Miracle-dz/UniFAR-FTUs huggingface dataset:
Proton Pump Inhibitor Use and Complications of Cirrhosis Are Linked With Distinct Gut Microbial Bacteriophage and Eukaryotic Viral-Like Particle Signatures in Cirrhosis

INTRODUCTION: Proton pump inhibitors (PPIs) modulate the progression of cirrhosis to hepatic encephalopathy (HE) and can affect the bacterial microbiome. However, the impact of PPI on the virome in cirrhosis using viral-like particle (VLP) analysis is unclear. METHODS: We determined the VLP in the stool microbiome in patients with cirrhosis cross-sectionally (ascites, HE, and PPI use analyzed) who were followed up for 6-month hospitalizations and through 2 clinical trials of PPI withdrawal and initiation. RESULTS: In a cross-sectional study, PPI users had greater ascites prevalence and 6-month hospitalizations, but VLP α diversity was similar. Among phages, PPI users had lower Autographviridae and higher Streptococcus phages and Herelleviridae than nonusers, whereas opposite trends were seen in ascites and HE. Trends of eukaryotic viruses (higher Adenoviridae and lower Virgaviridae/Smacoviridae) were similar for PPI, HE, and ascites. Twenty-one percent were hospitalized, mostly due to HE. α Diversity was similar in the hospitalized/nonhospitalized/not groups. Higher Gokushovirinae and lower crAssphages were related to hospitalizations such as HE-related cross-sectional VLP changes. As part of the clinical trial, PPIs were added and withdrawn in 2 different decompensated groups over 14 days. No changes in α diversity were observed. Withdrawal reduced crAssphages, and initiation reduced Gokushovirinae and Bacteroides phages. DISCUSSION: In cirrhosis, PPI use has a gut microbial VLP phage signature that is different from that in HE and ascites, and VLP changes are linked with hospitalizations over 6 months, independent of clinical biomarkers. Eukaryotic viral patterns were consistent across PPI use, HE, and ascites, indicating a relationship with the progression of cirrhosis. PPIs alone showed modest VLP changes with withdrawal or initiation. Distinct phage and eukaryotic viral patterns are associated with the use of PPIs in cirrhosis.
Real‐world effectiveness and safety of RC48‐ADC alone or in combination with PD‐1 inhibitors for patients with locally advanced or metastatic urothelial carcinoma: A multicenter, retrospective clinical study

Previous RC48 (Disitamab Vedotin) studies established that the safety and efficacy of RC48‐antibody–drug conjugate (ADC), either alone or combined with toripalimab, for metastatic urothelial carcinoma (mUC) patients exhibiting human epidermal growth factor receptor 2 (HER2)‐positive or even HER2‐negative status after standard chemotherapy failure.
Economic and social impacts of the migration of Sri Lankan transnational domestic workers on families and children left behind.

Some of the world's largest flows of temporary migrant workers originate in Asian countries. Almost all of these migration flows involve the separation of the migrant from their families whether extended or nuclear. Consequently, transnational families in which one or more members are out of the country for several years are increasingly common in the Asian region. Moreover, there are increasing numbers of migrant families with one or both parents being overseas for work for a significant part of the growing up of their children. In the Asian region, a large proportion of absent mothers are found in countries like the Philippines, Indonesia, and Sri Lanka. While the issue of the families and children left behind by migrant women has been intensively studied from a number of perspectives in the Asian Region, especially in the Philippines, it remains under-researched and indeed little understood in Sri Lanka, which is one of the major suppliers of overseas domestic workers. Currently, the Sri Lankan government faces a dilemma. On one hand, remittances from overseas migrant workers overseas are the second largest source of foreign export earnings, and 60 per cent of this is from the migrants in Middle East countries where the majority of domestic workers are employed. On the other hand, there is a growing concern with the social effects of that movement on the children left behind by migrant women. Some countries in the region have banned the deployment of women migrant workers, but this has simply channelled them into undocumented flows. Although the government of Sri Lanka had several discussions to restrict the migration of females, it was found such a decision would be unworkable. A virtual vacuum of empirical evidence regarding the effects of the absence of mothers on their families and children left behind is recognised. Therefore, by examining how the families and children left behind are influenced by the migration of the “light of the home”, this thesis provides valuable information that is urgently required by policy makers. The thesis reports on a field survey of 400 Sri Lankan families where the mother has gone to work in a foreign country as a domestic worker and detailed discussions with key stakeholders in the study area. It examines the effects of the migration of domestic workers on the economic and social situation of their families and children. On one hand, the effects of increased money on the overall economic well-being of their families and the education of children are positive. On the other hand, there are several negative impacts on the behavioural patterns and health of the children left behind and the family as a whole. This study also reports on the arrangements that are made by the migrant women for taking care of the children while they are away and how they maintain intimacy with their families from a distance. Differences in the impacts are investigated between urban, rural, and estate based households as well as according to the demographic and socio-economic characteristics of the…
Genetic independence between traits separated by metamorphosis is widespread but varies with biological function

Why is metamorphosis so pervasive? Does it facilitate the independent (micro)evolution of quantitative traits in distinct life stages, similarly to how it enables some limbs and organs to develop at specific life stages? We tested this hypothesis by measuring the expression of 6400 genes in 41 Drosophila melanogaster inbred lines at larval and adult stages. Only 30% of the genes showed significant genetic correlations between larval and adult expression. By contrast, 46% of the traits showed some level of genetic independence between stages. Gene ontology terms enrichment revealed that across stages correlated traits were often involved in proteins synthesis, insecticide resistance and innate immunity, while a vast number of genes expression traits associated with energy metabolism were independent between life stages. We compared our results to a similar case: genetic constraints between males and females in gonochoric species (i.e. sexual antagonism). We expected selection for the separation between males and females to be higher than between juvenile and adult functions, as gonochorism is a more common strategy in the animal kingdom than metamorphosis. Surprisingly, we found that inter-stage constraints were lower than inter-sexual genetic constraints. Overall, our results show that metamorphosis enables a large part of the transcriptome to evolve independently at different life stages.
Dabrafenib protects from cisplatin-induced hearing loss in a clinically relevant mouse model

The widely used chemotherapy cisplatin causes permanent hearing loss in 40%–60% of patients with cancer. One drug, sodium thiosulfate, is approved by the FDA for use in pediatric patients with localized solid tumors for preventing cisplatin-induced hearing loss, but more drugs are desperately needed. Here, we tested dabrafenib, an FDA-approved BRAF kinase inhibitor and anticancer drug, in a clinically relevant multidose cisplatin mouse model. The protective effects of dabrafenib, given orally twice daily with cisplatin, were determined by functional hearing tests and cochlear outer hair cell counts. Toxicity of the drug cotreatment was evaluated, and levels of phosphorylated ERK were measured. A dabrafenib dose of 3 mg/kg BW, twice daily, in mice, was determined to be the minimum effective dose, and it is equivalent to one-tenth of the daily FDA-approved dose for human cancer treatment. The levels of hearing protection acquired, 20–25 dB at the 3 frequencies tested, in both female and male mice, persisted for 4 months after completion of treatments. Moreover, dabrafenib exhibited a good in vivo therapeutic index (> 25), protected hearing in 2 mouse strains, and diminished cisplatin-induced weight loss. This study demonstrates that dabrafenib is a promising candidate drug for protection from cisplatin-induced hearing loss.
Belief updating when confronted with scientific evidence: Examining the role of trust in science

In one exploratory study (N = 985) and one preregistered study (N = 1100), we investigated whether trust in science influences belief change on a medico-scientific issue when laypersons are confronted with scientific evidence. Moreover, we tested whether individuals with high trust in science trust science “blindly,” meaning that their trust in a scientific claim’s source prevents them from adequately evaluating the claim itself. Participants read eight fictitious studies on the efficacy of acupuncture, which were experimentally manipulated regarding direction (evidence favoring acupuncture vs diverging evidence) and quality (high vs low; only Study 2). Acupuncture-related beliefs were measured before and after reading. Moderator and mediator analyses showed that the magnitude of belief change indeed depends on trust in science. Furthermore, we found that people with high trust in science are better able to evaluate the quality of scientific studies, which, in turn, protects them from being influenced by low-quality evidence.
Genetic Discontinuities and Sub structuring in buffaloes of Indo Gangetic Plains

The Indo-Gangetic plains of India are fertile basin and have more than 23% buffaloes of India. Bhadawari is the only one recognised breed of buffalo in the basin. The population structure of this vast buffalo population was not known. In this present study, we generated data on 11 microsatellite markers on 625 buffaloes from Indo- Gangetic plains. We utilised landscape genetic tools combining molecular genetic data and spatial coordinates to decipher the genetic structure. We utilised wombling analysis and Bayesian clustering using Markov models. We also utilised Monmonier's maximal difference algorithm for the identification of genetic barriers and tested their significance using 16 different genetic distances. The Womble analysis revealed three statistically significant barriers. The genetic bandwidth mapping revealed that buffaloes of Tarai area and Bhadawari buffaloes to have distinctive population structure. The buffaloes of Mau, Balia and Ghazipur also had a distinctive genetic structure. Most of the buffaloes of Central region of Indo-Gangetic plains were found to be heterogeneous. The variation in allele frequency in buffalo population in Indo Gangetic plains occurred at multiple scales. A sharp change in allele frequency in Eastern and Western Uttar Pradesh buffaloes was observed and detectable by all the techniques utilised and the buffalo population could be substructured into 5 clusters.
Association between sleep quality and cardiovascular disease in maintenance hemodialysis patients: a prospective cohort study

Abstract Objective This study aimed to analyze the association between sleep quality and cardiovascular disease in patients on maintenance hemodialysis (MHD). Methods A total of 601 patients with MHD in the second affiliated hospital of Nanjing Medical University, were prospectively enrolled in this cohort study from January 2019 to December2019. The global Pittsburgh sleep quality index (PSQI) score > 7 indicates that a person with poor sleep quality. Patients were divided into two groups according to the PSQI score. Follow-up was conducted about 3 years with all-cause death and major adverse cardiovascular events (MACEs) as the endpoint events. Results Of the 601 patients, 595 patients completed the PSQI assessment, with 278 patients having poor sleep quality. Patients in the PSQI > 7 group were older and had a higher proportion of cardiovascular disease or diabetes. Years of education, diastolic blood pressure, and heart rate were lower in the PSQI > 7 group. At a mean follow-up period of 3 years, 116 patients died, 64 patients were lost to follow-up, and 115 patients experienced MACEs. After adjusting for confounding factors such as age, gender, dialysis age, and previous cardiovascular disease, the risk of MACE in patients with poor sleep quality was twice that of patients with good sleep quality (HR = 2.037 (1.339, 3.097), p = 0.001). There was no significant difference in the risk of all-cause death between the two groups. Conclusion The prevalence of poor sleep quality was 46.7% in patients with MHD. Poor sleep quality was an independent risk factor for MACEs in patients with MHD.
Rhythmic modulation of prediction errors: A top-down gating role for the beta-range in speech processing

Natural speech perception requires processing the ongoing acoustic input while keeping in mind the preceding one and predicting the next. This complex computational problem could be handled by a dynamic multi-timescale hierarchical inferential process that coordinates the information flow up and down the language network hierarchy. Using a predictive coding computational model (Precoss-β) that identifies online individual syllables from continuous speech, we address the advantage of a rhythmic modulation of up and down information flows, and whether beta oscillations could be optimal for this. In the model, and consistent with experimental data, theta and low-gamma neural frequency scales ensure syllable-tracking and phoneme-level speech encoding, respectively, while the beta rhythm is associated with inferential processes. We show that a rhythmic alternation of bottom-up and top-down processing regimes improves syllable recognition, and that optimal efficacy is reached when the alternation of bottom-up and top-down regimes, via oscillating prediction error precisions, is in the beta range (around 20–30 Hz). These results not only demonstrate the advantage of a rhythmic alternation of up- and down-going information, but also that the low-beta range is optimal given sensory analysis at theta and low-gamma scales. While specific to speech processing, the notion of alternating bottom-up and top-down processes with frequency multiplexing might generalize to other cognitive architectures.
Multiple Arterial Thrombosis after COVID-19: A Case Report

Since the beginning of severe acute respiratory syndrome Coronavirus 2 pandemic, many reports have pointed to states of incrieased hypercoagulability during the acute phase of the disease. We report a 63-year-old female who developed acute mesenteric ischemia due to celiac trunk and superior mesenteric artery thrombi together with acute lower extremity ischemia caused by saddle embolism of the iliac bifurcation and thrombosis of the left external iliac artery. These thrombi developed 20 days after discharge from an intensive care unit due to severe pneumonia and pulmonary embolism associated with COVID-19. The patient had consecutive interventions. Surgical thrombectomy for aortoiliac thrombosis was performed and the mesenteric thrombosis was treated by percutaneous endovascular intervention. We emphasize that the prothrombotic state after COVID-19 infection may persist long after the acute symptomatic phase.
Pericentrin deficiency in smooth muscle cells augments atherosclerosis through HSF1-driven cholesterol biosynthesis and PERK activation

Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is caused by biallelic loss-of-function variants in pericentrin (PCNT), and premature coronary artery disease (CAD) is a complication of the syndrome. Histopathology of coronary arteries from patients with MOPDII who died of CAD in their 20s showed extensive atherosclerosis. Hyperlipidemic mice with smooth muscle cell–specific (SMC-specific) Pcnt deficiency (PcntSMC–/–) exhibited significantly greater atherosclerotic plaque burden compared with similarly treated littermate controls despite similar serum lipid levels. Loss of PCNT in SMCs induced activation of heat shock factor 1 (HSF1) and consequently upregulated the expression and activity of HMG-CoA reductase (HMGCR), the rate-limiting enzyme in cholesterol biosynthesis. The increased cholesterol biosynthesis in PcntSMC–/– SMCs augmented PERK signaling and phenotypic modulation compared with control SMCs. Treatment with the HMGCR inhibitor, pravastatin, blocked the augmented SMC modulation and reduced plaque burden in hyperlipidemic PcntSMC–/– mice to that of control mice. These data support the notion that Pcnt deficiency activates cellular stress to increase SMC modulation and plaque burden, and targeting this pathway with statins in patients with MOPDII has the potential to reduce CAD in these individuals. The molecular mechanism uncovered further emphasizes SMC cytosolic stress and HSF1 activation as a pathway driving atherosclerotic plaque formation independently of cholesterol levels.
Estimates of relationship between milk yield and age at first calving in Calcutta using multivariate REML

Relationship between milk yield and age at first calving in cattle were calculated from (co) variances estimated by multivariate restricted maximum likelihood with equal design matrix fitting a unbalanced mixed model with herd, year and calendar month of calving as fixed effects, and sire and residual errors as independent random effects. Univariate analyses were also carried out to compare the variances estimated by multivariate analysis. The data consisted of first lactation records on 733 purebred progeny of 69 Hariana sires in 3 herds from 1969 to 1981. The genetic correlation between yield and age was estimated to be 0.82+0.07 or 0.82-0.07, but the phenotypic correlation was only 0.37+0.05 or 0.37-0.05. Large differences were observed in the estimates of variances for milk yield from univariate and multivariate analysis, but for age at first calving the variances were quite similar.
LOCALIZATION OF ANDROID CONTENT IN RUNYAKITARA

The Android17 SDK supports thirty-seven languages, none of which are indigenous to Africa. The limited progress of the localization of ICT in Africa has been identified by several authors as one of the reasons for the digital divide between Africa and the rest of the world. However, several technology companies have translated their software (ranging from entire operating systems to specific application software) to indigenous African languages such as Kiswahili in East Africa, isiZulu in South Africa, and Dinka in Central Africa. This paper discusses the implementation of localization in Africa, as well as the contribution to these current efforts by translating Android English content to Runyakitara (one of Uganda’s indigenous languages). The paper explains the key parts of the translation process, which are: the translation of basic terms, nouns, and acronyms; vowel assimilation; and naturalization.
Better spiritual support for people living with early stage dementia: Developing the diamond conversation model

Background People with early-stage dementia could benefit greatly from on-going spiritual support. However, health care professionals working in dementia care often do not have a clear idea of what such support might entail. There is a lack of tools that can help professionals provide such support. The Diamond conversation model used in palliative care could provide such a support. Aims: To develop the Diamond model for early-stage dementia so that professionals can provide better spiritual support. Methods Participatory research was conducted. Reflective interviews with chaplains, case managers and health psychologists identified frequently occurring existential and spiritual issues of clients and family members. A core participatory group consisting of chaplains, a psychologist and a researcher further analysed these issues thematically and co-developed the Diamond model for early stage dementia over three co-creation sessions. Researchers with Diamond model expertise provided feedback to the core participatory group in between these sessions based on the session output. Findings Central existential and spiritual issues were found to be: self-confidence and –worth, adaptability and capacity, security and loss, burden and enrichment of memory and faith and meaning. The five polarities of the Diamond model were found helpful to understand tensions surrounding these issues. Specific tensions were identified between maintaining a self and being valued, finding direction in what to do and a way to bear changes in ability, a strong need for attachment and letting go of past ways to relate to one another, the renewed intensity of long term memories and decline of the short term ones and surrendering to one’s life situation and wanting certainty and meaning. Conclusions The newly developed Diamond model for people with early-stage dementia offers a valuable framework to help professionals provide conversational support. More research needs to be done to further test and develop the model in practice.
Histone retention preserves epigenetic marks during heat stress‐induced transcriptional memory in plants

Plants often experience recurrent stressful events, for example, during heat waves. They can be primed by heat stress (HS) to improve the survival of more severe heat stress conditions. At certain genes, sustained expression is induced for several days beyond the initial heat stress. This transcriptional memory is associated with hyper‐methylation of histone H3 lysine 4 (H3K4me3), but it is unclear how this is maintained for extended periods. Here, we determined histone turnover by measuring the chromatin association of HS‐induced histone H3.3. Genome‐wide histone turnover was not homogenous; in particular, H3.3 was retained longer at heat stress memory genes compared to HS‐induced non‐memory genes during the memory phase. While low nucleosome turnover retained H3K4 methylation, methylation loss did not affect turnover, suggesting that low nucleosome turnover sustains H3K4 methylation, but not vice versa. Together, our results unveil the modulation of histone turnover as a mechanism to retain environmentally mediated epigenetic modifications.