Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study

Objectives To evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls. Methods A prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2–6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2–6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample. Results The two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, p<0.0001, and 96.55% versus 74.26%, p<0.0001 at 2–6 weeks and at 6 months, respectively. The third vaccine dose restored the seropositive response in all controls and 80.47% of patients with AIIRD, p=0.0028. All patients treated with methotrexate monotherapy, anticytokine biologics, abatacept and janus kinase (JAK) inhibitors regained the humoral response after the third vaccine, compared with only a third of patients treated with rituximab, entailing a 16.1-fold risk for a negative humoral response, p≤0.0001. Cellular immune response in rituximab-treated patients was preserved before and after the third vaccine and was similar to controls. Breakthrough COVID-19 rate during the Delta surge was similar in patients and controls, 1.83% versus 1.43%, p=1. Conclusions The two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients.
Prone restraint cardiac arrest in in‐custody and arrest‐related deaths

We postulate that most atraumatic deaths during police restraint of subjects in the prone position are due to prone restraint cardiac arrest (PRCA), rather than from restraint asphyxia or a stress‐induced cardiac condition, such as excited delirium. The prone position restricts ventilation and diminishes pulmonary perfusion. In the setting of a police encounter, metabolic demand will be high from anxiety, stress, excitement, physical struggle, and/or stimulant drugs, leading to metabolic acidosis and requiring significant hyperventilation. Although oxygen levels may be maintained, prolonged restraint in the prone position may result in an inability to adequately blow off CO2, causing blood pCO2 levels to rise rapidly. The uncompensated metabolic acidosis (low pH) will eventually result in loss of myocyte contractility. The initial electrocardiogram rhythm will generally be either pulseless electrical activity (PEA) or asystole, indicating a noncardiac etiology, more consistent with PRCA and inconsistent with a primary role of any underlying cardiac pathology or stress‐induced cardiac etiology. We point to two animal models: in one model rats unable to breathe deeply due to an external restraint die when their metabolic demand is increased, and in the other model, pressure on the chest of rats results in decreased venous return and cardiac arrest rather than death from asphyxia. We present two cases of subjects restrained in the prone position who went into cardiac arrest and had low pHs and initial PEA cardiac rhythms. Our cases demonstrate the danger of prone restraint and serve as examples of PRCA.
Intergenerational transmission of lifetime stressor exposure in adolescent girls at differential maternal risk for depression.

OBJECTIVE Adolescent girls who grow up with mothers who are depressed are themselves highly vulnerable to developing depression (i.e., "intergenerational transmission of depression"). Stressor exposure is a strong risk factor for depression, and the transmission of depression risk from mothers to daughters is partly due to mothers experiencing more stressors, increasing daughters' stressor burden. However, research in this area has only assessed recent stressors, making the role of cumulative lifetime stressors unclear. METHOD To address this issue, we recruited 52 dyads of mothers and adolescent daughters, of which 22 daughters were at high maternal risk for depression. Participants completed diagnostic interviews, and daughters additionally self-reported their depressive symptoms. Participants also completed the Stress and Adversity Inventory, a new-generation instrument for assessing cumulative lifetime history of acute and chronic stressors based on the contextual threat approach. We tested moderated mediation models evaluating the conditional indirect effects of mothers' lifetime stressors on high- versus low-risk daughters' depressive symptoms through daughters' lifetime stressors. RESULTS As hypothesized, mothers of high-risk (but not low-risk) adolescent daughters who reported more lifetime acute stressors had daughters who reported more lifetime acute stressors and current depressive symptoms. Moreover, this finding was driven specifically by mothers' stressors occurring after their daughters' births. There was also tentative evidence that high-risk daughters' lifetime chronic stressors potentiated the impact of daughters' acute stressors on their depressive symptoms. CONCLUSION These findings provide new insights into how stressful contexts are transmitted intergenerationally.
Caregiver‐reported household food insecurity and child‐reported food insecurity in relation to eating disorder risk factors and symptoms among preadolescent children

Abstract Objective To examine the relation of caregiver‐reported household food insecurity (FI) and child‐reported FI with eating disorder (ED) risk factors and symptoms, including effect modification by gender, in preadolescent children. Method Data were from the Family Food Study, a cross‐sectional study of households with incomes ≤200% of the federal poverty line in southeastern Michigan. Children aged 8–10 years (n = 194) and their female primary caregivers reported separately on FI status. Children reported ED risk factors/symptoms via the 24‐item Children's Eating Attitudes Test (ChEAT‐24), with higher scores indicating more ED risk factors/symptoms. Linear mixed models were used to examine associations between FI measures with the ChEAT‐24 total score, plus subscale scores for dieting, food preoccupation, weight preoccupation, vomiting, and social pressure to eat/gain weight. Models were adjusted for child age, child gender, caregiver race/ethnicity, caregiver education, and household income. Results Among all children, child‐reported FI, but not caregiver‐reported household FI, was associated with more ED risk factors/symptoms. Child‐reported FI (vs. no FI) was associated with higher average ChEAT‐24 total score (β = 2.41, 95% CI: 0.57, 4.25). Child‐reported FI was also associated with more food preoccupation, more weight preoccupation, and more social pressure to eat. Caregiver‐reported household FI was marginally associated with less dieting in girls, and child‐reported FI was associated with more dieting in boys. Discussion Child‐reported FI may be more salient than caregiver‐reported household FI as a risk factor for ED‐related outcomes in preadolescent children. Gender may modify the association between FI and dieting behavior. Public Significance Statement More child‐reported food insecurity, but not parent‐reported household food insecurity, was associated with more eating disorder risk factors and symptoms among preadolescent boys and girls. These findings emphasize the need for future studies that investigate the role of food insecurity in the development of eating disorders, especially studies that measure child‐reported experience of food insecurity.
Ozonated oil is effective at killing Candida species and Streptococcus mutans biofilm-derived cells under aerobic and microaerobic conditions.

This study explores the growth of bacterial, fungal, and interkingdom biofilms under aerobiosis or microaerobic conditions and the effect of ozonated sunflower oil on these biofilms. Candida species and Streptococcus mutans were used to study this interaction due to their importance in oral health and disease as these microorganisms display a synergistic relationship that manifests in the onset of caries and tooth decay. Biofilms were developed in a 96-well microtiter plate at 37 ºC for 24 h, under aerobiosis or microaerobic conditions, and treated with ozonated oil for 5 to 120 min. All the microorganisms formed biofilms in both oxygenation conditions. Scanning electron microscopy was used to visualize biofilm morphology. Rodent experiments were performed to verify the oil-related toxicity and its efficacy in oral candidiasis. The growth of all Candida species was increased when co-cultured with S. mutans, whilst the growth of bacteria was greater only when co-cultured with C. krusei and C. orthopsilosis under aerobiosis and microaerobic conditions, respectively. Regardless of the oxygenation condition, ozonated oil significantly reduced the viability of all the tested biofilms and infected mice, showing remarkable microbicidal activity as corroborated with confocal microscopy and minimal toxicity. Thus, ozonated oil therapy can be explored as a strategy to control diseases associated with these biofilms especially in the oral cavity.
Impression management attenuates the effect of ability on trust in economic exchange

Significance It is often assumed that competent actors are trusted, but is this always true? In this report, we test the position that impression management decreases the amount of trust competent actors receive. Employing a variety of experimental paradigms and measures and confirming predictions based on attribution theory, we demonstrate that impression management can substantially backfire, at least for competent actors, and that this effect can be explained by decreases in perceived benevolence and integrity. Our findings make important contributions to the literatures on trust, status, and impression management.
Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration

Given that adult stem cells (ASCs) fuel homeostasis and healing by providing tissue-specific descendants, the fidelity of ASC fate determination is crucial for regeneration. Here, we established that an epigenetic control of epithelial ASC fate fidelity via Ezh2/H3K27me3 was indispensable for incisor homeostasis and regeneration. Mechanistically, in homeostasis, H3K27me3 upstream occupies the Sonic hedgehog (Shh) promoter to directly restrain Shh expression, thereby precisely confining Shh expression. When injury occurred, Ezh2/H3K27me3 was substantially induced within inner enamel epithelium and preameloblast zones, and such epigenetic response guaranteed the fidelity of ASC commitment via pulling injury-increased Shh back to homeostatic levels, utterly underlying regeneration progression. Once losing H3K27me3-dependent restriction of Shh expression through the Cre-Loxp system totally disrupted lineage commitment and stemness exhaustion, and abolished hard tissue regeneration emerged in vivo. We next uncovered the molecular mechanisms by which injury-induced Ezh2 mediated the spatiotemporal dynamics of H3K27me3 to repress Shh expression, thus epigenetically deciding ASC fate.
Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification

Abstract Aim Lipoprotein(a) [Lp(a)] is a potential causal factor in the pathogenesis of aortic valve disease. However, the relationship of Lp(a) with new onset and progression of aortic valve calcium (AVC) has not been studied. The purpose of the study was to assess whether high serum levels of Lp(a) are associated with AVC incidence and progression. Methods and results A total of 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men), whose Lp(a) measurements were available, underwent non-enhanced cardiac computed tomography imaging at baseline and after a median follow-up of 14.0 [interquartile range (IQR) 13.9–14.2] years. New-onset AVC was defined as an AVC score >0 on the follow-up scan in the absence of AVC on the first scan. Progression was defined as the absolute difference in AVC score between the baseline and follow-up scan. Logistic and linear regression analyses were performed to evaluate the relationship of Lp(a) with baseline, new onset, and progression of AVC. All analyses were corrected for age, sex, body mass index, smoking, hypertension, dyslipidaemia, and creatinine. AVC progression was analysed conditional on baseline AVC score expressed as restricted cubic splines. Of the 702 individuals without AVC at baseline, 415 (59.1%) developed new-onset AVC on the follow-up scan. In those with baseline AVC, median annual progression was 13.5 (IQR = 5.2–37.8) Agatston units (AU). Lipoprotein(a) concentration was independently associated with baseline AVC [odds ratio (OR) 1.43 for each 50 mg/dL higher Lp(a); 95% confidence interval (CI) 1.15–1.79] and new-onset AVC (OR 1.30 for each 50 mg/dL higher Lp(a); 95% CI 1.02–1.65), but not with AVC progression (β: −71 AU for each 50 mg/dL higher Lp(a); 95% CI −117; 35). Only baseline AVC score was significantly associated with AVC progression (P < 0.001). Conclusion In the population-based Rotterdam Study, Lp(a) is robustly associated with baseline and new-onset AVC but not with AVC progression, suggesting that Lp(a)-lowering interventions may be most effective in pre-calcific stages of aortic valve disease.
Germline Pathogenic Variant Prevalence Among Latin American and US Hispanic Individuals Undergoing Testing for Hereditary Breast and Ovarian Cancer: A Cross-Sectional Study

PURPOSE To report on pathogenic germline variants detected among individuals undergoing genetic testing for hereditary breast and/or ovarian cancer (HBOC) from Latin America and compare them with self-reported Hispanic individuals from the United States. METHODS In this cross-sectional study, unrelated individuals with a personal/family history suggestive of HBOC who received clinician-ordered germline multigene sequencing were grouped according to the location of the ordering physician: group A, Mexico, Central America, and the Caribbean; group B, South America; and group C, United States with individuals who self-reported Hispanic ethnicity. Relatives who underwent cascade testing were analyzed separately. RESULTS Among 24,075 unrelated probands across all regions, most were female (94.9%) and reported a personal history suggestive of HBOC (range, 65.0%-80.6%); the mean age at testing was 49.1 ± 13.1 years. The average number of genes analyzed per patient was highest in group A (A 63 ± 28, B 56 ± 29, and C 40 ± 28). Between 9.1% and 18.7% of patients had pathogenic germline variants in HBOC genes (highest yield in group A), with the majority associated with high HBOC risk. Compared with US Hispanics individuals the overall yield was significantly higher in both Latin American regions (A v C P = 1.64×10–9, B v C P < 2.2×10–16). Rates of variants of uncertain significance were similar across all three regions (33.7%-42.6%). Cascade testing uptake was low in all regions (A 6.6%, B 4.5%, and C 1.9%). CONCLUSION This study highlights the importance of multigene panel testing in Latin American individuals with newly diagnosed or history of HBOC, who can benefit from medical management changes including targeted therapies, eligibility to clinical trials, risk-reducing surgeries, surveillance and prevention of secondary malignancy, and genetic counseling and subsequent cascade testing of at-risk relatives.
Correlation of p53 immunohistochemistry with TP53 mutational status and overall survival in newly diagnosed acute myeloid leukaemia

TP53‐mutated acute myeloid leukaemia (AML) is associated with an adverse prognosis and poor response to traditional chemotherapy regimens. Next‐generation sequencing (NGS) is considered the gold standard method to determine TP53‐mutational status; however, molecular assays are costly and time‐consuming. In contrast, immunohistochemistry (IHC) can be performed within 1 day of biopsy. We sought to determine an optimal threshold of staining with p53 IHC to predict TP53‐mutational status.
Combination of Focused Ultrasound, Immunotherapy, and Chemotherapy

Focused ultrasound is a treatment modality increasingly used for diverse therapeutic applications, and currently approved for several indications, including prostate cancers and uterine fibroids. But what about breast cancer? Breast cancer is the most common and deadliest cancer in women worldwide. While there are different treatment strategies available, there is a need for development of more effective and personalized modalities, with fewer side effects. Therapeutic ultrasound is such an option, and this review summarizes the state of the art in their use for the treatment of breast cancer and evaluate potentials of novel treatment approaches combining therapeutic ultrasound, immuno‐ and chemo‐therapies.
Multiplexed high-throughput localized electroporation workflow with deep learning–based analysis for cell engineering

Manipulation of cells for applications such as biomanufacturing and cell-based therapeutics involves introducing biomolecular cargoes into cells. However, successful delivery is a function of multiple experimental factors requiring several rounds of optimization. Here, we present a high-throughput multiwell-format localized electroporation device (LEPD) assisted by deep learning image analysis that enables quick optimization of experimental factors for efficient delivery. We showcase the versatility of the LEPD platform by successfully delivering biomolecules into different types of adherent and suspension cells. We also demonstrate multicargo delivery with tight dosage distribution and precise ratiometric control. Furthermore, we used the platform to achieve functional gene knockdown in human induced pluripotent stem cells and used the deep learning framework to analyze protein expression along with changes in cell morphology. Overall, we present a workflow that enables combinatorial experiments and rapid analysis for the optimization of intracellular delivery protocols required for genetic manipulation.
Exercise-Induced Fatigue in Hamstring versus Quadriceps Muscles and Consequences on the Torque–Duration Relationship in Men

ABSTRACT Purpose The present study investigated the mechanisms of neuromuscular fatigue in quadriceps and hamstring muscles and its consequences on the torque–duration relationship. Methods Twelve healthy men performed a 5-min all-out exercise (3-s contraction, 2-s relaxation) with either quadriceps or hamstring muscles on separate days. Central fatigue and peripheral fatigue were quantified via changes in pre- to postexercise voluntary activation (VA) and potentiated twitch (PTw) torque evoked by supramaximal electrical stimulation, respectively. Critical torque was determined as the mean torque of the last six contractions, whereas W′ was calculated as the torque impulse done above critical torque. Results After exercise, maximal voluntary contraction (MVC) decreased to a greater magnitude (P < 0.001) in quadriceps (−67% ± 9%) compared with hamstring (−51% ± 10%). ∆PTw was also greater in quadriceps compared with hamstring (−69% ± 15% vs 55% ± 10%, P < 0.01), whereas central fatigue only developed in quadriceps (∆VA, −25% ± 28%). Hamstring demonstrated reduced critical torque compared with quadriceps (60 ± 12 vs 97 ± 26 N·m, P < 0.001) as well as drastically lower W′ (1001 ± 696 vs 8111 ± 2073 N·m·s, P < 0.001). No correlation was found between quadriceps and hamstring for any index of neuromuscular fatigue (∆MVC, ∆PTw, or ∆VA). Conclusions These findings revealed that hamstring presented different etiology and magnitude of neuromuscular fatigue compared with quadriceps. The absence of correlation observed between quadriceps and hamstring fatigue parameters (∆MVC, ∆PTw, or ∆VA) suggests no interrelation in fatigue etiology between these two muscle groups within individuals and, therefore, highlights the need to investigate specifically hamstring muscle fatigue.
Evaluation of sperm chromatin/DNA integrity, morphology, and Catsper expression on diabetic C57BL/6 mice.

BACKGROUND Diabetes is associated with reproductive impairment on the male reproductive system and causes complications such as decreased libido, fertility, spermatogenesis, sperm motility, and morphology. High levels of blood sugar may affect sperm quality and reduce the potential for male fertility. Increased levels of sperm DNA damage is often associated with reduced count and motility or abnormal morphology. METHODS This experimental study was conducted in Mashhad University of Medical Sciences. In this work, 40 mice (C57BL/6) were divided randomly into 4 groups: 1) Control, 2) Diabetic, 3) Diabetic + Insulin, and 4) Sham. After 35 days, the right epididymis of all specimens was used for Real-Time PCR and left epididymis for evaluation of sperm parameters using Aniline blue, Toluidine blue, Papanicolaou, and immunohistochemical study. Also, testes were applied for immunohistochemical, TUNEL studies, and biochemical assay. RESULTS Results of this study showed that chromatin integrity, morphology, cation channels of sperm (Catsper) expression, and biochemical factors level were significantly changed in diabetic mice in comparison to other groups (P<0.05) and treatment with insulin improved these parameters. CONCLUSION Our findings showed that the sperm parameters such as DNA integrity, morphology, and Catsper expression change in diabetic mice.