tbuckley/cabot-search huggingface dataset:
Quality and Safety in Healthcare, Part LXIII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2020)

Abstract A lack of well-being, including burnout, is common among residents. Suggestions to combat these issues include promoting a sense of collegiality and camaraderie in the medical community, talking to residents with respect, remedying the reasonable complaints of residents in a reasonable time frame, offering well-being newsletters, having curricula in narrative medicine, encouraging more exercise, and having coaching programs. Suicide prevention programs are also important.
Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985–2014
Authors: Elena Myasoedova, John Davis, Eric L Matteson, Cynthia S Crowson
Journal: Annals of the Rheumatic Diseases (2020)

To examine trends in the incidence of rheumatoid arthritis (RA) from 2005 to 2014 overall and by serological status as compared with 1995-2004 and 1985-1994.
Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China
Authors: Min Wei, Jingping Yuan, Yu Liu, Tao Fu, Xue Yu, Zhi-Jiang Zhang
Journal: JAMA (2020)

This study characterizes the demographic, epidemiologic, and clinical characteristics of hospitalized infants diagnosed with coronavirus disease 2019 infection between December 8, 2019, and February 6, 2020, in China.
Three Problems in Meta-analysis of Prevalence of Obesity in European Children
Authors: Pengfei Sun, Shuang Wang, Zhensheng Hu
Journal: JAMA Pediatrics (2020)

To the Editor We read the published study by Garrido-Miguel et al, "Prevalence and Trends of Overweight and Obesity in European Children from 1999 to 2016: a Systematic Review and Meta-analysis,"1 carefully. However, we found some points worth discussing in the article.
Accuracy of dermoscopic criteria for the differential diagnosis between irritated seborrheic keratosis and squamous cell carcinoma
Authors: Chryssoula Papageorgiou, Ioannis Spyridis, Sofia Magdalini Manoli, Iuliana Busila, Irina Elena Nasturica, Konstantinos Lallas, Angeliki Panagopoulou, Ilias Papadimitriou, Nikolaos Sideris, Theodosia Gentsidi, Ruben Gonzalez-Cuevas, Andjelka Ilieva, Dimitrios Ioannides, Zoe Apalla, Aimilios Lallas
Journal: Journal of the American Academy of Dermatology (2020)
Preventing catastrophic injury and death in collegiate athletes: interassociation recommendations endorsed by 13 medical and sports medicine organisations
Authors: John T Parsons, Scott A Anderson, Douglas J Casa, Brian Hainline
Journal: British Journal of Sports Medicine (2019)

The following organisations endorsed this document: American Association of Neurological Surgeons, American Medical Society for Sports Medicine, American Orthopaedic Society for Sports Medicine, American Osteopathic Academy of Sports Medicine, College Athletic Trainers’ Society, Collegiate Strength and Conditioning Coaches Association, Congress of Neurological Surgeons, Korey Stringer Institute, National Athletic Trainers’ Association, National Strength and Conditioning Association, National Operating Committee for Standards on Athletic Equipment, Sports Neuropsychology Society. The following organisation has affirmed the value of this document: American Academy of Neurology. The Second Safety in College Football Summit resulted in interassociation consensus recommendations for three paramount safety issues in collegiate athletics: (1) independent medical care for collegiate athletes; (2) diagnosis and management of sport-related concussion; and (3) year-round football practice contact for collegiate athletes. This document, the fourth arising from the 2016 event, addresses the prevention of catastrophic injury, including traumatic and non-traumatic death, in collegiate athletes. The final recommendations in this document are the result of presentations and discussions on key items that occurred at the summit. After those presentations and discussions, endorsing organisation representatives agreed on 18 foundational statements that became the basis for this consensus paper that has been subsequently reviewed by relevant stakeholders and endorsing organisations. This is the final endorsed document for preventing catastrophic injury and death in collegiate athletes. This document is divided into the following components. (1) Background—this section provides an overview of catastrophic injury and death in collegiate athletes. (2) Interassociation recommendations: preventing catastrophic injury and death in collegiate athletes—this section provides the final recommendations of the medical organisations for preventing catastrophic injuries in collegiate athletes. (3) Interassociation recommendations: checklist—this section provides a checklist for each member school. The checklist statements stem from foundational statements voted on by representatives of medical organisations during the summit, and they serve as the primary vehicle for each member school to implement the prevention recommendations. (4) References—this section provides the relevant references for this document. (5) Appendices—this section lists the foundational statements, agenda, summit attendees and medical organisations that endorsed this document.
Abstract P2-14-21: Adjuvant chemotherapy-associated lipid changes in breast cancer patients: A retrospective analysis
Authors: Tao He, Yunhao Wu, Xinyi Zhang, Jie Chen
Journal: Cancer Research (2020)

Abstract Background: Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy modalities remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare lipid level alterations among different chemotherapy modalities. Methods: We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy modalities: doxorubicin and cyclophosphamide followed by paclitaxel (AC-T); epirubicin and cyclophosphamide followed by paclitaxel (EC-T); cyclophosphamide and paclitaxel (TC); and fluorouracil, cyclophosphamide and epirubicin (FEC). Results: The levels of triglycerides (TGs), total cholesterol (TC) and low-density lipoprotein (LDL) were significantly elevated in patients who received chemotherapy (p&amp;lt;0.01). With respect to different chemotherapy modalities, AC-T elevated the lipid profiles more than FEC in premenopausal patients (p&amp;lt;0.05), while in postmenopausal patients, FEC had the smallest effects in terms of high-density lipoprotein (HDL) and LDL compared with the effects of other chemotherapy modalities (p&amp;lt;0.05). In addition, premenopausal BC patients had a higher incidence of dyslipidaemia (18.84%) after chemotherapy than postmenopausal BC patients (12.27%). Moreover, after adjusting for multiple baseline covariates, AC-T chemotherapy modality was still statistically associated with a high level of TGs after chemotherapy. Conclusions: BC patients receiving chemotherapy may have a high risk of dyslipidaemia, but the effects vary with different chemotherapy modalities. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and to monitor serum lipids regularly during chemotherapy.Key words: Breast cancer; Adjuvant chemotherapy; Dyslipidaemia Citation Format: Tao He, Yunhao Wu, Xinyi Zhang, Jie Chen. Adjuvant chemotherapy-associated lipid changes in breast cancer patients: A retrospective analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-21.
PS1144 TARGETING IRAK4 DISRUPTS INFLAMMATORY PATHWAYS AND DELAYS TUMOR DEVELOPMENT IN CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: L. Rosich Moya, N. Gimenez, R. Schulz, M. Higashi, M. Aymerich, N. Villamor, J. Delgado, M. Juan, M. Lopez‐Guerra, E. campo, M. Seiffert, D. Colomer
Journal: HemaSphere (2019)

Background: Interleukin‐1 receptor‐associated kinase 4 (IRAK4) plays a critical role in Toll‐like receptor (TLR) signal transduction and innate immune responses. Recruitment and subsequent activation of IRAK4 upon TLR stimulation is mediated by the myeloid differentiation primary response 88 (MYD88) adaptor protein. Around 3% of chronic lymphocytic leukemia (CLL) patients have activating mutations of MYD88 , a driver mutation in this disease. Aims: Here, we studied the effects of TLR activation and the pharmacological inhibition of IRAK4 with ND2158, an IRAK4 competitive inhibitor, as a therapeutic approach in CLL. Methods: TLR stimulation was performed with an agonist mix of Pam3CSK4, HKLM, FSL1 and ODN2006. Cytokine secretion and CLL proliferation were assessed by Luminex system and carboxyfluorescein succinimidyl ester staining, respectively. For in vivo studies, the Eμ‐TCL1 adoptive transfer mouse model was used. Results: Our in vitro studies demonstrated that ND2158 preferentially killed CLL cells in a dose‐dependent manner. We further observed a decrease in NF‐κB and STAT3 signaling, cytokine secretion, proliferation and migration of primary CLL cells from MYD88‐ mutated and –unmutated cases. In the Eμ ‐TCL1 adoptive transfer mouse model of CLL, ND2158 delayed tumor progression and modulated the activity of myeloid and T cells. Summary/Conclusion: Our findings show the importance of TLR signaling in CLL development and suggest IRAK4 as a therapeutic target for this disease.
Southern Chinese populations harbour non-nucleatum Fusobacteria possessing homologues of the colorectal cancer-associated FadA virulence factor
Authors: Yun Kit Yeoh, Zigui Chen, Martin C S Wong, Mamie Hui, Jun Yu, Siew C Ng, Joseph J Y Sung, Francis K L Chan, Paul K S Chan
Journal: Gut (2020)

Objective Fusobacteria are not common nor relatively abundant in non-colorectal cancer (CRC) populations, however, we identified multiple Fusobacterium taxa nearly absent in western and rural populations to be comparatively more prevalent and relatively abundant in southern Chinese populations. We investigated whether these represented known or novel lineages in the Fusobacterium genus, and assessed their genomes for features implicated in development of cancer. Methods Prevalence and relative abundances of fusobacterial species were calculated from 3157 CRC and non-CRC gut metagenomes representing 16 populations from various biogeographies. Microbial genomes were assembled and compared with existing reference genomes to assess novel fusobacterial diversity. Phylogenetic distribution of virulence genes implicated in CRC was investigated. Results Irrespective of CRC disease status, southern Chinese populations harboured increased prevalence (maximum 39% vs 7%) and relative abundances (average 0.4% vs 0.04% of gut community) of multiple recognised and novel fusobacterial taxa phylogenetically distinct from Fusobacterium nucleatum . Genomes assembled from southern Chinese gut metagenomes increased existing fusobacterial diversity by 14.3%. Homologues of the FadA adhesin linked to CRC were consistently detected in several monophyletic lineages sister to and inclusive of F. varium and F. ulcerans , but not F. mortiferum . We also detected increased prevalence and relative abundances of F. varium in CRC compared with non-CRC cohorts, which together with distribution of FadA homologues supports a possible association with gut disease. Conclusion The proportion of fusobacteria in guts of southern Chinese populations are higher compared with several western and rural populations in line with the notion of environment/biogeography driving human gut microbiome composition. Several non-nucleatum taxa possess FadA homologues and were enriched in CRC cohorts; whether this imposes a risk in developing CRC and other gut diseases deserves further investigation.
Distinct microbial and immune niches of the human colon
Authors: Kylie R. James, Tomas Gomes, Rasa Elmentaite, Nitin Kumar, Emily L. Gulliver, Hamish W. King, Mark D. Stares, Bethany R. Bareham, John R. Ferdinand, Velislava N. Petrova, Krzysztof Polański, Samuel C. Forster, Lorna B. Jarvis, Ondrej Suchanek, Sarah Howlett, Louisa K. James, Joanne L. Jones, Kerstin B. Meyer, Menna R. Clatworthy, Kourosh Saeb-Parsy, Trevor D. Lawley, Sarah A. Teichmann
Journal: Nature Immunology (2020)
How autophagy can restore proteostasis defects in multiple diseases?
Authors: Vibhuti Joshi, Arun Upadhyay, Vijay K. Prajapati, Amit Mishra
Journal: Medicinal Research Reviews (2020)

Abstract Cellular evolution develops several conserved mechanisms by which cells can tolerate various difficult conditions and overall maintain homeostasis. Autophagy is a well‐developed and evolutionarily conserved mechanism of catabolism, which endorses the degradation of foreign and endogenous materials via autolysosome. To decrease the burden of the ubiquitin‐proteasome system (UPS), autophagy also promotes the selective degradation of proteins in a tightly regulated way to improve the physiological balance of cellular proteostasis that may get perturbed due to the accumulation of misfolded proteins. However, the diverse as well as selective clearance of unwanted materials and regulations of several cellular mechanisms via autophagy is still a critical mystery. Also, the failure of autophagy causes an increase in the accumulation of harmful protein aggregates that may lead to neurodegeneration. Therefore, it is necessary to address this multifactorial threat for in‐depth research and develop more effective therapeutic strategies against lethal autophagy alterations. In this paper, we discuss the most relevant and recent reports on autophagy modulations and their impact on neurodegeneration and other complex disorders. We have summarized various pharmacological findings linked with the induction and suppression of autophagy mechanism and their promising preclinical and clinical applications to provide therapeutic solutions against neurodegeneration. The conclusion, key questions, and future prospectives sections summarize fundamental challenges and their possible feasible solutions linked with autophagy mechanism to potentially design an impactful therapeutic niche to treat neurodegenerative diseases and imperfect aging.
Changes in the Global Burden of Chronic Liver Diseases From 2012 to 2017: The Growing Impact of NAFLD
Authors: James M. Paik, Pegah Golabi, Youssef Younossi, Alita Mishra, Zobair M. Younossi
Journal: Hepatology (2020)

Chronic hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD) are main causes of chronic liver disease. We assessed the global incidence, mortality, and disability-adjusted life-years (DALYs) related to chronic liver disease (primary liver cancer [LC] and cirrhosis).We obtained data from the 2017 Global Burden of Disease study. In 2017, there were 2.14 million liver-related deaths (2.06-2.30 million), representing an 11.4% increase since 2012 (16.0% increase in LC deaths; 8.7% increase in cirrhosis deaths). LC and cirrhosis accounted for 38.3% and 61.7%, respectively, of liver deaths (LC and cirrhosis deaths were related to HBV [39% and 29%], HCV [29% and 26%], ALD [16% and 25%], and NAFLD [8% and 9%]). Between 2012 and 2017, age-standardized incidence rate, age-standardized death rate (ASDR), and age-standardized DALY rate increased for LC from 11.1 to 11.8, 10.1 to 10.2, and 250.4 to 253.6 per 100,000, respectively. Although age-standardized incidence rate for cirrhosis increased from 66.0 to 66.3, ASDR and age-standardized DALY rate decreased from 17.1 to 16.5 and 532.9 to 510.7, respectively. The largest increase in ASDR for LC occurred in Eastern Europe (annual percent change [APC] = 2.18% [0.89%-3.49%]), whereas the largest decrease occurred in high-income Asia Pacific (APC = -2.88% [-3.58 to -2.18%]). ASDR for LC-NAFLD and ALD increased annually by 1.42% (1.00%-1.83%) and 0.53% (0.08-0.89), respectively, whereas there were no increases for HBV (P = 0.224) and HCV (P = 0.054). ASDR for cirrhosis-NAFLD increased (APC = 0.29% [0.01%-0.59%]) but decreased for ALD (APC = -0.44% [-0.78% to -0.40%]), HCV (APC = -0.50% [-0.81% to -0.18%]), and HBV (APC = -1.43% [-1.71% to -0.40%]).From 2012 to 2017, the global burden of LC and cirrhosis has increased. Viral hepatitis remains the most common cause of liver deaths, and NAFLD is the most rapidly growing contributor to liver mortality and morbidity.
Conditional Survival, Cause-Specific Mortality, and Risk Factors of Late Mortality After Allogeneic Hematopoietic Cell Transplantation
Authors: F Lennie Wong, Jennifer Berano Teh, Liezl Atencio, Tracey Stiller, Heeyoung Kim, Dayana Chanson, Stephen J Forman, Ryotaro Nakamura, Saro H Armenian
Journal: JNCI Journal of the National Cancer Institute (2020)

Long-term mortality after hematopoietic cell transplantation (HCT) is conventionally calculated from the time of HCT, ignoring temporal changes in survivors' mortality risks. Conditional survival rates, accounting for time already survived, are relevant for optimal delivery of survivorship care but have not been widely quantified. We estimated conditional survival by elapsed survival time in allogeneic HCT patients and examined cause-specific mortality.We calculated conditional survival rates and standardized mortality ratio for overall and cause-specific mortality in 4485 patients who underwent HCT for malignant hematologic diseases at a large transplant center during 1976-2014. Statistical tests were two-sided.The 5-year survival rate from HCT was 48.6%. After surviving 1, 2, 5, 10, and 15 years, the subsequent 5-year survival rates were 71.2%, 78.7%, 87.4%, 93.5%, and 86.2%, respectively. The standardized mortality ratio was 30.3 (95% confidence interval [CI] = 29.2 to 35.5). Although the standardized mortality ratio declined in longer surviving patients, it was still elevated by 3.6-fold in survivors of 15 years or more (95% CI = 3.0 to 4.1). Primary disease accounted for 50% of deaths in the overall cohort and only 10% in 15-year survivors; the leading causes of nondisease-related mortality were subsequent malignancy (26.1%) and cardiopulmonary diseases (20.2%). We also identified the risk factors for nondisease-related mortality in 1- and 5-year survivors.Survival probability improves the longer patients survive after HCT. However, HCT recipients surviving 15 years or more remain at elevated mortality risk, largely because of health conditions other than their primary disease. Our study findings help inform preventive and interventional strategies to improve long-term outcomes after allogeneic HCT.
Child Health Accountability Tracking—extending child health measurement
Authors: Kathleen Strong, Jennifer Requejo, Ambrose Agweyu, Neil McKerrow, Joanna Schellenberg, Diparidé Abdourahmane Agbere, Sk Masum Billah, Cynthia Boschi-Pinto, Sayaka Horiuchi, Marzia Lazzerini, Abdoulaye Maiga, Melinda Munos, Ralf Weigel, Anshu Banerjee, Mark Hereward, Theresa Diaz
Journal: The Lancet Child & Adolescent Health (2020)
Association of Tuberculosis With Household Catastrophic Expenditure in South India
Authors: Malaisamy Muniyandi, Beena Elizabeth Thomas, Nagarajan Karikalan, Thiruvengadam Kannan, Krishnan Rajendran, Balakrishnan Saravanan, Vikram Vohra, Tuoyo Okorosobo, Knut Lönnroth, Srikanth Prasad Tripathy
Journal: JAMA Network Open (2020)

The high household costs associated with tuberculosis (TB) diagnosis and treatment can create barriers to access and adherence, highlighting the urgency of achieving the World Health Organization's End TB Strategy target that no TB-affected households should face catastrophic costs by 2020.To estimate the occurrence of catastrophic costs associated with TB diagnosis and treatment and to identify socioeconomic indicators associated with catastrophic costs in a setting where TB control strategies have been implemented effectively.In this cross-sectional study, 455 patients with TB in the Chennai metropolitan area of South India who were treated under the TB control program between February 2017 and March 2018 were interviewed. Patients were interviewed by trained field investigators at 3 time points: at the initiation of treatment, at the end of the intensive phase of treatment, and at the end of the continuation phase of treatment. A precoded interview schedule was used to collect information on demographic, socioeconomic, and clinical characteristics and direct medical, direct nonmedical, and indirect costs. Data analysis was performed from August 2018 to November 2019.Direct, indirect, and total costs to patients with TB. Catastrophic costs associated with TB were defined as costs exceeding 20% of the household's annual income. A binary response model was used to determine the factors that were significantly associated with catastrophic costs.Of 455 patients with TB interviewed, 205 (53%) were aged 19 to 45 years (mean [SD] age, 38.4 [16.0] years), 128 (33%) were female, 72 (19%) were illiterate, 126 (33%) were employed, and 186 (48%) had a single earning member in the family (percentages are based on the 384 patients who were interviewed through the end of the continuation phase of treatment). Sixty-one percent of patients (234 patients) had pulmonary smear positive TB. The proportion of patients with catastrophic costs was 31%. Indirect costs contributed more toward catastrophic cost than did direct costs. Multivariate logistic regression analysis found that unemployment (adjusted odds ratio, 0.2; 95% CI, 0.1-0.5; P < .001) and higher annual household income (Rs 1-200 000, adjusted odds ratio, 0.4; 95% CI, 0.2-0.7; P = .004; Rs >200 000, adjusted odds ratio, 0.2; 95% CI, 0.1-0.5; P < .001) were associated with a decreased likelihood of experiencing catastrophic costs.Despite the implementation of free diagnostic and treatment services under a national TB control program, TB-affected households had a high risk of catastrophic costs and further impoverishment. There is an urgent demand to provide additional financial protection for patients with TB.
Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays
Authors: Niccolo Candelise, Matthias Schmitz, Katrin Thüne, Maria Cramm, Alberto Rabano, Saima Zafar, Erik Stoops, Hugo Vanderstichele, Anna Villar-Pique, Franc Llorens, Inga Zerr
Journal: Translational Neurodegeneration (2020)

Abstract Background α-Synuclein is a small soluble protein, whose physiological function in the healthy brain is poorly understood. Intracellular inclusions of α-synuclein, referred to as Lewy bodies (LBs), are pathological hallmarks of α-synucleinopathies, such as Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). Main body Understanding of the molecular basis as well as the factors or conditions promoting α-synuclein misfolding and aggregation is an important step towards the comprehension of pathological mechanism of α-synucleinopathies and for the development of efficient therapeutic strategies. Based on the conversion and aggregation mechanism of α-synuclein, novel diagnostic tests, such as protein misfolding seeded conversion assays, e.g. the real-time quaking-induced conversion (RT-QuIC), had been developed. In diagnostics, α-synuclein RT-QuIC exhibits a specificity between 82 and 100% while the sensitivity varies between 70 and 100% among different laboratories. In addition, the α-synuclein RT-QuIC can be used to study the α-synuclein-seeding-characteristics of different α-synucleinopathies and to differentiate between DLB and PD. Conclusion The variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols, cohorts and material etc.. An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical heterogeneity of α-synucleinopathies .