tbuckley/cabot-search huggingface dataset:
Projections of Extreme Temperature–Related Deaths in the US
Authors: Sameed Ahmed M. Khatana, Jonathan J. Szeto, Lauren A. Eberly, Ashwin S. Nathan, Jagadeesh Puvvula, Aimin Chen
Journal: JAMA Network Open (2024)

Importance Extreme heat in the US is increasing due to climate change, while extreme cold is projected to decline. Understanding how extreme temperature along with demographic changes will affect population health is important for devising policies to mitigate the health outcome of climate change. Objective To assess the burden of extreme temperature–related deaths in the contiguous US currently (2008-2019) and estimate the burden in the mid–21st century (2036-2065). Design, Setting, and Participants This cross-sectional study used historical (1979-2000) daily mean temperatures to calculate monthly extreme heat (&amp;amp;gt;97.5th percentile value) and extreme cold days (&amp;amp;lt;2.5th percentile value) for all contiguous US counties for 2008 to 2019 (current period). Temperature projections from 20 climate models and county population projections were used to estimate extreme temperature–related deaths for 2036 to 2065 (mid–21st century period). Data were analyzed from November 2023 to July 2024. Exposure Current monthly frequency of extreme heat days and projected mid–21st century frequency using 2 greenhouse gas emissions scenarios: Shared Socioeconomic Pathway (SSP)2-4.5, representing socioeconomic development with a lower emissions increase, and SSP5-8.5, representing higher emissions increase. Main Outcomes and Measures Mean annual estimated number of extreme temperature–related excess deaths. Poisson regression model with county, month, and year fixed effects was used to estimate the association between extreme temperature and monthly all-cause mortality for older adults (aged ≥65 years) and younger adults (aged 18-64 years). Results Across the contiguous US, extreme temperature days were associated with 8248.6 (95% CI, 4242.6-12 254.6) deaths annually in the current period and with 19 348.7 (95% CI, 11 388.7-27 308.6) projected deaths in the SSP2-4.5 scenario and 26 574.0 (95% CI, 15 408.0-37 740.1) in the SSP5-8.5 scenario. The mortality data included 30 924 133 decedents, of whom 15 573 699 were males (50.4%), with 6.3% of Hispanic ethnicity, 11.5% of non-Hispanic Black race, and 79.3% of non-Hispanic White race. Non-Hispanic Black adults (278.2%; 95% CI, 158.9%-397.5%) and Hispanic adults (537.5%; 95% CI, 261.6%-813.4%) were projected to have greater increases in extreme temperature–related deaths from the current period to the mid–21st century period compared with non-Hispanic White adults (70.8%; 95% CI, −5.8% to 147.3%). Conclusions and Relevance This cross-sectional study found that extreme temperature–related deaths in the contiguous US were projected to increase substantially by mid–21st century, with certain populations, such as non-Hispanic Black and Hispanic adults, projected to disproportionately experience this increase. The results point to the need to mitigate the adverse outcome of extreme temperatures for population health.
Effect of Chemotherapy and Surgery Timing on Mortality in Upper and Lower Extremity Osteosarcoma
Authors: Mark D Danese, John S Groundland
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Surgery with both neoadjuvant and adjuvant chemotherapy represents the standard of care for extremity osteosarcoma despite a lack of high-quality evidence for its use, and trial evidence that suggests that up-front surgery may result in better outcomes. This study estimated the difference in overall survival for the standard of care (“Neoadjuvant First”) vs upfront surgery first followed by adjuvant chemotherapy (“Surgery First”). Patients and methods Using Surveillance, Epidemiology, and End Results data, we identified patients age 5-29, diagnosed with a primary cancer of upper or lower extremity osteosarcoma between 2007 and 2019 who received surgery and chemotherapy. Our primary endpoint was the 5-year survival difference between the Surgery First and Neoadjuvant First groups. Results Adjusted 5-year survival was 74% for Surgery First patients and 67% for Neoadjuvant First patients, with a survival difference of 6.9% (95% CI -4.2% - 16.1%). In sensitivity analyses of 5-year survival, the results were consistent, showing a 6.8% to 13.7% higher 5-year survival in Surgery First patients. Significant mortality risk factors included older age, larger tumor size, the type of resection (salvage vs amputation), and stage 3-4 disease (vs stage 1-2 disease). Conclusion The evidence supporting neoadjuvant therapy in osteosarcoma care is weak. However, there is evidence that pausing chemotherapy in the peri-surgical period might affect outcomes. Consequently, this study, and its consistency with the results from the only randomized trial, suggests that there is reason to revisit a prospective, randomized trial of osteosarcoma treatment regarding the timing of surgery and chemotherapy.
Early-Life Risk Factors for Carotid Intima-Media Thickness and Carotid Stiffness in Adolescence
Authors: Isabelle A. van der Linden, Rozan Roodenburg, Sanne L. Nijhof, Cornelis K. van der Ent, Roderick P. Venekamp, Sabine E. I. van der Laan, Henk S. Schipper
Journal: JAMA Network Open (2024)

Importance Atherogenesis starts during childhood, making childhood and adolescence an important window of opportunity to prevent atherosclerotic cardiovascular disease later in life. Objective To identify early-life risk factors for preclinical atherosclerosis in adolescence. Design, Setting, and Participants This cohort study is part of the ongoing Wheezing Illness Study in Leidsche Rijn (WHISTLER) prospective birth cohort study, which includes 3005 healthy newborns born between December 2001 and December 2012 in the Leidsche Rijn area of Utrecht, the Netherlands. Eligible participants included those from the WHISTLER cohort who visited the clinic between March 2019 and October 2020 for adolescent follow-up. This study’s analyses were performed in January 2024. Exposures Early-life growth was assessed at birth to 6 months, 5 years, and 12 to 16 years. Abdominal ultrasonography determined abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depth. Blood pressure (BP) percentiles and body mass index (BMI) z scores were used. Main Outcomes and Measures Carotid ultrasonography was performed at age 12 to 16 years to assess carotid intima-media thickness (cIMT) and the distensibility coefficient (DC), established measures of preclinical atherosclerosis. Multivariable linear regression models were used to identify early-life risk factors for cIMT and DC in adolescence. Results In total, 232 adolescents (median [IQR] age, 14.9 [13.7-15.8] years; 121 female [52.2%]) were included. More postnatal weight gain ( B = 12.34; 95% CI, 2.39 to 22.39), higher systolic BP at 5 years ( B = 0.52; 95% CI, 0.02 to 1.01), more VAT at 5 years ( B = 3.48; 95% CI, 1.55 to 5.40), and a larger change in VAT between 5 and 12 to 16 years ( B = 3.13; 95% CI, 1.87 to 4.39) were associated with a higher cIMT in adolescence. A higher BMI ( B = −2.70, 95% CI,−4.59 to −0.80) and VAT at 5 years ( B = −0.56; 95% CI, −0.87 to −0.25), as well as a larger change in BMI between 5 and 12 to 16 years ( B = −3.63; 95% CI, −5.66 to −1.60) were associated with a higher carotid stiffness in adolescence. On the contrary, a larger change in SAT between 5 and 12 to 16 years ( B = 0.37; 95% CI, 0.16 to 0.58) was associated with a higher carotid DC in adolescence. Conclusions and Relevance In this cohort study of 232 participants, early-life growth parameters, and particularly abdominal VAT development, were associated with a higher cIMT and carotid stiffness in adolescence. These findings suggest that assessment of adipose tissue development during childhood can aid characterization of lifetime risk trajectories and tailoring of cardiovascular prevention and risk management strategies.
Costs of Transfer From Nontrauma to Trauma Centers Among Patients With Minor Injuries
Authors: Bourke W. Tillmann, Avery B. Nathens, Matthew P. Guttman, Priscila Pequeno, Damon C. Scales, Petros Pechlivanoglou, Barbara Haas
Journal: JAMA Network Open (2024)

Nearly half the patients transferred from nontrauma centers to trauma centers have minor injuries, yet trauma center care is not associated with a difference in morality among patients with minor injuries. Consequently, reducing the frequency of such transfers has been postulated as a method to improve resource allocation. Currently, the economic implications of these transfers are not well understood.
Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation
Authors: Darren R. Heintzman, Rachael C. Sinard, Emilie L. Fisher, Xiang Ye, Andrew R. Patterson, Joel H. Elasy, Kelsey Voss, Channing Chi, Ayaka Sugiura, Gabriel J. Rodriguez-Garcia, Nowrin U. Chowdhury, Emily N. Arner, Evan S. Krystoviak, Frank M. Mason, Yasmine T. Toudji, KayLee K. Steiner, Wasay Khan, Lana M. Olson, Angela L. Jones, Hanna S. Hong, Lindsay Bass, Katherine L. Beier, Wentao Deng, Costas A. Lyssiotis, Dawn C. Newcomb, Alexander G. Bick, W. Kimryn Rathmell, John T. Wilson, Jeffrey C. Rathmell
Journal: Science Immunology (2024)

Heat is a cardinal feature of inflammation, yet its impacts on immune cells remain uncertain. We show that moderate-grade fever temperatures (39°C) increased murine CD4 T cell metabolism, proliferation, and inflammatory effector activity while decreasing regulatory T cell suppressive capacity. However, heat-exposed T helper 1 (T H 1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways. Although many T H 1 cells subjected to such temperatures died, surviving T H 1 cells exhibited increased mitochondrial mass and enhanced activity. Electron transport chain complex 1 (ETC1) was rapidly impaired under fever-range temperatures, a phenomenon that was specifically detrimental to T H 1 cells. T H 1 cells with elevated DNA damage and ETC1 signatures were also detected in human chronic inflammation. Thus, fever-relevant temperatures disrupt ETC1 to selectively drive apoptosis or adaptation of T H 1 cells to maintain genomic integrity and enhance effector functions.
Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response
Authors: Sachin H. Bhagchandani, Leerang Yang, Jonathan H. Lam, Laura Maiorino, Elana Ben-Akiva, Kristen A. Rodrigues, Anna Romanov, Heikyung Suh, Aereas Aung, Shengwei Wu, Anika Wadhera, Arup K. Chakraborty, Darrell J. Irvine
Journal: Science Immunology (2024)

Prolonging exposure to subunit vaccines during the primary immune response enhances humoral immunity. Escalating-dose immunization (EDI), administering vaccines every other day in an increasing pattern over 2 weeks, is particularly effective but challenging to implement clinically. Here, using an HIV Env trimer/saponin adjuvant vaccine, we explored simplified EDI regimens and found that a two-shot regimen administering 20% of the vaccine followed by the remaining 80% of the dose 7 days later increased T
Harnessing ZIKV NS2A RNA for alleviating acute hepatitis and cytokine release storm by targeting translation machinery
Authors: Jingfei Zhu, Rongsheng Wu, Tao Yang, Yi Yuan, Guodi Liu, Shengchuan Chen, Zhiqiang Chen, Siying Liu, Shiyou Wang, Dapei Li, Haiping Yao, Yuanqing He, Sudan He, Cheng-Feng Qin, Jianfeng Dai, Feng Ma
Journal: Hepatology (2024)

Background and Aims: Hyperactivated inflammatory responses induced by cytokine release syndrome (CRS) are the primary causes of tissue damage and even death. The translation process is precisely regulated to control the production of proinflammatory cytokines. However, it is largely unknown whether targeting translation can effectively limit the hyperactivated inflammatory responses during acute hepatitis and graft-versus-host disease (GVHD). Approach and Results: By using in vitro translation and cellular overexpression systems, we have found that the non-structural protein gene NS2A of Zika virus (ZIKV) functions as RNA molecules to suppress the translation of both ectopic genes and endogenous proinflammatory cytokines. Mechanistically, results from RNA pulldown and co-immunoprecipitation (Co-IP) assays have demonstrated that NS2A RNA interacts with the translation initiation factor eIF2α to disrupt the dynamic balance of the eIF2/eIF2B complex and translation initiation, which is the rate-limiting step during the translation process. In the acetaminophen (APAP)-, LPS/D-galactosamine (D-GalN)-, viral infection-induced acute hepatitis, and GVHD mouse models, mice with myeloid cell-specific knock-in of NS2A show decreased levels of serum proinflammatory cytokines and reduced tissue damage. Conclusions: ZIKV NS2A dampens the production of proinflammatory cytokines and alleviates inflammatory injuries by interfering translation process as RNA molecules, which suggests that NS2A RNA is potentially used to treat numerous acute inflammatory diseases characterized by CRS.
Response to Comment on Orlando et al. Acute Effects of Vibrating Insoles on Dynamic Balance and Gait Quality in Individuals With Diabetic Peripheral Neuropathy: A Randomized Crossover Study. Diabetes Care 2024;47:1004–1011
Authors: Giorgio Orlando, Steven Brown, Edward Jude, Frank L. Bowling, Andrew J.M. Boulton, Neil D. Reeves
Journal: Diabetes Care (2024)
Comment on Orlando et al. Acute Effects of Vibrating Insoles on Dynamic Balance and Gait Quality in Individuals With Diabetic Peripheral Neuropathy: A Randomized Crossover Study. Diabetes Care 2024;47:1004–1011
Authors: Yuan-You Wang, Zhong-Jie Hua, Shao-Ning Hu, Bo-Jing Zheng, Ze-Xin Chen, Yi-Yi Zheng, Peng-Fei Shan
Journal: Diabetes Care (2024)
<b>Emerging Pharmacotherapies for Obesity: A Systematic Review</b>
Authors: Michail Kokkorakis, Marlene Chakhtoura, Caline Rhayem, Jana Al Rifai, Malak Ghezzawi, Laura Valenzuela-Vallejo, Christos S Mantzoros
Journal: Pharmacological Reviews (2024)

The history of anti-obesity pharmacotherapies is marked by disappointments, often entangled with societal pressure promoting weight loss and the conviction that excess body weight signifies a lack of willpower. However, categories of emerging pharmacotherapies generate hope to reduce obesity rates. This systematic review of phase 2 and phase 3 trials in adults with overweight/obesity investigates the effect of novel weight loss pharmacotherapies, compared to placebo/control or Food and Drug Administration-approved weight loss medication, through searching Medline, Embase, and ClinicalTrials.gov (2012-2024). We identified 53 phase 3 and phase 2 trials, with 36 emerging anti-obesity drugs or combinations thereof and four withdrawn or terminated trials. Oral semaglutide 50 mg is the only medication that has completed a phase 3 trial. There are 14 ongoing phase 3 trials on glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) (ecnoglutide, orforglipron, TG103), GLP-1 RA/amylin agonist (CagriSema), GLP-1/glucagon RAs (mazdutide, survodutide), GLP-1/glucose-dependent insulinotropic polypeptide and glucagon RA (retatrutide), dapagliflozin, and the combination sibutramine/topiramate. Completed phase 2 trials on incretin-based therapies showed a mean percent weight loss of 7.4-24.2%. Almost half of the drugs undergoing phase 2 trials were incretin analogs. The obesity drug pipeline is expanding rapidly, with the most promising results reported with incretin analogs. Data on mortality and obesity-related complications, such as cardio-renal-metabolic events, are needed. Moreover, long-term follow-up data on the safety and efficacy of weight maintenance with novel obesity pharmacotherapies, along with studies focused on under-represented populations, cost-effectiveness assessments, and drug availability, are needed to bridge the care gap for patients with obesity. Significance Statement Obesity is the epidemic of the 21st century. Except for the newer injectable medications, drugs with suboptimal efficacy have been available in the clinician's armamentarium. However, emerging alternatives of novel agents and combinations populate the obesity therapeutic pipeline. This systematic review identifies the state and mechanism of action of emerging pharmacotherapies undergoing or having completed phase 2 and phase 3 clinical trials. The information provided herein furthers the understanding of obesity management, implying direct clinical implications and stimulating research initiatives.
Band-and-wire pulley traction: endoscopic submucosal dissection of a gigantic gastric polyp aided by a novel adaptive traction technique
Authors: Andrea Sorge, Maria Eva Argenziano, Pieter Jan Poortmans, Lynn Debels, Gian Eugenio Tontini, Maurizio Vecchi, David J. Tate
Journal: Endoscopy (2024)
Spinal astrocyte-derived interleukin-17A promotes pain hypersensitivity in bone cancer mice
Authors: Huizhu Liu, Xuejing Lv, Xin Zhao, Lanxing Yi, Ning Lv, Wendong Xu, Yuqiu Zhang
Journal: Acta Pharmaceutica Sinica B (2024)

Spinal microglia and astrocytes are both involved in neuropathic and inflammatory pain, which may display sexual dimorphism. Here, we demonstrate that the sustained activation of spinal astrocytes and astrocyte-derived interleukin (IL)-17A promotes the progression of mouse bone cancer pain without sex differences. Chemogenetic or pharmacological inhibition of spinal astrocytes effectively ameliorates bone cancer-induced pain-like behaviors. In contrast, chemogenetic or optogenetic activation of spinal astrocytes triggers pain hypersensitivity, implying that bone cancer-induced astrocytic activation is involved in the development of bone cancer pain. IL-17A expression predominantly in spinal astrocytes, whereas its receptor IL-17 receptor A (IL-17RA) was mainly detected in neurons expressing VGLUT2 and PAX2, and a few in astrocytes expressing GFAP. Specific knockdown of IL-17A in spinal astrocytes blocked and delayed the development of bone cancer pain. IL-17A overexpression in spinal astrocytes directly induced thermal hyperalgesia and mechanical allodynia, which could be rescued by CaMKIIα inhibitor. Moreover, selective knockdown IL-17RA in spinal Vglut2 + or Vgat +neurons, but not in astrocytes, significantly blocked the bone cancer-induced hyperalgesia. Together, our findings provide evidence for the crucial role of sex-independent astrocytic signaling in bone cancer pain. Targeting spinal astrocytes and IL-17A/IL-17RA-CaMKIIα signaling may offer new gender-inclusive therapeutic strategies for managing bone cancer pain.
Exploring Cytokines Dynamics: Uncovering Therapeutic Concepts for Metabolic Disorders in Postmenopausal Women- Diabetes, Metabolic Bone Diseases, and Non-Alcohol Fatty Liver Disease
Authors: Amin Ullah, Yongxiu Chen, Rajeev K Singla, Dan Cao, Bairong Shen
Journal: Ageing Research Reviews (2024)
Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Final Results of the ORATOR Randomized Trial
Authors: Anthony C. Nichols, Julie Theurer, Eitan Prisman, Nancy Read, Eric Berthelet, Eric Tran, Kevin Fung, John R. de Almeida, Andrew Bayley, David P. Goldstein, Michael Hier, Khalil Sultanem, Keith Richardson, Alex Mlynarek, Suren Krishnan, Hien Le, John Yoo, S. Danielle MacNeil, Eric Winquist, J. Alex Hammond, Varagur Venkatesan, Sara Kuruvilla, Andrew Warner, Sylvia Mitchell, Jeff Chen, Stephanie Johnson-Obaseki, Michael Odell, Martin Corsten, Christina Parker, Bret Wehrli, Keith Kwan, David A. Palma
Journal: Journal of Clinical Oncology (2024)

Radiotherapy (RT) and transoral robotic surgery (TORS) are both curative-intent treatment options for oropharyngeal squamous cell carcinoma (OPSCC). Herein, we report the final outcomes of the ORATOR trial comparing these modalities, 5 years after enrollment completion. We randomly assigned 68 patients with T1-2N0-2 OPSCC to RT (with chemotherapy if node-positive) versus TORS plus neck dissection (± adjuvant RT/chemoradiation). The primary end point was swallowing quality of life (QOL) assessed with the MD Anderson Dysphagia Inventory (MDADI). Secondary end points included overall and progression-free survival (OS, PFS), adverse events (AEs), and other QOL metrics. The primary end point has been previously reported (Nichols 2019). In this report, the median follow-up was 5.1 years (IQR, 5.0-5.3 years). MDADI total scores converged by 5 years and were not significantly different across the follow-up period ( P = .11). EORTC QLQ-C30 and H&amp;N35 scores demonstrated differing profiles, including worse dry mouth in the RT arm ( P = .032) and worse pain in the TORS arm ( P = .002). Grade 2-5 AE rates did not differ between arms (91% [n = 31] v 97% [n = 33] respectively, P = .61), with more neutropenia and hearing loss in the RT arm, and more dysphagia and other pain in the TORS arm based on grades 2-5 (all P &lt; .05). There were no differences in OS or PFS. In conclusion, toxicity and QOL profiles differ in some domains between RT and TORS, but oncologic outcomes were excellent in both arms. Choice of treatment should remain a shared decision between the patient and their providers.
Rapid Eczema Trials: Addressing patient priorities from the eczema priority setting partnership
Authors: Emma L Campbell, Wei C G Fong, Amanda Roberts, Kim S Thomas
Journal: British Journal of Dermatology (2024)

In this letter, we describe the Rapid Eczema Trials co-production project, which aims to plug some of the research gaps that remain following the 2011 James Lind Alliance Eczema Priority Setting Partnership (PSP) exercise. We highlight similarities between research priorities that have been recently identified by our eczema citizen science community and the original PSP priorities. This work shows that answering the fundamentals about self-management of eczema is still important to people with eczema, and that the Rapid Eczema Trials project provides a means by which we can address patient priorities.