tbuckley/cabot-search huggingface dataset:
Predicting radiation-induced immune trafficking and activation in localized prostate cancer
Authors: Simon Keam, Heloise Halse, Nguyen ThuNgoc, Catherine Mitchell, Franco Caramia, David Byrne, Sue Haupt, Georgina Ryland, Phillip Darcy, Shahneen Sandhu, Piers Blombery, Ygal Haupt, Scott Williams, Paul Neeson
Journal: Journal for ImmunoTherapy of Cancer (2019)

340  Background: Prostate cancer is frequently cured with high-dose rate brachytherapy as a front-line treatment. However, a significant number unfortunately develop intrinsic resistance. Although considered to be an immune-excluded tissue, immune responses are implicated in driving tumour-eradication in prostate cancer. This has not been proven, and yet is used as the rationale for numerous clinical trials combining radiation and immunotherapies. We hypothesise that there is a predictable but differential relationship between radiation and the immune responses in prostate cancer that could be used to fulfil a clinical need - identifying patients that would benefit from immune intervention in conjunction with radiation. Methods: We present here the results of comprehensive immunological profiling of a cohort of world-unique pre- and post-radiation tissues from 24 patients (RadBank cohort). These were assessed using pathological classification, tissue segmentation (cancer/surrounding stroma), multiplex IHC, gene expression profiling, T-cell receptor sequencing, and spatial computational analysis. Results: Our data resolved three classes of prostate cancer tissue based on immune infiltrate level, immune-activation and -checkpoint gene signatures, spatial clustering and T cell clone sequencing: We have begun to resolve clear patient and clinical classifiers based on immune responses to radiation, and identified patients groups likely to benefit from immune therapy alongside radiation. Conclusions: Importantly, these classifications are associated with baseline gene expression profiles that may be used for pre-clinical stratification and more sophisticated treatment paradigms.
Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes
Authors: Jae-Seung Yun, Seung-Hyun Ko
Journal: Metabolism (2021)

With the advances in diabetes care, the trend of incident cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) has been decreasing over past decades. However, given that CVD is still a major cause of death in patients with diabetes and that the risk of CVD in patients with T2DM is more than twice that in those without DM, there are still considerable challenges to the prevention of CVD in diabetes. Accordingly, there have been several research efforts to decrease cardiovascular (CV) risk in T2DM. Large-scale genome-wide association studies (GWAS) and clinical cohort studies have investigated the effects of factors, such as genetic determinants, hypoglycaemia, and insulin resistance, on CVD and can account for the unexplained CV risk in T2DM. Lifestyle modification is a widely accepted cornerstone method to prevent CVD as the first-line strategy in T2DM. Recent reports from large CV outcome trials have proven the positive CV effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with high CVD risk. Overall, current practice guidelines for the management of CVD in T2DM are moving from a glucocentric strategy to a more individualised patient-centred approach. This review will discuss the current epidemiologic trends of CVD in T2DM and the risk factors linking T2DM to CVD, including genetic contribution, hypoglycaemia, and insulin resistance, and proper care strategies, including lifestyle and therapeutic approaches.
A worldwide assessment of changes in adherence to COVID-19 protective behaviours and hypothesized pandemic fatigue
Authors: Anna Petherick, Rafael Goldszmidt, Eduardo B. Andrade, Rodrigo Furst, Thomas Hale, Annalena Pott, Andrew Wood
Journal: Nature Human Behaviour (2021)

As the COVID-19 pandemic lingers, the possibility of 'pandemic fatigue' has raised worldwide concerns. Here, we examine whether there was a gradual reduction in adherence to protective behaviours against COVID-19 from March through December 2020, as hypothesized in expectations of fatigue. We considered self-report behaviours from representative samples of the populations of 14 countries (N = 238,797), as well as mobility and policy data for 124 countries. Our results show that changes in adherence were empirically meaningful and geographically widespread. While a low-cost and habituating behaviour (mask wearing) exhibited a linear rise in adherence, high-cost and sensitizing behaviours (physical distancing) declined, but this decline decelerated over time, with small rebounds seen in later months. Reductions in adherence to physical distancing showed little difference across societal groups, but were less intense in countries with high interpersonal trust. Alternative underlying mechanisms and policy implications are discussed.
The US Preventive Services Task Force Recommendation on Lung Cancer Screening
Authors: Bryan S. Squires, Ronald Levitin, Inga S. Grills
Journal: JAMA (2021)

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
Department of Error
Authors: Rohini Mathur, Christopher Rentsch, Caroline Morton, Rosalind Eggo, Krishnan Bhaskaran, Laurie Tomlinsonn, Liam Smeeth, Ben Goldacre
Journal: The Lancet (2021)

the percentage of gastrointestinal or liver complications reported should have been 10•8%.This correction has been made to the online version as of July 29, 2021.
A perspective on therapies for amyotrophic lateral sclerosis: can disease progression be curbed?
Authors: Xiaojiao Xu, Dingding Shen, Yining Gao, Qinming Zhou, You Ni, Huanyu Meng, Hongqin Shi, Weidong Le, Shengdi Chen
Journal: Translational Neurodegeneration (2021)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons, leading to paralysis and eventually death. Symptomatic treatments such as inhibition of salivation, alleviation of muscle cramps, and relief of spasticity and pain still play an important role in enhancing the quality of life. To date, riluzole and edaravone are the only two drugs approved by the Food and Drug Administration for the treatment of ALS in a few countries. While there is adequate consensus on the modest efficacy of riluzole, there are still open questions concerning the efficacy of edaravone in slowing the disease progression. Therefore, identification of novel therapeutic strategies is urgently needed. Impaired autophagic process plays a critical role in ALS pathogenesis. In this review, we focus on therapies modulating autophagy in the context of ALS. Furthermore, stem cell therapies, gene therapies, and newly-developed biomaterials have great potentials in alleviating neurodegeneration, which might halt the disease progression. In this review, we will summarize the current and prospective therapies for ALS.
Effects of adjusting public health, travel, and social measures during the roll-out of COVID-19 vaccination: a modelling study
Authors: Kathy Leung, Joseph T Wu, Gabriel M Leung
Journal: The Lancet Public Health (2021)

Since the emergence of the COVID-19 pandemic in late 2019, various public health and social measures (PHSMs) have been used to suppress and mitigate the spread of SARS-CoV-2. With mass vaccination programmes against COVID-19 being rolled out in many countries in early 2021, we aimed to evaluate to what extent travel restrictions and other PHSMs can be relaxed without exacerbating the local and global spread of COVID-19.We adapted an existing age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics that can be parameterised with country-specific age demographics and contact patterns to simulate the effect of vaccination and PHSM relaxation on transmission. We varied assumptions by age-specific susceptibility and infectiousness, vaccine uptake, contact patterns, and age structures. We used Hong Kong as a case study and assumed that, before vaccination, the population is completely susceptible to SARS-CoV-2 infection. We applied our model to 304 jurisdictions (27 countries and 277 sub-national administrative regions from eight countries). We assumed that PHSMs have suppressed the effective reproductive number (Re) to fall between 1·0 and 9·0 locally before the commencement of vaccination programmes. We evaluated the levels of PHSMs that should be maintained during the roll-out of COVID-19 vaccination to avoid a large local outbreak of COVID-19, with different assumptions about vaccine efficacy, vaccination coverage, and travel restrictions. We assumed that the maximum capacity of the health system, in terms of daily hospital admissions, is 0·005% of the population size.At vaccine efficacy of 0·80 in reducing susceptibility to SARS-CoV-2 infection, 0·50 in reducing SARS-CoV-2 infectivity, and 0·95 in reducing symptomatic COVID-19 diseases, vaccination coverage would have to be 100% for all individuals aged 30 or older to avoid an outbreak, when relaxing PHSMs, that would overload the local health-care system, assuming a pre-vaccination Re of 2·5. Testing and quarantine of at least 5 days would have to be maintained for inbound travellers to minimise the risk of reintroducing a local outbreak until high vaccination coverages are attained locally and overseas in most countries.Gradual relaxation of PHSMs should be carefully planned during the roll-out of vaccination programmes, and easing of travel restrictions weighed against risk of reintroducing outbreaks, to avoid overwhelming health systems and minimise deaths related to COVID-19.Health and Medical Research Fund and the General Research Fund.
Tislelizumab (BGB-A317) for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL): Long-term follow-up efficacy and safety results from a phase 2 study.
Authors: Yuqin Song, Quanli Gao, Huilai Zhang, Lei Fan, Jianfeng Zhou, Dehui Zou, Wei Li, Haiyan Yang, Ting Liu, Quanshun Wang, Fangfang Lv, Haiyi Guo, Liudi Yang, Jane Huang, William F. Novotny, Yidi Wang, Jun Zhu
Journal: Journal of Clinical Oncology (2021)

e19507 Background: Tislelizumab is a humanized IgG4 monoclonal antibody with high affinity/specificity for programmed cell death protein 1 (PD-1). It was engineered to minimize binding to Fc-γ receptors on macrophages, thereby decreasing antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti–PD-1 therapy. Tislelizumab therapy was highly active in autologous stem cell transplant (ASCT)-failed or ineligible patients with R/R cHL ( Leukemia. 2020;34:533). Here we report results from up to 3 years follow-up. Methods: This asingle-arm, multicenter phase 2 study (NCT03209973) of 200 mg tislelizumab administered intravenously to patients (pts) with R/R cHL every 3 weeks until progressive disease (PD) or unacceptable toxicity. Patients were eligible if they: failed to achieve a response or progressed after ASCT, or: received ≥2 lines of prior systemic chemotherapy for cHL and were ineligible for ASCT. Primary endpoint was overall response rate (ORR) assessed by an independent review committee (IRC) per Lugano criteria ( J Clin Oncol. 2014;32:3059). Secondary endpoints were progression-free survival (PFS), duration of response (DOR), complete response (CR) rate, and time to response (TTR) per IRC, safety, and tolerability. Results: Pts (N=70) from 11 centers in China were enrolled and treated; characteristics have been previously reported. As of the data cutoff date (Nov 2, 2020), median follow-up was 33.8 months (range, 3.4-38.6). Pts still on treatment at the end of study (n=33; 47.1%) entered a long-term extension study. Efficacy data is presented in the Table below. In the 13 pts who received prior ASCT, 11 (84.6%) achieved CR. The most common treatment-emergent adverse events (AEs; ≥30%) were pyrexia (57.1%), upper respiratory tract infection (38.6%), hypothyroidism (37.1%), and increased weight (34.3%). Treatment-related grade ≥3 AEs (≥2 pts) were pneumonitis, hypertension, neutropenia, lipase increased, weight increased, and increased creatine phosphokinase (CPK; 2.9% each). Immune-related AEs were reported in 32 pts (45.7%), with grade ≥3 AEs in 8 pts (11.4%): pneumonitis (4) and skin adverse reactions, nephritis, lipase increased, and blood CPK increased (1 each). AEs led to treatment discontinuation in 6 pts (8.6%). Conclusions: Long-term follow-up of R/R cHL pts treated with tislelizumab further demonstrated the substantial therapeutic activity and continued PFS benefit. There were no new safety concerns identified for long-term treatment with tislelizumab. Clinical trial information: NCT03209973. [Table: see text]
T<sub>H</sub>2 cytokines and <i>Staphylococcus aureus</i> cooperatively induce atopic dermatitis‐like transcriptomes
Authors: Mika Murai‐Yamamura, Sandra Garcet, Kazuhiko Yamamura, Juana Gonzalez, Shunsuke Miura, Xuan Li, Hong Hur, Emma Guttman‐Yassky, James G. Krueger
Journal: Allergy (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
P-149 Integrative analysis of the genomic and transcriptomic landscape identifies novel key genes as a therapeutic target in bile duct cancer
Authors: M. Salati, B. Anna, F. Luigi, I. Antonella, G. Gennaro, C. Bardasi, G. Luppi, A. Bocconi, I. Antonino, S. Maria, G. Troncone, F. Brunella, L. Reggiani Bonetti, M. Dominici, P. Carotenuto
Journal: Annals of Oncology (2021)
A Trial of Albuterol Should Still be Considered for Children with Severe Bronchiolitis—Reply
Authors: Libby Haskell, Ed Oakley, Stuart R. Dalziel
Journal: JAMA Pediatrics (2021)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Low von Willebrand Factor in Children and Adolescents
Authors: Lakshmi Srivaths, Peter A. Kouides
Journal: JAMA Pediatrics (2021)

Recent studies have documented increased bleeding symptoms and related complications in patients with low von Willebrand factor (VWF), highlighting the clinical significance of this entity. Because children and adolescents with VWF deficiencies often present to primary care physicians with bleeding symptoms, physicians need to be aware of this condition for early detection.Studies have found that children and adolescents with low VWF (VWF levels of 30-50 IU/dL) can present with clinically significant bleeding, including mucosal, menstrual, postsurgical, and posttraumatic bleeding, leading to complications such as anemia, iron deficiency, transfusion, hospitalization, and poor quality of life. Detecting and promptly managing low VWF in children and adolescents with bleeding are essential because failure to do so can lead to significant morbidity in adulthood, especially among female patients, including continued heavy menstrual bleeding; postpartum hemorrhage; related gynecologic complications, such as hemorrhagic ovarian cysts; and surgical interventions for heavy menstrual bleeding, including hysterectomy. This narrative review summarizes the observations of several studies that have shed light on the pathophysiologic mechanisms of low VWF and bleeding in these patients and the available diagnostic modalities and treatment options.Studies in children and adolescents have provided important insights into the clinical phenotype, complications, pathophysiologic mechanisms, evaluation, and management of low VWF, now recognized as an important clinicopathologic entity, as presented in this review. As gatekeepers, primary care physicians play an important role in guiding patients with this recently recognized clinicopathologic entity toward appropriate specialty care and providing continued comanagement to prevent future complications as the patients enter adulthood.
Association of Genetic Testing Results With Mortality Among Women With Breast Cancer or Ovarian Cancer
Authors: Allison W Kurian, Paul Abrahamse, Irina Bondarenko, Ann S Hamilton, Dennis Deapen, Scarlett L Gomez, Monica Morrow, Jonathan S Berek, Timothy P Hofer, Steven J Katz, Kevin C Ward
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Breast cancer and ovarian cancer patients increasingly undergo germline genetic testing. However, little is known about cancer-specific mortality among carriers of a pathogenic variant (PV) in BRCA1/2 or other genes in a population-based setting. Methods Georgia and California Surveillance Epidemiology and End Results (SEER) registry records were linked to clinical genetic testing results. Women were included who had stages I-IV breast cancer or ovarian cancer diagnosed in 2013-2017, received chemotherapy, and were linked to genetic testing results. Multivariable Cox proportional hazard models were used to examine the association of genetic results with cancer-specific mortality. Results 22 495 breast cancer and 4320 ovarian cancer patients were analyzed, with a median follow-up of 41 months. PVs were present in 12.7% of breast cancer patients with estrogen and/or progesterone receptor-positive, HER2-negative cancer, 9.8% with HER2-positive cancer, 16.8% with triple-negative breast cancer, and 17.2% with ovarian cancer. Among triple-negative breast cancer patients, cancer-specific mortality was lower with BRCA1 (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.35 to 0.69) and BRCA2 PVs (HR = 0.60, 95% CI = 0.41 to 0.89), and equivalent with PVs in other genes (HR = 0.65, 95% CI = 0.37 to 1.13), vs noncarriers. Among ovarian cancer patients, cancer-specific mortality was lower with PVs in BRCA2 (HR = 0.35, 95% CI = 0.25 to 0.49) and genes other than BRCA1/2 (HR = 0.47, 95% CI = 0.32 to 0.69). No PV was associated with higher cancer-specific mortality. Conclusions Among breast cancer and ovarian cancer patients treated with chemotherapy in the community, BRCA1/2 and other gene PV carriers had equivalent or lower short-term cancer-specific mortality than noncarriers. These results may reassure newly diagnosed patients, and longer follow-up is ongoing.
4 Return to golf post arthroplasty
Authors: S Frankland, L Hoggett, P Hughes, C Nevill
Journal: British Journal of Sports Medicine (2021)

Aim To determine the impact of arthroplasty on player handicap, frequency of golf played, return to club competitions and overall mental and physical health using the SF-12. Method A three page, 30 item, open access survey was sent to a community of over 500,000 golfers via the newsletter for the HowDidIDo® app between 18/04/2019–30/04/2019, inviting users who had undergone a joint replacement to complete. Responses were analysed using Microsoft excel and StatsDirect. Results A total of 3043 valid responses were received, the majority were male (n=2392). Mean age was 70 years (25–92). Most respondents had only a single joint replacement (n=1977). Within the cohort, there were mostly hips (n=2092) and knees (n=2069) replaced with far fewer shoulders (n=101), although this concurred with NJR population data. Across the whole cohort, most respondents were playing more (40%) or the same (44%) amount of golf following arthroplasty. Across the cohort only 4% were assumed unable to return to club competitions, while 76% of respondents returned to competitions within six months. Mean handicap prior to arthroplasty was increased (17.6 to 18.9) with no significant difference between hips, knees and shoulders. The SF-12 results were completed for 1094 respondents which when matched for age, demonstrated higher physical (48.59 vs. 43.65) and mental health (55.59 vs.52.10) scores. Conclusions Joint replacement enables the vast majority of patients to continue or increase the amount of golf played with most returning to club competitions within six months. A slight increase in handicap is demonstrated following surgery in this cohort, with stabilisation after this initial increase. Patients playing golf following arthroplasty demonstrate better physical and mental health than their age matched counterparts.
Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial
Authors: Gavin A. Lewis, Susanna Dodd, Dannii Clayton, Emma Bedson, Helen Eccleson, Erik B. Schelbert, Josephine H. Naish, Beatriz Duran Jimenez, Simon G. Williams, Colin Cunnington, Fozia Zahir Ahmed, Anne Cooper, None Rajavarma Viswesvaraiah, Stuart Russell, Theresa McDonagh, Paula R. Williamson, Christopher A. Miller
Journal: Nature Medicine (2021)
Data, please
Authors: Gary J Schwitzer
Journal: BMJ (2008)

This was an interesting article about attempts to encourage developments in robotic surgery.1 But the story was completely devoid of any data.

We learn that robotic radical prostatectomies are much more common in the US than in the UK but we learn nothing about outcomes. We learn that there are ethical issues, but none is specified. We learn that a urologist believes robotic surgery has several advantages. But those are not quantified. What does “better results” mean?

We learn that “patients recover more quickly” but we’re not told how many patients. We learn of “better cancer control” without any definition of that term.

Ditto for reported claims of more precision, “less collateral damage, resulting in less blood loss, faster recovery, and fewer complications.” No numbers.

I’m trying to teach my health journalism students, “No numbers? No story.” I hope they weren’t reading this week’s BMJ News section.