tbuckley/cabot-search huggingface dataset:
The Association of Outdoor Temperature with Severe Hyponatremia
Authors: Issa Issa, Jakob Skov, Henrik Falhammar, Jonatan D. Lindh, Buster Mannheimer
Journal: Journal of the American Society of Nephrology (2024)

Hyponatremia is a common condition with unspecific symptoms and a complicated etiology. The impact of outdoor temperature on hyponatremia is not well-studied and varies depending on the climate and location. This study aimed to investigate the association between outdoor temperature and the prevalence of severe hyponatremia. This retrospective register-based cohort study based on the Stockholm Sodium Cohort investigated the association between ambient temperatures and severe hyponatremia (<125 mmol/L) in adults. Prevalence rates of severe hyponatremia were calculated as the number of days of severe hyponatremia divided by person-days at risk for the same temperature, using mean daily temperatures at the area of residence of each study participant to calculate exposure time. A prediction model incorporating changes in demographics and climate was used to estimate the burden of severe hyponatremia in Stockholm by 2050. We identified 51,143 episodes of severe hyponatremia in 21,924 adults. A near linear modest increase in prevalence with rising temperatures was observed up to 20°C, followed by rapidly increasing rates at higher temperatures. The prevalence was higher with older age, reaching >100 days of hyponatremia per million person-days among +80-years-olds at temperatures over 22°C. Women experienced twice the rate observed in men. Temperature rises of 1°C or 2°C by the year 2050 are expected to be associated with higher prevalence rates by 66% and 73%, respectively. There was a strong association between high temperatures and severe hyponatremia. The higher prevalence of severe hyponatremia was most pronounced among elderly.
Radiomultiomics: quantitative CT clusters of severe asthma associated with multi-omics
Authors: Nazanin Zounemat Kermani, Kian Fan Chung, Giuseppe Macis, Giuseppe Santini, Franz A. A. Clemeno, Ali Versi, Kai Sun, Mahmoud I. Abdel-Aziz, Lars I. Andersson, Charles Auffray, Yusef Badi, Per Bakke, Chris Brightling, Paul Brinkman, Massimo Caruso, Pascal Chanez, Bertrand De Meulder, Ratko Djukanovic, Leonardo Fabbri, Stephen J. Fowler, Ildiko Horvath, Peter Howarth, Anna J. James, Johan Kolmert, Monica Kraft, Chuan-Xing Li, Anke H. Maitland-van der Zee, Mario Malerba, Alberto Papi, Klaus Rabe, Marek Sanak, Dominick E. Shaw, Dave Singh, Maria Sparreman Mikus, Maarten van Den Berge, Asa M. Wheelock, Craig E. Wheelock, Valentyna Yasinska, Yi-ke Guo, Scott Wagers, Peter J. Barnes, Andrew Bush, Peter J. Sterk, Sven-Erik Dahlen, Ian M. Adcock, Salman Siddiqui, Paolo Montuschi
Journal: European Respiratory Journal (2024)

Rationale Lung quantitative computed tomographic (qCT) severe asthma clusters have been reported, but their replication and underlying disease mechanisms are unknown. We identified and replicated qCT clusters of severe asthma in two independent asthma cohorts and determined their association with molecular pathways. Methods We used consensus clustering on qCT measurements of airway and lung CT scans, performed in 105 severe asthmatic adults from the U-BIOPRED cohort. The same qCT measurements were used to replicate qCT clusters in a subsample of the ATLANTIS asthma cohort (n=97). We performed integrated enrichment analysis using blood, sputum, bronchial biopsies, bronchial brushings and nasal brushings transcriptomics and blood and sputum proteomics to characterize radiomultiomic-associated clusters (RACs). Results qCT clusters and clinical features in U-BIOPRED were replicated in the matched ATLANTIS cohort. In the U-BIOPRED cohort, RAC1 (n=30) was predominantly female with elevated BMI, mild airflow limitation, normal qCT parameters and upregulation of the complement pathway. RAC2 (n=34) subjects had a lower degree of airflow limitation, airway wall thickness and dilatation, with upregulation of proliferative pathways, including neurotrophic receptor tyrosine kinase 2/tyrosine kinase receptor B (NTRK2/TRKB), and down-regulation of semaphorin pathways. RAC3 (n=41) showed increased lung attenuation area and air trapping, severe airflow limitation, hyperinflation, and upregulation of cytokine signaling and signaling by interleukin pathways, and matrix metallopeptidase 1, 2 and 9. Conclusions U-BIOPRED severe asthma qCT clusters were replicated in a matched independent asthmatic cohort and associated with specific molecular pathways. Radiomultiomics might represent anovel strategy to identify new molecular pathways in asthma pathobiology.
Distinct trajectories of treatment response to mepolizumab toward remission in patients with severe eosinophilic asthma
Authors: Yuto Hamada, Dennis Thomas, Erin S. Harvey, Sean Stevens, Michael Fricker, Hayley Lewthwaite, Vanessa M. McDonald, Andrew Gillman, Mark Hew, Vicky Kritikos, John W. Upham, Peter G. Gibson
Journal: European Respiratory Journal (2024)

Patients with severe eosinophilic asthma, characterised by a high disease burden, benefit from mepolizumab, which improves symptoms and reduces exacerbations, potentially leading to clinical remission in a subgroup. This study aimed to identify treatment response trajectories to mepolizumab for severe eosinophilic asthma and to assess the achievement of clinical remission. Data from the Australian Mepolizumab Registry were used to assess treatment responses at 3, 6, and 12 months. The treatment response trajectories were identified using a group-based trajectory model. The proportions achieving clinical remission at 12 months, which was defined as well-controlled symptoms, no exacerbations, and no oral corticosteroid (OCS) use for asthma management, were compared between trajectories, and baseline predictors of the trajectories were identified using logistic regression analysis. We identified three trajectory groups: group 1, responsive asthma with less OCS use (n=170); group 2, responsive late-onset asthma (n=58); and group 3, obstructed and less responsive asthma (n=70). Groups 1 and 2 demonstrated higher proportions achieving clinical remission at 36.5% and 25.9%, respectively, compared to group 3 with 5.7% (p &lt;0.001). Baseline predictors for assigned groups included lower OCS dose in group 1; greater FEV 1 % predicted, higher Asthma Quality of Life Questionnaire score, higher OCS dose, and nasal polyps in group 2; with group 3 as the reference. Treatment response to mepolizumab in severe eosinophilic asthma follows 3 trajectories with varying proportions achieving clinical remission and differing baseline characteristics. Treatment response variability may influence the achievement of clinical remission with mepolizumab therapy.
More Efficient Smaller Multi-Cancer Screening Trials
Authors: Peter Sasieni, Adam R Brentnall
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background The NHS-Galleri trial has demonstrated feasibility for multi-cancer screening trial design where all participants provide a ‘sample’ for screening, but only samples from the intervention arm are tested and acted upon during the trial. We assess efficiency of analysis methods when the control arm may be retrospectively tested at time of analysis. Methods Analyses considered are: (1, traditional) by randomised allocation with all events included; (2, ‘intended-effect’) nested in those who tested positive in both arms and all events therein; and (3, targeted) by randomised allocation but with endpoint ‘test-positive event’. They are compared using approximate statistical methods and scenario analysis. Results Provided the number who die from cancer after a test-positive sample is a small fraction of the total number who die from cancer, intended-effect and targeted analyses require a much smaller sample size to evaluate cancer-specific mortality than the traditional approach. Intended-effect analysis has a smaller sample size requirement than targeted analysis. This gain is only substantial when the risk of cancer death in test positives is high. Conclusion Intended-effect or targeted analysis will substantially reduce the sample size needed to evaluate cancer-specific mortality in blood-based screening trials. Targeted analysis requires many fewer retrospective tests and avoids potential effects of needing to inform those whose stored samples test positive. Trialists should consider the trade-off of costs between sample size and retrospective testing requirements when choosing the analysis.
A prospective study of neoadjuvant pembrolizumab plus chemotherapy for resectable esophageal squamous cell carcinoma: The Keystone-001 trial
Authors: Xiaobin Shang, Yongjie Xie, Jinpu Yu, Chen Zhang, Gang Zhao, Fei Liang, Liang Liu, Weihong Zhang, Runmei Li, Wenwen Yu, Jie Yue, Chuangui Chen, Xiaofeng Duan, Zhao Ma, Zuoyu Chen, Yanjuan Xiong, Fan Yang, Jianyu Xiao, Rui Zhang, Pengpeng Liu, Yanan Cheng, Fuliang Cao, Feng Guo, Guoyan Liu, Bin Meng, Dejun Zhou, Yan Sun, Xiubao Ren, Jun Yu, Jihui Hao, Hongjing Jiang
Journal: Cancer Cell (2024)
SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data
Authors: Yunqing Liu, Ningshan Li, Ji Qi, Gang Xu, Jiayi Zhao, Nating Wang, Xiayuan Huang, Wenhao Jiang, Huanhuan Wei, Aurélien Justet, Taylor S. Adams, Robert Homer, Amei Amei, Ivan O. Rosas, Naftali Kaminski, Zuoheng Wang, Xiting Yan
Journal: Genome biology (2024)

Spatial barcoding-based transcriptomic (ST) data require deconvolution for cellular-level downstream analysis. Here we present SDePER, a hybrid machine learning and regression method to deconvolve ST data using reference single-cell RNA sequencing (scRNA-seq) data. SDePER tackles platform effects between ST and scRNA-seq data, ensuring a linear relationship between them while addressing sparsity and spatial correlations in cell types across capture spots. SDePER estimates cell-type proportions, enabling enhanced resolution tissue mapping by imputing cell-type compositions and gene expressions at unmeasured locations. Applications to simulated data and four real datasets showed SDePER's superior accuracy and robustness over existing methods.
Evidence for a lipofibroblast-to-<b><i>Cthrc1</i></b>+ myofibroblast reversible switch during the development and resolution of lung fibrosis in young mice
Authors: Arun Lingampally, Marin Truchi, Olivier Mauduit, Vanessa Delcroix, Esmeralda Vasquez-Pacheco, Marine Gautier-Isola, Xuran Chu, Ali Khadim, Cho-Ming Chao, Mahsa Zabihi, Sara Taghizadeh, Stefano Rivetti, Manuela Marega, Alena Moiseenko, Stefan Hadzic, Ana Ivonne Vazquez-Armendariz, Susanne Herold, Stefan Günther, Pamela Millar-Büchner, Janine Koepke, Christos Samakovlis, Jochen Wilhelm, Marek Bartkuhn, Thomas Braun, Norbert Weissmann, JinSan Zhang, Malgorzata Wygrecka, Helen p Makarenkova, Andreas Günther, Werner Seeger, Chengshui Chen, Elie El Agha, Bernard Mari, Saverio Bellusci
Journal: European Respiratory Journal (2024)

Background Fibrosis is often associated with aberrant repair mechanisms that ultimately lead to organ failure. In the lung, idiopathic pulmonary fibrosis (IPF) is a fatal form of interstitial lung disease (ILD) to which there is currently no curative therapy. From the cell biology point of view, the cell of origin and eventual fate of activated myofibroblasts (aMYFs) have taken center stage as these cells are believed to drive structural remodeling and lung function impairment. While aMYFs are now widely believed to originate from resident fibroblasts, the heterogeneity of aMYFs and ultimate fate during fibrosis resolution remain elusive. We have previously shown that aMYFs dedifferentiation and acquisition of a lipofibroblast (LIF)-like phenotype represent a route of fibrosis resolution. Methods In this study, we combined genetic lineage tracing and single-cell transcriptomics in mice, and data mining of human IPF datasets to decipher the heterogeneity of aMYFs and investigate differentiation trajectories during fibrosis resolution. Furthermore, organoid cultures were utilized as a functional readout for the alveolar mesenchymal niche activity during various phases of injury and repair in mice. Results Our data demonstrate that aMYFs consist of four subclusters displaying unique pro-alveologenic versus profibrotic profiles. Alveolar fibroblasts displaying a high LIF-like signature largely constitute both the origin and fate of aMYFs during fibrogenesis and resolution respectively. The heterogeneity of aMYFs is conserved in humans and a significant proportion of human aMYFs displays a high LIF signature. Conclusion Our work identifies a subcluster of aMYFs that is potentially relevant for future management of IPF.
Global Invasion History and Genomic Signatures of Adaptation of the Highly Invasive Sycamore Lace Bug
Authors: Zhenyong Du, Xuan Wang, Yuange Duan, Shanlin Liu, Li Tian, Fan Song, Wanzhi Cai, Hu Li
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Invasive species cause massive economic and ecological damage. Climate change has resulted in an unprecedented increase in the number and impact of invasive species; however, the mechanisms underlying these invasions are unclear. The sycamore lace bug, Corythucha ciliata, is a highly invasive species originating from North America and has expanded across the Northern Hemisphere since the 1960s. In this study, we assembled the C. ciliata genome using high-coverage Pacific Biosciences (PacBio), Illumina, and high-throughput chromosome conformation capture (Hi-C) sequencing. A total of 15,278 protein-coding genes were identified, and expansions of gene families with oxidoreductase and metabolic activities were observed. In-depth resequencing of 402 samples from native and nine invaded countries across three continents revealed 2.74 million single nucleotide polymorphisms. Two major invasion routes of C. ciliata were identified from North America to Europe and Japan, with a contact zone forming in East Asia. Genomic signatures of selection associated with invasion and long-term balancing selection in native ranges were identified. These genomic signatures overlapped with expanded genes, suggesting improvements in the oxidative stress and thermal tolerance of C. ciliata. These findings offer valuable insights into the genomic architecture and adaptive evolution underlying the invasive capabilities of species during rapid environmental changes.
Reading and conducting instrumental variable studies: guide, glossary, and checklist
Authors: Venexia Walker, Eleanor Sanderson, Michael G Levin, Scott M Damraurer, Timothy Feeney, Neil M Davies
Journal: BMJ (2024)

Instrumental variable analysis uses naturally occurring variation to estimate the causal effects of treatments, interventions, and risk factors on outcomes in the population from observational data. Under specific assumptions, instrumental variable methods can provide unbiased estimates of causal effects. This article explains these assumptions and the information and tests typically reported in instrumental variable studies, which can assess the credibility of the findings of instrumental variable studies.
Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition
Authors: Baptiste Libé-Philippot, Ryohei Iwata, Aleksandra J Recupero, Keimpe Wierda, Sergio Bernal Garcia, Luke Hammond, Anja van Benthem, Ridha Limame, Martyna Ditkowska, Sofie Beckers, Vaiva Gaspariunaite, Eugénie Peze-Heidsieck, Daan Remans, Cécile Charrier, Tom Theys, Franck Polleux, Pierre Vanderhaeghen
Journal: Neuron (2024)

Human-specific (HS) genes have been implicated in brain evolution, but their impact on human neuron development and diseases remains unclear. Here, we study SRGAP2B/C, two HS gene duplications of the ancestral synaptic gene SRGAP2A, in human cortical pyramidal neurons (CPNs) xenotransplanted in the mouse cortex. Downregulation of SRGAP2B/C in human CPNs led to strongly accelerated synaptic development, indicating their requirement for the neoteny that distinguishes human synaptogenesis. SRGAP2B/C genes promoted neoteny by reducing the synaptic levels of SRGAP2A,thereby increasing the postsynaptic accumulation of the SYNGAP1 protein, encoded by a major intellectual disability/autism spectrum disorder (ID/ASD) gene. Combinatorial loss-of-function experiments in vivo revealed that the tempo of synaptogenesis is set by the reciprocal antagonism between SRGAP2A and SYNGAP1, which in human CPNs is tipped toward neoteny by SRGAP2B/C. Thus, HS genes can modify the phenotypic expression of genetic mutations leading to ID/ASD through the regulation of human synaptic neoteny.
CRISPR screens unveil nutrient-dependent lysosomal and mitochondrial nodes impacting intestinal tissue-resident memory CD8+ T cell formation
Authors: Jana L Raynor, Nicholas Collins, Hao Shi, Cliff Guy, Jordy Saravia, Seon Ah Lim, Nicole M Chapman, Peipei Zhou, Yan Wang, Yu Sun, Isabel Risch, Haoran Hu, Anil Kc, Renqiang Sun, Sharad Shrestha, Hongling Huang, Jon P Connelly, Shondra M Pruett-Miller, Miguel Reina-Campos, Ananda W Goldrath, Yasmine Belkaid, Hongbo Chi
Journal: Immunity (2024)
Progress of nations in the organisation of, and structures for, kidney care delivery between 2019 and 2023: cross sectional survey in 148 countries
Authors: Ikechi G Okpechi, Adeera Levin, Somkanya Tungsanga, Silvia Arruebo, Fergus J Caskey, Innocent I Chukwuonye, Sandrine Damster, Jo-Ann Donner, Udeme E Ekrikpo, Anukul Ghimire, Vivekanand Jha, Valerie Luyckx, Masaomi Nangaku, Syed Saad, Elliot K Tannor, Marcello Tonelli, Feng Ye, Aminu K Bello, David W Johnson
Journal: BMJ (2024)

To assess changes in key measures of kidney care using data reported in 2019 and 2023.
Deep brain stimulation of the motor thalamus relieves experimentally induced air hunger
Authors: Tom p Chapman, Amir p Divanbeighi Zand, Emmanuel Debrah, Beth Petric, Sarah M Farrell, James J FitzGerald, Shakeeb H Moosavi, Alexander L Green
Journal: European Respiratory Journal (2024)

Research question We previously reported that Deep Brain Stimulation (DBS) of motor thalamus (MT), in a patient with post-stroke tremor, relieved breathlessness associated with chronic obstructive pulmonary disease. This raised the question of whether MT DBS mitigates the ascending dyspnoea signal. We therefore sought to conduct a fully powered cohort study of experimentally induced air hunger (AH), an uncomfortable urge to breathe in patients with MT DBS ON and OFF. Methods 16 patients (3 females) with DBS of the ventral intermediate nucleus (VIM) as treatment for tremor, underwent hypercapnic AH tests, with DBS “ON” and “OFF”. Patients rated AH on a visual analogue scale (VAS) every 15 s. Hypercapnia and ventilation were matched for ON and OFF states (mean± sd 43±4 and 43±4 mmHg for end-tidal P CO 2 , 13.7 and 13.4 L·min −1 for ventilation). Participants ventilation was constrained to baseline levels by breathing from a 3-litre inspiratory reservoir with fixed flow of fresh gas while targeting their resting breathing frequency to a metronome. Results Overall steady state AH was 52±28%VAS for “ON” and 67±20%VAS for “OFF” (p=0.002; two-tailed paired t-test). The mean reduction in AH during VIM DBS was −14.4%VAS. MT DBS relieved AH in thirteen patients, heightened AH in two and caused no change in one. Conclusion MT DBS for tremor relief also mitigates the AH component of dyspnoea. We posit that DBS of the MT heightens the gating control of the thalamus modulating the ascending air hunger signal. Extent of relief suggests that thalamic DBS may prove to be a viable therapy for intractable dyspnoea.
Ansa Cervicalis Stimulation Effects on Upper Airway Patency: A Structure-Based Analysis
Authors: Yike Li, Alan R. Schwartz, David Zealear, Matthew S. Shotwell, Megan E. Hall, Christopher J. Lindsell, Holly A. Budnick, Silvana Bellotto, David T. Kent
Journal: European Respiratory Journal (2024)

Rationale Ansa cervicalis stimulation (ACS) of the infrahyoid muscles has been proposed as a neurostimulation therapy for obstructive sleep apnea (OSA). ACS stabilizes the pharynx by pulling it caudally, but its specific effects on flow limitation caused by palatal, oropharyngeal lateral wall, tongue base, or epiglottis collapse remains unclear. Objectives To quantify the effect of ACS on collapsibility of different pharyngeal flow-limiting structures. Methods Participants with OSA underwent bilateral ACS during drug-induced sleep endoscopy. Maximum inspiratory airflow was assessed over a range of positive airway pressures while ACS was applied. The flow-limiting structure for each breath was classified based on manometric and endoscopic findings and a linear mixed-effects model characterized their response to ACS. The influence of patient characteristics was explored with univariate models. Measurements and Main Results Forty-one participants yielded 1761 breaths for analysis. On average, bilateral ACS decreased the observed pharyngeal critical closing (P CRIT ) and opening (P OPEN ) pressures by −3.0 [95% confidence interval: [-3.6, −2.3] and −3.7 [-4.4, −3.0] cmH2O, respectively (p&lt;0.001). During tongue base obstruction, modeled ACS effects for P CRIT and P OPEN were −2.0 [-2.7, −1.4] and −3.1 [-3.8, −2.4] cmH 2 O, respectively (p&lt;0.001). Greater reductions were generally observed for other flow-limiting structures. A lower apnea-hypopnea index was associated with a greater decrease in P OPEN (p&lt;0.01). Other patient characteristics, including body mass index, did not influence P CRIT or P OPEN (p&gt;0.05). Conclusions Bilateral ACS decreased collapsibility of all airway flow-limiting structures. ACS generally had greater effects on palatal, oropharyngeal lateral wall, and epiglottic collapse than the tongue base.
Application of Drug Delivery System Based on Nanozyme Cascade Technology in Chronic Wound
Authors: Wenyu Wang, Zhipeng Li, Chaolong Liu, Hongli Yu, Yong Sun
Journal: Advanced Healthcare Materials (2024)

Abstract Chronic wounds are characterized by long‐term inflammation, including diabetic ulcers, traumatic ulcers, etc., which provide an optimal environment for bacterial proliferation. At present, antibiotics are the main clinical treatment method for chronic wound infections. However, the overuse of antibiotics may accelerate the emergence of drug‐resistant bacteria, which poses a significant threat to human health. Therefore, there is an urgent need to develop new therapeutic strategies for bacterial infections. Nanozyme‐based antimicrobial therapy (NABT) is an emerging antimicrobial strategy with broad‐spectrum activity and low drug resistance compared to traditional antibiotics. NABT has shown great potential as an emerging antimicrobial strategy by catalyzing the generation of reactive oxygen species (ROS) with its enzyme‐like catalytic properties, producing a powerful bactericidal effect without developing drug resistance. Nanozyme‐based cascade antimicrobial technology offers a new approach to infection control, effectively improving antimicrobial efficacy by activating cascades against bacterial cell membranes and intracellular DNA while minimizing potential side effects. However, it is worth noting that this technology is still in the early stages of research. This article comprehensively reviews wound classification, current methods for the treatment of wound infection, different types of nanozymes, the application of nanozyme cascade reaction technology in antimicrobial therapy, and future challenges and prospects.