Miracle-dz/UniFAR-FTUs huggingface dataset:
Crinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia

Abstract Context Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is characterized by impaired cortisol synthesis and excess androgen production. Corticotropin-releasing factor type 1 receptor (CRF1R) antagonism may decrease adrenal androgen production. Objective This work aimed to evaluate the safety, tolerability, and efficacy of crinecerfont (NBI-74788), a selective CRF1R antagonist, in 21OHD. Methods This open-label, phase 2 study, with sequential cohort design (NCT03525886), took place in 6 centers in the United States. Participants included men and women, aged 18 to 50 years, with 21OHD. Interventions included 4 crinecerfont regimens, each administered orally for 14 consecutive days: 50 or 100 mg once daily at bedtime (cohorts 1 and 2, respectively); 100 mg once daily in the evening (cohort 3); and 100 mg twice daily (cohort 4). Participants could enroll in more than 1 cohort. Main outcomes included changes from baseline to day 14 in adrenocorticotropin (ACTH), 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone. Results Eighteen participants (11 women, 7 men) were enrolled: cohort 1 (n = 8), cohort 2 (n = 7), cohort 3 (n = 8), cohort 4 (n = 8). Mean age was 31 years; 94% were White. Median percent reductions were more than 60% for ACTH (–66%), 17OHP (–64%), and androstenedione (–64%) with crinecerfont 100 mg twice a day. In female participants, 73% (8/11) had a 50% or greater reduction in testosterone levels; male participants had median 26% to 65% decreases in androstenedione/testosterone ratios. Conclusion Crinecerfont treatment for 14 days lowered ACTH and afforded clinically meaningful reductions of elevated 17OHP, androstenedione, testosterone (women), or androstenedione/testosterone ratio (men) in adults with 21OHD. Longer-term studies are required to evaluate the effects of crinecerfont on clinical end points of disordered steroidogenesis and glucocorticoid exposure in patients with 21OHD.
TAS2R38 polymorphisms, Helicobacter pylori infection and susceptibility to gastric cancer and premalignant gastric lesions

Background Gastric cancer is worldwide the fourth more common cancer type by incidence, and the third by mortality. We analyzed three missense variants of TAS2R38 gene: rs713598 (A49P), rs1726866 (V262A), and rs10246939 (I296V). These variants and their combination in haplotypes (proline, alanine and valine/tasters or alanine, valine and isoleucine/nontasters) and diplotypes are responsible for individual differences in bitter perception. The single-nucleotide polymorphisms and the related phenotypes are known to be associated with susceptibility to Gram-negative bacterial infections, such as Helicobacter pylori, and with risk of various cancer types. An association between intermediate tasters (as defined by TAS2R38 diplotypes) and increased risk of gastric cancer was reported in a Korean population. Methods We analyzed 2616 individuals of Latin American origin, representing the whole spectrum of lesions from gastritis to gastric cancer. Results Comparing cancer cases vs. noncancers we observed a decrease in risk associated with heterozygous carriers of rs10246939 (P = 0.006) and rs1726866 (P = 0.003) when compared with homozygotes of the more common allele. Also, the analysis of diplotypes/phenotypes reflected the same association, with super-tasters showing a borderline increased risk of developing gastric cancer compared to medium-tasters [odds ratio (OR) = 1.63; 95% confidence interval (CI), 1.04–2.56; P = 0.033]. Also, nontasters showed an increased risk when compared to medium-tasters although not reaching statistical significance (OR = 1.58; 95% CI, 0.80–2.87; P = 0.203). We also tested the interactions between the TAS2R38 genotypes and H. pylori cagA status in a subset of samples and found no interaction. Conclusion In conclusion, our results suggest only a modest contribution of TAS2R38 gene genetic variability in gastric cancer etiology.
Understanding the Presence of Mental Fatigue in Elite Female Football

ABSTRACT Purpose: Previous research investigating the impact of induced mental fatigue in football (soccer) has demonstrated associated performance decrements in physical, technical, tactical and decision-making performance. A common limitation amongst this research is the protocols used to induce mental fatigue which provides low ecological validity, and the inclusion of recreational or sub-elite players. Therefore, understanding the presence of mental fatigue in elite football can provide insight into protocols with greater ecological validity. Methods: The current study used focus groups with 10 elite female football players, focusing on five topics (travel, fixture congestion, receiving tactical information, pre-match routine and pressure to win) related to the perceived causes of mental fatigue in elite football (directed by anecdotal quotes in elite football and research-based theories). Results: Several themes emerged from the data; travel fatigue, inability to switch off from football, fatigue experienced following team meetings, use of pre-match music and internal pressure to succeed. Conclusion: These findings present practical recommendations to reduce mental fatigue in elite football settings, such as considering the timing, content and duration of team meetings, providing players with free time/rest where possible, and considering the modality of coaching instructions during matches.
Association of Sinusitis and Upper Respiratory Tract Diseases With Incident Rheumatoid Arthritis: A Case-control Study

Objective We aimed to determine whether specific respiratory tract diseases are associated with increased rheumatoid arthritis (RA) risk. Methods This case-control study within the Mass General Brigham Biobank matched newly diagnosed RA cases to 3 controls on age, sex, and electronic health record history. We identified RA using a validated algorithm and confirmed by medical record review. Respiratory tract disease exposure required 1 inpatient or 2 outpatient codes at least 2 years before the index date of RA clinical diagnosis or matched date. Logistic regression models calculated ORs for RA with 95% CIs, adjusting for confounders. We then stratified by serostatus (“seropositive” was positive rheumatoid factor and/or anticitrullinated protein antibodies) and smoking. Results We identified 741 RA cases and 2223 controls (both median age 55, 76% female). Acute sinusitis (OR 1.61, 95% CI 1.05–2.45), chronic sinusitis (OR 2.16, 95% CI 1.39–3.35), and asthma (OR 1.39, 95% CI 1.03–1.87) were associated with increased risk of RA. Acute respiratory tract disease burden during the preindex exposure period was also associated with increased RA risk (OR 1.30 per 10 codes, 95% CI 1.08–1.55). Acute pharyngitis was associated with seronegative (OR 1.68, 95% CI 1.02–2.74) but not seropositive RA; chronic rhinitis/pharyngitis was associated with seropositive (OR 2.46, 95% CI 1.01–5.99) but not seronegative RA. Respiratory tract diseases tended towards higher associations in smokers, especially > 10 pack-years (OR 1.52, 95% CI 1.02–2.27, P = 0.10 for interaction). Conclusion Acute and chronic sinusitis, pharyngitis, and acute respiratory burden increased RA risk. The mucosal paradigm of RA pathogenesis may involve the upper respiratory tract.
Association of Social Support With Overall Survival and Healthcare Utilization in Patients With Aggressive Hematologic Malignancies.

BACKGROUND Social support plays a crucial role for patients with aggressive hematologic malignancies as they navigate their illness course. The aim of this study was to examine associations of social support with overall survival (OS) and healthcare utilization in this population. METHODS A cross-sectional secondary analysis was conducted using data from a prospective longitudinal cohort study of 251 hospitalized patients with aggressive hematologic malignancies at Massachusetts General Hospital from 2014 through 2017. Natural Language Processing (NLP) was used to identify the extent of patients' social support (limited vs adequate as defined by NLP-aided chart review of the electronic health record). Multivariable regression models were used to examine associations of social support with (1) OS, (2) death or readmission within 90 days of discharge from index hospitalization, (3) time to readmission within 90 days, and (4) index hospitalization length of stay. RESULTS Patients had a median age of 64 years (range, 19-93 years), and most were White (89.6%), male (68.9%), and married (65.3%). A plurality of patients had leukemia (42.2%) followed by lymphoma (37.9%) and myelodysplastic syndrome/myeloproliferative neoplasm (19.9%). Using NLP, we identified that 8.8% (n=22) of patients had limited social support. In multivariable analyses, limited social support was associated with worse OS (hazard ratio, 2.00; P=.042) and a higher likelihood of death or readmission within 90 days of discharge (odds ratio, 3.11; P=.043), but not with time to readmission within 90 days or with index hospitalization length of stay. CONCLUSIONS In this cohort of hospitalized patients with aggressive hematologic malignancies, we found associations of limited social support with lower OS and a higher likelihood of death or readmission within 90 days of hospital discharge. These findings underscore the utility of NLP for evaluating the extent of social support and the need for larger studies evaluating social support in patients with aggressive hematologic malignancies.
Phase 1 Randomized, Placebo-Controlled, Dose-Escalating Study to Evaluate OVX836, a Nucleoprotein-Based Influenza Vaccine: Intramuscular Results

Abstract Background OVX836 is a recombinant protein vaccine targeting the highly conserved influenza nucleoprotein (NP), which could confer broad-spectrum protection against this disease. Methods A randomized, placebo-controlled, double-blind, dose-escalating, single- center, first-in-human study was conducted in 36 healthy adults aged 18–49 years. Twelve subjects per cohort (9 vaccine and 3 placebo) received 2 OVX836 intramuscular administrations on days 1 and 28 at the dose level of 30 µg, 90 µg, or 180 µg. Safety and immunogenicity were assessed after each vaccination and for 150 days in total. Results OVX836 was safe and well tolerated at all dose levels, with no difference in solicited local and systemic symptoms, and unsolicited adverse events between the first and second administration, or between dose levels. All subjects presented pre-existing NP-specific immunity at baseline. OVX836 induced a significant increase in NP-specific interferon-gamma T cells and anti-NP immunoglobulin G at all dose levels after the first vaccination. The second vaccination did not further increase the response. There was a trend for a dose effect in the immune response. Conclusions The safety and reactogenicity profile, as well as the humoral and cellular immune responses, encourage further evaluation of OVX836 in a larger Phase 2a study.
Polymorphism in cytochrome P4502A6 reduces the risk to head and neck cancer and modifies the treatment outcome

The present case–control study consisting of 1300 cases of head and neck squamous cell carcinoma (HNSCC) and the equal number of controls aimed to investigate the association of functionally important polymorphisms in cytochrome P4502A6 (CYP2A6*1B, CYP2A6*4C, CYP2A6*9‐rs28399433) with HNSCC and the treatment response in cases receiving a combination of chemotherapy/radiotherapy (CT/RT). A significant decrease in risk to HNSCC was observed in the cases with deletion (CYP2A6*4B and CYP2A6*4C) or reduced activity genotypes (CYP2A6*9) of CYP2A6. This risk to HNSCC was further reduced significantly in tobacco users among the cases when compared to nontobacco users among the cases. The risk was also reduced to a slightly greater extent in alcohol users among the cases when compared to nonalcohol users among the cases. In contrast with decreased risk to HNSCC, almost half of the cases with variant genotypes of CYP2A6 (CYP2A6*1A/*4C+*1B/*4C+*4C/*4C and *9/*9) did not respond to the treatment. Likewise, the survival rate in cases receiving the treatment, after 55 months of follow‐up was significantly lower in cases with deletion (6.3%) or reduced activity (11.9%) allele than in the cases with common alleles (41%). The present study has shown that CYP2A6 polymorphism significantly reduces the risk to HNSCC. Our data further suggested that CYP2A6 polymorphism may worsen the treatment outcome in the cases receiving CT/RT.
Utility of the Limited Prosocial Emotions Specifier in Preschoolers With Conduct Problems

This study examined the clinical utility of the “Limited Prosocial Emotions” (LPE) specifier (i.e., prevalence rates, group differences, and predictive utility) in a high-risk preschool sample (N = 109, M age = 4.77) presenting with conduct problems (CPs; n = 59). First, LPE prevalence rates ranged from 7.7% to 89.8%. Next, few group differences were observed between with CP-only and CP+LPE; youth with CP+LPE differed from youth with CP-only on callous-unemotional (CU) traits and verbal ability, but not on externalizing or internalizing psychopathology, nor on parenting experiences. In the full sample, youth with LPE differed from youth without LPE on externalizing and internalizing psychopathology, parenting, and verbal ability. Finally, LPE predicted greater baseline CP but did not predict trajectories of CP. Findings highlight the clinical utility of the LPE specifier during early childhood and call for a refinement of the LPE specifier to improve its clinical value.
Development of DO*A and DO*B Allele Detections to Predict Transfusion-Induced Alloimmunization Risks in Thai Populations.

BACKGROUND Two antithetical antigens, Doa and Dob of the Dombrock (DO) blood group system are implicated in acute to delayed hemolytic transfusion reactions among patients with anti-Doa or anti-Dob. Given the unavailability of specific antiserum, a polymerase chain reaction with sequence-specific primer (PCR-SSP) was developed to identify DO*A and DO*B alleles. This study aimed to determine DO*A and DO*B allele frequencies and to predict transfusion-induced alloimmunization risks in three Thai blood donor populations. METHODS DNA samples obtained from 1,300, 300, and 400 blood donors from central, northern, and southern Thailand, respectively, were genotyped for the DO*A and DO*B allele detections using developed PCR-SSP. The results were confirmed by DNA sequencing. RESULTS The validated genotyping results by PCR-SSP were in concordance with DNA sequencing. The DO*B/ DO*B was the most common genotype (77.0, 76.0, and 71.0%), followed by DO*A/DO*B (21.0, 22.7, and 25.2%) and DO*A/DO*A (2.0, 1.3, and 3.8%) among central, northern and southern Thais, respectively. The alleles found among central Thais showed significant differences from those found among southern Thais but not from those of northern Thais. The risk of anti-Doa production was higher than anti-Dob production among Thais. Concerning regional groups, the risk of Doa alloimmunization among southern Thais (0.2059) was higher than those among central (0.1771) and northern Thais (0.1824). CONCLUSIONS This was the first study to distinguish DO*A and DO*B genotypes in Thai populations using in-house PCR-SSP. This would be useful to predict alloimmunization risks that might result from transfusion-induced reactions of undetermined red cell antigens among blood donors and in reagent red cells.
Integrated emergency department and general intensive care unit management on health outcomes

The emergency department (ED) should reliably provide the required medical treatment to patients who are in an emergency or are critically ill. However, the ED faced two challenges in China. There were no limitations to the medical resources that could be accessed by ED patients, and health care providers could not deny patients. Thus, the ED was overcrowded, making it difficult to distinguish critically ill patients from those requiring non-emergency treatment.
Changes in selection pressure can facilitate hybridization during biological invasion in a Cuban lizard

Significance Hybridization is common in invasive species and can be important for their success. The connection between hybridization and bioinvasions could result in part because of a disruption in the selection pressures that limit hybridization in the native range. We demonstrate that, in the lizard Anolis sagrei, hybridization is rare in native populations, which show frequent evidence of natural selection at a large-effect X chromosome locus. Conversely, little selection at this locus was detected in invasive populations, which do not experience large-scale contemporary gene flow, but instead maintain a mosaic of hybrid ancestries formed during invasive range colonization. Ecological changes during biological invasions can affect hybridization frequency and stability, which can in turn drive the success of invasive taxa. Hybridization is among the evolutionary mechanisms most frequently hypothesized to drive the success of invasive species, in part because hybrids are common in invasive populations. One explanation for this pattern is that biological invasions coincide with a change in selection pressures that limit hybridization in the native range. To investigate this possibility, we studied the introduction of the brown anole (Anolis sagrei) in the southeastern United States. We find that native populations are highly genetically structured. In contrast, all invasive populations show evidence of hybridization among native-range lineages. Temporal sampling in the invasive range spanning 15 y showed that invasive genetic structure has stabilized, indicating that large-scale contemporary gene flow is limited among invasive populations and that hybrid ancestry is maintained. Additionally, our results are consistent with hybrid persistence in invasive populations resulting from changes in natural selection that occurred during invasion. Specifically, we identify a large-effect X chromosome locus associated with variation in limb length, a well-known adaptive trait in anoles, and show that this locus is often under selection in the native range, but rarely so in the invasive range. Moreover, we find that the effect size of alleles at this locus on limb length is much reduced in hybrids among divergent lineages, consistent with epistatic interactions. Thus, in the native range, epistasis manifested in hybrids can strengthen extrinsic postmating isolation. Together, our findings show how a change in natural selection can contribute to an increase in hybridization in invasive populations.
Perceived social support in the social distancing era: the association between circles of potential support and COVID-19 reactive psychopathology

ABSTRACT Background and Objectives Stressors related to the COVID-19 pandemic are risk factors for psychopathology, but psychosocial protective factors might play a crucial role in buffering the pathogenic effects of the outbreak. Design In the current study, we examined the association of inner resources and potential external sources of support for coping with the pandemic and related lockdowns to mental health during the pandemic, while controlling for sociodemographic variables as covariates. Methods We tested the model in a probability-based internet survey of a representative sample of the Israeli adult population (N = 812) conducted during the COVID-19 pandemic. Results Perceived support in close relationships was negatively associated with the intensity of depression, anxiety, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). Larger rings of potential support such as perceived belongingness to a community and trust in government were also negatively related to anxiety and depression but were positively associated with the intensity of OCD and PTSD. Conclusions Findings support the “tend and befriend” theory in the social distancing era and highlight the importance of keeping personal relationships alive when facing a mass trauma.
Experiences of current vital signs monitoring practices and views of wearable monitoring: A qualitative study in patients and nurses

Abstract Aims To understand current experiences of vital signs monitoring of patients and clinical staff on a surgical ward, and views on the introduction of wearable ambulatory monitoring into the general ward environment. Design Qualitative study. Methods Semi‐structured interviews using topic guides were conducted with 15 patients and 15 nurses on a surgical ward between July 2018 and August 2019. The concept of ambulatory wearable devices for clinical monitoring was introduced at the end of the interview. Results Three interconnected themes were identified. Vital sign data as evidence for escalation, examined nurses' use of data to support escalation of care and the implications for patients perceived to be deteriorating who have not reached the threshold for escalation. The second theme, Trustworthiness of vital sign data, described nurses’ practice of using manual measurements to recheck or confirm automated vital signs readings when concerned. The final theme, finding a balance between continuous and intermittent monitoring, both patients and nurses agreed that although continuous monitoring may improve safety and reassurance, these needed to be balanced with multiple limitations. Factors to be considered included noise pollution, comfort, and impact on patient mobility and independence. Introduction of the concept of ambulatory wearable devices was viewed positively by both groups as offering solutions to some of the issues identified with traditional monitoring. However, most agreed that this would not be suitable for all patients and should not replace direct nurse/patient contact. Conclusion Both patients and staff identified the benefits of continuous monitoring to improve patient safety but, due to limitations, use should be carefully considered and patient‐centred. Impact Feedback from nurses and patients suggests there is scope for ambulatory monitoring systems to be integrated into the hospital environment; however, both groups emphasized these should not add more noise to the ward nor replace direct nursing contact.
Tanshinone IIA inhibits Leu27IGF‐II‐induced insulin‐like growth factor receptor II signaling and myocardial apoptosis via estrogen receptor‐mediated Akt activation

Different stress condition stimulates the expression level of insulin‐like growth factor receptor II (IGF‐IIR) in cardiomyoblasts that lead to apoptosis. Tanshinone IIA (TSN), a pharmacologically active component from Danshen, has been shown cardioprotective effects against cardiac apoptosis induced by several stress conditions. Therefore, this study was conducted to assess the cardioprotective effects of TSN IIA mediated through the estrogen receptor (ER) in order to inhibit the Leu27IGF‐II‐enhanced IGF‐IIR‐mediated cardiac apoptosis. The estrogenic activity of TSN IIA was examined after myocardial cells were pretreated with the ER antagonist, and inhibited the phospho‐inositide‐3 kinase (PI3K). Here, we found that TSN IIA significantly induced ER that phosphorylated Akt. Further, Akt activation considerably suppressed the Leu27IGF‐II induced IGF‐IIR expression level and the downstream effectors, including Gαq and calcineurin as well as mitochondrial dependent apoptosis proteins including Bad, cytochrome c, and active caspase‐3 that result in cardiac apoptosis resistance. However, the western blot analysis, JC‐1 staining, and terminal deoxynucleotide transferase‐mediated dUTP nick end labeling assay revealed that TSN IIA attenuated Leu27IGF‐II‐induced IGF‐IIR mediated cardiac apoptosis was reversed by an ER antagonist such as ICI 182780, and PI3K inhibition. All these findings demonstrate that TSN IIA exerts estrogenic activity, which can activate PI3K‐Akt pathway, and thereby inhibits Leu27IGFII induced IGF‐IIR mediated cardiac apoptosis. Thus, TSN IIA can be considered as an effective therapeutic strategy against IGF‐IIR signaling cascade to suppress cardiac apoptosis.