of indefinite pathological findings. HRMA is simple, low cost tool for BRAF-V600E analysis in comparison to DNA sequencing method.
Comparing physician associates and foundation year two doctors-in-training undertaking emergency medicine consultations in England: a mixed-methods study of processes and outcomes

Objectives To compare the contribution of physician associates to the processes and outcomes of emergency medicine consultations with that of foundation year two doctors-in-training. Design Mixed-methods study: retrospective chart review using 4 months’ anonymised clinical record data of all patients seen by physician associates or foundation year two doctors-in-training in 2016; review of a subsample of 40 records for clinical adequacy; semi-structured interviews with staff and patients; observations of physician associates. Setting Three emergency departments in England. Participants The records of 8816 patients attended by 6 physician associates and 40 foundation year two doctors-in-training; of these n=3197 had the primary outcome recorded (n=1129 physician associates, n=2068 doctor); 14 clinicians and managers and 6 patients or relatives for interview; 5 physician associates for observation. Primary and secondary outcome measures The primary outcome was unplanned re-attendance at the same emergency department within 7 days. Secondary outcomes: consultation processes, clinical adequacy of care, and staff and patient experience. Results Re-attendances within 7 days (n=194 (6.1%)) showed no difference between physician associates and foundation year two doctors-in-training (OR 0.87, 95% CI 0.61 to 1.24, p=0.437). If seen by a physician associate, patients were more likely receive an X-ray investigation (OR 2.10, 95% CI 1.72 to 4.24), p<0.001), after adjustment for patient characteristics, triage severity of condition and statistically significant clinician intraclass correlation. Clinical reviewers found almost all patients’ charts clinically adequate. Physician associates were evaluated as assessing patients in a similar way to foundation year two doctors-in-training and providing continuity in the team. Patients were positive about the care they had received from a physician associate, but had poor understanding of the role. Conclusions Physician associates in emergency departments in England treated patients with a range of conditions safely, and at a similar level to foundation year two doctors-in-training, providing clinical operational efficiencies.
Comparison of Preoperative Remission Scores and Diabetes Duration Alone as Predictors of Durable Type 2 Diabetes Remission and Risk of Diabetes Complications After Bariatric Surgery: A Post Hoc Analysis of Participants From the Swedish Obese Subjects Study

OBJECTIVE Bariatric surgery is associated with diabetes remission and prevention of diabetes-related complications. The ABCD, DiaRem, Ad-DiaRem, DiaBetter, and individualized metabolic surgery scores were developed to predict short- to medium-term diabetes remission after bariatric surgery. However, they have not been tested for predicting durable remission nor the risk of diabetes complications, nor compared with diabetes duration alone. RESEARCH DESIGN AND METHODS We identified 363 individuals from the surgically treated group in the prospective Swedish Obese Subjects study with preoperative type 2 diabetes and for whom data (preoperative age, BMI, C-peptide, HbA1c, oral diabetes medications, insulin use, and diabetes duration) were available for calculation of remission scores. Partial remission (after 2 and 10 years) was defined as blood glucose <6.1 mmol/L or HbA1c <6.5% (48 mmol/mol) and no diabetes medication. Information on diabetes complications (at baseline and over 15 years of follow-up) was obtained from national health registers. Discrimination was evaluated by area under receiver operating characteristic curves (AUROCs). RESULTS For 2-year diabetes remission, AUROCs were between 0.79 and 0.88 for remission scores and 0.84 for diabetes duration alone. After 10 years, the predictive ability of scores decreased markedly (AUROCs between 0.70 and 0.76), and no score had higher predictive capacity than diabetes duration alone (AUROC = 0.73). For development of microvascular and macrovascular diabetes complications over 15 years, AUROCs for remission scores were 0.70–0.80 and 0.62–0.71, respectively, and AUROCs for diabetes duration alone were 0.77 and 0.66, respectively. CONCLUSIONS Remission scores and diabetes duration are good predictors of short-term diabetes remission. However, for durable remission and risk of complications, remission scores and diabetes duration alone have limited predictive ability.
Rates of new human papillomavirus detection and loss of detection in middle-aged women by recent and past sexual behavior.

BACKGROUND Understanding the source of newly detected human papillomavirus (HPV) in middle-aged women is important to inform preventive strategies, such as screening and HPV vaccination. METHODS We conducted a prospective cohort study in Baltimore, Maryland. Women aged 35-60 years underwent HPV testing and completed health and sexual behavior questionnaires every 6-months over a 2-year period. New detection/loss of detection rates were calculated and adjusted hazard ratios (aHR) were used to identify risk factors for new detection. RESULTS 731 women and 104 high-risk (HR) HPV-positive women were included in the new and loss of detection analyses, respectively. The rate of new HR HPV detection was 5.0/1000 woman-months. Reporting a new sex partner was associated with higher detection rates (aHR 8.1; 95% CI 3.5, 18.6), but accounted only for 19.4% of all new detections. Among monogamous and sexually abstinent women, new detection was higher in women reporting ≥5 lifetime sexual partners compared to women reporting &5 (aHR 2.2; 95% CI 1.2, 4.2). CONCLUSION While women remain at risk of HPV acquisition from new sex partners as they age, our results suggest that most new detections in mid-adult women reflect recurrence of previously acquired HPV.
Rapid creation of an emergency department telehealth program during the COVID-19 pandemic

Coronavirus disease 2019 (COVID-19) has spread to nearly every continent, with over 2.6 m cases confirmed worldwide. Emergency departments care for a significant number of patients who are under investigation for COVID-19 or are COVID-19-positive. When patients present in the emergency department, there is an increased risk of spreading the virus to other patients and staff. We designed an emergency department telehealth program for patients physically in the emergency department, to reduce exposure and conserve personal protective equipment. While traditional telehealth is designed to be patient-specific and device-independent, our emergency department telehealth program was device-specific and patient-independent. In this article, we describe how we rapidly implemented our emergency department telehealth program, used for 880 min of contact time and 523 patient encounters in a 30-day period, which decreased exposure to COVID-19 and conserved personal protective equipment. We share our challenges, successes and recommendations for designing an emergency department telehealth program, building the technological aspects, and deploying telehealth devices in the emergency department environment. Our recommendations can be adopted by other emergency departments to create and run their own emergency department telehealth initiatives.
Rhabdovirus Infection Is Dependent on Serine/Threonine Kinase AP2-Associated Kinase 1

Rabies virus (RABV) causes a fatal neurological disease in both humans and animals. Understanding the mechanism of RABV infection is vital for prevention and therapy of virulent rabies infection. Our previous proteomics analysis based on isobaric tags for relative and absolute quantitation to identify factors revealed that RABV infection enhanced AP-2-associated protein kinase 1 (AAK1) in N2a cells. In this study, to further confirm the role of AAK1, we showed that RABV infection increased the transcription and expression of AAK1 in N2a cells. AAK1 knockdown significantly decreased RABV infection in both N2a and BHK-21 cells. AAK1 knockout inhibited RABV infection in N2a cells. Furthermore, inhibition of AAK1 kinase activity using sunitinib decreased RABV infection. However, AAK1 overexpression did not change RABV infection in vitro. Therapeutic administration of sunitinib did not significantly improve the survival rate of mice following lethal RABV challenge. In addition, AAK1 knockdown decreased infection in N2a cells by vesicular stomatitis virus, which is another rhabdovirus. These results indicate that rhabdovirus infection is dependent on AAK1 and inhibition of AAK1 is a potential strategy for the prevention and therapy of rabies.