tbuckley/cabot-search huggingface dataset:
Call to increase statistical collaboration in sports science, sport and exercise medicine and sports physiotherapy
Authors: Kristin L Sainani, David N Borg, Aaron R Caldwell, Michael L Butson, Matthew S Tenan, Andrew J Vickers, Andrew D Vigotsky, John Warmenhoven, Robert Nguyen, Keith R. Lohse, Emma J Knight, Norma Bargary
Journal: British Journal of Sports Medicine (2020)

Statistical errors are common in many biomedical fields.1–5 We believe the nature and impact of these errors to be great enough in sports science and medicine to warrant special attention.6–14 Poor methodological and statistical practices have led to calls for change in other fields, such as psychology.15–18 We believe that a similar call to action is needed in sports science and medicine. Specifically, we see two pressing needs: (1) to increase collaboration between researchers and statisticians, and (2) to increase statistical training within the exercise science/medicine/physiotherapy (PT) discipline. Our call to action extends the work of those who have previously called for increased statistical collaboration in sports medicine and sports injury research.19–21 

Though some academic sports science and medicine studies employ statisticians, such collaborations are an exception rather than the norm. To determine the extent of collaboration, we performed a systematic review of articles published in quartile one sports science journals in 2019 (see online supplementary file 1 for methods and online supplementary file 2 for data). The initial extraction included 8970 articles; of the 400 articles selected at random, 299 were deemed eligible and included in the review (figure 1). We found that only 13.3% (95% CI: 9.5% to 17.2%) of papers had at least one coauthor affiliated with a biostatistics, statistics, data science, data analytics, epidemiology, maths, computer science or economics department (figure 2). It should be noted that we included a broad set of methodological departments because we recognise that individuals from these fields may possess considerable statistical expertise. When we use the term ‘statistician’ in this paper, we broadly include individuals from other methods-focussed disciplines if they have extensive statistical training and experience.### Supplementary data

[bjsports-2020-102607supp001.pdf] 

### Supplementary data

[bjsports-2020-102607supp002.pdf] 



Figure 1 
Flowchart of the article search and inclusion for the systematic review.





Figure 2 
Percentage of …
Evinacumab for Homozygous Familial Hypercholesterolemia
Authors: Frederick J. Raal, Robert S. Rosenson, Laurens F. Reeskamp, G. Kees Hovingh, John J.P. Kastelein, Paolo Rubba, Shazia Ali, Poulabi Banerjee, Kuo-Chen Chan, Daniel A. Gipe, Nagwa Khilla, Robert Pordy, David M. Weinreich, George D. Yancopoulos, Yi Zhang, Daniel Gaudet
Journal: New England Journal of Medicine (2020)

Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null–null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia.
Determining the mutational status of the BCR-ABL kinase domain in Chronic Myeloid Leukaemia patients with resistance to the tyrosine kinase inhibitor Imatinib Mesylate
Authors: Lisa O' Connor, Steven Langabeer, Eibhlin Conneally, Shaun McCann
Journal: Cancer Research (2007)

LB-330  Chronic Myeloid Leukaemia (CML) is a stem cell malignancy characterised by the t(9;22) translocation resulting in formation of the hybrid oncogene BCR-ABL. The BCR-ABL chimeric protein product has enhanced tyrosine kinase activity relative to the normal ABL, is leukaemogenic and provides an attractive target for molecular based therapies. Treatment for CML was revolutionised by the introduction of Imatinib Mesylate (IM), a tyrosine kinase inhibitor which specifically binds the inactive conformation of the BCR-ABL kinase domain. It functions as a competitive inhibitor of ATP binding, inhibiting phosphorylation of down-stream BCR-ABL targets resulting in cell cycle arrest & growth inhibition.  Resistance to IM is predominantly mediated by single base-pair substitutions within the BCR-ABL gene resulting in changes to the amino acid sequence of the kinase domain. These mutations result in conformational changes in the kinase domain that inhibit IM binding whilst retaining BCR-ABL phosphorylation capacity. We undertook to examine the molecular mechanisms underlying IM resistance. A cohort of 24 CML patients with primary or acquired resistance to IM were identified by ≥1 log increase in BCR-ABL peripheral blood transcript levels determined by real-time quantitative PCR. Samples were screened for the presence of the clinically significant T315I mutation, which renders patients insensitive to currently available tyrosine kinase inhibitors using allele-specific PCR; 2 patients (8.3% of total) were T315I positive. To further elucidate the molecular mechanisms of resistance, samples were screened for the presence of mutations in the BCR-ABL kinase domain using a sensitive denaturing high performance liquid chromatography (dHPLC) approach. dHPLC can detect a single base pair substitution within the BCR-ABL kinase domain based on hybridization to a non-mutated wild-type control. Mutated samples display reduced hybridization capacity to the dHPLC column and are eluted at an earlier time-point. Over 80% of samples analysed on the dHPLC showed evidence of a mutation, with BCR-ABL gene amplification or multi-drug resistance over-expression possible causative factors in mutation-negative cases. Samples showing evidence of mutation on the dHPLC were examined by direct sequencing to identify the mutation(s) present. Sensitivity of dHPLC (0.1-10%) is greater than that of sequencing (15-25%) & to date patients harboring the G250E, V379I & T315I mutations have been identified by sequencing. The identification of clinically significant mutations enables selection of alternative approaches to therapy such as the second generation tyrosine kinase inhibitors e.g. Dasatinib/Nilotinib or allogeneic stem cell transplant at early stage in a patients disease and facilitates patient-specific approaches to therapy.
Comparison of Survival After Transoral Robotic Surgery vs Nonrobotic Surgery in Patients With Early-Stage Oropharyngeal Squamous Cell Carcinoma
Authors: Anthony T. Nguyen, Michael Luu, Jon Mallen-St Clair, Alain C. Mita, Kevin S. Scher, Diana J. Lu, Stephen L. Shiao, Allen S. Ho, Zachary S. Zumsteg
Journal: JAMA Oncology (2020)

Transoral robotic surgery has been widely adopted since approval by the US Food and Drug Administration in December 2009, despite limited comparative data.To compare the long-term outcomes of transoral robotic surgery with those of nonrobotic surgery for patients with early-stage oropharyngeal cancer.A retrospective cohort comparative effectiveness analysis was performed of patients in the National Cancer Database with clinical T1 and T2 oropharyngeal squamous cell carcinoma diagnosed between January 1, 2010, and December 31, 2015, who underwent definitive robotic and nonrobotic surgery. Multivariable Cox proportional hazards regression analysis and propensity score matching were performed in patients with known human papillomavirus status to adjust for patient- and disease-related covariates. Survival after robotic and nonrobotic surgery was also compared in 3 unrelated cancers: prostate, endometrial, and cervical cancer. Statistical analysis was performed from April 10, 2019, to May 21, 2020.Overall survival.Of 9745 patients (7652 men [78.5%]; mean [SD] age, 58.8 [9.6] years) who met inclusion criteria, 2694 (27.6%) underwent transoral robotic surgery. There was a significant increase in the use of robotic surgery from 18.3% (240 of 1309) to 35.5% (654 of 1841) of all surgical procedures for T1 and T2 oropharyngeal cancers from 2010 to 2015 (P = .003). Robotic surgery was associated with lower rates of positive surgical margins (12.5% [218 of 1746] vs 20.3% [471 of 2325]; P < .001) and lower use of adjuvant chemoradiotherapy (28.6% [500 of 1746] vs 35.7% [831 of 2325]; P < .001). Among 4071 patients with known human papillomavirus status, robotic surgery was associated with improved overall survival compared with nonrobotic surgery in multivariable Cox proportional hazards regression (hazard ratio [HR], 0.74; 95 CI, 0.61-0.90; P = .002). Similar results were seen when analyzing only the subset of facilities offering both robotic and nonrobotic surgery. The 5-year overall survival was 84.8% vs 80.3% among patients undergoing robotic vs nonrobotic surgery in propensity score-matched cohorts (P = .001). By contrast, there was no evidence that robotic surgery was associated with improved survival in other cancers, such as prostate cancer (HR, 0.92; 95% CI, 0.79-1.07; P = .26), endometrial cancer (HR, 0.97; 95% CI, 0.90-1.04; P = .36), and cervical cancer (HR, 1.27; 95% CI, 0.96-1.69; P = .10).This study suggests that transoral robotic surgery was associated with improved surgical outcomes and survival compared with nonrobotic surgery in patients with early-stage oropharyngeal cancer. Evaluation in comparative randomized trials is warranted.
Uncemented vs Cemented Hemiarthroplasty for Hip Fracture
Authors: Yang Yu, Shitao Lu, Jianzhong Xu
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effectiveness of a peer-delivered, psychosocial intervention on maternal depression and child development at 3 years postnatal: a cluster randomised trial in Pakistan
Authors: Joanna Maselko, Siham Sikander, Elizabeth L Turner, Lisa M Bates, Ikhlaq Ahmad, Najia Atif, Victoria Baranov, Sonia Bhalotra, Amina Bibi, Tayyaba Bibi, Samina Bilal, Pietro Biroli, Esther Chung, John A Gallis, Ashley Hagaman, Anam Jamil, Katherine LeMasters, Karen O'Donnell, Elissa Scherer, Maria Sharif, Ahmed Waqas, Ahmed Zaidi, Shaffaq Zulfiqar, Atif Rahman
Journal: The Lancet Psychiatry (2020)
DiMSum: an error model and pipeline for analyzing deep mutational scanning data and diagnosing common experimental pathologies
Authors: Andre J. Faure, Jörn M. Schmiedel, Pablo Baeza-Centurion, Ben Lehner
Journal: Genome biology (2020)

Abstract Deep mutational scanning (DMS) enables multiplexed measurement of the effects of thousands of variants of proteins, RNAs, and regulatory elements. Here, we present a customizable pipeline, DiMSum, that represents an end-to-end solution for obtaining variant fitness and error estimates from raw sequencing data. A key innovation of DiMSum is the use of an interpretable error model that captures the main sources of variability arising in DMS workflows, outperforming previous methods. DiMSum is available as an R/Bioconda package and provides summary reports to help researchers diagnose common DMS pathologies and take remedial steps in their analyses.
Impaired cytoplasmic domain interactions cause co-assembly defect and loss of function in the p.Glu293Lys <i>KNCJ2</i> variant isolated from an Andersen–Tawil syndrome patient
Authors: Szilvia Déri, János Borbás, Teodóra Hartai, Lidia Hategan, Beáta Csányi, Ádám Visnyovszki, Tamara Madácsy, József Maléth, Zoltán Hegedűs, István Nagy, Rohit Arora, Alain J Labro, László Környei, András Varró, Róbert Sepp, Balázs Ördög
Journal: Cardiovascular Research (2020)

Subunit interactions at the cytoplasmic domain interface (CD-I) have recently been shown to control gating in inward rectifier potassium channels. Here we report the novel KCNJ2 variant p.Glu293Lys that has been found in a patient with Andersen-Tawil syndrome type 1 (ATS1), causing amino acid substitution at the CD-I of the inward rectifier potassium channel subunit Kir2.1. Neither has the role of Glu293 in gating control been investigated nor has a pathogenic variant been described at this position. This study aimed to assess the involvement of Glu293 in CD-I subunit interactions and to establish the pathogenic role of the p.Glu293Lys variant in ATS1.
Drug-Coated Balloons for Dysfunctional Dialysis Arteriovenous Fistulas
Authors: Robert A. Lookstein, Hiroaki Haruguchi, Kenneth Ouriel, Ido Weinberg, Lanyu Lei, Stephanie Cihlar, Andrew Holden
Journal: New England Journal of Medicine (2020)

Standard percutaneous transluminal angioplasty is the current recommended treatment for dysfunctional hemodialysis fistulas, yet long-term outcomes of this treatment are poor. Drug-coated balloons delivering the antirestenotic agent paclitaxel may improve outcomes.
Giant Cell Tumor With Atypical Imaging Implying Osteosarcoma
Authors: Akane Ariga, Hiroaki Kanda, Yoshiaki Ando, Tabu Gokita
Journal: Clinical Nuclear Medicine (2020)

Abstract Giant cell tumor (GCT) of bone is benign and typically shows osteolytic changes on x-ray, whereas osteosarcoma is malignant and generally shows osteolytic and osteoblastic mixed images. We experienced a rare case of GCT with atypical radiological findings. The tumor found in the right knee of a 15-year-old girl comprised a wide range of osteoblastic and osteolytic lesion in medial femur. Technetium uptake, however, was detected only in osteoblastic part, and immunohistochemical staining of biopsy showed diffusely positive for antihistone G34W and almost negative for Ki-67. These results strongly suggest the tumor was GCT.
Metastasis-Directed Therapy for Oligorecurrent Prostate Cancer—Not All That Glitters Is Gold—Reply
Authors: Phuoc T. Tran, Matthew P. Deek, Ryan M. Phillips
Journal: JAMA Oncology (2020)

In Reply The famous allegory within this play involves suitors of Portia choosing among gold, silver, or iron caskets for the right to her hand in marriage. Ultimately, a poor Venetian correctly chooses the iron casket and they return to Venice to marry.
EZH1/2, SWI/SNF, and MLL2 Dependent Heterochromatin Formation and Abnormal Transcriptome in Hematological Malignancies
Authors: Makoto Yamagishi, Dai Fujikawa, Makoto Hori, Daisuke Honma, Nobuaki Adachi, Seiichiro Kobayashi, Masako Iwanaga, Atae Utsunomiya, Seiji Okada, Kunihiro Tsukasaki, Kensei Tobinai, Kazushi Araki, Toshiki Watanabe, Kaoru Uchimaru
Journal: Blood (2017)
Therapeutic drug monitoring practice in patients with active tuberculosis: assessment of opportunities
Authors: Hannah Yejin Kim, Evan Ulbricht, Yu Kyung Ahn, Isabelle Sarah Gillooly, Kher Jing Lee, Jessica Lieu, William Nguyen, Sylvia Young, Jin-Gun Cho, Jan-Willem Alffenaar
Journal: European Respiratory Journal (2020)

<b>Increased hepatotoxicity, adverse effects and tuberculosis (TB) treatment duration were seen in patients without therapeutic drug monitoring (TDM) when indicated. Implementation of TDM facilitated by programmatic strategies is urgently needed.</b>https://bit.ly/3kCZHd3
Do changes in STEC diagnostics mislead interpretation of disease surveillance data in Switzerland? Time trends in positivity, 2007 to 2016
Authors: Fabienne Beatrice Fischer, Apolline Saucy, Claudia Schmutz, Daniel Mäusezahl
Journal: Eurosurveillance (2020)

Background Laboratory-confirmed cases of Shiga toxin-producing Escherichia coli (STEC) have been notifiable to the National Notification System for Infectious Diseases in Switzerland since 1999. Since 2015, a large increase in case numbers has been observed. Around the same time, syndromic multiplex PCR started to replace other diagnostic methods in standard laboratory practice for gastrointestinal pathogen testing, suggesting that the increase in notified cases is due to a change in test practices and numbers. Aim This study examined the impact of changes in diagnostic methods, in particular the introduction of multiplex PCR panels, on routine STEC surveillance data in Switzerland. Methods We analysed routine laboratory data from 11 laboratories, which reported 61.9% of all STEC cases from 2007 to 2016 to calculate the positivity, i.e. the rate of the number of positive STEC tests divided by the total number of tests performed. Results The introduction of multiplex PCR had a strong impact on STEC test frequency and identified cases, with the number of tests performed increasing sevenfold from 2007 to 2016. Still, age- and sex-standardised positivity increased from 0.8% in 2007 to 1.7% in 2016. Conclusion Increasing positivity suggests that the increase in case notifications cannot be attributed to an increase in test numbers alone. Therefore, we cannot exclude a real epidemiological trend for the observed increase. Modernising the notification system to address current gaps in information availability, e.g. diagnostic methods, and improved triangulation of clinical presentation, diagnostic and serotype information are needed to deal with emerging disease and technological advances.
EBV-induced gene 3 augments IL-23Rα protein expression through a chaperone calnexin
Authors: Izuru Mizoguchi, Mio Ohashi, Hideaki Hasegawa, Yukino Chiba, Naoko Orii, Shinya Inoue, Chiaki Kawana, Mingli Xu, Katsuko Sudo, Koji Fujita, Masahiko Kuroda, Shin-ichi Hashimoto, Kouji Matsushima, Takayuki Yoshimoto
Journal: Journal of Clinical Investigation (2020)

Epstein-Barr virus–induced gene 3 (EBI3) is a subunit common to IL-27, IL-35, and IL-39. Here, we explore an intracellular role of EBI3 that is independent of its function in cytokines. EBI3-deficient naive CD4+ T cells had reduced IFN-γ production and failed to induce T cell–dependent colitis in mice. Similarly reduced IFN-γ production was observed in vitro in EBI3-deficient CD4+ T cells differentiated under pathogenic Th17 polarizing conditions with IL-23. This is because the induction of expression of one of the IL-23 receptor (IL-23R) subunits, IL-23Rα, but not another IL-23R subunit, IL-12Rβ1, was selectively decreased at the protein level, but not the mRNA level. EBI3 augmented IL-23Rα expression via binding to the chaperone molecule calnexin and to IL-23Rα in a peptide-dependent manner, but not a glycan-dependent manner. Indeed, EBI3 failed to augment IL-23Rα expression in the absence of endogenous calnexin. Moreover, EBI3 poorly augmented the expression of G149R, an IL-23Rα variant that protects against the development of human colitis, because binding of EBI3 to the variant was reduced. Taken together with the result that EBI3 expression is inducible in T cells, the present results suggest that EBI3 plays a critical role in augmenting IL-23Rα protein expression via calnexin under inflammatory conditions.
Helen Salisbury: Teleconsultations for all
Authors: Helen Salisbury
Journal: BMJ (2020)

England’s health and social care secretary, Matt Hancock, announced in a speech to the Royal College of Physicians that all future GP consultations should be done remotely by phone or video, unless there’s a compelling clinical reason not to.1 I wonder what he considers to be “compelling clinical reasons”?

Since mid-March we’ve been talking to all of our patients by phone, before seeing some of them face to face. There have been some increases in efficiency, and it’s helpful for patients with a simple problem or request to discuss it without having to spend time in our waiting room. But to suggest that because 70% of appointments have been remote there’s no …
IP6 selectively inhibits proliferation, causes G0/G1 cell cycle arrest and induces apoptosis in human breast cancer cells
Authors: Ivana Vucenik
Journal: Cancer Research (2005)

5189  Breast cancer is the most prevalent malignancy in women and constitutes 30% of all cancers reported in the U.S., and approximately 44,000 women die of breast cancer per year despite the introduction of newer anticancer drugs. Most of the currently used chemotherapeutic agents do not discriminate between normal and tumor cells. As a result, new drug development approaches are aimed at developing compounds or testing natural products that specifically attack tumor cells, while sparing normal cells. Inositol hexaphosphate (IP6) is a polyphosphorylated carbohydrate naturally occurring in a great majority of plants, particularly cereals and legumes, and virtually all mammalian cells, with a striking efficacy against various cancers. IP6 reduces cell proliferation and induces differentiation of malignant cells, restores immune system, acts synergistically with conventional chemotherapy and controls cancer metastases in vitro. Here, the specificity of anti-proliferative and pro-apoptotic effects of IP6 in human breast cancer cells and in the non-transformed MCF-10A human breast epithelial cells was investigated. IP6 treatment (50 μM to 2.0 mM) resulted in a significant growth inhibition and G1 arrest of tumorigenic MCF-7 and MBA-MB-231 cells, while the proliferation of MCF-10A cells was not affected. In mechanistic studies, IP6 exposure resulted in significant induction of p27Kip1, and marked reduction of pRb phosphorylation. Although IP6 has been shown to affect various signaling pathways, such as PI3-K/Akt, MEK/Erk1/2, and PKC, by inhibiting the survival/pro-proliferative and stimulating the anti-proliferative and pro-apoptotic molecules, it appears that this action is mediated by PKC δ, as we previously reported. Additionally, IP6 causes a time- and dose-dependent apoptotic death, assessed by TUNEL staining and status of PARP protein, and PKC δ seems to be important mediator in IP6-induced apoptosis of breast cancer cells as well. This appears to be a novel molecular mechanism implicated in IP6 mode of action. Because of the possible role of IP6 either as an adjuvant or as an “alternative” to current chemotherapy for breast cancer, further investigation is warranted.