Miracle-dz/UniFAR-FTUs huggingface dataset:
Mood Homeostasis, Low Mood, and History of Depression in 2 Large Population Samples.

Importance Existing therapeutic options are insufficient to tackle the disease burden of depression, and new treatments are sorely needed. Defining new psychotherapeutic targets is challenging given the paucity of coherent mechanistic explanations for depression. Objective To assess whether mood homeostasis (ie, the stabilization of one's mood by engaging in mood-modifying activities) is a possible new therapeutic target by testing the hypothesis that people with low (vs high) mean mood and people with (vs without) a history of depression have impaired mood homeostasis. Design, Setting, and Participants The quantitative association between mood and daily activities was computed in 2 large case-control studies based on the 58sec data set (collected from December 1, 2012, to May 31, 2014, and analyzed from April 1 to 30, 2019), and the World Health Organization Study on Global Aging and Adult Health (WHO SAGE) data set (collected from January 1, 2007, to December 31, 2010, and analyzed from June 1 to 30, 2019). The 58sec data set consists of self-enrolled participants from high-income countries. The WHO SAGE data set consists of nationally representative participants in low- and middle-income countries recruited via cluster sampling. Main Outcomes and Measures The main outcome (defined before data analysis) was the difference in mood homeostasis between people with high vs low mean mood (58sec data) and between people with vs without a history of depression (WHO SAGE data). Results A total of 28 212 participants from the 58sec data set (65.8% female; mean [SD] age, 28.1 [9.0] years) and 30 116 from the WHO SAGE data set (57.0% female; mean [SD] age, 57.8 [14.7] years) were included, for an overall study population of 58 328 participants. Mood homeostasis was significantly lower in people with low (vs high) mean mood (0.63 [95% CI, 0.45 to 0.79] vs 0.96 [95% CI, 0.96 to 0.98]; P < .001) and in people with (vs without) a history of depression (0.03 [95% CI, -0.26 to 0.24] vs 0.68 [95% CI, 0.55 to 0.75]; P < .001). In dynamic simulations, lower mood homeostasis led to more depressive episodes (11.8% vs 3.8% yearly risk; P < .001) that lasted longer (4.19 vs 2.90 weeks; P = .006). Conclusions and Relevance In this study, mood homeostasis appeared to have been impaired in people with low mood and in those with a history of depression. Mood homeostasis may therefore provide new insights to guide the development of treatments for depression.
Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction, but its progression is due to different pathological mechanisms, including oxidative stress, inflammatory cells infiltration, inflammation and fibrosis. Macrophages (Mφ) accumulation in kidneys correlates strongly with serum creatinine, interstitial myofibroblast accumulation and interstitial fibrosis scores. However, whether or not Mφ polarization is involved in the progression of DN has not been adequately defined. The prevalence of the different phenotypes during the course of DN, the existence of hybrid phenotypes and the plasticity of these cells depending of the environment have led to inconclusive results. In the same sense the role of the different macrophage phenotype in fibrosis associated or not to DN warrants additional investigation into Mφ polarization and its role in fibrosis. Due to the association between fibrosis and the progressive decline of renal function in DN, and the role of the different phenotypes of Mφ in fibrosis, in this review we examine the role of macrophage phenotype control in DN and highlight the potential factors contributing to phenotype change and injury or repair in DN.
Maternal Plasma Perfluoroalkyl Substances and Miscarriage: A Nested Case–Control Study in the Danish National Birth Cohort

Background: Per- and polyfluoroalkyl substances (PFAS) are widespread persistent organic pollutants and endocrine disruptors. High doses of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure can cause pregnancy loss and infant deaths in animals, but the associations between PFAS exposures and risk of miscarriage in humans are not well studied. Methods: Using a case–control study nested within the Danish National Birth Cohort (DNBC, 1996–2002), we compared 220 pregnancies ending in miscarriage during weeks 12–22 of gestation, with 218 pregnancies resulting in live births. Levels of seven types of PFAS [PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctanesulfonic acid (PFOSA)] were measured in maternal plasma collected in early gestation (mean gestational week 8). We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PFAS as a continuous variable or in quartiles, controlling for maternal age, parity, socio-occupational status, smoking and alcohol intake, gestational week of blood sampling, and maternal history of miscarriage. Stratification by parity and PFAS mixture analyses using weighted quantile sum (WQS) regression were also conducted. Results: We observed a monotonic increase in odds for miscarriage associated with increasing PFOA and PFHpS levels. The ORs comparing the highest PFOA or PFHpS quartile to the lowest were 2.2 (95% CI: 1.2, 3.9) and 1.8 (95% CI: 1.0, 3.2). The ORs were also elevated for the second or third quartile of PFHxS or PFOS, but no consistent exposure–outcome pattern emerged. An interquartile range (IQR) increment in the WQS index of seven PFAS was associated with 64% higher odds for miscarriage (95% CI: 1.15, 2.34). The associations were stronger in parous women, while findings were inconsistent among nulliparous women. Conclusion: Maternal exposures to higher levels of PFOA, PFHpS, and PFAS mixtures were associated with the risk of miscarriage and particularly among parous women. Larger replication studies among nulliparous women are needed to allay concerns about confounding by reproductive history. https://doi.org/10.1289/EHP6202
Population Screening for Inherited Predisposition to Breast and Ovarian Cancer.

The discovery of genes underlying inherited predisposition to breast and ovarian cancer has revolutionized the ability to identify women at high risk for these diseases before they become affected. Women who are carriers of deleterious variants in these genes can undertake surveillance and prevention measures that have been shown to reduce morbidity and mortality. However, under current strategies, the vast majority of women carriers remain undetected until they become affected. In this review, we show that universal testing, particularly of the BRCA1 and BRCA2 genes, fulfills classical disease screening criteria. This is especially true for BRCA1 and BRCA2 in Ashkenazi Jews but is translatable to all populations and may include additional genes. Utilizing genetic information for large-scale precision prevention requires a paradigmatic shift in health-care delivery. To address this need, we propose a direct-to-patient model, which is increasingly pertinent for fulfilling the promise of utilizing personal genomic information for disease prevention. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 21 is August 31, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
The Role of Apoptin in Chicken Anemia Virus Replication

Apoptin is the Vp3 protein of chicken anemia virus (CAV), which infects the thymocytes and erythroblasts in young chickens, causing chicken infectious anemia and immunosuppression. Apoptin is highly studied for its ability to selectively induce apoptosis in human tumor cells and, thus, is a protein of interest in anti-tumor therapy. CAV apoptin is known to localize to different subcellular compartments in transformed and non-transformed cells, depending on the DNA damage response, and the phosphorylation of several identified threonine residues. In addition, apoptin interacts with molecular machinery such as the anaphase promoting complex/cyclosome (APC/C) to inhibit the cell cycle and induce arrest in G2/M phase. While these functions of apoptin contribute to the tumor-selective effect of the protein, they also provide an important fundamental framework to apoptin’s role in viral infection, pathogenesis, and propagation. Here, we reviewed how the regulation, localization, and functions of apoptin contribute to the viral life cycle and postulated its importance in efficient replication of CAV. A model of the molecular biology of infection is critical to informing our understanding of CAV and other related animal viruses that threaten the agricultural industry.
Formation and Glomerular Deposition of Immune Complexes in Mice Administered Human Antibodies: Evaluation of Dose, Frequency, and Biomarkers

Administration of human protein–based drugs to animals often leads to formation of antidrug antibodies (ADAs) that may form circulating immune complexes (CICs) with the dosed protein. Circulating immune complexes can activate and bind complement (cCICs), and if large amount of CICs or cCICs is formed, the clearance mechanism potentially becomes saturated, which can lead to immune complex (IC) deposition and inflammation. To obtain a better understanding of the underlying factors, including the relationship between different dose regimes on IC formation and deposition and identification of possible biomarkers of IC deposition and IC-related pathological changes in kidneys, BALB/c and C57BL/6J mice were administered with human anti-tumor necrosis factor α (aTNFα, adalimumab) or a humanized anti-TNP (aTNP) antibody for 13 weeks. Particularly, ADA, CIC, cCIC formation, IC deposition, and glomerulonephritis were observed in C57BL/6J administered with aTNFα, whereas the immunologic response was minor in BALB/c mice administered with aTNFα and in BALB/c and C57BL/6J mice administered aTNP. Changing dose levels or increasing dosing frequency of aTNFα on top of an already-established CIC and cCIC response did not lead to substantial changes in CIC, cCIC formation, or IC deposition. Finally, no association between the presence of CICs or cCIC in plasma and glomerular IC deposition and/or glomerulonephritis was observed.
In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP

Colobomata, persistent optic fissures, frequently cause congenital blindness. Here, we focused on optic fissure fusion using in vivo time-lapse imaging in zebrafish. We identified the fusion initiating cells, which we termed “pioneer cells. ” Based on morphology, localization, and downregulation of the neuroretinal (NR) precursor marker rx2, these cells could be considered as retinal pigment epithelial (RPE) progenitors. Notably, pioneer cells regain rx2 expression and integrate into the NR after fusion, indicating that they do not belong to the pool of RPE progenitors, supported by the lack of RPE marker expression in pioneer cells. They establish the first cellular contact between the margins in the proximal fissure region and separate the hyaloid artery and vein. After initiation, the fusion site is progressing distally, increasing the distance between the hyaloid artery and vein. A timed BMP (Bone Morphogenetic Protein) induction, resulting in coloboma, did not alter the morphology of the fissure margins, but it did affect the expression of NR and RPE markers within the margins. In addition, it resulted in a persisting basal lamina and persisting remnants of periocular mesenchyme and hyaloid vasculature within the fissure, supporting the necessity of BMP antagonism within the fissure margins. The hampered fissure fusion had severe effects on the vasculature of the eye.
Assessing variability and uncertainty in orthopedic randomized controlled trials

Background and purpose — Low statistical power remains endemic in clinical medicine including orthopedics and manifests as high uncertainty and wide confidence intervals (CI). We evaluated the reporting and correspondence between power calculation and observed data on key parameters of variability and uncertainty in orthopedic randomized controlled trials (RCTs). Material and methods — RCTs with 1:1 allocation published in 8 major orthopedic journals between 2016 and 2017 with one continuous primary outcome were included in the review. The components of power calculation and observed standard deviation (SD), mean difference (MD), and confidence interval (CI) of MD between groups were assessed for primary outcome. Results — 160 RCTs were included, of which 93 (58%) and 138 (86%) studies reported the estimated SD and MD in the power calculation, respectively. The median ratio of the estimated SD and SDs observed in the data was 1.0 (IQR –0.76 to 1.32) for 69 (43%) studies. Only 31 of 138 studies reported the CI of MD in primary outcome. In 42% of the negative studies, the estimated MD was included in the CI of the observed MD. Interpretation — The key parameters of data variability, both in power analyses and in final study results, were poorly reported. Low power in orthopedics may result from too high an estimated effect size due to an overoptimistic estimate of MD between study groups. In almost half of the studies, overlap of the CI of the observed MD and estimated MD suggested that the reported results of these studies were inconclusive.
Self-Perception of Periodontal Health and Associated Factors: A Cross-Sectional Population-Based Study

The aim of this cross-sectional study was to explore sociodemographic, behavioral, and clinical factors associated with self-awareness of periodontal health. Data were collected from a representative sample of 736 adults (25–75 years old) in a city of Northern Italy who self-assessed gingival bleeding, oral malodor, and tooth mobility in a questionnaire and who underwent clinical periodontal examination and organoleptic evaluation. Approximately 50% of the subjects were aware of their actual gingival health status and oral odor. The logistic regression analysis revealed that females presented higher odds of correctly perceiving their gingival conditions and mouth odor, while those who were older and smokers had a greater probability of being less objective in reporting them. Tooth type and position in the dental arches were positively associated with self-perception of tooth mobility. These findings reflected a low level of self-awareness that may influence oral care-seeking behavior. Subjects may be unconcerned about their periodontal health condition or lack enough knowledge to be aware of it. This points to the need for planning strategies to improve education and knowledge about periodontal health, which, by enhancing self-perception of periodontal symptoms, could help everyone to seek treatment in the initial stage of the disease.
Spatiotemporal Mislocalization of Nuclear Membrane-Associated Proteins in γ-Irradiation-Induced Senescent Cells

Cellular senescence, induced by genotoxic or replication stress, is accompanied by defects in nuclear morphology and nuclear membrane-heterochromatin disruption. In this work, we analyzed cytological and molecular changes in the linker of nucleoskeleton and cytoskeleton (LINC) complex proteins in senescence triggered by γ-irradiation. We used human mammary carcinoma and osteosarcoma cell lines, both original and shRNA knockdown clones targeting lamin B receptor (LBR) and leading to LBR and lamin B (LB1) reduction. The expression status and integrity of LINC complex proteins (nesprin-1, SUN1, SUN2), lamin A/C, and emerin were analyzed by immunodetection using confocal microscopy and Western blot. The results show frequent mislocalization of these proteins from the nuclear membrane to cytoplasm and micronuclei and, in some cases, their fragmentation and amplification. The timing of these changes clearly preceded the onset of senescence. The LBR deficiency triggered neither senescence nor changes in the LINC protein distribution before irradiation. However, the cytological changes following irradiation were more pronounced in shRNA knockdown cells compared to original cell lines. We conclude that mislocalization of LINC complex proteins is a significant characteristic of cellular senescence phenotypes and may influence complex events at the nuclear membrane, including trafficking and heterochromatin attachment.
Pembrolizumab for the treatment of programmed death–ligand 1‒positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE‐028 study

Despite a protracted disease course and multiple available therapies, patients with well‐differentiated neuroendocrine tumors (NETs) inevitably experience disease progression. Programmed death–ligand 1 (PD‐L1) has been associated with NET progression and prognosis. The multicohort, phase 1 KEYNOTE‐028 study (ClinicalTrials.gov identifier NCT02054806) evaluated the activity and safety of the anti–programmed cell death protein 1 immunotherapy pembrolizumab in patients with well‐differentiated or moderately‐differentiated NETs.
First isolation of SARS-CoV-2 from clinical samples in India.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has, as on March 31, 2020, spread to over 207 countries around the world1,2, with a total of 896,475 confirmed cases and 45,525 deaths2. The number of reported SARS-CoV-2 cases in India is also on an increase with 1,636 cases and 38 deaths2. In the current pandemic situation, the isolation of SARS-CoV-2 is important for developing and evaluating diagnostic reagents, for antiviral studies and for screening of vaccine candidates. Earlier studies showed that SARS-CoV-2 could not replicate in several cell lines, which are routinely used for isolation of respiratory viruses3. Human and animal cell lines that were found to support SARS-CoV-1 replication during the first outbreak of SARS in China, 20024, are currently being studied. The virus was first isolated in the human airway epithelial cells from clinical specimens as part of early attempts to identify the aetiologic agent of infection5. We describe here the successful isolation and characterization of SARS-CoV-2 from clinical samples in India using Vero CCL-81 cells by observing cytopathic effects (CPEs) and cycle threshold (Ct) values in real-time reverse transcription-polymerase chain reaction (RT-PCR), electron microscopy and next-generation sequencing (NGS).
Enablers and barriers to implementation of and compliance with school-based healthy food and beverage policies: a systematic literature review and meta-synthesis

Abstract Objective: Schools have been recognised as a potential setting for improving young peoples’ food and beverage choices; however, many schools fail to adhere to healthy food and beverage policy standards. The current study aimed to explore the enablers and barriers to effective implementation of and compliance with school-based food and beverage policies. Design: Systematic review and meta-synthesis. Eight electronic databases were searched for articles in June 2019. Studies were eligible for inclusion if they reported on implementation and/or compliance of school-based food and/or beverage policies with outcomes relating to enablers and/or barriers. This review had no restrictions on study design, year of publication or language. Seventy-two full-text articles were assessed for eligibility, of which twenty-eight were included in this review. Setting: Studies conducted globally that focused on schools. Participants: School-based healthy food and beverage policies. Results: Financial (cost of policy-compliant foods, decreased profit and revenue), physical (availability of policy-compliant foods, close geographical proximity to unhealthy food outlets) and social (poor knowledge, understanding, and negative stakeholders’ attitudes towards policy) factors were the most frequently reported barriers for policy implementation. Sufficient funding, effective policy communication and management, and positive stakeholders’ attitudes were the most frequently reported enablers for policy implementation. Conclusions: There is a need for better communication strategies, financial and social support prior to school-based food policy implementation. Findings of this review contribute to a thorough understanding of factors that underpin best practice recommendations for the implementation of school-based food policy, and inform those responsible for improving public health nutrition.
PGE2 stimulates COX-2 expression via EP2/4 receptors and acts in synergy with IL-1β in human follicular dendritic cell-like cells

PGE2 is the major lipid mediator of inflammation produced by multiple cell types including follicular dendritic cells (FDCs) of the lymphoid tissue. We have investigated the immunoregulatory function of PGE2 and its production mechanism using FDC-like cells isolated from human tonsil. Our recent observation of COX-2-inducing effect of PGE2 prompted us to identify the responsible receptor in this study. Pharmacologic approaches were adopted and Western blotting was utilized to measure protein expression levels. Agonists selective for EP2 and EP4 significantly stimulated COX-2 expression, while antagonists for these receptors prevented PGE2 from triggering COX-2 induction. The combined addition of EP2 and EP4 antagonists resulted in further inhibition of PGE2. In contrast, EP1 and EP3 antagonists failed to exhibit the inhibitory effect on PGE2-induced COX-2 expression. Since PGE2 achieves COX-2 induction by repressing Akt activation in FDC-like cells, we confirmed EP2 and EP4 being the targets of PGE2 by examining the effects of E-prostanoid (EP) agonists and antagonists on the level of Akt phosphorylation. After the identification of PGE2 receptor, we examined the effect of PGE2 on IL-1β-induced COX-2 expression. PGE2 and IL-1β brought about a synergistic induction of COX-2 expression. Taken together, this study implies the impact of the combined role of eicosanoids and cytokines in inflammatory milieu.
Emissions and health risks from the use of 3D printers in an occupational setting

ABSTRACT The aim of this study was to determine concentrations of particulates and volatile organic compounds (VOCs) emitted from 3D printers using polylactic acid (PLA) filaments at a university workroom to assess exposure and health risks in an occupational setting. Under typical-case (one printer) and worst-case (three printers operating simultaneously) scenarios, particulate concentration (total and respirable), VOCs and formaldehyde were measured. Air samples were collected in the printing room and adjacent hallway. Size-resolved levels of nano-diameter particles were also collected in the printing room. Total particulate levels were higher in the worst-case scenario (0.7 mg/m3) vs. typical-case scenario (0.3 mg/m3). Respirable particulate and formaldehyde concentrations were similar between the two scenarios. Size-resolved measurements showed that most particles ranged from approximately 27 to 116 nm. Total VOC levels were approximately 6-fold higher during the worst-case scenario vs. typical situation with isopropyl alcohol being the predominant VOC. Airborne concentrations in the hallway were generally lower than inside the printing room. All measurements were below their respective occupational exposure limits. In summary, emissions of particulates and VOCs increased when multiple 3D printers were operating simultaneously. Airborne levels in the adjacent hallway were similar between the two scenarios. Overall, data suggest a low risk of significant and persistent adverse health effects. Nevertheless, the health effects attributed to 3D printing are not fully known and adherence to good hygiene principles is recommended during use of this technology.