tbuckley/cabot-search huggingface dataset:
National and State Estimates of SELECT Trial Eligibility and Its Public Health Impact in the US
Authors: John Erhabor, Michael Khorsandi, Michael J. Blaha
Journal: JAMA Network Open (2024)

This cross-sectional study of US adults examines the geographical distribution of individuals eligible to participate in the Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial to estimate potential cardiovascular health impacts of implementing the trial findings at state and national levels.
Cancer Survivorship Services Across the US—Time to Leverage the Data to Promote a System Change
Authors: Larissa Nekhlyudov, Nicole L. Stout
Journal: JAMA Network Open (2024)

Julia Stal, PhD; Kimberly A. Miller, PhD, MPH; Timothy W. Mullett, MD, MBA; Judy C. Boughey, MD; Amanda B. Francescatti, MS; Elizabeth Funk, MSW; Heidi Nelson, MD; David R. Freyer, DO, MS
Population-Based Intraoperative Disease Severity Criteria for Pediatric Appendicitis
Authors: Kerri A. McKie, Donne A. Graham, Shannon L. Cramm, Jacqueline M. Saito, Shawn J. Rangel
Journal: JAMA Surgery (2024)

Importance A standardized severity assessment approach is needed in children with appendicitis for postoperative adverse event estimation and severity adjustment for hospital-level comparative performance reporting. Objective To examine the association between the presence and number of National Surgical Quality Improvement Program (NSQIP) Pediatric–defined intraoperative criteria for complicated appendicitis and outcomes in a population-based sample of children. Design, Setting, and Participants This cohort study used data from the American College of Surgeons NSQIP Pediatric Appendectomy Procedure Targeted Participant Use Data File and General Participant Use Data File for children younger than 18 years who underwent appendectomy from January 1, 2019, through December 31, 2022, at 148 hospitals participating in NSQIP Pediatric. Exposure The presence of NSQIP Pediatric intraoperative criteria for complicated appendicitis (ie, visible perforation, intraperitoneal abscess, extraluminal fecalith, and diffuse fibrinopurulent exudate). Main Outcomes and Measures Adverse event outcomes included postoperative rates of any surgical site infection (incisional or organ space), percutaneous drainage, sepsis, and reoperation. Resource use outcomes included operative duration and hospital length of stay, and rates of postoperative imaging, parenteral nutrition use, and revisits. Multivariable regression was used to explore the influence of individual and combinations of intraoperative criteria on outcomes after adjusting for patient characteristics. Results Of 82 950 patients included, 23 221 (27.9%) had at least 1 finding of complicated appendicitis. Compared with cases without any criteria present, the presence of each finding of complicated appendicitis was independently associated with higher rates of any adverse events; adjusted odds ratios (AORs) by finding were 5.57 (95% CI, 5.04-6.15) for visible hole, 4.83 (95% CI, 4.17-5.59) for diffuse fibrinopurulent exudate, 7.06 (95% CI, 5.77-8.63) for abscess, and 6.62 (95% CI, 4.78-9.15) for fecalith. An increasing number of criteria was associated with a stepwise increase in risk of any adverse events; AOR by number of criteria met were 5.55 (95% CI, 5.09-6.05) for 1 criterion, 8.86 (95% CI, 8.16-9.62) for 2 criteria, and 16.65 (95% CI, 15.10-18.35) for ≥3 criteria. Similar patterns in criteria-specific and cumulative implications for outcomes were observed with each individual adverse event and resource use measure. Conclusions and Relevance This cohort study found that postoperative complications and increased resource use are associated with the presence and number of NSQIP Pediatric criteria for complicated appendicitis. These criteria should be considered the gold standard, evidence-based severity assessment framework for estimating risk of adverse events and resource use in children with appendicitis.
Web-Based Cognitive Behavioral Treatment for Bulimia Nervosa
Authors: Steffen Hartmann, Christina Timm, Sven Barnow, Julian A. Rubel, Christopher Lalk, Luise Pruessner
Journal: JAMA Network Open (2024)

Importance Despite the existence of effective treatments, many individuals with bulimia nervosa (BN) do not receive evidence-based therapies. Integrating digital interventions into routine care might reach more patients and reduce the clinical burden of BN. Objective To evaluate the effectiveness of a web-based cognitive behavioral self-help intervention for individuals with BN. Design, Setting, and Participants A 2-group randomized clinical trial without follow-up was conducted between February 2, 2021, and July 9, 2022, in Germany. Participants aged between 18 and 65 years who met the diagnostic criteria for BN were enrolled online via self-referral. Data analyses were conducted from October 24, 2022, to December 23, 2023. Interventions A web-based cognitive behavioral self-help intervention including 12 weekly modules was compared with a waiting-list control group only having access to routine care. Main Outcomes and Measures The primary outcome was the change in the number of bulimic episodes between baseline and posttreatment. Secondary outcomes included changes in global eating disorder symptoms, clinical impairment, well-being, work capacity, comorbid symptoms, self-esteem, and emotion regulation complemented by weekly measures and ecological momentary assessment. Intention-to-treat analyses were performed. Results Participants (N = 154; mean [SD] age, 29.6 [8.6] years; 149 [96.8%] female) receiving the web-based intervention demonstrated a significantly greater decrease in bulimic episodes compared with the control group (Cohen d = −0.48; 95% CI, −0.75 to −0.20; P &amp;amp;lt; .001), representing a significant change in binge-eating episodes (Cohen d = −0.61; 95% CI, −0.89 to −0.33; P &amp;amp;lt; .001), but not in compensatory behaviors (Cohen d = −0.25; 95% CI, −0.51 to 0.02; P = .21). The intervention was superior in improving global eating disorder symptoms (Cohen d = −0.61; 95% CI, −0.89 to −0.32; P &amp;amp;lt; .001) and clinical impairment (Cohen d = −0.62; 95% CI, −0.92 to −0.33; P &amp;amp;lt; .001). No significant effects were found for well-being (Cohen d = −0.08; 95% CI, −0.37 to 0.22; P &amp;amp;gt; .99) and work capacity (Cohen d = −0.01; 95% CI, −0.68 to 0.66; P = .99). Exploratory analyses indicated significant changes in self-esteem and emotion regulation difficulties, but not in comorbid symptoms. Conclusions and Relevance In this randomized clinical trial, a web-based cognitive behavioral self-help intervention effectively decreased eating disorder symptoms and illness-related burden in individuals with BN, underlining the potential of digital interventions to complement established treatments. Trial Registration ClinicalTrials.gov Identifier: NCT04876196
Unintentional Intoxication or Injury and Risk for Self-Harm in Adolescents and Young Adults
Authors: Ariel Frajerman, Karine Goueslard, Catherine Quantin, Fabrice Jollant
Journal: JAMA Psychiatry (2024)

This cohort study explores the risk of nonfatal self-harm in French adolescents and young adults hospitalized for unintentional intoxication or injury.
Primary nasal influenza infection rewires tissue-scale memory response dynamics
Authors: Samuel W. Kazer, Colette Matysiak Match, Erica M. Langan, Marie-Angèle Messou, Thomas J. LaSalle, Elise O’Leary, Jessica Marbourg, Katherine Naughton, Ulrich H. von Andrian, Jose Ordovas-Montanes
Journal: Immunity (2024)
Oncogenic KRAS-Dependent Stromal Interleukin-33 Directs the Pancreatic Microenvironment to Promote Tumor Growth
Authors: Katelyn L. Donahue, Hannah R. Watkoske, Padma Kadiyala, Wenting Du, Kristee Brown, Michael K. Scales, Ahmed M. Elhossiny, Carlos E. Espinoza, Emily L. Lasse Opsahl, Brian D. Griffith, Yukang Wen, Lei Sun, Ashley Velez-Delgado, Nur M. Renollet, Jacqueline Morales, Nicholas M. Nedzesky, Rachael K. Baliira, Rosa E. Menjivar, Paola I. Medina-Cabrera, Arvind Rao, Benjamin Allen, Jiaqi Shi, Timothy L. Frankel, Eileen S. Carpenter, Filip Bednar, Yaqing Zhang, Marina Pasca di Magliano
Journal: Cancer Discovery (2024)

Abstract Pancreatic cancer is characterized by an extensive fibroinflammatory microenvironment. During carcinogenesis, normal stromal cells are converted to cytokine-high cancer-associated fibroblasts (CAF). The mechanisms underlying this conversion, including the regulation and function of fibroblast-derived cytokines, are poorly understood. Thus, efforts to therapeutically target CAFs have so far failed. Herein, we show that signals from epithelial cells expressing oncogenic KRAS—a hallmark pancreatic cancer mutation—activate fibroblast autocrine signaling, which drives the expression of the cytokine IL33. Stromal IL33 expression remains high and dependent on epithelial KRAS throughout carcinogenesis; in turn, environmental stress induces interleukin-33 (IL33) secretion. Using compartment-specific IL33 knockout mice, we observed that lack of stromal IL33 leads to profound reprogramming of multiple components of the pancreatic tumor microenvironment, including CAFs, myeloid cells, and lymphocytes. Notably, loss of stromal IL33 leads to an increase in CD8+ T-cell infiltration and activation and, ultimately, reduced tumor growth. Significance: This study provides new insights into the mechanisms underlying the programming of CAFs and shows that during this process, expression of the cytokine IL33 is induced. CAF-derived IL33 has pleiotropic effects on the tumor microenvironment, supporting its potential as a therapeutic target.
Eltrombopag plus diacerein vs. eltrombopag in patients with ITP: a multicenter, randomized, open-label, phase 2 trial
Authors: Lu Sun, Xiaoyang Huang, Juan Wang, Chenglu Yuan, Hongyu Zhao, Daqi Li, Ruirong Xu, Yan Wang, Pin Qin, Yan Shi, Jun Peng, Ming Hou, Yu Hou
Journal: Blood (2024)
Molecular taxonomy of myelodysplastic syndromes and its clinical implications
Authors: Elsa Bernard, Robert P. Hasserjian, Peter L. Greenberg, Juan Esteban Arango Ossa, Maria Creignou, Heinz Tuechler, Jesús Gutiérrez-Abril, Dylan Domenico, Juan Santiago Medina-Martinez, Max Fine Levine, Konstantinos Liosis, Noushin Farnoud, Maria Sirenko, Martin Jädersten, Ulrich Germing, Guillermo F. Sanz, Arjan A Van de Loosdrecht, Yasuhito Nannya, Olivier Kosmider, Matilde Y Follo, Felicitas R. Thol, Lurdes Zamora, Ronald Feitosa Pinheiro, Andrea Pellagatti, Harold Kunal Elias, Detlef Thomas Haase, Christina Ganster, Lionel Ades, Magnus Tobiasson, Laura Palomo, Matteo Giovanni Della Porta, Pierre Fenaux, Monika Belickova, Michael R. Savona, Virginia Klimek, Fabio P S Santos, Jacqueline Boultwood, Ioannis Kotsianidis, Valeria Santini, Francesc Sole, Uwe Platzbecker, Michael Heuser, Peter Valent, Carlo Finelli, Maria Teresa Voso, Lee Yung Shih, Michaela Fontenay, Joop H Jansen, José Cervera, Norbert Gattermann, Benjamin L Ebert, Rafael Bejar, Luca Malcovati, Seishi Ogawa, Mario Cazzola, Eva S Hellstrom-Lindberg, Elli Papaemmanuil
Journal: Blood (2024)
Efficacy of T cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis
Authors: Samuel C. C. Chiang, Laura E. Covill, Bianca Tesi, Tessa M. Campbell, Heinrich Schlums, Jelve Nejati-Zendegani, Karina Mördrup, Stephanie Wood, Jakob Theorell, Takuya Sekine, Waleed Al-Herz, Himmet Haluk Akar, Fatma Burcu Belen, Mei Yoke Chan, Omer Devecioglu, Tekin Aksu, Marianne Ifversen, Iwona Malinowska, Magnus Sabel, Ekrem Unal, Sule Unal, Wendy J. Introne, Konrad Krzewski, Kimberly C. Gilmour, Stephan Ehl, Hans-Gustaf Ljunggren, Magnus Nordenskjöld, AnnaCarin Horne, Jan-Inge Henter, Marie Meeths, Yenan T. Bryceson
Journal: Blood (2024)

Abstract Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder associated with autosomal recessive variants in genes required for perforin-mediated lymphocyte cytotoxicity. A rapid diagnosis is crucial for successful treatment. Although defective cytotoxic T lymphocyte (CTL) function causes pathogenesis, quantification of natural killer (NK)–cell exocytosis triggered by K562 target cells currently represents a standard diagnostic procedure for primary HLH. We have prospectively evaluated different lymphocyte exocytosis assays in 213 patients referred for evaluation for suspected HLH and related hyperinflammatory syndromes. A total of 138 patients received a molecular diagnosis consistent with primary HLH. Assessment of Fc receptor–triggered NK-cell and T-cell receptor (TCR)–triggered CTL exocytosis displayed higher sensitivity and improved specificity for the diagnosis of primary HLH than routine K562 cell–based assays, with these assays combined providing a sensitivity of 100% and specificity of 98.3%. By comparison, NK-cell exocytosis after K562 target cell stimulation displayed a higher interindividual variability, in part explained by differences in NK-cell differentiation or large functional reductions after shipment. We thus recommend combined analysis of TCR-triggered CTL and Fc receptor–triggered NK-cell exocytosis for the diagnosis of patients with suspected familial HLH or atypical manifestations of congenital defects in lymphocyte exocytosis.
Leptin‐mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer
Authors: Jian Xiao, Shuqing Cao, Jiawei Wang, Pengyu Li, Quan Cheng, Xinyi Zhou, Jiacheng Dong, Yuan Li, Xinyu Zhao, Zekuan Xu, Li Yang
Journal: Cancer Communications (2024)

Abstract Background Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis, yet the role of lipoprotein lipase (LPL), a pivotal enzyme involved in exogenous lipid uptake, remains uncertain in tumor metastasis. Therefore, the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process. Methods Intracellular lipid levels were quantified using oil red O staining, BODIPY 493/503 staining, and flow cytometry. Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown. Protein expression levels were assessed through immunohistochemistry, Western blotting, and enzyme‐linked immunosorbent assays. The mouse popliteal LNM model was utilized to investigate differences in LNM. Immunoprecipitation and mass spectrometry were employed to examine protein associations. In vitro phosphorylation assays and Phos‐tag sodium dodecyl‐sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin‐like protein 4 (ANGPTL4) phosphorylation. Results We identified that an elevated intracellular lipid level represents a crucial characteristic of node‐positive (N+) GC and further demonstrated that a high‐fat diet can expedite LNM. LPL was found to be significantly overexpressed in N+ GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells. Leptin, an obesity‐related hormone, intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage. Circulating leptin binding to the leptin receptor could induce the activation of inositol‐requiring enzyme‐1 (IRE1) kinase, leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL. Moreover, our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid, which then triggered the cyclooxygenase‐2/prostaglandin E2 (PGE2) pathway, thereby promoting tumor lymphangiogenesis. Conclusions Leptin‐induced phosphorylation of ANGPTL4 facilitates LPL‐mediated lipid uptake and consequently stimulates the production of PGE2, ultimately facilitating LNM in GC.
PAQR4 regulates adipocyte function and systemic metabolic health by mediating ceramide levels
Authors: Qingzhang Zhu, Shiuhwei Chen, Jan-Bernd Funcke, Leon G Straub, Qian Lin, Shangang Zhao, Chanmin Joung, Zhuzhen Zhang, Dae-Seok Kim, Na Li, Christy M Gliniak, Charlotte Lee, Alberto Cebrian-Serrano, Line Pedersen, Nils Halberg, Ruth Gordillo, Christine M Kusminski, Philipp E Scherer
Journal: Nature Metabolism (2024)
Epidermal growth factor receptor‑targeted antibody nimotuzumab combined with chemoradiotherapy improves survival in patients with locally advanced head and neck squamous cell carcinoma: a propensity score matching real‐world study
Authors: Peng Zhang, Xinxin Zhang, Jinyi Lang, Shaoxiong Wu, Yan Sun, Peiguo Wang, Sufang Qiu, Xiaodong Huang, Guoxin Ren, Kun Liu, Xiaojing Du, Shaowen Xiao, Zhongqiu Wang, Youliang Weng, Ye Zhang, Hang Zhou, Wenyong Tu, Chenping Zhang, Junlin Yi
Journal: MedComm (2024)

Abstract Patients with locally advanced head and neck squamous cell carcinoma (LA‐HNSCC) have poor survival outcomes. The real‐world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)‐based chemoradiotherapy in patients with LA‐HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3‐year overall survival (OS) rate. Log‐rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow‐up time was 54.2 (95% confidence interval [CI]: 52.7–55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57–0.99, p = 0.038) and progression‐free survival (PFS) (HR = 0.74, 95% CI: 0.58–0.96, p = 0.021). Subgroup analysis revealed that aged 50–60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab‐related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA‐HNSCC patients in an IMRT era.
Reported Incidence of Infections Caused by Pathogens Transmitted Commonly Through Food: Impact of Increased Use of Culture-Independent Diagnostic Tests — Foodborne Diseases Active Surveillance Network, 1996–2023
Authors: Hazel J. Shah, Rachel H. Jervis, Katie Wymore, Tamara Rissman, Bethany LaClair, Michelle M. Boyle, Kirk Smith, Sarah Lathrop, Suzanne McGuire, Rosalie Trevejo, Marcy McMillian, Stic Harris, Joanna Zablotsky Kufel, Kennedy Houck, Carey E. Lau, Carey J. Devine, Dave Boxrud, Daniel L. Weller
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Reducing foodborne disease incidence is a public health priority. This report summarizes preliminary 2023 Foodborne Diseases Active Surveillance Network (FoodNet) data and highlights efforts to increase the representativeness of FoodNet. During 2023, incidences of domestically acquired campylobacteriosis, Shiga toxin-producing Escherichia coli infection, yersiniosis, vibriosis, and cyclosporiasis increased, whereas those of listeriosis, salmonellosis, and shigellosis remained stable compared with incidences during 2016-2018, the baseline used for tracking progress towards federal disease reduction goals. During 2023, the incidence and percentage of infections diagnosed by culture-independent diagnostic tests (CIDTs) reported to FoodNet continued to increase, and the percentage of cases that yielded an isolate decreased, affecting observed trends in incidence. Because CIDTs allow for diagnosis of infections that previously would have gone undetected, lack of progress toward disease reduction goals might reflect changing diagnostic practices rather than an actual increase in incidence. Continued surveillance is needed to monitor the impact of changing diagnostic practices on disease trends, and targeted prevention efforts are needed to meet disease reduction goals. During 2023, FoodNet expanded its catchment area for the first time since 2004. This expansion improved the representativeness of the FoodNet catchment area, the ability of FoodNet to monitor trends in disease incidence, and the generalizability of FoodNet data.
Reported Xylazine Use Among Adults Aged ≥18 Years Evaluated for Substance Use Treatment — United States, July 2022–September 2023
Authors: Xinyi Jiang, Sarah Connolly, Andrea E. Strahan, Liz Rivera Blanco, Christina A. Mikosz, Gery P. Guy, Deborah Dowell
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Xylazine has been increasingly detected in illegally manufactured fentanyl (IMF) products and overdose deaths in the United States; most xylazine-involved overdose deaths involve IMF. A convenience sample of U.S. adults aged ≥18 years was identified from those evaluated for substance use treatment during July 2022-September 2023. Data were collected using the Addiction Severity Index-Multimedia Version clinical assessment tool. Among 43,947 adults, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance-use problem; 5,344 (12.2%) reported recent (i.e., past-30-day) IMF or heroin use. Among adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. Among adults reporting recent IMF or heroin use, 443 (8.3%) reported recent xylazine use. Among adults reporting IMF or heroin use recently or as their primary lifetime substance-use problem, those reporting xylazine use reported a median of two past nonfatal overdoses from any drug compared with a median of one overdose among those who did not report xylazine use; as well, higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use. Provision of nonjudgmental care and services, including naloxone, wound care, and linkage to and retention of persons in effective substance use treatment, might reduce harms including overdose among persons reporting xylazine use.
Single‐cell transcriptome dissecting the microenvironment remodeled by PD1 blockade combined with photodynamic therapy in a mouse model of oral carcinogenesis
Authors: Yunmei Dong, Kan Zeng, Ruixue Ai, Chengli Zhang, Fei Mao, Hongxia Dan, Xin Zeng, Ning Ji, Jing Li, Xin Jin, Qianming Chen, Yu Zhou, Taiwen Li
Journal: MedComm (2024)

Abstract Oral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4‐nitroquinoline 1‐oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single‐cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor‐promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor‐promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment‐associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.
PI3Kγ in B cells promotes antibody responses and generation of antibody-secreting cells
Authors: Stephen M. Lanahan, Lucas Yang, Kate M. Jones, Zhihong Qi, Emylette Cruz Cabrera, Lauren Y. Cominsky, Anjali Ramaswamy, Anis Barmada, Gisela Gabernet, Dinesh Babu Uthaya Kumar, Lan Xu, Peiying Shan, Matthias P. Wymann, Steven H. Kleinstein, V. Koneti Rao, Peter Mustillo, Neil Romberg, Roshini S. Abraham, Carrie L. Lucas
Journal: Nature Immunology (2024)