tbuckley/cabot-search huggingface dataset:
Infrahyoid Myocutaneous Flap for Reconstruction in Head and Neck Cancer Patients
Authors: Vikas Sharma, Gandhi Ajeet, Nidhi Anand, Rastogi Madhup, Sandhya Pandey, Sethi Rohini, Vikas Sharma
Journal: International Journal of Surgery (2024)

Objective: Oral cancers are one of the most common cancers in India. Tongue and lower gingiva-buccal sulcus are the most common subsites in oral cancers. Good reconstruction after resection of primary is a demanding task and determines quality of life. This study reviews our experience with infrahyoid flap (IHF) in reconstruction of small and medium sized defects after oral cancer resection. Materials and Methods: This study retrospectively analyzes all patients of oral cavity squamous cell carcinoma who underwent IHF flap by a single surgeon from July 2018 till June 2022 with a median follow‑up of 12 months. Results were analyzed based on characteristics of the patients, site and size of defect, postoperative complications and clinical outcome. Results: Out of 14 patients, 4 patients had skin paddle necrosis (2 total and 2 partial). None of the patient suffered a total flap loss. All cases of partial flap loss resolved with conservative treatment and none of the patient required a revision surgery or developed orocutaneous fistula. The largest flap size was 9 × 4.5 cm. Conclusion: The infrahyoid myocutaneous flap is a fairly reliable and easy to perform flap for small and medium‑sized defects of the oral cavity.
Incidental discovery of <i>KIT</i>‐mutated mastocytoma in a colon polyp
Authors: Naseema Gangat, Ellen McPhail, Kaaren Reichard, Attilio Orazi, Animesh Pardanani, Ayalew Tefferi
Journal: American Journal of Hematology (2024)

Mastocytoma in a colon polyp positive for tryptase, CD117/KIT, S100, weakly positive for CD25. No relevant conflicts to disclose. The data that support the findings of this study are available on request from the corresponding author.
Mitochondrial CISD1/Cisd accumulation blocks mitophagy and genetic or pharmacological inhibition rescues neurodegenerative phenotypes in Pink1/parkin models
Authors: Aitor Martinez, Alvaro Sanchez-Martinez, Jake T. Pickering, Madeleine J. Twyning, Ana Terriente-Felix, Po-Lin Chen, Chun-Hong Chen, Alexander J. Whitworth
Journal: Molecular Neurodegeneration (2024)

Abstract Background Mitochondrial dysfunction and toxic protein aggregates have been shown to be key features in the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease (PD). Functional analysis of genes linked to PD have revealed that the E3 ligase Parkin and the mitochondrial kinase PINK1 are important factors for mitochondrial quality control. PINK1 phosphorylates and activates Parkin, which in turn ubiquitinates mitochondrial proteins priming them and the mitochondrion itself for degradation. However, it is unclear whether dysregulated mitochondrial degradation or the toxic build-up of certain Parkin ubiquitin substrates is the driving pathophysiological mechanism leading to PD. The iron-sulphur cluster containing proteins CISD1 and CISD2 have been identified as major targets of Parkin in various proteomic studies. Methods We employed in vivo Drosophila and human cell culture models to study the role of CISD proteins in cell and tissue viability as well as aged-related neurodegeneration, specifically analysing aspects of mitophagy and autophagy using orthogonal assays. Results We show that the Drosophila homolog Cisd accumulates in Pink1 and parkin mutant flies, as well as during ageing. We observed that build-up of Cisd is particularly toxic in neurons, resulting in mitochondrial defects and Ser65-phospho-Ubiquitin accumulation. Age-related increase of Cisd blocks mitophagy and impairs autophagy flux. Importantly, reduction of Cisd levels upregulates mitophagy in vitro and in vivo, and ameliorates pathological phenotypes in locomotion, lifespan and neurodegeneration in Pink1/parkin mutant flies. In addition, we show that pharmacological inhibition of CISD1/2 by rosiglitazone and NL-1 induces mitophagy in human cells and ameliorates the defective phenotypes of Pink1/parkin mutants. Conclusion Altogether, our studies indicate that Cisd accumulation during ageing and in Pink1/parkin mutants is a key driver of pathology by blocking mitophagy, and genetically and pharmacologically inhibiting CISD proteins may offer a potential target for therapeutic intervention. Graphical Abstract
Correction to: TAL1 hijacks MYCN enhancer that induces MYCN expression and dependence on mevalonate pathway in T-cell acute lymphoblastic leukemia
Authors: Shi Hao Tan, Tze King Tan, Rui Yokomori, Minghui Liao, Xiao Zi Huang, Allen Eng Juh Yeoh, Takaomi Sanda
Journal: Leukemia (2024)
CD4+ T cells with latent HIV-1 have reduced proliferative responses to T cell receptor stimulation
Authors: Joshua T. Kufera, Ciara Armstrong, Fengting Wu, Anushka Singhal, Hao Zhang, Jun Lai, Hannah N. Wilkins, Francesco R. Simonetti, Janet D. Siliciano, Robert F. Siliciano
Journal: The Journal of Experimental Medicine (2024)

The latent reservoir for HIV-1 in resting CD4+ T cells persists despite antiretroviral therapy as a barrier to cure. The antigen-driven proliferation of infected cells is a major mechanism of reservoir persistence. However, activation through the T cell antigen receptor (TCR) can induce latent proviruses, leading to viral cytopathic effects and immune clearance. In single-cell studies, we show that, relative to uninfected cells or cells with a defective provirus, CD4+ T cells with an intact provirus have a profound proliferative defect in response to TCR stimulation. Virion production was observed in only 16.5% of cultures with an intact provirus, but proliferation was reduced even when no virion production was detected. Proliferation was inversely correlated with in vivo clone size. These results may reflect the effects of previous in vivo proliferation and do not support attempts to reduce the reservoir with antiproliferative agents, which may have greater effects on normal T cell responses.
Predicting operative time for metabolic and bariatric surgery using machine learning models: a retrospective observational study
Authors: Dong-Won Kang, Shouhao Zhou, Suman Niranjan, Ann Rogers, Chan Shen
Journal: International Journal of Surgery (2024)

Background: Predicting operative time is essential for scheduling surgery and managing the operating room. This study aimed to develop machine learning (ML) models to predict the operative time for metabolic and bariatric surgery (MBS) and to compare each model. Methods: The authors used the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database between 2016 and 2020 to develop ML models, including linear regression, random forest, support vector machine, gradient-boosted tree, and XGBoost model. Patient characteristics and surgical features were included as variables in the model. The authors used the mean absolute error, root mean square error, and R 2 score to evaluate model performance. The authors identified the 10 most important variables in the best-performing model using the Shapley Additive exPlanations algorithm. Results: In total, 668 723 patients were included in the study. The XGBoost model outperformed the other ML models, with the lowest root mean square error and highest R 2 score. Random forest performed better than linear regression. The relative performance of the ML algorithms remained consistent across the models, regardless of the surgery type. The surgery type and surgical approach were the most important features to predict the operative time; specifically, sleeve gastrectomy (vs. Roux-en-Y gastric bypass) and the laparoscopic approach (vs. robotic-assisted approach) were associated with a shorter operative time. Conclusions: The XGBoost model best predicted the operative time for MBS among the ML models examined. Our findings can be useful in managing the operating room scheduling and in developing software tools to predict the operative times of MBS in clinical settings.
Suicidal Thoughts and Trajectories of Psychopathological and Behavioral Symptoms in Adolescence
Authors: Akito Uno, Daiki Nagaoka, Satoshi Usami, Satoshi Yamaguchi, Rin Minami, Riki Tanaka, Yutaka Sawai, Ayako Okuma, Syudo Yamasaki, Mitsuhiro Miyashita, Atsushi Nishida, Kiyoto Kasai, Shuntaro Ando
Journal: JAMA Network Open (2024)

Importance The suicidal risk of psychopathology in adolescence is suggested to differ based on its longitudinal trajectory, but the comorbidity of these symptom trajectories has not been well examined. This study comprehensively clustered trajectories of multiple psychopathological and behavioral symptoms and examined their associations with suicidal thoughts in adolescence. Objective To determine which categories and trajectories of psychopathological and behavioral symptoms are associated with suicidal thoughts in adolescence, accounting for comorbid symptoms. Design, Setting, and Participants This population-based cohort study in Japan used data from the Tokyo Teen Cohort (TTC) study, which was established in 2012 and is currently ongoing. Data from 3 waves of surveys conducted at ages 10, 12, and 16 years from October 2012 to September 2021 were used. Of the adolescents in the cohort, participants with at least 2 evaluations of psychopathological and behavioral symptoms were included. Data were analyzed from December 2022 to March 2023. Exposure Latent class growth analysis was used to cluster the trajectory of each psychopathological and behavioral symptom. Main Outcomes and Measures The associations between symptom trajectories and suicidal thoughts at age 16 were examined. Suicidal thoughts were assessed using a self-report questionnaire. Psychopathological and behavioral symptoms were assessed using the 8 subscale scores of the caregiver-report Child Behavior Checklist. Results This study included 2780 adolescents (1306 female participants [47.0%]). Of the 1920 adolescents with data on suicidal thoughts, 158 (8.2%) had suicidal thoughts. The median (IQR) age was 10.2 (10.0-10.3) years at the first evaluation, 11.9 (11.8-12.1) years at the second evaluation, and 16.3 (16.1-16.5) years at the last evaluation. The clustering pattern of trajectories varied depending on symptom categories. After adjusting for each symptom trajectory and confounders, adolescents with persistent high withdrawn symptoms (odds ratio [OR], 1.88; 95% CI, 1.10-3.21) and those with increasing somatic symptoms (OR, 1.97; 95% CI, 1.16-3.34) had a significantly higher risk of suicidal thoughts than adolescents without these symptoms. There was no interaction between these symptom trajectories and the risk of suicidal thoughts. Conclusions and Relevance This cohort study found that persistent withdrawn symptoms and increasing somatic symptoms during early to midadolescence were associated with an increased risk of suicidal thoughts in midadolescence, even after accounting for comorbid symptoms and confounders. Attention should be paid to the suicidal risk associated with these symptoms, particularly when they persist or increase in the longitudinal follow-up.
Mismatch repair protein MLH1 suppresses replicative stress in BRCA2-deficient breast tumors
Authors: Satheesh K. Sengodan, Xiaoju Hu, Vaishnavi Peddibhotla, Kuppusamy Balamurugan, Alexander Y. Mitrophanov, Lois McKennett, Suhas S. Kharat, Rahul Sanawar, Vinod Kumar Singh, Mary E. Albaugh, Sandra S. Burkett, Yongmei Zhao, Bao Tran, Tyler Malys, Esta Sterneck, Subhajyoti De, Shyam K. Sharan
Journal: Journal of Clinical Investigation (2024)

Loss of BRCA2 (breast cancer 2) is lethal for normal cells. Yet it remains poorly understood how, in BRCA2 mutation carriers, cells undergoing loss of heterozygosity overcome the lethality and undergo tissue-specific neoplastic transformation. Here, we identified mismatch repair gene mutL homolog 1 (MLH1) as a genetic interactor of BRCA2 whose overexpression supports the viability of Brca2-null cells. Mechanistically, we showed that MLH1 interacts with Flap endonuclease 1 (FEN1) and competes to process the RNA flaps of Okazaki fragments. Together, they restrained the DNA2 nuclease activity on the reversed forks of lagging strands, leading to replication fork (RF) stability in BRCA2-deficient cells. In these cells, MLH1 also attenuated R-loops, allowing the progression of stable RFs, which suppressed genomic instability and supported cell viability. We demonstrated the significance of their genetic interaction by the lethality of Brca2-mutant mice and inhibition of Brca2-deficient tumor growth in mice by Mlh1 loss. Furthermore, we described estrogen as inducing MLH1 expression through estrogen receptor α (ERα), which might explain why the majority of BRCA2 mutation carriers develop ER-positive breast cancer. Taken together, our findings reveal a role of MLH1 in relieving replicative stress and show how it may contribute to the establishment of BRCA2-deficient breast tumors.
Public Attitudes Toward Ethics and Practices in End-of-Life Decision-Making for Neonates
Authors: Katja Schneider, Stephanie Roll, Tatjana Tissen-Diabaté, Christoph Bührer, Lars Garten
Journal: JAMA Network Open (2024)

Importance Attitudes toward end-of-life decision-making in neonatology have been studied in physicians and other health care professionals and are mostly shaped by their clinical education and work experiences. In contrast, attitudes among the general public have not yet been investigated. Objective To assess (1) attitudes in the general public toward euthanasia and withdrawal of life-prolonging treatment in neonates with severe life-limiting conditions, (2) knowledge of current German recommendations, and (3) values in the German society regarding ethical issues and proxy decisions at the beginning of life. Design, Setting, and Participants This cross-sectional study was performed in Germany and used an exploratory design to analyze responses to an interview conducted by an independent, established commissioned polling institute in March and April 2022. Participants were 16 years or older, with German language fluency and comprehension and living in Germany. Main Outcomes and Measures Knowledge about recommendations for euthanasia and withdrawal of life-prolonging treatment as well as personal attitudes toward (1) euthanasia and withdrawal of life-prolonging treatment and (2) surrogate end-of-life decision-making for newborn infants were assessed. Results The study included 2116 participants (1077 females [50.9%]; mean [SD] age 52.1 [18.7] years). Of the participants, 16.8% (311 of 1851) reported knowing the German recommendations for euthanasia and withdrawal of life-prolonging treatment for neonates. Euthanasia and withdrawal of life-prolonging treatment were supported by 64.7% (1369 of 2116) and 77.9% (1649 of 2116) of respondents, respectively. Shared decision-making between parents and physicians for neonates in end-of-life situations was supported by 65.6% of participants (1388). In situations where shared decision-making was not possible, 73.4% of respondents (1019 of 1388) put the ultimate decision to the parents. The magnitude of the associations was low between sociodemographic factors and views on ethical issues and customary practices involved in end-of-life decisions for neonates. Conclusions and Relevance Results of this cross-sectional study suggested that most respondents were not aware of the national German recommendations for euthanasia and withdrawal of life-prolonging treatment for sick and extremely preterm newborns. When counseling parents of periviable newborns, clinicians may need to exert more effort in explaining the legal and ethical framework; a highly individualized approach is warranted.
Cost-Effectiveness of Fractional Flow Reserve–Guided Complete Revascularization in Acute Myocardial Infarction—Tipping the Scales?
Authors: Rebecca C. Chester, William F. Fearon, Rushi V. Parikh
Journal: JAMA Network Open (2024)

David Hong, MD; Seung Hun Lee, MD; Jin Lee, MPH; Hankil Lee, PhD; Doosup Shin, MD; Hyun Kuk Kim, MD; Keun Ho Park, MD; Eun Ho Choo, MD; Chan Joon Kim, MD; Min Chul Kim, MD; Young Joon Hong, MD; Myung Ho Jeong, MD, PhD; Sung Gyun Ahn, MD; Joon-Hyung Doh, MD; Sang Yeub Lee, MD; Sang Don Park, MD; Hyun-Jong Lee, MD; Min Gyu Kang, MD; Jin-Sin Koh, MD; Yun-Kyeong Cho, MD; Chang-Wook Nam, MD; Ki Hong Choi, MD; Taek Kyu Park, MD; Jeong Hoon Yang, MD; Young Bin Song, MD; Seung-Hyuk Choi, MD; Hyeon-Cheol Gwon, MD; Eliseo Guallar, MD, PhD; Juhee Cho, PhD; Joo-Yong Hahn, MD; Danbee Kang, PhD; Joo Myung Lee, MD, MPH, PhD; FRAME-AMI Investigators
The BMJ Appeal 2023-24: Gaza’s mothers and babies need your help
Authors: Mun-Keat Looi
Journal: BMJ (2024)

This baby in an incubator at al-Aqsa Martyrs' Hospital in the Gaza strip's central city Deir al-Balah on 12 January faces the danger of death, like most premature babies in Gaza, who can't get the health services they need because of power outages in hospitals caused by fuel shortages.
Efficacy of Tixagevimab-Cilgavimab as Immunoprophylaxis in Patients With Hematologic Cancer
Authors: Marco Salvini, Paolo Antonio Grossi, Alessandro Cacioppo, Michele Merli, Giacomo Pellegrini, Marco Brociner, Francesco Passamonti
Journal: JAMA Oncology (2024)

This cohort study compares outcomes for patients with hematologic malignant tumors who prophylactically received tixagevimab-cilgavimab against SARS-CoV-2 with those who did not.
Comprehensive assessment of immune context and immunotherapy response via noninvasive imaging in gastric cancer
Authors: Zepang Sun, Taojun Zhang, M. Usman Ahmad, Zixia Zhou, Liang Qiu, Kangneng Zhou, Wenjun Xiong, Jingjing Xie, Zhicheng Zhang, Chuanli Chen, Qingyu Yuan, Yan Chen, Wanying Feng, Yikai Xu, Lequan Yu, Wei Wang, Jiang Yu, Guoxin Li, Yuming Jiang
Journal: Journal of Clinical Investigation (2024)

BACKGROUND. The tumor immune microenvironment can provide prognostic and therapeutic information. We aimed to develop noninvasive imaging biomarkers from computed tomography (CT) for comprehensive evaluation of immune context, and investigate their associations with prognosis and immunotherapy response in gastric cancer (GC).
p40 homodimers bridge ischemic tissue inflammation and heterologous alloimmunity in mice via IL-15 transpresentation
Authors: Hidetoshi Tsuda, Karen S. Keslar, William M. Baldwin, Peter S. Heeger, Anna Valujskikh, Robert L. Fairchild
Journal: Journal of Clinical Investigation (2024)

Virus-induced memory T cells often express functional cross-reactivity, or heterologous immunity, to other viruses and to allogeneic MHC molecules that is an important component of pathogenic responses to allogeneic transplants. During immune responses, antigen-reactive naive and central memory T cells proliferate in secondary lymphoid organs to achieve sufficient cell numbers to effectively respond, whereas effector memory T cell proliferation occurs directly within the peripheral inflammatory microenvironment. Mechanisms driving heterologous memory T cell proliferation and effector function expression within peripheral tissues remain poorly understood. Here, we dissected proliferation of heterologous donor-reactive memory CD8+ T cells and their effector functions following infiltration into heart allografts with low or high intensities of ischemic inflammation. Proliferation within both ischemic conditions required p40 homodimer-induced IL-15 transpresentation by graft DCs, but expression of effector functions mediating acute allograft injury occurred only in high-ischemic allografts. Transcriptional responses of heterologous donor-reactive memory CD8+ T cells were distinct from donor antigen-primed memory CD8+ T cells during early activation in allografts and at graft rejection. Overall, the results provide insights into mechanisms driving heterologous effector memory CD8+ T cell proliferation and the separation between proliferation and effector function that is dependent on the intensity of inflammation within the tissue microenvironment.
Significantly Higher 68Ga-FAPI Than 18F-FDG Uptake by Hidradenocarcinoma of Head and Neck on PET/CT
Authors: Haoyuan Ding, Yudi Wang, Juan Liang, Ya Liu, Yue Chen
Journal: Clinical Nuclear Medicine (2024)

Abstract Hidradenocarcinoma is quite rare in clinical practice. Herein, we describe the 68 Ga-FAPI and 18 F-FDG PET/CT findings of hidradenocarcinoma of the head and neck in a 75-year-old man. In the present case, the primary tumor and secondary lesions showed intense accumulation of 68 Ga-FAPI but only slight 18 F-FDG uptake. This case demonstrates that 68 Ga-FAPI PET/CT might be used as a helpful tool for evaluating hidradenocarcinoma.
FDG-Avid Periprosthetic Particle Disease Mimicking Osteosarcoma Recurrence
Authors: Ziqian Dong, Ziyu Guo, Meichao Guan, Yingjie Zhang, Peng Xie
Journal: Clinical Nuclear Medicine (2024)

Abstract A 24-year-old man with a history of osteosarcoma presented with swelling in his right thigh for more than 1 year. 18 F-FDG PET/CT demonstrated increased FDG uptake in multiple juxtacortical masses around the prosthesis, which highly suggested the possibility of osteosarcoma recurrence. A biopsy was performed, and the pathology confirmed the diagnosis of particle disease. The current case indicates that particle disease should be considered when interpreting the PET/CT images with high FDG uptake around the prosthesis.
Pulmonary Amyloidoma Imitating Lung Cancer on 18F-FDG PET/CT
Authors: Tatjana Leike, Teodor Svantesson, Fabrizio Minervini, Ujwal Bhure, Hannes Grünig
Journal: Clinical Nuclear Medicine (2024)

Abstract Localized pulmonary amyloidosis forming a solitary mass known as “amyloidoma of the lung” is rare. Differentiation from lung cancer can be difficult due to suspicious features on CT and high 18 F-FDG uptake. We present a case of a 77-year-old woman with an incidental lung lesion on abdominal CT. Further evaluation with chest CT and 18 F-FDG PET/CT maintained the suspicion of lung cancer. However, histology revealed amyloidoma without signs of malignancy. Knowledge of imaging similarities between pulmonary amyloidomas and malignancies is important for interpreting 18 F-FDG PET/CT of lung tumors; however, only biopsy can confirm the rare differential diagnosis such as pulmonary amyloidoma.
False-Positive Metastatic Bone Disease on FDG PET/CT Due to Multilevel Tophaceous Gout of the Spine
Authors: Anna Drazyk, Han Loh, Chuong Bui, Pei Ding, Robert Mansberg
Journal: Clinical Nuclear Medicine (2024)

Abstract A 74-year-old woman was referred for 18 F-FDG PET/CT for the evaluation of incidental CT finding of expansile destruction of left L4/5 facet joint with associated soft tissue mass concerning for a metastatic deposit. The FDG PET/CT revealed variable abnormally increased FDG activity involving multiple facet joints in all regions of the spine with corresponding expansile “punched-out” lytic lesions with sclerotic rims and overhanging margins on CT, raising the possibility of inflammatory polyarthropathy, including gout, as a differential diagnosis. Dual-energy CT of lumbar spine and CT-guided biopsy and culture of the left L4/5 facet joint demonstrated the presence of urate crystal deposition with no evidence of malignancy or infection, confirming the diagnosis of multilevel tophaceous gout of the spine.
Pattern of Bone Marrow Hypometabolism on 18F-FDG PET CT in Systemic Lupus Erythematous–Associated Aplastic Anemia
Authors: Alexandra Dudek, Saima Riaz, Dimitrios Priftakis, Jamshed Bomanji
Journal: Clinical Nuclear Medicine (2024)

Abstract We present the case of a 23-year-old woman with juvenile onset systemic lupus erythematous on a background of thrombotic thrombocytopenic purpura, who was referred for 18 F-FDG PET CT scan due to pyrexia of unknown origin with raised inflammatory markers, severe thrombocytopenia, and anemia. An interesting pattern of predominantly photopenic hypometabolic bone marrow activity was demonstrated on 18 F-FDG PET CT.