Miracle-dz/UniFAR-FTUs huggingface dataset:
Myeloma patients with COVID‐19 have superior antibody responses compared to patients fully vaccinated with the BNT162b2 vaccine

Patients with multiple myeloma (MM) have a suboptimal antibody response following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and lower seroconversion rates following coronavirus disease 2019 (COVID‐19) compared with healthy individuals. In this context, we evaluated the development of neutralising antibodies (NAbs) against SARS‐CoV‐2 in non‐vaccinated patients with MM and COVID‐19 compared with patients after vaccination with two doses of the BNT162b2 vaccine. Serum was collected either four weeks post confirmed diagnosis or four weeks post a second dose of BNT162b2. NAbs were measured with a Food and Drug Administration‐approved enzyme‐linked immunosorbent assay methodology. Thirty‐five patients with COVID‐19 and MM along with 35 matched patients were included. The two groups did not differ in age, sex, body mass index, prior lines of therapy, disease status, lymphocyte count, immunoglobulin levels and comorbidities. Patients with MM and COVID‐19 showed a superior humoral response compared with vaccinated patients with MM. The median (interquartile range) NAb titre was 87·6% (71·6–94%) and 58·7% (21·4–91·8%) for COVID‐19‐positive and vaccinated patients, respectively (P = 0·01). Importantly, there was no difference in NAb production between COVID‐19‐positive and vaccinated patients who did not receive any treatment (median NAb 85·1% vs 91·7%, P = 0·14). In conclusion, our data indicate that vaccinated patients with MM on treatment without prior COVID‐19 should be considered for booster vaccine doses.
Effect of regular and irregular stimulation cycles of dexamethasone on circadian clock in NIH3T3 cells

ABSTRACT Animal studies have shown that irregular light-dark cycles cause circadian desynchronization, while few studies have addressed the effect of regular/irregular stimulation cycles of signaling hormones on the cellular clock in vitro. Here, we examined how cellular clocks respond to regular and irregular stimulation cycles of dexamethasone, using NIH3T3 cells transfected with the Bmal1 promoter-driven luciferase (Bmal1-Luc) reporter gene. Cyclic stimulation with dexamethasone at different time intervals (18–28 h, 3 times regularly) revealed that Bmal1-Luc bioluminescence rhythms can be entrained to 22 and 24 h cycles during the stimulation period, but not to other cycles. The rhythm entrained for 24 h cycles persisted for at least one day after the last stimulation. Irregular dexamethasone treatment (16, 24, and 16 h, sequentially; short-term jet lag protocol) resulted in an overall upregulation and phase shifts of the temporal expression of several clock genes and cell cycle genes, including c-Myc and p53. Regular dexamethasone stimulation three times with 24 h cycles also caused upregulation of Per1 and Per2 expression, but not c-Myc and p53 expression. In conclusion, our study identified the entrainable range of the circadian clock in NIH3T3 cells to the dexamethasone stimulation cycle and demonstrated that irregular dexamethasone treatment could disturb the expression of cell cycle genes.
Trypanosoma brucei triggers a broad immune response in the adipose tissue

Adipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2–5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this study, we tested whether the AT environment responds immunologically to the presence of the parasite. Transcriptome analysis of T. brucei infected adipose tissue revealed that most upregulated host genes are involved in inflammation and immune cell functions. Histochemistry and flow cytometry confirmed an increasingly higher number of infiltrated macrophages, neutrophils and CD4+ and CD8+ T lymphocytes upon infection. A large proportion of these lymphocytes effectively produce the type 1 effector cytokines, IFN-γ and TNF-α. Additionally, the adipose tissue showed accumulation of antigen-specific IgM and IgG antibodies as infection progressed. Mice lacking T and/or B cells (Rag2-/-, Jht-/-), or the signature cytokine (Ifng-/-) displayed a higher parasite load both in circulation and in the AT, demonstrating the key role of the adaptive immune system in both compartments. Interestingly, infections of C3-/- mice showed that while complement system is dispensable to control parasite load in the blood, it is necessary in the AT and other solid tissues. We conclude that T. brucei infection triggers a broad and robust immune response in the AT, which requires the complement system to locally reduce parasite burden.
Satisfaction and continuation with LNG-IUS 12: findings from the real-world kyleena® satisfaction study

Abstract Purpose The Kyleena® Satisfaction Study (KYSS) aimed to assess satisfaction and continuation with levonorgestrel-releasing intrauterine system (LNG-IUS) 12 (Kyleena®) in routine clinical practice and to evaluate factors that influence satisfaction. Materials and methods This prospective, observational, multicentre, single-arm cohort study, with 1-year follow-up, was conducted in Belgium, Canada, Germany, Mexico, Norway, Sweden, Spain and the United States from 2017 to 2018. During routine counselling, women who independently selected to use LNG-IUS 12 were invited to participate in the study. KYSS assessed LNG-IUS 12 satisfaction, continuation and safety. Results Overall, there were 1126 successful LNG-IUS 12 placements, with insertion attempted in 1129 women. Most participants (833/968, 86.1%, 95% CI 83.7–88.2%, with satisfaction outcome data available) reported satisfaction with LNG-IUS 12 at 12 months (or at the final visit if the device was discontinued prematurely). Satisfaction was not associated with age, parity or motivation for choosing LNG-IUS 12. The majority of women (919/1129, 81.4%) chose to continue after 12 months. Discontinuation was not correlated with age or parity. Overall, 191 women (16.9%) reported a treatment-emergent adverse event. Conclusions Results from KYSS provide the first real-world evidence assessing LNG-IUS 12, and demonstrate high satisfaction and continuation rates irrespective of age or parity. Clinical trial registration: NCT03182140
CARes‐UNet: Content‐aware residual UNet for lesion segmentation of COVID‐19 from chest CT images

Abstract Purpose Coronavirus disease 2019 (COVID‐19) has caused a serious global health crisis. It has been proven that the deep learning method has great potential to assist doctors in diagnosing COVID‐19 by automatically segmenting the lesions in computed tomography (CT) slices. However, there are still several challenges restricting the application of these methods, including high variation in lesion characteristics and low contrast between lesion areas and healthy tissues. Moreover, the lack of high‐quality labeled samples and large number of patients lead to the urgency to develop a high accuracy model, which performs well not only under supervision but also with semi‐supervised methods. Methods We propose a content‐aware lung infection segmentation deep residual network (content‐aware residual UNet (CARes‐UNet)) to segment the lesion areas of COVID‐19 from the chest CT slices. In our CARes‐UNet, the residual connection was used in the convolutional block, which alleviated the degradation problem during the training. Then, the content‐aware upsampling modules were introduced to improve the performance of the model while reducing the computation cost. Moreover, to achieve faster convergence, an advanced optimizer named Ranger was utilized to update the model's parameters during training. Finally, we employed a semi‐supervised segmentation framework to deal with the problem of lacking pixel‐level labeled data. Results We evaluated our approach using three public datasets with multiple metrics and compared its performance to several models. Our method outperforms other models in multiple indicators, for instance in terms of Dice coefficient on COVID‐SemiSeg Dataset, CARes‐UNet got the score 0.731, and semi‐CARes‐UNet further boosted it to 0.776. More ablation studies were done and validated the effectiveness of each key component of our proposed model. Conclusions Compared with the existing neural network methods applied to the COVID‐19 lesion segmentation tasks, our CARes‐UNet can gain more accurate segmentation results, and semi‐CARes‐UNet can further improve it using semi‐supervised learning methods while presenting a possible way to solve the problem of lack of high‐quality annotated samples. Our CARes‐UNet and semi‐CARes‐UNet can be used in artificial intelligence‐empowered computer‐aided diagnosis system to improve diagnostic accuracy in this ongoing COVID‐19 pandemic.
Acute Watery Diarrhea Surveillance During the Rohingya Crisis 2017–2019 in Cox’s Bazar, Bangladesh

Abstract Background Forcibly Displaced Myanmar Nationals (FDMNs) fled into Cox’s Bazar, Bangladesh due to internal conflict. Considering the public health situation, a surveillance network was established to identify the enteric pathogens and early detection of cholera epidemics. The purpose of this manuscript is to report the clinical, epidemiological determinants of cholera and other enteric pathogens among hospitalized diarrheal patients from FDMNs and host community. Methods A total of 11 sentinel surveillance sites were established around the camps in Ukhia and Teknaf Upazila, Cox’s Bazar. Rapid diagnostic testing was conducted for immediate detection of cholera cases. Stool samples were transferred to the Infectious Diseases Division, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) laboratory for culture. Results A total of 8134 participants with diarrhea were enrolled from 2017 to 2019: 4881 were FDMNs and 3253 were from the Bangladeshi host community. Among the FDMNs, the proportion of Vibrio cholerae was 0.7%, the proportion of enterotoxigenic Escherichia coli (ETEC) was 4.9%, and the proportion of Shigella was 1.5%. The distributions from host community were 1.2% V cholerae, 1.8% ETEC, and 1.1% Shigella. Similar risk factors have been identified for the diarrheal pathogens for both communities. Conclusions This surveillance helped to monitor the situation of diarrheal diseases including cholera in refugee camps as well as in the neighboring host community. These findings lead policymakers to take immediate preventive measures.
Unstable Childhood, Adult Adversity, and Smoking Accelerate Biological Aging Among Middle-Age African Americans: Similar Findings for GrimAge and PoAm

Objectives: The recent biological clocks GrimAge and PoAm are robust predictors of morbidity and mortality. Little research, however, has investigated the factors that influence their ticking speed. No study has used multivariate analyses to examine whether childhood adversity, adult hardship, lifestyle practices, or some combination of these factors best explains acceleration of these indices. Methods: Using a sample of 506 middle-age African Americans, the present study investigated the extent to which childhood instability, adult adversity, and lifestyle predict accelerated GrimAge and PoAm. Results: The two clocks were highly correlated and the pattern of findings was very similar for the two measures. Childhood instability, adult financial hardship, and smoking were significant predictors of both clocks. Discussion: The findings support a life course perspective where both the long arm of childhood as well as later life conditions influence speed of aging. Similar results across the two clocks enhance confidence in the findings.
Medication-related problems identified by pharmacists in an enhanced medication therapy management model.

OBJECTIVES To describe the types of clinically actionable medication-related problems (MRPs) identified and the types of resolving recommendations issued by pharmacists using an advanced clinical decision support system (CDSS) for Medicare Part D beneficiaries. STUDY DESIGN Retrospective cross-sectional study. METHODS We examined frequencies of MRPs and recommendations for beneficiaries who received a first-ever medication safety review (MSR) during plan years 2018-2019. MRPs were considered clinically actionable if implementation of a recommendation would alter the medication regimen. RESULTS Pharmacists identified ≥ 1 clinically actionable MRP for 82.4% (18,703/22,696) beneficiaries receiving an MSR. Among these beneficiaries, 36,455 MRPs were identified (mean [SD] number of MRPs: 1.9 [1.0]). "Adverse drug reaction" (n = 14,788; 40.6%), "drug interaction" (n = 9716; 26.7%), and "medication use without indication" (n = 6496; 17.8%) represented 85.0% of all MRPs. "Start alternative therapy" was most frequently recommended to resolve "adverse drug reactions" (6724/14,788; 45.5%), followed by "change time of administration" to resolve "drug interactions" (5189/9716; 53.4%) and "discontinue medication" to resolve "drug use without indication" (5718/6496; 88.0%). Overall, "start alternative therapy" (n = 12,219) and "discontinue medication" (n = 12,059) made up 66.6% of all recommendations. CONCLUSIONS In Medicare Part D beneficiaries, pharmacists using an advanced CDSS identified a substantial number of MRPs pertaining to medication safety and issued recommendations to decrease the risk of adverse drug events.
Correlation between serum miR-122 and myocardial damage and ventricular function in patients with essential hypertension

Background Myocardial damage and decreased ventricular function are risk factors leading to a bad prognosis in patients with essential hypertension (EH). MicroRNAs play important roles in myocardial function impairment in patients with hypertension. The purpose of our research was to investigate the correlation between serum miR-122 and myocardial damage and ventricular functions in EH patients. Methods The clinic data of EH patients (group A, n=60) and healthy individuals (group B, n=60) from December 2016 to December 2019 in our hospital were collected and analyzed. Serum miR-122, myocardial damage markers [B-type brain natriuretic peptide (BNP), homocysteine (Hcy), cardiac troponin T (cTnT) and creatine kinase MB isoenzyme (CK-MB)] and cardiac function indicators [ejection fraction (EF), left ventricular septal thickness (IVST), left ventricular isovolumic relaxation time (IVRT), left ventricular end-diastolic diameter (LVEDD), left ventricular posterior wall thickness (LVPWT), and left ventricular end-systolic diameter (LVESD)] were assessed in both groups. The correlation between serum miR-122 and myocardial damage markers and ventricular function indicators was analyzed. Results (I) The mean serum miR-122 concentration in group A and group B was 6.86±1.23 and 3.36±1.87 µmol/L, respectively. The serum miR-122 concentration in group A was evidently increased compared with that in group B. (II) The levels of BNP, Hcy, cTnT, and CK-MB in the peripheral blood in group A were evidently increased compared with those in group B (P<0.05). (III) EF and IVRT were evidently decreased in group A compared with that in group B (P<0.05). (IV) Serum miR-122 concentration was positively correlated with the myocardial damage markers BNP, Hcy, cTnT and CK-MB, and serum miR-122 concentration was negatively correlated with the ventricular function indicators EF and IVRT but not significantly correlated with other ventricular function indicators (IVST, LVEDD, LVPWT and LVESD). Conclusions The serum miR-122 concentration in EH patients was higher than that in healthy individuals, and miR-122 concentration was positively correlated with myocardial damage markers. Serum miR-122 level was negatively correlated with the ventricular function indicators EF and IVRT but was not significantly correlated with other ventricular function indicators (IVST, LVEDD, LVPWT, and LVESD).
Nonresponder bias in hand surgery: analysis of 1945 cases lost to follow-up over a 6-year period

The primary aim of this study was to identify factors associated with nonresponse to routinely collected patient-reported outcome measures (PROMs) after hand surgery. The secondary aim was to investigate the impact of nonresponder bias on postoperative PROMs. We identified 4357 patient episodes for which the patients received pre- and 1-year postoperative questionnaires. The response rate was 55%. Univariate and regression analyses were undertaken to determine factors predicting nonresponse. We developed a predictive model for the postoperative Quick version of the Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores for nonresponders using imputation. Younger age, increasing deprivation, higher comorbidity, worse preoperative QuickDASH scores and unemployment predicted nonresponse. No significant difference in mean postoperative QuickDASH score was observed between the responders, and the scores for the responders combined with the predicted scores for the nonresponders. Preoperative function was the primary predictor of postoperative outcome. These results challenge the dogma that ‘loss to follow-up’ automatically invalidates the results of a study. Level of evidence: III
Critical Item Analysis Enhances the Classification Accuracy of the Logical Memory Recognition Trial as a Performance Validity Indicator

ABSTRACT Objective : Replicate previous research on Logical Memory Recognition (LM Recog ) and perform a critical item analysis. Method : Performance validity was psychometrically operationalized in a mixed clinical sample of 213 adults. Classification of the LM Recog and nine critical items (CR-9) was computed. Results : LM Recog ≤20 produced a good combination of sensitivity (.30-.35) and specificity (.89-.90). CR-9 ≥5 and ≥6 had comparable classification accuracy. CR-9 ≥5 increased sensitivity by 4% over LM Recog ≤20; CR-9 ≥6 increased specificity by 6–8% over LM Recog ≤20; CR-9 ≥7 increased specificity by 8–15%. Conclusions : Critical item analysis enhances the classification accuracy of the optimal LM Recog cutoff (≤20).
Impact of septal myectomy on diastolic function in patients with obstructive hypertrophic cardiomyopathy

Background The impact of septal myectomy on diastolic function in patients with obstructive hypertrophic cardiomyopathy is not well studied. Methods A transcatheter hemodynamic study was performed before and 3 to 6 months after septal myectomy in 12 patients with obstructive hypertrophic cardiomyopathy (HCM). Results Postoperative hemodynamic studies were done 4.4±1.2 months after myectomy. The left ventricular outﬂow tract peak-to-peak gradient decreased from 83.2±43.3 mmHg preoperatively to 11.6±4.3 mmHg after myectomy (P<0.00). The left ventricular diastolic time constant (Tau) was 64.2±26.1 ms before surgery and 42.2±15.7 ms postoperatively (P=0.029). The average left atrial pressure (LAP) decreased from 20.2±7.0 to 12.1±4.5 mmHg after myectomy (P=0.008). Pulmonary artery hypertension was present in 6 patients preoperatively and remained in 2 patients after myectomy. Mean pulmonary artery pressure decreased from 29.3±16.2 to 20±6.7 mmHg after surgery (P=0.05), and the systolic pulmonary artery pressure decreased from 46±26.9 to 30.5±8.3 mmHg (P=0.048). Pulmonary vascular resistance decreased from 5.7±4.1 to 3.6±1.6 wood after surgery (P=0.032). Conclusions Septal myectomy improved left ventricular diastolic function and subsequently relieved the right ventricular congestion in patients with obstructive HCM.
The Black Box effect: sensory stimulation after learning interferes with the retention of long-term object location memory in rats

Reducing sensory experiences during the period that immediately follows learning improves long-term memory retention in healthy humans, and even preserves memory in patients with amnesia. To date, it is entirely unclear why this is the case, and identifying the neurobiological mechanisms underpinning this effect requires suitable animal models, which are currently lacking. Here, we describe a straightforward experimental procedure in rats that future studies can use to directly address this issue. Using this method, we replicated the central findings on quiet wakefulness obtained in humans: We show that rats that spent 1 h alone in a familiar dark and quiet chamber (the Black Box) after exploring two objects in an open field expressed long-term memory for the object locations 6 h later, while rats that instead directly went back into their home cage with their cage mates did not. We discovered that both visual stimulation and being together with conspecifics contributed to the memory loss in the home cage, as exposing rats either to light or to a cage mate in the Black Box was sufficient to disrupt memory for object locations. Our results suggest that in both rats and humans, everyday sensory experiences that normally follow learning in natural settings can interfere with processes that promote long-term memory retention, thereby causing forgetting in form of retroactive interference. The processes involved in this effect are not sleep-dependent because we prevented sleep in periods of reduced sensory experience. Our findings, which also have implications for research practices, describe a potentially useful method to study the neurobiological mechanisms that might explain why normal sensory processing after learning impairs memory both in healthy humans and in patients suffering from amnesia.
Phosphorylation of p53 by Cdk5 contributes to benzo[a]pyrene‐induced neuronal apoptosis

Benzo[a]pyrene (B[a]P) is a ubiquitous carcinogenic pollutant in the environment, however, the potential neurotoxic effects of B[a]P has not been elucidated clearly. In the present study, we explored the potential involvement of p53 phosphorylation by Cdk5 in B[a]P‐induced neuronal apoptosis at both in vitro and in vivo settings. For in vitro studies, primary cortical neurons isolated from the brains of Sprague Dawley (SD) rat pup were exposed to 0, 10, 20, and 40 μM of B[a]P for 12, 24, or 48 h. For in vivo studies, SD rats were injected intraperitoneally with 0, 1.0, 2.5, and 6.25 mg/kg of B[a]P every other day for 1, 2, or 3 months. Our results demonstrated that exposure to B[a]P caused a dose‐ and a time‐dependent increase in neuronal apoptotic ratio in both in vitro and in vivo studies. There was also a dose‐ and a time‐dependent upregulation of p35, p25, Cdk5, and phosphorylated p53 at Ser15 after B[a]P exposure. In order to explore whether B[a]P‐induced increased neuronal apoptosis was through Cdk5/p53 pathway, roscovitine, a specific Cdk5 inhibitor, was applied to pretreat neurons prior to B[a]P exposure. The results showed that pretreatment of neurons with roscovitine partially rescued cells from B[a]P‐induced apoptosis, and alleviated B[a]P‐induced upregulation of phosphorylated p53 at Ser15. Our results suggest that Cdk5/p53 signaling pathway may be involved in B[a]P‐induced neuronal apoptosis, which will provide information to further elucidate the molecular mechanisms of B[a]P‐induced neurotoxicity.
Waiting for a Match: Mitigating Reactance in Prosocial Health Behavior Using Psychological Distance

ABSTRACT This study examined how psychological distance, both social and temporal, can be leveraged in prosocial health behavior messages to mitigate perceived psychological reactance. Following the construal level and psychological reactance theories, we conducted a 2 × 2 between-subjects factorial design (N = 245), which manipulated naturalistic messages regarding a prosocial communications campaign. Structural equation modeling showed that far temporal distance combined with far social distance could significantly reduce threat to freedom and therefore positively affect attitudes and behavioral intentions toward prosocial health topics. The effect of social distance was found not significant, differing from past findings. Further, intertwined and parallel psychological reactance models were tested and discussed. We suggest the need for more psychological reactance research, particularly examining prosocial health behavior. Strategies for practical persuasion strategies in prosocial messages are proposed.