tbuckley/cabot-search huggingface dataset:
Acceptability of ‘as needed’ biologic therapy in psoriasis: insights from a multistakeholder mixed-methods study
Authors: David Gleeson, Maneeha Naveed, Lucy Moorhead, Helen McAteer, Georgia Sewell, Arlene McGuire, John Weinman, Jonathan N W N Barker, Sam Norton, Sarah C E Chapman, Catherine H Smith, Satveer K Mahil
Journal: British Journal of Dermatology (2024)

Abstract Background Biologic therapies have led to increasing numbers of patients with psoriasis who have clear or nearly clear skin. It is current practice to continue biologic therapy indefinitely in these patients, which contributes to a substantial long-term drug and healthcare burden. ‘As needed’ biologic therapy in psoriasis may address this; however, our understanding of patient and clinician perceptions of this strategy is limited. Objectives The aim of this mixed-methods study was to gain insight into the perspectives of both patients and clinicians regarding the acceptability of an ‘as needed’ approach to biologic therapy in psoriasis, including potential barriers and enablers to implementation in routine care. Methods We first conducted UK-wide online scoping surveys of patients with psoriasis and dermatology clinicians to explore their views on ‘as needed’ biologic therapy. Using topic guides informed by these survey findings, we then carried out qualitative focus groups with patients and clinicians. Themes were identified using reflexive thematic analysis. Results Of 67 patients and 27 clinicians completing the scoping surveys, 67% (43 of 64 patients) and 78% (21 of 27 clinicians) supported the use of ‘as needed’ biologic therapy, respectively. Respondents highlighted advantages such as a reduction in healthcare burden and greater ownership of care. Challenges included logistics of ‘as needed’ drug provision and potential risks of disease flare and drug immunogenicity. Focus groups comprised 15 patients with psoriasis [9 female patients (60%), average disease duration 32 years (range 9–64)] and 9 dermatology clinicians [8 female clinicians (89%), average dermatology experience 20 years (range 8–33)]. Both patients and clinicians felt that an ‘as needed’ treatment approach will deliver a reduction in treatment burden and present an opportunity for patient-led ownership of care. Both groups highlighted the importance of ensuring ongoing access to medication and discussing the potential impact of psoriasis recurrence. Patient preferences were influenced by their lived experiences, particularly previous difficulties with medication delivery logistics and establishing disease control. Clinician perspectives were informed by personal experience of their patients adapting their own dosing schedules. Clinicians highlighted the importance of targeted patient selection for an ‘as needed’ approach, ongoing disease monitoring, and prompt reaccess to medications upon psoriasis recurrence. Conclusions These data indicate that ‘as needed’ biologic therapy in psoriasis is acceptable for both patients and clinicians. Formal assessment of clinical effectiveness and cost-effectiveness is warranted to enable the real-world potential of this approach to be realized.
Cancer type and histology influence cutaneous immunotherapy toxicities: a multi-institutional cohort study
Authors: Guihong Wan, Sara Khattab, Bonnie W Leung, Shijia Zhang, Nga Nguyen, Matthew Tran, Chuck Lin, Crystal Chang, Nora Alexander, Ruple Jairath, Jordan Phillipps, Kimberly Tang, Ahmad Rajeh, Leyre Zubiri, Steven T Chen, Shadmehr Demehri, Kun-Hsing Yu, Alexander Gusev, Shawn G Kwatra, Nicole R LeBoeuf, Kerry L Reynolds, Yevgeniy R Semenov
Journal: British Journal of Dermatology (2024)

Abstract Background Cutaneous immune-related adverse events (cirAEs) are the most common toxicities to occur in the setting of immune checkpoint inhibitor (ICI) therapy. Identifying patients who are at increased risk of developing cirAEs may improve quality of life and outcomes. Objectives To investigate the influence of cancer type and histology on the development of cirAEs in the setting of ICI therapy and survival outcomes. Methods This retrospective cohort study included patients recruited between 1 December 2011 and 30 October 2020. They received ICI from 2011 to 2020 with follow-up of outcomes through October 2021. We identified 3668 recipients of ICI therapy who were seen at Massachusetts General Brigham and Dana-Farber. Of these, 669 developed cirAEs. Records that were incomplete or categories of insufficient sample size were excluded from the study cohort. Multivariate Cox proportional hazards models were used to investigate the impact of cancer organ system and histology on cirAE development, after adjusting for demographics, Charlson Comorbidity Index, ICI type, cancer stage at ICI initiation, and year of ICI initiation. Time-varying Cox proportional hazards modelling was used to examine the impact of cirAE development on mortality. Results Compared with other nonepithelial cancers (neuroendocrine, leukaemia, lymphoma, myeloma, sarcoma and central nervous system malignancies), cutaneous squamous cell carcinoma [cSCC; hazard ratio (HR) 3.57, P &amp;lt; 0.001], melanoma (HR 2.09, P &amp;lt; 0.001), head and neck adenocarcinoma (HR 2.13, P = 0.009), genitourinary transitional cell carcinoma (HR 2.15, P &amp;lt; 0.001) and genitourinary adenocarcinoma (HR 1.53, P = 0.037) were at significantly higher risk of cirAEs in multivariate analyses. The increased risk of cirAEs translated into an adjusted survival benefit for melanoma (HR 0.37, P &amp;lt; 0.001) and cSCC (HR 0.51, P = 0.011). Conclusions The highest rate of cirAEs and subsequent survival benefits were observed in cutaneous malignancies treated with ICI therapies. This study improves our understanding of patients who are at highest risk of developing cirAEs and would, therefore, benefit from appropriate counselling and closer monitoring by their oncologists and dermatologists throughout their ICI therapy. Limitations include its retrospective nature and cohort from one geography.
Neoadjuvant platinum-based chemotherapy and lymphadenectomy for penile cancer: an international, multi-institutional, real-world study
Authors: Kyle M Rose, Rachel Pham, Niki M Zacharias, Filip Ionescu, Mahati Paravathaneni, Kathryn A Marchetti, Darren Sanchez, Arfa Mustasam, Reagan Sandstrom, Raghu Vikram, Jasreman Dhillon, Priya Rao, Amy Schneider, Lance Pagliaro, Constantine Alifrangis, Maarten Albersen, Eduard Roussel, Viraj A Master, Bassel Nazha, Cindy Hernandez, Kelvin A Moses, Chris Protzel, Jeffrey Montgomery, Martin Angel, Marcos Tobias-Machado, Philippe E Spiess, Curtis A Pettaway, Jad Chahoud
Journal: JNCI Journal of the National Cancer Institute (2024)

This study investigated the efficacy and safety of neoadjuvant chemotherapy for locally advance penile squamous cell carcinoma for which current evidence is lacking.
Secondary Contact, Introgressive Hybridization, and Genome Stabilization in Sticklebacks
Authors: Xueyun Feng, Juha Merilä, Ari Löytynoja
Journal: Molecular Biology and Evolution (2024)

Advances in genomic studies have revealed that hybridization in nature is pervasive and raised questions about the dynamics of different genetic and evolutionary factors following the initial hybridization event. While recent research has proposed that the genomic outcomes of hybridization might be predictable to some extent, many uncertainties remain. With comprehensive whole-genome sequence data, we investigated the genetic introgression between 2 divergent lineages of 9-spined sticklebacks (Pungitius pungitius) in the Baltic Sea. We found that the intensity and direction of selection on the introgressed variation has varied across different genomic elements: while functionally important regions displayed reduced rates of introgression, promoter regions showed enrichment. Despite the general trend of negative selection, we identified specific genomic regions that were enriched for introgressed variants, and within these regions, we detected footprints of selection, indicating adaptive introgression. Geographically, we found the selection against the functional changes to be strongest in the vicinity of the secondary contact zone and weaken as a function of distance from the initial contact. Altogether, the results suggest that the stabilization of introgressed variation in the genomes is a complex, multistage process involving both negative and positive selection. In spite of the predominance of negative selection against introgressed variants, we also found evidence for adaptive introgression variants likely associated with adaptation to Baltic Sea environmental conditions.
PM2.5, vegetation density, and childhood cancer: a case-control registry-based study from Texas 1995-2011
Authors: Lindsay A Williams, David Haynes, Jeannette M Sample, Zhanni Lu, Ali Hossaini, Laura A McGuinn, Thanh T Hoang, Philip J Lupo, Michael E Scheurer
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Air pollution is positively associated with some childhood cancers, whereas greenness is inversely associated with some adult cancers. The interplay between air pollution and greenness in childhood cancer etiology is unclear. We estimated the association between early-life air pollution and greenness exposure and childhood cancer in Texas (1995 to 2011). Methods We included 6101 cancer cases and 109 762 controls (aged 0 to 16 years). We linked residential birth address to census tract annual average fine particulate matter &amp;lt;2.5 µg/m³ (PM2.5) and Normalized Difference Vegetation Index (NDVI). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) between PM2.5/NDVI interquartile range increases and cancer. We assessed statistical interaction between PM2.5 and NDVI (likelihood ratio tests). Results Increasing residential early-life PM2.5 exposure was associated with all childhood cancers (OR = 1.10, 95% CI = 1.06 to 1.15), lymphoid leukemias (OR = 1.15, 95% CI = 1.07 to 1.23), Hodgkin lymphomas (OR = 1.27, 95% CI = 1.02 to 1.58), non-Hodgkin lymphomas (OR = 1.24, 95% CI = 1.02 to 1.51), ependymoma (OR = 1.27, 95% CI = 1.01 to 1.60), and others. Increasing NDVI exposure was inversely associated with ependymoma (0- to 4-year-old OR = 0.75, 95% CI = 0.58 to 0.97) and medulloblastoma (OR = 0.75, 95% CI = 0.62 to 0.91) but positively associated with malignant melanoma (OR = 1.75, 95% CI = 1.23 to 2.47) and Langerhans cell histiocytosis (OR = 1.56, 95% CI = 1.07 to 2.28). There was evidence of statistical interaction between NDVI and PM2.5 (P &amp;lt; .04) for all cancers. Conclusion Increasing early-life exposure to PM2.5 increased the risk of childhood cancers. NDVI decreased the risk of 2 cancers yet increased the risk of others. These findings highlight the complexity between PM2.5 and NDVI in cancer etiology.
Palliative prognostic scores for survival prediction of cancer patients: a systematic review and meta-analysis
Authors: Si Qi Yoong, Priyanka Bhowmik, Sreerag Kapparath, Davina Porock
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background The palliative prognostic score is the most widely validated prognostic tool for cancer survival prediction, with modified versions available. A systematic evaluation of palliative prognostic score tools is lacking. This systematic review and meta-analysis aimed to evaluate the performance and prognostic utility of palliative prognostic score, delirium–palliative prognostic score, and palliative prognostic score without clinician prediction in predicting 30-day survival of cancer patients and to compare their performance. Methods Six databases were searched for peer-reviewed studies and grey literature published from inception to June 2, 2023. English studies must assess palliative prognostic score, delirium–palliative prognostic score, or palliative prognostic score without clinician-predicted survival for 30-day survival in adults aged 18 years and older with any stage or type of cancer. Outcomes were pooled using the random effects model or summarized narratively when meta-analysis was not possible. Results A total of 39 studies (n = 10 617 patients) were included. Palliative prognostic score is an accurate prognostic tool (pooled area under the curve [AUC] = 0.82, 95% confidence interval [CI] = 0.79 to 0.84) and outperforms palliative prognostic score without clinician-predicted survival (pooled AUC = 0.74, 95% CI = 0.71 to 0.78), suggesting that the original palliative prognostic score should be preferred. The meta-analysis found palliative prognostic score and delirium–palliative prognostic score performance to be comparable. Most studies reported survival probabilities corresponding to the palliative prognostic score risk groups, and higher risk groups were statistically significantly associated with shorter survival. Conclusions Palliative prognostic score is a validated prognostic tool for cancer patients that can enhance clinicians’ confidence and accuracy in predicting survival. Future studies should investigate if accuracy differs depending on clinician characteristics. Reporting of validation studies must be improved, as most studies were at high risk of bias, primarily because calibration was not assessed.
Supporting the health and wellbeing of trans autistic school-aged youth: a systematic literature review
Authors: Jessica Manley, Charlotte Brownlow, Annette Brömdal
Journal: International Journal of Transgender Health (2024)

This systematic literature review (SLR) aims to synthesize available research which examines the supports required for trans autistic school-aged youth to improve their mental health, wellbeing, and quality of life. Current literature highlights the need to support this specific school-aged population, but the research that synthesizes the existing limited research is lacking. This SLR brings together existing literature and highlights recommended inclusive interventions, programs, support mechanisms, and protective factors needed to support and promote optimal mental health and wellbeing.
Genomic alterations in oral multiple primary cancers
Authors: Xuan Zhou, Xinjia Cai, Fengyang Jing, Xuefen Li, Jianyun Zhang, Heyu Zhang, Tiejun Li
Journal: International Journal of Oral Science (2024)

Abstract Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n = 202) and oral MPCs ( n = 34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs. Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8 , TP53 and MUC16 , in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A . Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.
A novel saliva-based miRNA profile to diagnose and predict oral cancer
Authors: Jaikrishna Balakittnen, Chameera Ekanayake Weeramange, Daniel F. Wallace, Pascal H. G. Duijf, Alexandre S. Cristino, Gunter Hartel, Roberto A. Barrero, Touraj Taheri, Liz Kenny, Sarju Vasani, Martin Batstone, Omar Breik, Chamindie Punyadeera
Journal: International Journal of Oral Science (2024)

Abstract Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD). The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC ( n = 50), OPMD ( n = 52), and controls ( n = 60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p, miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was: area under curve (AUC): 0.954, sensitivity: 86%, specificity: 90%, positive predictive value (PPV): 87.8% and negative predictive value (NPV): 88.5% whereas between OC and OPMD was: AUC: 0.911, sensitivity: 90%, specificity: 82.7%, PPV: 74.2% and NPV: 89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC, revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.
Brief Communication: The Predictable Network Topology of Evolutionary Genomic Constraint
Authors: Katharina C Wollenberg Valero
Journal: Molecular Biology and Evolution (2024)

Large-scale comparative genomics studies offer valuable resources for understanding both functional and evolutionary rate constraints. It is suggested that constraint aligns with the topology of genomic networks, increasing toward the center, with intermediate nodes combining relaxed constraint with higher contributions to the phenotype due to pleiotropy. However, this pattern has yet to be demonstrated in vertebrates. This study shows that constraint intensifies toward the network's center in placental mammals. Genes with rate changes associated with emergence of hibernation cluster mostly toward intermediate positions, with higher constraint in faster-evolving genes, which is indicative of a "sweet spot" for adaptation. If this trend holds universally, network node metrics could predict high-constraint regions even in clades lacking empirical constraint data.
Long-term efficacy of a recombinant hepatitis E vaccine in adults: 10-year results from a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Shoujie Huang, Xuefeng Zhang, Yingying Su, Chunlan Zhuang, Zimin Tang, Xingcheng Huang, Qi Chen, Kongxin Zhu, Xiaowen Hu, Dong Ying, Xiaohui Liu, Hanmin Jiang, Xia Zang, Zhongze Wang, Changlin Yang, Donglin Liu, Yijun Wang, Quan Tang, Wentong Shen, Huanhuan Cao, Huirong Pan, Shengxiang Ge, Yue Huang, Ting Wu, Zizheng Zheng, Fengcai Zhu, Jun Zhang, Ningshao Xia
Journal: The Lancet (2024)
Mortality After Major Cardiovascular Events in Survivors of Childhood Cancer
Authors: Wendy Bottinor, Cindy Im, David R. Doody, Saro H. Armenian, Alexander Arynchyn, Borah Hong, Rebecca M. Howell, David R. Jacobs, Kirsten K. Ness, Kevin C. Oeffinger, Alexander P. Reiner, Gregory T. Armstrong, Yutaka Yasui, Eric J. Chow
Journal: Journal of the American College of Cardiology (2024)
“Food Is Medicine” Strategies for Nutrition Security and Cardiometabolic Health Equity
Authors: Dariush Mozaffarian, Karen E. Aspry, Kathryn Garfield, Penny Kris-Etherton, Hilary Seligman, Gladys P. Velarde, Kim Williams, Eugene Yang
Journal: Journal of the American College of Cardiology (2024)

"Food Is Medicine" (FIM) represents a spectrum of food-based interventions integrated into health care for patients with specific health conditions and often social needs. Programs include medically tailored meals, groceries, and produce prescriptions, with varying levels of nutrition and culinary education. Supportive advances include expanded care pathways and payment models, e-screening for food and nutrition security, and curricular and accreditation requirements for medical nutrition education. Evidence supports positive effects of FIM on food insecurity, diet quality, glucose control, hypertension, body weight, disease self-management, self-perceived physical and mental health, and cost-effectiveness or cost savings. However, most studies to date are quasiexperimental or pre/post interventions; larger randomized trials are ongoing. New national and local programs and policies are rapidly accelerating FIM within health care. Remaining research gaps require rigorous, iterative evaluation. Successful incorporation of FIM into health care will require multiparty partnerships to assess, optimize, and scale these promising treatments to advance health and health equity.
Sex Differences in Association of Physical Activity With All-Cause and Cardiovascular Mortality
Authors: Hongwei Ji, Martha Gulati, Tzu Yu Huang, Alan C. Kwan, David Ouyang, Joseph E. Ebinger, Kaitlin Casaletto, Kerrie L. Moreau, Hicham Skali, Susan Cheng
Journal: Journal of the American College of Cardiology (2024)

Although physical activity is widely recommended for reducing cardiovascular and all-cause mortality risks, female individuals consistently lag behind male individuals in exercise engagement. The goal of this study was to evaluate whether physical activity derived health benefits may differ by sex. In a prospective study of 412,413 U.S. adults (55% female, age 44 ± 17 years) who provided survey data on leisure-time physical activity, we examined sex-specific multivariable-adjusted associations of physical activity measures (frequency, duration, intensity, type) with all-cause and cardiovascular mortality from 1997 through 2019. During 4,911,178 person-years of follow-up, there were 39,935 all-cause deaths including 11,670 cardiovascular deaths. Regular leisure-time physical activity compared with inactivity was associated with 24% (HR: 0.76; 95% CI: 0.73-0.80) and 15% (HR: 0.85; 95% CI: 0.82-0.89) lower risk of all-cause mortality in women and men, respectively (Wald F = 12.0, sex interaction P < 0.001). Men reached their maximal survival benefit of HR 0.81 from 300 min/wk of moderate-to-vigorous physical activity, whereas women achieved similar benefit at 140 min/wk and then continued to reach a maximum survival benefit of HR 0.76 also at ∼300 min/wk. Sex-specific findings were similar for cardiovascular death (Wald F = 20.1, sex interaction P < 0.001) and consistent across all measures of aerobic activity as well as muscle strengthening activity (Wald F = 6.7, sex interaction P = 0.009). Women compared with men derived greater gains in all-cause and cardiovascular mortality risk reduction from equivalent doses of leisure-time physical activity. These findings could enhance efforts to close the "gender gap" by motivating especially women to engage in any regular leisure-time physical activity.