tbuckley/cabot-search huggingface dataset:
Online cognitive monitoring technology for people with Parkinson’s disease and REM sleep behavioural disorder
Authors: Maria Bălăeţ, Falah Alhajraf, Tanja Zerenner, Jessica Welch, Jamil Razzaque, Christine Lo, Valentina Giunchiglia, William Trender, Annalaura Lerede, Peter J. Hellyer, Sanjay G. Manohar, Paresh Malhotra, Michele Hu, Adam Hampshire
Journal: npj Digital Medicine (2024)

Abstract Automated online cognitive assessments are set to revolutionise clinical research and healthcare. However, their applicability for Parkinson’s Disease (PD) and REM Sleep Behavioural Disorder (RBD), a strong PD precursor, is underexplored. Here, we developed an online battery to measure early cognitive changes in PD and RBD. Evaluating 19 candidate tasks showed significant global accuracy deficits in PD (0.65 SD, p = 0.003) and RBD (0.45 SD, p = 0.027), driven by memory, language, attention and executive underperformance, and global reaction time deficits in PD (0.61 SD, p = 0.001). We identified a brief 20-min battery that had sensitivity to deficits across these cognitive domains while being robust to the device used. This battery was more sensitive to early-stage and prodromal deficits than the supervised neuropsychological scales. It also diverged from those scales, capturing additional cognitive factors sensitive to PD and RBD. This technology offers an economical and scalable method for assessing these populations that can complement standard supervised practices.
Hypothalamic Inflammation Improves Through Bariatric Surgery, and Hypothalamic Volume Predicts Short-Term Weight Loss Response in Adults With or Without Type 2 Diabetes
Authors: Adriana Pané, Laura Videla, Àngels Calvet, Judith Viaplana, Lídia Vaqué-Alcázar, Ainitze Ibarzabal, Mateus Rozalem-Aranha, Jordi Pegueroles, Violeta Moize, Josep Vidal, Emilio Ortega, Isabel Barroeta, Valle Camacho, Gemma Chiva-Blanch, Juan Fortea, Amanda Jiménez
Journal: Diabetes Care (2024)

Preclinical research implicates hypothalamic inflammation (HI) in obesity and type 2 diabetes pathophysiology. However, their pathophysiological relevance and potential reversibility need to be better defined. We sought to evaluate the effect of bariatric surgery (BS) on radiological biomarkers of HI and the association between the severity of such radiological alterations and post-BS weight loss (WL) trajectories. The utility of cerebrospinal fluid large extracellular vesicles (CSF-lEVs) enriched for microglial and astrocyte markers in studying HI was also explored.
Impaired Awareness of Hypoglycemia in Older Adults With Type 1 Diabetes: A Post Hoc Analysis of the WISDM Study
Authors: Anika Bilal, Fanchao Yi, Keri Whitaker, Daria Igudesman, Richard Pratley, Anna Casu
Journal: Diabetes Care (2024)

OBJECTIVE Up to one-third of older adults with type 1 diabetes experience impaired awareness of hypoglycemia (IAH), yet the factors associated with IAH remain underexplored in older adults. RESEARCH DESIGN AND METHODS This post hoc analysis evaluated the clinical and glycemic correlates of IAH in adults ≥60 years old with type 1 diabetes in the WISDM study. IAH and normal awareness of hypoglycemia (NAH) were defined by a Clarke score of ≥4 or &amp;lt;4, respectively. Demographic, clinical, and glycemic metrics were compared in those with IAH and NAH at baseline and in whom IAH did or did not improve over 26 weeks, using descriptive statistics and a multiple logistic regression variable selection procedure. RESULTS Of the 199 participants (age 68.1 ± 5.7 years, 52% female), 30.6% had IAH. At baseline, participants with IAH had a longer diabetes duration and greater daytime hypoglycemia and glycemic variability, and more participants had nondetectable C-peptide levels than those with NAH. Logistic regression associated longer diabetes duration (odds ratio [OR] 1.03, 95% CI 1.01–1.05; P = 0.008) and greater daytime hypoglycemia (OR 1.31, 95% CI, 1.15–1.51; P &amp;lt; 0.0001) with a greater odds of IAH. A similar modeling procedure identified less daytime hypoglycemia (OR per additional percentage point 0.55, 95% CI 0.32–0.94; P = 0.029) and shorter diabetes duration (OR per additional year 0.96, 95% CI 0.91–1.004; P = 0.07) as predictors of restored awareness at 26 weeks, although the effect size for diabetes duration was not statistically significant. CONCLUSIONS In older adults with type 1 diabetes, longer diabetes duration and greater daytime hypoglycemia are drivers of IAH. Dedicated research can personalize IAH management.
Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation
Authors: Weize Zhu, Ying Hong, Zhaowei Tong, Xiaofang He, Yan Li, Hao Wang, Xinxin Gao, Pengtao Song, Xianshan Zhang, Xiaochang Wu, Zhenhua Tan, Wenjin Huang, Zekun Liu, Yiyang Bao, Junli Ma, Ningning Zheng, Cen Xie, Xisong Ke, Wen Zhou, Wei Jia, Mingxiao Li, Jing Zhong, Lili Sheng, Houkai Li
Journal: Cell Reports Medicine (2024)
Probable extinction of influenza B/Yamagata and its public health implications: a systematic literature review and assessment of global surveillance databases
Authors: Saverio Caini, Adam Meijer, Marta C Nunes, Laetitia Henaff, Malaika Zounon, Bronke Boudewijns, Marco Del Riccio, John Paget
Journal: The Lancet Microbe (2024)
Approach to patients with positive vertical margins after endoscopic resection of Barrett’s neoplasia
Authors: Sachin Wani
Journal: Endoscopy (2024)

Endoscopic eradication therapy (EET) has revolutionized the management of Barrett's esophagus (BE)-related neoplasia (patients with early esophageal adenocarcinoma [EAC], high grade dysplasia [HGD], and select cases with low grade dysplasia), reducing the morbidity and mortality related to esophagectomy and preventing EAC-related mortality [1] [2] [3]. The basic principles of EET include endoscopic resection (ER) using endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for any visible lesion (technique of ER ideally based on lesion characteristics), followed by ablation of the remaining BE epithelium to reduce the risk of metachronous neoplasia. The goal of EET should be complete eradication of intestinal metaplasia and complete eradication of neoplasia, followed by enrollment in endoscopic surveillance programs for early detection of BE-related neoplasia recurrence. ER plays a pivotal role in both the management of patients with BE-related neoplasia and the overall success of any EET program. ER specimens routinely undergo histopathological assessment for overall highest grade of neoplasia, depth of neoplastic invasion, tumor differentiation, lymphovascular invasion, and tumor/dysplasia involvement of lateral and vertical margins. It is expected that the number of patients with a tumor-positive vertical margin (R1v) will increase given the expanding indications of EET and increased overall uptake of this management strategy for this patient population. While current guidelines recommend consideration of adjunct surgery in patients with R1v, this recommendation is based on minimal data describing outcomes and risk of residual neoplasia after R1v. Should all patients with R1v undergo esophagectomy? What is the risk of residual neoplasia in patients with R1v on follow-up endoscopy or surgical specimens after esophagectomy?
Snare traction-assisted endoscopic submucosal dissection for removal of rare giant laryngeal liposarcoma
Authors: Rui Zhao, Jiaxin Yan, Ye-Han Zhou, Yu Bao, Yan Zhang
Journal: Endoscopy (2024)

A 78-year-old man presented with a foreign body sensation in the throat for 1 year. Endoscopy revealed a large pedunculated tumor in the throat, extending deep into the mid-thoracic esophagus ([Fig. 1]). Computed tomography (CT) of the throat showed a column-like region with a density similar to fat located within the larynx and esophageal entrance to the mid-thoracic lumen, without significant contrast enhancement ([Fig. 2]).
Emerging trends and future challenges of advanced 2D nanomaterials for combating bacterial resistance
Authors: Saima Hameed, Sumaira Sharif, Muhammad Ovais, Hai Xiong
Journal: Bioactive Materials (2024)

The number of multi-drug-resistant bacteria has increased over the last few decades, which has caused a detrimental impact on public health worldwide. In resolving antibiotic resistance development among different bacterial communities, new antimicrobial agents and nanoparticle-based strategies need to be designed foreseeing the slow discovery of new functioning antibiotics. Advanced research studies have revealed the significant disinfection potential of two-dimensional nanomaterials (2D NMs) to be severed as effective antibacterial agents due to their unique physicochemical properties. This review covers the current research progress of 2D NMs-based antibacterial strategies based on an inclusive explanation of 2D NMs' impact as antibacterial agents, including a detailed introduction to each possible well-known antibacterial mechanism. The impact of the physicochemical properties of 2D NMs on their antibacterial activities has been deliberated while explaining the toxic effects of 2D NMs and discussing their biomedical significance, dysbiosis, and cellular nanotoxicity. Adding to the challenges, we also discussed the major issues regarding the current quality and availability of nanotoxicity data. However, smart advancements are required to fabricate biocompatible 2D antibacterial NMs and exploit their potential to combat bacterial resistance clinically.
Diatomite-incorporated hierarchical scaffolds for osteochondral regeneration
Authors: Cuijun Deng, Chen Qin, Zhenguang Li, Laiya Lu, Yifan Tong, Jiaqi Yuan, Feng Yin, Yu Cheng, Chengtie Wu
Journal: Bioactive Materials (2024)

Osteochondral regeneration involves the highly challenging and complex reconstruction of cartilage and subchondral bone. Silicon (Si) ions play a crucial role in bone development. Current research on Si ions mainly focuses on bone repair, by using silicate bioceramics with complex ion compositions. However, it is unclear whether the Si ions have important effect on cartilage regeneration. Developing a scaffold that solely releases Si ions to simultaneously promote subchondral bone repair and stimulate cartilage regeneration is critically important. Diatomite (DE) is a natural diatomaceous sediment that can stably release Si ions, known for its abundant availability, low cost, and environmental friendliness. Herein, a hierarchical osteochondral repair scaffold is uniquely designed by incorporating gradient DE into GelMA hydrogel. The adding DE microparticles provides a specific Si source for controlled Si ions release, which not only promotes osteogenic differentiation of rBMSCs (rabbit bone marrow mesenchymal stem cells) but also enhances proliferation and maturation of chondrocytes. Moreover, DE-incorporated hierarchical scaffolds significantly promoted the regeneration of cartilage and subchondral bone. The study suggests the significant role of Si ions in promoting cartilage regeneration and solidifies their foundational role in enhancing bone repair. Furthermore, it offers an economic and eco-friendly strategy for developing high value-added osteochondral regenerative bioscaffolds from low-value ocean natural materials.
Accelerated infected wound healing by probiotic-based living microneedles with long-acting antibacterial effect
Authors: Yinli Jin, Yun Lu, Xue Jiang, Min Wang, Yaqi Yuan, Yongnian Zeng, Liang Guo, Wei Li
Journal: Bioactive Materials (2024)

Delays in infected wound healing are usually a result of bacterial infection and local inflammation, which imposes a significant and often underappreciated burden on patients and society. Current therapies for chronic wound infection generally suffer from limited drug permeability and frequent drug administration, owing to the existence of a wound biofilm that acts as a barrier restricting the entry of various antibacterial drugs. Here, we report the design of a biocompatible probiotic-based microneedle (MN) patch that can rapidly deliver beneficial bacteria to wound tissues with improved delivery efficiency. The probiotic is capable of continuously producing antimicrobial substances by metabolizing introduced glycerol, thereby facilitating infected wound healing through long-acting antibacterial and anti-inflammatory effects. Additionally, the beneficial bacteria can remain highly viable (>80 %) inside MNs for as long as 60 days at 4 °C. In a mouse model of Staphylococcus aureus-infected wounds, a single administration of the MN patch exhibited superior antimicrobial efficiency and wound healing performance in comparison with the control groups, indicating great potential for accelerating infected wound closure. Further development of live probiotic-based MN patches may enable patients to better manage chronically infected wounds.
Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, randomised, controlled, double-blind, non-inferiority trial
Authors: Anthony M Mills, Giuliano Rizzardini, Moti N Ramgopal, Olayemi O Osiyemi, Johannes R Bogner, Debbie P Hagins, Roger Paredes, Jacques Reynes, Jürgen K Rockstroh, Andrew Carr, Feng-Hsiu Su, Stephanie O Klopfer, Karen Eves, Rebeca M Plank, Todd Correll, Michelle C Fox
Journal: The Lancet HIV (2024)
HDAC Inhibition Increases CXCL12 Secretion to Recruit Natural Killer Cells in Peripheral T Cell Lymphoma
Authors: Jiayan Zhu, Feng Wang, Lining Wang, Bo Dai, Guilin Xu, Luyao Zhao, Huimin Jiang, Wenhui Gao, Tingting Zhang, Chenxi Zhao, Yun-Xuan Li, Jiong Hu, Ke Li
Journal: Cancer Research (2024)

Peripheral T-cell lymphoma (PTCL) is a heterogeneous and aggressive disease with a poor prognosis. Histone deacetylase (HDAC) inhibitors have shown inhibitory effects on PTCL. A better understanding of the therapeutic mechanism underlying the effects of HDAC inhibitors could help improve treatment strategies. Herein, we found that high expression of HDAC3 is associated with poor prognosis in PTCL. HDAC3 inhibition suppressed lymphoma growth in immunocompetent mice but not in immunodeficient mice. HDAC3 deletion delayed the progression of lymphoma, reduced the lymphoma burden in the thymus, spleen, and lymph nodes, and prolonged the survival of mice bearing N-methyl-N-nitrosourea-induced lymphoma. Furthermore, inhibiting HDAC3 promoted the infiltration and enhanced the function of natural killer (NK) cells. Mechanistically, HDAC3 mediated ATF3 deacetylation, enhancing its transcriptional inhibitory activity. Targeting HDAC3 enhanced CXCL12 secretion through an ATF3-dependent pathway to stimulate NK-cell recruitment and activation. Finally, HDAC3 suppression improved the response of PTCL to conventional chemotherapy. Collectively, this study provides insights into the mechanism by which HDAC3 regulates ATF3 activity and CXCL12 secretion, leading to immune infiltration and lymphoma suppression. Combining HDAC3 inhibitors with chemotherapy may be a promising strategy for treating PTCL. Significance: Targeting HDAC3 suppresses progression of T-cell lymphoma by activating ATF3 to induce secretion of CXCL12 and promote infiltration of NK cells, providing an immunostimulatory approach for treating T-cell lymphoma patients.
The Circadian Clock Component RORA Increases Immunosurveillance in Melanoma by Inhibiting PD-L1 Expression
Authors: Dandan Liu, Benliang Wei, Long Liang, Yue Sheng, Shengjie Sun, Xing Sun, Maohua Li, Haobo Li, Chaoying Yang, Yuanliang Peng, Yifang Xie, Chengcai Wen, Lu Chen, Xionghao Liu, Xiang Chen, Hong Liu, Jing Liu
Journal: Cancer Research (2024)

Circadian clock perturbation frequently occurs in cancer and facilitates tumor progression by regulating malignant growth and shaping the immune microenvironment. Emerging evidence has indicated that clock genes are disrupted in melanoma and linked to immune escape. Herein, we found that the expression of retinoic acid receptor-related orphan receptor-α (RORA) is downregulated in melanoma patients and that patients with higher RORA expression have a better prognosis after immunotherapy. Additionally, RORA was significantly positively correlated with T-cell infiltration and recruitment. Overexpression or activation of RORA stimulated cytotoxic T-cell-mediated antitumor responses. RORA bound to the CD274 promoter and formed an inhibitory complex with HDAC3 to suppress PD-L1 expression. In contrast, the DEAD-box helicase family member DDX3X competed with HDAC3 for binding to RORA, and DDX3X overexpression promoted RORA release from the suppressive complex and thereby increased PD-L1 expression to generate an inhibitory immune environment. The combination of a RORA agonist with an anti-CTLA4 antibody synergistically increased T-cell antitumor immunity in vivo. A score based on the combined expression of HDAC3, DDX3X, and RORA correlated with immunotherapy response in melanoma patients. Together, this study elucidates a mechanism of clock component-regulated antitumor immunity, which will help inform the use of immunotherapy and lead to improved outcomes for melanoma patients receiving combined therapeutic treatments. Significance: RORA forms a corepressor complex to inhibit PD-L1 expression and activate antitumor T-cell responses, indicating that RORA is a potential target and predictive biomarker to improve immunotherapy response in melanoma patients.
The Specificity of Left Ventricular Bite-Like Fibrofatty Replacement for Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Muhammad Umair, Babken Asatryan, Mounes Aliyari Ghasabeh, Laurens P. Bosman, Brittney Murray, Crystal Tichnell, Anneline S.J.M. te Riele, Birgitta K. Velthuis, Cynthia A. James, Stefan L. Zimmerman
Journal: JACC. Cardiovascular imaging (2024)
Inter3D: Capture of TAD Reorganization Endows Variant Patterns of Gene Transcription
Authors: Tianyi Ding, Shaliu Fu, Xiaoyu Zhang, Fan Yang, Jixing Zhang, Haowen Xu, Jiaqi Yang, Chaoqun Chen, Yibing Shi, Yiran Bai, Wannian Li, Xindi Chang, Shanjin Wang, Chao Zhang, Qi Liu, He Zhang
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Topologically associating domain (TAD) reorganization commonly occurs in the cell nucleus and contributes to gene activation and inhibition through the separation or fusion of adjacent TADs. However, functional genes impacted by TAD alteration and the underlying mechanism of TAD reorganization regulating gene transcription remain to be fully elucidated. Here, we first developed a novel approach termed Inter3D to specifically identify genes regulated by TAD reorganization. Our study revealed that the segregation of TADs led to the disruption of intrachromosomal looping at the myosin light chain 12B (MYL12B) locus, via the meticulous reorganization of TADs mediating epigenomic landscapes within tumor cells, thereby exhibiting a significant correlation with the down-regulation of its transcriptional activity. Conversely, the fusion of TADs facilitated intrachromosomal interactions, suggesting a potential association with the activation of cytochrome P450 family 27 subfamily B member 1 (CYP27B1). Our study provides comprehensive insight into the capture of TAD rearrangement-mediated gene loci and moves toward understanding the functional role of TAD reorganization in gene transcription. The Inter3D pipeline developed in this study is freely available at https://github.com/bm2-lab/inter3D and https://ngdc.cncb.ac.cn/biocode/tool/BT7399.
<i>CDKN2A/B </i>homozygous deletion sensitizes IDH-mutant glioma to CDK4/6 inhibition
Authors: Ali M. Nasser, Lisa Melamed, Ethan A. Wetzel, Jenny Chia-Chen Chang, Hiroaki Nagashima, Yosuke Kitagawa, Logan Muzyka, Hiroaki Wakimoto, Daniel P. Cahill, Julie J. Miller
Journal: Clinical Cancer Research (2024)

Treatment paradigms for isocitrate dehydrogenase (IDH)-mutant gliomas are rapidly evolving. Although typically indolent and responsive to initial treatment, these tumors invariably recur at a higher grade and require salvage treatment. Homozygous deletion of the tumor suppressor gene CDKN2A/B frequently emerges at recurrence in these tumors, driving poor patient outcomes. We investigated the effect of CDK-Rb pathway blockade on IDH-mutant glioma growth in vitro and in vivo using CDK4/6 inhibitors (CDKi).
Iron controls the development of airway hyperreactivity by regulating ILC2 metabolism and effector function
Authors: Benjamin P. Hurrell, Yoshihiro Sakano, Stephen Shen, Doumet Georges Helou, Meng Li, Pedram Shafiei-Jahani, Mohammad Hossein Kazemi, Kei Sakano, Xin Li, Christine Quach, Richard Barbers, Omid Akbari
Journal: Science Translational Medicine (2024)

Group 2 innate lymphoid cells (ILC2s) rapidly induce a type 2 inflammation in the lungs in response to allergens. Here, we focused on the role of iron, a critical nutritional trace element, on ILC2 function and asthma pathogenesis. We found that transferrin receptor 1 (TfR1) is rapidly up-regulated and functional during ILC2 activation in the lungs, and blocking transferrin uptake reduces ILC2 expansion and activation. Iron deprivation reprogrammed ILC2 metabolism, inducing a HIF-1α–driven up-regulation of glycolysis and inhibition of oxidative mitochondrial activity. Consequently, we observed that in vivo iron chelation or induction of hypoferremia reduced the development of airway hyperreactivity in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s rapidly induced TfR1 during activation, whereas inhibition of iron uptake or iron deprivation reduced effector functions. Last, we found a negative relationship between circulating ILC2 TfR1 expression and airway function in cohorts of patients with asthma. Collectively, our studies define cellular iron as a critical regulator of ILC2 function.