tbuckley/cabot-search huggingface dataset:
Allocating scarce intensive care resources during the COVID-19 pandemic: practical challenges to theoretical frameworks
Authors: Alexander Supady, J Randall Curtis, Darryl Abrams, Roberto Lorusso, Thomas Bein, Joachim Boldt, Crystal E Brown, Daniel Duerschmied, Victoria Metaxa, Daniel Brodie
Journal: The Lancet Respiratory Medicine (2021)

The COVID-19 pandemic strained health-care systems throughout the world. For some, available medical resources could not meet the increased demand and rationing was ultimately required. Hospitals and governments often sought to establish triage committees to assist with allocation decisions. However, for institutions operating under crisis standards of care (during times when standards of care must be substantially lowered in the setting of crisis), relying on these committees for rationing decisions was impractical-circumstances were changing too rapidly, occurring in too many diverse locations within hospitals, and the available information for decision making was notably scarce. Furthermore, a utilitarian approach to decision making based on an analysis of outcomes is problematic due to uncertainty regarding outcomes of different therapeutic options. We propose that triage committees could be involved in providing policies and guidance for clinicians to help ensure equity in the application of rationing under crisis standards of care. An approach guided by egalitarian principles, integrated with utilitarian principles, can support physicians at the bedside when they must ration scarce resources.
Abstract 12300: Differential Impact of Plasma Brain Natriuretic Peptide Level on Long-term Clinical Outcomes in Acute Heart Failure Patients With Reduced, Mid-range and Preserved Ejection Fraction
Authors: Yasuhiro Hamatani, Toshiyuki Nagai, Yasuyuki Shiraishi, Shun Kohsaka, Michikazu Nakai, Kunihiro Nishimura, Takashi Kohno, Yuji Nagatomo, Yasuhide Asaumi, Ayumi Goda, Atsushi Mizuno, Satoshi Yasuda, Hisao Ogawa, Tsutomu Yoshikawa, Toshihisa Anzai
Journal: Circulation (2017)

Introduction: Plasma brain natriuretic peptide (BNP) is an important prognostic marker in acute heart failure (AHF) patients. Measurement of BNP level is recommended for estimating the risk of adve...
Gene variations in Autism Spectrum Disorder are associated with alternation of gut microbiota, metabolites and cytokines
Authors: Zhi Liu, Xuhua Mao, Zhou Dan, Yang Pei, Rui Xu, Mengchen Guo, Kangjian Liu, Faming Zhang, Junyu Chen, Chuan Su, Yaoyao Zhuang, Junming Tang, Yankai Xia, Lianhong Qin, Zhibin Hu, Xingyin Liu
Journal: Gut Microbes (2021)

The genetic variations and dysbiosis of gut microbiota are associated with ASD. However, the role of the microbiota in the etiology of ASD in terms of host genetic susceptibility remains unclear. This study aims to systematically explore the interplay between host genetic variation and gut microbiota in ASD children. Whole-exon sequencing was applied to 26 ASD children and 26 matched controls to identify the single nucleotide variations (SNVs) in ASD. Our previous study revealed alteration in gut microbiota and disorder of metabolism activity in ASD for this cohort. Systematic bioinformatic analyses were further performed to identify associations between SNVs and gut microbiota, as well as their metabolites. The ASD SNVs were significantly enriched in genes associated with innate immune response, protein glycosylation process, and retrograde axonal transport. These SNVs were also correlated with the microbiome composition and a broad aspect of microbial functions, especially metabolism. Additionally, the abundance of metabolites involved in the metabolic network of neurotransmitters was inferred to be causally related to specific SNVs and microbes. Furthermore, our data suggested that the interaction of host genetics and gut microbes may play a crucial role in the immune and metabolism homeostasis of ASD. This study may provide valuable clues to investigate the interaction of host genetic variations and gut microbiota in the pathogenesis of ASD.
Fusion Transcripts without Corresponding Cytogenetic Abnormalities in Acute Myeloid Leukemia: Implications for AML Pathogenesis
Authors: I. J. Locher, W. Arindrarto, D. M. Borras, M. W. Honders, R. H. de Leeuw, W. G. M. Kroes, P. de Knijff, C. A. M. van Bergen, P. A. C. t. Hoen, S. M. Kielbasa, J. F. J. Laros, M. Griffioen, H. Veelken
Journal: Blood (2017)
Exercise-induced bronchoconstriction and bronchodilation: investigating the effects of age, sex, airflow limitation and FEV<sub>1</sub>
Authors: Imran Satia, Eldar Priel, Baraa K. Al-Khazraji, Graham Jones, Andy Freitag, Paul M. O'Byrne, Kieran J. Killian
Journal: European Respiratory Journal (2021)

Exercise-induced bronchoconstriction (EIBc) is a recognised response to exercise in asthmatic subjects and athletes but is less well understood in an unselected broad population. Exercise-induced bronchodilation (EIBd) has received even less attention. The objective of this study was to investigate the effects of age, sex, forced expiratory volume in 1 s (FEV 1 ) and airflow limitation (FEV 1 /forced vital capacity (FVC) &lt;0.7) on the prevalence of EIBc and EIBd. This was a retrospective study based on incremental cardiopulmonary exercise testing on cycle ergometry to symptom limitation performed between 1988 and 2012. FEV 1 was measured before and 10 min after exercise. EIBc was defined as a percentage fall in FEV 1 post-exercise below the 5th percentile, while EIBd was defined as a percentage increase in FEV 1 above the 95th percentile. 35 258 subjects aged 6–95 years were included in the study (mean age 53 years, 60% male) and 10.3% had airflow limitation (FEV 1 /FVC &lt;0.7). The lowest 5% of subjects demonstrated a ≥7.6% fall in FEV 1 post-exercise (EIBc), while the highest 5% demonstrated a &gt;11% increase in FEV 1 post-exercise (EIBd). The probability of both EIBc and EIBd increased with age and was highest in females across all ages (OR 1.76, 95% CI 1.60–1.94; p&lt;0.0001). The probability of EIBc increased as FEV 1 % pred declined (&lt;40%: OR 4.38, 95% CI 3.04–6.31; p&lt;0.0001), with a &gt;2-fold increased likelihood in females (OR 2.31, 95% CI 1.71–3.11; p&lt;0.0001), with a trend with airflow limitation (p=0.06). The probability of EIBd increased as FEV 1 % pred declined, in the presence of airflow limitation (OR 1.55, 95% CI 1.24–1.95; p=0.0001), but sex had no effect. EIBc and EIBd can be demonstrated at the population level, and are influenced by age, sex, FEV 1 % pred and airflow limitation.
FYN–TRAF3IP2 induces NF-κB signaling-driven peripheral T-cell lymphoma
Authors: Christine S. Moon, Clara Reglero, Jose R. Cortes, S. Aidan Quinn, Silvia Alvarez, Junfei Zhao, Wen-Hsuan W. Lin, Anisha J. Cooke, Francesco Abate, Craig R. Soderquist, Claudia Fiñana, Giorgio Inghirami, Elias Campo, Govind Bhagat, Raul Rabadan, Teresa Palomero, Adolfo A. Ferrando
Journal: Nature Cancer (2021)
A Subset of Large Cell Neuroendocrine Carcinomas in the Gastroenteropancreatic Tract May Evolve from Pre-existing Well-Differentiated Neuroendocrine Tumors
Authors: Giuseppe Pelosi, Fabrizio Bianchi, Elisa Dama, Jasna Metovic, Marco Barella, Angelica Sonzogni, Adriana Albini, Mauro Papotti, Yulan Gong, Namrata Vijayvergia
Journal: Endocrine Pathology (2021)
A randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced mucosal melanoma.
Authors: Xi Nan Sheng, Lu Si, Zhihong Chi, Chuanliang Cui, Si Ming Li, Li Li Mao, BIN LIAN, Bixia Tang, Xieqiao Yan, Xuan Wang, Yan Kong, Jie Dai, Xiao-Shi Zhang, Song Xin, Jun Guo
Journal: Journal of Clinical Oncology (2015)

e20076 Background: Mucosal melanoma is rare in Caucasian but account for 25% in Asian population and usually associated with poor prognosis. No standard treatment for advanced mucosal melanoma has been established. BEAM study has shown the potential effectiveness of bevacizumab combined with carboplatin plus paclitaxel in patients with previously untreated advanced cutaneous melanoma. This study aimed to evaluate the activity of bevacizumab combined with carboplatin plus paclitaxel in patients with previously untreated advanced mucosal melanoma. Methods: This study is an open-label, multi-center, randomized phase II trial. Eligible patients had metastatic, recurrent or unresectable mucosal melanoma without previous systemic therapy. Additional inclusion criteria included: ≥ 1 measurable disease, ECOG PS 0/1, and adequate organ functions. C-KIT or BRAF mut will be excluded from this study. Patients were randomly allocated in a 1:1 ratio to receive intravenous infusion of bevacizumab (CPB arm, 5mg/kg every two weeks) or placebo (CP arm) in combination with carboplatin (area under the curve, 5) plus paclitaxel (175 mg/m2) until occurrence of disease progression, unacceptable toxicity, death or withdrawal of consent. The primary study endpoint is progress-free survival (PFS). Overall survival, disease control rate, and safety will also be assessed. Results: The first patient visit was on December 1, 2013. Fifty-seven of a planned 182 evaluable pts have been enrolled: 63.2% female, median age 58 (CBP (n = 29) and CP arm (n = 28). The median follow-up time was 11 months, and the median PFS was 6.3 and 3.1 months respectively (p = 0.023). The objective response rate was 10.3% and 7.4% respectively. The median overall survival has not been reached. Treatment emergent grade 3 or 4 adverse events were neutropenia (13.8%), hypertension (3.4%), proteinuria (3.4%) in the PCB arm, and neutropenia (7.4%) in the PC arm. Conclusions: The primary data show that bevacizumab combined with carboplatin plus paclitaxel might benefit for patients with advanced mucosal melanoma. Clinical trial information: NCT02023710.
Structural tuning of oligonucleotides for enhanced blood circulation properties of unit polyion complexes prepared from two-branched poly(ethylene glycol)-block-poly(l-lysine)
Authors: Mitsuru Naito, Hiroyuki Chaya, Kazuko Toh, Beob Soo Kim, Kotaro Hayashi, Shigeto Fukushima, Tetsuya Nagata, Takanori Yokota, Kazunori Kataoka, Kanjiro Miyata
Journal: Journal of Controlled Release (2021)
Functional Divergence of Multiple Duplicated <i>Foxl2</i> Homeologs and Alleles in a Recurrent Polyploid Fish
Authors: Rui-Hai Gan, Yang Wang, Zhi Li, Zhao-Xi Yu, Xi-Yin Li, Jin-Feng Tong, Zhong-Wei Wang, Xiao-Juan Zhang, Li Zhou, Jian-Fang Gui
Journal: Molecular Biology and Evolution (2021)

Evolutionary fates of duplicated genes have been widely investigated in many polyploid plants and animals, but research is scarce in recurrent polyploids. In this study, we focused on foxl2, a central player in ovary, and elaborated the functional divergence in gibel carp (Carassius gibelio), a recurrent auto-allo-hexaploid fish. First, we identified three divergent foxl2 homeologs (Cgfoxl2a-B, Cgfoxl2b-A, and Cgfoxl2b-B), each of them possessing three highly conserved alleles and revealed their biased retention/loss. Then, their abundant sexual dimorphism and biased expression were uncovered in hypothalamic-pituitary-gonadal axis. Significantly, granulosa cells and three subpopulations of thecal cells were distinguished by cellular localization of CgFoxl2a and CgFoxl2b, and the functional roles and the involved process were traced in folliculogenesis. Finally, we successfully edited multiple foxl2 homeologs and/or alleles by using CRISPR/Cas9. Cgfoxl2a-B deficiency led to ovary development arrest or complete sex reversal, whereas complete disruption of Cgfoxl2b-A and Cgfoxl2b-B resulted in the depletion of germ cells. Taken together, the detailed cellular localization and functional differences indicate that Cgfoxl2a and Cgfoxl2b have subfunctionalized and cooperated to regulate folliculogenesis and gonad differentiation, and Cgfoxl2b has evolved a new function in oogenesis. Therefore, the current study provides a typical case of homeolog/allele diversification, retention/loss, biased expression, and sub-/neofunctionalization in the evolution of duplicated genes driven by polyploidy and subsequent diploidization from the recurrent polyploid fish.
<i>CBL</i> mutations drive PI3K/AKT signaling via increased interaction with LYN and PIK3R1
Authors: Roger Belizaire, Sebastian H. J. Koochaki, Namrata D. Udeshi, Alexis Vedder, Lei Sun, Tanya Svinkina, Christina Hartigan, Marie McConkey, Veronica Kovalcik, Amanuel Bizuayehu, Caroline Stanclift, Monica Schenone, Steven A. Carr, Eric Padron, Benjamin L. Ebert
Journal: Blood (2021)
OA05.04 Real-World Progression-Free Survival in Oncogenic Driver-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated With Single-Agent Immunotherapy
Authors: J. Bodor, J. Bauman, E. Handorf, C. Zawislak, E. Ross, M. Clapper, J. Treat
Journal: Journal of Thoracic Oncology (2021)
Analysis Methods for Observational Studies: Effects of Cardiac Rehabilitation on Mortality of Coronary Patients⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Therese A. Stukel, David A. Alter
Journal: Journal of the American College of Cardiology (2009)
Covid-19: “Shkreli Awards” go to pandemic’s top profiteers
Authors: Owen Dyer
Journal: BMJ (2021)

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The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia
Authors: Anita Mitra, David A. MacIntyre, Maria Paraskevaidi, Anna-Barbara Moscicki, Vishakha Mahajan, Ann Smith, Yun S. Lee, Deirdre Lyons, Evangelos Paraskevaidis, Julian R. Marchesi, Phillip R. Bennett, Maria Kyrgiou
Journal: Genome Medicine (2021)

Abstract Background Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. Methods We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls. Results Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- ( p &lt; 0.0001 and p = 0.0014, respectively) and post-treatment ( p &lt; 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision ( p &lt; 0.0001); however, their levels remained lower than controls post-treatment. Conclusions Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus -enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.
SAT0084 Development and initial psychometric validation of the arthritis treatment satisfaction questionnaire (arts)
Authors: J Pouchot, E Trudeau, J Goguel
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To develop and examine the reliability and validity of a questionnaire assessing patient satisfaction with their osteoarthritis treatment. <h3>Methods</h3> Item generation: Semi-structured interviews were performed among 20 French patients (6 suffering from arthritis of the knee, 6 of the hip and 8 of the hand), and 10 clinicians (5 rheumatologists and 5 general practitioners (GPs)). Interviews were recorded, transcribed and analysed. The first version of the questionnaire was produced in French and reviewed by 5 rheumatologists and 5 GPs. Content validity and cognitive debriefing were performed on 10 arthritis patients. The resulting arthritis treatment satisfaction (ARTS) questionnaire comprised 24 items. Validation study: Psychometric analysis was performed to establish the structure (Principal Component Analysis (PCA) and multi-trait analysis) and the internal consistency (Cronbach alpha) of the questionnaire on a cross-sectional sample of 797 arthritis patients recruited by their clinicians. Patients were on average 67.5 years old (sd = 10.4), 64.5% were women, 26%had arthritis of the hip, 58%had arthritis of the knee, and all patients had suffered from arthritis for an average of 7 years (sd = 6.4). <h3>Results</h3> PCA revealed a clear four dimensional structure. In order to reduce the number of items, 6 out of the 24 items were discarded because of moderate to low item convergent validity, and because they did not modify the internal reliability coefficient and content validity of the questionnaire. The final questionnaire comprised 18 items consisting of 4 dimensions measuring treatment advantages, treatment convenience, apprehensions about treatment and satisfaction with medical care. Item convergent and discriminant validity and the internal consistency reliability were satisfactory (Cronbach alpha of 0.84 for the global questionnaire which varied between 0.63 and 0.88 per dimension). PCA and multitrait analysis were reproduced on an independent sample of 137 patients, thus confirming the relevance of the 4 dimensional structure and internal consistency reliability of the questionnaire. <h3>Conclusion</h3> Psychometric validity of this first treatment satisfaction questionnaire specific to arthritis is promising and further psychometric validation (clinical validity and reproducibility) is presently underway.
Quality and Safety in Healthcare, Part LXXXIV
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2021)

An important approach to improve the reliability of healthcare organizations is the use of patient safety culture surveys to identify areas that need improvement. Commonly found areas that need development include having more superior leadership regarding safety, improving communications such as with the Ticket to Ride Program and WalkRounds, enhancing teamwork, and using certain collections of "reliability-enhancing work practices."
Value-Based Healthcare in Urology: A Collaborative Review
Authors: Chanan Reitblat, Paul A. Bain, Michael E. Porter, David N. Bernstein, Thomas W. Feeley, Markus Graefen, Santosh Iyer, Matthew J. Resnick, C.J. Stimson, Quoc-Dien Trinh, Boris Gershman
Journal: European Urology (2021)
Validation of the new DSM‐5‐TR criteria for prolonged grief disorder and the <scp>PG‐13‐Revised</scp> (<scp>PG‐13‐R</scp>) scale
Authors: Holly G. Prigerson, Paul A. Boelen, Jiehui Xu, Kirsten V. Smith, Paul K. Maciejewski
Journal: World Psychiatry (2021)

Although the concept of pathological grief dates back at least as far as Freud’s “ Mourning and Melancholia ”, there has been opposition to its recognition as a distinct mental disorder. Resistance has been overcome by evidence demonstrating that distinctive symptoms of prolonged grief disorder (PGD) – an attachment disturbance featuring yearning for the deceased, loss of meaning and identity disruption – can endure, prove distressing and disabling, and require targeted treatment. In acknowledgement of this evidence, the American Psychiatric Association Assembly has recently voted to include PGD as a new mental disorder in the DSM‐5‐TR. We tested the validity of the new DSM criteria for PGD and of an adapted version of our PG‐13 scale, the PG‐13‐Revised (PG‐13‐R), designed to map onto these criteria, using data from investigations conducted at Yale University (N=270), Utrecht University (N=163) and Oxford University (N=239). Baseline assessments were performed at 12‐24 months post‐loss; follow‐up assessments took place 5.3‐12.0 months later. Results indicated that the PG‐13‐R grief symptoms represent a unidimensional construct, with high degrees of internal consistency (Cronbach's alpha = 0.83, 0.90 and 0.93, for Yale, Utrecht and Oxford, respectively). The DSM PGD diagnosis was distinct from post‐traumatic stress disorder (phi=0.12), major depressive disorder (phi=0.25) and generalized anxiety disorder (phi=0.26) at baseline. Temporal stability was remarkable for this diagnosis (r=0.86, p&lt;0.001). Kappa agreement between a PG‐13‐R threshold symptom summary score of 30 and the DSM symptom criterion for PGD was 0.70‐0.89 across the datasets. Both the DSM PGD diagnosis and the PG‐13‐R symptom summary score at baseline were significantly associated (p&lt;0.05) with symptoms and diagnoses of major depressive disorder, post‐traumatic stress disorder and/or generalized anxiety disorder, suicidal ideation, worse quality of life and functional impairments at baseline and at follow‐up, in the Yale, Utrecht and Oxford datasets. Overall, the DSM‐5‐TR criteria for PGD and the PG‐13‐R both proved reliable and valid measures for the classification of bereaved individuals with maladaptive grief responses.