tbuckley/cabot-search huggingface dataset:
Hypertension Interventions for African American Patients in the Rural South
Authors: Deborah Grady, Lona Mody
Journal: JAMA Internal Medicine (2024)

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Extracellular Kir2.1 <sup>C122Y</sup> Mutant Upsets Kir2.1-PIP <sub>2</sub> Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome
Authors: Francisco M. Cruz, Álvaro Macías, Ana I. Moreno-Manuel, Lilian K. Gutiérrez, María Linarejos Vera-Pedrosa, Isabel Martínez-Carrascoso, Patricia Sánchez Pérez, Juan Manuel Ruiz Robles, Francisco J. Bermúdez-Jiménez, Aitor Díaz-Agustín, Fernando Martínez de Benito, Salvador Arias-Santiago, Aitana Braza-Boils, Mercedes Martín-Martínez, Marta Gutierrez-Rodríguez, Juan A. Bernal, Esther Zorio, Juan Jiménez-Jaimez, José Jalife
Journal: Circulation Research (2024)

Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K
Competitive fungal commensalism mitigates candidiasis pathology
Authors: Jarmila Sekeresova Kralova, Catalina Donic, Bareket Dassa, Ilana Livyatan, Paul Mathias Jansen, Shifra Ben-Dor, Lena Fidel, Sébastien Trzebanski, Lian Narunsky-Haziza, Omer Asraf, Ori Brenner, Hagit Dafni, Ghil Jona, Sigalit Boura-Halfon, Noa Stettner, Eran Segal, Sascha Brunke, Yitzhak Pilpel, Ravid Straussman, David Zeevi, Petra Bacher, Bernhard Hube, Neta Shlezinger, Steffen Jung
Journal: The Journal of Experimental Medicine (2024)

The mycobiota are a critical part of the gut microbiome, but host–fungal interactions and specific functional contributions of commensal fungi to host fitness remain incompletely understood. Here, we report the identification of a new fungal commensal, Kazachstania heterogenica var. weizmannii, isolated from murine intestines. K. weizmannii exposure prevented Candida albicans colonization and significantly reduced the commensal C. albicans burden in colonized animals. Following immunosuppression of C. albicans colonized mice, competitive fungal commensalism thereby mitigated fatal candidiasis. Metagenome analysis revealed K. heterogenica or K. weizmannii presence among human commensals. Our results reveal competitive fungal commensalism within the intestinal microbiota, independent of bacteria and immune responses, that could bear potential therapeutic value for the management of C. albicans–mediated diseases.
Myeloablation Followed by Hematopoietic Stem Cell Transplantation and Long‐Term Normalization of Systemic Sclerosis Molecular Signatures
Authors: Nancy Wareing, Xuan Wang, Lynette Keyes‐Elstein, Ellen A. Goldmuntz, Marka A. Lyons, Peter McSweeney, Daniel E. Furst, Richard A. Nash, Leslie J. Crofford, Beverly Welch, Ashley Pinckney, Maureen D. Mayes, Keith M. Sullivan, Shervin Assassi
Journal: Arthritis & Rheumatology (2024)

Objective In the randomized Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial, myeloablation, followed by hematopoietic stem cell transplantation (HSCT), led to the normalization of systemic sclerosis (SSc) peripheral blood cell (PBC) gene expression signature at the 26‐month visit. Herein, we examined long‐term molecular changes ensuing 54 months after randomization for individuals receiving an HSCT or 12 months of intravenous cyclophosphamide (CYC). Methods Global PBC transcript studies were performed in study participants at pretreatment baseline and at 38 months and 54 months after randomization, as well as in healthy controls using Illumina HT‐12 arrays. Results Thirty (HSCT = 19 and CYC = 11) participants had 38‐month samples available, and 26 (HSCT = 16 and CYC = 11) had 54‐month samples available. In the paired comparison to baseline, a significant down‐regulation of interferon modules and an up‐regulation of cytotoxic/natural killer module were observed at the 38‐month and 54‐month visits in the HSCT arm, indicating a long‐term normalization of baseline SSc gene expression signature. No differentially expressed modules were detected in the CYC arm. In comparison to samples from healthy controls, 38‐month visit samples in the HSCT arm showed an up‐regulation of B cell and plasmablast modules and a down‐regulation of myeloid and inflammation modules. Importantly, 54‐month HSCT samples did not show any differentially expressed modules compared to healthy control samples, suggesting completion of immune reconstitution. Participants in the CYC arm continued to show an SSc transcript signature in comparison to controls at both time points. Conclusion Paralleling the observed clinical benefit, HSCT leads to durable long‐term normalization of the molecular signature in SSc, with completion of immune resetting to 54 months after HSCT. image
Decolonization strategies against multidrug resistant organisms in the ICU
Authors: Pedro Póvoa, Paula Ramirez, Stijn Blot
Journal: Intensive Care Medicine (2024)

Multiple-drug resistant organisms (MDRO) are a consequence of antibiotic pressure, selection, and infection control failure.Regional variation in MDRO rates is evident [1].Important however, healthcare workers rarely become colonized with MDRO, probably because of a wellbalanced microbiota offering 'colonization resistance' against new invaders.Antibiotics disrupt this equilibrium leading to an increased risk of MRDO colonization and infection, potentially taking months to restore.Additionally, through horizontal transmission, the risk of MDRO colonization goes beyond antibiotic exposure.Our aim is to present practical recommendations for bedside clinicians concerning screening for MDRO and decolonization strategies (nasal, oropharyngeal, and skin).
Caring for frail patients in the ICU: a multidimensional approach
Authors: Maurizio Cecconi, Susannah Leaver, Christian Jung
Journal: Intensive Care Medicine (2024)

What is frailty?Frailty is a state of high vulnerability for adverse health outcomes, including disability, dependency, falls, need for long-term care, and mortality.This condition is associated with geriatric symptoms such as sarcopenia, cognitive impairment and dementia.Whilst it is more frequent in older age, it is not synonymous with old age and should, therefore, be considered separately.Frailty is characterised by the loss of biological reserves and heightens a patient's vulnerability to adverse health outcomes, hospitalisation, long-term dependency and mortality.Thus, recognising frailty in the clinical setting is crucial and necessitates a tailored approach [1,2].Frailty is identified through a comprehensive assessment of medical, cognitive and functional problems that aims to look at the patient's physiological reserve, identify and manage long-term health conditions, identify goals and ultimately develop a personalised treatment and support plan.This syndrome, a consequence of cumulative decline across multiple physiological systems, poses significant challenges in healthcare, particularly in acute settings such as the intensive care unit (ICU).Understanding the nuances of frailty and how to measure, it is critical to improving patient management and outcome [3].The tool used to measure frailty should be easy to understand, collect, and show good agreement amongst users.The Clinical Frailty Scale (CFS) is probably the most suitable tool in urgent situations [2].
Placebo-controlled trial of fluoxetine and phenelzine for obsessive- compulsive disorder
Authors: M A Jenike, L Baer, W E Minichiello, S L Rauch, M L Buttolph
Journal: American Journal of Psychiatry (1997)

It is now well documented that fluoxetine is a viable treatment option for patients with obsessive-compulsive disorder (OCD), and there is a small body of evidence indicating that monoamine oxidase inhibitors may be effective in at least a subset of patients. The authors conducted a 10-week placebo-controlled trial of these two agents in patients who met DSM-III-R criteria for OCD.Sixty-four subjects were randomly assigned to receive placebo, phenelzine (60 mg/day), or fluoxetine (80 mg/day). These doses were achieved by the end of week 3 of the active phase of the study. Outcomes were assessed with standardized instruments to measure OCD, mood, and anxiety.Fifty-four patients completed the study. There was a significant difference among the three treatments on one OCD scale, with fluoxetine-treated patients improving significantly more than those in the placebo or phenelzine group. A subgroup of OCD patients with symmetry obsessions did respond to phenelzine.This study provides no evidence to support the use of phenelzine in OCD except possibly for those patients with symmetry or other atypical obsessions. There was also no support for the hypothesis that patients with high levels of anxiety would respond preferentially to phenelzine.
A neoteric antibacterial ceria-silver nanozyme for abiotic surfaces
Authors: Abinaya Sindu Pugazhendhi, Craig J. Neal, Khoa Minh Ta, Marco Molinari, Udit Kumar, Fei Wei, Elayaraja Kolanthai, Andrew Ady, Christina Drake, Megan Hughes, Shibu Yooseph, Sudipta Seal, Melanie J. Coathup
Journal: Biomaterials (2024)
International nomenclature guidelines for the IL-1 family of cytokines and receptors
Authors: Joseph M. Gaballa, Jesper Falkesgaard Højen, Dennis M. De Graaf, Jesus Amo-Aparicio, Carlo Marchetti, Giulio Cavalli, Alberto Dinarello, Suzhao Li, Michaele Francesco Corbisiero, Isak W. Tengesdal, Jasmina S. Redzic, Tania Azam, William S. Webber, Karl A. Pankratz, Makenna J. May, Fabio Cominelli, Elan Z. Eisenmesser, Soohyun Kim, Charles A. Dinarello, Diana Boraschi
Journal: Nature Immunology (2024)
Musculoskeletal crosstalk in chronic obstructive pulmonary disease and comorbidities: Emerging roles and therapeutic potentials
Authors: Kevin Mou, Stanley M.H. Chan, Ross Vlahos
Journal: Pharmacology & Therapeutics (2024)

Chronic Obstructive Pulmonary Disease (COPD) is a multifaceted respiratory disorder characterized by progressive airflow limitation and systemic implications. It has become increasingly apparent that COPD exerts its influence far beyond the respiratory system, extending its impact to various organ systems. Among these, the musculoskeletal system emerges as a central player in both the pathogenesis and management of COPD and its associated comorbidities. Muscle dysfunction and osteoporosis are prevalent musculoskeletal disorders in COPD patients, leading to a substantial decline in exercise capacity and overall health. These manifestations are influenced by systemic inflammation, oxidative stress, and hormonal imbalances, all hallmarks of COPD. Recent research has uncovered an intricate interplay between COPD and musculoskeletal comorbidities, suggesting that muscle and bone tissues may cross-communicate through the release of signalling molecules, known as "myokines" and "osteokines". We explored this dynamic relationship, with a particular focus on the role of the immune system in mediating the cross-communication between muscle and bone in COPD. Moreover, we delved into existing and emerging therapeutic strategies for managing musculoskeletal disorders in COPD. It underscores the development of personalized treatment approaches that target both the respiratory and musculoskeletal aspects of COPD, offering the promise of improved well-being and quality of life for individuals grappling with this complex condition. This comprehensive review underscores the significance of recognizing the profound impact of COPD on the musculoskeletal system and its comorbidities. By unravelling the intricate connections between these systems and exploring innovative treatment avenues, we can aspire to enhance the overall care and outcomes for COPD patients, ultimately offering hope for improved health and well-being.
Genetically determined telomere length and risk for haematologic diseases: results from large prospective cohorts and Mendelian Randomization analysis
Authors: Yang Li, Jia Chen, Ting Sun, Yunfei Chen, Rongfeng Fu, Xiaofan Liu, Feng Xue, Wei Liu, Mankai Ju, Xinyue Dai, Huan Dong, Huiyuan Li, Wentian Wang, Ying Chi, Lei Zhang
Journal: Blood Cancer Journal (2024)
Monitoring capillary refill time in septic shock
Authors: Glenn Hernandez, Paula Carmona, Hafid Ait-Oufella
Journal: Intensive Care Medicine (2024)

Capillary refill time (CRT) has been proposed as a marker of tissue hypoperfusion based on physiological and clinical-epidemiological data and is increasingly used as a monitor in shock states and other conditions [1][2][3][4].Indeed, besides being costless and universally available, CRT is a dynamic parameter which changes rapidly in response to hemodynamic interventions, thus making it a suitable bedside tool to monitor and guide septic shock resuscitation [1].Unfortunately, specific guidelines to standardize how to estimate CRT do not currently exist.This toolbox aims to provide a practical overview of the fundamentals of CRT assessment to facilitate and optimize its use at the bedside.
Nanotherapeutics targeting autophagy regulation for improved cancer therapy
Authors: Yunmeng Liu, Yaxin Wang, Jincheng Zhang, Qikai Peng, Xingdong Wang, Xiyue Xiao, Kai Shi
Journal: Acta Pharmaceutica Sinica B (2024)

The clinical efficacy of current cancer therapies falls short, and there is a pressing demand to integrate new targets with conventional therapies. Autophagy, a highly conserved self-degradation process, has received considerable attention as an emerging therapeutic target for cancer. With the rapid development of nanomedicine, nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance. Hence, considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy, we outline the latest advances in autophagy-based nanotherapeutics. Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression, the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated. Further, emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways, including modulation of the mammalian target of rapamycin (mTOR) pathway, autophagy-related (ATG) and its complex expression, reactive oxygen species (ROS) and mitophagy, interference with autophagosome-lysosome fusion, and inhibition of hypoxia-mediated autophagy. In addition, combination therapies in which nano-autophagy modulation is combined with chemotherapy, phototherapy, and immunotherapy are also described. Finally, the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.
Mapping the distribution of tension across paxillin upon shear stress with FRET-based biosensor
Authors: Shuai Shao, Sha Deng, Na Li, Zhengyao Zhang, Hangyu Zhang, Bo Liu
Journal: Med-X (2024)

Abstract Paxillin communicates with multiple signalling molecules in focal adhesions (FAs) and participates in the intracellular force transmission upon shear stress. Thus, paxillin is likely to contribute to establishing the shear stress induced-cell polarity. However, it is still unclear whether the tension across FAs proteins can direct the polarity establishments by providing spatial features, due to a lack of efficient manners. This work proposes a visualization approach containing a DNA-encoded biosensor and fluorescent image processing algorithm to collect the spatiotemporal features of tension across paxillin. The results indicate that the tension across paxillin shows polarity between the upstream and downstream zones of the cell along the direction of shear stress, which was mediated by the membrane fluidity and integrity of the cytoskeleton. It demonstrates that the spatial information from the upper surface of cells upon shear stress can be transmitted to the interior of FAs on the basal layer by the architecture consisting of plasma membrane and cytoskeleton. Paxillin is a potential participant in activating cell polarity by providing a spatial mechanical guide to related signaling molecules upon shear stress. Graphical Abstract
EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update
Authors: Laure Gossec, Andreas Kerschbaumer, Ricardo J O Ferreira, Daniel Aletaha, Xenofon Baraliakos, Heidi Bertheussen, Wolf-Henning Boehncke, Bente Appel Esbensen, Iain B McInnes, Dennis McGonagle, Kevin L Winthrop, Andra Balanescu, Peter V Balint, Gerd R Burmester, Juan D Cañete, Pascal Claudepierre, Lihi Eder, Merete Lund Hetland, Annamaria Iagnocco, Lars Erik Kristensen, Rik Lories, Rubén Queiro, Daniele Mauro, Helena Marzo-Ortega, Philip J Mease, Peter Nash, Wendy Wagenaar, Laura Savage, Georg Schett, Stephanie J W Shoop-Worrall, Yoshiya Tanaka, Filip E Van den Bosch, Annette van der Helm-van Mil, Alen Zabotti, Désirée van der Heijde, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2024)

New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA.
Orthodontic retention: Rationale and periodontal implications
Authors: Padhraig S. Fleming, Nikolaos Pandis
Journal: Periodontology 2000 (2024)

Abstract Post‐treatment change in the form of true relapse and physiological and maturational effects is common following orthodontics. The unpredictable nature of these manifestations dictates a conservative, near‐universal approach to retention. Both fixed and removable forms of retention are popular with the latter constrained by variable levels of adherence particularly in the medium‐ to long‐term. Fixed retention may offer a more predictable means of preservation of orthodontic outcomes; however, this advantage is offset by the requirement for prolonged supervision and the potential for adverse changes including periodontal breakdown. Nevertheless, while examples of severe complications are common, a clear causal relationship between intact, passive retainers and periodontal issues does not appear to exist. Nevertheless, the importance of diligent maintenance and careful supervision during fixed retention, in particular, cannot be disregarded.
Impact of post-COVID-19 condition on health status and activities of daily living: the PRIME post-COVID study
Authors: Maarten Van Herck, Demi M E Pagen, Céline J A van Bilsen, Stephanie Brinkhues, Kevin Konings, Casper D J den Heijer, Suhreta Mujakovic, Henriëtte L G ter Waarbeek, Chris Burtin, Daisy J A Janssen, Christian J P A Hoebe, Martijn A Spruit, Nicole H T M Dukers-Muijrers
Journal: Thorax (2024)

Objective To assess health and activities of daily living (ADL) in SARS-CoV-2-positive adults with and without post-COVID-19 condition (PCC) and compare this with negative tested individuals. Furthermore, different PCC case definitions were compared with SARS-CoV-2-negative individuals. Methods All adults tested PCR positive for SARS-CoV-2 at the Public Health Service South Limburg (Netherlands) between June 2020 and November 2021 (n=41 780) and matched PCR negative individuals (2:1, on age, sex, year-quarter test, municipality; n=19 875) were invited by email. Health (five-level EuroQol five-dimension (EQ5D) index and EuroQol visual analogue scale (EQVAS)) and ADL impairment were assessed. PCC classification was done using the WHO case definition and five other common definitions. Results In total, 8409 individuals (6381 SARS-CoV-2 positive; 53±15 years; 57% female; 9 (7–11) months since test) were included. 39.4% of positives had PCC by the WHO case definition (EQVAS: 71±20; EQ5D index: 0.800±0.191; ADL impairment: 30 (10–70)%) and perceived worse health and more ADL impairment than negatives, that is, difference of −8.50 points (95% CI −9.71 to −7.29; p&lt;0.001) for EQVAS, which decreased by 1.49 points (95% CI 0.86 to 2.12; p&lt;0.001) in individuals with PCC for each comorbidity present, and differences of −0.065 points (95% CI −0.074 to −0.056; p&lt;0.001) for EQ5D index, and +16.72% (95% CI 15.01 to 18.43; p&lt;0.001) for ADL impairment. Health and ADL impairment were similar in negatives and positives without PCC. Replacing the WHO case definition with other PCC definitions yielded comparable results. Conclusions Individuals with PCC have substantially worse health and more ADL impairment than negative controls, irrespective of the case definition. Authorities should inform the public about the associated burden of PCC and enable adequate support.
New entity of adult ultra-short coeliac disease: the first international cohort and case–control study
Authors: Suneil A Raju, Emily A Greenaway, Annalisa Schiepatti, Giovanni Arpa, Nicoletta Vecchione, Chao LA Jian, Charlotte Grobler, Margherita Maregatti, Olivia Green, Freya J Bowker-Howell, Mohamed G Shiha, Hugo A Penny, Simon S Cross, Carolina Ciacci, Kamran Rostami, Shokoufeh Ahmadipour, Afshin Moradi, Mohammad Rostami-Nejad, Federico Biagi, Umberto Volta, Michelangelo Fiorentino, Benjamin Lebwohl, Peter HR Green, Suzanne Lewis, Javier Molina-Infante, Pilar Mata-Romero, Valentina Vaira, Luca Elli, Irfan Soykan, Arzu Ensari, David S Sanders
Journal: Gut (2024)

Background Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. Methods Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. Findings Patients with USCD (n=137, median age 27 years, IQR 21–43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p&lt;0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1–5.9) vs 12.6×ULN (IQR 3.3–18.3), p&lt;0.001). Patients with USCD had the same number of symptoms overall (median 3 (IQR 2–4) vs 3 (IQR 1–4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006). Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4. At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440–2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2–1.4) vs 0.7 ULN (IQR 0.2–2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. Interpretation Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.