tbuckley/cabot-search huggingface dataset:
Inhibition of Aberrantly Overexpressed Polo-like Kinase 4 Is a Potential Effective Treatment for DNA Damage Repair–Deficient Uterine Leiomyosarcoma
Authors: Horace H.Y. Lee, Kin Long Chow, Ho Shing Wong, Tsz Yan Chong, Alice S.T. Wong, Grace H.W. Cheng, Jasmine M.K. Ko, Hoi Cheong Siu, Maximus C.F. Yeung, Michael S.Y. Huen, Ka Yu Tse, Mark R. Bray, Tak Wah Mak, Suet Yi Leung, Philip P.C. Ip
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Uterine leiomyosarcoma (LMS) is an aggressive sarcoma and a subset of which exhibits DNA repair defects. Polo-like kinase 4 (PLK4) precisely modulates mitosis, and its inhibition causes chromosome missegregation and increased DNA damage. We hypothesize that PLK4 inhibition is an effective LMS treatment. Experimental Design: Genomic profiling of clinical uterine LMS samples was performed, and homologous recombination (HR) deficiency scores were calculated. A PLK4 inhibitor (CFI-400945) with and without an ataxia telangiectasia mutated (ATM) inhibitor (AZD0156) was tested in vitro on gynecologic sarcoma cell lines SK-UT-1, SKN, and SK-LMS-1. Findings were validated in vivo using the SK-UT-1 xenograft model in the Balb/c nude mouse model. The effects of CFI-400945 were also evaluated in a BRCA2-knockout SK-UT-1 cell line. The mechanisms of DNA repair were analyzed using a DNA damage reporter assay. Results: Uterine LMS had a high HR deficiency score, overexpressed PLK4 mRNA, and displayed mutations in genes responsible for DNA repair. CFI-400945 demonstrated effective antitumor activity in vitro and in vivo. The addition of AZD0156 resulted in drug synergism, largely due to a preference for nonhomologous end-joining DNA repair. Compared with wild-type cells, BRCA2 knockouts were more sensitive to PLK4 inhibition when both HR and nonhomologous end-joining repairs were impaired. Conclusions: Uterine LMS with DNA repair defects is sensitive to PLK4 inhibition because of the effects of chromosome missegregation and increased DNA damage. Loss-of-function BRCA2 alterations or pharmacologic inhibition of ATM enhanced the efficacy of the PLK4 inhibitor. Genomic profiling of an advanced-stage or recurrent uterine LMS may guide therapy.
Nonbinary identity and pronoun use: A qualitative analysis
Authors: Manon St Amant, Jieyi Cai, G. Nic Rider, Richard Lee
Journal: International Journal of Transgender Health (2024)

Background and Aims Limited psychological research focuses on the identities and pronoun use experiences of nonbinary and genderqueer people. The purpose of this qualitative study was to examine the experiences of nonbinary and genderqueer young people, particularly with respect to the use and significance of pronouns.
Potential of body mass index as a screening indicator for extracranial-intracranial bypass surgery in patients with symptomatic artery occlusion: a post-hoc analysis of the CMOSS trial
Authors: Guangdong Lu, Tao Wang, Fan Yang, Xinyi Sun, Renjie Yang, Jichang Luo, Xiaoguang Tong, Yuxiang Gu, Jiyue Wang, Zhiyong Tong, Dong Kuai, Yiling Cai, Jun Ren, Donghai Wang, Lian Duan, Aisha Maimaitili, Chunhua Hang, Jiasheng Yu, Yan Ma, Sheng Liu, Liqun Jiao
Journal: International Journal of Surgery (2024)

Background: To investigate the association between BMI and the incidence of ischemic stroke in patients with symptomatic artery occlusion, and further to evaluate the utility of BMI as a screening tool for identifying candidates for extracranial–intracranial bypass surgery. Materials and Methods: The authors analyzed the relationship between BMI and the occurrence of ipsilateral ischemic stroke (IIS) among patients receiving only medical management in the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS). Additionally, the authors compared the primary endpoint of CMOSS—stroke or death within 30 days, or IIS after 30 days up to 2 years—among patients with varying BMIs who underwent either surgery or medical treatment. Results: Of the 165 patients who treated medically only, 16 (9.7%) suffered an IIS within 2 years. BMI was independently associated with the incidence of IIS (hazard ratio: 1.16 per kg/m 2 ; 95% CI: 1.06–1.27). The optimal BMI cutoff for predicting IIS was 24.5 kg/m 2 . Patients with BMI ≥24.5 kg/m 2 experienced a higher incidence of IIS compared to those with BMI &lt;24.5 kg/m 2 (17.4 vs. 0.0%, P &lt;0.01). The incidence of the CMOSS primary endpoint was significantly different between the surgical and medical groups for patients with BMI ≥24.5 kg/m 2 (5.3 vs. 19.8%, P &lt;0.01) and those with BMI &lt;24.5 kg/m 2 (10.6 vs. 1.4%; P =0.02). Surgical intervention was independently associated with a reduced rate of the CMOSS primary endpoint in patients with BMI ≥24.5 kg/m 2 . Conclusion: Data from the CMOSS trial indicate that patients with BMI ≥24.5 kg/m 2 are at a higher risk of IIS when treated medically only and appear to derive greater benefit from bypass surgery compared to those with lower BMIs. Given the small sample size and the inherent limitations of retrospective analyses, further large-scale, prospective studies are necessary to confirm these findings.
Influence of intraoperative blood salvage and autotransfusion on tumor recurrence after deceased donor liver transplantation: a large nationwide cohort study
Authors: Mengfan Yang, Xuyong Wei, Wenzhi Shu, Xiangyu Zhai, Zhisheng Zhou, Jinzhen Cai, Jiayin Yang, Bin Jin, Shusen Zheng, Xiao Xu
Journal: International Journal of Surgery (2024)

Background and aims: The practice of intraoperative blood salvage and autotransfusion (IBSA) during deceased donor liver transplantation for hepatocellular carcinoma (HCC) can potentially reduce the need for allogeneic blood transfusion. However, implementing IBSA remains debatable due to concerns about its possible detrimental effects on oncologic recurrence. Methods: This study retrospectively enrolled nationwide recipients of deceased donor liver transplantation for HCC between 2015 and 2020. The focus was on comparing the cumulative recurrence rate and the recurrence-free survival rate. Propensity score matching was conducted repeatedly for further subgroup comparison. Recipients were categorized based on the Milan criteria, macrovascular invasion, and pretransplant α-Fetoprotein (AFP) level to identify subgroups at risk of HCC recurrence. Results: A total of 6196 and 329 patients were enrolled in the non-IBSA and IBSA groups in this study. Multivariable competing risk regression analysis identified IBSA as independent risk factors for HCC recurrence ( P &lt;0.05). Postmatching, the cumulative recurrence rate and recurrence-free survival rate revealed no significant difference in the IBSA group and non-IBSA group (22.4 vs. 16.5%, P =0.12; 60.3 vs. 60.9%, P =0.74). Recipients beyond Milan criteria had higher, albeit not significant, risk of HCC recurrence if receiving IBSA (33.4 vs. 22.5%, P =0.14). For recipients with macrovascular invasion, the risk of HCC recurrence has no significant difference between the two groups (32.2 vs. 21.3%, P =0.231). For recipients with an AFP level &lt;20 ng/ml, the risk of HCC recurrence was comparable in the IBSA group and the non-IBSA group (12.8 vs. 18.7%, P =0.99). Recipients with an AFP level ≥20 ng/ml, the risk of HCC recurrence was significantly higher in the IBSA group. For those with an AFP level ≥400 ng/ml, the impact of IBSA on the cumulative recurrence rate was even more pronounced (49.8 vs. 21.9%, P =0.011). Conclusions: IBSA does not appear to be associated with worse outcomes for recipients with HCC exceeding the Milan criteria or with macrovascular invasion. IBSA could be confidently applied for recipients with a pretransplant AFP level &lt;20 ng/ml. For recipients with AFP levels ≥20 ng/ml, undertaking IBSA would increase the risk of HCC recurrence.
PSMA-Avid Liver Metastasis in a Case of Prostate Carcinoma and Poorly Differentiated Thyroid Carcinoma
Authors: Meric Coskun, Uguray Aydos, Umit Ozgur Akdemir, Mehmet Muhittin Yalcin, Fusun Balos Toruner
Journal: Clinical Nuclear Medicine (2024)

Abstract Although PSMA-targeted PET imaging is predominantly used for prostate carcinoma (PC), it has also been reported for thyroid carcinoma (TC). A 77-year-old man had a liver metastasectomy for poorly differentiated TC, which had elevated 18 F-FDG uptake. Two years later, he was diagnosed with acinar-type modified Gleason score of 7 (3 + 4) PC. Four years later, he had metastatic liver lesions that had no radioactive iodine and 18 F-FDG avidity. These lesions were 68 Ga-PSMA avid, and the biopsy confirmed TC metastasis. This case emphasizes the importance of 68 Ga-PSMA–based imaging in poorly differentiated TC and pathological confirmation for lesions that were 68 Ga-PSMA–positive.
Re-exploration for bleeding and long-term survival after adult cardiac surgery: a meta-analysis of reconstructed time-to-event data
Authors: Giovanni Jr Soletti, Gianmarco Cancelli, Michele Dell’Aquila, Tulio Caldonazo, Lamia Harik, Camilla Rossi, Panagiotis Tasoudis, Jordan Leith, Kevin R. An, Arnaldo Dimagli, Michelle Demetres, Mario Gaudino
Journal: International Journal of Surgery (2024)

Background: Postoperative bleeding requiring re-exploration is a serious complication that occurs in 2.8–4.6% of patients undergoing cardiac surgery. Re-exploration has previously been associated with a higher risk of short-term mortality. However, a comprehensive analysis of long-term outcomes after re-exploration for bleeding has not been published. Materials and methods: The authors performed a systematic, three databases search to identify studies reporting long-term outcomes in patients who required re-exploration for bleeding after cardiac surgery compared to patients who did not, with at least 1-year of follow-up. Long-term survival was the primary outcome. Secondary outcomes were operative mortality, myocardial infarction, stroke, renal and respiratory complications, and hospital length of stay. Random-effects models was used. Individual patient survival data was extracted from available survival curves and reconstructed using restricted mean survival time. Results: Six studies totaling 135 456 patients were included. The average follow-up was 5.5 years. In the individual patient data, patients who required re-exploration had a significantly higher risk of death compared with patients who did not [hazard ratio (HR): 1.21; 95% CI: 1.14–1.27; P &lt;0.001], which was confirmed by the study-level survival analysis (HR: 1.32; 95% CI: 1.12–1.56; P &lt;0.01). Re-exploration was also associated with a higher risk of operative mortality [odds ratio (OR): 5.25, 95% CI: 4.74–5.82, P &lt;0.0001], stroke (OR: 2.05, 95% CI: 1.72–2.43, P &lt;0.0001), renal (OR: 4.13, 95% CI: 3.43–4.39 P &lt;0.0001) respiratory complications (OR: 3.91, 95% CI: 2.96–5.17, P &lt;0.0001), longer hospital length of stay (mean difference: 2.69, 95% CI: 1.68–3.69, P &lt;0.0001), and myocardial infarction (OR: 1.85, 95% CI: 1.30–2.65, P =0.0007). Conclusion: Postoperative bleeding requiring re-exploration is associated with lower long-term survival and increased risk of short-term adverse events including operative mortality, stroke, renal and respiratory complications, and longer hospital length of stay. To improve both short-term and long-term outcomes, strategies to prevent the need for re-exploration are necessary.
Gut microbiome changes associated with chronic pancreatitis and pancreatic cancer: A systematic review and Meta-analysis
Authors: Jiaze Hong, Yufan Fu, Xiaoqian Chen, Yurui Zhang, Xinyi Li, Tianhang Li, Yilin Liu, Mengke Fan, Rong Lin
Journal: International Journal of Surgery (2024)

Background: The study of changes in the microbiome in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) holds significant potential for developing noninvasive diagnostic tools as well as innovative interventions to alter the progression of diseases. This systematic review and meta-analysis aimed to analyze in detail the taxonomic and functional characteristics of the gut microbiome in patients with CP and PDAC. Methods: Two researchers conducted a systematic search across public databases to gather all published research up to June 2023. Diversity and gut microbiota composition are the main outcomes the authors focus on. Results: This meta-analysis included 14 studies, involving a total of 1511 individuals in the PDAC ( n =285), CP ( n =342), and control ( n =649) groups. Our results show a significant difference in the composition of gut microbiota between PDAC/CP patients compared to healthy controls (HC), as evidenced by a slight decrease in α-diversity, including Shannon (SMD=−0.33; P =0.002 and SMD=−0.59; P &lt;0.001, respectively) and a statistically significant β-diversity ( P &lt;0.05). The pooled results showed that at the phylum level, the proportion of Firmicutes was lower in PDAC and CP patients than in HC patients. At the genus level, more than two studies demonstrated that four genera were significantly increased in PDAC patients compared to HC (e.g. Escherichia-Shigella and Veillonella ). CP patients had an increase in four genera (e.g. Escherichia-Shigella and Klebsiella ) and a decrease in eight genera (e.g. Coprococcus and Bifidobacterium ) compared to HC. Functional/metabolomics results from various studies also showed differences between PDAC/CP patients and HC. In addition, this study found no significant differences in gut microbiota between PDAC and CP patients. Conclusions: Current evidence suggests changes in gut microbiota is associated with PDAC/CP, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species. Further studies are needed to confirm these findings and explore therapeutic possibilities.
Not “all in the mind”
Authors: Tessa Richards
Journal: BMJ (2024)

unexplained symptoms" patients need supportive doctors who don't trivialise their problems, says Tessa Richards Tessa Richards associate editor 1, 2 Patients with persistent, severe, but medically unexplained physical symptoms baffle and frustrate doctors.Without a diagnosis they can't be put on established disease pathways and it's hard to know how best to manage them.Patients struggle with "unvalidated" illness and seek views from many different practitioners.Recently, a multidisciplinary group of clinicians and patients with an interest in "medically unexplained symptoms" (MUS) got together in London to shed light on a problem which deserves more attention than it gets.
Regulating the proinflammatory response to composite biomaterials by targeting immunometabolism
Authors: Chima V Maduka, Ashley V Makela, Anthony Tundo, Evran Ural, Katlin B Stivers, Maxwell M Kuhnert, Mohammed Alhaj, Ehsanul Hoque Apu, Nureddin Ashammakhi, Kurt D Hankenson, Ramani Narayan, Jennifer H Elisseeff, Christopher H Contag
Journal: Bioactive Materials (2024)
A qualitative inquiry into the lived experiences of menstrual health and hygiene in the transgender and non-binary people in urban areas of India
Authors: Priyanka Dubey, Muthusamy Sivakami, Shannon Lea Watkins, Kelly K. Baker, William T. Story, Rima A. Afifi
Journal: International Journal of Transgender Health (2024)

Significance Most global research on menstrual health and hygiene (MHH) focuses on cisgender women and girls, with limited evidence on the experiences of transgender and non-binary (TNB) people. This study aimed to document the lived experiences of menstruation management among TNB people in urban India.
Correction: TET2–STAT3–CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition
Authors: Yun Xue, Yuting Chen, Sijia Sun, Xinyuan Tong, Yujia Chen, Shijie Tang, Xue Wang, Simin Bi, Yuqin Qiu, Qiqi Zhao, Zhen Qin, Qin Xu, Yingjie Ai, Leilei Chen, Beizhen Zhang, Zhijie Liu, Minbiao Ji, Meidong Lang, Luonan Chen, Guoliang Xu, Liang Hu, Dan Ye, Hongbin Ji
Journal: The Journal of Experimental Medicine (2024)
Urine scRNAseq reveals new insights into the bladder tumor immune microenvironment
Authors: Michelle A. Tran, Dina Youssef, Sanjana Shroff, Disha Chowhan, Kristin G. Beaumont, Robert Sebra, Reza Mehrazin, Peter Wiklund, Jenny J. Lin, Amir Horowitz, Adam M. Farkas, Matthew D. Galsky, John P. Sfakianos, Nina Bhardwaj
Journal: The Journal of Experimental Medicine (2024)

Due to bladder tumors’ contact with urine, urine-derived cells (UDCs) may serve as a surrogate for monitoring the tumor microenvironment (TME) in bladder cancer (BC). However, the composition of UDCs and the extent to which they mirror the tumor remain poorly characterized. We generated the first single-cell RNA-sequencing of BC patient UDCs with matched tumor and peripheral blood mononuclear cells (PBMC). BC urine was more cellular than healthy donor (HD) urine, containing multiple immune populations including myeloid cells, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs) in addition to tumor and stromal cells. Immune UDCs were transcriptionally more similar to tumor than blood. UDCs encompassed cytotoxic and activated CD4+ T cells, exhausted and tissue-resident memory CD8+ T cells, macrophages, germinal-center-like B cells, tissue-resident and adaptive NK cells, and regulatory DCs found in tumor but lacking or absent in blood. Our findings suggest BC UDCs may be surrogates for the TME and serve as therapeutic biomarkers.
Evaluation of Treatment Outcomes of Prostate Cancer Patients With Lymph Node Metastasis Treated With Definitive Radiotherapy
Authors: Cem Onal, Ozan Cem Guler, Petek Erpolat, Pervin Hurmuz, Philip Sutera, Matthew P. Deek, Aysenur Elmali, Melek Tugce Yilmaz, Ummu Habibe Koken, Melek Yavuz, Gokhan Ozyigit, Phuoc T. Tran
Journal: Clinical Nuclear Medicine (2024)

Purpose We investigated the impact of prostate-specific membrane antigen (PSMA) PET/CT compared with conventional imaging on treatment outcomes for node-positive prostate cancer (PCa) patients who underwent androgen deprivation therapy (ADT) and external radiotherapy (RT). Patients and Methods A multicentric, retrospective study recruited patients with node-positive PCa patients who underwent conventional radiological evaluation or PSMA PET/CT and received ADT and RT at 3 hospitals from 2009 to 2021 were enrolled. Patients underwent prostate and pelvis RT, accompanied by a minimum of 6 months of ADT. The primary endpoints were progression-free survival (PFS) and PCa-specific survival (PCSS). Cox regression analyzed the association of survival with potential prognostic factors, whereas logistic regression identified the predictors of bone and lymph node metastasis. Results The median follow-up time was 64.0 months. The majority of patients (64.1%) underwent PSMA PET/CT for staging. The 5-year rates of PFS and PCSS were 63.7% and 83.7%, respectively. Disease progression was observed in 90 patients (36.3%). In multivariable analysis, ADT duration of less than 24 months and post-RT prostate-specific antigen (PSA) nadir were prognostic for PFS. Early clinical T stage and PSMA PET/CT predicted better PCSS. Patients staged with PSMA PET/CT had exhibited significantly higher 5-year PCSS rates than compared with those staged with conventional imaging (95.1% vs 76.9%; P = 0.01). Shorter ADT duration and higher PSA levels after RT independently predicted bone metastasis in multivariable logistic regression. Advanced T stage, shorter ADT duration, and higher PSA levels after neoadjuvant ADT predicted nonregional lymph node recurrence. Conclusions ADT with pelvis RT is an effective treatment option for node-positive PCa patients. The PSMA PET/CT outperformed conventional imaging in PCSS, emphasizing the importance of precise clinical staging for patients undergoing definitive RT.
Injectable Liposome‐Loaded Hydrogel Formulations with Controlled Release of Curcumin and <i>α</i>‐Tocopherol for Dental Tissue Engineering
Authors: Deniz Atila, Ali Deniz Dalgic, Agnieszka Krzemińska, Joanna Pietrasik, Edyta Gendaszewska‐Darmach, Dorota Bociaga, Magdalena Lipinska, Fouad Laoutid, Julie Passion, Vignesh Kumaravel
Journal: Advanced Healthcare Materials (2024)

An injectable hydrogel formulation is developed utilizing low- and high-molecular-weight chitosan (LCH and HCH) incorporated with curcumin and α-tocopherol-loaded liposomes (Lip/Cur+Toc). Cur and Toc releases are delayed within the hydrogels. The injectability of hydrogels is proved via rheological analyses. In vitro studies are conducted using human dental pulp stem cells (hDPSCs) and human gingival fibroblasts (hGFs) to examine the biological performance of the hydrogels toward endodontics and periodontics, respectively. The viability of hDPSCs treated with the hydrogels with Lip/Cur+Toc is the highest till day 14, compared to the neat hydrogels. During odontogenic differentiation tests, alkaline phosphatase (ALP) enzyme activity of hDPSCs is induced in the Cur-containing groups. Biomineralization is enhanced mostly with Lip/Cur+Toc incorporation. The viability of hGFs is the highest in HCH combined with Lip/Cur+Toc while wound healing occurs almost 100% in both (Lip/Cur+Toc@LCH and Lip/Cur+Toc@HCH) after 2 days. Antioxidant activity of Lip/Cur+Toc@LCH on hGFs is significantly the highest among the groups. Antimicrobial tests demonstrate that Lip/Cur+Toc@LCH is more effective against Escherichia coli whereas so is Lip/Cur+Toc@HCH against Staphylococcus aureus. The antimicrobial mechanism of the hydrogels is investigated for the first time through various computational models. LCH and HCH loaded with Lip/Cur+Toc are promising candidates with multi-functional features for endodontics and periodontics.
Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement
Authors: Brian P. Lee, Katie Witkiewitz, Jessica Mellinger, Frank A. Anania, Ramon Bataller, Thomas G. Cotter, Brenda Curtis, Srinivasan Dasarathy, Kelly S. DeMartini, Ivan Diamond, Nancy Diazgranados, Andrea F. DiMartini, Daniel E. Falk, Anne C. Fernandez, Margarita N. German, Patrick S. Kamath, Kelley M. Kidwell, Lorenzo Leggio, Raye Litten, Alexandre Louvet, Michael R. Lucey, Mary E. McCaul, Arun J. Sanyal, Ashwani K. Singal, Norman L. Sussman, Norah A. Terrault, Mark R. Thursz, Elizabeth C. Verna, Svetlana Radaeva, Laura E. Nagy, Mack C. Mitchell
Journal: Nature Reviews Gastroenterology & Hepatology (2024)

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions. Alcohol-associated liver disease is the main cause of liver-related morbidity and mortality globally. This Consensus Statement makes recommendations for the design, best practice and conduct of clinical trials to evaluate the effects of alcohol use in alcohol-associated liver disease and alcohol use disorder.