tbuckley/cabot-search huggingface dataset:
Modeling type 1 diabetes progression using machine learning and single-cell transcriptomic measurements in human islets
Authors: Abhijeet R Patil, Jonathan Schug, Chengyang Liu, Deeksha Lahori, Hélène C Descamps, Ali Naji, Klaus H Kaestner, Robert B Faryabi, Golnaz Vahedi
Journal: Cell Reports Medicine (2024)

Type 1 diabetes (T1D) is a chronic condition in which beta cells are destroyed by immune cells. Despite progress in immunotherapies that could delay T1D onset, early detection of autoimmunity remains challenging. Here, we evaluate the utility of machine learning for early prediction of T1D using single-cell analysis of islets. Using gradient-boosting algorithms, we model changes in gene expression of single cells from pancreatic tissues in T1D and non-diabetic organ donors. We assess if mathematical modeling could predict the likelihood of T1D development in non-diabetic autoantibody-positive donors. While most autoantibody-positive donors are predicted to be non-diabetic, select donors with unique gene signatures are classified as T1D. Our strategy also reveals a shared gene signature in distinct T1D-associated models across cell types, suggesting a common effect of the disease on transcriptional outputs of these cells. Our study establishes a precedent for using machine learning in early detection of T1D.
Recurrent splanchnic and extrasplanchnic thrombotic events in patients with non-cirrhotic portal vein thrombosis associated with local factors
Authors: Isabelle Ollivier-Hourmand, Louise Lebedel, Berta Bartroli Alabau, Odile Goria, Christophe Bureau, Jérome Dumortier, Alexandra Heurgué, Christine Silvain, Victor De-Ledinghen, Pierre-Emmanuel Rautou, Audrey Payancé, Teresa García Ballester, Edilmar Alvarado-Tapias, Virginia Hernández-Gea, Dominique Valla, Kamal Zekrini, Thi Thu Nga Nguyen, Thong Dao, Juan Carlos Garcia Pagan, Rémy Morello, Aurélie Plessier
Journal: Journal of Hepatology (2024)
Bimetallic DNAsome Decorated with G<sub>4</sub>‐DNA as a Nanozyme for Targeted and Enhanced Chemo/Chemodynamic Cancer Therapy
Authors: Gowtham Raj, Anu P. Vasantha, Vasudev D. Sreekumar, Athul V. Beena, Viswa Kalyan Kumar Dommeti, Harsha Perozhy, Alwin T. Jose, Satish Khurana, Reji Varghese
Journal: Advanced Healthcare Materials (2024)

Abstract Cancer is indisputably one of the major threats to mankind, and hence the design of new approaches for the improvement of existing therapeutic strategies is always wanted. Herein, the design of a tumor microenvironment‐responsive, DNA‐based chemodynamic therapy (CDT) nanoagent with dual Fenton reaction centers for targeted cancer therapy is reported. Self‐assembly of DNA amphiphile containing copper complex as the hydrophobic Fenton reaction center results in the formation of CDT‐active DNAsome with Cu 2+ ‐based Fenton catalytic site as the hydrophobic core and hydrophilic ssDNA protrude on the surface. DNA‐based surface addressability of the DNAsome is then used for the integration of second Fenton reaction center, which is a peroxidase‐mimicking DNAzyme noncovalently loaded with Hemin and Doxorubicin, via DNA hybridization to give a CDT agent having dual Fenton reaction centers. Targeted internalization of the CDT nanoagent and selective generation of • OH inside HeLa cell are also shown. Excellent therapeutic efficiency is observed for the CDT nanoagent both in vitro and in vivo, and the enhanced efficacy is attributed to the combined and synergetic action of CDT and chemotherapy.
De novo autoimmune connective tissue disease and mortality in patients treated with anti-PD-1 and anti-PD-L1 therapy: a population-level cohort study
Authors: Kimberly Tang, Ahmad Rajeh, Katharina S Shaw, Nga Nguyen, Guihong Wan, Kimberly B Hashemi, Rochelle L Castillo, Shawn G Kwatra, Nicole R LeBoeuf, Ruth Ann Vleugels, Yevgeniy R Semenov
Journal: British Journal of Dermatology (2024)

Using a population-level cohort analysis, our study demonstrates that, although rare, de novo autoimmune cutaneous connective tissue diseases (AiCTDs) in the setting of immune checkpoint inhibitors (ICIs) are not associated with a greater risk of mortality and overall approach a statistically significant decrease in mortality when compared with patients treated with ICIs who do not experience cutaneous immune-related adverse events. These findings are significant and highly relevant to dermatologists and oncologists caring for ICI recipients as it adds to the limited information on development of cutaneous AiCTD following ICI administration, for which enhanced understanding is critical to improving the care for this challenging patient population.
The addition of bortezomib to rituximab, high-dose cytarabine and dexamethasone in relapsed or refractory mantle cell lymphoma—a randomized, open-label phase III trial of the European mantle cell lymphoma network
Authors: Luca Fischer, Linmiao Jiang, Jan Dürig, Christian Schmidt, Stephan Stilgenbauer, Krimo Bouabdallah, Philippe Solal-Celigny, Christian W Scholz, Pierre Feugier, Maike de Wit, Ralf Ulrich Trappe, Michael Hallek, Ullrich Graeven, Mathias Hänel, Martin Hoffmann, Vincent Delwail, Margaret Macro, Jochen Greiner, Aristoteles A N Giagounidis, Beate Dargel, Eric Durot, Charles Foussard, Elisabeth Silkenstedt, Oliver Weigert, Christiane Pott, Wolfram Klapper, Wolfgang Hiddemann, Michael Unterhalt, Eva Hoster, Vincent Ribrag, Martin Dreyling
Journal: Leukemia (2024)

Abstract The therapy of relapsed or refractory (r/r) mantle cell lymphoma (MCL) patients remains a major clinical challenge to date. We conducted a randomized, open-label, parallel-group phase-III trial hypothesizing superior efficacy of rituximab, high-dose cytarabine and dexamethasone with bortezomib (R-HAD + B) versus without (R-HAD) in r/r MCL ineligible for or relapsed after autologous stem cell transplant (ASCT). Primary endpoint was time to treatment failure (TTF), secondary endpoints included response rates, progression free survival, overall survival, and safety. In total, 128 of 175 planned patients were randomized to R-HAD + B ( n = 64) or R-HAD ( n = 64). Median TTF was 12 vs. 2.6 months ( p = 0.045, MIPI-adjusted HR 0.69; 95%CI 0.47–1.02). Overall and complete response rates were 63 vs. 45% ( p = 0.049) and 42 vs. 19% ( p = 0.0062). A significant treatment effect was seen in the subgroup of patients &gt;65 years (aHR 0.48, 0.29–0.79) and without previous ASCT (aHR 0.52, 0.28–0.96). Toxicity was mostly hematological and attributable to the chemotherapeutic backbone. Grade ≥3 leukocytopenia and lymphocytopenia were more common in R-HAD + B without differences in severe infections between both arms. Bortezomib in combination with chemotherapy can be effective in r/r MCL and should be evaluated further as a therapeutic option, especially if therapy with BTK inhibitors is not an option. Trial registration: NCT01449344.
Time-lagged panel models in psychotherapy process and mechanisms of change research: Methodological challenges and advances
Authors: Fredrik Falkenström
Journal: Clinical Psychology Review (2024)

In recent years, there has been increasing interest in utilizing time-lagged panel models to study mechanisms of change in psychotherapy. These models offer valuable insights into the dynamic relationships between variables over time and offer stronger causal inference capabilities than cross-sectional analyses. Therefore, they are well-suited for modeling the intricate relationships between mechanisms of change and outcomes in psychotherapy studies, which are typically beyond experimental control. However, their complexity, coupled with the fact that detailed explanations are often embedded in dense statistical or econometric texts, poses challenges. This paper provides a background on cross-lagged panel models and delves deeper into explaining the issues of 1) dynamic panel bias, 2) long-run effects, and 3) testing whether different treatments work by different mechanisms. Using data from a psychotherapy study on treatment of adolescent depression, I demonstrate how these issues manifest in real data. In conclusion, I recommend using structural equation modeling to circumvent dynamic panel bias, reporting long-run effects to reveal the long-term impact of sustained therapeutic work on mechanisms of change, and carefully considering whether mediation, moderation, or a combination of both, best describes differential effects of mechanisms between treatments.
Lipopolysaccharides in combination with amoxicillin increases basophil activation test sensitivity to amoxicillin <scp>IgE</scp>‐mediated hypersensitivity
Authors: Jose A. Céspedes, Rubén Fernández‐Santamaría, Gador Bogas, Adriana Ariza Veguillas, Inmaculada Doña, María Salas, Marina Labella, Tahia D. Fernández Duarte, Cristobalina Mayorga, María J. Torres, Cecilia A. Frecha
Journal: Allergy (2024)
Strategic approaches in oral squamous cell carcinoma diagnostics using liquid biopsy
Authors: Denis F. Kinane, Joerg Gabert, George Xynopoulos, Esra Guzeldemir‐Akcakanat
Journal: Periodontology 2000 (2024)

Abstract Liquid biopsy is a noninvasive diagnostic technique used for monitoring cancer utilizing specific genetic biomarkers present in bodily fluids, such as blood, saliva, or urine. These analyses employ multiple biomolecular sources including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes (that contain DNA fragments) to detect genetic biomarkers that can predict, disclose, and/or monitor cancers. Levels of these biomarkers can inform on the presence of cancer, its genetic characteristics, and its potential treatment response and also provide predictive genetic predisposition information for specific cancers including oral squamous cell carcinomas (OSCC). Liquid biopsies can aid cancer management as they offer real‐time dynamic information on the response to say chemotherapy or radiotherapy and recurrence following surgical excision. Unlike traditional tissue biopsies, which are invasive with a degree of morbidity and require specific tumor location sampling, liquid biopsies are noninvasive and can be repeated frequently. For oral squamous cell carcinoma, on which this review focuses, liquid biopsy of blood or saliva can be valuable in predicting susceptibility, providing early detection, and monitoring the disease's progression and response to therapy. This review gives a general narrative overview of the technology, its current medical usage, and advantages and disadvantages compared with current techniques and discusses a range of current potential biomarkers for disclosing OSCC and predicting its risk. Oral squamous cell carcinoma is all too often detected in the late stages. In future, liquid biopsy may provide an effective screening process such that cancers including OSCC will be detected in the early stages rather than later when prognosis is poor and morbidity and debilitation are greater. In this screening process, periodontists and hygienists have a critical role in that they are adept in examining mucosa, they see patients with shared risk factors for periodontitis and OSCC, namely smoking and poor oral hygiene, and they see patients frequently such that OSCC examinations should be a routine part of the recall visit. With this additional screening manpower, oral medicine and oral surgery colleagues will detect OSCC earlier and this coupled with new techniques such as liquid biopsy may greatly decrease global morbidity in OSCC.
R-loop and diseases: the cell cycle matters
Authors: Yuqin Xu, Yue Jiao, Chengbin Liu, Rui Miao, Chunyan Liu, Yilong Wang, Chunming Ma, Jiao Liu
Journal: Molecular Cancer (2024)

Abstract The cell cycle is a crucial biological process that is involved in cell growth, development, and reproduction. It can be divided into G1, S, G2, and M phases, and each period is closely regulated to ensure the production of two similar daughter cells with the same genetic material. However, many obstacles influence the cell cycle, including the R-loop that is formed throughout this process. R-loop is a triple-stranded structure, composed of an RNA: DNA hybrid and a single DNA strand, which is ubiquitous in organisms from bacteria to mammals. The existence of the R-loop has important significance for the regulation of various physiological processes. However, aberrant accumulation of R-loop due to its limited resolving ability will be detrimental for cells. For example, DNA damage and genomic instability, caused by the R-loop, can activate checkpoints in the cell cycle, which in turn induce cell cycle arrest and cell death. At present, a growing number of factors have been proven to prevent or eliminate the accumulation of R-loop thereby avoiding DNA damage and mutations. Therefore, we need to gain detailed insight into the R-loop resolution factors at different stages of the cell cycle. In this review, we review the current knowledge of factors that play a role in resolving the R-loop at different stages of the cell cycle, as well as how mutations of these factors lead to the onset and progression of diseases.
The Carbon Footprint of Peritoneal Dialysis in Australia
Authors: Scott McAlister, Ben Talbot, John Knight, Susan Blair, Forbes McGain, Stephen McDonald, Craig Nelson, Richard Knight, Katherine A. Barraclough
Journal: Journal of the American Society of Nephrology (2024)

Key Points Automated peritoneal dialysis (APD) had a higher carbon impact than continuous ambulatory peritoneal dialysis (CAPD). This was due to higher emissions from the manufacture and disposal of APD consumables, and their higher weight, meaning greater transport emissions. Polyvinyl chloride recycling can partially mitigate peritoneal dialysis–associated emissions. Background As climate change escalates with increasing health impacts, health care must address its carbon footprint. The first critical step is understanding the sources and extent of emissions from commonly utilized clinical care pathways. Methods We used attributional process-based life-cycle analysis to quantify CO 2 equivalent emissions associated with the delivery of Baxter’s HomeChoice automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) in Australia. Results The annual per-patient carbon emissions attributable to the manufacture and disposal of peritoneal dialysis (PD) fluids and consumables were 1992 kg CO 2 equivalent emissions for APD and 1245 kg CO 2 equivalent emissions for CAPD. Transport impacts varied depending on the distance between the site of manufacture of PD fluids and consumables and the state of origin of the patient. Therefore, the total impact of providing PD also differed by Australian state, ranging from 2350 to 4503 kg CO 2 equivalent emissions for APD and from 1455 to 2716 kg CO 2 equivalent emissions for CAPD. Recycling of polyvinyl chloride (PVC) could reduce emissions by up to 14% for APD and 30% for CAPD depending on the distance between the site of PVC waste generation and the recycling center. Conclusions This study demonstrated higher per-patient carbon emissions from APD compared with CAPD, owing to both higher fluid and consumable requirements and the consequent higher transport impacts. PVC recycling can partially mitigate PD-associated carbon emissions.
Klotho
Authors: Christopher Yanucil, Christian Faul
Journal: Journal of the American Society of Nephrology (2024)

1Alpha Young LLC, Carlsbad, CA, USA 2Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA. aCorrespondence: Christian Faul, PhD, Tinsley Harrison Tower 611L, 1720 2nd Avenue South, Birmingham, AL 35294, USA, Telephone: 205-996-9641, Fax: 205-996-6650, Email: [email protected]
Association between Apgar scores within normal range and development of asthma, allergic rhinitis and eczema in childhood: A Danish nationwide register study
Authors: Erik Sören Halvard Hansen, Hannah Kaiser, Kristine Tronier Hansen, Klaus Bønnelykke, Bo Chawes, Vibeke Backer, Christian Torp‐Pedersen, Charlotte Suppli Ulrik, Nicklas Brustad
Journal: Allergy (2024)

Data are not available. Appendix S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
<i>Journal</i> Voices in the Civil Rights Era — New Horizons and Limits in Medical Publishing
Authors: Merlin Chowkwanyun
Journal: New England Journal of Medicine (2024)

D uring the social tumult of the 1960s and 1970s, many people in the United States began demanding a more egalitarian restructuring of society, including its many manifestations of racism.American medicine was not exempt, and the Journal opened its pages to advocates of reform in the profession and to civil rights activists fighting on the front lines.The shift, however, was hardly linear.The Journal also continued to publish material ref lecting more reactionary and conventional ways of thinking.Like the larger medical profession, it found that the new reform impulse did not mean a complete break with a troubled racial past. Medical Civil Rights Activism in the Early-to-Mid-1960sU.S. hospitals remained racially segregated into the 1960s, with Black patients admitted to different wards from White patients or excluded altogether.][3] In the early 1960s, the Journal published correspondence and commentaries on hospital segregation.In 1963, it gave space to longtime physician-activist Hyman Gold, who excoriated the incoming Recognizing His toric al Injus tices in Medicine and the
Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates
Authors: Junqi Kuang, Pengli Li, Ziwei Zhai, Yixin Fan, HuaiYuan Xu, Chengchen Zhao, Wei Li, Xiaoxi Li, Zechuan Liang, Tao Huang, Yue Qin, Huiru Gao, Zhaoyi Ma, Dong Liu, Guifa Zhong, Bo Wang, Jing Liu, Jin Wang, Micky D. Tortorella, Baojian Liao, Duanqing Pei
Journal: Molecular Cancer (2024)

Abstract Nuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates, not wild type ones, readily exclude HDAC1 and 2 complexes, thus, allowing aberrant accumulation of H3K27ac on chromatin loci, leading to oncogenic expression of key target genes. These results provide the first case for condensate remodeling as a transforming event to generate oncogene and such condensates can be targeted for therapy. One sentence summary : Expulsion of HDACs complexes leads to oncogenic transformation.
In Situ Engineering Cancer Mask to Immobilize Tumor Cells and Block Metastasis
Authors: Xiaoke Zhang, Cheng Li, Dan Zhu, Hui Mao, Xiqun Jiang
Journal: Advanced Healthcare Materials (2024)

Abstract This work reports a new concept of cancer mask in situ to alter the specific biological functions of cancer cells. Metastatic cancer cells are highly invasive in part due to the presence of the glycan matrix in the cell membrane. Using a rational designed bio‐orthogonal reaction, the cancer cell surface is reconstructed in situ by incorporating endogenous polysialic acids in the glycan matrix on the cell membrane to form a mesh‐like network, called cancer mask. The network of the glycan matrix can not only immobilize cancer cells but also effectively block the stimulation of metastasis promoters to tumor cells and inhibit the formation of epithelial to mesenchymal transition (EMT), causing metastatic cancer cells incarceration. The results demonstrate a new strategy to control and even eliminate the cancer metastasis that is a major cause of treatment failure and poor patient outcome.
Natural Killer Cell‐Derived Extracellular Vesicles as Potential Anti‐Viral Nanomaterials
Authors: Siyoung A. Lim, Nathan Ho, Sophia Chen, Eun Ji Chung
Journal: Advanced Healthcare Materials (2024)

Abstract In viral infections, natural killer (NK) cells exhibit anti‐viral activity by inducing apoptosis in infected host cells and impeding viral replication through heightened cytokine release. Extracellular vesicles derived from NK cells (NK‐EVs) also contain the membrane composition, homing capabilities, and cargo that enable anti‐viral activity. These characteristics, and their biocompatibility and low immunogenicity, give NK‐EVs the potential to be a viable therapeutic platform. This study characterizes the size, EV‐specific protein expression, cell internalization, biocompatibility, and anti‐viral miRNA cargo to evaluate the anti‐viral properties of NK‐EVs. After 48 h of NK‐EV incubation in inflamed A549 lung epithelial cells, or conditions that mimic lung viral infections such as during COVID‐19, cells treated with NK‐EVs exhibit upregulated anti‐viral miRNA cargo (miR‐27a, miR‐27b, miR‐369‐3p, miR‐491‐5p) compared to the non‐treated controls and cells treated with control EVs derived from lung epithelial cells. Additionally, NK‐EVs effectively reduce expression of viral RNA and pro‐inflammatory cytokine (TNF‐α, IL‐8) levels in SARS‐CoV‐2 infected Vero E6 kidney epithelial cells and in infected mice without causing tissue damage while significantly decreasing pro‐inflammatory cytokine compared to non‐treated controls. Herein, this work elucidates the potential of NK‐EVs as safe, anti‐viral nanomaterials, offering a promising alternative to conventional NK cell and anti‐viral therapies.
Effectiveness of DialBetesPlus, a self-management support system for diabetic kidney disease: Randomized controlled trial
Authors: Kayo Waki, Mitsuhiko Nara, Syunpei Enomoto, Makiko Mieno, Eiichiro Kanda, Akiko Sankoda, Yuki Kawai, Kana Miyake, Hiromichi Wakui, Yuya Tsurutani, Nobuhito Hirawa, Tadashi Yamakawa, Shiro Komiya, Akihiro Isogawa, Shinobu Satoh, Taichi Minami, Tamio Iwamoto, Tatsuro Takano, Yasuo Terauchi, Kouichi Tamura, Toshimasa Yamauchi, Masaomi Nangaku, Naoki Kashihara, Kazuhiko Ohe
Journal: npj Digital Medicine (2024)

Abstract We evaluated the effectiveness of a mobile health (mHealth) intervention for diabetic kidney disease patients by conducting a 12-month randomized controlled trial among 126 type 2 diabetes mellitus patients with moderately increased albuminuria (urinary albumin-to-creatinine ratio (UACR): 30-299 mg/g creatinine) recruited from eight clinical sites in Japan. Using a Theory of Planned Behavior (TPB) behavior change theory framework, the intervention provides patients detailed information in order to improve patient control over exercise and dietary behaviors. In addition to standard care, the intervention group received DialBetesPlus, a self-management support system allowing patients to monitor exercise, blood glucose, diet, blood pressure, and body weight via a smartphone application. The primary outcome, change in UACR after 12 months (used as a surrogate measure of renal function), was 28.8% better than the control group’s change ( P = 0.029). Secondary outcomes also improved in the intervention group, including a 0.32-point better change in HbA1c percentage ( P = 0.041). These improvements persisted when models were adjusted to account for the impacts of coadministration of drugs targeting albuminuria (GLP-1 receptor agonists, SGLT-2 inhibitors, ACE inhibitors, and ARBs) (UACR: −32.3% [95% CI: −49.2%, −9.8%] between-group difference in change, P = 0.008). Exploratory multivariate regression analysis suggests that the improvements were primarily due to levels of exercise. This is the first trial to show that a lifestyle intervention via mHealth achieved a clinically-significant improvement in moderately increased albuminuria.