Miracle-dz/UniFAR-FTUs huggingface dataset:
Ddhd1 knockout mouse as a model of locomotive and physiological abnormality in familial spastic paraplegia

Abstract We have previously reported a novel homozygous 4-bp deletion in DDHD1 as the responsible variant for spastic paraplegia type 28 (SPG28; OMIM#609340). The variant causes a frameshift, resulting in a functionally null allele in the patient. DDHD1 encodes phospholipase A1 (PLA1) catalyzing phosphatidylinositol to lysophosphatidylinositol (LPI). To clarify the pathogenic mechanism of SPG28, we established Ddhd1 knockout mice (Ddhd1[−/−]) carrying a 5-bp deletion in Ddhd1, resulting in a premature termination of translation at a position similar to that of the patient. We observed a significant decrease in foot–base angle (FBA) in aged Ddhd1(−/−) (24 months of age) and a significant decrease in LPI 20:4 (sn-2) in Ddhd1(−/−) cerebra (26 months of age). These changes in FBA were not observed in 14 months of age. We also observed significant changes of expression levels of 22 genes in the Ddhd1(−/−) cerebra (26 months of age). Gene Ontology (GO) terms relating to the nervous system and cell–cell communications were significantly enriched. We conclude that the reduced signaling of LPI 20:4 (sn-2) by PLA1 dysfunction is responsible for the locomotive abnormality in SPG28, further suggesting that the reduction of downstream signaling such as GPR55 which is agonized by LPI is involved in the pathogenesis of SPG28.
The rationale for use of clinically defined outcomes in assessing the impact of pneumococcal conjugate vaccines against pneumonia

ABSTRACT Introduction: When evaluating the public health value of adult pneumococcal conjugate vaccine (PCV) for pneumonia, regulatory agencies and vaccine technical committees (VTCs) emphasize vaccine serotype (VT), radiologically confirmed community-acquired pneumonia (CAP) to the exclusion of clinically defined pneumonia and thus may underestimate PCV’s public health value. Areas covered: We review the critiques that have been raised to using clinically defined pneumonia as a complement to VT-CAP in evaluating the public health value of adult PCVs. Expert opinion: PCV13 efficacies for preventing hospitalized CAP ranged from 6% to 11% and for a combination of primary and secondary care from 4% to 12%, with relatively high associated rate reductions. These efficacy values are larger than estimated from multiplying PCV13 efficacy against vaccine-type CAP by the proportion of CAP identified as vaccine-type through tests, such as a serotype-specific urinary antigen detection assay. Current understanding of pneumococcal epidemiology and limitations of diagnostic tests suggest the efficacy values for clinically defined outcomes are plausible and potentially generalizable. Regulatory agencies and VTCs have accepted clinically defined outcomes for assessing pediatric vaccines and – while additional studies assessing adult clinical CAP VE are needed – they might consider existing data when evaluating adult PCV use.
Polygenic Risk Score for Alcohol Drinking Behavior Improves Prediction of Inflammatory Bowel Disease Risk.

BACKGROUND Epidemiological studies have long recognized risky behaviors as potentially modifiable factors for onset and flares of inflammatory bowel disease (IBD); yet the underlying mechanisms are largely unknown. Recently, the genetic susceptibilities to cigarette smoking, alcohol and cannabis use (i.e. substance use [SU]) have been characterized by well-powered genome-wide association studies (GWAS). We aimed to assess the impact of genetic determinants of SU on IBD risk. METHODS Using Mount Sinai Crohn and Colitis Registry (MSCCR) cohort of 1058 IBD cases and 188 healthy controls, we computed polygenic risk score (PRS) for SU, and correlated them with observed IBD diagnoses, while adjusting for genetic ancestry, PRS for IBD and SU behavior at enrollment. The results were validated in a pediatric cohort with no SU exposure. RESULTS PRS of alcohol consumption (DrnkWk), smoking cessation, and age of smoking initiation, were associated with IBD risk in MSCCR, even after adjustment for PRSIBD and actual smoking status. One interquartile range decrease in PRSDrnkWk was significantly associated to higher IBD risk (ie, inverse association) with OR = 1.65 and 95%CI: 1.32, 2.06). The association was replicated in a pediatric CD cohort. Colocalization analysis identified a locus on chromosome 16 with polymorphisms in IL27, SULT1A2, and SH2B1, that reached genome-wide statistical significance in GWAS (p < 7.7e-9) for both alcohol consumption and IBD risk. CONCLUSIONS This study demonstrated that genetic predisposition to SU was associated with IBD risk independent of PRSIBD and in the absence of SU behaviors. Our study may help further stratify individuals at risk of IBD.
Urantide decreases hepatic steatosis in rats with experimental atherosclerosis via the MAPK/Erk/JNK pathway

Hepatic steatosis, an indicator of atherosclerosis (AS), is always accompanied by inflammatory responses and disturbances in lipid metabolism. The present study investigated the protective effect of urantide, a urotensin II (UII) receptor antagonist, on the liver of rats with AS with hepatic steatosis by regulating the MAPK pathway. AS was induced in rats via an intraperitoneal injection of vitamin D3 and the administration of a high-fat diet. Urantide treatment was then administered to the rats. Pathology, liver index, lipid levels and liver function were measured to determine liver injury. The expression levels of UII and G protein-coupled receptor 14 (GPR14) were determined using immunohistochemistry, reverse transcription-quantitative PCR and western blotting. The expression levels of MAPK-related proteins in hepatocytes from each group were quantified using western blotting and immunofluorescence staining. Rats with AS had typical pathological changes associated with AS and hepatic steatosis, which were significantly improved by urantide treatment. Blood lipid levels, body weight, liver index and liver function were recovered in rats with AS after urantide treatment. Urantide downregulated the expression levels of UII and GPR14 in the livers of rats with AS; concurrently, the phosphorylation of Erk1/2 and JNK was significantly decreased. Moreover, no significant changes were observed in the phosphorylation of p38 MAPK in AS rat livers. In conclusion, urantide inhibits the activation of Erk1/2 and JNK by blocking the binding of UII and GPR14, thereby alleviating hepatic steatosis in rats with AS, ultimately restoring lipid metabolism in the liver and alleviating AS lesions.
Estimation of sarcopenia prevalence in individuals at different ages from Zheijang province in China

In this study, we analyzed sarcopenia prevalence and the cut-off points for skeletal muscle mass index (SMI), gait speed, and handgrip strength in young (18-39 years), middle-aged (40-59 years), and elderly (>60 years) individuals (n=1685) from Zhejiang Province in China. The prevalence of sarcopenia among individuals above 65 years was 2.21%, 4.87%, 5.31%, 14.16%, and 16.37% according to five diagnostic criteria (AWGS2019, AWGS2014, EWGSOP1, EWGSOP2, and local standard). The mean SMI (Kg/m2) was 7.961±0.7966, 7.801±0.7276, and 7.544±0.7493, respectively, in young, middle-aged, and elderly males. The mean SMI in young, middle-aged, and elderly females was 6.1570±0.5658, 6.604±0.5658, and 6.248±0.7483, respectively. SMI correlated negatively with age (r=-0.2344, P<0.001), but was not associated with age in females (r=0.0573, P=0.1463). The cut-off point of SMI for sarcopenia was ≤6.3678 kg/m2 in males and ≤5.0254 kg/m2 in females. These findings shows that the prevalence of sarcopenia increased gradually with age and varied significantly based on the diagnostic criteria used for this analysis. The mean SMI of young women was lower than in middle-aged women, making them an unsuitable reference population for determining cut-off values for sarcopenia diagnosis.
Sexing the bony labyrinth: A morphometric investigation in a subadult and adult Belgian identified sample

In forensic anthropology, sex estimation is a fundamental step in assessing individual biological profiles when analyzing human skeletons. Yet, current methods are not reliable enough to allow an accurate sex identification of highly fragmented, burnt, or subadult remains. This paper aims to investigate sexual dimorphism of the bony labyrinth on both identified subadult and adult individuals. The bony labyrinth is of particular interest for sex estimation since it is alleged to complete size and maturation pre‐pubertally and is located inside the petrous part of the temporal bone which protects it from taphonomic processes. The study was performed on 93 CT scans of identified individuals from two Belgian osteological collections (19–20th century) and from current pediatric images (Erasme hospital, Brussels). Linear and angular measurements were taken on 2D slices of right bony labyrinths. Intra‐ and interobservers error measurements were calculated. Statistical tests were used to unravel any morphological variations between subadult and adult bony labyrinths and to highlight differences between females and males, separately in subadults and adults. Linear discriminant functions were established by cross‐validation and tested on an independent sample from Belgium. Some measurements were significantly different between subadults and adults, and between females and males within both subadult and adult samples. Univariate functions achieved 72.7% in subadults and 68.4% in adults whereas multivariate equations increased accuracy respectively up to 84.9% and 78.4%. This study entails promising results to design a sex estimation method suitable for fragmented and/or subadult remains. Further metric approaches are needed to explore bony labyrinth sexual dimorphism.
Brain-Derived Neurotrophic Factor Val66Met and Behavioral Adjustment following Early Childhood Traumatic Brain Injury.

The present study examined the differential effect of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on behavioral adjustment in children with traumatic brain injury (TBI) relative to children with orthopedic injury (OI). Participants were drawn from a prospective, longitudinal study of children who sustained a TBI (n=69) or OI (n=72) between 3 and 7 years of age. Parents completed the Child Behavior Checklist (CBCL) at the immediate post-acute period, 6, 12, and 18 months after injury, and an average of 3.5 and 7 years after injury. Longitudinal mixed models examined the BDNF Val66Met allele status (Met carriers vs. Val/Val homozygotes) x injury group (TBI vs. OI) interaction in association with behavioral adjustment. After adjusting for continental ancestry, socioeconomic status, time since injury, and pre-injury functioning, the allele status x injury group interaction was statistically significant for Internalizing, Externalizing, and Total Behavior problems. Post hoc within-group analysis suggested a consistent trend of poorer behavioral adjustment in Met carriers relative to Val/Val homozygotes in the TBI group; in contrast, the opposite trend was observed in the OI group. These within-group differences, however, did not reach statistical significance. The results support a differential effect of the BDNF Val66Met polymorphism on behavioral adjustment in children with early TBI relative to OI, and suggest that the Met allele associated with reduced activity-dependent secretion of BDNF may impart risk for poorer long-term behavioral adjustment in children with TBI.
An α–β-Divergence-Generalized Recommender for Highly Accurate Predictions of Missing User Preferences

To quantify user–item preferences, a recommender system (RS) commonly adopts a high-dimensional and sparse (HiDS) matrix. Such a matrix can be represented by a non-negative latent factor analysis model relying on a single latent factor (LF)-dependent, non-negative, and multiplicative update algorithm. However, existing models’ representative abilities are limited due to their specialized learning objective. To address this issue, this study proposes an <inline-formula> <tex-math notation="LaTeX">$\alpha - \beta $ </tex-math></inline-formula>-divergence-generalized model that enjoys fast convergence. Its ideas are three-fold: 1) generalizing its learning objective with <inline-formula> <tex-math notation="LaTeX">$\alpha - \beta $ </tex-math></inline-formula>-divergence to achieve highly accurate representation of HiDS data; 2) incorporating a generalized momentum method into parameter learning for fast convergence; and 3) implementing self-adaptation of controllable hyperparameters for excellent practicability. Empirical studies on six HiDS matrices from real RSs demonstrate that compared with state-of-the-art LF models, the proposed one achieves significant accuracy and efficiency gain to estimate huge missing data in an HiDS matrix.
Electrodeposition of chromium–cobalt alloy from Cr(III) formate-urea electrolyte

Abstract To study the electrodeposition of Cr–Co alloy, as a possible alternative to the deposition of pure Cr, in particular from hexavalent Cr baths, Cr(III) formate–urea electrolyte containing various concentrations of CoCl2 was used. The deposition rate, composition, phase state and structure of Cr–Co deposits were investigated. The data obtained suggest that the electrodeposition of Cr–Co alloy occurs under acceleration of Cr(III) and inhibition of Co(II) ions electroreductions. It was found that the presence of 1–2 g L–1 CoCl2 in Cr(III) bath has an optimum effect on the electrodeposition of the good quality thick (30 μm) Cr–Co alloy obtained. The X-ray diffraction data reveal that the Cr–Co alloy deposit has an X-ray amorphous structure with a grain size of ∼1·3 nm. The morphology of the deposit shows a significant dependence of the nodular structure on the percentage of Co. X-ray photoemission spectroscopic spectra indicate the presence of oxide and metal phases for both metals in the top layers of as deposited Cr–Co alloy.
If I stop, then what am I supposed to do? The experiences of sexual intimacy of women who live with provoked vestibulodynia

Abstract We explored the experiences of sexual intimacy in women living with provoked vestibulodynia (PVD), a chronic pain condition where pain at the vaginal opening is triggered by touch. We conducted in-depth interviews with nine women who had suffered from PVD. Our findings reveal that their ability to trust and accept themselves is essential to how they cope when pain disrupts their freedom to have sexual intercourse. The tendency to endure painful intercourse and not tell the partner is driven by fear of rejection and conflict. Those who are able to overcome their fear, experience deeper intimacy and more sexual pleasure.
Identification of elastofibroma and elastofibroma-like lesions in cases diagnosed as oral fibromas

ABSTRACT We investigated elastofibromas (EF) and elastofibroma-like structures (EFL) in 95 cases that had been diagnosed as oral fibromas (OF). Histological sections were stained with Verhoeff-Van Gieson, Congo red and hematoxylin and eosin to enable possible reclassification to EF or EFL, or to retain the diagnosis of OF. To do this, we identified amyloid and used histopathological descriptions and epidemiological clinical profiles. We found 56 EF and 21 EFL cases, while 18 diagnoses of OF were retained. We observed a predilection for EF in females. Also, the most common site for OF was the cheek mucosa. We also found a longer time course for lesion development for OF compared to the other lesions. We found a relation between elastic fibers and amyloid material in EF. We also observed perivascular fibrotic lesions (PVFL) in EF. Most cases of EF exhibited more elastic fibers, thicker fibers, stronger relation with amyloid material deposition, rare evidence of PVFL and a longer time course for development compared to the other lesions. We suggest that EFL may give rise to oral EF.
Investigating the Clinical Utility of the Combined Use of Objective and Subjective Measures of ADHD During Treatment Optimization

Supplemental digital content is available in the text. Abstract Background This study investigated the clinical utility of the combined use of objective and subjective measures of attention-deficit/hyperactivity disorder (ADHD) prepharmacological and postpharmacological treatment. Methods Adults with ADHD (N = 77) completed the Quantified Behavioral Test, self-ratings of ADHD-related symptoms, and quality of life measures pretreatment and posttreatment. Results The use of objective and subjective measures of ADHD-related symptoms during initiation and follow-up of pharmacological treatment resulted in significant improvements in quality of life after 6 months. Both objective and subjective measures captured changes in ADHD-related symptoms, with more patients showing clinically relevant treatment effects on objective measures. Convergence rates between objective and subjective measures were low to moderate, and improvements on these measures correlated with increased quality of life. Conclusions Objective and subjective measures of ADHD capture important components of the condition. The findings from this study have important implications for clinical practice.
Comment on: Bronchoalveolar lavage fluid lymphocytosis in chronic hypersensitivity pneumonitis: a systematic review and meta-analysis

We commend Adderley et al. [1] for their meta-analysis assessing bronchoalveolar lavage fluid (BALF) lymphocytosis in the diagnosis of chronic hypersensitivity pneumonitis. Distinguishing chronic hypersensitivity pneumonitis (cHP) from idiopathic pulmonary fibrosis (IPF) has prognostic and therapeutic implications. Since there are no studies using lung biopsy as the gold standard to answer this question, the authors had to rely on observational studies, some of which used BALF lymphocytosis as a criterion to diagnose cHP. The authors acknowledge that this can cause diagnostic test incorporation bias. Incorporation bias can result in falsely increased estimates of the association between BALF lymphocytosis and cHP, or in biased conclusions that a bronchoalveolar lavage (BAL) lymphocyte count can rule in or rule out cHP. This is because specificity and sensitivity can be affected when the test under study is used as part of the gold standard to diagnose the condition of interest [2]. Bronchoalveolar lavage fluid lymphocytosis may be useful in the diagnosis of chronic hypersensitivity pneumonitis. However, reanalysis after eliminating studies that used bronchoalveolar lavage lymphocytosis as part of the diagnostic criteria is needed. https://bit.ly/34AmHmm
The socioeconomic distribution of alcohol-related violence in England and Wales

Inequalities in alcohol-related health harms have been repeatedly identified. However, the socioeconomic distribution of alcohol-related violence (violence committed by a person under the influence of alcohol)–and of subtypes such as alcohol-related domestic violence–remains under-examined. To examine this, data are drawn from nationally representative victimisation survey, the Crime Survey for England and Wales, from years 2013/14 to 2017/18. Socioeconomic status specific incidence and prevalence rates for alcohol-related violence (including subtypes domestic, stranger, and acquaintance violence) were created. Binomial logistic regressions were performed to test whether the likelihood of experiencing these incidents was affected by socioeconomic status when controlling for a range of pre-established risk factors associated with violence victimisation. Findings generally show lower socioeconomic groups experience higher prevalence rates of alcohol-related violence overall, and higher incidence and prevalence rates for alcohol-related domestic and acquaintance violence. Binomial logistic regression results show that the likelihood of experiencing these types of violence is affected by a person’s socioeconomic status–even when other risk factors known to be associated with violence are held constant. Along with action to address environmental and economic drivers of socioeconomic inequality, provision of publicly funded domestic violence services should be improved, and alcohol pricing and availability interventions should be investigated for their potential to disproportionately benefit lower socioeconomic groups.
Winter is coming–Temperature affects immune defenses and susceptibility to Batrachochytrium salamandrivorans

Environmental temperature is a key factor driving various biological processes, including immune defenses and host-pathogen interactions. Here, we evaluated the effects of environmental temperature on the pathogenicity of the emerging fungal pathogen, Batrachochytrium salamandrivorans (Bsal), using controlled laboratory experiments, and measured components of host immune defense to identify regulating mechanisms. We found that adult and juvenile Notophthalmus viridescens died faster due to Bsal chytridiomycosis at 14°C than at 6 and 22°C. Pathogen replication rates, total available proteins on the skin, and microbiome composition likely drove these relationships. Temperature-dependent skin microbiome composition in our laboratory experiments matched seasonal trends in wild N. viridescens, adding validity to these results. We also found that hydrophobic peptide production after two months post-exposure to Bsal was reduced in infected animals compared to controls, perhaps due to peptide release earlier in infection or impaired granular gland function in diseased animals. Using our temperature-dependent susceptibility results, we performed a geographic analysis that revealed N. viridescens populations in the northeastern United States and southeastern Canada are at greatest risk for Bsal invasion, which shifted risk north compared to previous assessments. Our results indicate that environmental temperature will play a key role in the epidemiology of Bsal and provide evidence that temperature manipulations may be a viable disease management strategy.
Production of β‐carotene in Saccharomyces cerevisiae through altering yeast lipid metabolism

Saccharomyces cerevisiae is a widely used cell factory for the production of fuels and chemicals. However, as a non‐oleaginous yeast, S. cerevisiae has a limited production capacity for lipophilic compounds, such as β‐carotene. To increase its accumulation of β‐carotene, we engineered different lipid metabolic pathways in a β‐carotene producing strain and investigated the relationship between lipid components and the accumulation of β‐carotene. We found that overexpression of sterol ester synthesis genes ARE1 and ARE2 increased β‐carotene yield by 1.5‐fold. Deletion of phosphatidate phosphatase (PAP) genes (PAH1, DPP1, and LPP1) also increased β‐carotene yield by twofold. Combining these two strategies resulted in a 2.4‐fold improvement in β‐carotene production compared with the starting strain. These results demonstrated that regulating lipid metabolism pathways is important for β‐carotene accumulation in S. cerevisiae, and may also shed insights to the accumulation of other lipophilic compounds in yeast.