tbuckley/cabot-search huggingface dataset:
A commentary on ‘The number of metastatic lymph nodes is more predictive of prognosis than location-based N stage for non-small cell lung cancer: a retrospective cohort study’
Authors: Lin-chuan Liang, Zhi-yu Peng, Jian-dong Mei
Journal: International Journal of Surgery (2023)

aDepartment of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China bWestern China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China Assistance with the study: none These authors contributed equally to this work and joint first authors Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: No. 37, Guoxue Alley, Chengdu 610041, China. E-mail address: [email protected] (Jian-dong. Mei). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Outcomes of selective non-operative management in adults with abdominal gunshot wounds: a systematic review and meta-analysis
Authors: Tingwei Liu, Xiaohui Fang, Zhaohui Bai, Lu Liu, Hui Lu, Xingshun Qi
Journal: International Journal of Surgery (2023)

Background and Aims: Abdominal gunshot wounds (GSWs), a clinically devastating injury, can result in a variety of severe and lethal complications. Traditionally, exploratory laparotomy is the first-line approach for the management of abdominal GSWs, but associated with a considerable amount of unnecessary surgeries. At present, selective non-operative management (SNOM) of abdominal GSWs is becoming an effective and well-recognized approach, but remains widely disputed since many surgeons are skeptical about the validity of SNOM in clinical practice. This meta-analysis aims to estimate the outcomes of SNOM and immediate laparotomy in patients with GSWs by collecting the currently available evidence. Methods: The PubMed , EMBASE , and Cochrane Library databases were searched. A random-effects model was employed. Pooled proportion with 95% confidence intervals (CIs) was calculated. Heterogeneity was evaluated using the Cochran’s Q test and I 2 statistics. Results: Overall, 53 studies involving 60,291 participants were included. The pooled proportions of SNOM and SNOM failure were 27.0% (95%CI=24.0%-30.0%) and 10.0% (95%CI=7.0%-13.0%), respectively. The pooled mortality after SNOM and SNOM failure were 0.0% (95%CI=0.0%-1.0%) and 0.0% (95%CI=0.0%-0.0%), respectively. The pooled proportions of immediate laparotomy and unnecessary immediate laparotomy were 73.0% (95%CI=70.0%-76.0%) and 10.0% (95%CI=8.0%-13.0%), respectively. The pooled mortality after immediate laparotomy and unnecessary immediate laparotomy were 10.0% (95%CI=8.0%-13.0%) and 0.0% (95%CI=0.0%-1.0%), respectively. Heterogeneity was statistically significant in nearly all meta-analyses. Conclusion: Immediate laparotomy is still the mainstay approach for the management of abdominal GSWs. Approximately one third of patients with abdominal GSWs undergo SNOM. SNOM failure is not frequent and its related mortality is also rare.
Hyperinsulinemia, an overlooked clue and potential way forward in metabolic dysfunction–associated steatotic liver disease
Authors: Stephen A. Harrison, Julie Dubourg, Maddie Knott, Jerry Colca
Journal: Hepatology (2023)

Metabolic dysfunction–associated steatotic liver disease is closely associated with other features of the metabolic syndrome such as type 2 diabetes. The progression of the disease may lead to liver fibrosis, which is the main predictor of major adverse liver outcomes. Insulin resistance plays a major role in the pathogenesis of the disease. A component of fasting hyperinsulinemia is a failure of the liver to adjust the peripheral level of insulin due to reduced clearance. The associated fasting hyperinsulinemia has been independently associated as a predictor of major adverse liver outcomes and major adverse cardiovascular events. In this review, we discuss the potential mechanism and entanglement between liver fibrosis and hyperinsulinemia, and we hypothesize that the measure of fasting insulin could become a hepatic functional test within the armamentarium of noninvasive tests for the assessment of Metabolic dysfunction–associated steatotic liver disease.
HLA Haplotypes and Relapse After Hematopoietic Cell Transplantation
Authors: Effie W. Petersdorf, Caroline McKallor, Mari Malkki, Meilun He, Stephen R. Spellman, Theodore Gooley, Philip Stevenson
Journal: Journal of Clinical Oncology (2023)

PURPOSE Recurrence of blood malignancy is the major cause of hematopoietic cell transplant failure. HLA class II molecules play a fundamental role in antitumor responses but the role of class II haplotypes is not known. METHODS HLA-DR, -DQ, -DM, and -DO allele variation was determined in 1,629 related haploidentical transplants to study the clinical significance of individual molecules and haplotypes. RESULTS Outcome correlated with patient and donor variation for HLA-DRβ residue 86 (Gly/Val), HLA-DQ (G1/G2) heterodimers, and donor HLA-DM (DM11,11/nonDM11,11) molecules, and depended on patient-donor mismatching. Risks of relapse were lower for DRβ-86 GlyGly patients when the donor was GlyVal (hazard ratio [HR], 0.46 [95% CI, 0.30 to 0.68]; P &lt; .001); GlyVal patients benefited from HLA-DRB1–matched donors, whereas no donor was superior to another for ValVal patients. G1G2 patients with G1G2-mismatched donors had lower relapse. Transplantation from donors with DMα residue 184 ArgHis was associated with higher risk of relapse (HR, 1.60 [95% CI, 1.09 to 2.36]; P = .02) relative to ArgArg. Relapse and mortality risks differed across HLA-DR-DQ-DM haplotypes. CONCLUSION HLA class II haplotypes may be functional constituents of the transplantation barrier, and their consideration in patients and donors may improve the success of transplantation.
Lung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study
Authors: Svetlana Herasevich, Phillip J. Schulte, William J. Hogan, Hassan Alkhateeb, Zhenmei Zhang, Bradley A. White, Nandita Khera, Vivek Roy, Ognjen Gajic, Hemang Yadav
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes.
Commensal Oral Microbiota, Disease Severity, and Mortality in Fibrotic Lung Disease
Authors: David N. O’Dwyer, John S. Kim, Shwu-Fan Ma, Piyush Ranjan, Promi Das, Jay H. Lipinski, Joseph D. Metcalf, Nicole R. Falkowski, Eric Yow, Kevin Anstrom, Robert P. Dickson, Yong Huang, Jack A. Gilbert, Fernando J. Martinez, Imre Noth
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Oral microbiota associate with diseases of the mouth and serve as a source of lung microbiota. However, the role of oral microbiota in lung disease is unknown.
Prenatal Infection by Respiratory Viruses Is Associated with Immunoinflammatory Responses in the Fetus
Authors: Ivy V. Trinh, Srushti P. Desai, Sylvia H. Ley, Zhiyin Mo, Ryosuke Satou, Gabriella C. Pridjian, Sherri A. Longo, Jeffrey G. Shaffer, James E. Robinson, Elizabeth B. Norton, Giovanni Piedimonte
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Respiratory viral infections can be transmitted from pregnant women to their offspring, but frequency, mechanisms, and postnatal outcomes remain unclear.
Diabetes Stigma and Psychosocial Outcomes in Adolescents and Young Adults: The SEARCH for Diabetes in Youth Study
Authors: Kelsey B. Eitel, Alissa J. Roberts, Ralph D’Agostino, Catherine E. Barrett, Ronny A. Bell, Anna Bellatorre, Angelica Cristello, Dana Dabelea, Lawrence M. Dolan, Elizabeth T. Jensen, Angela D. Liese, Kristi Reynolds, Santica M. Marcovina, Catherine Pihoker
Journal: Diabetes Care (2023)

OBJECTIVE To examine the association between diabetes stigma, socioeconomic status, psychosocial variables, and substance use in adolescents and young adults (AYAs) with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS This is a cross-sectional analysis of AYAs from the SEARCH for Diabetes in Youth study who completed a survey on diabetes-related stigma, generating a total diabetes stigma score. Using multivariable modeling, stratified by diabetes type, we examined the relationship of diabetes stigma with variables of interest. RESULTS Of the 1,608 AYAs who completed the diabetes-related stigma survey, 78% had type 1 diabetes, and the mean age was 21.7 years. Higher diabetes stigma scores were associated with food insecurity (P = 0.001), disordered eating (P &amp;lt; 0.0001), depressive symptoms (P &amp;lt; 0.0001), and decreased health-related (P &amp;lt; 0.0001) and diabetes-specific quality of life (P &amp;lt; 0.0001). CONCLUSIONS Diabetes stigma is associated with food insecurity, disordered eating, and lower psychosocial well-being.
Association of Continued Use of SGLT2 Inhibitors From the Ambulatory to Inpatient Setting With Hospital Outcomes in Patients With Diabetes: A Nationwide Cohort Study
Authors: Lakshmi G. Singh, Spyridon Ntelis, Tariq Siddiqui, Stephen L. Seliger, John D. Sorkin, Elias K. Spanakis
Journal: Diabetes Care (2023)

OBJECTIVE Limited data are available on the continuation of outpatient sodium glucose cotransporter 2 inhibitors (SGLT2is) during hospitalization. The objective was to evaluate associations of SGLT2i continuation in the inpatient setting with hospital outcomes. RESEARCH DESIGN AND METHODS This nationwide cohort study used Veterans Affairs health care system data of acute care hospitalizations between 1 April 2013 and 31 August 2021. A total of 36,505 admissions of patients with diabetes with an outpatient prescription for an SGLT2i prior to hospitalization were included. The exposure was defined as SGLT2i continuation during hospitalization. Admissions where SGLT2i was continued were compared with admissions where it was discontinued. The primary outcome was in-hospital mortality. Secondary outcomes were acute kidney injury (AKI) and length of stay (LOS). Negative binomial propensity score–weighted and zero-truncated analyses were used to compare outcomes and adjusted for multiple covariates, including demographics and comorbidities. RESULTS Mean (SE) age was 67.2 (0.1) and 67.5 (0.1) years (P = 0.03), 97.0% and 96.6% were male (P = 0.1), 71.3% and 72.1% were White, and 20.8% and 20.5% were Black (P = 0.52) for the SGLT2i continued and discontinued groups, respectively. After adjustment for covariates (age, sex, race, BMI, Elixhauser comorbidity index, procedures/surgeries, and insulin use), the SGLT2i continued group had a 45% lower mortality rate (incidence rate ratio [IRR] 0.55, 95% CI 0.42–0.73, P &amp;lt; 0.01), no difference in AKI (IRR 0.96, 95% CI 0.90–1.02, P = 0.17), and decreased LOS (4.7 vs. 4.9 days) (IRR 0.95, 95% CI 0.93–0.98, P &amp;lt; 0.01) versus the SGLT2i discontinued group. Similar associations were observed across multiple sensitivity analyses. CONCLUSIONS Continued SGLT2i during hospitalization among patients with diabetes was associated with lower mortality, no increased AKI, and shorter LOS.
Pulmonary Artery Wedge Pressure in the Diagnosis of Pulmonary Arterial Hypertension
Authors: Robert Naeije, Adriano R. Tonelli
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Pulmonary Artery Wedge Pressure in the Diagnosis of Pulmonary Arterial Hypertension." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Hepatocyte CHRNA4 mediates the MASH-promotive effects of immune cell-produced acetylcholine and smoking exposure in mice and humans
Authors: Chuyue Pan, Jun Liu, Yingsheng Gao, Maohui Yang, Haiyang Hu, Chang Liu, Minyi Qian, Hai-Yang Yuan, Song Yang, Ming-Hua Zheng, Lirui Wang
Journal: Cell Metabolism (2023)
A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer
Authors: Paul B. Romesser, Jaume Capdevila, Rocio Garcia-Carbonero, Tony Philip, Carlos Fernandez Martos, Richard Tuli, Almudena Rodriguez-Gutierrez, Mirjam Kuipers, Andreas Becker, Anna Coenen-Stass, Barbara Sarholz, Xiaoli You, Eric D. Miller
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Peposertib—an orally administered DNA-dependent protein kinase inhibitor—has shown potent radiosensitization in preclinical models. This dose-escalation study (NCT03770689) aimed to define the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of peposertib plus capecitabine-based chemoradiotherapy (CRT) and assessed its safety and efficacy in locally advanced rectal cancer. Patients and Methods: Patients were treated for 5 to 5.5 weeks with 50- to 250-mg peposertib once daily, capecitabine 825 mg/m2 twice daily, and radiotherapy (RT), 5 days per week. Following clinical restaging (8 weeks after CRT completion), patients with clinical complete response (cCR) could opt for surveillance. Total mesorectal excision was recommended upon incomplete response (IR). Results: Nineteen patients were treated with peposertib at doses of 50 mg (n = 1), 100 mg, 150 mg, and 250 mg (n = 6 each). Dose-limiting toxicities occurred in one out of five (100 mg), one out of six (150 mg), and three out of six (250 mg) evaluable patients. Peposertib ≤150 mg once daily was tolerable in combination with CRT. After 8 weeks of treatment with peposertib and CRT, the cCR was 15.8% (n = 3). Among the three patients with cCR, two underwent surgery and had residual tumors. Among the 16 patients with IR, seven underwent surgery and had residual tumors; five of the remaining nine patients opted for consolidative chemotherapy. The combined cCR/pathologic complete response (pCR) rate was 5.3% (n = 1, 100 mg cohort). Conclusions: Peposertib did not improve complete response rates at tolerable dose levels. The study was closed without declaring the MTD/RP2D.
Single-cell sequencing reveals Hippo signaling as a driver of fibrosis in hidradenitis suppurativa
Authors: Kelsey R. van Straalen, Feiyang Ma, Pei-Suen Tsou, Olesya Plazyo, Mehrnaz Gharaee-Kermani, Marta Calbet, Xianying Xing, Mrinal K. Sarkar, Ranjitha Uppala, Paul W. Harms, Rachael Wasikowski, Lina Nahlawi, Mio Nakamura, Milad Eshaq, Cong Wang, Craig Dobry, Jeffrey H. Kozlow, Jill Cherry-Bukowiec, William D. Brodie, Kerstin Wolk, Özge Uluçkan, Megan N. Mattichak, Matteo Pellegrini, Robert L. Modlin, Emanual Maverakis, Robert Sabat, J. Michelle Kahlenberg, Allison C. Billi, Lam C. Tsoi, Johann E. Gudjonsson
Journal: Journal of Clinical Investigation (2023)

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by abscesses, nodules, dissecting/draining tunnels, and extensive fibrosis. Here, we integrate single-cell RNA sequencing, spatial transcriptomics, and immunostaining to provide an unprecedented view of the pathogenesis of chronic HS, characterizing the main cellular players and defining their interactions. We found a striking layering of the chronic HS infiltrate and identified the contribution of 2 fibroblast subtypes (SFRP4+ and CXCL13+) in orchestrating this compartmentalized immune response. We further demonstrated the central role of the Hippo pathway in promoting extensive fibrosis in HS and provided preclinical evidence that the profibrotic fibroblast response in HS can be modulated through inhibition of this pathway. These data provide insights into key aspects of HS pathogenesis with broad therapeutic implications.
ACSS2 gene variants determine kidney disease risk by controlling de novo lipogenesis in kidney tubules
Authors: Dhanunjay Mukhi, Lingzhi Li, Hongbo Liu, Tomohito Doke, Lakshmi P. Kolligundla, Eunji Ha, Konstantin Kloetzer, Amin Abedini, Sarmistha Mukherjee, Junnan Wu, Poonam Dhillon, Hailong Hu, Dongyin Guan, Katsuhiko Funai, Kahealani Uehara, Paul M. Titchenell, Joseph A. Baur, Kathryn E. Wellen, Katalin Susztak
Journal: Journal of Clinical Investigation (2023)

Worldwide, over 800 million people are affected by kidney disease, yet its pathogenesis remains elusive, hindering the development of novel therapeutics. In this study, we employed kidney-specific expression of quantitative traits and single-nuclear open chromatin analysis to show that genetic variants linked to kidney dysfunction on chromosome 20 target the acyl-CoA synthetase short-chain family 2 (ACSS2). By generating ACSS2 knock-out mice, we demonstrated their protection from kidney fibrosis in multiple disease models. Our analysis of primary tubular cells revealed that ACSS2 regulates de novo lipogenesis (DNL), causing NADPH depletion and increasing ROS levels, ultimately leading to NLRP3-dependent pyroptosis. Additionally, we discovered that pharmacological inhibition or genetic ablation of fatty acid synthase safeguarded kidney cells against profibrotic gene expression and prevented kidney disease in mice. Lipid accumulation and the expression of genes related to DNL were elevated in the kidneys of patients with fibrosis. Our findings pinpoint ACSS2 as a critical kidney disease gene and reveal the role of DNL in kidney disease.
Bacteroides methylmalonyl-CoA mutase produces propionate that promotes intestinal goblet cell differentiation and homeostasis
Authors: Xingyu Wang, Zhongle Cai, Qiaoling Wang, Chao Wu, Yingkai Sun, Zhifeng Wang, Xiaoqiang Xu, Wenzhi Xue, Zhiwen Cao, Minchun Zhang, Yinmeng Zhu, Huibin Lin, Yi Zhang, Mingyang Yuan, Yuxiao Zhao, Aibo Gao, Yuqiang Yu, Yufang Bi, Guang Ning, Weiqing Wang, Jiqiu Wang, Ruixin Liu
Journal: Cell Host & Microbe (2023)
Phase I/II Study of the WEE1 Inhibitor Adavosertib (AZD1775) in Combination with Carboplatin in Children with Advanced Malignancies: Arm C of the AcSé-ESMART Trial
Authors: Susanne A. Gatz, Anne C. Harttrampf, Caroline Brard, Francisco Bautista, Nicolas André, Samuel Abbou, Jonathan Rubino, Windy Rondof, Marc Deloger, Marc Rübsam, Lynley V. Marshall, Daniel Hübschmann, Souad Nebchi, Isabelle Aerts, Estelle Thebaud, Emilie De Carli, Anne Sophie Defachelles, Xavier Paoletti, Robert Godin, Kowser Miah, Peter G.S. Mortimer, Gilles Vassal, Birgit Geoerger
Journal: Clinical Cancer Research (2023)

Abstract Purpose: AcSé-ESMART Arm C aimed to define the recommended dose and activity of the WEE1 inhibitor adavosertib in combination with carboplatin in children and young adults with molecularly enriched recurrent/refractory malignancies. Patients and Methods: Adavosertib was administered orally, twice every day on Days 1 to 3 and carboplatin intravenously on Day 1 of a 21-day cycle, starting at 100 mg/m2/dose and AUC 5, respectively. Patients were enriched for molecular alterations in cell cycle and/or homologous recombination (HR). Results: Twenty patients (median age: 14.0 years; range: 3.4–23.5) were included; 18 received 69 treatment cycles. Dose-limiting toxicities were prolonged grade 4 neutropenia and grade 3/4 thrombocytopenia requiring transfusions, leading to two de-escalations to adavosertib 75 mg/m2/dose and carboplatin AUC 4; no recommended phase II dose was defined. Main treatment-related toxicities were hematologic and gastrointestinal. Adavosertib exposure in children was equivalent to that in adults; both doses achieved the cell kill target. Overall response rate was 11% (95% confidence interval, 0.0–25.6) with partial responses in 2 patients with neuroblastoma. One patient with medulloblastoma experienced unconfirmed partial response and 5 patients had stable disease beyond four cycles. Seven of these eight patients with clinical benefit had alterations in HR, replication stress, and/or RAS pathway genes with or without TP53 alterations, whereas TP53 pathway alterations alone (8/10) or no relevant alterations (2/10) were present in the 10 patients without benefit. Conclusions: Adavosertib–carboplatin combination exhibited significant hematologic toxicity. Activity signals and identified potential biomarkers suggest further studies with less hematotoxic DNA-damaging therapy in molecularly enriched pediatric cancers.
An excitatory projection from the basal forebrain to the ventral tegmental area that underlies anorexia-like phenotypes
Authors: Jing Cai, Yanyan Jiang, Yuanzhong Xu, Zhiying Jiang, Claire Young, Hongli Li, Joshua Ortiz-Guzman, Yizhou Zhuo, Yulong Li, Yong Xu, Benjamin R. Arenkiel, Qingchun Tong
Journal: Neuron (2023)
Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial
Authors: Jenna H. Rannikko, Loic Verlingue, Maria de Miguel, Annika Pasanen, Debbie Robbrecht, Tanja Skytta, Sanna Iivanainen, Shishir Shetty, Yuk Ting Ma, Donna M. Graham, Sukeshi Patel Arora, Panu Jaakkola, Christina Yap, Yujuan Xiang, Jami Mandelin, Matti K. Karvonen, Juho Jalkanen, Sinem Karaman, Jussi P. Koivunen, Anna Minchom, Maija Hollmén, Petri Bono
Journal: Cell Reports Medicine (2023)

Macrophage Clever-1 contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial investigates the safety and tolerability of Clever-1 blockade with bexmarilimab in patients with treatment-refractory solid tumors and assesses preliminary anti-tumor efficacy, pharmacodynamics, and immunologic correlates. Bexmarilimab shows no dose-limiting toxicities in part I (n = 30) and no additional safety signals in part II (n = 108). Disease control (DC) rates of 25%-40% are observed in cutaneous melanoma, gastric, hepatocellular, estrogen receptor-positive breast, and biliary tract cancers. DC associates with improved survival in a landmark analysis and correlates with high pre-treatment intratumoral Clever-1 positivity and increasing on-treatment serum interferon γ (IFNγ) levels. Spatial transcriptomics profiling of DC and non-DC tumors demonstrates bexmarilimab-induced macrophage activation and stimulation of IFNγ and T cell receptor signaling selectively in DC patients. These data suggest that bexmarilimab therapy is well tolerated and show that macrophage targeting can promote immune activation and tumor control in late-stage cancer.
Duffy antigen is expressed during erythropoiesis in Duffy-negative individuals
Authors: Celia Dechavanne, Sebastien Dechavanne, Jürgen Bosch, Sylvain Metral, Karli R. Redinger, Quentin D. Watson, Arsene C. Ratsimbasoa, Brooke Roeper, Sushma Krishnan, Rich Fong, Seth Bennett, Lenore Carias, Edwin Chen, Nichole D. Salinas, Anil Ghosh, Niraj H. Tolia, Philip G. Woost, James W. Jacobberger, Yves Colin, Benoit Gamain, Christopher L. King, Peter A. Zimmerman
Journal: Cell Host & Microbe (2023)