tbuckley/cabot-search huggingface dataset:
Prevalence, correlates, tolerability-related outcomes, and efficacy-related outcomes of antipsychotic polypharmacy: a systematic review and meta-analysis
Authors: Mikkel Højlund, Ole Köhler-Forsberg, Anton T Gregersen, Christopher Rohde, Angelina I Mellentin, Simon J Anhøj, Adam F Kemp, Nina B Fuglsang, Anne Christine Wiuff, Louise Nissen, Marc A Sørensen, Nanna M Madsen, Christina B Wagner, Armaghan Agharazi, Cecilie Søndergaard, Marie Sandmark, Jana Reinhart, Christoph U Correll
Journal: The Lancet Psychiatry (2024)
Traditional Chinese medicine FYTF-919 (Zhongfeng Xingnao oral prescription) for the treatment of acute intracerebral haemorrhage: a multicentre, randomised, placebo-controlled, double-blind, clinical trial
Authors: Jianwen Guo, Xiaoying Chen, Manli Wu, Dou Wang, Yang Zhao, Qiang Li, Guanghai Tang, Fengyuan Che, Zhangyong Xia, Zai Liang, Liu Shi, Qiuhua Jiang, Yajie Chen, Xiaoqiu Liu, Xinwen Ren, Menglu Ouyang, Borui Wang, Shoujiang You, Laurent Billot, Xia Wang, Zhenchuan Liu, Hongyan Jing, Wei Meng, Song Tian, Enzhi Liu, Yong Xiang, Xiaoping Tang, Tingting Xie, Wanzhen Cui, Yanwen Zheng, Jiamin Cao, Jingbei Zhang, Zehuai Wen, Tao Huang, Lixin Wang, Chao You, Suyue Pan, Yefeng Cai, Yun Lu, Graeme J Hankey, Rustam Al-Shahi Salman, Craig S Anderson, Lili Song
Journal: The Lancet (2024)
Multisource representation learning for pediatric knowledge extraction from electronic health records
Authors: Mengyan Li, Xiaoou Li, Kevin Pan, Alon Geva, Doris Yang, Sara Morini Sweet, Clara-Lea Bonzel, Vidul Ayakulangara Panickan, Xin Xiong, Kenneth Mandl, Tianxi Cai
Journal: npj Digital Medicine (2024)

Electronic Health Record (EHR) systems are particularly valuable in pediatrics due to high barriers in clinical studies, but pediatric EHR data often suffer from low content density. Existing EHR code embeddings tailored for the general patient population fail to address the unique needs of pediatric patients. To bridge this gap, we introduce a transfer learning approach, MUltisource Graph Synthesis (MUGS), aimed at accurate knowledge extraction and relation detection in pediatric contexts. MUGS integrates graphical data from both pediatric and general EHR systems, along with hierarchical medical ontologies, to create embeddings that adaptively capture both the homogeneity and heterogeneity between hospital systems. These embeddings enable refined EHR feature engineering and nuanced patient profiling, proving particularly effective in identifying pediatric patients similar to specific profiles, with a focus on pulmonary hypertension (PH). MUGS embeddings, resistant to negative transfer, outperform other benchmark methods in multiple applications, advancing evidence-based pediatric research.
In vivo gene editing and in situ generation of chimeric antigen receptor cells for next-generation cancer immunotherapy
Authors: Weiyue Zhang, Xin Huang
Journal: Journal of Hematology & Oncology (2024)

Chimeric antigen receptor (CAR) cell therapy has achieved groundbreaking success in treating hematological malignancies. However, its application to solid tumors remains challenging due to complex manufacturing processes, limited in vivo persistence, and transient therapeutic effects. In vivo CAR-immune cells induced by gene delivery systems loaded with CAR genes and gene-editing tools have shown efficiency for anti-tumor immunotherapy. In situ programming of autologous immune cells avoids the safety concerns of allogeneic immune cells, and the manufacture of gene delivery systems could be standardized. Therefore, the in vivo editing and in situ generation of CAR-immune cells might potentially overcome the abovementioned limitations of current CAR cell therapy. This review mainly focuses on CAR structures, gene-editing tools, and gene delivery techniques applied in anti-tumor immunotherapy to help design and develop in situ CAR-immune cell therapy. The recent applications of in vivo CAR-immune cell therapy in both hematologic malignancies and solid tumors are investigated. To sum up, the in vivo editing and in situ generation of CAR therapy holds promise for offering a practical, cost-effective, efficient, safe, and widely applicable approach to the next-generation anti-tumor immunotherapy.
Mitochondrial genome diversity drives heterogeneity in hepatocellular carcinoma
Authors: Tatsuhiro Shibata, Yujin Hoshida
Journal: Hepatology (2024)

1Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, Japan 2Division of Cancer Genomics, National Cancer Center, 5-1-1, Tsukiji, Chuo-ku, Tokyo, Japan 3Division of Digestive and Liver Diseases, Department of Internal Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA Abbreviation: HCC, hepatocellular carcinoma; ICI, immune checkpoint inhibitor; ITH, inter/intra-tumor heterogeneities; mtDNA, mitochondrial DNA; sc-CAMS, single-cell capture-based mtDNA sequencing Correspondence. Email: [email protected]
Comparative genomics provides insights into adaptive evolution and demographics of bats
Authors: Gaoming Liu, Qi Pan, Pingfen Zhu, Xinyu Guo, Zhan Zhang, Zihao Li, Yaolei Zhang, Xiaoxiao Zhang, Jiahao Wang, Weiqiang Liu, Chunyan Hu, Yang Yu, Xiao Wang, Weixiao Chen, Meng Li, Wenhua Yu, Xin Liu, Inge Seim, Guangyi Fan, Xuming Zhou
Journal: Molecular Biology and Evolution (2024)

Abstract Bats possess a range of distinctive characteristics, including flight, echolocation, impressive longevity, and the ability to harbor various zoonotic pathogens. Additionally, they account for the second-highest species diversity among mammalian orders, yet their phylogenetic relationships and demographic history remain underexplored. Here, we generated de novo assembled genomes for 17 bat species and 2 of their mammalian relatives (the Amur hedgehog and Chinese mole shrew), with 12 genomes reaching chromosome-level assembly. Comparative genomics and ChIP-seq assays identified newly gained genomic regions in bats potentially linked to the regulation of gene activity and expression. Notably, some antiviral infection-related gene under positive selection exhibited the activity of suppressing cancer, evidencing the linkage between virus tolerance and cancer resistance in bats. By integrating published bat genome assemblies, phylogenetic reconstruction established the proximity of noctilionoid bats to vesper bats. Interestingly, we found 2 distinct patterns of ancient population dynamics in bats and population changes since the last glacial maximum does not reflect species phylogenetic relationships. These findings enriched our understanding of adaptive mechanisms and demographic history of bats.
Regulation of blood pressure by METTL3 via RUNX1b-eNOS pathway in endothelial cells in mice
Authors: Yanhong Zhang, Xiaoxiao Yang, Mei Lan, Ze Yuan, Shuai Li, Yangping Liu, Cha Han, Ding Ai, Yang Yang, Yi Zhu, Bochuan Li
Journal: Cardiovascular Research (2024)

Endothelial cells regulate vascular tone to control the blood pressure (BP) by producing both relaxing and contracting factors. Previously, we identified methyltransferase-like 3 (METTL3), a primary N6-methyladenosine (m6A) methyltransferase, as a key player in alleviating endothelial atherogenic progression. However, its involvement in BP regulation remains unclear.
Inflammaging, a targetable pathway for preventing cardiovascular diseases
Authors: Juan Francisco Aranda, Cristina M Ramírez, María Mittelbrunn
Journal: Cardiovascular Research (2024)

Abstract Inflammageing, characterized by persistent chronic inflammation in older adults, has emerged as a critical factor linked to age-related diseases, such as cardiovascular diseases (CVDs), metabolic disorders, and cognitive decline, which collectively contribute to the leading causes of death globally. Elevated levels of cytokines, chemokines, and other inflammatory mediators characterize inflammageing and serve as indicators of biological age. Among the causes of inflammageing, deterioration of the immune system, mitochondrial dysfunction, dysbiosis, accumulation of DAMPs, together with genetic or epigenetic factors, contribute to inflammageing not only in CVD but also in other age-related conditions. This review examines the causes and consequences of inflammageing, particularly its implications for atherosclerosis and heart failure with preserved ejection fraction and explores potential strategies to mitigate it in the onset of CVD.
Long‐term risk of heart failure in patients with postoperative atrial fibrillation following non‐cardiac surgery: Insights from a nationwide cohort
Authors: Munise N. Karacan, Adelina Yafasova, Emil L. Fosbøl, Amine Tas, Katia Al‐Chaer, Anna Gundlund, Finn Gustafsson, Anna Stahl, Morten Schou, Emil Wolsk, Nadia P. Dridi, Lars Køber, Jawad H. Butt
Journal: European Journal of Heart Failure (2024)

Aims Atrial fibrillation (AF) is associated with heart failure (HF). However, it is unclear if postoperative AF (POAF) following non‐cardiac surgery differs from non‐surgical AF in terms of the risk of HF. We compared the long‐term rate of incident HF in patients developing new‐onset POAF following non‐cardiac surgery with patients who did not develop POAF following non‐cardiac surgery and patients with non‐surgical non‐valvular AF (NVAF). Methods and results Using Danish nationwide registries, all patients aged ≥30 years who developed POAF following non‐cardiac surgery (1996–2020) were identified and matched in a 1:3 ratio by age, sex, surgery type (only for the surgery group), selected comorbidities, and inclusion year with patients without POAF following non‐cardiac surgery and individuals with NVAF, respectively. A total of 2270 patients with POAF were matched with 6810 patients without POAF following non‐cardiac surgery, and 1846 patients with POAF were matched with 5538 patients with NVAF. The median follow‐up was 7.2 years. Compared with patients without POAF, those with POAF had a higher associated long‐term rate of incident HF (2.6 vs. 1.2 events per 100 person‐years; adjusted hazard ratio [HR] 2.39, 95% confidence interval [CI] 2.06–2.78). Compared with individuals with NVAF, patients with POAF did not have a significantly different rate of incident HF (2.7 vs. 3.0 events per 100 person‐years; adjusted HR 0.89, 95% CI 0.78–1.03). Conclusion Patients with new‐onset POAF following non‐cardiac surgery had a higher associated long‐term rate of incident HF compared to those without POAF, with no significant difference in the rate of incident HF when compared to patients with NVAF.
The multifaceted nature of lack of access to antibiotics: types of shortage and specific causes, consequences, and solutions
Authors: Enrico Baraldi, Christine Årdal, Emil Aho, Gabriel-Adrian Popescu, Tsegaye Melaku
Journal: Clinical Microbiology and Infection (2024)

Maintaining access to a broad range of old and new antibiotics is increasingly difficult due to supply, market, and demand issues. Next to immediate negative consequences for individual patients and healthcare systems, antibiotic unavailability can accelerate resistance development due to unmotivated use of suboptimal broad-spectrum antibiotics.
Risk of uveitis among E-Cigarette Users: a multi-institutional TriNetX study
Authors: Alan Y Hsu, Yu-Hsun Wang, Ning-Yi Hsia, Chun-Ting Lai, Hou-Ting Kuo, Bing-Qi Wu, Chun-Ju Lin, Chun-Chi Chiang, Yi-Ching Shao, Huan-Sheng Chen, Yi-Yu Tsai, James Cheng-Chung Wei
Journal: Ophthalmology (2024)
Impact of Vaginal Seeding on the Gut Microbiome of Infants Born via Cesarean Section: A Systematic Review
Authors: Xiaochuan Wang, Hong Cui, Na Li, Borui Liu, Xiaoyan Zhang, Jing Yang, Ju-Sheng Zheng, Chong Qiao, Hui-Xin Liu, Jiajin Hu, Deliang Wen
Journal: Journal of Infection (2024)

This systematic review summarizes eight studies involving 558 cesarean section (CS)-born infants (274 exposed to vaginal seeding (VS), 284 not exposed) and 261 infants born vaginally to investigate the effect of VS on gut microbiome colonization and development in CS-born infants.
Convergent degenerated regulatory elements associated with limb loss in limbless amphibians and reptiles
Authors: Chenglong Zhu, Shengyou Li, Daizhen Zhang, Jinjin Zhang, Gang Wang, Botong Zhou, Jiangmin Zheng, Wenjie Xu, Zhengfei Wang, Xueli Gao, Qiuning Liu, Tingfeng Xue, Huabin Zhang, Chunhui Li, Baoming Ge, Yuxuan Liu, Qiang Qiu, Huixian Zhang, Jinghui Huang, Boping Tang, Kun Wang
Journal: Molecular Biology and Evolution (2024)

Abstract Limbs are a defining characteristic of tetrapods, yet numerous taxa, primarily among amphibians and reptiles, have independently lost limbs as an adaptation to new ecological niches. To elucidate the genetic factors contributing to this convergent limb loss, we present a 12 Gb chromosome-level assembly of the Banna caecilian (Ichthyophis bannanicus), a limbless amphibian. Our comparative analysis, which includes the reconstruction of amphibian karyotype evolution, reveals constrained gene length evolution in a subset of developmental genes across 3 large genomes. Investigation of limb development genes uncovered the loss of Grem1 in caecilians and Tulp3 in snakes. Interestingly, caecilians and snakes share a significantly larger number of convergent degenerated conserved noncoding elements than limbless lizards, which have a shorter evolutionary history of limb loss. These convergent degenerated conserved noncoding elements overlap significantly with active genomic regions during mouse limb development and are conserved in limbed species, suggesting their essential role in limb patterning in the tetrapod common ancestor. While most convergent degenerated conserved noncoding elements emerged in the jawed vertebrate ancestor, coinciding with the origin of paired appendage, more recent degenerated conserved noncoding elements also contribute to limb development, as demonstrated through functional experiments. Our study provides novel insights into the regulatory elements associated with limb development and loss, offering an evolutionary perspective on the genetic basis of morphological specialization.
Hyperparathyroidism and the Hematologist
Authors: Hajer Oun, Kirsteen Harper, Mike Leach, Barbara J. Bain
Journal: American Journal of Hematology (2024)

A 76-year-old man with a history of chronic obstructive pulmonary disease with lung fibrosis, type 2 diabetes mellitus, and chronic kidney disease underwent computed tomography imaging of the chest due to increasing dyspnea. The bones appeared sclerotic, and a bone scan showed diffuse tracer uptake throughout the axial and appendicular skeleton. The prostate showed no features of malignancy on magnetic resonance imaging and prostate-specific antigen was 6.6 μg/L (normal range (NR) 0–5). Serum tryptase levels were mildly elevated at 16 μg/L (NR 2–14) on two occasions. Biochemical investigations showed vitamin D < 14 nmol/L (NR > 50), alkaline phosphatase 665 U/L (NR 30–130), parathyroid hormone 52.8 pmol/L (NR 1.6–7.5), calcium 2.43 mmol/L (NR 2.2–2.6) and phosphate 1.07 mmol/L (NR 0.8–1.5), in keeping with hyperparathyroidism secondary to vitamin D deficiency and chronic kidney disease (creatinine 169 μmol/L and estimated glomerular filtration rate 34 mL/min). Bone marrow trephine biopsy sections showed areas of active bone resorption by multinucleate osteoclasts forming recesses known as Howship's lacunae (top and bottom left, all histological images hematoxylin and eosin, ×50 objective). In other areas, lamellar bone was being actively laid down by rows of osteoblasts (top center). There was patchy fibrosis at sites of previous bone resorption (bottom center). Notably, there were osteoclasts also visible in the marrow aspirate (top and bottom right, May–Grünwald–Giemsa, ×100 objective). There was no abnormal mast cell population. These features are typical of hyperparathyroidism where osteoclasts strive to release calcium whilst osteoblasts attempt to repair the trabecular damage. This active bone remodeling with the associated trabecular changes generates the sclerotic radiological appearance of the affected bones. Osteoblasts and osteoclasts normally work together in bone repair, remodeling, and growth but this process is exaggerated under the influence of increased parathyroid hormone whether primary, due to a parathyroid adenoma, or secondary, as a result of vitamin D deficiency or chronic kidney disease. The recognition of the features of bone disorders with associated bone marrow fibrosis is important so that they are not confused with myeloproliferative neoplasms. The authors declare no conflicts of interest.
Dynamic changes in the structure and function of brain mural cells around chronically implanted microelectrodes
Authors: Steven M Wellman, Adam M Forrest, Madeline M Douglas, Ashwat Subbaraman, Guangfeng Zhang, Takashi D Y Kozai
Journal: Biomaterials (2024)

Integration of neural interfaces with minimal tissue disruption in the brain is ideal to develop robust tools that can address essential neuroscience questions and combat neurological disorders. However, implantation of intracortical devices provokes severe tissue inflammation within the brain, which requires a high metabolic demand to support a complex series of cellular events mediating tissue degeneration and wound healing. Pericytes, peri-vascular cells involved in blood-brain barrier maintenance, vascular permeability, waste clearance, and angiogenesis, have recently been implicated as potential perpetuators of neurodegeneration in brain injury and disease. While the intimate relationship between pericytes and the cortical microvasculature have been explored in other disease states, their behavior following microelectrode implantation, which is responsible for direct blood vessel disruption and dysfunction, is currently unknown. Using two-photon microscopy we observed dynamic changes in the structure and function of pericytes during implantation of a microelectrode array over a 4-week implantation period. Pericytes respond to electrode insertion through transient increases in intracellular calcium and underlying constriction of capillary vessels. Within days following the initial insertion, we observed an influx of new, proliferating pericytes which contribute to new blood vessel formation. Additionally, we discovered a potentially novel population of reactive immune cells in close proximity to the electrode-tissue interface actively engaging in encapsulation of the microelectrode array. Finally, we determined that intracellular pericyte calcium can be modulated by intracortical microstimulation in an amplitude- and frequency-dependent manner. This study provides a new perspective on the complex biological sequelae occurring at the electrode-tissue interface and will foster new avenues of potential research consideration and lead to development of more advanced therapeutic interventions towards improving the biocompatibility of neural electrode technology.
Advances in Therapy for Refractory Epilepsy
Authors: Lara Jehi
Journal: Annual Review of Medicine (2024)

Drug-resistant epilepsy (DRE) is defined as failure to achieve sustained seizure control with adequate trials of two appropriate antiseizure medications (ASMs). DRE affects one-third of patients with epilepsy and is associated with significant morbidity and mortality. Newer ASMs provide pharmacological therapy that is better tolerated but not necessarily more effective than older ASMs. Resective brain surgery is the gold standard to treat DRE and achieve seizure freedom, with laser ablation offering an alternative with less morbidity but lower effectiveness. For patients who are not candidates for resection or ablation, multiple neuromodulation options can reduce seizure burden. These neuromodulation devices have shown comparable effectiveness in randomized clinical trials, but the results vary in open-label follow-up cohorts, as do the risks of complications and associated costs. Dietary therapies can help, particularly in pediatric genetic epilepsies. Innovative genetic therapy approaches are being pursued, offering the promise of precision medicine.
Hypothalamic obesity: from basic mechanisms to clinical perspectives
Authors: Jesús Argente, I Sadaf Farooqi, Julie A Chowen, Peter Kühnen, Miguel López, Eugenia Morselli, Hoong-Wei Gan, Helen A Spoudeas, Martin Wabitsch, Manuel Tena-Sempere
Journal: The Lancet Diabetes & Endocrinology (2024)
The roles of IL-17A and IL-17F in hidradenitis suppurativa pathogenesis: evidence from human <i>in vitro</i> preclinical experiments and clinical samples
Authors: Joseph Rastrick, Hannah Edwards, Alex S Ferecskó, Gaëlle Le Friec, Avneet Manghera, Matthew Page, Stevan Shaw
Journal: British Journal of Dermatology (2024)

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease associated with significant comorbidities and poor quality of life. Despite uncertainty about pathways driving inflammation in HS lesions, the cytokines IL-17A and IL-17F have been shown to be upregulated in patients with HS. Previous studies demonstrated that the monoclonal IgG1 antibody bimekizumab selectively inhibits IL-17F in addition to IL-17A.
Diversity of transcriptional regulatory adaptation in <i>E. coli</i>
Authors: Christopher Dalldorf, Ying Hefner, Richard Szubin, Josefin Johnsen, Elsayed Mohamed, Gaoyuan Li, Jayanth Krishnan, Adam M Feist, Bernhard O Palsson, Daniel C Zielinski
Journal: Molecular Biology and Evolution (2024)

Abstract The transcriptional regulatory network (TRN) in bacteria is thought to rapidly evolve in response to selection pressures, modulating transcription factor (TF) activities and interactions. In order to probe the limits and mechanisms surrounding the short-term adaptability of the TRN, we generated, evolved, and characterized knockout (KO) strains in Escherichia coli for 11 regulators selected based on measured growth impact on glucose minimal media. All but one knockout strain (Δlrp) were able to recover growth and did so requiring few convergent mutations. We found that the TF knockout adaptations could be divided into four categories: (i) Strains (ΔargR, ΔbasR, Δlon, ΔzntR, and Δzur) that recovered growth without any regulator-specific adaptations, likely due to minimal activity of the regulator on the growth condition, (ii) Strains (ΔcytR, ΔmlrA, and ΔybaO) that recovered growth without TF-specific mutations but with differential expression of regulators with overlapping regulons to the KO’ed TF, (iii) Strains (Δcrp and Δfur) that recovered growth using convergent mutations within their regulatory networks, including regulated promoters and connected regulators, and (iv) Strains (Δlrp) that were unable to fully recover growth, seemingly due to the broad connectivity of the TF within the TRN. Analyzing growth capabilities in evolved and unevolved strains indicated that growth adaptation can restore fitness to diverse substrates often despite a lack of TF-specific mutations. This work reveals the breadth of TRN adaptive mechanisms and suggests these mechanisms can be anticipated based on the network and functional context of the perturbed TFs.
Corrigendum to “Dual-step irradiation strategy to sequentially destroy singlet oxygen-responsive polymeric micelles and boost photodynamic cancer therapy” [Biomater. 275 (2021) 120959]
Authors: Kai Deng, Hui Yu, Jia-Mi Li, Kun-Heng Li, Hong-Yang Zhao, Min Ke, Shi-Wen Huang
Journal: Biomaterials (2024)
Venetoclax in combination with hypomethylating agents in chronic myelomonocytic leukemia: a propensity score matched multicenter cohort study
Authors: Douglas Tremblay, Clifford Csizmar, Courtney D DiNardo, Somedeb Ball, Noa Rippel, Danielle Hammond, Tapan M Kadia, Farhad Ravandi, Kelly Chien, Grace Van Hyfte, Madhu Mazumdar, Antoine Saliba, Abhishek Mangaonkar, Terra Lasho, Aref Al-Kali, Marina Kremyanskaya, Jonathan Feld, Lewis R Silverman, Rami Komrokji, John Mascarenhas, Eric Padron, Guillermo Garcia-Manero, David A Sallman, Mrinal M Patnaik, Guillermo Montalban-Bravo
Journal: Leukemia (2024)