tbuckley/cabot-search huggingface dataset:
Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C
Authors: Yanfang P. Zhu, Isaac Shamie, Jamie C. Lee, Cameron J. Nowell, Weiqi Peng, Shiela Angulo, Linh N.N. Le, Yushan Liu, Huilai Miao, Hainan Xiong, Cathleen J. Pena, Elizabeth Moreno, Eric Griffis, Stephanie G. Labou, Alessandra Franco, Lori Broderick, Hal M. Hoffman, Chisato Shimizu, Nathan E. Lewis, John T. Kanegaye, Adriana H. Tremoulet, Jane C. Burns, Ben A. Croker
Journal: Journal of Clinical Investigation (2021)

BACKGROUND. Multisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Kawasaki disease (KD) shares several clinical features with MIS-C, which prompted the use of intravenous immunoglobulin (IVIG), a mainstay therapy for KD. Both diseases share a robust activation of the innate immune system, including the IL-1 signaling pathway, and IL-1 blockade has been used for the treatment of both MIS-C and KD. The mechanism of action of IVIG in these 2 diseases and the cellular source of IL-1β have not been defined.
die rol van coping in die verband tussen geestelike welstand en depressie by predikante
Authors: Philé Swanepoel, Karel G.F. Esterhuyse, Roelf Beukes, Nico Nortjé
Journal: JAMA Pediatrics (2012)

The role of coping in the relationship between spiritual wellbeing and depression amongst  ministers.   The aim of this study was to determine the role of coping in the relationship  between spiritual well-being and depression among ministers. The research group consisted  of 53 Dutch Reformed ministers, all serving in the Northern Cape. Coping was measured  by means of the  Coping Orientation to Problems Experienced Questionnaire  (Carver, Scheier &  Weintraub 1989), spiritual well-being by means of the   Spiritual Well-being Questionnaire   (Gomez & Fisher 2003:1977), and depression by means of the   Beck Depression Inventory-II   (Beck, Steer & Brown 1996:1−2). The results of this study indicated that problem-focused  coping and emotion-focused coping showed no direct relationship with depression. Problem- focused coping also plays no significant role in the relationship between spiritual well-being  and depression. Emotion-focused coping, however, plays a role in the relationship between  environment-related spiritual well-being and depression. Significant negative relationships  between spiritual well-being and depression were found. A significant positive relationship  was found between dysfunctional coping and depression. Dysfunctional coping was identified  as a mediator in the relationship between personal spiritual well-being and depression. The  results of this study are supported by the literature.
Use of artificial intelligence for image analysis in breast cancer screening programmes: systematic review of test accuracy
Authors: Karoline Freeman, Julia Geppert, Chris Stinton, Daniel Todkill, Samantha Johnson, Aileen Clarke, Sian Taylor-Phillips
Journal: BMJ (2021)

Abstract Objective To examine the accuracy of artificial intelligence (AI) for the detection of breast cancer in mammography screening practice. Design Systematic review of test accuracy studies. Data sources Medline, Embase, Web of Science, and Cochrane Database of Systematic Reviews from 1 January 2010 to 17 May 2021. Eligibility criteria Studies reporting test accuracy of AI algorithms, alone or in combination with radiologists, to detect cancer in women’s digital mammograms in screening practice, or in test sets. Reference standard was biopsy with histology or follow-up (for screen negative women). Outcomes included test accuracy and cancer type detected. Study selection and synthesis Two reviewers independently assessed articles for inclusion and assessed the methodological quality of included studies using the QUality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A single reviewer extracted data, which were checked by a second reviewer. Narrative data synthesis was performed. Results Twelve studies totalling 131 822 screened women were included. No prospective studies measuring test accuracy of AI in screening practice were found. Studies were of poor methodological quality. Three retrospective studies compared AI systems with the clinical decisions of the original radiologist, including 79 910 women, of whom 1878 had screen detected cancer or interval cancer within 12 months of screening. Thirty four (94%) of 36 AI systems evaluated in these studies were less accurate than a single radiologist, and all were less accurate than consensus of two or more radiologists. Five smaller studies (1086 women, 520 cancers) at high risk of bias and low generalisability to the clinical context reported that all five evaluated AI systems (as standalone to replace radiologist or as a reader aid) were more accurate than a single radiologist reading a test set in the laboratory. In three studies, AI used for triage screened out 53%, 45%, and 50% of women at low risk but also 10%, 4%, and 0% of cancers detected by radiologists. Conclusions Current evidence for AI does not yet allow judgement of its accuracy in breast cancer screening programmes, and it is unclear where on the clinical pathway AI might be of most benefit. AI systems are not sufficiently specific to replace radiologist double reading in screening programmes. Promising results in smaller studies are not replicated in larger studies. Prospective studies are required to measure the effect of AI in clinical practice. Such studies will require clear stopping rules to ensure that AI does not reduce programme specificity. Study registration Protocol registered as PROSPERO CRD42020213590.
Corporate political activity in the context of unhealthy food advertising restrictions across Transport for London: A qualitative case study
Authors: Kathrin Lauber, Daniel Hunt, Anna B. Gilmore, Harry Rutter
Journal: PLoS Medicine (2021)

Diets with high proportions of foods high in fat, sugar, and/or salt (HFSS) contribute to malnutrition and rising rates of childhood obesity, with effects throughout the life course. Given compelling evidence on the detrimental impact HFSS advertising has on children's diets, the World Health Organization unequivocally supports the adoption of restrictions on HFSS marketing and advertising. In February 2019, the Greater London Authority introduced novel restrictions on HFSS advertising across Transport for London (TfL), one of the most valuable out-of-home advertising estates. In this study, we examined whether and how commercial actors attempted to influence the development of these advertising restrictions.Using requests under the Freedom of Information Act, we obtained industry responses to the London Food Strategy consultation, correspondence between officials and key industry actors, and information on meetings. We used an existing model of corporate political activity, the Policy Dystopia Model, to systematically analyse arguments and activities used to counter the policy. The majority of food and advertising industry consultation respondents opposed the proposed advertising restrictions, many promoting voluntary approaches instead. Industry actors who supported the policy were predominantly smaller businesses. To oppose the policy, industry respondents deployed a range of strategies. They exaggerated potential costs and underplayed potential benefits of the policy, for instance, warning of negative economic consequences and questioning the evidence underlying the proposal. Despite challenging the evidence for the policy, they offered little evidence in support of their own claims. Commercial actors had significant access to the policy process and officials through the consultation and numerous meetings, yet attempted to increase access, for example, in applying to join the London Child Obesity Taskforce and inviting its members to events. They also employed coalition management, engaging directly and through business associations to amplify their arguments. Some advertising industry actors also raised the potential of legal challenges. The key limitation of this study is that our data focused on industry-policymaker interactions; thus, our findings are unable to present a comprehensive picture of political activity.In this study, we identified substantial opposition from food and advertising industry actors to the TfL advertising restrictions. We mapped arguments and activities used to oppose the policy, which might help other public authorities anticipate industry efforts to prevent similar restrictions in HFSS advertising. Given the potential consequences of commercial influence in these kinds of policy spaces, public bodies should consider how they engage with industry actors.
SUPERGNOVA: local genetic correlation analysis reveals heterogeneous etiologic sharing of complex traits
Authors: Yiliang Zhang, Qiongshi Lu, Yixuan Ye, Kunling Huang, Wei Liu, Yuchang Wu, Xiaoyuan Zhong, Boyang Li, Zhaolong Yu, Brittany G. Travers, Donna M. Werling, James J. Li, Hongyu Zhao
Journal: Genome biology (2021)

Local genetic correlation quantifies the genetic similarity of complex traits in specific genomic regions. However, accurate estimation of local genetic correlation remains challenging, due to linkage disequilibrium in local genomic regions and sample overlap across studies. We introduce SUPERGNOVA, a statistical framework to estimate local genetic correlations using summary statistics from genome-wide association studies. We demonstrate that SUPERGNOVA outperforms existing methods through simulations and analyses of 30 complex traits. In particular, we show that the positive yet paradoxical genetic correlation between autism spectrum disorder and cognitive performance could be explained by two etiologically distinct genetic signatures with bidirectional local genetic correlations.
Predictors of Suicide Attempt Within 30 Days After First Medically Documented Suicidal Ideation in U.S. Army Soldiers
Authors: Holly B. Herberman Mash, Robert J. Ursano, Ronald C. Kessler, James A. Naifeh, Carol S. Fullerton, Pablo A. Aliaga, Charlotte A. Riggs-Donovan, Hieu M. Dinh, Mary C. Vance, Gary H. Wynn, Alan M. Zaslavsky, Nancy A. Sampson, Tzu-Cheg Kao, Murray B. Stein
Journal: American Journal of Psychiatry (2021)

The authors sought to identify predictors of imminent suicide attempt (within 30 days) among U.S. Army soldiers following their first documented suicidal ideation.Using administrative data from the Army Study to Assess Risk and Resilience in Servicemembers, the authors identified 11,178 active-duty Regular Army enlisted soldiers (2006-2009) with medically documented suicidal ideation and no prior medically documented suicide attempts. The authors examined risk factors for suicide attempt within 30 days of first suicidal ideation using logistic regression analyses, including sociodemographic and service-related characteristics, psychiatric diagnoses, physical health care visits, injuries, and history of family violence or crime perpetration or victimization.Among soldiers with first documented suicidal ideation, 830 (7.4%) attempted suicide, 46.3% of whom (N=387) attempted suicide within 30 days (rate, 35.4 per 1,000 soldiers). Following a series of multivariate analyses, the final model identified females (odds ratio=1.3, 95% CI=1.0, 1.8), combat medics (odds ratio=1.6, 95% CI=1.1, 2.2), individuals with an anxiety disorder diagnosis prior to suicidal ideation (odds ratio=1.3, 95% CI=1.0, 1.6), and those who received a sleep disorder diagnosis on the same day as the recorded suicidal ideation (odds ratio=2.3, 95% CI=1.1, 4.6) as being more likely to attempt suicide within 30 days. Black soldiers (odds ratio=0.6, 95% CI=0.4, 0.9) and those who received an anxiety disorder diagnosis on the same day as suicidal ideation (odds ratio=0.7, 95% CI=0.5, 0.9) were less likely.Suicide attempt risk is highest in the first 30 days following ideation diagnosis and is more likely among women, combat medics, and soldiers with an anxiety disorder diagnosis before suicidal ideation and a same-day sleep disorder diagnosis. Black soldiers and those with a same-day anxiety disorder diagnosis were at decreased risk. These factors may help identify soldiers at imminent risk of suicide attempt.
Effect of Maternal Metformin Treatment in Pregnancy on Neonatal Metabolism: Evidence From Newborn Metabolic Screening
Authors: Jane Estrella, Veronica Wiley, David Simmons, Tien-Ming Hng, Mark McLean
Journal: Diabetes Care (2021)

To investigate effects of maternal diabetes and metformin treatment on metabolic newborn screening (NBS) results of infants born to mothers with hyperglycemia during pregnancy.Retrospective case-control study. NBS results of infants born to mothers treated with metformin for hyperglycemia during pregnancy were compared with diet-treated subjects with diabetes and matched normal control subjects.maternal type 1 diabetes, major fetal anomalies, and incomplete infant data. Inclusions: maternal hyperglycemia in pregnancy treated with diet alone or diet plus metformin. Results from the New South Wales Newborn Screening Program (dried infant blood spot sample, 24-72 h after birth) for 25 routinely studied analytes were measured using mass spectrometry. Data from metformin-exposed and control infants were compared using nonparametric methods and multiples of the median for each analyte.A total of 574 case subjects were compared with 952 diet-treated case subjects with diabetes and 979 control subjects. Metformin-exposed infants had shorter gestational age (266 ± 7 vs. 272 ± 10 vs. 274 ± 9 days) (P < 0.001) and lower birth weights (3.28 ± 0.51 vs. 3.29 ± 0.49 vs. 3.33 ± 0.43 kg) (P = 0.008). Short-, medium-, and one long-chain acylcarntine (tetradecanoylcarnitine [C14]) concentrations were higher in the metformin-exposed group compared with normal control subjects. Comparison with diet-treated control subjects with diabetes (to eliminate confounding by hyperglycemia) continued to show raised butyrylcarnitine (C4), isovalerylcarnitine (C5), and glutarylcarnitine (C5D) in the metformin-exposed group. There was no evidence of vitamin B12 deficiency (low methionine and elevated propionylcarnitine [C3]) in metformin-exposed infants. All results were within normal population limits.We have identified subtle (nonpathological) changes in neonatal metabolism that represent a signature effect of fetal metformin exposure.
Elimination of covid-19: beware of surveillance bias
Authors: Stefano Tancredi, Daniela Anker, Laura Rosella, Arnaud Chiolero
Journal: BMJ (2021)

Surveillance bias occurs when looking at health conditions that have differential intensity across populations, over time, or according to care setting or type of patient. 1 As a result, any difference in frequency of the condition might not reflect a change in the actual risk of this condition but rather differences in the modality of detection or patient characteristics.
Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment
Authors: Sheng-Kai Hsu, Chia-Yang Li, I-Ling Lin, Wun-Jyun Syue, Yih-Fung Chen, Kai-Chun Cheng, Yen-Ni Teng, Yi-Hsiung Lin, Chia-Hung Yen, Chien-Chih Chiu
Journal: Theranostics (2021)

In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or bypassing apoptotic cell death. Several novel types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have recently been reported to play significant roles in the modulation of cancer progression and are considered a promising strategy for cancer treatment. Thus, the switch between apoptosis and pyroptosis is also discussed. Cancer immunotherapy has gained increasing attention due to breakthroughs in immune checkpoint inhibitors; moreover, ferroptosis, necroptosis, and pyroptosis are highly correlated with the modulation of immunity in the tumor microenvironment. Compared with necroptosis and ferroptosis, pyroptosis is the primary mechanism for host defense and is crucial for bridging innate and adaptive immunity. Furthermore, recent evidence has demonstrated that pyroptosis exerts benefits on cancer immunotherapies, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T). Hence, in this review, we elucidate the role of pyroptosis in cancer progression and the modulation of immunity. We also summarize the potential small molecules and nanomaterials that target pyroptotic cell death mechanisms and their therapeutic effects on cancer.
Exercise effects on cardiovascular disease: from basic aspects to clinical evidence
Authors: Fabian Sanchis-Gomar, Carl J Lavie, Jorge Marín, Carme Perez-Quilis, Thijs M H Eijsvogels, James H O’Keefe, Marco V Perez, Steven N Blair
Journal: Cardiovascular Research (2021)

Abstract Cardiovascular (CV) disease (CVD) remains the leading cause of major morbidity and CVD- and all-cause mortality in most of the world. It is now clear that regular physical activity (PA) and exercise training (ET) induces a wide range of direct and indirect physiologic adaptations and pleiotropic benefits for human general and CV health. Generally, higher levels of PA, ET, and cardiorespiratory fitness (CRF) are correlated with reduced risk of CVD, including myocardial infarction, CVD-related death, and all-cause mortality. Although exact details regarding the ideal doses of ET, including resistance and, especially, aerobic ET, as well as the potential adverse effects of extreme levels of ET, continue to be investigated, there is no question that most of the world’s population have insufficient levels of PA/ET, and many also have lower than ideal levels of CRF. Therefore, assessment and promotion of PA, ET, and efforts to improve levels of CRF should be integrated into all health professionals’ practices worldwide. In this state-of-the-art review, we discuss the exercise effects on many areas related to CVD, from basic aspects to clinical practice.
Altering the Binding Properties of PRDM9 Partially Restores Fertility across the Species Boundary
Authors: Benjamin Davies, Anjali Gupta Hinch, Alberto Cebrian-Serrano, Samy Alghadban, Philipp W Becker, Daniel Biggs, Polinka Hernandez-Pliego, Chris Preece, Daniela Moralli, Gang Zhang, Simon Myers, Peter Donnelly
Journal: Molecular Biology and Evolution (2021)

Abstract Sterility or subfertility of male hybrid offspring is commonly observed. This phenomenon contributes to reproductive barriers between the parental populations, an early step in the process of speciation. One frequent cause of such infertility is a failure of proper chromosome pairing during male meiosis. In subspecies of the house mouse, the likelihood of successful chromosome synapsis is improved by the binding of the histone methyltransferase PRDM9 to both chromosome homologs at matching positions. Using genetic manipulation, we altered PRDM9 binding to occur more often at matched sites, and find that chromosome pairing defects can be rescued, not only in an intersubspecific cross, but also between distinct species. Using different engineered variants, we demonstrate a quantitative link between the degree of matched homolog binding, chromosome synapsis, and rescue of fertility in hybrids between Mus musculus and Mus spretus. The resulting partial restoration of fertility reveals additional mechanisms at play that act to lock-in the reproductive isolation between these two species.
Impact of healthy aging on active bacterial assemblages throughout the gastrointestinal tract
Authors: Kerstin Schütte, Christian Schulz, Ramiro Vilchez-Vargas, Riccardo Vasapolli, Frederike Palm, Bianca Simon, Dirk Schomburg, Anke Lux, Robert Geffers, Dietmar H. Pieper, Alexander Link, Peter Malfertheiner
Journal: Gut Microbes (2021)

The adaption of gut microbiota (GM) throughout human life is a key factor in maintaining health. Interventions to restore a healthy GM composition may have the potential to improve health and disease outcomes in the elderly. We performed a comprehensive characterization of changes in the luminal and mucosa-associated microbiota composition in elderly compared with younger healthy individuals. Samples from saliva and feces, and biopsies from the upper and lower gastrointestinal tract (UGIT, LGIT), were collected from 59 asymptomatic individuals grouped by age: 40–55, 56–70, and 71–85 years). All underwent anthropometric, geriatric, and nutritional assessment. RNA was extracted and reverse-transcribed into complementary DNA; the V1–V2 regions of 16S ribosomal RNA genes were amplified and sequenced. Abundances of the taxa in all taxonomic ranks in each sample type were used to construct sample-similarity matrices by the Bray–Curtis algorithm. Significant differences between defined groups were assessed by analysis of similarity. The bacterial community showed strong interindividual variations and a clear distinction between samples from UGIT, LGIT, and feces. While in saliva some taxa were affected by aging, this number was considerably greater in UGIT and was subsequently higher in LGIT. Unexpectedly, aging scarcely influenced the bacterial community of feces over the age range of 40–85 years. The development of interventions to preserve and restore human health with increased age by establishing a healthy gut microbiome should not rely solely on data from fecal analysis, as the intestinal mucosa is affected by more significant changes, which differ from those observed in fecal analyses.
LOXL2-enriched small extracellular vesicles mediate hypoxia-induced premetastatic niche and indicates poor outcome of head and neck cancer
Authors: Guiquan Zhu, Linlin Wang, Wanrong Meng, Shun Lu, Bangrong Cao, Xinhua Liang, Chuanshi He, Yaying Hao, Xueyu Du, Xiaoyi Wang, Longjiang Li, Ling Li
Journal: Theranostics (2021)

Small extracellular vesicles (sEVs) operate as a signaling platform due to their ability to carry functional molecular cargos. However, the role of sEVs in hypoxic tumor microenvironment-mediated premetastatic niche formation remains poorly understood.