Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of Need for Recovery and Its Relationship With Work Characteristics and Health in a Sample of Chinese Doctors: A Cross-Sectional Survey

Background: China is launching an unprecedented health care system reform. However, the long-term interests of doctors seem to have been ignored during this process especially considering that the work environment and work-life balance for doctors have severely deteriorated over the past decade.Their well-being and health are facing substantial threats due to heavy workloads and inadequate recovery opportunities. This study aimed to investigate the extent of need for recovery (NFR) among Chinese doctors and to examine their work-related fatigue. The study also examines the relationship of NFR with workplace satisfaction and health outcomes among Chinese doctors. Methods: A total of 2,617 doctors from 30 administrative regions in China participated in this study to assess the need for recovery and its relationship with work characteristics and health. A cross-sectional survey was conducted using the Chinese version of the Need for Recovery Scale (NFRS). Participants were invited to complete an anonymous online survey during May 2016. Data were analyzed using descriptive statistics, one-way ANOVA, reliability analysis, Pearson correlations, and hierarchical multiple regression analysis. Results: Significant differences in NFR scores were found across demographic characteristics such as age, service years, hospital levels, educational attainment, professional positions, work shifts, and working time. Regardless of any illnesses they might be experiencing, about 70.0% of participants remained at their job even though many doctors (22.1%) must continue working under the policies of the organization, which led to more pronounced NFR (P < 0.001). Further, a higher NFR was negatively related to workplace well-being and self-reported health outcomes of participants. Conclusions: Work-induced fatigue is a growing threat to doctors in China and their recovery opportunities are extremely limited in the workplace. High NFR exerts a considerable effect on their workplace well-being and health. China's hospital managers should pay close attention to the fact that doctors have little chance of recovery, and should offer doctors' positive encouragement and support to enhance well-being. To improve doctors' working conditions, targeted prevention policies must be introduced by policymakers to control this spreading crisis.
A20/TNFAIP3 Increases ENOS Expression in an ERK5/KLF2-Dependent Manner to Support Endothelial Cell Health in the Face of Inflammation

Rationale: Decreased expression and activity of endothelial nitric oxide synthase (eNOS) in response to inflammatory and metabolic insults is the hallmark of endothelial cell (EC) dysfunction that preludes the development of atherosclerosis and hypertension. We previously reported the atheroprotective properties of the ubiquitin-editing and anti-inflammatory protein A20, also known as TNFAIP3, in part through interrupting nuclear factor-kappa B (NF-κB) and interferon signaling in EC and protecting these cells from apoptosis. However, A20's effect on eNOS expression and function remains unknown. In this study, we evaluated the impact of A20 overexpression or knockdown on eNOS expression in EC, at baseline and after tumor necrosis factor (TNF) treatment, used to mimic inflammation. Methods and Results: A20 overexpression in human coronary artery EC (HCAEC) significantly increased basal eNOS mRNA (qPCR) and protein (western blot) levels and prevented their downregulation by TNF. Conversely, siRNA-induced A20 knockdown decreased eNOS mRNA levels, identifying A20 as a physiologic regulator of eNOS expression. By reporter assays, using deletion and point mutants of the human eNOS promoter, and knockdown of eNOS transcriptional regulators, we demonstrated that A20-mediated increase of eNOS was transcriptional and relied on increased expression of the transcription factor Krüppel-like factor (KLF2), and upstream of KLF2, on activation of extracellular signal-regulated kinase 5 (ERK5). Accordingly, ERK5 knockdown or inhibition significantly abrogated A20's ability to increase KLF2 and eNOS expression. In addition, A20 overexpression in HCAEC increased eNOS phosphorylation at Ser-1177, which is key for the function of this enzyme. Conclusions: This is the first report demonstrating that overexpression of A20 in EC increases eNOS transcription in an ERK5/KLF2-dependent manner and promotes eNOS activating phosphorylation. This effect withstands eNOS downregulation by TNF, preventing EC dysfunction in the face of inflammation. This novel function of A20 further qualifies its therapeutic promise to prevent/treat atherosclerosis.
Impact of the COVID-19 Pandemic on the Intensity of Health Services Use in General Practice: A Retrospective Cohort Study

Objectives: We aimed to explore the impact of the Swiss shutdown in spring 2020 on the intensity of health services use in general practice. Methods: Based on an electronic medical records database, we built one patient cohort each for January-June 2019 (control, 173,523 patients) and 2020 (179,086 patients). We used linear regression to model weekly consultation counts and blood pressure (BP) and glycated hemoglobin (HbA1c) measurement counts per 100 patients and predicted non-shutdown values. Analyses were repeated for selected at-risk groups and different age groups. Results: During the shutdown, weekly consultation counts were lower than predicted by −17.2% (total population), −16.5% (patients with hypertension), −17.5% (diabetes), −17.6% (cardiovascular disease), −15.7% (patients aged <60 years), −20.4% (60–80 years), and −14.5% (>80 years). Weekly BP counts were reduced by −35.3% (total population) and −35.0% (hypertension), and HbA1c counts by −33.2% (total population) and −29.8% (diabetes). p-values <0.001 for all reported estimates. Conclusion: Our results document consequential decreases in consultation counts and chronic disease monitoring during the shutdown. It is crucial that health systems remain able to meet non-COVID-19-related health care needs.
The Interplay Between Thematic Resolution, Forest Cover, and Heterogeneity for Explaining Euglossini Bees Community in an Agricultural Landscape

Human activities have modified the landscape composition. The changes in the landscape structure can be evaluated by metrics, which are influenced, among other factors, by the number of cover classes used for the landscape classification (thematic resolution). In high thematic resolutions, landscape covers that can influence biological responses are identified and detailed. In low thematic resolutions, this detail level is lower because it aggregates different landscape covers in a few classes. However, how the thematic resolution influences our ability to understand landscape structure on biodiversity is poorly explored, particularly for pollinators. Here we asked how thematic resolution affects the explanatory power of landscape composition on explaining Euglossini bees (richness and abundance) within 15 landscapes composed mainly of coffee and pasture. To address this issue, we quantified the association between five attributes of the euglossine bee community and landscape composition: landscape cover classes (%) and landscape heterogeneity. Moreover, we also evaluated how the thematic resolution influences bee responses to landscape structure. We found a strong and positive influence of landscape heterogeneity in low thematic resolutions (i.e., few cover classes on maps) over the richness and rare species abundance. We also observed that- in addition to the forest cover in the landscape- the pasture cover (%) quantified in high thematic resolution positively influenced the total abundance and abundance of common and intermediate species. Our study highlights the importance of maintaining compositional heterogeneity for the orchid bee community in agroecosystems, and forest cover for the biological requirements and conservation of these pollinators. Moreover, the use of different thematic resolutions showed how specific types of landscape covers influence the euglossine community attributes. This can highlight the species preferences for habitats and landscape covers. Thus, we call the attention of landscape ecologists to the importance of the definition of thematic resolution, as our ability to quantify the association between biological responses and landscape structure may be influenced by the number of classes used when building thematic maps.
Efficacy of Laparoscopic Hepatectomy versus Open Surgery for Hepatocellular Carcinoma With Cirrhosis: A Meta-analysis of Case-Matched Studies

Background The role of laparoscopic hepatectomy (LH) in hepatocellular carcinoma (HCC) with cirrhosis remains controversial and needs to be further assessed. The present meta-analysis aimed to compare the surgical and oncological outcomes of LH with those of open hepatectomy (OH) for HCC with cirrhosis. Methods The PubMed, Embase, and Cochrane Library databases were searched for studies comparing LH and OH until Mar 2021. Weighted mean differences (WMDs), odds ratios (ORs), and hazard ratios (HRs) were calculated for continuous, dichotomous, and long-term variables, respectively, with 95% confidence intervals (CIs). Subgroup analysis was performed according to different resection types: major resection and minor resection. The meta-analysis was performed using the STATA 12.0. Results A total of 16 case-matched studies (784 patients in the LH group and 1,191 patients in the OH group.) were included in this meta-analysis. In terms of primary outcomes, LH was associated with decreased overall complication rate (OR 0.57; 95% CI 0.46 to 0.71; P <0.01), major complication rate (OR 0.52; 95% CI 0.33 to 0.82; P < 0.01), postoperative mortality (OR 0.27; 95% CI 0.11 to 0.66; P <0.01), 1-y overall survival (OS) rate (HR 0.48; 95% CI 0.31 to 0.73; P <0.01), 2-y OS (HR 0.61; 95% CI 0.45 to 0.83; P < 0.01), and 5-y OS (0.67; 95% CI 0.53 to 0.85; P < 0.01). With respect to secondary outcomes, blood loss (WMD −69.16; 95% CI −101.72 to −36.61; P < 0.01), length of hospitalization (LOH) (WMD −2.65; 95% CI −3.41 to −1.89; P < 0.01), minor complication rate (OR 0.70; 95% CI 0.53 to 0.94; P = 0.02), postoperative liver failure (OR 0.60; 95% CI 0.38 to 0.95; P = 0.03), and postoperative ascites (OR 0.44; 95% CI 0.28 to 0.72; P < 0.01) was lower in LH than in OH. No significant differences in operation time (P = 0.07), transfusion rate (P = 0.05), 1-, 2-, and 5-year DFS rate (1-year, P = 0.08; 2-year, P = 0.08; 5-year, P = 0.23) were noted between LH and OH. Subgroup analysis based on minor resection revealed that LH had similar favored outcomes in comparison with those in the overall pooled analysis. However, LH had a longer operation time than OH in the setting of major resection (P < 0.01). Conclusion LH is technically feasible and safe for selected HCC patients with cirrhosis. LH can achieve favored short-term and long-term oncological outcomes in minor liver resection. Laparoscopic major hepatectomy (LMH) seems to offer some advantages over the open approach; however concerns about surgical and oncological safety remain. More evidence on LMH is warranted before expanding its indication to patients with cirrhosis.
Cytolethal Distending Toxin Promotes Replicative Stress Leading to Genetic Instability Transmitted to Daughter Cells

The cytolethal distending toxin (CDT) is produced by several Gram-negative pathogenic bacteria. In addition to inflammation, experimental evidences are in favor of a protumoral role of CDT-harboring bacteria such as Escherichia coli, Campylobacter jejuni, or Helicobacter hepaticus. CDT may contribute to cell transformation in vitro and carcinogenesis in mice models, through the genotoxic action of CdtB catalytic subunit. Here, we investigate the mechanism of action by which CDT leads to genetic instability in human cell lines and colorectal organoids from healthy patients’ biopsies. We demonstrate that CDT holotoxin induces a replicative stress dependent on CdtB. The slowing down of DNA replication occurs mainly in late S phase, resulting in the expression of fragile sites and important chromosomic aberrations. These DNA abnormalities induced after CDT treatment are responsible for anaphase bridge formation in mitosis and interphase DNA bridge between daughter cells in G1 phase. Moreover, CDT-genotoxic potential preferentially affects human cycling cells compared to quiescent cells. Finally, the toxin induces nuclear distension associated to DNA damage in proliferating cells of human colorectal organoids, resulting in decreased growth. Our findings thus identify CDT as a bacterial virulence factor targeting proliferating cells, such as human colorectal progenitors or stem cells, inducing replicative stress and genetic instability transmitted to daughter cells that may therefore contribute to carcinogenesis. As some CDT-carrying bacterial strains were detected in patients with colorectal cancer, targeting these bacteria could be a promising therapeutic strategy.
Increased Organic Fertilizer and Reduced Chemical Fertilizer Increased Fungal Diversity and the Abundance of Beneficial Fungi on the Grape Berry Surface in Arid Areas

Fertilizer practices can significantly impact the fruit quality and microbial diversity of the orchards. The fungi on the surface of fruits are essential for fruit storability and safety. However, it is not clear whether fertilization affects the fungal diversity and community structure on the surface of grape berries. Here, grape quality and the fungal diversity on the surface of grapes harvested from three fertilizer treatments were analyzed shortly after grape picking (T0) and following 8 days of storage (T1). The study involved three treatments: (1) common chemical fertilizer for 2 years (CH); (2) increased organic fertilizer and reduced chemical fertilizer for 1 year (A.O); and (3) increased organic fertilizer and reduced chemical fertilizer for 2 years (B.O). The application of increased organic fertilizer and reduced chemical fertilizer increased the soluble solids content (SSC) of the grape berries and decreased the pH of the grape juice. A total of 827,947 high-quality fungal sequences were recovered and assigned to 527 operational taxonomic units. Members of the Ascomycota phylum were dominant in all samples and accounted for 94.41% of the total number of detected sequences, followed by the Basidiomycota (5.05%), and unidentified fungi (0.54%). Alpha and beta diversity analyses revealed significantly different fungal populations in the three fertilizer treatments over the two time periods. The fungal diversity and richness on the grape berry surface in the B.O and A.O treatments were higher than those in the CH treatment. Among the detected fungi, the B.O treatments were mainly Pichia, Aureobasidium, and Candida genera, while the CH treatments were Botrytis, Aspergillus, and Penicillium. Moreover, significant differences were revealed between the two assessment times (T0 and T1). The samples from the T0 timepoint had higher fungal richness and diversity than the samples from T1 timepoint. Increasing organic fertilizer usage in grape management could improve grape quality and went on to increase the fungal diversity, as well as the relative abundance (RA) of beneficial fungi on grape berry surfaces. The correlation analysis suggested that the pH of the grape juice was significantly negatively correlated with fungal diversity parameters.
Associations of Genetic Polymorphisms and Neuroimmune Markers With Some Parameters of Frontal Lobe Dysfunction in Schizophrenia

We investigated the associations of DRD3 rs6280, HTR1A rs6295, BDNF rs6265, SCL6A4 rs16965628, and 5HT2A rs7322347 with schizophrenia in a case–control study, and associations of these genetic variants with several clinical features. We also investigated markers of inflammatory response (C-reactive protein, IL-2, IL-6, IL-10), the activity of leukocytic elastase (LE) and α1-proteinase inhibitor (a1-PI), antibodies to S100B and myelin basic protein (MBP) in schizophrenia. Clinical symptoms were assessed on three scales: Positive and Negative Syndrome Scale, The Bush – Francis Catatonia Rating Scale and Frontal Assessment Battery. All SNPs were typed using predesigned TaqMan SNP genotyping assays. The biomarkers related to the immune system were routinely tested using ELISA kits. The association with schizophrenia was found for DRD3 rs6280 (p = 0.05) and HTR2A rs7322347 (p = 0.0013). We found differences between groups by parameters of LE and a1-PI and LE/a1-PI (p < 0.001). And IL-6 was evaluated in the schizophrenia group (p < 0.001). We showed that patients with the TT allele (BDNF rs6265) had more severe impairments in frontal lobe function. a1-PI can serve as a marker for assessing the severity of frontal lobe damage in patients with frontal dementia. We found some biological parameters reflecting the severity of frontal dysfunction in schizophrenia.
High Seeding Rates and Low Soil Nitrogen Environments Optimize Weed Suppression and Profitability in Organic No-Till Planted Soybean

No-till planting crops into rolled-crimped cover crops can improve soil health while reducing labor and fuel requirements compared with traditional tillage-based production. However, little information is available to help farmers optimize the management of organic no-till planted crops. Weed suppression, crop yield, and profitability were assessed across soybean [Glycine max (L.) Merr. ] seeding rates and soil nitrogen environments in an experiment conducted at two sites in central New York. Soybeans were no-till planted into rolled-crimped cereal rye (Secale cereale L.) at 0, 185,000, 371,000, 556,000, and 741,000 seeds ha−1. Three rates (0, 63, or 125 kg ha−1) of sodium nitrate (15-0-2) were applied across seeding rates to create different soil nitrogen environments. When pooled over sites, the lowest weed biomass occurred at the highest soybean density in the lowest soil nitrogen environment. An interaction was observed between soybean seeding rate and nitrogen treatments on weed communities. Soybean yield increased asymptotically with crop density and was not affected by nitrogen or site treatments. When pooled over nitrogen treatments and sites, partial returns to the soybean seeding rates were maximized at $2,238 ha−1 with 527,800 seeds ha−1. Results suggest that crop density is an important lever for optimizing weed suppression and crop yield in organic no-till soybean, and that managing for low soil nitrogen conditions may further enhance weed suppression while maintaining high yields.
Echocardiographic Prognosis Relevance of Attenuated Right Heart Remodeling in Idiopathic Pulmonary Arterial Hypertension

Background: Right ventricular (RV) function is a great determination of the fate in patients with pulmonary arterial hypertension (PAH). Monitoring RV structure back to normal or improvement should be useful for evaluation of RV function. The aims of this study were to assess the prognostic relevance of changed right heart (RH) dimensions by echocardiography and attenuated RH remodeling (ARHR) in idiopathic PAH (IPAH). Methods: We retrospectively analyzed 232 consecutive adult IPAH patients at baseline assessment and included RH catheterization and echocardiography. ARHR at the mean 20 ± 12 months' follow-up was defined by a decreased right atrium area, RV mid-diameter, and left ventricular end-diastolic eccentricity index. The follow-up end point was all-cause mortality. Results: At mean 20 ± 12 months' follow-up, 33 of 232 patients (14.2%) presented with ARHR. The remaining 199 surviving patients were monitored for another 25 ± 20 months. At the end of follow-up, the survival rates at 1, 3, and 5 years were 89, 89, and 68% in patients with ARHR, respectively, and 84, 65 and 41% in patients without ARHR (log-rank p = 0.01). ARHR was an independent prognostic factor for mortality. Besides, ARHR was available to further stratify patients' risk assessment through the French PAH non-invasive-risk criteria. Conclusions: Echocardiographic ARHR is an independent determinant of prognosis in IPAH at long-term follow-up. ARHR might be a useful tool to indicate the RV morphologic and functional improvement associated with better prognostic likelihood.
The Role of PI3K Inhibition in the Treatment of Breast Cancer, Alone or Combined With Immune Checkpoint Inhibitors

Dysregulation of phosphoinositide 3-kinase (PI3K) signaling is highly implicated in tumorigenesis, disease progression, and the development of resistance to the current standard of care treatments in breast cancer patients. This review discusses the role of PI3K pathway in breast cancer and evaluates the clinical development of PI3K inhibitors in both early and metastatic breast cancer settings. Further, this review examines the evidence for the potential synergistic benefit for the combination treatment of PI3K inhibition and immunotherapy in breast cancer treatment.
Overexpression of Endogenous Retroviruses and Malignancy Markers in Neuroblastoma Cell Lines by Medium-Induced Microenvironmental Changes

Neuroblastoma (NB) is the commonest solid tumor outside the central nervous system in infancy and childhood with a unique biological heterogeneity. In patients with advanced, metastasizing neuroblastoma, treatment failure and poor prognosis is often marked by resistance to chemo- or immunotherapy. Thus, identification of robust biomarkers seems essential for understanding tumor progression and developing effective therapy. Here, we have studied the expression of human endogenous retroviruses (HERV) as potential targets in NB cell lines during stem-cell medium-induced microenvironmental change. Quantitative PCR revealed that relative expression of the HERV-K family and HERV-W1 ENV were increased in all three NB cell lines after incubation in stem-cell medium. Virus transcriptome analyses revealed the transcriptional activation of three endogenous retrovirus elements: HERV-R ENV (ERV3-1), HERV-E1 and HERV-Fc2 ENV (ERVFC1-1). Known malignancy markers in NB, e.g. proto-oncogenic MYC or MYCN were expressed highly heterogeneously in the three investigated NB cell lines with up-regulation of MYC and MYCN upon medium-induced microenvironmental change. In addition, SiMa cells exclusively showed a phenotype switching from loosely-adherent monolayers to low proliferating grape-like cellular aggregates, which was accompanied by an enhanced CD133 expression. Interestingly, the overexpression of HERV was associated with a significant elevation of immune checkpoint molecule CD200 in both quantitative PCR and RNA-seq analysis suggesting tumor escape mechanism in NB cell lines after incubation in serum-free stem cell medium.