Miracle-dz/UniFAR-FTUs huggingface dataset:
Identify potential prognostic indicators and tumor-infiltrating immune cells in pancreatic adenocarcinoma

Abstract Background: Pancreatic adenocarcinoma (PAAD) is a kind of highly malignant tumor and lacks early diagnosis method and effective treatment. Tumor microenvironment (TME) is of great importance for the occurrence and development of PAAD. Thus, a comprehensive overview of genes and tumor-infiltrating immune cells (TICs) related to TME dynamic changes conduce to develop novel therapeutic targets and prognostic indicators. Methods: We used MAlignant Tumors using Expression data (ESTIMATE) algorithm to analyze the transcriptome RNA-seq data of 182 PAAD cases on The Cancer Genome Atlas (TCGA) platform. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI) network, COX regression analysis and gene set enrichment analysis (GSEA) were carried out to get the hub genes related to the prognosis of PAAD patients. These core genes were validated in GEPIA. CXCL10 expression as a poor prognostic indicator was validated in GEO database. Finally, CIBERSORT algorithm was applied to understand the status of TICs. Results: A total of 715 up-regulated differential expression genes (DEGs) and 57 down-regulated DEGs were found simultaneously in stromal and immune groups. These DEGs were mainly enriched in immune recognition, activation and response processes. CD4, CXCL12, CXCL10, CCL5 and CXCL9 were the top five core genes. Then, the validation of these genes showed that CD4, CXCL10, CXCL5, CXCL9 were up-regulated in PAAD. Among the core genes, CXCL10 had a negative correlation with the survival time of PAAD patients. CD8+ T cells, CD4+ T cells memory activated, macrophages M1 had positive correlation of CXCL10 expression, whereas regulatory T cells (Tregs), macrophages M0 and B cells memory had negative correlation. Conclusion: We generated a series of genes related to TME with prognostic implications and TICs in PAAD, which have the potential to be novel immunotherapy targets and prognostic markers. The data showed that CXCL10 was favorable as a poor prognostic indicator in PAAD patients.
Safety and efficacy of early augmentation with repetitive transcranial magnetic stimulation in the treatment of drug-free patients with obsessive–compulsive disorder

Abstract Background Obsessive–compulsive disorder (OCD) is a chronic psychiatric disorder that results in significant disability and substantial compromise in the quality of life. Until now, the role of repetitive transcranial magnetic stimulation (rTMS) has been primarily explored in individuals with treatment-resistant OCD. In this study, we investigated the safety and efficacy of rTMS as an early augmentation strategy in drug-free patients with OCD. Methods This is a randomized double-blind, placebo-controlled study that involved the administration of a total of 20 sessions of rTMS (active/sham) to drug-naïve OCD patients using a standard protocol (1-Hz; 20 trains [80 pulses/train]; 1600 pulses per session at 100% resting motor threshold) at supplementary motor area. All patients (active and sham) were started on escitalopram 10 mg/d, which was subsequently increased to 20 mg/d after 10 days. Results Out of the 24 patients, 13 received active and 11 received sham rTMS. At the end of rTMS therapy, there was a substantial reduction (P = .001) in total Yale-Brown Obsessive–Compulsive Scale, obsessions (P = .030) and compulsions (P = .001) between the groups. Only few patients (N = 8) reported mild side effect with rTMS, local pain, and headache being the commonest. The study revealed large effect size (Cohen’s d = 1.6) of rTMS as an early augmentation strategy in drug-free patients of OCD. Conclusions rTMS is a safe and effective early augmentation strategy in the management of OCD. Larger randomized controlled trials are required to establish the therapeutic role of rTMS as early augmentation in OCD.
Efficacy of D‐cycloserine augmented brief intensive cognitive‐behavioural therapy for paediatric obsessive‐compulsive disorder: A randomised clinical trial

To examine the efficacy of weight‐adjusted D‐cycloserine (DCS) (35 or 70 mg) relative to placebo augmentation of intensive exposure therapy for youth with obsessive‐compulsive disorder (OCD) in a double‐blind, randomised controlled trial, and examine whether antidepressant medication or patient age moderated outcomes.
Long-term exposure to zinc oxide nanoparticles improves PAOs function in enhanced biological phosphorus removal

ABSTRACT As the most widely applied process for biological phosphorus removal, enhanced biological phosphorus removal (EBPR) relies on phosphorus accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs), whose function is crucial for the removal of phosphorus. In this study, the effect of zinc oxide nanoparticles (ZnO NPs, 0–50 mg/L) on EBPR performance was investigated in both long-term reactors and batch experiments. It was found that the performance of biological phosphorus removal was recovered from 0% (day 0) to >99% (day 70) after long-term exposure of ZnO NPs (50 mg/L). Further studies revealed that ZnO NPs treatment caused no significant effects on the morphology and settleability of activated sludge, but enhanced the release and uptake of phosphorus as well as the transformations of polyhydroxyalkanoates and glycogen in activated sludge, which suggested that PAOs were re-activated during long-term exposure to ZnO NPs. Fluorescence in-situ hybridization (FISH) analysis showed that the relative abundance of PAOs was increased after long-term exposure. Meanwhile, the enzymatic activities of PPX and PPK were also enhanced. These results indicated that compared with short-term exposure, long-term exposure to ZnO NPs favours PAOs function and thus led to the recovery of biological phosphorus removal. GRAPHICAL ABSTRACT
Zac1 and the Imprinted Gene Network program juvenile NAFLD in response to maternal metabolic syndrome

Within the next decade, NAFLD is predicted to become the most prevalent cause of childhood liver failure in developed countries. Predisposition to juvenile NAFLD can be programmed during early life in response to maternal metabolic syndrome (MetS), but the underlying mechanisms are poorly understood. We hypothesized that imprinted genes, defined by expression from a single parental allele, play a key role in maternal MetS‐induced NAFLD, due to their susceptibility to environmental stressors and their functions in liver homeostasis. We aimed to test this hypothesis and determine the critical periods of susceptibility to maternal MetS.
Loneliness, coping practices and masculinities in later life: Findings from a study of older men living alone in England

Abstract While much attention has been given to loneliness as a public health and societal problem less consideration has been given to men's experiences, particularly in later life, and there is a limited evidence based on what works with supporting older men to counteract the impact of loneliness on their mental and social wellbeing. In this paper, we focus on the experiences of older men living alone in the community. Between 2017–2018 72 men residing in England (65–95 years) took part in the study and shared their accounts of experiencing and addressing loneliness on an everyday basis. We generated qualitative data through semi‐structured interviews. Interview data were analysed thematically using the framework analysis approach. We present and discuss findings on the difficulties older men experience in responding to and discussing loneliness and the range of coping practices men applied within their home environments. Three core themes are presented: 1. Maintaining silence around loneliness and distress; 2. Getting on with it versus feeling stuck in loneliness and, 3. Temporary remedies and distractions from loneliness from within the home. Across men's accounts, ‘the home’ is constructed as a space of biographical connections with others as well as a restrictive environment of separation from others. In relation to help‐seeking and efforts to break silence surrounding loneliness, the findings speak to the ways in which masculinities and social expectations attached to male roles complicate older men's varying attempts at help‐seeking and underpin some of their everyday methods of coping with loneliness. The findings reiterate the importance of targeted individual support for older men, particularly for those feeling frozen in loneliness. Facilitators of group‐based support for older men need to recognise the different and potentially conflicting positions older male service users may adopt in relation to help‐seeking that are configured around masculine ideals but in diverging ways.
Anthracycline-induced atrial structural and electrical remodeling characterizes early cardiotoxicity and contributes to atrial conductive instability and dysfunction.

AIMS Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF), while the mechanisms remain unclear. Due to sudden and unpredictable features, prediction of anthracycline-induced AF at early phase is difficult. Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effects of dexrazoxane and antioxidants. METHODS AND RESULTS Post-surgery breast cancer patients with an anthracycline-containing or exclusion regimen were recruited for echocardiography at pre-chemotherapy, and 3 and 6 months post-chemotherapy. Mice were injected with doxorubicin or vehicle (5 mg/kg/week, 4 weeks), left atrial diameter, electrical transmission and AF inducibility were measured. Meanwhile, level of ROS, activity of antioxidant enzymes, cardiomyocyte size, vacuolization, inflammation and fibrosis were also measured in mouse atria. The therapeutic effect of dexrazoxane and antioxidants on doxorubicin-induced changes in the aforementioned parameters were also determined. Whilst ventricular parameters and functions were unchanged in cancer patients receiving anthracyclines at pre- and post-chemotherapy, left atrial reservoir and conduit function were decreased at 3 months post-chemotherapy vs pre-chemotherapy. Doxorubicin-induced susceptibility to AF occurred in mice prior to onset of ventricular dysfunction. Doxorubicin-induced AF was via inducing structural remodeling (cardiomyocyte death, hypotrophy and vacuolization) and electrical remodeling (reduction and redistribution of connexin 43) in atria, which was effectively prevented by dexrazoxane or antioxidants through inhibiting ROS generation or enhancing ROS elimination. Innovation and Conclusion: AF inducibility was induced after doxorubicin injection, which can be inhibited by repressing ROS level.
Implementation of a prostate cancer‐specific targeted sequencing panel for credentialing of patient‐derived cell lines and genomic characterization of patient samples

Primary and metastatic prostate cancers have low mutation rates and recurrent alterations in a small set of genes, enabling targeted sequencing of prostate cancer‐associated genes as an efficient approach to characterizing patient samples (compared to whole‐exome and whole‐genome sequencing). For example, targeted sequencing provides a flexible, rapid, and cost‐effective method for genomic assessment of patient‐derived cell lines to evaluate fidelity to initial patient tumor samples.
Modulation of CD36‐mediated lipid accumulation and senescence by vitamin E analogs in monocytes and macrophages

The CD36/FAT scavenger receptor/fatty acids transporter regulates cellular lipid accumulation important for inflammation, atherosclerosis, lipotoxicity, and initiation of cellular senescence. Here we compared the regulatory effects of the vitamin E analogs alpha‐tocopherol (αT), alpha‐tocopheryl phosphate (αTP), and αTP/βCD (a nanocarrier complex between αTP and β‐cyclodextrin [βCD]) and investigated their regulatory effects on lipid accumulation, phagocytosis, and senescence in THP‐1 monocytes and macrophages. Both, αTP and αTP/βCD inhibited CD36 surface exposition stronger than αT leading to more pronounced CD36‐mediated events such as inhibition of DiI‐labeled oxLDL uptake, phagocytosis of fluorescent Staphylococcus aureus bioparticles, and cell proliferation. When compared to βCD, the complex of αTP/βCD extracted cholesterol from cellular membranes with higher efficiency and was associated with the delivery of αTP to the cells. Interestingly, both, αTP and more so αTP/βCD inhibited lysosomal senescence‐associated beta‐galactosidase (SA‐β‐gal) activity and increased lysosomal pH, suggesting CD36‐mediated uptake into the endo‐lysosomal phagocytic compartment. Accordingly, the observed pH increase was more pronounced with αTP/βCD in macrophages whereas no significant increase occurred with αT, alpha‐tocopheryl acetate (αTA) or βCD. In contrast to αT and αTA, the αTP molecule is di‐anionic at neutral pH, but upon moving into the acidic endo‐lysosomal compartment becomes protonated and thus is acting as a base. Moreover, it is expected to be retained in lysosomes since it still carries one negative charge, similar to lysosomotropic drugs. Thus, treatment with αTP or αTP/βCD and/or inhibition of conversion of αTP to αT as it occurs in aged cells may counteract CD36‐mediated overlapping inflammatory, senescent, and atherosclerotic events.
Changes in apparent diffusion coefficient and pathological response in colorectal liver metastases after preoperative chemotherapy

Background The pathological response to preoperative chemotherapy of colorectal liver metastases (CRLMs) is predictive of long-term prognosis after liver resection. Accurate preoperative assessment of chemotherapy response could enable treatment optimization. Purpose To investigate whether changes in lesion-apparent diffusion coefficient (ADC) measured with diffusion-weighted magnetic resonance imaging (MRI) can be used to assess pathological treatment response in patients with CRLMs undergoing preoperative chemotherapy. Material and Methods Patients who underwent liver resection for CRLMs after preoperative chemotherapy between January 2011 and December 2019 were retrospectively included if they had undergone MRI before and after preoperative chemotherapy on the same 1.5-T MRI scanner with diffusion-weighted imaging with b-values 50, 400, and 800 s/mm2. The pathological chemotherapy response was assessed using the tumor regression grade (TRG) by AJCC/CAP. Lesions were divided into two groups: pathological responding (TRG 0–2) and non-responding (TRG 3). The change in lesion ADC after preoperative chemotherapy was compared between responding and non-responding lesions. Results A total of 27 patients with 49 CRLMs were included, and 24/49 lesions showed a pathological chemotherapy response. After chemotherapy, ADC increased in both pathological responding (pretreatment ADC: 1.26 [95% confidence interval (CI)=1.06–1.37] vs. post-treatment ADC: 1.33 [95% CI=1.13–1.56] × 10−3 mm2/s; P = 0.026) and non-responding lesions (1.12 [95% CI=0.980–1.21] vs. 1.20 [95% CI=1.09–1.43] × 10−3 mm2/s; P = 0.018). There was no difference in median relative difference in ADC after chemotherapy between pathological responding and non-responding lesions (15.8 [95% CI=1.42–26.3] vs. 7.17 [95% CI=−4.31 to 31.2]%; P = 0.795). Conclusion Changes in CRLM ADCs did not differ between pathological responding and non-responding lesions.
Climate change, land cover change, and overharvesting threaten a widely used medicinal plant in South Africa

Abstract Medicinal plants contribute substantially to the well‐being of people in large parts of the world, providing traditional medicine and supporting livelihoods from trading plant parts, which is especially significant for women in low‐income communities. However, the availability of wild medicinal plants is increasingly threatened; for example, the Natal Lily (Clivia miniata), which is one of the most widely traded plants in informal medicine markets in South Africa, lost over 40% of individuals over the last 90 years. Understanding the species’ response to individual and multiple pressures is essential for prioritizing and planning conservation actions. To gain this understanding, we simulated the future range and abundance of C. miniata by coupling Species Distribution Models with a metapopulation model (RAMAS‐GIS). We contrasted scenarios of climate change (RCP2.6 vs. RCP8.5), land cover change (intensification vs. expansion), and harvesting (only juveniles vs. all life‐stages). All our scenarios pointed to continuing declines in suitable habitat and abundance by the 2050s. When acting independently, climate change, land cover change, and harvesting each reduced the projected abundance substantially, with land cover change causing the most pronounced declines. Harvesting individuals from all life stages affected the projected metapopulation size more negatively than extracting only juveniles. When the three pressures acted together, declines of suitable habitat and abundance accelerated but uncertainties were too large to identify whether pressures acted synergistically, additively, or antagonistically. Our results suggest that conservation should prioritize the protection of suitable habitat and ensure sustainable harvesting to support a viable metapopulation under realistic levels of climate change. Inadequate management of C. miniata populations in the wild will likely have negative consequences for the well‐being of people relying on this ecosystem service, and we expect there may be comparable consequences relating to other medicinal plants in different parts of the world.
Implementation Frameworks for Artificial Intelligence Translation Into Health Care Practice: Scoping Review

Background Significant efforts have been made to develop artificial intelligence (AI) solutions for health care improvement. Despite the enthusiasm, health care professionals still struggle to implement AI in their daily practice. Objective This paper aims to identify the implementation frameworks used to understand the application of AI in health care practice. Methods A scoping review was conducted using the Cochrane, Evidence Based Medicine Reviews, Embase, MEDLINE, and PsycINFO databases to identify publications that reported frameworks, models, and theories concerning AI implementation in health care. This review focused on studies published in English and investigating AI implementation in health care since 2000. A total of 2541 unique publications were retrieved from the databases and screened on titles and abstracts by 2 independent reviewers. Selected articles were thematically analyzed against the Nilsen taxonomy of implementation frameworks, and the Greenhalgh framework for the nonadoption, abandonment, scale-up, spread, and sustainability (NASSS) of health care technologies. Results In total, 7 articles met all eligibility criteria for inclusion in the review, and 2 articles included formal frameworks that directly addressed AI implementation, whereas the other articles provided limited descriptions of elements influencing implementation. Collectively, the 7 articles identified elements that aligned with all the NASSS domains, but no single article comprehensively considered the factors known to influence technology implementation. New domains were identified, including dependency on data input and existing processes, shared decision-making, the role of human oversight, and ethics of population impact and inequality, suggesting that existing frameworks do not fully consider the unique needs of AI implementation. Conclusions This literature review demonstrates that understanding how to implement AI in health care practice is still in its early stages of development. Our findings suggest that further research is needed to provide the knowledge necessary to develop implementation frameworks to guide the future implementation of AI in clinical practice and highlight the opportunity to draw on existing knowledge from the field of implementation science.
Predictive Utility of Alternate Measures of Physical Activity and Diet for Overweight and Obesity in Low-Income Minority Women

Purpose The purpose is to compare the predictive utility of alternate measures of diet and physical activity for overweight and obesity among low-income minority women. Design Cross-sectional analysis of baseline data from a cohort study. Setting Three public housing developments in South Los Angeles. Subjects: Adult women (N = 425). Measures Primary outcome—weight status (normal BMI, overweight, or obese). Primary predictors— diet: 24-hour dietary recalls (Healthy Eating Index), dietary screener (intake of specific food groups), and single-item survey question (diet quality); physical activity: accelerometry (minutes/day of moderate-to-vigorous activity), short recall questionnaire (minutes/week of moderate and vigorous activity), and single-item questions (days per week did exercise; self-assessment of overall activity level). Analysis Multinomial logistic regression models, controlling for socio-demographic covariates. Models are built up starting with least resource-intensive measures of diet and physical activity (single items) and sequentially adding more resource-intensive measures. Model performance is assessed via information-based model selection indices. Results Adjusted relative risk for obesity for single-item measures ranged from . 61 to . 64 for diet (P < .01) and from . 80 to . 81 for physical activity (P <.05). The added value of resource-intensive measures was negligible for physical activity and at best small for diet. Conclusion Single-item questions for diet and physical activity can provide valuable information about risk for overweight and obesity in low-income minority women when more resource-intensive assessments are infeasible.