Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of tumor microenvironment-related signature for predicting prognosis and immunotherapy response in patients with bladder cancer

The tumor microenvironment (TME) not only provides fertile soil for tumor growth and development but also widely involves immune evasion as well as the resistance towards therapeutic response. Accumulating interest has been attracted from the biological function of TME to its effects on patient outcomes and treatment efficacy. However, the relationship between the TME-related gene expression profiles and the prognosis of bladder cancer (BLCA) remains unclear. The TME-related genes expression data of BLCA were collected from The Cancer Genome Atlas (TCGA) database. NFM algorithm was used to identify the distinct molecular pattern based on the significantly different TME-related genes. LASSO regression and Cox regression analyses were conducted to identify TME-related gene markers related to the prognosis of BLCA and to establish a prognostic model. The predictive efficacy of the risk model was verified through integrated bioinformatics analyses. Herein, 10 TME-related genes (PFKFB4, P4HB, OR2B6, OCIAD2, OAS1, KCNJ15, AHNAK, RAC3, EMP1, and PRKY) were identified to construct the prognostic model. The established risk scores were able to predict outcomes at 1, 3, and 5 years with greater accuracy than previously known models. Moreover, the risk score was closely associated with immune cell infiltration and the immunoregulatory genes including T cell exhaustion markers. Notably, the predictive power of the model in immunotherapy sensitivity was verified when it was applied to patients with metastatic urothelial carcinoma (mUC) undergoing immunotherapy. In conclusion, TME risk score can function as an independent prognostic biomarker and a predictor for evaluating immunotherapy response in BLCA patients, which provides recommendations for improving patients’ response to immunotherapy and promoting personalized tumor immunotherapy in the future.
Contribution of gut microbiota toward renal function in sepsis

Sepsis most often involves the kidney and is one of the most common causes of acute kidney injury. The prevalence of septic acute kidney injury has increased significantly in recent years. The gut microbiota plays an important role in sepsis. It interacts with the kidney in a complex and multifactorial process, which is not fully understood. Sepsis may lead to gut microbiota alteration, orchestrate gut mucosal injury, and cause gut barrier failure, which further alters the host immunological and metabolic homeostasis. The pattern of gut microbiota alteration also varies with sepsis progression. Changes in intestinal microecology have double-edged effects on renal function, which also affects intestinal homeostasis. This review aimed to clarify the interaction between gut microbiota and renal function during the onset and progression of sepsis. The mechanism of gut–kidney crosstalk may provide potential insights for the development of novel therapeutic strategies for sepsis.
The addiction behavior of short-form video app TikTok: The information quality and system quality perspective

TikTok has one of the most advanced algorithm systems and is the most addictive as compared to other social media platforms. While research on social media addiction is abundant, we know much less about how the TikTok information system environment affects users’ internal states of enjoyment, concentration, and time distortion (which scholars define as the flow experience), which in turn influences their addiction behavior. To fill this gap, this study collects responses from 659 adolescents in China aged between 10 and 19 years old, and the data is then analyzed using Partial Least Square (PLS). We find that the system quality has a stronger influence than information quality in determining adolescents’ experience with TikTok and that the flow experience has significant direct and indirect effects on TikTok addiction behavior. Notably, this study finds that TikTok addiction is determined by users’ mental concentration on the medium and its content. Several theoretical insights from the stimulus–organism–response (S–O–R) model and the flow theory are used to explain the findings.
Factors associated with self-perceived health status in Portugal: Results from the National Health Survey 2014

Background Self-perceived health is an important indicator of illness and mortality. This study aims at identifying a wide range of factors that can influence self-perceived health status among a representative sample in Portugal. Methods We used the 2014 National Health Survey (n = 17,057), whereby participants were required to assess their health status from “Very good,” “Good,” “Fair,” “Poor” to “Very poor. ” We grouped the answers “Very good” and “Good,” and “Poor” and “Very poor,” respectively. Multinomial logistic regression was used to compare participants' characteristics across groups by computing odds ratio and corresponding 95% confidence intervals. Models included Socioeconomic/demographic characteristics, objective health status, healthcare use, functional disability, barriers to healthcare services utilization, lifestyle variables, mental health status, social support, and satisfaction with life as potential factors that can affect self-perceived health. Models were adjusted for sex, age, educational level, degree of urbanization, and presence of chronic diseases. Results About 45% of participants reported good/very good, 39% reported fair, while ~16% reported poor/very poor health perception. Poor/very poor health was more reported by women when compared to men (19.1 vs. 11.4%, respectively, p < 0.001). A higher prevalence of poor/very poor health status was reported by participants living in thinly populated areas or among older populations. Lower educational levels, lower income, as well as unemployment, were found to increase the risk of reporting poor/very poor health status. Utilizing healthcare services more frequently, experiencing barriers to access healthcare services, having depressive symptoms or activity limitations, or lacking social support were found to be significantly associated with poor/very poor self-perceived health. Conclusion Subjects living in Portugal tend to report less good/very good health status and more poor/very poor health when compared to the rest of Europe. This study stresses the importance of socioeconomic factors, chronic illness, barriers to access healthcare services, social isolation, and mental health status in influencing self-perceived health and highlights the urgent need for social-informed policies, strategies, and interventions to reduce health inequalities in Portugal.
EGCG protects the mouse brain against cerebral ischemia/reperfusion injury by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway

Stroke remains one of the leading reasons of mortality and physical disability worldwide. The treatment of cerebral ischemic stroke faces challenges, partly due to a lack of effective treatments. In this study, we demonstrated that autophagy was stimulated by transient middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R). Treatment with (−)-epigallocatechin-3-gallate (EGCG), a bioactive ingredient in green tea, was able to mitigate cerebral ischemia/reperfusion injury (CIRI), given the evidence that EGCG administration could reduce the infarct volume and protect poststroke neuronal loss in MCAO/R mice in vivo and attenuate cell loss in OGD/R-challenged HT22 cells in vitro through suppressing autophagy activity. Mechanistically, EGCG inhibited autophagy via modulating the AKT/AMPK/mTOR phosphorylation pathway both in vivo and in vitro models of stroke, which was further confirmed by the results that the administration of GSK690693, an AKT/AMPK inhibitor, and rapamycin, an inhibitor of mTOR, reversed aforementioned changes in autophagy and AKT/AMPK/mTOR signaling pathway. Overall, the application of EGCG relieved CIRI by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway.
Role of LGR5-positive mesenchymal cells in craniofacial development

Leucine Rich Repeat Containing G Protein-Coupled Receptor 5 (LGR5), a Wnt pathway member, has been previously recognised as a stem cell marker in numerous epithelial tissues. In this study, we used Lgr5-EGFP-CreERT2 mice to analyse the distribution of LGR5-positive cells during craniofacial development. LGR5 expressing cells were primarily located in the mesenchyme adjacent to the craniofacial epithelial structures undergoing folding, such as the nasopharyngeal duct, lingual groove, and vomeronasal organ. To follow the fate of LGR5-positive cells, we performed lineage tracing using an inducible Cre knock-in allele in combination with Rosa26-tdTomato reporter mice. The slight expansion of LGR5-positive cells was found around the vomeronasal organ, in the nasal cavity, and around the epithelium in the lingual groove. However, most LGR5 expressing cells remained in their original location, possibly supporting their signalling function for adjacent epithelium rather than exerting their role as progenitor cells for the craniofacial structures. Moreover, Lgr5 knockout mice displayed distinct defects in LGR5-positive areas, especially in the reduction of the nasopharyngeal duct, the alteration of the palatal shelves shape, abnormal epithelial folding in the lingual groove area, and the disruption of salivary gland development. The latter defect manifested as an atypical number and localisation of the glandular ducts. The gene expression of several Wnt pathway members (Rspo1-3, Axin2) was altered in Lgr5-deficient animals. However, the difference was not found in sorted EGFP-positive cells obtained from Lgr5 +/+ and Lgr5 −/− animals. Expression profiling of LGR5-positive cells revealed the expression of several markers of mesenchymal cells, antagonists, as well as agonists, of Wnt signalling, and molecules associated with the basal membrane. Therefore, LGR5-positive cells in the craniofacial area represent a very specific population of mesenchymal cells adjacent to the epithelium undergoing folding or groove formation. Our results indicate a possible novel role of LGR5 in the regulation of morphogenetic processes during the formation of complex epithelial structures in the craniofacial areas, a role which is not related to the stem cell properties of LGR5-positive cells as was previously defined for various epithelial tissues.
Development of Clinical Risk Scores for Detection of COVID-19 in Suspected Patients During a Local Outbreak in China: A Retrospective Cohort Study

Objectives: To develop and internally validate two clinical risk scores to detect coronavirus disease 2019 (COVID-19) during local outbreaks. Methods: Medical records were extracted for a retrospective cohort of 336 suspected patients admitted to Baodi hospital between 27 January to 20 February 2020. Multivariate logistic regression was applied to develop the risk-scoring models, which were internally validated using a 5-fold cross-validation method and Hosmer-Lemeshow (H-L) tests. Results: Fifty-six cases were diagnosed from the cohort. The first model was developed based on seven significant predictors, including age, close contact with confirmed/suspected cases, same location of exposure, temperature, leukocyte counts, radiological findings of pneumonia and bilateral involvement (the mean area under the receiver operating characteristic curve [AUC]:0.88, 95% CI: 0.84–0.93). The second model had the same predictors except leukocyte and radiological findings (AUC: 0.84, 95% CI: 0.78–0.89, Z = 2.56, p = 0.01). Both were internally validated using H-L tests and showed good calibration (both p > 0.10). Conclusion: Two clinical risk scores to detect COVID-19 in local outbreaks were developed with excellent predictive performances, using commonly measured clinical variables. Further external validations in new outbreaks are warranted.
Vicarious structural racism and infant health disparities in Michigan: The Flint Water Crisis

Building on nascent literature examining the health-related effects of vicarious structural racism, we examined indirect exposure to the Flint Water Crisis (FWC) as a predictor of birth outcomes in Michigan communities outside of Flint, where residents were not directly exposed to lead-contaminated water. Using linear regression models, we analyzed records for all singleton live births in Michigan from 2013 to 2016, excluding Flint, to determine whether birth weight (BW), gestational age (GA), and size-for-gestational-age (SzGA) decreased among babies born to Black people, but not among babies born to White people, following the highly publicized January 2016 emergency declaration in Flint. In adjusted regression models, BW and SzGA were lower for babies born to both Black and White people in the 37 weeks following the emergency declaration compared to the same 37-week periods in the previous 3 years. There were no racial differences in the association of exposure to the emergency declaration with BW or SzGA. Among infants born to Black people, GA was 0.05 weeks lower in the 37-week period following the emergency declaration versus the same 37-week periods in the previous 3 years (95% CI: −0.09, −0.01; p = 0.0177), while there was no change in GA for infants born to White people following the emergency declaration (95% CI: −0.01, 0.03; p = 0.6962). The FWC, which was widely attributed to structural racism, appears to have had a greater impact, overall, on outcomes for babies born to Black people. However, given the frequency of highly publicized examples of anti-Black racism over the study period, it is difficult to disentangle the effects of the FWC from the effects of other racialized stressors.
Classification of expert-level therapeutic decisions for degenerative cervical myelopathy using ensemble machine learning algorithms

Background Therapeutic decisions for degenerative cervical myelopathy (DCM) are complex and should consider various factors. We aimed to develop machine learning (ML) models for classifying expert-level therapeutic decisions in patients with DCM. Methods This retrospective cross-sectional study included patients diagnosed with DCM, and the diagnosis of DCM was confirmed clinically and radiologically. The target outcomes were defined as conservative treatment, anterior surgical approaches (ASA), and posterior surgical approaches (PSA). We performed the following classifications using ML algorithms: multiclass, one-versus-rest, and one-versus-one. Two ensemble ML algorithms were used: random forest (RF) and extreme gradient boosting (XGB). The area under the receiver operating characteristic curve (AUC-ROC) was the primary metric. We also identified the variable importance for each classification. Results In total, 304 patients were included (109 conservative, 66 ASA, 125 PSA, and 4 combined surgeries). For multiclass classification, the AUC-ROC of RF and XGB models were 0.91 and 0.92, respectively. In addition, ML models showed AUC-ROC values of >0.9 for all types of binary classifications. Variable importance analysis revealed that the modified Japanese Orthopaedic Association score and central motor conduction time were the two most important variables for distinguishing between conservative and surgical treatments. When classifying ASA and PSA, the number of involved levels, age, and body mass index were important contributing factors. Conclusion ML-based classification of DCM therapeutic options is valid and feasible. This study can be a basis for establishing generalizable ML-based surgical decision models for DCM. Further studies are needed with a large multicenter database.
Value assessment of medicinal products by the Italian Medicines Agency (AIFA) and French National Authority for Health (HAS): Similarities and discrepancies

The evaluation of pharmaceutical innovation and therapeutic value is an increasingly complex exercise for which different approaches are adopted at the national level, despite the need for standardisation of processes and harmonisation of public health decisions. The objective of our analysis was to compare the approaches of the AIFA (Agenzia Italiana del Farmaco) and the HAS (Haute Autorité de Santé) in assessing the same medicinal products. In Italy, the 1525/2017 AIFA Deliberation introduces a transparent scheme for the evaluation of innovative status (innovative, conditional, not innovative) based on the therapeutic added value (TAV), therapeutic need, and quality of evidence. In contrast, in France, the HAS makes judgements using the effective clinical benefit (Service Médical Rendu) and improvement of effective clinical benefit (Amélioration du Service Médical Rendu, ASMR). This analysis focused on medicinal products evaluated both by the AIFA and by the HAS from July 2017 to September 2021. Similarities between AIFA and HAS evaluations were investigated in terms of the TAV, recognition of innovativeness, and the ASMR. Both total and partial agreements were considered relevant. Therefore, raw agreement, Cohen's kappa (weighted and unweighted), and Bangdiwala's B-statistic were estimated. A total of 102 medicinal products were included in this study. Out of these, 38 (37.2%) were orphan drugs, while 56 (54.9%) had a clinical indication for the treatment of cancer. The AIFA and HAS reached a higher level of agreement on the innovativeness status compared with the TAV. A moderate total agreement emerged in the recognition of innovativeness (k = 0.463, p-value ≤0.0001), and partial agreement was substantial (equal weight k = 0.547, squared k = 0.638), while a lack of agreement resulted in a comparison of the TAV according to the AIFA and the ASMR recognised by the HAS. Indeed, whereas the AIFA determined the TAV to be important, the HAS considered it to be moderate. In addition, whereas the AIFA identified a bias towards a moderate TAV, the HAS identified a bias towards a minor ASMR. A higher level of agreement was reached, both on the TAV and on innovative status, for less critical medical products (non-cancer-related, or non-orphan, or with a standard European Medicines Agency approval). These results underline the importance of implementing European procedures that are more broadly aligned in terms of value definition criteria.
Ethnicity-based classifications and medical genetics: One Health approaches from a Western Pacific perspective

A new era presently dawns for medical genetics featuring individualised whole genome sequencing and promising personalised medical genetics. Accordingly, we direct readers attention to the continuing value of allele frequency data from Genome-Wide Association Surveys (GWAS) and single gene surveys in well-defined ethnic populations as a guide for best practice in diagnosis, therapy, and prescription. Supporting evidence is drawn from our experiences working with Austronesian volunteer subjects across the Western Pacific. In general, these studies show that their gene pool has been shaped by natural selection and become highly diverged from those of Europeans and Asians. These uniquely evolved patterns of genetic variation underlie contrasting schedules of disease incidence and drug response. Thus, recognition of historical bonds of kinship among Austronesian population groups across the Asia Pacific has distinct public health advantages from a One Health perspective. Other than diseases that are common among them like gout and diabetes, Austronesian populations face a wide range of climate-dependent infectious diseases including vector-borne pathogens as they are now scattered across the Pacific and Indian Oceans. However, we caution that the value of genetic survey data in Austronesians (and other groups too) is critically dependent on the accuracy of attached descriptive information in associated metadata, including ethnicity and admixture.
Expression of extracellular matrix components in the meibomian gland

Purpose Extracellular matrix (ECM) is a key component of the stem cell local microenvironment. Our study aims to explore the periglandular distribution of major components of ECM in the Meibomian gland (MG). Methods Human eyelids and mouse eyelids were collected and processed for immunofluorescence staining. Results Human MG tissues stained positive for collagen IV α1, collagen IV α2, collagen IV α5, and collagen IV α6 around the acini and duct, but negative for collagen IV α3 and collagen IV α4. The mouse MG were stained positive for the same collagen IV subunits as early as postnatal day 15. Laminin α2, laminin β1 and perlecan stained the regions surrounding the acini and the acinar/ductal junction in the human MG, but not the region around the duct. Tenascin-C was found specifically located at the junctions between the acini and the central ducts. Neither agrin nor endostatin was found in the human MG tissues. Conclusion The ECM expresses specific components in different regions around the MG, which may play a role in MG stem cell regulation, renewal, and regeneration.
Rapid changes in heatwaves pose dual challenge in Eastern China and its adjacent seas

This paper performs a comparative analysis of the spatiotemporal variations of the statistical characteristics of both atmospheric heatwaves over the land (AHWs) in eastern China and marine heatwaves (MHWs) in adjacent seas using a unified heatwave definition. The multi-year average total days and frequency of MHWs during 1982-2019 were 5 and 2 times higher than those of AHWs, respectively, while the mean intensities of AHWs and MHWs were unchanged. The future frequency and duration of AHWs will continue to increase, leading to a superimposed increase in AHW total days. The decreasing frequency and increasing duration of MHWs will result in nearly year-round MHWs from 2060. Under the control of high-pressure systems, clear skies dominate the summer weather conditions in eastern China and its adjacent seas, which will trigger heatwaves. Heatwaves in turn can release substantial ocean latent heat. Enhanced convection and heating will further drive a stronger anticyclone over the western North Pacific, leading to a stronger and more westward-extending western North Pacific subtropical high (WNPSH). Moreover, super El Niño can promote an anomalous WNPSH in decaying summer, which may cause more serious heatwaves. The multi-year average persons affected by AHWs (PAHWs) during 1982-2019 were larger in the North China Plain, Yangtze River Delta, and Sichuan Basin with the regional sum exceeding 3 million. The future maximum PAHWs under SSP2-4.5 and SSP5-8.5 scenarios will be 3.9 billion in 2076 and 4.7 billion in 2085, respectively. Marine ecosystems like artificial ranches and coral reefs will be more threatened by longer-lasting MHWs.
A cohort study of vitamins contents in human milk from maternal-infant factors

Human milk vitamin content is an important indicator to evaluate the nutritional composition of human milk. This paper investigates the influence of maternal and infant factors on the dynamics of human milk vitamin content. A total of 147 mother-infant pairs from 3 different cities (north-south distribution) in China were selected and 9 major vitamins were measured in 332 human milk samples. The three vitamins (vitamin A, β-carotene, and pantothenic acid) showed significant downward trends with lactation period (| r | > 0.3, p < 0.05). The lactation period factor could explain the negative variation of vitamin A (21.2%) and pantothenic acid (9.5%). The factors of lactation period and oils intake could jointly explain variations of β-carotene (11.8%). (Registration number: NCT02658500).