bluuebunny/crossref_metadata_2025_split huggingface dataset:
Left ventricular trabecular layer operates at high ejection fraction: implications for pump function assessment in excessive trabeculation
Authors: Visoiu Ionela Simona , Rimbas Roxana Cristina , Nicula Alina Ioana , Vinereanu Dragos , Jensen Bjarke 
Published: January 2024

ABSTRACTAimsNumerous diagnostic criteria for excessive trabeculation (ET), or so-called “noncompaction”, score the extent of the trabecular layer, yet whether the trabeculations themselves have a negative or positive impact on pump function is largely unknown. This study aimed to measure the ejection fraction (EF) of the trabecular layer and its impact on pump function assessment.Methods and resultsWe retrospectively analyzed cardiac magnetic resonance (CMR) findings in patients with ET of the left ventricle (LV). The LV was labelled into four regions: compact wall, central cavity (CC), trabeculations, and intertrabecular recesses (IR). For each label we calculated the systolic fractional volume change (SFVC) in short-axis images (n=15) and systolic fractional area change (SFAC) in 4-chamber images (n=30), by dividing end-systolic to end-diastolic values. We measured the EF of IR, CC, and total cavity (TC). Three methods to calculate EF of the TC were compared: trabeculations included (per guidelines), IR excluded (Jacquier criterion), trabeculations contoured and excluded (contour-EF).The SFVC and SFAC of the compact wall were similar with SFVC and SFAC of trabeculations (both P>0.05). In contrast, the IR were more diminished in systole by comparison with the CC, having lower SFVC (39±17% vs. 56±16%, P<0.001) and SFAC (37±22% vs. 72±12%, P<0.001). EF of the IR was also greater than EF of the CC (61±17% vs. 44±16%, P<0.001). Excluding IR from the TC or including trabeculations underestimates the contour-EF (44±16% and 40±12%, respectively, vs. 51±16%; both P<0.001).ConclusionsThe trabecular layer has a high EF. Values of key prognostic indicators are better when this is accounted for.Graphical AbstractEF, ejection fraction; LVEF, left ventricular ejection fraction; SAX, short-axis; 4c, 4 chamber. *P<0001
The antidepressant effects of vaporized N,N-Dimethyltryptamine: a preliminary report in treatment-resistant depression
Authors: Falchi-Carvalho Marcelo , Barros Handersson , Bolcont Raynara , Laborde Sophie , Wießner Isabel , Silva Sérgio Ruschi B. , Montanini Daniel , Barbosa David C. , Teixeira Ewerton , Florence-Vilela Rodrigo , Almeida Raissa , de Macedo Rosana K. A. , Arichelle Flávia , Pantrigo Érica J. , Arcoverde Emerson , Galvão-Coelho Nicole , Araujo Draulio B. , Palhano-Fontes Fernanda 
Published: January 2024

AbstractIntroductionN,N-Dimethyltryptamine (DMT), a naturally occurring psychedelic tryptamine contained in the indigenous ayahuasca brew has shown antidepressant effects. This Phase 2a clinical trial investigates for the first time the efficacy of isolated DMT in treatment-resistant depression (TRD).MethodsSix TRD patients participated in an open-label, fixed-order, dose-escalation study, receiving a lower (15 mg) and then a higher (60 mg) dose of vaporized DMT in a single-day session. Depression severity was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Patient Health Questionnaire-9 (PHQ-9) up to one-month post-dosing.ResultsSignificant reductions in MADRS and PHQ-9 scores were noted from Day 1 to M1. The mean MADRS score variation from baseline to D7 was −22 points and −17 points at M1. PHQ-9 scores also showed significant decreases, mirroring the MADRS results. By D7, 83.33% of patients responded to treatment, with 66.67% achieving remission. At M1, 66.67% maintained response, and 50% maintained remission.DiscussionThe rapid onset and sustained antidepressant effects of vaporized DMT align with the paradigm of rapid-acting antidepressants to be used in the scope of interventional psychiatry. The non-invasive route and short-acting nature of DMT offer practical advantages, potentially enhancing accessibility to psychedelic treatments.Clinical Trial registrationClinicaltrials.govNCT06094907
Quantification of Cerebrospinal Fluid Tumor DNA in Lung Cancer Patients with Suspected Leptomeningeal Carcinomatosis
Authors: Azad Tej D. , Nanjo Shigeki , Jin Michael C. , Chabon Jacob J. , Kurtz David M. , Chaudhuri Aadel A. , Connolly Ian D. , Hui Angela Bik-Yu , Liu Chih Long , Merriott David , Ko Ryan , Yoo Christopher , Carter Justin , Chen Emily , Bonilla Rene , Hata Akito , Katakami Nobuyuki , Irie Kei , Yano Seiji , Okimoto Ross , Bivona Trever G. , Newman Aaron M. , Iv Michael , Nagpal Seema , Gephart Melanie Hayden , Alizadeh Ash A. , Diehn Maximilian 
Published: January 2024

AbstractIntroductionCerebrospinal fluid tumor-derived DNA (CSF-tDNA) analysis is a promising approach for monitoring neoplastic processes of the central nervous system. We hypothesize that analysis of CSF-tDNA in patients with advanced lung cancer improves the sensitivity of leptomeningeal disease (LMD) diagnosis and enables central nervous system response monitoring.MethodsWe applied CAPP-Seq using a lung cancer-specific sequencing panel to 81 CSF, blood, and tissue samples from 24 patients with advanced lung cancer who underwent lumbar puncture (LP) for suspected LMD. A subset of the cohort (N = 12) participated in a prospective clinical trial of osimertinib for refractory LMD in which serial LPs were performed before and during treatment with.ResultsCSF-tDNA variant allele fractions (VAFs) were significantly higher than plasma circulating tumor DNA (ctDNA) VAFs (median CSF-tDNA, 32.7%; median plasma ctDNA, 1.8%;P< 0.0001). Concentrations of tumor DNA in CSF and plasma were positively correlated (Spearman’s ρ, 0.45;P= 0.03). For LMD diagnosis, cytology was 81.8% sensitive and CSF-tDNA was 91.7% sensitive. CSF-tDNA was also strongly prognostic for overall survival (HR = 7.1;P= 0.02). Among patients with progression on targeted therapy, resistance mutations, such asEGFRT790M andMETamplification, were common in peripheral blood but were rare in time-matched CSF, indicating differences in resistance mechanisms based on anatomic compartment. In the osimertinib cohort, patients with CNS progression had increased CSF-tDNA VAFs at follow up LP. Post-osimertinib CSF-tDNA VAF was strongly prognostic for CNS progression (HR = 6.2,P= 0.009).ConclusionsDetection of CSF-tDNA in lung cancer patients with suspected LMD is feasible and may have clinical utility. CSF-tDNA may improve the sensitivity of LMD diagnosis, enable improved prognostication, and drive therapeutic strategies that account for spatial heterogeneity in resistance mechanisms.
The Solute Carrier Family 26 Member 9 Is a Modifier of the Rapidly Progressing Cystic Fibrosis Associated with F508del CFTR Mutations
Authors: Luo Shiyu , Rollins Stuart , Schmitz-Abe Klaus , Tam Amy , Li Qifei , Shi Jiahai , Lin Jasmine , Wang Ruobing , Agrawal Pankaj B. 
Published: January 2024

AbstractCystic fibrosis (CF) is an autosomal recessive disease caused by mutations to the CF transmembrane conductance regulator (CFTR). Symptoms and severity of the disease vary shown that modifier genes influence disease severity and clinical course. We previously reported epithelial sodium channel (ENaC) genes as modifiers of disease severity in long-term non-progressors sharing deltaF508 homozygous forCFTRgenotype. Here we describe the opposite, modifier genes that may be associated with rapidly progressing CF (RPCF) in a cohort of patients with the shared deltaF508 homozygous genotype. We have identified three rare missenseSLC26A9variants in four individuals (out of six) deemed to have RPCF: c.229G>A; p.G77S (present in two patients), c.1885C>T; p.P629S and c.2546G>A; p.R849Q. By analyzing publicly available single cell sequencing dataset from LungMAP, we revealed that bothSLC26A9andCFTRmRNA are highly enriched in Alveolar type 2 (AT2) cells, with a few (greater than 1%) in respiratory airway secretory (RAS) cells and ionocytes. Structural modeling suggests deleterious effects of these mutations as they are in critical protein domains which might affect the ion transportation capability of SLC26A9. The enrichment of rare and potentially deleteriousSLC26A9mutations in patients with RPCF suggestsSLC26A9is a modifier gene associated with RPCF.
Depletion of effector regulatory T cells drives major response to induction dual immune checkpoint blockade
Authors: Jiang Xianli , Rudqvist Nils-Petter , Jiang Bo , Ye Shengbin , He Shan , Liang Qingnan , Dou Jinzhuang , Williams Michelle , Dunn Joe Dan , Johnson Jason M. , Akagi Keiko , Xiao Weihong , Liang Shaoheng , Elayavalli Satvik , Sun Baohua , Cuentas Edwin Roger Parra , Ferrarotto Renata , Garden Adam , Fuller Clifton , Reddy Jay , Gross Neil , Lango Miriam , Leung Cheuk Hong , Liu Suyu , Liu Diane , Lee J Jack , Curran Michael A. , Phan Jack , Chen Ken , Gillison Maura L. 
Published: January 2024

ABSTRACTIn a phase 2 trial, local-regionally advanced HPV-positive oropharyngeal carcinoma (OPC) patients received ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) as induction immunotherapy and concurrently with radiotherapy (NCT03799445). Co-primary endpoints achieved included 6-month complete metabolic response rate (94%) and 2-year progression-free survival (84%). Induction yielded a 46% major histological response rate. Single-cell profiling revealed responders had higher baseline intratumoral tissue-resident memory (TRM) CD8+T cells and NK cells expressing Fc Gamma Receptor IIIa (FCGR3A). Decreases in effector regulatory T (eTreg) cells, which highly expressedCTLA4, occurred only in responders, suggesting ipilimumab-dependent depletion byFCGR3A+NK cells. eTreg depletion correlated with increased Interferon Gamma (IFNG)+effector CD8+T cells. CD8+T-cell clonotypes transitioned from TRM to effector memory andIFNG+effector cells in responders, whereas clonotypes transitioned to exhausted TRM and proliferating cells in nonresponders. We conclude that eTreg depletion is critical for major response to induction dual immune checkpoint blockade.
Using clinical text to refine unspecific condition codes in Dutch general practitioner EHR data
Authors: Seinen Tom M , Kors Jan A , van Mulligen Erik M , Fridgeirsson Egill , Verhamme Katia MC , Rijnbeek Peter R 
Published: January 2024

AbstractObjectiveObservational studies using electronic health record (EHR) databases often face challenges due to unspecific clinical codes that can obscure detailed medical information, hindering precise data analysis. In this study, we aimed to assess the feasibility of refining these unspecific condition codes into more specific codes in a Dutch general practitioner (GP) EHR database by leveraging the available clinical free text.MethodsWe utilized three approaches for text classification—search queries, semi-supervised learning, and supervised learning—to improve the specificity of ten unspecific International Classification of Primary Care (ICPC-1) codes. Two text representations and three machine learning algorithms were evaluated for the (semi-)supervised models. Additionally, we measured the improvement achieved by the refinement process on all code occurrences in the database.ResultsThe classification models performed well for most codes. In general, no single classification approach consistently outperformed the others. However, there were variations in the relative performance of the classification approaches within each code and in the use of different text representations and machine learning algorithms. Class imbalance and limited training data affected the performance of the (semi-)supervised models, yet the simple search queries remained particularly effective. Ultimately, the developed models improved the specificity of over half of all the unspecific code occurrences in the database.ConclusionsOur findings show the feasibility of using information from clinical text to improve the specificity of unspecific condition codes in observational healthcare databases, even with a limited range of machine-learning techniques and modest annotated training sets. Future work could investigate transfer learning, integration of structured data, alternative semi-supervised methods, and validation of models across healthcare settings. The improved level of detail enriches the interpretation of medical information and can benefit observational research and patient care.
Effect ofAPOEε4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD
Authors: Wang Yi Zhe , Zhao Wei , Moorjani Priya , Gross Alden L. , Zhou Xiang , Dey Aparajit B. , Lee Jinkook , Smith Jennifer A. , Kardia Sharon L.R. 
Published: January 2024

ABSTRACTBACKGROUNDWe investigated effects ofAPOEε4 and its interactions with sociodemographic characteristics on cognitive measures in 2,563 South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD).METHODSLinear regression models were used to assess the association betweenAPOEε4 and global- and domain-specific cognitive function. Effect modification by age, sex, and education were explored using cross-product interaction terms and subgroup analyses.RESULTSAPOEε4 was inversely associated with most cognitive measures. This association was stronger in the older age group (age >68) for general cognitive function, orientation, and language/fluency, as well as in females for memory and language/fluency. Interaction betweenAPOEε4 and education was mostly nonsignificant.DISCUSSIONAPOEε4 is associated with lower cognitive function in South Asians from India, with a more pronounced impact observed in females and older individuals.
Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 × 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D Trial) in adults with cystic fibrosis
Authors: Sivapiromrat Alisa K. , Suppakitjanusant Pichatorn , Wang Yanling , Binongo Jose , Hunt William R. , Gewirtz Andrew , Alvarez Jessica A. , Hu Chengcheng , Weinstein Samuel , Jathal Ishaan , Ziegler Thomas R. , Tangpricha Vin 
Published: January 2024

AbstractIndividuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI dysbiosis and improving intestinal functions. Thus, a 2 × 2 factorial design, placebo-controlled, double-blind, clinical trial was proposed to test this hypothesis. Forty adult participants with CF will be block-randomized into one of four groups: 1) high-dose oral vitamin D3(50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3weekly; 3) combined oral vitamin D3weekly and oral prebiotic inulin daily; and 4) oral vitamin D3placebo weekly and oral prebiotic placebo. The primary endpoints will include 12-week changes in the reduced relative abundance of gammaproteobacteria, and gut microbiota richness and diversity before and after the intervention. This clinical study will examine whether vitamin D3with or without prebiotics will improve intestinal health and reduce GI dysbiosis, which in turn, should improve health outcomes and quality of life of patients with CF.
Noradrenergic modulation of saccades in Parkinson’s disease
Authors: Orlando Isabella F. , Hezemans Frank H. , Ye Rong , Murley Alexander G. , Holland Negin , Regenthal Ralf , Barker Roger A. , Williams-Gray Caroline H. , Passamonti Luca , Robbins Trevor W. , Rowe James B. , O’Callaghan Claire 
Published: January 2024

AbstractNoradrenaline is a powerful modulator of cognitive processes, including action-decisions underlying saccadic control. Changes in saccadic eye movements are common across neurodegenerative diseases of ageing, including Parkinson’s disease. With growing interest in noradrenergic treatment potential for non-motor symptoms in Parkinson’s disease, the temporal precision of oculomotor function is advantageous to assess the effects of this modulation. Here we studied the effect of 40 mg atomoxetine, a noradrenaline reuptake inhibitor, in nineteen people with idiopathic Parkinson’s disease using a single dose, randomised double-blind crossover placebo-controlled design. Twenty-five healthy adult participants completed the assessments to provide normative data. Participants performed prosaccade and antisaccade tasks. The latency, velocity and accuracy of saccades, and resting pupil diameter, were measured. Increased pupil diameter on the drug confirmed its expected effect on the locus coeruleus ascending arousal system. Atomoxetine improved key aspects of saccade performance: prosaccade latencies were faster and the saccadic main sequence was normalised. These improvements were accompanied by increased antisaccade error rates on the drug. Together these findings suggest a shift in the speed-accuracy trade-off for visuo-motor decisions in response to noradrenergic treatment. Our results provide new evidence to substantiate a role for noradrenergic modulation of saccades, and based on known circuitry we advance the hypothesis that this reflects modulation at the level of the locus coeruleus–superior colliculus pathway. Given the potential for noradrenergic treatment of non-motor symptoms of Parkinson’s disease and related conditions, the oculomotor system can support the assessment of cognitive effects without limb-motor confounds on task performance.
Large language models in simplifying radiological reports: systematic review
Authors: Artsi Yaara , Sorin Vera , Konen Eli , Glicksberg Benjamin S. , Nadkarni Girish , Klang Eyal 
Published: January 2024

AbstractObjectivesSimplifying medical information to make it understandable for patients, specifically in the case of radiology reports, is challenging. It requires time and effort from medical personnel. This systematic review focuses on the application of large language models (LLMs) in generating simplified radiological imaging reports, as well as answering patient inquiries regarding radiological procedures.Materials and MethodsThe authors searched for studies published up to January 2024. Search terms focused on LLMs generated simplified radiological reports and answers to patient inquiries regarding radiological procedures. MEDLINE was used as a search database.ResultsOverall, eight studies published between May 2023 and November 2023 were included. All studies showed that LLMs can produce simplified medical information for patients. Four studies (50%) used GPT-3.5, Two studies (25%) conducted a comparative analysis between GPT-3.5 and GPT-4. One study (12.5%) examined Microsoft Bing. One study (12.5%) utilized GPT-4. Four studies (50%) used LLMs to simplify radiological reports. Four studies (50%) used LLMs to answer patient questions regarding radiological procedures. Only two studies (25%) used patients to evaluate the LLMs output. One study (12.5%) compared their initial prompt with optimized prompt. Five studies (62.5%) showed missing, inaccurate and potentially harmful AI outputs.ConclusionLLMs can be used to simplify medical imaging reports and procedures, for improved patient comprehension. However, their limitations cannot be ignored. Further study in this field is essential and more conclusive evidence is needed.
Variant-specific humoral immune response to SARS-CoV-2 escape mutants arising in clinically severe, prolonged infection
Authors: Günther Theresa , Schöfbänker Michael , Lorentzen Eva Ulla , Romberg Marie-Luise , Hennies Marc Tim , Neddermeyer Rieke , Müller Marlin Maybrit , Mellmann Alexander , Lenz Georg , Stelljes Matthias , Hrincius Eike Roman , Vollenberg Richard , Ludwig Stephan , Tepasse Phil-Robin , Kühn Joachim Ewald 
Published: January 2024

AbstractNeutralising antibodies against the SARS-CoV-2 spike (S) protein are major determinants of protective immunity, though insufficient antibody responses may cause the emergence of escape mutants. We studied the intra-host evolution and the humoral immune response in a B-cell depleted, haemato-oncologic patient experiencing clinically severe, prolonged SARS-CoV-2 infection with a virus of lineage B.1.177.81.Bamlanivimab treatment early in infection was associated with the emergence of the bamlanivimab escape mutation S:S494P. Ten days before virus elimination, additional mutations within the N-terminal domain (NTD) and the receptor binding domain (RBD) of S were observed, of which the triple mutant S:Delta141-4 E484K S494P became dominant. Routine serology revealed no evidence of an antibody response in the patient. A detailed analysis of the variant-specific immune response by pseudotyped virus neutralisation test (pVNT), surrogate VNT (sVNT), and immunoglobulin-capture EIA showed that the onset of an IgM-dominated antibody response coincided with the appearance of escape mutations. The formation of neutralising antibodies against S:Delta141-4 E484K S494P correlated with virus elimination. One year later, the patient experienced clinically mild re-infection with Omicron BA.1.18, which was treated with sotrovimab and resulted in a massive increase of Omicron-reactive antibodies.In conclusion, the onset of an IgM-dominated endogenous immune response in an immunocompromised patient coincided with the appearance of additional mutations in the NTD and RBD of S in a bamlanivimab-resistant virus. Although virus elimination was ultimately achieved, this humoral immune response escaped detection by routine diagnosis and created a situation temporarily favouring the emergence of escape variants with known epidemiological relevance.
The Impact of Electronic Order Communications on Laboratory Turnaround Times in Acute Hospital Care
Authors: Gallier S. , Zou X. , Evison F. , Hodson J. , Atia J. , Webster C , Garrick M. , Coleman J. , Pankhurst T. , Ball S. , Nirantharakumar K. , Sapey E. 
Published: January 2024

AbstractObjectiveTo examine the impact of computerised physician order entry (CPOE) systems upon laboratory turnaround times (LTAT), namely the time from recording the collection of a blood sample to the results being reported, within a large acute hospital.Materials and methods1,810,311 blood samples taken between 1stJanuary 2014 and 31stDecember 2019 were included. Changes in LTAT over the 24 months pre- and 18 months post-CPOE implementation were analysed using a segmented regression approach. The primary analysis assessed the median LTAT across the whole hospital, with secondary analyses assessing subgroups defined by clinical settings.ResultsCPOE implementation was associated with a step-change reduction in the median LTAT of 31.7 minutes (95% CI: 25.5-37.9, p<0.001). This was sustained over eighteen months post- implementation of CPOE despite the number of samples increasing by an average of 31% in this post-implementation period. Analysis by broad clinical specialty found all subgroups of wards considered to have a significant reduction in LTAT post-CPOE, either in the form of a step-change reduction, or an increasing rate of change.Discussion and ConclusionThe implementation of CPOE within an acute hospital improves the average LTAT over a prolonged period, despite an increase in the number of samples collected. This could improve care efficiencies. Understanding the likely reduction in LTAT also provides information to support an economic evaluation of the implementation of such a system into a new setting.