Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptomic analysis of the Non-Obstructive Azoospermia (NOA) to address gene expression regulation in human testis

Abstract There is a need to understand the molecular basis of testes under Non-Obstructive Azoospermia (NOA), a state of failed spermatogenesis. There has been a lack of attention to the transcriptome at the level of alternatively spliced mRNAs (iso-mRNAs) and the mechanism of gene expression regulation. Hence, we aimed to establish a reliable iso-mRNA profile of NOA-testes, and explore molecular mechanisms – especially those related to gene expression regulation. We sequenced mRNAs from testicular samples of donors with complete spermatogenesis (control samples) and a failure of spermatogenesis (NOA samples). We identified differentially expressed genes and their iso-mRNAs via standard NGS data analyses. We then listed these iso-mRNAs hierarchically based on the extent of consistency of differential quantities across samples and groups, and validated the lists via RT-qPCRs (for 80 iso-mRNAs). In addition, we performed extensive bioinformatic analysis of the splicing features, domains, interactions, and functions of differentially expressed genes and iso-mRNAs. Many top-ranking down-regulated genes and iso-mRNAs, i.e., those down-regulated more consistently across the NOA samples, are associated with mitosis, replication, meiosis, cilium, RNA regulation, and post-translational modifications such as ubiquitination and phosphorylation. Most down-regulated iso-mRNAs correspond to full-length proteins that include all expected domains. The predominance of alternative promoters and termination sites in these iso-mRNAs indicate their gene expression regulation via promoters and UTRs. We compiled a new, comprehensive list of human transcription factors (TFs) and used it to identify TF-'TF gene’ interactions with potential significance in down-regulating genes under the NOA condition. The results indicate that RAD51 suppression by HSF4 prevents SP1-activation, and SP1, in turn, could regulate multiple TF genes. This potential regulatory axis and other TF interactions identified in this study could explain the down-regulation of multiple genes in NOA-testes. Such molecular interactions may also have key regulatory roles during normal human spermatogenesis.
Association between in situ steroids and spine surgical site infections among instrumented procedures

Abstract Objective: To estimate the association between in situ steroids and spine surgical-site infections (SSIs), assessing spinal instrumentation as an effect modifier and adjusting for confounders. Design: Case–control study. Setting: Rural academic medical center. Participants: We identified 1,058 adults undergoing posterior fusion and laminectomy procedures as defined by the National Healthcare Safety Network without a pre-existing SSI between January 2020 and December 2021. We identified 26 SSI as cases and randomly selected 104 controls from the remaining patients without SSI. Methods: The primary exposure was the intraoperative administration of methylprednisolone in situ (ie, either in the wound bed or as an epidural injection). The primary outcome was a clinical diagnosis of SSI within 6 months of a patient’s first spine surgery at our facility. We quantified the association between the exposure and outcome using logistic regression, using a product term to assess for effect modification by spinal instrumentation and the change-in-estimate approach to select significant confounders. Results: Adjusting for Charlson comorbidity index and malignancy, in situ steroids were significantly associated with spine SSI relative to no in situ steroids for instrumented procedures (adjusted odds ratio [aOR], 9.93; 95% confidence interval [CI], 1.54–64.0), but they were not associated with spine SSIs among noninstrumented procedures (aOR, 0.86; 95% CI, 0.15–4.93). Conclusions: In situ steroids were significantly associated with spine SSI among instrumented procedures. The benefits of in situ steroids for pain management following spine surgery should be weighed against the risk of SSI, especially for instrumented procedures.
More or Less Job Performance in an Insecure Job? A Study on the Relationship between Job Insecurity and In-Role and Extra-Role Performance

Findings caution for the strategic management of job insecurity in today’s workplaces to increase employee performance. Instead, organizations are advised to either directly prevent perceived job insecurity and/or to foster autonomous work motivation in employees in a way that the negative consequences of job insecurity on employee performance are mitigated. Objective To gain insight into the complex relationship between job insecurity and in-role and extra-role performance. Autonomous work motivation is investigated as a mediator in this relationship. The quality of the employee-supervisor relationship (LMX) is investigated as a moderator between job insecurity and autonomous work motivation. Methods Cross-sectional data were collected by online surveys among 206 Dutch and Belgian employees. Multiple regression analyses were performed to test the hypotheses. Results Job insecurity was negatively associated with both in-role and extra-role performance. Autonomous work motivation mediated the negative relationship between job insecurity and in-role and extra-role performance. LMX did not moderate the negative relationship between job insecurity and autonomous work motivation. Conclusions Organizations need to prevent job insecurity and limit the negative consequences of job insecurity for sustaining employees' autonomous work motivation and job performance.
Asymptotical statistics of misspecified HMM

Deals with the fitting of hidden Markov models to data generated by ergodic stochastic processes. More specifically we consider the problem of fitting a family of partially observed finite state Markov chain parameters (or hidden Markov models, HMMs) with continuous output to an ergodic process, with continuous values, which is not necessarily a member of the family. In this context we derive the main asymptotic results: almost sure consistency, asymptotic normality and rate of convergence of the MLE estimator.
Effective extraction of polyribosomes exposes gene expression strategies in primary astrocytes

Abstract Regulation of mRNA translation in astrocytes gains a growing interest. However, until now, successful ribosome profiling of primary astrocytes has not been reported. Here, we optimized the standard ‘polysome profiling’ method and generated an effective protocol for polyribosome extraction, which enabled genome-wide assessment of mRNA translation dynamics along the process of astrocyte activation. Transcriptome (RNAseq) and translatome (Riboseq) data generated at 0, 24 and 48 h after cytokines treatment, revealed dynamic genome-wide changes in the expression level of ∼12 000 genes. The data clarify whether a change in protein synthesis rate results from a change in mRNA level or translation efficiency per se. It exhibit different expression strategies, based on changes in mRNA abundance and/or translation efficiency, which are specifically assigned to gene subsets depending on their function. Moreover, the study raises an important take-home message related to the possible presence of ‘difficult to extract’ polyribosome sub-groups, in all cell types, thus illuminating the impact of ribosomes extraction methodology on experiments addressing translation regulation.
Trapped Entanglements in Rubbers. A Unification of Models

An expression for the contribution of trapped entanglements to stress in a cross-linked polymer network is obtained using a slip-link model. This is intended as a simplified alternative to the replica calculation (Ball et al.), and is a more exact treatment of the "hoop" model (Adolf) and a generalization of the "belt-loop" model (Kosc). We discuss the relationship between slip-link and tube models and consider under what circumstances the two ideas are equivalent.
Relationship between Menopause and Complications of Hyperthyroidism in Female Patients in Iraq.

Hyperthyroidism is a health problem characterized by an overactive thyroid gland, resulting in extra triiodothyronine (T3) and thyroxine (T4) production, as well as a decrease in thyroid-stimulating hormone (TSH). The oxidative stress indicators in hyperthyroid patients and the relationship with impaired metabolism of lipid are still controversial, especially in menopausal women suffering from a lack of ovulation hormones. In this study, blood samples were withdrawn from 120 subjects, including healthy premenopausal (n=30) and postmenopausal women (n=30) as control groups (G1 and G2), as well as 30 hyperthyroid women in each group of premenopausal and postmenopausal patient groups (G3 and G4). The levels of T3, T4, and TSH, blood pressure, and lipid profiles, such as triglyceride, total cholesterol (TC), high-density lipoprotein, and low-density lipoprotein, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and advanced oxidation protein products (AOPP) in the two healthy control groups and patient groups with hyperthyroidism were measured. In addition, serum progesterone levels were measured by the Bio-Merieux kit France, according to the manufacturer's instructions. The results revealed a significant decrease in SOD activity in the postmenopausal group, as compared to that in premenopausal women and control groups. Hyperthyroidism groups demonstrated a significant increase in MDA and AOPP levels, compared to control groups. Patient groups reported a decreased level of progesterone, in comparison with control groups. Moreover, there was a significant increase in T3 and T4 in patient groups (G3 and G4), compared to that in control groups (G1 and G2). There was a significant increase in systolic and diastolic blood pressure in menopausal hyperthyroidism (G4), compared to that in other groups. The TC decreased significantly in G3 and G4, compared to that in both control groups (P<0.05); nonetheless, there was no significant difference between patient groups (G3 and G4), as well as between control groups (G1 and G2). The study suggested that hyperthyroidism causes an increase in oxidative stress, which negatively affects the antioxidant system and drops levels of progesterone in both premenopausal and postmenopausal female patients. Therefore, low levels of progesterone are linked with hyperthyroidism, leading to aggravating symptoms of the disease.
Predictive value of liver fibrosis scores in cardiovascular diseases among hypertensive population

Purpose: To explore the predictive value of liver fibrosis scores [fibrosis-4, AST/platelet ratio index, BAAT score (BMI Age ALT TG), and BARD score (BMI AST/ALT Ratio Diabetes)] for the risk of cardiovascular disease (CVD) in a hypertensive population. Methods: A total of 4164 hypertensive participants without history of CVD were enrolled in the follow-up. Four liver fibrosis scores (LFSs) were used, including the fibrosis-4 (FIB-4), APRI, BAAT score, and BARD score. The endpoint was CVD incidence which was defined as stroke or coronary heart disease (CHD) during the follow-up period. Cox regression analyses were used to calculate hazard ratios between LFSs and CVD. Kaplan–Meier curve was used to show the probability of CVD in different levels of LFSs. Restricted cubic spline further explored whether the relationship between LFSs and CVD was linear. Finally, we assessed the discriminatory ability of each LFS for CVD was assessed using C-statistics, net reclassification index (NRI), and integrated discrimination improvement (IDI). Results: During a median follow-up time of 4.66 years, 282 hypertensive participants had CVD. Kaplan–Meier curve showed that four LFSs were associated with CVD and high levels of LFSs significantly increase the probability of CVD in hypertensive population. In the multivariate Cox regression analysis, the adjusted hazard ratios for four LFSs were 3.13 in FIB-4, 1.66 in APRI, 1.47 in BAAT score, and 1.36 in BARD score. Moreover, after adding LFSs to original risk prediction model, we find that all four new models have higher C-statistics of CVD than the traditional model. Furthermore, the results of both NRI and IDI were positive, indicating that LFSs enhanced the effect on the prediction of CVD. Conclusions: Our study showed that LFSs were associated with CVD in hypertensive populations in northeastern China. Furthermore, it suggested that LFSs could be a new tool for identifying patients at high risk of primary CVD in a hypertensive population.
Effects of continuous positive airway pressure on very short-term blood pressure variability associated with sleep-disordered breathing by pulse transit time-based blood pressure measurements

Background: Blood pressure (BP) variability (BPV) is a predictor of cardiovascular outcomes independently of BP absolute values. We previously reported that pulse transit time (PTT) enables monitoring beat-to-beat BP, identifying a strong relationship between the extent of very short-term BPV and the severity of sleep-disordered breathing (SDB). Here, we investigated the effects of continuous positive airway pressure (CPAP) on very short-term BPV. Methods: We studied 66 patients (mean age 62 years old, 73% male) with newly diagnosed SDB who underwent full polysomnography on two consecutive days for diagnosis (baseline) and CPAP, together with PTT-driven BP continuous recording. PTT index was defined as the average number of acute transient rises in BP (≥12 mmHg) within 30 s/h. Results: CPAP treatment effectively improved SDB parameters, and attenuated PTT-based BP absolute values during the night-time. Very short-term BPV that includes PTT index and standard deviation (SD) of systolic PTT-BP was significantly reduced by CPAP therapy. The changes in PTT index from baseline to CPAP were positively correlated with the changes in apnea-hypopnea index, obstructive apnea index (OAI), oxygen desaturation index, minimal SpO2, and mean SpO2. Multivariate regression analysis revealed that changes in OAI and minimal SpO2, as well as heart failure, were the independent factors in determining the reduction of PTT index following CPAP. Conclusion: PTT-driven BP monitoring discovered the favorable effects of CPAP on very short-term BPV associated with SDB events. Targeting very short-term BPV may be a novel approach to identifying individuals who experience greater benefits from CPAP.
“Live a normal life”: Constructions of resilience among people in mixed HIV status relationships in Canada

Positive Plus One is a mixed-methods study of long-term mixed HIV-serostatus relationships in Canada (2016–19). Qualitative interviews with 51 participants (10 women, 41 men, including 27 HIV-positive and 24 HIV-negative partners) were analyzed using inductive thematic analysis to examine notions of relationship resilience in the context of emerging HIV social campaigns. Relationship resilience meant finding ways to build and enact life as a normal couple, that is, a couple not noticeably affected by HIV, linked to the partner with HIV maintaining viral suppression and achieving “undetectable = untransmittable” (U = U). Regardless of serostatus, participants with material resources, social networks, and specialized care were better able to construct resilience for HIV-related challenges within their relationships. Compared to heterosexual couples and those facing socioeconomic adversity, gay and bisexual couples were easier able to disclose, and access capital, networks and resources supporting resilience. We conclude that important pathways of constructing, shaping, and maintaining resilience were influenced by the timing of HIV diagnosis in the relationship, access to HIV-related information and services, disclosure, stigma and social acceptance.
Mitochondrial redox adaptations enable alternative aspartate synthesis in SDH-deficient cells

The oxidative tricarboxylic acid (TCA) cycle is a central mitochondrial pathway integrating catabolic conversions of NAD +to NADH and anabolic production of aspartate, a key amino acid for cell proliferation. Several TCA cycle components are implicated in tumorigenesis, including loss-of-function mutations in subunits of succinate dehydrogenase (SDH), also known as complex II of the electron transport chain (ETC), but mechanistic understanding of how proliferating cells tolerate the metabolic defects of SDH loss is still lacking. Here, we identify that SDH supports human cell proliferation through aspartate synthesis but, unlike other ETC impairments, the effects of SDH inhibition are not ameliorated by electron acceptor supplementation. Interestingly, we find aspartate production and cell proliferation are restored to SDH-impaired cells by concomitant inhibition of ETC complex I (CI). We determine that the benefits of CI inhibition in this context depend on decreasing mitochondrial NAD+/NADH, which drives SDH-independent aspartate production through pyruvate carboxylation and reductive carboxylation of glutamine. We also find that genetic loss or restoration of SDH selects for cells with concordant CI activity, establishing distinct modalities of mitochondrial metabolism for maintaining aspartate synthesis. These data therefore identify a metabolically beneficial mechanism for CI loss in proliferating cells and reveal how compartmentalized redox changes can impact cellular fitness.
The North Atlantic jet stream: a look at preferred positions, paths and transitions

Preferred jet stream positions and their link to regional circulation patterns over the winter North Atlantic/European sector are investigated to corroborate findings of multimodal behaviour of the jet positions and to analyse patterns of preferred paths and transition probabilities between jet regimes using ERA‐40 data. Besides the multivariate Gaussian mixture model, hierarchical clustering and data image techniques are used for this purpose. The different approaches all yield circulation patterns that correspond to the preferred jet regimes, namely the southern, central and the northern positions associated respectively with the Greenland anticyclone or blocking, and two opposite phases of an East Atlantic‐like flow pattern. Growth and decay patterns as well as preferred paths of the system trajectory are studied using the mixture model within the delay space. The analysis shows that the most preferred paths are associated with central to north and north to south jet stream transitions with a typical time‐scale of about 5 days, and with life cycles of 1–2 weeks. The transition paths are found to be consistent with transition probabilities. The analysis also shows that wave breaking seems to be the dominant mechanism behind Greenland blocking. Copyright © 2011 Royal Meteorological Society
Evidence for Ni-56 yields Co-56 yields Fe-56 decay in type Ia supernovae

In the prevailing picture of Type Ia supernovae (SN Ia), their explosive burning produces Ni-56, and the radioactive decay chain Ni-56 yields Co-56 yields Fe-56 powers the subsequent emission. We test a central feature of this theory by measuring the relative strengths of a (Co III) emission feature near 5900 A and a (Fe III) emission feature near 4700 A. We measure 38 spectra from 13 SN Ia ranging from 48 to 310 days after maximum light. When we compare the observations with a simple multilevel calculation, we find that the observed Fe/Co flux ratio evolves as expected when the Fe-56/Co-56 abundance ratio follows from Ni-56 yields Co-56 yields Fe-56 decay. From this agreement, we conclude that the cobalt and iron atoms we observe through SN Ia emission lines are produced by the radioactive decay of Ni-56, just as predicted by a wide range of models for SN Ia explosions.
Defensive medicine and its related risk factors: evidence from a sample of Iranian surgeons

ABSTRACT Objectives Defensive medicine (DM) is the deviation of a physician from normal behavior or what is a good practice and is aimed at reducing or avoiding the risk of legal litigation from patients or their families. Therefore, this study aimed to determine DM-related behaviors and associated risk factors among Iranian surgeons. Methods In this cross-sectional study, 235 surgeons were selected using convenience sampling. The data gathering tool was a researcher-made questionnaire confirmed as a reliable and valid tool. Factors associated with DM-related behaviors were identified using logistic regression analysis. Results DM-related behaviors ranged from 14.9% to 88.9%. The most common positive DM-related behaviors, including unnecessary biopsy (78.7%), imaging and laboratory tests (72.4% and 70.6%), and refusing high-risk patients (61.7%), was the most common negative DM-related behavior. The likelihood of DM-related behaviors was more in younger and less experienced surgeons. Other variables, such as gender, specialty, and lawsuit history, positively affected some DM-related behaviors (p < 0.05). Conclusion This study showed that the proportion of surgeons who frequently performed DM-related behaviors was higher than those who rarely performed it. Therefore, strategies including reforming the rules and regulations for medical errors and litigations, developing and implementing medical guidelines and evidence-based medicine, and improving the medical liability insurance system can reduce DM-related behaviors.
Poor sleep quality during COVID-19 pandemic restrictions associated with reduced psychological wellbeing in healthcare students

ABSTRACT Sleep is inexorably linked to both physiological and psychological wellbeing. Restrictions imposed to control the COVID-19 pandemic likely impacted upon daily and weekly routines, which can have a negative impact on a range of factors including sleep quality, and/or quantity and general wellbeing. The aim of this study was to investigate the effect of COVID-19 related restrictions on sleep patterns and psychological wellbeing of healthcare students. A survey was delivered to healthcare students across three faculties at a single institution. Participants completed questionnaires on the effect of COVID-19 restrictions on course delivery and clinical placements, its effect on sleep-wake times, sleep quality, sleep hygiene, psychological wellbeing, their current sleep knowledge and sleep education in their current course. Using the Pittsburgh Sleep Quality Index (PSQI), over 75% of participants were found to have poor sleep quality. Changes in sleep habits and sleep behaviours during COVID-19 restrictions were associated with poorer sleep quality, and this poor sleep quality was associated with poor psychological wellbeing, particularly, motivation, stress and fatigue. Increases in negative sleep hygiene behaviours were associated with a statistically significant increase in PSQI global score. Positive emotions were positively correlated with PSQI (r = 0.22–0.24, p < .001), negative emotions were negatively correlated with PSQI (r = −0.22 - −0.31, p < .001). Also, a self-perceived lack of sleep education was identified. This study illustrates the negative association between self-reported poor sleep behaviour and poor sleep quality during COVID-19 restrictions on university student mental health and wellbeing. Additionally, there is a self-perceived lack of sleep education with little to no time spent educating students in their current degree. Hence, appropriate sleep education may improve sleep behaviours and subsequent sleep quality, which may prove to be a protective factor against poor mental health in the face of unexpected changes to routines.
The use of FDA-approved medications for preventing vaso-occlusive events in sickle cell disease

Sickle cell disease (SCD) is a chronic disease affecting people across their lifespans. Individuals with SCD face life-threatening complications, including vaso-occlusive pain episodes and chronic end-organ damage. Although SCD affects about 110 000 Americans, health care costs for this population are about $3 billion per year or $30 000 per person. 1,