Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic profiles of renal cell carcinoma in a small Chinese cohort

Objectives Our aim was to describe the molecular characteristics of Renal Cell Carcinoma (RCC) and develop a small panel of RCC-associated genes from a large panel of cancer-related genes. Materials and methods Clinical data of 55 patients with RCC diagnosed in four hospitals from September 2021 to August 2022 were collected. Among the 55 patients, 38 were diagnosed with clear cell RCC (ccRCC), and the other 17 were diagnosed with non-clear cell RCC (nccRCC), including 10 cases of papillary renal cell carcinoma, 2 cases of hereditary leiomyomatosis and RCC syndrome (HLRCC), 1 eosinophilic papillary RCC, 1 tubular cystic carcinoma, 1 TFE3 gene fusion RCC, and 2 RCC with sarcomatoid differentiation. For each patient, 1123 cancer-related genes and 79 RCC-associated genes were analyzed. Results The most frequent mutations in a large panel of 1123 cancer-related genes in the overall population of RCC patients were VHL (51%), PBRM1 (35%), BAP1 (16%), KMT2D (15%), PTPRD (15%), and SETD2 (15%). For ccRCC patients, mutations in VHL, PBRM1, BAP1, and SERD2 can reach 74%, 50%, 24%, and 18%, respectively, while for nccRCC patients, the most frequent mutation was FH (29%), MLH3 (24%), ARID1A (18%), KMT2D (18%), and CREBBP (18%). The germline mutation rate in all 55 patients reached 12.7% (five with FH, one with ATM, and one with RAD50). The small panel containing only 79 RCC-associated genes demonstrated that mutations of VHL, PBRM1, BAP1, and SETD2 in ccRCC patients were 74%, 50%, 24%, and 18% respectively, while for the nccRCC cohort, the most frequent mutations were FH (29%), ARID1A (18%), ATM (12%), MSH6 (12%), BRAF (12%), and KRAS (12%). For ccRCC patients, the spectrum of mutations by large and small panels was almost the same, while for nccRCC patients, the mutation spectrum showed some differences. Even though the most frequent mutations (FH and ARID1A) in nccRCC were both demonstrated by large panels and small panels, other less frequent mutations such as MLH3, KMT2D, and CREBBP were not shown by the small panel. Conclusion Our study revealed that nccRCC is more heterogeneous than ccRCC. For nccRCC patients, the small panel shows a more clear profile of genetic characteristics by replacing MLH3, KMT2D, and CREBBP with ATM, MSH6, BRAF, and KRAS, which may help predict prognosis and make clinical decisions.
eHealth literacy was associated with anxiety and depression during the COVID-19 pandemic in Nigeria: a cross-sectional study

Background Electronic health (eHealth) literacy may play an important role in individuals’ engagement with online mental health-related information. Aim To examine associations between eHealth literacy and psychological outcomes among Nigerians during the Coronavirus disease-2019 (COVID-19) pandemic. Methods This was a cross-sectional study among Nigerians conducted using the ‘COVID-19’s impAct on feaR and hEalth (CARE) questionnaire. The exposure: eHealth literacy, was assessed using the eHealth literacy scale, and psychological outcomes were assessed using the PHQ-4 scale, which measured anxiety and depression; and the fear scale to measure fear of COVID-19. We fitted logistic regression models to assess the association of eHealth literacy with anxiety, depression, and fear, adjusting for covariates. We included interaction terms to assess for age, gender, and regional differences. We also assessed participants’ endorsement of strategies for future pandemic preparedness. Results This study involved 590 participants, of which 56% were female, and 38% were 30 years or older. About 83% reported high eHealth literacy, and 55% reported anxiety or depression. High eHealth literacy was associated with a 66% lower likelihood of anxiety (adjusted odds ratio aOR, 0·34; 95% confidence interval, 0·20–0·54) and depression (aOR: 0·34; 95% CI, 0·21–0·56). There were age, gender, and regional differences in the associations between eHealth literacy and psychological outcomes. eHealth-related strategies such as medicine delivery, receiving health information through text messaging, and online courses were highlighted as important for future pandemic preparedness. Conclusion Considering that mental health and psychological care services are severely lacking in Nigeria, digital health information sources present an opportunity to improve access and delivery of mental health services. The different associations of e-health literacy with psychological well-being between age, gender, and geographic region highlight the urgent need for targeted interventions for vulnerable populations. Policymakers must prioritize digitally backed interventions, such as medicine delivery and health information dissemination through text messaging, to address these disparities and promote equitable mental well-being.
Life situation of a caregiver of a child with congenital heart defect and/or other cardiac problems: structure and preliminary validation of a new questionnaire

Background Illness in a child with cardiac disease causes stress, brings additional responsibilities, reorganizes family life, and changes the functioning of the family. Aim This study aimed to validate a new questionnaire evaluating the life situations of caregivers/parents of children with congenital heart disease (CHD) and/or other cardiac diseases (OCD). Materials and methods The questionnaire comprised 10 questions aimed at assessing the life situation of an ill child’s caregiver in two main areas: personal and spiritual. The total score of the questionnaire assessing the life situation of the caregiver of a child with a CHD and/or OCD can range from 0 to 32 points, with scores <26 indicating a poor, 25 to 32 indicating an average, and >32 indicating a good level of life situation in the personal sphere of the caregiver. The questionnaire was assessed using Cronbach’s alpha tests, and repeatability was assessed using Cohen’s Kappa test (retest) within a time interval of two to 4 weeks from the first measurement. Results The research covered 50 respondents. Cohesion in the personal sphere obtained a satisfactory value of Cronbach’s α = 0.72, in the spiritual sphere: Cronbach’s α = 0.83, and the result common for both sections was: Cronbach’s α = 0.66. Conclusion The Life Situation Assessment Questionnaire for caregivers of children with CHD and OCD is a reliable and homogeneous tool for measuring the functioning of parents in the event of a child’s illness.
Cariprazine for negative symptoms in early psychosis: a pilot study with a 6-month follow-up

Background Cariprazine, a novel antipsychotic drug that is a partial agonist with preferential binding to the D3 receptor, has demonstrated efficacy in clinical trials across all symptom domains, including negative symptoms, which can occur early in the course of psychotic illness. However, evidence, to date regarding its effects in early psychosis patients with primary negative symptoms has been limited. Objectives To evaluate the efficacy of cariprazine for negative symptoms in early psychosis patients. Methods Demographic and clinical information of the study population were collected from the electronic records and PANSS scale administered at baseline, 3 and 6 months. Tolerability and discontinuation reasons, where applicable, were also recorded. Results Ten patients with early psychosis (four men and six women, mean age – 25.5 years) with prominent or predominant negative symptoms were treated with cariprazine (range 1.5 – 3 mg). Three patients discontinued cariprazine within the first 3 months due to patient choice, lack of response and non-compliance, respectively. In the remaining patients, there was a significant reduction in the mean negative PANSS score from baseline to 6 months (from 26.3 to 10.6), mean total PANSS score (from 81.4 to 43.3) and in the mean positive PANSS score (from 14.4 to 9.9) which correspond to a 53.1, 41.5, and 28.5% mean score reduction. Conclusion This pilot study suggests that cariprazine is a safe and effective treatment in early psychosis, particularly for the alleviation of negative symptoms which remains an area of unmet treatment need.
Earlier sexual debut predicts higher (not lower) levels of father care measured across 12 weeks: an experience sampling study

Across the lifespan, males negotiate the tradeoff between current and future reproduction. From a life history theory (LHT) perspective, resources invested into earlier reproduction pose a cost to later reproduction. The age of sexual debut is a commonplace measure of sexual maturation. However, in males, thorarche (age of first ejaculation) and years from thorarche to age of first reproduction both represent milestones related to reproductive timing. A fundamental prediction from LHT is that earlier sexual maturation—a “quantity” strategy—predicts decreased levels of care per offspring. In the current study, we test this straightforward relationship looking specifically at a father’s investment of time. In a sample of first-time fathers, we measured the amount of time spent with their 9-to-12-month infants longitudinally using an experience sampling method (ESM)—an ecologically valid method of collecting self-report data on fathers’ use of time Fathers contributed data on their time allocation across a 12-week period. They reported on ages of sexual debut, thorarche, and the years between thorarche and first reproduction (i.e., current age) was calculated. Only age of sexual debut had a relationship with time allocated toward infants. Importantly however, this effect was in a direction opposite of our LHT derived hypothesis. Males with earlier sexual debut spent more time with their infants. Discussion focuses on the potential contributions to this finding and limitations related to small effect size, methods and measurement, and sample demographics.
A triphosphate tunnel metalloenzyme from pear (PbrTTM1) moonlights as an adenylate cyclase

Adenylyl cyclase (AC) is the vital enzyme for generating 3′,5′-cyclic adenosine monophosphate, an important signaling molecule with profound nutritional and medicinal values. However, merely, a dozen of AC proteins have been reported in plants so far. Here, a protein annotated as triphosphate tunnel metalloenzyme (PbrTTM1) in pear, the important worldwide fruit plant, was firstly identified to possess AC activity with both in vivo and in vitro methods. It exhibited a relatively low AC activity but was capable of complementing AC functional deficiencies in the E. coli SP850 strain. Its protein conformation and potential catalytic mechanism were analyzed by means of biocomputing. The active site of PbrTTM1 is a closed tunnel constructed by nine antiparallel β-folds surrounded with seven helices. Inside the tunnel, the charged residues were possibly involved in the catalytic process by coordinating with divalent cation and ligand. The hydrolysis activity of PbrTTM1 was tested as well. Compared to the much higher capacity of hydrolyzing, the AC activity of PbrTTM1 tends to be a moonlight function. Through a comparison of protein structures in various plant TTMs, it is reasonable to speculate that many plant TTMs might possess AC activity as a form of moonlighting enzyme function.
A Cattaneo-Mindlin problem for a rigid punch with tangential load applied above the interface line

We study the contact between a rigid flat punch and an elastic half-space using Coulomb friction for a normal load followed by a tangential load applied at a certain height above the interface line. The study is inspired by recent experiments by the group of Jay Fineberg in Israel. Three regimes are found in the evolution of slip at the interface depending on a dimensionless parameter α = a 2 μ h , the ratio between the halfwidth of the contact and the product of twice friction coefficient and height of the loading point. Normal pressure and shear tractions are plotted for each case. It is shown that the effect of height does not collapse the data, contrary to the experimental data of Fineberg’s setup. However, this is not surprising given the many deviations from the ideal configuration we have studied, namely the finite thickness of the bottom block, the presence of vertical surfaces on the upper block (both not permitting the assumption of halfspace elasticity) and finally local effects due to concentrated tangential load which give rise to local and not only global induced moment.
Whole blood transcriptome analysis of lactating Murrah buffaloes divergent to contrasting genetic merits for milk yield

Functional genome profiling of Murrah buffaloes (Bubalus bubalis) was performed for milk-production trait by whole blood transcriptome analysis comparing RNA-seq data assembled from high and low milk producing multiparous (5 -6 parity) animals. These buffaloes reflected the genetic merit inherited as daughters born to extremely high- and low-end bulls evaluated under a progeny testing scheme and ranked by the estimated breeding value. The average standard milk yield (SMY) over the 305 d during the parity was recorded as 2909.50L ± 492.63 and 1869.57 ± 189.36L in high- and low-performance buffaloes, respectively. The “reference” assembly data was assembled from transcriptome libraries of a group of buffaloes (n=16), comprising of animals in different physiological states. Replicates selected within each category of the high and low genetic merit animals showed a correlation coefficient of high order (R2=0.98) while comparing with the `reference' assembly. The sequence data of selected buffaloes, mapped over the Mediterranean water buffalo genome, revealed differentially expressed genes (DEGs) distinctly depicted via heat maps and volcano plots obtained for two categories of animals, determining more than 25,000 genes via the Cufflink analysis. DEGs included 83 down-regulating and 142 up-regulating genes (p<0.05, FDR<0.05). Functional classification of the DEGs revealed a fine networking of biological processes, primarily cell signaling, cell proliferation, cell differentiation, RNA splicing, fat metabolism, and inflammasome generation. These processes are regulated by transcription factors and binding proteins covered under the network of TNF alpha signaling, NF-kappa B signaling and MAPK PI3K-AKT signaling pathways/ cascade emerged as main biological pathways. Emerged pathways revealed remarkably intricate tuning of metabolic and cell development processes converging into milk production in buffaloes. Segregated patterns of gene expression obtained for high and low milk producing buffaloes using the non-invasive method of whole blood transcriptome analysis has emerged as a promising resource comprising gene network and protein -protein interactions, primarily involved in lactation. Synergism of transcription factors and binding proteins promoting epigenetic regulation at all development stages of mammary tissue induce mammogenic and lactogenic responses for subsequent milk secretion under optimum feeding management. These findings may help improve breeding strategies to achieve the desired milk yield in Murrah buffaloes.
Are older people worse off in 2040 regarding health and resources to deal with it? - Future developments in complex health problems and in the availability of resources to manage health problems in the Netherlands

Introduction Developing sustainable health policy requires an understanding of the future demand for health and social care. We explored the characteristics of the 65+ population in the Netherlands in 2020 and 2040, focusing on two factors that determine care needs: (1) the occurrence of complex health problems and (2) the availability of resources to manage health and care (e.g., health literacy, social support). Methods Estimations of the occurrence of complex health problems and the availability of resources for 2020 were based on registry data and patient-reported data. Estimations for 2040 were based on (a) expected demographic developments, and (b) expert opinions using a two-stage Delphi study with 26 experts from policy making, practice and research in the field of health and social care. Results The proportion of people aged 65+ with complex health problems and limited resources is expected to increase from 10% in 2020 to 12% in 2040 based on demographic developments, and to 22% in 2040 based on expert opinions. There was high consensus (>80%) that the proportion with complex health problems would be greater in 2040, and lower consensus (50%) on an increase of the proportion of those with limited resources. Developments that are expected to drive the future changes refer to changes in multimorbidity and in psychosocial status (e.g., more loneliness). Conclusion The expected increased proportion of people aged 65+ with complex health problems and limited resources together with the expected health and social care workforce shortages represent large challenges for public health and social care policy.
The activation of GABAergic neurons in the hypothalamic tuberomammillary nucleus attenuates sevoflurane and propofol-induced anesthesia in mice

Background: The histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) have been suggested to play a vital role in maintaining a rising state. But the neuronal types of the TMN are in debate and the role of GABAergic neurons remains unclear. Methods: In the present study, we examined the role of TMN GABAergic neurons in general anesthesia using chemogenetics and optogenetics strategies to regulate the activity of TMN GABAergic neurons. Results: The results indicated that either chemogenetic or optogenetic activation of TMN GABAergic neurons in mice decreased the effect of sevoflurane and propofol anesthesia. In contrast, inhibition of the TMN GABAergic neurons facilitates the sevoflurane anesthesia effect. Conclusion: Our results suggest that the activity of TMN GABAergic neurons produces an anti-anesthesia effect in loss of consciousness and analgesia.
Altered brain connectivity in Long Covid during cognitive exertion: a pilot study

Introduction Debilitating Long-Covid symptoms occur frequently after SARS-COVID-19 infection. Methods Functional MRI was acquired in 10 Long Covid (LCov) and 13 healthy controls (HC) with a 7 Tesla scanner during a cognitive (Stroop color-word) task. BOLD time series were computed for 7 salience and 4 default-mode network hubs, 2 hippocampus and 7 brainstem regions (ROIs). Connectivity was characterized by the correlation coefficient between each pair of ROI BOLD time series. We tested for HC versus LCov differences in connectivity between each pair of the 20 regions (ROI-to-ROI) and between each ROI and the rest of the brain (ROI-to-voxel). For LCov, we also performed regressions of ROI-to-ROI connectivity with clinical scores. Results Two ROI-to-ROI connectivities differed between HC and LCov. Both involved the brainstem rostral medulla, one connection to the midbrain, another to a DM network hub. Both were stronger in LCov than HC. ROI-to-voxel analysis detected multiple other regions where LCov connectivity differed from HC located in all major lobes. Most, but not all connections, were weaker in LCov than HC. LCov, but not HC connectivity, was correlated with clinical scores for disability and autonomic function and involved brainstem ROI. Discussion Multiple connectivity differences and clinical correlations involved brainstem ROIs. Stronger connectivity in LCov between the medulla and midbrain may reflect a compensatory response. This brainstem circuit regulates cortical arousal, autonomic function and the sleep–wake cycle. In contrast, this circuit exhibited weaker connectivity in ME/CFS. LCov connectivity regressions with disability and autonomic scores were consistent with altered brainstem connectivity in LCov.
Cognition, prior aggression, and psychopathic traits in relation to impaired multimodal emotion recognition in psychotic spectrum disorders

Background Psychopathic traits have been associated with impaired emotion recognition in criminal, clinical and community samples. A recent study however, suggested that cognitive impairment reduced the relationship between psychopathy and emotion recognition. We therefore investigated if reasoning ability and psychomotor speed were impacting emotion recognition in individuals with psychotic spectrum disorders (PSD) with and without a history of aggression, as well as in healthy individuals, more than self-rated psychopathy ratings on the Triarchic Psychopathy Measure (TriPM). Methods Eighty individuals with PSD (schizophrenia, schizoaffective disorder, delusional disorder, other psychoses, psychotic bipolar disorder) and documented history of aggression (PSD+Agg) were compared with 54 individuals with PSD without prior aggression (PSD-Agg) and with 86 healthy individuals on the Emotion Recognition Assessment in Multiple Modalities (ERAM test). Individuals were psychiatrically stable and in remission from possible substance use disorders. Scaled scores on matrix reasoning, averages of dominant hand psychomotor speed and self-rated TriPM scores were obtained. Results Associations existed between low reasoning ability, low psychomotor speed, patient status and prior aggression with total accuracy on the ERAM test. PSD groups performed worse than the healthy group. Whole group correlations between total and subscale scores of TriPM to ERAM were found, but no associations with TriPM scores within each group or in general linear models when accounting for reasoning ability, psychomotor speed, understanding of emotion words and prior aggression. Conclusion Self-rated psychopathy was not independently linked to emotion recognition in PSD groups when considering prior aggression, patient status, reasoning ability, psychomotor speed and emotion word understanding.
Polynomial metamodeling with dimensional analysis and the effect heredity principle

Abstract Polynomial metamodels (PMs) are widely used in simulation experiments for product design. However, construction of these metamodels is difficult if the number of inputs is large or the degree of the polynomial used to approximate the true function is high because the number of basis functions would be very large. This paper describes the use of dimensional information and the effect of heredity principle to reduce the number of models that need to be considered. A version of the Buckingham π Theorem is employed to reduce the inputs, some of which may be fixed physical quantities, to a smaller number of dimensionless variables. The effect heredity principle is generalized for arbitrary polynomial basis functions and a justification for the generalization is provided. A simple Bayesian approach that incorporates the principle is employed for model selection. Realistic examples show that PMs obtained by utilizing dimensional analysis and the effect heredity principle have better prediction accuracy.
Retention of older veterans with serious mental illness in a clinical exercise program

Older adults with serious mental illness (SMI) have compromised physical function that could be improved with exercise; however, retention in exercise programs is a challenge. This study was a retrospective analysis of retention for the 150 older veterans with SMI that enrolled in Gerofit, a clinical exercise program offered in the Veterans Health Administration. Chi-square and t-tests were conducted to evaluate baseline differences between those that were and were not retained at six and 12 months. Retention was 33% and better health-related quality of life and endurance were related to retention. Future work is needed to improve exercise program retention in this population.