tbuckley/cabot-search huggingface dataset:
Characteristics of metabolic syndrome in the servicemen with erosive esophagitis in wartime conditions
Authors: L.M. Mosiychuk, O.M. Shevtsova, O.M. Tatarchuk, O.P. Petishko
Journal: GASTROENTEROLOGY (2024)

Background. Among the well-known factors contribu­ting to the prevalence of erosive esophagitis, the leading one is an increase in the number of individuals with obesity and insulin resistance. The assessment of metabolic syndrome in the servicemen of the Armed Forces of Ukraine with erosive esopha­gitis in wartime conditions is of particular importance, as the effectiveness of their professional activities depends on it. The purpose of the study: to evaluate the body composition and insulin resistance in the servicemen of the Armed Forces of Ukraine with erosive esophagitis, taking into account the level of the stress index, exhaustion and adaptative capacity of the body. Materials and me­thods. The study included 24 men aged 33 to 57 years, the average age was (42.7 ± 2.1) years. All military personnel were assessed for maladjustment, increased cardiovascular risk, anxiety, and fatigue using the cardiorhythmography method based on the ana­lysis of heart rate variability on the CONTEC8000GW system. Body composition was assessed using Tanita MC-780МА (Japan) scales-analyzers whose mechanism is based on the technique of bioimpedance analysis with computer processing. Insulin resistance was evaluated using the HOMA-IR index, for the calculation of which the level of insulin was determined by enzyme-linked immunosorbent assay systems of the Xema company (Ukraine) on the Stat Fax 303 Plus analyzer (USA). Results. According to precise diagnostics, half of the servicemen of the Armed Forces of Ukraine with erosive esophagitis were diagnosed with vegetative imbalance, which was manifested by an increase in the stress index in 37.5 % of cases, a disruption or violation of adaptation in 25.0 %, and exhaustion of the body in 54.2 % of cases. The HOMA-IR index was 1.5 times higher (p = 0.006) compared to that of the control group. 37.5 % of the servicemen of the Armed Forces of Ukraine with erosive esophagitis showed signs of metabolic syndrome. Correlation analysis revealed relationship of heart rate variability with body composition indicators (body mass index, fat mass, and amount of visceral fat). In addition, an increase in insulin resistance is associated with an increase in the stress index and cardiovascular risk, as well as a decrease in the adaptive capacity of the body and its exhaustion. Conclusions. The correlations found between indicators of heart rate variability, insulin resistance and body composition will allow for the development of a personalized approach to the management of the servicemen of the Armed Forces of Ukraine with erosive esophagitis.
Post-translational histone modifications associated with the development of metabolic dysfunction-associated fatty liver disease. Part 2. Histone methylation
Authors: O.E. Abaturov, A.O. Nikulina
Journal: GASTROENTEROLOGY (2024)

Based on the analysis of literary sources of databa­ses Pubmed, MEDLINE, The Cochrane Library, Embase, the authors highlight the essential role of epigenetic modulations in the pathogenesis of metabolic dysfunction-associated fatty liver disease. They give general provisions regarding post-translational histone modifications, which are associated with the development of metabolic dysfunction-associated fatty liver disease, namely, the features of their methylation, post-translational modifications of methylation of lysine residues (sites H3K4, H3K27, H3K36, H3K79, H4K20, H3K23, H3K63 and H4K12), arginine residues (sites H2AR3, H4R3, H3R2, H3R8 and H3R26). Histone methy­lation and demethylation, mediating the expression of key genes involved in carbohydrate and lipid metabolism, determine both the occurrence and development of steatosis, inflammation and fibrosis of the liver in patients with metabolic dysfunction-­associated fatty liver disease. Methylated markers H3K9, H3K27, H4K20 of histones are associated with packed heterochromatin and repression of gene transcription, while methylated markers H3K4, H3K36, H3K79 of histones are associated with activation of gene transcription. Methylation of lysine or arginine residues of histones is carried out by methyltransferases that use S-adenosylmethionine as a donor molecule. The methylated site of an arginine residue can be represented by a monomethylated, asymmetrically demethylated, or symmetrically demethylated marker, whereas demethylation of a lysine marker is mediated by demethylases. The authors provide data that in metabolic dysfunction-associated fatty liver disease, the main sites in which aberrant methylation is observed are H3K4, H3K9, H3K27, H4R3, H3R8, and H2AR3. Several genes of histone methyltransferases and histone demethylases have been identified, which are differentially expressed in patients with metabolic dysfunction-associated fatty liver disease and healthy people. The authors emphasize that the enzymes involved in the histone methylation and demethylation are targets of future drugs, which will certainly improve the effectiveness of drug therapy in patients with metabolic dysfunction-associated fatty liver disease.
MEGA12: Molecular Evolutionary Genetic Analysis version 12 for adaptive and green computing
Authors: Sudhir Kumar, Glen Stecher, Michael Suleski, Maxwell Sanderford, Sudip Sharma, Koichiro Tamura
Journal: Molecular Biology and Evolution (2024)

Abstract We introduce the 12th version of the Molecular Evolutionary Genetics Analysis (MEGA12) software. This latest version brings many significant improvements by reducing the computational time needed for selecting optimal substitution models and conducting bootstrap tests on phylogenies using maximum likelihood (ML) methods. These improvements are achieved by implementing heuristics that minimize likely unnecessary computations. Analyses of empirical and simulated datasets show substantial time savings by using these heuristics without compromising the accuracy of results. MEGA12 also links-in an evolutionary sparse learning approach to identify fragile clades and associated sequences in evolutionary trees inferred through phylogenomic analyses. In addition, this version includes fine-grained parallelization for ML analyses, support for high-resolution monitors, and an enhanced Tree Explorer. MEGA12 can be downloaded from https://www.megasoftware.net.
Application of Ultrasound Localization Microscope in Evaluating the Type 2 Diabetes Progression
Authors: Tao Zhang, Jipeng Yan, Xinhuan Zhou, Bihan Wu, Chao Zhang, Mengxing Tang, Pintong Huang
Journal: Cyborg and Bionic Systems (2024)

Type 2 diabetes is considered as a chronic inflammatory disease in which the dense microvasculature reorganizes with disease progression and is highly correlated with β cell mass and islet function. In this study, we constructed rat models of type 2 diabetes and used ultrasound localization microscopy (ULM) imaging to noninvasively map the pancreatic microvasculature at microscopy resolution in vivo to reflect β cell loss and islet function deterioration, and evaluate the efficacy after anti-cytokine immunotherapy. It was unveiled that ULM morphological and hemodynamic parameters have a strong link with β cell loss and deterioration of pancreatic islet function. This correlation aligns with the observed pathological alterations in the microvessels of islet and demonstrated that ULM can effectively mirror the functionality of β cells during rapid fluctuations in blood glucose levels by observing changes in mean velocity. Furthermore, it was revealed that treatment with anti-cytokine immunotherapy enhances the function and health of β cells by restoring the microvascular environment. Remarkable improvements in vessel morphology (measured by fractal dimension) and hemodynamics (indicated by mean velocity and vessel density) were noted following the anti-cytokine immunotherapy, signifying a significant enhancement at the treatment’s conclusion ( P &lt; 0.05). These observations suggested that ULM technology holds promise as a visible and efficient tool for monitoring the effectiveness of anti-cytokine immunotherapy in managing type 2 diabetes. Pancreatic microvessel-based ULM may serve as a novel noninvasive method to assess β cells, providing a valuable clinical tool for tracking the progression of type 2 diabetes.
Towards Cyborg: Exploring Long-term Clinical Outcomes of a Multi-DOF Myoelectric Prosthetic Hand
Authors: Yuki Kuroda, Yusuke Yamanoi, Hai Jiang, Yoshiko Yabuki, Yuki Inoue, Dianchun Bai, Yinlai Jiang, Jinying Zhu, Hiroshi Yokoi
Journal: Cyborg and Bionic Systems (2024)

Recent advancements in robotics and sensor technology have facilitated the development of myoelectric prosthetic hands (MPHs) featuring multiple degrees of freedom and heightened functionality, but their practical application has been limited. In response to this situation, formulating a control theory ensuring the hand dexterity of highly functional MPHs has garnered marked attention. Progress in this field has been directed toward employing machine-learning algorithms to process electromyogram patterns, enabling a broad spectrum of hand movements. In particular, the practical application of 5-finger-driven MPHs with such control functions to real users remains limited, and their attributes and challenges have not been thoroughly examined. In this study, we developed a 5-finger MPH equipped with pattern recognition capabilities. Through a long-term clinical trial, encompassing task assessments and subjective evaluations via questionnaires, we explored the MPH's range of applications. The task assessments revealed an expanded range of achievable tasks as the variety of motions increased. However, this enhanced adaptability was paralleled by a decrease in control reliability. Additionally, findings from the questionnaires indicated that enhancements in task performance with MPHs might be more effective in reducing workplace-related disability than in improving activities in everyday life. This study offers valuable insights into the long-term clinical prospects and constraints associated with multi-degree-of-freedom MPHs incorporating pattern recognition functionality.
Smart Design of Targeted Drug Delivery System for Precise Drug Delivery and Visual Treatment of Brain Gliomas
Authors: Baoqin Song, Mengru Wu, Lijing Qin, Wanjun Liang, Xiu Wang
Journal: Advanced Healthcare Materials (2024)

Abstract In the treatment of glioma, which is one of the malignant tumors, although chemotherapy is used as the most common treatment method, it often suffers from low bioavailability. Therefore, improving the precision and efficiency of drugs is crucial in treating gliomas and a great challenge. Here, an advanced drug delivery system is reported for gliomas (CZQD@HA@DOX), which aggregates multiple features such as the susceptible imaging tracer property due to the use of CZQD and the targeting of HA to the receptor cluster 44 (CD44) of glioma cells, which provides the system with the functions of targeted enrichment and precise drug delivery at the tumor site. The pH‐responsive drug delivery system has not only an excellent encapsulation rate but also a high drug loading capacity, and the doxorubicin loaded on it can be released centrally at the tumor microenvironment site and causes an increase of reactive oxygen species in the mitochondria and trigger oxidative stress, which leads to high expression of Bax apoptotic proteins, ultimately activating the mitochondrial pathway‐mediated apoptotic process in glioma cells. Overall, this drug delivery system has great potential for application in precision targeted therapy and visual tracer imaging of gliomas.
Recent Advances in Microfluidics for Nucleic Acid Analysis of Small Extracellular Vesicles in Cancer
Authors: Sareh Zhand, Dale Mark Goss, Yuen Yee Cheng, Majid Ebrahimi Warkiani
Journal: Advanced Healthcare Materials (2024)

Small extracellular vesicles (sEVs) are membranous vesicles released from cellular structures through plasma membrane budding. These vesicles contain cellular components such as proteins, lipids, mRNAs, microRNAs, long-noncoding RNA, circular RNA, and double-stranded DNA, originating from the cells they are shed from. Ranging in size from ≈25 to 300 nm and play critical roles in facilitating cell-to-cell communication by transporting signaling molecules. The discovery of sEVs in bodily fluids and their involvement in intercellular communication has revolutionized the fields of diagnosis, prognosis, and treatment, particularly in diseases like cancer. Conventional methods for isolating and analyzing sEVs, particularly their nucleic acid content face challenges including high costs, low purity, time-consuming processes, limited standardization, and inconsistent yield. The development of microfluidic devices, enables improved precision in sorting, isolating, and molecular-level separation using small sample volumes, and offers significant potential for the enhanced detection and monitoring of sEVs associated with cancer. These advanced techniques hold great promise for creating next-generation diagnostic and prognostic tools given their possibility of being cost-effective, simple to operate, etc. This comprehensive review explores the current state of research on microfluidic devices for the detection of sEV-derived nucleic acids as biomarkers and their translation into practical point-of-care and clinical applications.
Silk Fibroin Hydrogel for Pulse Waveform Precise and Continuous Perception
Authors: Yingmei Yan, Weijun Deng, Du Xie, Jing Hu
Journal: Advanced Healthcare Materials (2024)

Precise and continuous monitoring of blood pressure and cardiac function is of great importance for early diagnosis and timely treatment of cardiovascular diseases. The common tests rely on on-site diagnosis and bulky equipments, hindering early diagnosis. The emerging hydrogels have gained considerable attention in skin bioelectronics by virtue of the similarities to biological tissues and versatility in mechanical, electrical, and biofunctional engineering. However, hydrogels should overcome intrinsic issues such as poor mechanical strength, easy dehydration and freezing, weak adhesiveness and self-recovery, severely limiting their precision and reliability in practical applications. Here, silk fibroin hydrogels are developed as resistive sensors for pulse waveform monitoring. The silk fibroin hydrogel is simultaneously transparent, extremely stretchable, extra tough, adhesive, printable, and environmentally endurable. The silk fibroin hydrogel is also conductive with high sensitivity, short self-healing time, highly repeatable and reliable response, meeting the requirements for wearable sensors for continuous monitoring. The sensors with silk fibroin hydrogel present high-quality and stable waveforms of radical and brachial pulses with high precision and rich features, providing physiological signals of blood pressure and cardiac function. The sensors are promising for personalized health management, daily monitoring and timely diagnosis.
Pilot study of topical ruxolitinib demonstrates efficacy and blunting of heterogeneous inflammatory processes in mild hidradenitis suppurativa
Authors: Stephanie L Schell, Mackenzie L Sennett, Robert P Feehan, Tierney E Wallace, Elizabeth C Meiszberg, Amy L Longenecker, Matthew F Helm, Joslyn S Kirby, Amanda M Nelson
Journal: British Journal of Dermatology (2024)

Abstract Background Therapeutic options for mild hidradenitis suppurativa (HS) represent a significant gap in the current treatment landscape, with no FDA approved therapies for early stage HS. Topical JAnus Kinase inhibitors (JAKi) are a compelling option due to the known upregulation of inflammatory JAK signaling in HS lesions and the recent success of systemic JAKi for moderate to severe HS. Objectives This is a pilot, single-site, open-label, prospective 24-week clinical trial with topical ruxolitinib (NCT04414514). The goals of this study were to assess clinical efficacy in a pilot cohort and investigate the underlying biological mechanisms associated with clinical response. Methods Male and female patients with mild HS (Hurley stage I or II), with active inflammatory nodules, were recruited. All subjects were observed for 8 weeks to monitor lesion counts (observational phase), then proceeded with active therapy (treatment phase) for 16 weeks. 1.5% topical ruxolitinib cream was applied twice daily, covering the entirety of each HS-affected body site. Clinician and patient reported outcome measures were recorded throughout the study. Lesional skin punch biopsies were obtained at the start and end of therapy for downstream mechanistic RNA-seq and histological analyses. Results Ten subjects enrolled in this study, four subjects dropped out of the study before the treatment phase of the trial. Six individuals with Hurley stage I (no tunnels) completed the entire study, with five of six successfully achieving HiSCR through 16 weeks of therapy. In this interim analysis, differential gene expression and gene set enrichment analyses revealed reduced activation of JAK-dependent IFN, IL-6, IL-2, and EGFR signaling, antimicrobial responses, and keratinocyte responses. In contrast, signatures of wound healing and lipid metabolism were increased following JAKi treatment, indicating a return toward homeostasis. Histological analyses revealed that clinically-responsive patients had significantly reduced epidermal and dermal inflammation. Affected inflammatory infiltrate included neutrophils, T cells, and plasma cells, with the predominantly affected cell types specific to the patient. Conclusions Collectively, the broad activity of topical ruxolitinib on inflammatory signaling processes resulted in promising efficacy, even with heterogeneity in baseline inflammation, in this pilot cohort. Importantly, topical treatment not only resolved epidermal inflammation, but also cleared deeper inflammatory infiltrate. The efficacy observed in this trial provides rationale to further investigate topical JAKi and other novel topical therapies in HS.
Faecal metaproteomics analysis reveals a high cardiovascular risk profile across healthy individuals and heart failure patients
Authors: Chaoran Yang, Leticia Camargo Tavares, Han-Chung Lee, Joel R. Steele, Rosilene V. Ribeiro, Anna L. Beale, Stephanie Yiallourou, Melinda J. Carrington, David M. Kaye, Geoffrey A. Head, Ralf B. Schittenhelm, Francine Z. Marques
Journal: Gut Microbes (2024)

The gut microbiota is a crucial link between diet and cardiovascular disease (CVD). Using fecal metaproteomics, a method that concurrently captures human gut and microbiome proteins, we determined the crosstalk between gut microbiome, diet, gut health, and CVD. Traditional CVD risk factors (age, BMI, sex, blood pressure) explained < 10% of the proteome variance. However, unsupervised human protein-based clustering analysis revealed two distinct CVD risk clusters (low-risk and high-risk) with different blood pressure (by 9 mmHg) and sex-dependent dietary potassium and fiber intake. In the human proteome, the low-risk group had lower angiotensin-converting enzymes, inflammatory proteins associated with neutrophil extracellular trap formation and auto-immune diseases. In the microbial proteome, the low-risk group had higher expression of phosphate acetyltransferase that produces SCFAs, particularly in fiber-fermenting bacteria. This model identified severity across phenotypes in heart failure patients and long-term risk of cardiovascular events in a large population-based cohort. These findings underscore multifactorial gut-to-host mechanisms that may underlie risk factors for CVD.
Krebs von den Lungen-6 surveillance in immune checkpoint inhibitor-induced pneumonitis
Authors: Ryosuke Matsukane, Shoji Nakamura, Haruna Minami, Kazuya Tsubouchi, Yasuto Yoneshima, Kojiro Hata, Sai Yasukochi, Kimitaka Suetsugu, Isamu Okamoto, Takeshi Hirota
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background The immune-related adverse event (irAE), pneumonitis, is a potentially fatal complication of immune checkpoint inhibitors (ICIs). Preventing its progression is crucial, emphasizing the need for effective screening tests. We evaluated the feasibility of using Krebs von den Lungen-6 (KL-6), a marker for interstitial pneumonitis, as a screening tool for pneumonitis. Methods We examined 500 patients with cancer divided into two groups: those with cancer other than non-small cell lung cancer (NSCLC) (Group 1, n=382) and those with NSCLC (Group 2, n=118). KL-6 levels were monitored before and during ICI treatment and analyzed for their correlation with pneumonitis. Results In Group 1, 37 patients (9.7%) developed pneumonitis. KL-6 levels were significantly elevated at irAE onset (pre: 222.0 U/mL, post: 743.0 U/mL, p&lt;0.0001). Receiver operating characteristic curve analysis showed an area under the curve (AUC) of 0.903 (sensitivity 81.1%, specificity 91.6%) with a cut-off value 1.52 times pre-KL-6 levels, indicating that KL-6 is a reliable biomarker for pneumonitis. In these patients, the KL-6 level increased regardless of pneumonitis severity and was significantly elevated in patients with both symptomatic (pre: 205.0 U/mL, post: 674.5 U/mL, p&lt;0.0001) and asymptomatic pneumonitis (pre: 314.0 U/mL, post: 743.0 U/mL, p&lt;0.0001) at irAE onset. After irAE treatment, KL-6 levels in steroid-responsive patients remained unchanged; however, steroid-unresponsive patients had a significant increase in KL-6 levels at 1 month (1078 U/mL, p=0.031) compared with at irAE onset (678.0 U/mL). In Group 2, 24 patients (20.3%) developed irAE pneumonitis, with KL-6 levels elevated (pre: 360.5 U/mL, post: 506.5 U/mL, p=0.029) and an AUC of 0.683, indicating that KL-6 was less reliable in patients with NSCLC. Conclusions KL-6 is a viable screening biomarker in ICI-induced pneumonitis, particularly in patients without NSCLC. In patients with NSCLC, the significance of KL-6 monitoring is limited as it is not effective for detecting ICI-induced pneumonitis; their treatment is typically managed by pulmonary specialists. Early detection through KL-6 monitoring facilitates timely intervention for ICI-induced pneumonitis, potentially preventing treatment interruptions and reducing the need for immunosuppressants.
Oncolytic vaccinia virus armed with anti-CD47 nanobody elicit potent antitumor effects on multiple tumor models via enhancing innate and adoptive immunity
Authors: Zengpeng Li, Mengyuan Li, Liu Yang, Jie Chen, Qian Ye, Wenbin Qian, Shibing Wang
Journal: Journal for ImmunoTherapy of Cancer (2024)

Objective Targeting CD47 for cancer immunotherapy has been studied in many clinical trials for the treatment of patients with advanced tumors. However, this therapeutic approach is often hampered by on-target side effects, physical barriers, and immunosuppressive tumor microenvironment (TME). Methods To improve therapeutic efficacy while minimizing toxicities, we engineered an oncolytic vaccinia virus (OVV) encoding an anti-CD47 nanobody (OVV-αCD47nb). We demonstrated the specific binding activity of αCD47nb secreted from the virus-infected cells to CD47 and that both secreted αCD47nb and OVV-αCD47nb blocked the “don’t eat me” signal of macrophages. Results Intratumorally injected OVV-αCD47nb continuously releases the αCD47nb in tumor tissues, thereby conferring superior systemic activity against breast and colon tumor cells and prolonging survival compared with OVV control. Furthermore, treatment with OVV-αCD47nb also remodeled the TME, as shown by increased T cell infiltration, CD8 + T cell activation and tumor-associated macrophages polarization, significantly enhancing innate and adoptive immunity. Additionally, the inclusion of programmed cell death protein-1 inhibiting boosted the anticancer efficacy of OVV-αCD47nb and raised the full response rate in tumor-bearing animals. Conclusion Overall, our findings highlight the therapeutic potential of OVV-αCD47nb for breast and colon cancer, and demonstrate its ability to modulate the immune cell profiles within tumors. This has established a rationale for further exploring OVV-αCD47nb as a potential therapy in the clinic.