tbuckley/cabot-search huggingface dataset:
Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer’s disease
Authors: Elisabet A. Frick, Valur Emilsson, Thorarinn Jonmundsson, Anna E. Steindorsdottir, Erik C. B. Johnson, Raquel Puerta, Eric B. Dammer, Anantharaman Shantaraman, Amanda Cano, Mercè Boada, Sergi Valero, Pablo García-González, Elias F. Gudmundsson, Alexander Gudjonsson, Rebecca Pitts, Xiazi Qiu, Nancy Finkel, Joseph J. Loureiro, Anthony P. Orth, Nicholas T. Seyfried, Allan I. Levey, Agustin Ruiz, Thor Aspelund, Lori L. Jennings, Lenore J. Launer, Valborg Gudmundsdottir, Vilmundur Gudnason
Journal: Nature Aging (2024)

A deeper understanding of the molecular processes underlying late-onset Alzheimer's disease (LOAD) could aid in biomarker and drug target discovery. Using high-throughput serum proteomics in the prospective population-based Age, Gene/Environment Susceptibility-Reykjavik Study (AGES) cohort of 5,127 older Icelandic adults (mean age, 76.6 ± 5.6 years), we identified 303 proteins associated with incident LOAD over a median follow-up of 12.8 years. Over 40% of these proteins were associated with LOAD independently of APOE-ε4 carrier status, were implicated in neuronal processes and overlapped with LOAD protein signatures in brain and cerebrospinal fluid. We identified 17 proteins whose associations with LOAD were strongly dependent on APOE-ε4 carrier status, with mostly consistent associations in cerebrospinal fluid. Remarkably, four of these proteins (TBCA, ARL2, S100A13 and IRF6) were downregulated by APOE-ε4 yet upregulated due to LOAD, a finding replicated in external cohorts and possibly reflecting a response to disease onset. These findings highlight dysregulated pathways at the preclinical stages of LOAD, including those both independent of and dependent on APOE-ε4 status.
Circular RNAs in tumor immunity and immunotherapy
Authors: Wenjie Zhang, Chen Xu, Zhipeng Yang, Jingshi Zhou, Wei Peng, Xuan Zhang, Haimin Li, Shibin Qu, Kaishan Tao
Journal: Molecular Cancer (2024)

Circular RNAs (circRNAs) are unique noncoding RNAs that have a closed and stable loop structure generated through backsplicing. Due to their conservation, stability and tissue specificity, circRNAs can potentially be used as diagnostic indicators and therapeutic targets for certain tumors. Many studies have shown that circRNAs can act as microRNA (miRNA) sponges, and engage in interactions with proteins and translation templates to regulate gene expression and signal transduction, thereby participating in the occurrence and development of a variety of malignant tumors. Immunotherapy has revolutionized the treatment of cancer. Early researches have indicated that circRNAs are involved in regulating tumor immune microenvironment and antitumor immunity. CircRNAs may have the potential to be important targets for increasing sensitivity to immunotherapy and expanding the population of patients who benefit from cancer immunotherapy. However, few studies have investigated the correlation between circRNAs and tumor immunity. In this review, we summarize the current researches on circRNAs involved in antitumor immune regulation through different mechanisms and their potential value in increasing immunotherapy efficacy with the goal of providing new targets for cancer immunotherapy.
Magnetic Foreign Bodies of the Gastrointestinal Tract in a Child. Clinical Observations
Authors: E. B. Olkhova, K. A. Shchedrina
Journal: Radiology - Practice (2024)

Background . Ingestion of magnetic foreign bodies (MFBs) in pediatric practice has become common in recent years due to the prevalence of toys containing magnets. Ingestion of one small MFB rarely causes damage to the gastrointestinal tract (GIT). However, with the non-simultaneous ingestion of multiple MFBs, there is a risk of complications (intestinal perforation, formation of infiltrate, development of intestinal obstruction, peritonitis), which determines the importance of accurate diagnosis and active surgical tactics for patient management. Objective. Demonstration of the capabilities of ultrasound diagnostics in detecting fixed MFBs of the digestive tract in children. Materials and Methods . Two clinical observations of MFBs are presented: in the first case, the absence of passage of MFBs through the GIT in an 8-year-old child was the reason for a targeted ultrasound search for magnets with determination of their localization. In the second case, in a 2.5-year-old girl, long-standing MFBs in the GIT simulated the clinical picture of celiac disease due to the formation of gastrointestinal fistulas. The children underwent X-ray examination and ultrasound. Results . In the first case, echographically it was possible to clearly differentiate the location of MFBs in the lumen of the colon; in the second case, fixed MFBs were echographically differentiated in the upper parts of the abdominal cavity. Complex radiological diagnostics made it possible to optimize the tactics of patient management: in the first case, MFBs were successfully removed during colonoscopy; in the second observation, endoscopic removal of 3 MFBs from the stomach and laparoscopic removal of 24 MFBs from the small intestine and large intestine and separation of interintestinal anastomoses were performed. Both children recovered. Conclusion . Ultrasound can be recommended as an additional diagnostic method for MFBs of the digestive tract in children to clarify the localization of MFBs and assess complications. Performing an ultrasound is advisable after an X-ray examination, when the approximate localization of MFBs is known.
Selected Aspects of Radiation Diagnostics of Complications of Breast Plastic Surgery (Literature Review with Own Observations)
Authors: N. V. Klimova, A. A. Kuznetsov
Journal: Radiology - Practice (2024)

Aim. To demonstrate the possibilities of radiation examination of late complications of some types of cosmetic breast surgery. Materials and methods . A few clinical examples demonstrate certain types of late complications of aesthetic breast surgery. Conclusion. It is advisable to carry out a preoperative examination in a specialized medical and diagnostic institution in compliance with all the canons of early diagnosis of breast cancer. Cases of breast cancer omissions at the pre- and postoperative stages of aesthetic surgery require further investigation.
Radiation Semiotics of Genetic Forms of Medulloblastomas
Authors: G. V. Tereshchenko, A. E. Drui, L. I. Papusha, I. N. Pronin
Journal: Radiology - Practice (2024)

Objective. To determine a possible assessment of the verification of the genetic group of medulloblastomas based on MRI imaging and quantitative assessment indicators. Materials and Methods . MRI data of 60 patients with a verified molecular genetic subgroup based on the expression level of selected genes on the Nano String platform were retrospectivel analyzed. Results. Based on MRI signs of the shape and contrast intensity of the tumor, taking into account the age of the patients, 76 % of medulloblastomas were correctly identified by genetic groups. Conclusion . The ability to predict the genetic group of the disease in children with medulloblastoma during an initial MRI study with an accuracy of 76 % seems to us important and relevant. Only the first steps have been taken in the development of radiogenomics of medulloblastomas in children. The classification of CNS tumors with the molecular subgroups of medulloblastomas has allowed modern pediatric oncological practice to apply a differentiated approach to stratification of risk groups and prognosis of the disease. This affects the determination of the scope and the tactics of treatment. The aim of our study was an attempt to systematize and definition the diagnostic radiological signs of the currently known four molecular subgroups of medulloblastomas in children. Thirty-nine (76%) patients diagnosed with medulloblastoma were correctly classified into genetic groups based on radiographic features of shape, contrast intensity, and patient age.
Prognostic Significance of Diffusion-Weighted Imaging and ASL-Perfusion in Evaluation the Progression of Chronic Kidney Disease
Authors: Yu. Yu. Shkuratova, T. G. Morozova, T. D. Gel’t
Journal: Radiology - Practice (2024)

Objective. To determinate the significance of diffusion-weighted imaging and ASL-perfusion in evaluation the progression of chronic kidney disease. Materials and methods . The study included 77 patients with chronic kidney disease: 34 (44.2 %) men and 43 (55.8 %) women. All subjects underwent Magnetic Resonance Imaging of the kidneys, with the inclusion of diffusion-weighted imaging (DWI) and ASL (arterial spinal label) perfusion in the research protocol. These results helped divide the patients into three groups. The comparison group included 61 healthy people. Results. There is statistically significant difference data in DWI and ASL perfusion between patients with CKD and the comparison group. The comparison group has the next counts: no diffusion restriction, ADC is 4.8 ± 0.1 × 10-3 mm2 /s, ASL-perfusion is 482–496 ml/100 g/min. The first group has no diffusion restriction, ADC is 1–4 × 10-3 mm2 /s, ASL-perfusion is 390–436 ml/100 g/min, the second group has no diffusion restriction, ADC is more than 4 × 10-3 mm2 /s and ASL-perfusion 294–402 ml/100 g/min. The third group has diffusion restriction with different ADC and ASL-perfusion. Conclusion . Absence of diffusion restriction, ADC is 1–4 × 10-3 mm2 /s, ASL-perfusion is 390–436 ml/100 g/min is indication of the beginning of injury to intact nephrons, the stage of hyperfiltration (r = 0,973). Absence of diffusion restriction, ADC is more than 4 × 10-³ mm2 /s and ASL-perfusion 294–402 ml/100 g /min is risk of metabolic disorders in CKD (r = 0,981). If it has diffusion restriction with different ADC and ASL-perfusion, there is high correlation with CKD stage 3b (r = 0.923) and hypokalemia (r = 0.988). DWI and ASL perfusion must be included in the examination algorithm for patients with CKD to create a personalized diagnostic and treatment algorithm.
Experience of Using of the Additional Submillimeter Mode 3D-FSE (3D-PD-FS-WI) in MRI of Complete and Partial Tears of the Shoulder Supraspinatus Tendon (Clinical Case)
Authors: A. P. Ivankov, P. V. Seliverstov, D. V. Menshova
Journal: Radiology - Practice (2024)

A clinical example is presented that demonstrates the capabilities of an additional magnetic resonance 3D-FSE (3D-PD-FS-WI) of complete and partial ruptures of the supraspinatus tendon of the shoulder. The article provides an MRI protocol that allows for successful diagnosis of these rupture types. Aim. Demonstration of the diagnostic capabilities of the additional submillimeter isotropic mode 3D-FSE (3D-PD-FS-WI) in the MRI diagnosis of complete and partial tears of the supraspinatus tendon. Clinical case. A clinical case of the successful use of submillimeter isotropic 3D-FSE mode (3D-PD-FS-WI) in a patient with a rupture of the supraspinatus tendon is demonstrated. Conclusion . The 3D-FSE (3D-PD-FS-WI) mode demonstrated: excellent detailing of the rupture zone, the ability to assess pathology in any plane using a 3D cursor and more suitable «showing» of pathology in the desired plane.
Decongestion in acute heart failure: Is it time to change diuretic‐centred paradigm?
Authors: Jan Biegus, Gad Cotter, Marco Metra, Piotr Ponikowski
Journal: European Journal of Heart Failure (2024)

Abstract Congestion is a common cause of clinical deterioration and the most common clinical presentation at admission in acute heart failure (HF). Therefore, finding effective and sustainable ways to alleviate congestion has become a crucial goal for treating HF patients. Congestion is a result of complex underlying pathophysiology; therefore, it is not a direct cause of the disease but its consequence. Any therapy that directly promotes sodium/water removal only, thus targeting only clinical symptoms, neither modifies the natural course of the disease nor improves prognosis. This review aims to provide a comprehensive evaluation of the current decongestive therapies and propose a new (not diuretic‐centred) paradigm of long‐term congestion management in HF that attempts to correct the underlying pathophysiology, thus improving congestion, preventing its development, and favourably altering the natural course of the disease rather than merely treating its symptoms.
Breast Cancer Screening Interval: Effect on Rate of Late-Stage Disease at Diagnosis and Overall Survival
Authors: Margarita L. Zuley, Andriy I. Bandos, Stephen W. Duffy, Durwin Logue, Rohit Bhargava, Priscilla F. McAuliffe, Adam M. Brufsky, Robert M. Nishikawa
Journal: Journal of Clinical Oncology (2024)

PURPOSE Controversy continues regarding the effect of screening mammography on breast cancer outcomes. We evaluated late-stage cancer rate and overall survival (OS) for different screening intervals using a real-world institutional research data mart. METHODS Patients having both a cancer registry record of new breast cancer diagnosis and prediagnosis screening history between 2004 and 2019 were identified from our institutional research breast data mart. Time interval between the two screening mammograms immediately preceding diagnosis and the time to cancer diagnosis were determined. Screening interval was deemed annual if ≤15 months, biennial if &gt;15 and ≤27 months, intermittent if &gt;27 months, and baseline if only one prediagnosis screen was known. The primary end point was late-stage cancer (TNM stage IIB or worse), and the secondary end point was OS. The association of screening interval and late-stage cancer was analyzed using multivariable logistic regression adjusting for prediagnosis characteristics. Proportional hazards regression was used for survival analysis. Potential lead time was analyzed using survival from a uniform fixed time point. RESULTS In total, 8,145 patients with breast cancer had prediagnosis screening mammography in the timeframe. The percentage of late-stage cancers diagnosed increased significantly with screening interval with 9%, 14%, and 19% late stages for annual, biennial, and intermittent groups ( P &lt; .001), respectively. The trend persisted regardless of age, race, and menopausal status. Biennial and intermittent groups had substantially worse OS than the annual screened group, with relative hazards of 1.42 (95% CI, 1.11 to 1.82) and 2.69 (95% CI, 2.11 to 3.43), respectively, and 1.39 (95% CI, 1.08 to 1.78) and 2.01 (95% CI, 1.58 to 2.55) after adjustment for potential lead time. CONCLUSION Annual mammographic screening was associated with lower risk of late-stage cancer and better OS across clinical and demographic subgroups. Our study suggests benefit of annual screening for women 40 years and older.
Human Leukocyte Antigen Mismatching and Survival in Contemporary Hematopoietic Cell Transplantation for Hematologic Malignancies
Authors: Esteban Arrieta-Bolaños, Edouard F. Bonneville, Pietro Crivello, Marie Robin, Tobias Gedde-Dahl, Urpu Salmenniemi, Nicolaus Kröger, Ibrahim Yakoub-Agha, Charles Crawley, Goda Choi, Annoek E.C. Broers, Edouard Forcade, Martin Carre, Xavier Poiré, Anne Huynh, Stig Lenhoff, Fabio Ciceri, Eleni Tholouli, Thomas Schroeder, Eric Deconinck, Kristina Carlson, Liesbeth C. de Wreede, Jorinde D. Hoogenboom, Florent Malard, Annalisa Ruggeri, Katharina Fleischhauer
Journal: Journal of Clinical Oncology (2024)

PURPOSE Human leukocyte antigen (HLA) mismatching can reduce survival of patients with blood cancer after hematopoietic cell transplantation (HCT). How recent advances in HCT practice, in particular graft-versus-host disease (GVHD) prophylaxis by post-transplantation cyclophosphamide (PTCy), influence HLA risk associations is unknown. PATIENTS AND METHODS The study included 17,292 unrelated HCTs with 6-locus high-resolution HLA typing, performed mainly for acute leukemia or related myeloid neoplasms between 2016 and 2020, including 1,523 transplants with PTCy. HLA risk associations were evaluated by multivariable Cox regression models, with overall survival (OS) as primary end point. RESULTS OS was lower in HLA mismatched compared with fully matched transplants (hazard ratio [HR], 1.23 [99% CI, 1.14 to 1.33]; P &lt; .001). This was driven by class I HLA-A, HLA-B, HLA-C (HR, 1.29 [99% CI, 1.19 to 1.41]; P &lt; .001) but not class II HLA-DRB1 and HLA-DQB1 (HR, 1.07 [99% CI, 0.93 to 1.23]; P = .19). Class I antigen-level mismatches were associated with worse OS than allele-level mismatches (HR, 1.36 [99% CI, 1.24 to 1.49]; P &lt; .001), as were class I graft-versus-host peptide-binding motif (PBM) mismatches compared with matches (HR, 1.42 [99% CI, 1.28 to 1.59]; P &lt; .001). The use of PTCy improved GVHD, relapse-free survival compared with conventional prophylaxis in HLA-matched transplants (HR, 0.77 [0.66 to 0.9]; P &lt; .001). HLA mismatching increased mortality in PTCy transplants (HR, 1.32 [1.04 to 1.68]; P = .003) similarly as in non-PTCy transplants (interaction P = .43). CONCLUSION Class I but not class II HLA mismatches, especially at the antigen and PBM level, are associated with inferior survival in contemporary unrelated HCT. These effects are not significantly different between non-PTCy compared with PTCy transplants. Optimized HLA matching should still be considered in modern HCT.
Pattern and extent of intrahepatic infiltration of perihilar cholangiocarcinoma - A case-control study based on liver panoramic digital pathology
Authors: Shuo Jin, Nan Jiang, Jing-Min Zhao, Ying Xiao, Si-Yuan Wang, Can-Hong Xiang, Qian Lu, Si-Qiao Shan, Hao-Tian Ruan, Shao-Qing Yu, Jian-Ping Zeng, Shi-Zhong Yang, Li Li, Jia-Hong Dong
Journal: International Journal of Surgery (2024)

Background: The extent of intrahepatic infiltration of perihilar cholangiocarcinoma (PHCC) remains unclear. This research aimed to explore the pattern and extent of intrahepatic infiltration of PHCC to guide surgical treatment and pathological research. Materials and Methods: This study included 62 patients diagnosed with PHCC who underwent major hepatectomy. A whole-mount digital liver pathology system (WDLPS) for hepatectomy specimens greater than 10 × 10 cm was used to panoramically assess the intrahepatic infiltration extent of PHCC. Results: The distal intrahepatic infiltration (DIHI) and radial liver invasion (RLI) were important parts of intrahepatic infiltration for PHCC explored by WDLPS. The study confirmed that 75.8% of PHCCs had RLI and the infiltration distance in all patients were within 15,000 µm, 62.9% of PHCCs had DIHI greater than 1 cm away from the main tumor in liver parenchyma. The recurrence-free survival rates and overall survival rates of patients with DIHI were poorer than the patients without DIHI (P＜0.0001, P =0.0038). Arterial invasion on the resected side could be an excellent predictor. A total of 105 liver lobes were resected from 62 PHCC patients. The invasion rates of the left lateral, left medial, right anterior, and right posterior lobe of PHCC were 79%, 100, 100%, and 69% respectively. Conclusion: The presence of DIHI in most PHCCs was a significant predictor of poor postoperative recurrence and survival. Based on the extent of intrahepatic infiltration, minor hepatectomy was not suitable as the curative surgery for PHCC. Major hepatectomy and liver transplantation were the ideal radical treatment.
Unraveling the Genetic Susceptibility of Irritable Bowel Syndrome: integrative genome-wide analyses in 845,492 individuals: a diagnostic study
Authors: Wentao Huang, Lijun Zhang, Yuying Ma, Shiyi Yu, Yanlin Lyu, Shuangshuang Tong, Jiaxuan Wang, Rui Jiang, Meijun Meng, Yanjun Wu, Ruibang Luo, Xinqi Qiu, Weihong Sha, Hao Chen
Journal: International Journal of Surgery (2024)

Background: Irritable bowel syndrome (IBS) significantly impacts individuals due to its prevalence and negative effect on quality of life. Current genome-wide association studies (GWAS) have only identified a small number of crucial single nucleotide polymorphisms (SNPs), not fully elucidating IBS’s pathogenesis. Objective: To identify genomic loci at which common genetic variation influence IBS susceptibility. Methods: Combining independent cohorts that in total comprise 65,840 cases of IBS and 788,652 controls, we performed a meta-analysis of genome-wide association studies (GWAS) of IBS. We also carried out gene mapping and pathway enrichment to gain insights into the underlying genes and pathways through which the associated loci contribute to disease susceptibility. Furthermore, we performed transcriptome analysis to deepen our understanding. IBS risk models were developed by combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. We detect the phenotype association for IBS utilizing PRS-based phenome-wide association (PheWAS) analyses, linkage disequilibrium score regression, and Mendelian randomization. Results: The GWAS meta-analysis identified 10 IBS risk loci, seven of which were novel (rs12755507, rs34209273, rs34365748, rs67427799, rs2587363, rs13321176, rs1546559). Multiple methods identified nine promising IBS candidate gene ( PRRC2A, COP1, CADM2, LRP1B, SUGT1, MED12L, P2RY14, PHF2, SHISA6 ) at 10 GWAS loci. Transcriptome validation also revealed differential expression of these genes. Phenome-wide associations between PRS-IBS and nine traits (neuroticism, diaphragmatic hernia, asthma, diverticulosis, cholelithiasis, depression, insomnia, COPD, and BMI) were identified. The six diseases (asthma, diaphragmatic hernia, diverticulosis, insomnia major depressive disorder and neuroticism) were found to show genetic association with IBS and only major depressive disorder and neuroticism were found to show causality with IBS. Conclusion: We identified seven novel risk loci for IBS and highlight the substantial influence on genetic risk harboured. Our findings offer novel insights into aetiology and phenotypic association of IBS and lay the foundation for therapeutic targets and interventional strategies.
Genomic landscape of gallbladder cancer: insights from whole exome sequencing
Authors: Supriya Awasthi, Rahul Kumar, Dibyabhaba Pradhan, Neetu Rawal, Harsh Goel, Parameswar Sahu, Sandeep Sisodiya, Rashmi Rana, Sunil Kumar, Nihar Ranjan Dash, Prasenjit Das, Usha Agrawal, GK Rath, Tanvir Kaur, RS Dhaliwal, Showket Hussain, Sundeep Singh Saluja, Pranay Tanwar
Journal: International Journal of Surgery (2024)

Gallbladder cancer (GBC) is a common gastrointestinal malignancy noted for its aggressive characteristics and poor prognosis, which is mostly caused by delayed detection. However, the scarcity of information regarding somatic mutations in Indian patients with GBC has hampered the development of efficient therapeutic options. In the present study, the authors attempted to bridge this gap by revealing the mutational profile of GBC.