Miracle-dz/UniFAR-FTUs huggingface dataset:
Accelerometer-derived physical activity and risk of atrial fibrillation.

AIMS Physical activity may be an important modifiable risk factor for atrial fibrillation (AF), but associations have been variable and generally based on self-reported activity. METHODS AND RESULTS We analysed 93 669 participants of the UK Biobank prospective cohort study without prevalent AF who wore a wrist-based accelerometer for 1 week. We categorized whether measured activity met the standard recommendations of the European Society of Cardiology, American Heart Association, and World Health Organization [moderate-to-vigorous physical activity (MVPA) ≥150 min/week]. We tested associations between guideline-adherent activity and incident AF (primary) and stroke (secondary) using Cox proportional hazards models adjusted for age, sex, and each component of the Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) risk score. We also assessed correlation between accelerometer-derived and self-reported activity. The mean age was 62 ± 8 years and 57% were women. Over a median of 5.2 years, 2338 incident AF events occurred. In multivariable adjusted models, guideline-adherent activity was associated with lower risks of AF [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75-0.89; incidence 3.5/1000 person-years, 95% CI 3.3-3.8 vs. 6.5/1000 person-years, 95% CI 6.1-6.8] and stroke (HR 0.76, 95% CI 0.64-0.90; incidence 1.0/1000 person-years, 95% CI 0.9-1.1 vs. 1.8/1000 person-years, 95% CI 1.6-2.0). Correlation between accelerometer-derived and self-reported MVPA was weak (Spearman r = 0.16, 95% CI 0.16-0.17). Self-reported activity was not associated with incident AF or stroke. CONCLUSIONS Greater accelerometer-derived physical activity is associated with lower risks of AF and stroke. Future preventive efforts to reduce AF risk may be most effective when targeting adherence to objective activity thresholds.
Targeting nectin-4 by antibody-drug conjugates for the treatment of urothelial carcinoma

ABSTRACT Introduction Nectin-4 is a tumor-associated antigen overexpressed in urothelial carcinoma and several other malignancies. It has emerged as a compelling target for novel tumor-directed therapies, particularly as a component of antibody-drug conjugates (ADCs), a growing class of anti-cancer therapeutic agents. Development of nectin-4-directed therapies has been led by enfortumab vedotin (EV), an ADC comprised of a fully human monoclonal antibody specific for nectin-4 conjugated via a cleavable linker to the microtubule inhibitor MMAE. EV was approved in 2019 as a first-in-class agent for the treatment of urothelial carcinoma. Areas covered This article discusses general principles relevant to ADC design and our current understanding of nectin-4 in normal physiology and malignancy, followed by a review of the development of EV as well as additional drug conjugate strategies targeting nectin-4. Expert opinion EV offers proof-of-concept for the clinical utility of nectin-4-directed therapies and provides further support for ADCs as an important class of anti-cancer agents. Future development of nectin-4-targeted approaches will benefit from a deeper understanding of nectin-4 biology in both health and disease, as well as a detailed exploration of the mechanisms underlying therapeutic activity and resistance.
Profiling Active Enzymes for Polysorbate Degradation in Biotherapeutics by Activity-Based Protein Profiling

Polysorbate is widely used to maintain stability of biotherapeutic proteins in formulation development. Degradation of polysorbate can lead to particle formation in drug products, which is a major quality concern and potential patient risk factor. Enzymatic activity from residual enzymes such as lipases and esterases can cause polysorbate degradation. Their high activity, even at low concentration, constitutes a major analytical challenge. In this study, we evaluated and optimized the activity-based protein profiling (ABPP) approach to identify active enzymes responsible for polysorbate degradation. Using chemical probes to enrich active serine hydrolases, more than 80 proteins were identified in harvested cell culture fluid (HCCF) from monoclonal antibodies (mAb) production. A total of 8 known lipases were identified by ABPP, while only 5 lipases were identified by a traditional abundance-based proteomics (TABP) approach. Interestingly, phospholipase B-like 2 (PLBL2), a well-known problematic HCP was not found to be active in process-intermediates from two different mAbs. In a proof-of-concept study, phospholipase A2 group VII (PLA2G7) and sialic acid acetylesterase (SIAE) were identified by ABPP as possible root causes of polysorbate-80 degradation. The established ABBP approach can fill the gap between lipase abundance and activity, which enables more meaningful polysorbate degradation investigations for biotherapeutic development.
Pathogen-specific changes in composition and quality traits of milk from goats affected by subclinical intramammary infections

Abstract We investigated the effects of pathogens associated with subclinical intramammary infections on yield, composition and quality indicators of goat milk. By means of a longitudinal study, individual half udder milk samples (n = 132) were collected at different lactation periods and assessed for milk yield and physicochemical composition, somatic cell count (SCC), total bacteria count (TBC) and microbiological culture. Staphylococci species accounted for the great majority of the isolates (96.1%). Intramammary infections significantly reduced fat and total solids in goat milk and increased both SCC and TBC. However, these indicators were significantly higher in udder halves affected by S. aureus compared with other staphylococci species.
Improved first trimester maternal iodine status with preconception supplementation: The Women First Trial

Abstract Maternal iodine (I) status is critical in embryonic and foetal development. We examined the effect of preconception iodine supplementation on maternal iodine status and on birth outcomes. Non‐pregnant women in Guatemala, India and Pakistan (n ~ 100 per arm per site) were randomized ≥ 3 months prior to conception to one of three intervention arms: a multimicronutrient‐fortified lipid‐based nutrient supplement containing 250‐μg I per day started immediately after randomization (Arm 1), the same supplement started at ~12 weeks gestation (Arm 2) and no intervention supplement (Arm 3). Urinary I (μg/L) to creatinine (mg/dl) ratios (I/Cr) were determined at 12 weeks for Arm 1 versus Arm 2 (before supplement started) and 34 weeks for all arms. Generalized linear models were used to assess the relationship of I/Cr with arm and with newborn anthropometry. At 12 weeks gestation, adjusted mean I/Cr (μg/g) for all sites combined was significantly higher for Arm 1 versus Arm 2: (203 [95% CI: 189, 217] vs. 163 [95% CI: 152, 175], p < 0.0001). Overall adjusted prevalence of I/Cr < 150 μg/g was also lower in Arm 1 versus Arm 2: 32% (95% CI: 26%, 38%) versus 43% (95% CI: 37%, 49%) (p = 0.0052). At 34 weeks, adjusted mean I/Cr for Arm 1 (235, 95% CI: 220, 252) and Arm 2 (254, 95% CI: 238, 272) did not differ significantly but were significantly higher than Arm 3 (200, 95% CI: 184, 218) (p < 0.0001). Nominally significant positive associations were observed between I/Cr at 12 weeks and birth length and head circumference z‐scores (p = 0.028 and p = 0.005, respectively). These findings support the importance of first trimester iodine status and suggest need for preconception supplementation beyond salt iodization alone.
TRIM44 facilitates ovarian cancer proliferation, migration, and invasion by inhibiting FRK.

Ovarian cancer (OC) is the leading cause of gynecologic cancer-related death in the world. Accumulating evidence indicated the important role of TRIM44 in cancer development. However, how TRIM44 displays in OC and the underlying mechanism remained unclear. TRIM44 and FRK expression in OC tissues and cell lines were investigated by western blot and RT-qPCR. Histotype of tissue samples and patients' data were analyzed. Kaplan-Meier Curve was performed to validate the effect of TRIM44. Colony formation assay, MTT assay, Transwell assay, and wound-healing assay were applied to elucidate the function of TRIM44 in OC cells. CHIP assay was used to explore the association between TRIM44 and FRK. Finally, we performed SKOV3 xenografts in Balb/c nude mice to further confirm the involvement of TRIM44 in OC development. We found TRIM44 highly expressed while FRK displayed low expression in OC cell lines and tissues. Moreover, analysis of histotype of tissues and patients' data and Kaplan-Meier Curve implied the important role of TRIM44 and FRK in tumor progression. Further in vitro study suggested knocking down TRIM44 inhibited OC cells proliferation, migration, and invasion. Besides, FRK was identified as the target gene of TRIM44 in OC, and TRIM44 promoted OC cells proliferation, migration, and invasion by inhibiting FRK. Finally, in vivo animal experiment further confirmed the promotive effect of TRIM44 on OC progression. Our findings demonstrated that TRIM44 facilitated OC proliferation, migration, and invasion by inhibiting FRK, providing new insights for theoretical research and therapy of OC.
From coarse to fine: the absolute Escherichia coli proteome under diverse growth conditions

Accurate measurements of cellular protein concentrations are invaluable to quantitative studies of gene expression and physiology in living cells. Here, we developed a versatile mass spectrometric workflow based on data‐independent acquisition proteomics (DIA/SWATH) together with a novel protein inference algorithm (xTop). We used this workflow to accurately quantify absolute protein abundances in Escherichia coli for > 2,000 proteins over > 60 growth conditions, including nutrient limitations, non‐metabolic stresses, and non‐planktonic states. The resulting high‐quality dataset of protein mass fractions allowed us to characterize proteome responses from a coarse (groups of related proteins) to a fine (individual) protein level. Hereby, a plethora of novel biological findings could be elucidated, including the generic upregulation of low‐abundant proteins under various metabolic limitations, the non‐specificity of catabolic enzymes upregulated under carbon limitation, the lack of large‐scale proteome reallocation under stress compared to nutrient limitations, as well as surprising strain‐dependent effects important for biofilm formation. These results present valuable resources for the systems biology community and can be used for future multi‐omics studies of gene regulation and metabolic control in E. coli.
Repetition Suppression in Visual and Auditory Modalities Affects the Sound-Induced Flash Illusion

Sound-induced flash illusion (SiFI) refers to the illusion that the number of visual flashes is equal to the number of auditory sounds when the visual flashes are accompanied by an unequal number of auditory sounds presented within 100 ms. The effect of repetition suppression (RS), an adaptive effect caused by stimulus repetition, upon the SiFI has not been investigated. Based on the classic SiFI paradigm, the present study investigated whether RS would affect the SiFI differently by adding preceding stimuli in visual and auditory modalities prior to the appearance of audiovisual stimuli. The results showed the auditory RS effect on the SiFI varied with the number of preceding auditory stimuli. The hit rate was higher with two preceding auditory stimuli than one preceding auditory stimulus in fission illusion, but it did not affect the size of the fusion illusion. However, the visual RS had no effect on the size of the fission and fusion illusions. The present study suggested that RS could affect the SiFI, indicating that the RS effect in different modalities would differentially affect the magnitude of the SiFI. In the process of multisensory integration, the visual and auditory modalities had asymmetrical RS effects.
Psychological exhaustion of nursing professionals who care for patients with neoplasms.

OBJECTIVE Identify, analyze and understand the social representations of nursing professionals about burnout syndrome. METHOD Qualitative study with nursing professionals who worked in the direct assistance to oncologic patients, conducted through semi-structured interview, using the technique of content analysis, anchoring the interpretations in the theory of social representations. RESULTS Seven professionals participated; after analysis, two categories emerged: "The stress of professionals, the naturalization of suffering and self-care strategies"; and "Ressignifications, learning in the oncologic sector and network gaps". The representations about stress and the relationship of the professionals with the daily practice were predominant. FINAL CONSIDERATIONS The nursing professionals represented the burnout syndrome socially as stress and made important reflections on the subject in the context of daily work. Concepts that determine the behavior of professionals were perceived as mechanisms of confrontation. In the vision of this social group, spirituality was revealed as a therapeutic strategy.
Cognitive and body manifestations of driving anxiety according to different onsets

Abstract Background: Driving anxiety can have deleterious effects not only on driving behavior, but also on life quality. The interaction between motor vehicle collision (MVC) experiences and driving anxiety has been studied from different standpoints. However, the comparison with other events triggering it has been scarcely considered. Objectives: To analyze the body manifestations and the driving cognitions related to the accident, social and panic concerns in people suffering from different levels of driving anxiety. Method : A total of 260 participants suffering from driving anxiety were included in a survey, including Driving Cognition Questionnaire and Body Sensation Questionnaire. Results: Panic attacks and criticisms are the most relevant onsets of driving anxiety, more than MVC. Only 11.4% of MVC victims considered it as the onset. People with MVC history showed lower scores in social concerns than people without MVC experience and neither the responsibility of the MVC nor the role (driver/passenger) seemed to have an impact on the anxiety level. Conclusions: Although the most relevant body sensations, heart palpitations and sweating, were the same in people with panic attack experiences and MVC victims, a discrimination of the emotions behind the concept of “driving anxiety” is desirable to clarify the psychological effects of different onsets.
Morphological variations and prevalence of aberrant traits of primary molars

Abstract Background Morphological variations in tooth structure exhibit as metric and non-metric traits which play an important role in dental anthropology. Aim The purpose of this study was to determine the prevalence of morphometric traits and mean crown dimensions of primary molars in children Subjects and methods This cross-sectional study was carried out in 4256 sectional dye casts of caries-free children aged 2.5–4 years from Puducherry. Two calibrated examiners graded the non-metric traits utilising the Arizona State University Dental Anthropological System classification and measured the crown dimensions in primary molars. The results are expressed in the form of numbers and percentages. Results Of the eight non-metric traits studied, metaconule (30.17%), Cusp of Carabelli (90.6%), and deflecting wrinkle (87.41%) in second primary molars, and distal trigonid crest (93.06%) and parastyle (3.48%) in first primary molars, seemed to have higher prevalence, and the overall crown dimensions were found to be smaller in comparison with those in other populations. Conclusion This study highlights the prevalence of aberrant dental traits in primary molars in a population. The study describes, for the first time, the existence of these traits in first primary molars, adding anthropological significance of primary dentition in various other populations.
Doxazosin improved COVID-19 associated nightmare in a patient with major depressive disorder: a case report with a positive rechallenge

This article reports on the treatment of a patient with nightmares who was treated with doxazosin of an alpha 1-adrenergic antagonists. A 71-year-old Japanese major depressive disorder (MDD) woman experienced nightmares after the coronavirus disease 2019 pandemic. She had nightmares about being chased by a coronavirus and catching the corona virus. After adding doxazosin 1 mg daily in the morning, her nightmares led to remission without side effects. We also had a rechallenge regimen with doxazosin. The nightmares ceased on the second night of the rechallenge and did not return with continued treatment. This case report suggests that doxazosin may be a useful therapeutic option to target nightmares in individuals with MDD.
Systemic and mucosal mobilization of granulocyte subsets during lentivirus infection

Granulocytes mediate broad immunoprotection through phagocytosis, extracellular traps, release of cytotoxic granules, antibody effector functions and recruitment of other immune cells against pathogens. However, descriptions of granulocytes in HIV infection and mucosal tissues are limited. Our goal was to characterize granulocyte subsets in systemic, mucosal and lymphoid tissues during lentivirus infection using the rhesus macaque (RM) model. Mononuclear cells from jejunum, colon, cervix, vagina, lymph nodes, spleen, liver, and whole blood from naïve, and chronically SHIVsf162p3-infected RM were analyzed by microscopy and polychromatic flow cytometry. Granulocytes were identified using phenotypes designed specifically for RM: eosinophils – CD45+CD66+CD49d+; neutrophils – CD45+CD66+CD14+; and basophils – CD45+CD123+FcRε+. Nuclear visualization with DAPI staining and surface marker images by ImageStream (cytometry/microscopy) further confirmed granulocytic phenotypes. Flow cytometric data showed that all RM granulocytes expressed CD32 (FcRγII) but did not express CD16 (FcRγIII). Additionally, constitutive expression of CD64 (FcRγI) on neutrophils and FcRε on basophils, indicates the differential expression of Fc receptors on granulocyte subsets. Granulocytic subsets in naïve whole blood ranged 25.4-81.5% neutrophils, 0.59-13.3% eosinophils and 0.059-1.8% basophils. Interestingly, elevated frequencies of circulating neutrophils, colorectal neutrophils, and colorectal eosinophils were all observed in chronic lentivirus disease. Conversely, circulating basophils, jejunal eosinophils, vaginal neutrophils, and vaginal eosinophils of SHIVsf162p3-infected RM declined in frequency. Overall, our data suggest modulation of granulocytes in chronic lentivirus infection, most notably in the gastrointestinal mucosae where significant inflammation and disruption occurs in lentivirus-induced disease. Furthermore, granulocytes may migrate to inflamed tissues during infection and could serve as targets of immunotherapeutic intervention.
Satisfaction With Expectations-Based Education in Women Undergoing Breast Reconstruction

Women undergoing breast reconstruction sometimes have unrealistic or unformed expectations regarding the reconstructive process and outcomes. The objectives of this study were to assess preoperative expectations in women undergoing mastectomy and initial breast reconstruction, provide expectations-based education, and evaluate satisfaction with education. Fifty-one women undergoing mastectomy and breast tissue expander placement participated in this study. At a preoperative education appointment, participants completed a questionnaire to determine whether their expectations were realistic, unrealistic, or unformed. A nurse practitioner reviewed the results and provided patient-centered, expectations-based education to modify expectations from unrealistic to realistic or to set expectations from unformed to realistic. Four to 6 weeks after surgery, a second questionnaire was provided to assess perceived satisfaction with education. Unrealistic and unformed expectations were identified related to complications, pain, scarring, sensation, symmetry, and aesthetic results. After receiving patient-centered, expectations-based preoperative education, participants agreed they had received the appropriate amount of information and felt well prepared for their surgery and recovery. Most participants reported they were aware of possible complications, had effective tools to manage their pain, and had received adequate information about scarring and sensation changes. Some participants continued to have unrealistic or unformed expectations related to aesthetic results. Women undergoing breast reconstruction often have unrealistic or unformed expectations before surgery. Identifying these expectations and proving expectations-based education resulted in satisfaction with information provided.
Laser enucleation for prostates larger than 100 mL: Comparison of HoLEP and ThuLEP

Recently, with the advancements in laser technology, Holmium laser enucleation of the prostate (HoLEP) and Thulium laser enucleation of the prostate (ThuLEP) have come to the fore in the surgical treatment of benign prostatic hyperplasia (BPH). We aimed to evaluate and compare the outcomes of HoLEP and ThuLEP in patients with >100 ml prostate volume. Patients who underwent HoLEP and ThuLEP between July 2017 and March 2020 were reviewed retrospectively. The patients were divided into two groups as HoLEP (Group 1, n = 121) and ThuLEP (Group 2, n = 104). Perioperative parameters, functional outcomes, continence status, intra and post‐operative complications were compared between groups in the post‐operative 1st and 6th month. No significant difference was found in terms of total laser energy (TLE), morcellation efficiency (ME), enucleated tissue weight (ETW), complication rates (CR) and continence status of patients between both groups (p > .05). In favour of ThuLEP group, there were statistically significant differences regarding total operation time (TOT), laser efficiency (LE), enucleation time (ET) and enucleation efficiency (EE) between groups (p ≤ .05). HoLEP and ThuLEP can be used safely and effectively in prostates larger than 100 ml.
Electronic Modulation of Non‐van der Waals 2D Electrocatalysts for Efficient Energy Conversion

The exploration of efficient electrocatalysts for energy conversion is important for green energy development. Owing to their high surface areas and unusual electronic structure, 2D electrocatalysts have attracted increasing interest. Among them, non‐van der Waals (non‐vdW) 2D materials with numerous chemical bonds in all three dimensions and novel chemical and electronic properties beyond those of vdW 2D materials have been studied increasingly over the past decades. Herein, the progress of non‐vdW 2D electrocatalysts is critically reviewed, with a special emphasis on electronic structure modulation. Strategies for heteroatom doping, vacancy engineering, pore creation, alloying, and heterostructure engineering are analyzed for tuning electronic structures and achieving intrinsically enhanced electrocatalytic performances. Lastly, a roadmap for the future development of non‐vdW 2D electrocatalysts is provided from material, mechanism, and performance viewpoints.