bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Potassium-competitive Acid Blockers Versus Proton Pump Inhibitors in Treating Erosive Esophagitis
Authors: Fang Yingying , Lou Dandi , Zhou Jie , Zhang Qiufeng , Dai Youran , Ren Wei 
Published: July 2024

Objective:
This meta-analysis aimed to investigate the efficacy and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) in treating erosive esophagitis (EE).

Methods:
PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using predefined search terms up to January 2024. Relevant randomized controlled trials were included. The outcoming were the EE healing rate and treatment-related adverse events incidence.

Results:
Nine randomized controlled trials involving 4012 patients were included. Patients receiving P-CAB exhibited a significantly better overall healing rate compared with PPI at week 2 [risk ratio (RR) = 1.06], but no statistical difference was observed at week 4 and week 8. Subgroup analysis revealed that P-CAB demonstrated a higher healing rate for patients with Los Angeles (LA) grade C/D, regardless of the assessment at week 2 (RR = 1.17), week 4 (RR = 1.10), or week 8 (RR = 1.08). However, no significant difference was found between PPI and P-CAB for patients with LA grade A/B at week 2, week 4, or week 8. Furthermore, patients treated with P-CAB had lower recurrence rates during maintenance therapy compared with PPI (RR = 0.79). In terms of safety, P-CAB was associated with a lower incidence of headache compared with PPI (RR = 0.32), with no statistical difference found in any treatment-related adverse events between the two groups.

Conclusions:
P-CAB was found to be safe and effective for EE treatment compared with PPI, particularly in 2-week short-term treatment, severe EE (LA grade C/D) treatment, or maintenance therapy. Limitations such as potential heterogeneity among included trials should be considered in the interpretation of these findings.
Diagnostic Performance of Stool-based Testing for Colorectal Lesions Among Average-risk Individuals
Authors: Cheney Catherine , Parish Alice , Niedzwiecki Donna , Oko Chukwuemeka , Walters Christy , Sullivan Brian A. 
Published: July 2024

Objective:
We assessed the real-world performance of stool-based tests (SBTs) for colorectal cancer screening.

Materials and Methods:
Retrospective review of average-risk individuals with positive SBT for advanced neoplasia (adenocarcinoma, advanced adenoma, and/or advanced serrated lesions) detection at follow-up colonoscopy.

Results:
There was no statistical difference in the detection of advanced neoplasia (P= 0.16) between SBTs [30.7% for multitargeted stool DNA (mt-sDNA) vs 22.8% for fecal immunochemical test]. However, there was a significant difference in the detection of advanced serrated lesions (11.3% for mt-sDNA vs 1.8% for fecal immunochemical test, P< 0.001).

Conclusion:
There was no difference between SBTs for advanced neoplasia detection, though mt-sDNA detected significantly more advanced serrated lesions.
Elexacaftor–tezacaftor–ivacaftor use after solid organ transplant
Authors: Kapnadak Siddhartha G. , Ramos Kathleen J. 
Published: July 2024

Purpose of review
In 2019, the United States Food and Drug Administration approved a breakthrough therapeutic for cystic fibrosis, elexacaftor–tezacaftor–ivacaftor (ETI), because of its profound effect on lung function in large phase III clinical trials. ETI acts directly on the dysfunctional protein that causes the systemic manifestations of cystic fibrosis and also leads to improvement in nonpulmonary symptoms of cystic fibrosis. Transplant recipients were excluded from the pivotal clinical trials of ETI but may stand to benefit from correction of the underlying protein defect. Drug interactions between the three drugs in ETI and immunosuppression medications are one of the primary concerns about using ETI after transplant. No rigorous studies exist to assess the safety of ETI in transplant recipients.

Recent findings
Multiple recent publications describe the use of ETI after solid organ transplantation, including lung and nonlung transplants, and the real-world evidence for drug interactions between ETI and immunosuppression medications. In nonlung transplant recipients, the pulmonary benefits of ETI have been confirmed, but adverse events occur and may have implications for their transplanted organ (e.g. liver biopsy in the setting of elevated transaminases). Lung transplant recipients may have higher rates of ETI discontinuation than nontransplant recipients given a lack of direct pulmonary benefit and frequency of side effects. Drug interactions have not been difficult to manage, with most studies reporting variable rates of mild to moderate increased tacrolimus levels after initiation of ETI.

Summary
Limited data exist to support the use of ETI after solid organ transplantation and further research is warranted. Given the unknown risks and benefits, case by case consideration of ETI use is indicated when extra-pulmonary manifestations are present in lung transplant recipients with cystic fibrosis. Given the proven benefit in cystic fibrosis lung disease, benefits likely outweigh the risks of ETI for nonlung solid organ transplant recipients.
Association of early doses of diuretics and nitrates in acute heart failure with 30 days outcomes: ancillary analysis of ELISABETH study
Authors: Gorlicki Judith , Nekrouf Célia , Miró Òscar , Cotter Gad , Davison Beth , Mebazaa Alexandre , Simon Tabassome , Freund Yonathan 
Published: July 2024

Aims
The optimal dose of diuretics and nitrates for acute heart failure treatment remains uncertain. This study aimed to assess the association between intravenous nitrates and loop diuretics doses within the initial 4 h of emergency department presentation and the number of days alive and out of hospital (NDAOH) through 30 days.

Methods
This was an ancillary study of the ELISABETH stepped-wedge cluster randomized trial that included 502 acute heart failure patients 75 years or older in 15 French emergency departments. The primary endpoint was the NDAOH at 30 days. The total dose of intravenous nitrates and loop diuretics administered in the initial 4 h were each categorized into three classes: ‘no nitrate’, ‘> 0–16’, and ‘> 16 mg’ for nitrates and ‘< 60’, ‘60’, and ‘> 60 mg’ for diuretics. Secondary endpoints included 30-day mortality, 30-day hospital readmission, and hospital length of stay in patients alive at 30 days. Generalized linear mixed models were used to examine associations with the endpoints.

Results
Of 502 patients, the median age was 87 years, with 59% women. The median administered dose within the initial 4 h was 16 mg (5.0; 40.0) for nitrates and 40 mg (40.0; 80.0) for diuretics. The median NDAOH at 30 days was 19 (0.0–24.0). The adjusted ratios of the NDAOH were 0.88 [95% confidence interval (CI): 0.63–1.23] and 0.76 (95% CI: 0.58–1.00) for patients that received 60 and > 60 mg, respectively, compared with patients that received 40 mg or less of diuretics. Compared with patients who did not receive nitrates, the adjusted ratios of the NDAOH were 1.17 (95% CI: 0.82–1.67) and 1.45 (95% CI: 0.90–2.33) for patients who received 1–16 and > 16 mg, respectively. There was no significant association with any of the secondary endpoints.

Conclusion
In this ancillary analysis, there was no significant association between different doses of diuretics and nitrates with the NDAOH at 30 days. Point estimates and CIs may suggest that the optimal doses are less than 60 mg of diuretics, and more than 16 mg of nitrates in the first 4 h.
Correlation of PSA blood levels with standard uptake value maximum (SUVmax) and total metabolic tumor volume (TMTV) in 18F-PSMA-1007 and 18F-choline PET/CT in patients with biochemically recurrent prostate cancer
Authors: Fragkiadaki Vasiliki , Panagiotidis Emmanouil , Vlontzou Evaggelia , Kalathas Theodoros , Paschali Anna , Kypraios Charalampos , Chatzipavlidou Vasiliki , Datseris Ioannis 
Published: July 2024

Objectives
In this prospective study, we investigated the correlation between prostate-specific antigen (PSA) levels in the blood of patients with prostate cancer in biochemical recurrence after radical treatment with the semiquantitative parameters standard uptake value maximum (SUVmax) and the total metabolic tumor volume (TMTV) in the metastatic foci depicted in 18F-prostate-specific membrane antigen (PSMA)-1007 and 18F-choline PET/computed tomography (CT) imaging.

Methods
We prospectively examined 104 patients with biochemical relapse of prostate cancer after primary definitive treatment. All patients underwent one 18F-PSMA-1007 and one 18F-choline PET/CT examination in randomized order within a time frame of 10 days and were followed for at least 6 months (182 ± 10 days). The semiquantitative parameters of SUVmax and metabolic tumor volume (MTV) of each neoplastic lesion in PET/CT imaging were calculated, and further summation of each MTV value was done to calculate the TMTV.

Results
According to the Spearman correlation analysis, a positive correlation was found between PSA levels and SUVmax and TMTV scores in the metastatic foci of 18F-PSMA-1007 PET/CT (r = 0.24 and 0.35, respectively; P < 0.05) and SUVmax in the lesions of 18F-choline PET/CT (r = 0.28; P < 0.0239). However, a positive but NS correlation was demonstrated between values of PSA and TMTV for each lesion in the 18F-choline PET/CT study (r = 0.22; P = 0.0795). The detection rate of the different PSA levels with a cutoff of 1 ng/ml was higher for 18F-PSMA-1007 than 18F-choline.

Conclusion
In biochemical relapse patients there is a positive correlation between PSA levels in the blood and the semiquantitative parameters SUVmax and TMTV of the metastatic foci in the 18F-PSMA-1007 and 18F-Choline PET/CT imaging.
Are the lipid-lowering effects of incretin-based therapies relevant for cardiovascular benefit?
Authors: Alnima Teba , Smits Mark M. , Hanssen Nordin M.J. 
Published: July 2024

Purpose of review
This review examines the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on lipid profiles in individuals with type 2 diabetes mellitus and/or obesity, crucial for optimizing cardiovascular risk management.

Recent findings
GLP-1RAs affect lipid levels by reducing intestinal apolipoprotein B48 production and mesenteric lymph flow, while increasing catabolism of apolipoprotein B100. It remains unknown whether these effects are direct or indirect, but the improvements in lipid levels are strongly correlated to the drug-induced weight loss. Clinical trials demonstrate improvements in lipid profiles, with different effects per agent and dose. We deem it unlikely that improved lipid levels are sufficient to explain the beneficial effects of GLP-1RA on cardiovascular risk, especially given the improvement of many other risk factors (body weight, glycemic control, inflammation) while using these agents. Posthoc mediation analyses of large cardiovascular outcome trials may shed some light on the relative importance of each risk factor.

Summary
GLP-1RAs improve lipid profiles in clinical trials, but their complete cardiovascular benefits likely involve multifactorial mechanisms beyond lipid modulation.
Extracorporeal Cardiopulmonary Resuscitation
Authors: Stratton Michael , Edmunds Katherine 
Published: July 2024

Abstract
Extracorporeal cardiopulmonary resuscitation (eCPR) is increasingly being used for refractory cardiac arrest for both in-hospital and out-of-hospital cardiac arrests. The term eCPR refers to cannulating a patient to an extracorporeal membrane oxygenation (ECMO) circuit to provide perfusion after cardiac arrest refractory to standard cardiopulmonary resuscitation. Extracorporeal cardiopulmonary resuscitation has been shown to offer increased survival benefit among a select group of adult and pediatric patients experiencing refractory cardiac arrests, both in hospital and out of hospital. Extracorporeal cardiopulmonary resuscitation should be considered when (1) the cardiac arrest is witnessed, (2) the patient receives high-quality cardiopulmonary resuscitation, (3) the patient is at or in close proximity to an ECMO center, (4) there is a reversible cause for the cardiac arrest where the perfusion from the ECMO circuit serves as a bridge to recovery, and (5) the treating facility has a robust multidisciplinary system in place to facilitate rapidly moving patients from site of arrest to site of cannulation to intensive care unit. To develop an eCPR system of care, a multidisciplinary team consisting of prehospital, emergency medicine, in-hospital, proceduralist, perfusionist, and intensive care medical professionals must be established who support the use of eCPR for refractory cardiac arrest. The future of eCPR is the development of systems of care that use eCPR for a narrow subset of pediatric out-of-hospital cardiac arrests.
My model, it has three layers: a reduced model of smectic formation in two dimensions
Authors: King David A. 
Published: July 2024

My model, it has three layers,

Three layers is nematic.

And had it just two layers,

it would be a smectic.

We study a reduced model of smectic formation in two dimensions where the particles occupy three equally spaced layers. The role of particle geometry comes in through the interactions between particles on the central layer and those above and below. The system is understood to be a perfect smectic when the central layer is empty, and nematic when all three are equally occupied. It is possible to compute the free energies of these states exactly. We find that the free energy of the nematic can only exceed that of the perfect smectic if the particle tips are sufficiently wide. While not an indication of a true smectic transition, this mirrors the fact that ellipsoids do not make a smectic but sphero-cylinders do.
Haplotype Analysis Reveals Pleiotropic Disease Associations in the HLA Region
Authors: Smith Courtney J. , Strausz Satu ,   FinnGen, Spence Jeffrey P. , Ollila Hanna M. , Pritchard Jonathan K. 
Published: July 2024

AbstractThe human leukocyte antigen (HLA) region plays an important role in human health through involvement in immune cell recognition and maturation. While genetic variation in the HLA region is associated with many diseases, the pleiotropic patterns of these associations have not been systematically investigated. Here, we developed a haplotype approach to investigate disease associations phenome-wide for 412,181 Finnish individuals and 2,459 traits. Across the 1,035 diseases with a GWAS association, we found a 17-fold average per-SNP enrichment of hits in the HLA region. Altogether, we identified 7,649 HLA associations across 647 traits, including 1,750 associations uncovered by haplotype analysis. We find some haplotypes show trade-offs between diseases, while others consistently increase risk across traits, indicating a complex pleiotropic landscape involving a range of diseases. This study highlights the extensive impact of HLA variation on disease risk, and underscores the importance of classical and non-classical genes, as well as non-coding variation.
Associations of circulating T-cell subsets in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis
Authors: DeConne Theodore M. , Buzkova Petra , Pewowaruk Ryan , Delaney Joseph A. , Psaty Bruce M. , Tracy Russell P. , Doyle Margaret F. , Sitlani Colleen M. , Landay Alan L. , Huber Sally A. , Hughes Timothy M. , Bertoni Alain G. , Gepner Adam D. , Olson Nels C. , Ding Jingzhong 
Published: July 2024

ABSTRACTBackgroundArterial stiffness measured by total pulse wave velocity (T-PWV) is associated with increased risk of multiple age-related diseases. T-PWV can be described by structural (S-PWV) and load-dependent (LD-PWV) arterial stiffening. T-cells have been associated with arterial remodeling, blood pressure, and arterial stiffness in humans and animals; however, it is unknown whether T-cells are related to S-PWV or LD-PWV. Therefore, we evaluated the cross-sectional associations of peripheral T-cell subpopulations with T-PWV, S-PWV, and LD-PWV stiffness.MethodsPeripheral blood T-cells were characterized using flow cytometry and the carotid artery was measured using B-mode ultrasound to calculate T-PWV at the baseline examination in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA, n=1,984). A participant-specific exponential model was used to calculate S-PWV and LD-PWV based on elastic modulus and blood pressure gradients. The associations between five primary (p-significance<0.01) and twenty-five exploratory (p-significance<0.05) immune cell subpopulations, per 1-SD increment, and arterial stiffness measures were assessed using adjusted, linear regressions.ResultsFor the primary analysis, higher CD4+CD28-CD57+T-cells were associated with higher LD-PWV (β=0.04 m/s, p<0.01) after adjusting for co-variates. For the exploratory analysis, T-cell subpopulations that commonly shift with aging towards memory and differentiated/immunosenescent phenotypes were associated with greater T-PWV, S-PWV, and LD-PWV after adjusting for co-variates.ConclusionsIn this cross-sectional study, several T-cell subpopulations commonly associated with aging were related with measures of arterial stiffness. Longitudinal studies that examine changes in T-cell subpopulations and measures of arterial stiffness are warranted.
Immunological presentations and clinical features associated with Thymic Malignancies: The potential role of histological classifications and tumour grading on the future recurrence of opportunistic infections and paraneoplastic autoimmune conditions
Authors: Abikenari Matthew A , Delgado Sofia , Ashraghi Mohammad , Greco Giacomo , Tucker Andrew , Taberham Rhona , Quirke Mary , Stavroulias Dionisios , Yancheva Slaveya , Mccole Mark , Buckley Camilla , Leite Maria Isabel 
Published: July 2024

AbstractThymic malignancies are rare cancer tumours of the thymus arising from thymic epithelial cells and are characterized by a highly diversified clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent presentations of associated paraneoplastic autoimmune syndromes. Myasthenia Gravis (MG) is the most prevalent of such autoimmune conditions, presenting in roughly half of thymoma patients, and is associated with substantial hyperactivation of T lymphocytes, highly dysregulated negative and positive T lymphocyte selection, leading to a systemic imbalance of the immune system, and consequently aiding and abetting the manifestation of severe opportunistic infections and multiple autoimmune comorbidities such as Pure Red Cell Aplasia and Good’s syndrome. Although the clinical, immunological and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumour staging and histological gradings on the occurrence and recurrence of infections and multiple autoimmune comorbidities. The current study aimed to interrogate the role of WHO thymoma classification criteria and Masaoka staging on the recurrence of severe opportunistic infections and the presentation of multiple paraneoplastic autoimmune syndromes post-thymectomy. The current study collected clinical and immunological data from 109 patients suffering from both MG and a pathologically proven thymoma. Statistical analysis of the collected data yielded significant associations between different stages of Masaoka grading and WHO classification on the number of autoimmune comorbidity and presence of severe recurrent infections, leading to the conclusion that early histological gradings and tumour infiltration patterns play a significant role in predicting future immunological behaviour, clinical outcomes, and susceptibility to recurrent infections. Future studies must further investigate the role of autoimmunity, its associated antibody expression profiles and thymic tissue pathology. Furthermore, novel therapeutics must further explore the role of emergent immunotherapeutics, such as adoptive cell therapies, as a viable patient-stratified treatment strategy for thymic malignancies.
Mapping protein conformational landscapes from crystallographic drug fragment screens
Authors: Saeed Ammaar A. , Klureza Margaret A. , Hekstra Doeke R. 
Published: July 2024

AbstractProteins are dynamic macromolecules. Knowledge of a protein’s thermally accessible conformations is critical to determining important transitions and designing therapeutics. Accessible conformations are highly constrained by a protein’s structure such that concerted structural changes due to external perturbations likely track intrinsic conformational transitions. These transitions can be thought of as paths through a conformational landscape. Crystallographic drug fragment screens are high-throughput perturbation experiments, in which thousands of crystals of a drug target are soaked with small-molecule drug precursors (fragments) and examined for fragment binding, mapping potential drug binding sites on the target protein. Here, we describe an open-source Python package, COLAV (COnformational LAndscape Visualization), to infer conformational landscapes from such large-scale crystallographic perturbation studies. We apply COLAV to drug fragment screens of two medically important systems: protein tyrosine phosphatase 1B (PTP-1B), which regulates insulin signaling, and the SARS CoV-2 Main Protease (MPro). With enough fragment-bound structures, we find that such drug screens also enable detailed mapping of proteins’ conformational landscapes.
Lesion location changes the association between brain excitability and motor skill acquisition post-stroke
Authors: De Las Heras Bernat , Rodrigues Lynden , Cristini Jacopo , Moncion Kevin , Dancause Numa , Thiel Alexander , Edwards Jodi D. , Eng Janice J. , Tang Ada , Roig Marc 
Published: July 2024

AbstractBackgroundThe capacity to reacquire motor skills lost after a stroke is crucial to promote upper-limb motor recovery but the impact of lesion location on motor skill acquisition and the underlying neurophysiological mechanisms remain uncertain.MethodsWe used transcranial magnetic stimulation to investigate associations between excitatory and inhibitory cortico-spinal excitability measures and the capacity to acquire a novel motor skill with the most affected hand in 103 individuals with cortical (n=34) or subcortical (n=69) lesions.ResultsBoth groups showed similar motor skill acquisition, but subcortical lesions exhibited more impairment in the most affected hand and lower excitability in the ipsilesional hemisphere. In cortical lesions, motor skill acquisition was associated with lower motor thresholds (β=-0.25, 95% CI [−0.47,-0.03]; p=0.024) and higher intracortical inhibition (β=-3.93, 95% CI [−6.89,-0.98]; p=0.011) in the ipsilesional hemisphere. In contrast, in subcortical lesions motor skill acquisition was associated with smaller motor evoked potentials (β=-4.46, 95% CI [−8.54,-0.38]; p=0.033), less intracortical inhibition (β=3.45, 95% CI [0.34,6.56]; p=0.030) and higher facilitation (β=1.34,95% CI [0.15,2.54]; p= 0.028) ipsilesionally. Sensitivity analyses revealed that associations with intracortical inhibition and facilitation in the subcortical group were driven by lesions affecting the corticospinal tract. No associations were found in the contralesional hemisphere.ConclusionsReinforcing the existence of lesion-specific neurophysiological patterns, individuals with cortical and subcortical lesions show divergent associations between cortico-spinal excitability and motor skill acquisition. The use of cortico-spinal excitability as a biomarker to predict upper-limb recovery post-stroke or guide motor recovery interventions such as non-invasive brain stimulation should consider lesion location.