bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of programmed cell death ligand 1 expression in a contemporary cohort of penile squamous cell carcinoma and its correlation with clinicopathologic and survival parameters: A study of 134 patients
Authors: Lobo Anandi , Mishra Sourav K , Jha Shilpy , Tiwari Ankit , Kapoor Rahul , Sharma Shivani , Kaushal Seema , Kiranmai N Sri , Das M Rakshitha , Peddinti Kamal P , Sharma Shailendra K , Bhardwaj Nitin , Arora Samriti , Jain Deepika , Jain Ekta , Munjal Gauri , Shinde Sayali , Malik Vipra , Singh Hena , Varshney Juhi , Pradhan Dinesh , Dixit Mallika , Pattnaik Niharika , Sharma Ashish K , Barapatre Yogesh R , Pradhan Manas , Satapathy Kaliprasad , Rath Debadarshi , Jaiswal Sunil , Das Stithi , Khadenga Chiraranjan , Routa Sudhasmita , Baisakh Manas R , Tiwari Romila , Sampat Nakul Y , Chakrabarti Indranil , Parwani Anil V , Mohanty Sambit K 
Published: August 2023

Abstract

Objectives
Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC.

Methods
A cohort of 134 patients with PC was studied for PD-L1 immunohistochemistry. The PD-L1 expression was evaluated using a combined proportion score with a cutoff of 1 or higher to define positivity. The results were correlated with various clinicopathologic parameters.

Results
Overall, 77 (57%) patients had positive PD-L1 expression. Significantly high PD-L1 expression was observed in high-grade tumors (P = .006). We found that 37% of human papillomavirus (HPV)–associated subtypes and 73% of other histotype tumors expressed PD-L1, while 63% of HPV-associated tumors and 27% of other histotype tumors did not (odds ratio, 1.35; P = .002 when compared for HPV-associated groups vs all others). Similarly, PD-L1–positive tumors had a 3.61-times higher chance of being node positive than PD-L1–negative tumors (P = .0009). In addition, PD-L1 high–positive tumors had a 5-times higher chance of being p16ink4a negative than PD-L1 low–positive tumors (P = .004). The PD-L1–positive tumors had a lower overall survival and cancer-specific survival than PD-L1–negative tumors.

Conclusions
Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1–based immunotherapeutics in PC.
Arterial Health After Preeclampsia: Role of Chronic Hypertension in the Early Vascular Aging (EVA) Study
Authors: Paquin Amelie , Werlang Ana , Coutinho Thais 
Published: August 2023

Abstract

BACKGROUND
Preeclampsia (PE) is associated with increased cardiovascular risk. Recent data have shown worse left ventricular remodeling and diastolic function in women with PE and persistent hypertension (HTN). We performed a comprehensive arterial hemodynamic assessment to evaluate the contribution of persistent HTN on arterial health after PE.

METHODS
We recruited 40 women with PE history and 40 age-matched controls (6 months to 6 years postpartum). We evaluated arterial hemodynamics with validated techniques combining applanation tonometry and transthoracic echocardiography, comparing three groups: previous PE with persistent HTN (PE-HTN), previous PE with normalized blood pressure (PE-noHTN) and controls, using multivariable linear regression adjusted for age, body surface area, heart rate, diabetes, smoking history, creatinine, and gravidity.

RESULTS
Eight (20%) of the post-PE women had persistent HTN. Mean age was 35.8 ± 3.9 years, median number of pregnancies was 2 (range 1–7), and time since last pregnancy 2.1 (range 0.5–5.7) years (not different between groups, P &gt; 0.05). Compared to controls and to PE-noHTN, PE-HTN had higher aortic stiffness, wave reflections, pulsatile, and steady arterial load (P &lt; 0.05 for each). Among PE-noHTN, aortic stiffness, wave reflections and steady arterial load were worse than controls (P &lt; 0.05 for each), with smaller effect sizes.

CONCLUSIONS
This is the most comprehensive assessment of arterial hemodynamics and first to demonstrate the contribution of persistent HTN on worse arterial health following PE. Since measures of arterial health are associated with cardiovascular events in the population, the combination of previous PE and chronic HTN may represent a higher risk subgroup who could benefit from targeted prevention strategies.
Disease activity in chronic inflammatory demyelinating polyneuropathy: association between circulating B-cell subsets, cytokine levels, and clinical outcomes
Authors: Ozdag Acarli Ayse Nur , Tuzun Erdem , Sanli Elif , Koral Gizem , Akbayir Ece , Cakar Arman , Sirin Nermin Gorkem , Soysal Aysun , Aysal Fikret , Durmus Hacer , Parman Yesim , Yilmaz Vuslat 
Published: August 2023

Abstract
Chronic inflammatory demyelinating polyneuropathy (CIDP), a common and treatable autoimmune neuropathy, is frequently misdiagnosed. The aim of this study is to evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages. Twenty-three typical, 16 multifocal and five distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot–Marie–Tooth type 1A (CMT1A) disease served as controls. Peripheral B-cell populations were analyzed by flow cytometry. IL6, IL10, TNFA mRNA and mir-21, mir-146a, and mir-155-5p expression levels were evaluated by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) and/or skin biopsy specimens. Results were then assessed for a possible association with clinical disability scores and intraepidermal nerve fiber densities (IENFD) in the distal leg. We detected a significant reduction in naive B cells (P ≤ 0.001), plasma cells (P ≤ 0.001) and regulatory B cells (P &lt; 0.05), and an elevation in switched memory B cells (P ≤ 0.001) in CIDP compared to healthy controls. CMT1A and CIDP patients had comparable B-cell subset distribution. CIDP cases had significantly higher TNFA and IL10 gene expression levels in PBMC compared to healthy controls (P &lt; 0.05 and P ≤ 0.01, respectively). IENFDs in the distal leg showed a moderate negative correlation with switched memory B-cell ratios (r = –0.51, P &lt; 0.05) and a moderate positive correlation with plasma cell ratios (r = 0.46, P &lt; 0.05). INCAT sum scores showed a moderate positive correlation with IL6 gene expression levels in PBMC (r = 0.54, P &lt; 0.05). Altered B-cell homeostasis and IL10 and TNFA gene expression levels imply chronic antigen exposure and overactivity in the humoral immune system, and seem to be a common pathological pathway in both typical CIDP and CIDP variants.
Design of Experiment-Based Green UPLC-DAD Method for the Simultaneous Determination of Indacaterol, Glycopyrronium and Mometasone in their Combined Dosage Form and Spiked Human Plasma
Authors: Tarek Mohamed , Ghoniem Nermine S , Hegazy Maha A , Wagdy Hebatallah A 
Published: August 2023

Abstract

Indacaterol, is an ultra-long-acting β2 agonist, glycopyrronium is a long-acting muscarinic-antagonist and mometasone is a synthetic corticosteroid. They were used recently in combination for the treatment of severe asthma symptoms and chronic obstructive pulmonary disease. In this work, it was the first time to develop a green and environment friendly ultra-performance liquid chromatographic method using design expert program for the analysis of the three drugs in their combined dosage form. Also, the method was bioanalytically validated for the analysis of the three drugs in spiked human plasma samples. The method was linear in range from 0.50 to 100.0 μg mL−1 for indacaterol and mometasone and from 1.0 to 150.0 μg mL−1 for glycopyrronium. It showed high accuracy where, the % recovery for indacaterol, glycopyrronium and mometasone in plasma were ranged from 94.27 to 97.86%, 96.43 to 98.75% and 96.86 to 98.43%, respectively. Also, it was precise where, the % relative standard deviation for the inter-day precision was ranged from 2.571 to 3.484%, 3.180 to 4.123% and 3.150 to 3.984% and the intra-day precision was ranged from 2.351 to 3.125%, 2.512 to 3.544% and 2.961 to 3.983% for indacaterol, glycopyrronium and mometasone, respectively. The limit of detection and the limit of quantification for indacaterol and mometasone were 0.03 and 0.10 μg mL−1 while for glycopyrronium, they were 0.16 and 0.50 μg mL−1.

Highlights
Simultaneous Estimation of Berberine and Piperine in a Novel Nanoformulation for Epilepsy Control via HPLC
Authors: El-Nahas Amira E , Elbedaiwy Heba M , Helmy Maged W , El-Kamel Amal H 
Published: August 2023

Abstract
Berberine (Brb) and piperine (Pip) are salient examples of bioactive nutraceuticals possessing a promising role in controlling epilepsy. However, during the development of novel nanoformulation that augments their effects, an adequate determination of each one separately was a challenge since they have nearly the same detection wavelength and diverse solubility profiles. Consequently, a tailored high-performance liquid chromatography technique was developed for their simultaneous detection in routine analyses. The chromatographic separation was achieved using a C18 column. The linear gradient flow of acetonitrile: 0.1%v/v aqueous phosphoric acid was altered from 55:45 to 80:20 v/v over 3 min at a 1.2 mL/min flow rate until the end of the run. Brb and Pip were eluted at 1.6 and 3.4 min, respectively. The linearity of the standard curves was found to be ≥0.999, and the mean % recovery for Brb and Pip lay within the accepted limit. Moreover, the percentage coefficient of variation was &lt;2% for intra- and inter-day precision. Consequently, the developed assay was successfully applied for the quantification of both drugs rapidly with high resolution and minimum interference from each other during the different steps conducted during the nanoformulation development.
Prognostic value of myocardial performance index in individuals with type 1 and type 2 diabetes: Thousand&1 and Thousand&2 studies
Authors: Bahrami Hashmat Sayed Zohori , Jørgensen Peter Godsk , Hove Jens Dahlgaard , Dixen Ulrik , Biering-Sørensen Tor , Rossing Peter , Jensen Magnus T 
Published: August 2023

Abstract

Aims
Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in type 1 (T1D) and type 2 diabetes (T2D). Despite diabetes affects the myocardium, risk prediction models do not include myocardial function parameters. Myocardial performance index (MPI) reflects left ventricular function. The prognostic value of MPI has not been evaluated in large-scale diabetes populations.

Methods and results
We evaluated two prospective cohort studies: Thousand&1 (1093 individuals with T1D) and Thousand&2 (1030 individuals with T2D). Clinical data, including echocardiography, were collected at baseline. We collected follow-up data from national registries. We defined major adverse cardiovascular events (MACE) as incident events of hospital admission for acute coronary syndrome, heart failure, stroke, or all-cause mortality. For included individuals (56% male, 54 ± 15 years, MPI 0.51 ± 0.1, 63% T1D), follow-up was 100% after median of 5.3 years (range: 4.8–6.3). MPI was associated with MACE (HR 1.2, 95%CI 1.0–1.3, P = 0.012, per 0.10-unit increase) and heart failure (HR 1.3, 95%CI 1.1–1.6, P = 0.005, per 0.10-unit increase) after adjusting for clinical and echocardiographic variables. MPI predicted MACE and heart failure better in T1D than T2D (P = 0.031 for interaction). MPI added discriminatory power to the Steno T1 Risk Engine, based on clinical characteristics, in predicting MACE [area under the curve (AUC) from 0.77 to 0.79, P = 0.030] and heart failure (AUC from 0.77 to 0.83, P = 0.009) in T1D.

Conclusion
MPI is independently associated with MACE and heart failure in T1D but not T2D and improves prediction in T1D. Echocardiographic assessment in T1D may enhance risk prediction.
ACTH and prolactin synergistically and selectively regulate CYP17 expression and adrenal androgen production in human foetal adrenal organ cultures
Authors: Schneider Grégoire , Ruggiero Carmen , Renault Lucie , Doghman-Bouguerra Mabrouka , Durand Nelly , Hingrai Guillaume , Dijoud Frédérique , Plotton Ingrid , Lalli Enzo 
Published: August 2023

Abstract

Objective
The essential role of ACTH on the growth and function of the human foetal adrenal (HFA) has long been recognized. In addition, many studies have suggested a role of the pituitary hormone prolactin (PRL) in the regulation of the HFA, but the effects of this hormone on steroidogenesis and gene expression are still unknown. Our objective was to investigate the effect of ACTH and PRL on the steroidogenic capacities of the HFA.

Design
In vitro/ex vivo experimental study.

Methods
We used a hanging drop in vitro organ culture system. First trimester HFA samples were cultured for 14 days in basal conditions or treated with ACTH, PRL, or a combination of the 2 (3 to 11 replicates depending on the experiment). Steroids were measured by liquid chromatography/tandem mass spectrometry or immunoassay, gene expression by RT-qPCR, and protein expression by immunoblot.

Results
ACTH significantly increased corticosterone, cortisol, and cortisone production, both by itself and when used together with PRL. PRL stimulation by itself had no effect. Combined stimulation with ACTH + PRL synergistically and selectively increased adrenal androgen (DHEAS and Δ4-androstenedione) production and CYP17A1 expression in the HFA, while treatment with each single hormone had no significant effect on those steroids.

Conclusions
These results have important implications for our understanding of the hormonal cues regulating adrenal steroidogenesis in the HFA during the first trimester in physiological and pathological conditions and warrant further studies to characterize the molecular mechanisms of converging ACTH and PRL signalling to regulate CYP17A1 expression.
Emery–Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure
Authors: Cannie Douglas E , Syrris Petros , Protonotarios Alexandros , Bakalakos Athanasios , Pruny Jean-François , Ditaranto Raffaello , Martinez-Veira Cristina , Larrañaga-Moreira Jose M , Medo Kristen , Bermúdez-Jiménez Francisco José , Ben Yaou Rabah , Leturcq France , Mezcua Ainhoa Robles , Marini-Bettolo Chiara , Cabrera Eva , Reuter Chloe , Limeres Freire Javier , Rodríguez-Palomares José F , Mestroni Luisa , Taylor Matthew R G , Parikh Victoria N , Ashley Euan A , Barriales-Villa Roberto , Jiménez-Jáimez Juan , Garcia-Pavia Pablo , Charron Philippe , Biagini Elena , García Pinilla José M , Bourke John , Savvatis Konstantinos , Wahbi Karim , Elliott Perry M 
Published: August 2023

Abstract

Background and Aims
Emery–Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterize the cardiac complications of EMD variants.

Methods
Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidences in male and female variant-carriers were determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared with consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC).

Results
Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers [mean (SD) ages 33.4 (13.3) and 43.3 (16.8) years, respectively]. Nine (23.7%) males developed MVA and five (13.2%) developed ESHF during a median (inter-quartile range) follow-up of 65.0 (24.3–109.5) months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median (inter-quartile range) age of 58.6 (53.2–60.4) years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank P = .49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank P = .09).

Conclusions
Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease.
Atrial pacing minimization in sinus node dysfunction and risk of incident atrial fibrillation: a randomized trial
Authors: Kronborg Mads Brix , Frausing Maria Hee Jung Park , Malczynski Jerzy , Riahi Sam , Haarbo Jens , Holm Katja Fiedler , Larroudé Charlotte Ellen , Albertsen Andi Eie , Svendstrup Lene , Hintze Ulrik , Pedersen Ole Dyg , Davidsen Ulla , Fischer Thomas , Johansen Jens Brock , Kristensen Jens , Gerdes Christian , Nielsen Jens Cosedis ,   DANPACE II Investigators, Nielsen Jens Cosedis , Kronborg Mads Brix , Hee Maria , Malczynski Jerzy , Riahi Sam , Holm Katja Fiedler , Haarbo Jens , Larroudé Charlotte Ellen , Albertsen Andi Eie , Svendstrup Lene , Hinze Ulrik , Pedersen Ole Dyg , Davidsen Ulla , Fischer Thomas , Johansen Jens Brock , Kristensen Jens , Gerdes Christian 
Published: August 2023

Abstract

Background and Aims
High percentages of atrial pacing have been associated with an increased risk of atrial fibrillation. This study is aimed at evaluating whether atrial pacing minimization in patients with sinus node dysfunction reduces the incidence of atrial fibrillation.

Methods
In a nationwide, randomized controlled trial, 540 patients with sinus node dysfunction and an indication for first pacemaker implantation were assigned to pacing programmed to a base rate of 60 bpm and rate-adaptive pacing (DDDR-60) or pacing programmed to a base rate of 40 bpm without rate-adaptive pacing (DDD-40). Patients were followed on remote monitoring for 2 years. The primary endpoint was time to first episode of atrial fibrillation longer than 6 min. Secondary endpoints included longer episodes of atrial fibrillation, and the safety endpoint comprised a composite of syncope or presyncope.

Results
The median percentage of atrial pacing was 1% in patients assigned to DDD-40 and 49% in patients assigned to DDDR-60. The primary endpoint occurred in 124 patients (46%) in each treatment group (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.76–1.25, P = .83). There were no between-group differences in atrial fibrillation exceeding 6 or 24 h, persistent atrial fibrillation, or cardioversions for atrial fibrillation. The incidence of syncope or presyncope was higher in patients assigned to DDD-40 (HR 1.71, 95% CI 1.13–2.59, P = .01).

Conclusions
Atrial pacing minimization in patients with sinus node dysfunction does not reduce the incidence of atrial fibrillation. Programming a base rate of 40 bpm without rate-adaptive pacing is associated with an increased risk of syncope or presyncope.
Prevalence and incidence of diastolic dysfunction in atrial fibrillation: clinical implications
Authors: Naser Jwan A , Lee Eunjung , Scott Christopher G , Kennedy Austin M , Pellikka Patricia A , Lin Grace , Pislaru Sorin V , Borlaug Barry A 
Published: August 2023

Abstract

Background and Aims
Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are intimately associated disorders; HFpEF may be overlooked in AF when symptoms are simply attributed to dysrhythmia, and incident AF may identify patients at risk for developing diastolic dysfunction (DD). This study aimed to investigate the prevalence and incidence of DD in patients with new-onset AF compared with sinus rhythm (SR).

Methods
Adults with new-onset AF (n = 1747) or SR (n = 29 623) and no structural heart disease were identified. Propensity score matching was performed (1:3 ratio) between AF and SR based on age, sex, body mass index, and comorbidities. Severe DD (SDD) was defined by ≥3/four abnormal parameters (medial e’, medial E/e’, tricuspid regurgitation velocity, and left atrial volume index) and ≥moderate DD (&gt;MDD) by ≥2/4. Annualized changes in DD indices were determined.

Results
New-onset AF was independently associated with SDD (8% vs. 3%) and ≥MDD (25% vs. 16%); 62% of patients with AF had high-risk H2FPEF scores, and 5% had clinically recognized HFpEF. Over a median follow-up of 3.2 (interquartile range 1.6–5.8) years, DD progressed two–four-fold more rapidly in those with new-onset AF (P &lt; .001 for all). The risk for incident DD was increased in new-onset AF [hazard ratio (95% confidence interval) 2.69 (2.19–3.32) for SDD and 1.73 (1.49–2.02) for ≥MDD].

Conclusions
Patients with new-onset AF display high-risk features for HFpEF at diagnosis, emphasizing the importance of evaluating for HFpEF among symptomatic patients with AF. Patients with new-onset AF have accelerated progression in DD over time, which may identify patients with preclinical HFpEF, where preventive therapies may be tested.
The Rise and Fall of the ‘World Economy’ in Weimar Germany
Authors: Müller Philipp 
Published: August 2023

Abstract
Recent studies have emphasized the role of international institutions in the emergence of a transnational culture of economic experts in the interwar period. According to this view, collaboration over the difficulties of international trade in goods and finance was driven by a common language of problem diagnosis and solution finding. This interpretation has pushed the relevance of the domestic context for ‘agents of the international’ into the background. The World Economic Conference in Geneva organized by the League of Nations in 1927 shows that Weimar business representatives saw their participation as an opportunity to improve their position in their national federations and vis-à-vis the Reich government. Therefore, on the one hand, they sought to be appointed by state authorities to participate in the Geneva discussions. On the other hand, they stressed the relevance of the World Economy as well as their competence in solving world economic problems. As a consequence, immediately before and after the meeting in Geneva, the World Economy was a prominent topic among Weimar’s business representatives. However, this strategy counted on the implementation of the conference’s economic policy proposals by national governments. As it became apparent that the Geneva recommendations would not have lasting impact, interest in the World Economy waned and its spokesmen turned to other forms of international cooperation, in particular regional customs alliances and cartel agreements. The rise and fall of the topic of the World Economy among German business representatives cannot be understood independently of its interaction with the domestic context of Weimar Germany.