bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of telemonitoring combined with intensive patient support with standard care in patients with chronic cardiovascular disease - a randomized clinical trial
Authors: Öner Alper , Dittrich Hermann , Arslan Fatih , Hintz Sissy , Ortak Jasmin , Brandewiede Bernard , Mann Miriam , Krockenberger Katja , Thiéry Alexandre , Ziegler Andreas , Schmidt Christian ,   the CardioCare MV Study Group, Bleschke H , Buchner T , Buckow C , Bunge K , Duda S , El-Sourani H , Frey K , Greiner-Leben H , Henschel F , Hering R , Knispel O , Kram J , Martschewski A , Mitusch R , Plietzsch S , Rausch S , Rink A , Wejda M , Wißmann R , Wolf. B 
Published: January 2023

Abstract
Importance
Healthcare concepts for chronic diseases based on tele-monitoring have become increasingly important during COVID-19 pandemic.

Objective
To study the effectiveness of a novel integrated care concept (NICC) that combines tele-monitoring with the support of a call centre in addition to guideline therapy for patients with atrial fibrillation, heart failure, or treatment-resistant hypertension.

Design
A prospective, parallel-group, open-label, randomized, controlled trial.

Setting
Between December 2017 and August 2019 at the Rostock University Medical Center (Germany).

Participants
Including 960 patients with either atrial fibrillation, heart failure, or treatment-resistant hypertension.

Interventions
Patients were randomized to either NICC (n = 478) or standard-of-care (SoC) (n = 482) in a 1:1 ratio. Patients in the NICC group received a combination of tele-monitoring and intensive follow-up and care through a call centre.

Main outcomes and measures
Three primary endpoints were formulated: (1) composite of all-cause mortality, stroke, and myocardial infarction; (2) number of inpatient days; (3) the first plus cardiac decompensation, all measured at 12-months follow-up. Superiority was evaluated using a hierarchical multiple testing strategy for the 3 primary endpoints, where the first step is to test the second primary endpoint (hospitalization) at two-sided 5%-significance level. In case of a non-significant difference between the groups for the rate of hospitalization, the superiority of NICC over SoC is not shown.

Results
The first primary endpoint occurred in 1.5% of NICC and 5.2% of SoC patients (OR: 3.3 [95%CI 1.4–8.3], p = 0.009). The number of inpatient treatment days did not differ significantly between both groups (p = 0.122). The third primary endpoint occurred in 3.6% of NICC and 8.1% of SoC patients (OR: 2.2 [95%CI 1.2–4.2], p = 0.016). Four patients died of all-cause death in the NICC and 23 in the SoC groups (OR: 4.4 [95%CI 1.6–12.6], p = 0.006). Based on the prespecified hierarchical statistical analysis protocol for multiple testing, the trial did not meet its primary outcome measure.

Conclusions and relevance
Among patients with atrial fibrillation, heart failure, or treatment-resistant hypertension, the NICC approach was not superior over SoC, despite a significant reduction in all-cause mortality, stroke, myocardial infarction and cardiac decompensation.
Trial registration ClinicalTrials.gov Identifier: NCT03317951.
Unmet need for family planning among married women in sub-Saharan Africa: a meta-analysis of DHS data (1995 – 2020)
Authors: Phiri Million , Odimegwu Clifford , Kalinda Chester 
Published: January 2023

Abstract
Background
Closing the gap of unmet needs for family planning (FP) in sub-Saharan Africa remains critical in improving maternal and child health outcomes. Determining the prevalence of unmet needs for family planning among married women in the reproductive age is vital for designing effective sexual reproductive health interventions and programmes. Here, we use nationally representative data drawn from sub-Saharan countries to estimate and examine heterogeneity of unmet needs for family planning among currently married women of reproductive age.

Methods
This study used secondary data from Demographic and Health Surveys (DHS) conducted between January 1, 1995 to December 31, 2020 from 37 countries in sub-Saharan African. An Inverse Heterogeneity model (IVhet) in MetaXL application was used to estimate country and sub-regional level pooled estimates and confidence intervals of unmet needs for FP in SSA.

Results
The overall prevalence of unmet need for family planning among married women of reproductive age in the sub-region for the period under study was 22.9% (95% CI: 20.9–25.0). The prevalence varied across countries from 10% (95% CI: 10–11%) in Zimbabwe to 38% (95% CI: 35–40) and 38 (95% CI: 37–39) (I2 = 99.8% and p-value < 0.0001) in Sao Tome and Principe and Angola, respectively. Unmet needs due to limiting ranged from 6%; (95% CI: 3–9) in Central Africa to 9%; (95% CI: 8–11) in East Africa. On the other hand, the prevalence of unmet needs due to spacing was highest in Central Africa (Prev: 18; 95% CI: 16–21) and lowest in Southern Africa (Prev: 12%; 95% CI: 8–16). Our study indicates that there was no publication bias because the Luis Furuya-Kanamori index (0.79) was within the symmetry range of -1 and + 1.

Conclusion
The prevalence of unmet need for FP remains high in sub-Saharan Africa suggesting the need for health policymakers to consider re-evaluating the current SRH policies and programmes with the view of redesigning the present successful strategies to address the problem.
Optimal reduction and equilibrium carbon allowance price for the thermal power industry under China’s peak carbon emissions target
Authors: Sun Jiaojiao , Dong Feng 
Published: January 2023

AbstractAs the largest source of carbon emissions in China, the thermal power industry is the only emission-controlled industry in the first national carbon market compliance cycle. Its conversion to clean-energy generation technologies is also an important means of reducing CO2 emissions and achieving the carbon peak and carbon neutral commitments. This study used fractional Brownian motion to describe the energy-switching cost and constructed a stochastic optimization model on carbon allowance (CA) trading volume and emission-reduction strategy during compliance period with the Hurst exponent and volatility coefficient in the model estimated. We defined the optimal compliance cost of thermal power enterprises as the form of the unique solution of the Hamilton–Jacobi–Bellman equation by combining the dynamic optimization principle and the fractional Itô’s formula. In this manner, we obtained the models for optimal emission reduction and equilibrium CA price. Our numerical analysis revealed that, within a compliance period of 2021–2030, the optimal reductions and desired equilibrium prices of CAs changed concurrently, with an increasing trend annually in different peak-year scenarios. Furthermore, sensitivity analysis revealed that the energy price indirectly affected the equilibrium CA price by influencing the Hurst exponent, the depreciation rate positively impacted the CA price, and increasing the initial CA reduced the optimal reduction and the CA price. Our findings can be used to develop optimal emission-reduction strategies for thermal power enterprises and carbon pricing in the carbon market.
Genetic diversity of Plasmodium vivax populations from the China–Myanmar border identified by genotyping merozoite surface protein markers
Authors: Wang Xun , Bai Yao , Xiang Zheng , Zeng Weilin , Wu Yanrui , Zhao Hui , Zhao Wei , Chen Xi , Duan Mengxi , Li Xiaosong , Zhu Wenya , Sun Kemin , Wu Yiman , Zhang Yanmei , Li Xiaomei , Rosenthal Benjamin M. , Cui Liwang , Yang Zhaoqing 
Published: January 2023

Abstract
Background
Parasite diversity and population structure influence malaria control measures. Malaria transmission at international borders affects indigenous residents and migrants, defying management efforts and resulting in malaria re-introduction. Here we aimed to determine the extent and distribution of genetic variations in Plasmodium vivax populations and the complexity of infections along the China–Myanmar border.

Methods
We collected clinical P. vivax samples from local and migrant malaria patients from Laiza and Myitsone, Kachin State, Myanmar, respectively. We characterized the polymorphisms in two P. vivax merozoite surface protein markers, Pvmsp-3α and Pvmsp-3β, by PCR-restriction fragment length polymorphism (PCR–RFLP) analysis. We sought to determine whether these genetic markers could differentiate these two neighboring parasite populations.

Results
PCR revealed three major size variants for Pvmsp-3α and four for Pvmsp-3β among the 370 and 378 samples, respectively. PCR–RFLP resolved 26 fragment-size alleles by digesting Pvmsp-3α with Alu I and Hha I and 28 alleles by digesting Pvmsp-3β with Pst I. PCR–RFLP analysis of Pvmsp-3α found that infections in migrant laborers from Myitsone bore more alleles than did infections in residents of Laiza, while such difference was not evident from genotyping Pvmsp-3β. Infections originating from these two places contained distinct but overlapping subpopulations of P. vivax. Infections from Myitsone had a higher multiplicity of infection as judged by the size of the Pvmsp-3α amplicons and alleles after Alu I/Hha I digestion.

Conclusions
Migrant laborers from Myitsone and indigenous residents from Laiza harbored overlapping but genetically distinct P. vivax parasite populations. The results suggested a more diverse P. vivax population in Myitsone than in the border town of Laiza. PCR–RFLP of Pvmsp-3α offers a convenient method to determine the complexity of P. vivax infections and differentiate parasite populations.
An Assessment of the Feasibility and Utility of an ACCC-ASCO Implicit Bias Training Program to Enhance Racial and Ethnic Diversity in Cancer Clinical Trials
Authors: Barrett Nadine J. , Boehmer Leigh , Schrag Janelle , Benson Al B. , Green Sybil , Hamroun-Yazid Leila , Howson Alexandra , Matin Khalid , Oyer Randall A. , Pierce Lori , Jeames Sanford E. , Winkfield Karen , Yang Eddy S. , Zwicker Victoria , Bruinooge Suanna , Hurley Patricia , Williams Jen Hanley , Guerra Carmen E. 
Published: January 2023

PURPOSE: Cancer trial participants do not reflect the racial and ethnic diversity in the population of people with cancer in the United States. As a result of multiple system-, patient-, and provider-level factors, including implicit bias, cancer clinical trials are not consistently offered to all potentially eligible patients. MATERIALS AND METHODS: ASCO and ACCC evaluated the utility (pre- and post-test knowledge changes) and feasibility (completion rates, curriculum satisfaction metrics, survey questions, and interviews) of a customized online training program combined with facilitated peer-to-peer discussion designed to help research teams identify their own implicit biases and develop strategies to mitigate them. Discussion focused on (1) specific elements of the training modules; (2) how to apply lessons learned; and (3) key considerations for developing a facilitation guide to support peer-to-peer discussions in cancer clinical research settings. We evaluated discussion via a qualitative assessment. RESULTS: Participant completion rate was high: 49 of 50 participating cancer programs completed training; 126 of 129 participating individuals completed the training (98% response rate); and 119 completed the training and evaluations (92% response rate). Training increased the mean percentage change in knowledge scores by 19%-45% across key concepts (eg, causes of health disparities) and increased the mean percentage change in knowledge scores by 10%-31% about strategies/actions to address implicit bias and diversity concerns in cancer clinical trials. Knowledge increases were sustained at 6 weeks. Qualitative evaluation validated the utility and feasibility of facilitated peer-to-peer discussion. CONCLUSION: The pilot implementation of the training program demonstrated excellent utility and feasibility. Our evaluation affirms that an online training designed to raise awareness about implicit bias and develop strategies to mitigate biases among cancer research teams is feasible and can be readily implemented in cancer research settings.
Future Directions for Adrenal Insufficiency: Cellular Transplantation and Genetic Therapies
Authors: Graves Lara E , Torpy David J , Coates P Toby , Alexander Ian E , Bornstein Stefan R , Clarke Brigette 
Published: January 2023

Abstract
Primary adrenal insufficiency (PAI) occurs in 1 in 5 to 7000 adults. Leading etiologies are autoimmune adrenalitis in adults and congenital adrenal hyperplasia (CAH) in children. Oral replacement of cortisol is lifesaving, but poor quality of life, repeated adrenal crises, and dosing uncertainty related to lack of a validated biomarker for glucocorticoid sufficiency persists. Adrenocortical cell therapy and gene therapy may obviate many of the shortcomings of adrenal hormone replacement. Physiological cortisol secretion regulated by pituitary adrenocorticotropin could be achieved through allogeneic adrenocortical cell transplantation, production of adrenal-like steroidogenic cells from either stem cells or lineage conversion of differentiated cells, or for CAH, gene therapy to replace or repair a defective gene. The adrenal cortex is a high-turnover organ and thus failure to incorporate progenitor cells within a transplant will ultimately result in graft exhaustion. Identification of adrenocortical progenitor cells is equally important in gene therapy, for which new genetic material must be specifically integrated into the genome of progenitors to ensure a durable effect. Delivery of gene-editing machinery and a donor template, allowing targeted correction of the 21-hydroxylase gene, has the potential to achieve this. This review describes advances in adrenal cell transplants and gene therapy that may allow physiological cortisol production for children and adults with PAI.
Prevaccination Glucose Time in Range Correlates With Antibody Response to SARS-CoV-2 Vaccine in Type 1 Diabetes
Authors: Alhamar Ghadeer , Briganti Silvia , Maggi Daria , Viola Viola , Faraj Malak , Zannella Carla , Galdiero Massimiliano , Franci Gianluigi , Fusco Clorinda , Isgrò Camilla , Leanza Giulia , Malandrucco Ilaria , Spinelli Andrea , Tramontana Flavia , Iaria Domenico , Tortoriello Rachele , Pieralice Silvia , Rosati Milena , Matarese Giuseppe , Pozzilli Paolo , Galgani Mario , Strollo Rocky 
Published: January 2023

Abstract

Context
Poor glucose control has been associated with increased mortality in COVID-19 patients with type 1 diabetes (T1D).

Objective
This work aimed to assess the effect of prevaccination glucose control on antibody response to the SARS-CoV-2 vaccine BNT162b2 in T1D.

Methods
We studied 26 patients with T1D scheduled to receive 2 doses, 21 days apart, of BNT162b2, followed prospectively for 6 months with regular evaluation of SARS-CoV-2 antibodies and glucose control. Immunoglobulin G (IgG) to spike glycoprotein were assessed by enzyme-linked immunosorbent assay, and serum neutralization by a live SARS-CoV-2 assay (Vero E6 cells system). Glycated hemoglobin A1c (HbA1c) and continuous glucose monitoring (CGM), including time in range (TIR) and above range (TAR), were collected. The primary exposure and outcome measures were prevaccination glucose control, and antibody response after vaccination, respectively.

Results
Prevaccination HbA1c was unrelated to postvaccine spike IgG (r = −0.33; P = .14). Of note, the CGM profile collected during the 2 weeks preceding BNT162b2 administration correlated with postvaccine IgG response (TIR: r = 0.75; P = .02; TAR: r = −0.81; P = .008). Patients meeting the recommended prevaccination glucose targets of TIR (≥ 70%) and TAR (≤ 25%) developed stronger neutralizing antibody titers (P &lt; .0001 and P = .008, respectively), regardless of HbA1c. Glucose control along the study time frame was also associated with IgG response during follow-up (TIR: r = 0.93; P &lt; .0001; TAR: r = −0.84; P &lt; .0001).

Conclusion
In T1D, glucose profile during the 2 weeks preceding vaccination is associated with stronger spike antibody binding and neutralization, highlighting a role for well-controlled blood glucose in vaccination efficacy.
Genomic Profiling Reveals the Variant Landscape of Sporadic Parathyroid Adenomas in Chinese Population
Authors: Tao Xiaohui , Xu Tian , Lin Xiaoyun , Xu Shuqin , Fan Youben , Guo Bomin , Deng Xianzhao , Jiao Qiong , Chen Lihui , Wei Zhe , Chen Chengkun , Yang Wendi , Zhang Zhenlin , Yu Xiangtian , Yue Hua 
Published: January 2023

Abstract

Objective
To define somatic variants of parathyroid adenoma (PA) and to provide novel insights into the underlying molecular mechanism of sporadic PA.

Methods
Basic clinical characteristics and biochemical indices of 73 patients with PA were collected. Whole-exome sequencing was performed on matched tumor-constitutional DNA pairs to detect somatic alterations. Functional annotation was carried out by ingenuity pathway analysis afterward. The protein expression of the variant gene was confirmed by immunohistochemistry, and the relationship between genotype and phenotype was analyzed.

Results
Somatic variants were identified in 1549 genes, with an average of 69 variants per tumor (range, 13-2109; total, 9083). Several novel recurrent somatic variants were detected, such as KMT2D (15/73), MUC4 (14/73), POTEH (13/73), CD22 (12/73), HSPA2 (12/73), HCFC1 (11/73), MAGEA1 (11/73), and SLC4A3 (11/73), besides the previously reported PA-related genes, including MEN1 (11/73), CASR (6/73), MTOR (4/73), ASXL3 (3/73), FAT1 (3/73), ZFX (5/73), EZH1 (2/73), POT1 (2/73), and EZH2 (1/73). Among them, KMT2D might be the candidate driver gene of PA. Crucially, 5 patients carried somatic mutations in CDC73, showed an aggressive phenotype similar to that of parathyroid carcinoma (PC), and had a decreased expression of parafibromin. Pathway analysis of recurrent potential PA-associated driver variant genes revealed functional enrichments in the signaling pathway of Notch.

Conclusion
Our study expanded the pathogenic variant spectrum of PA and indicated that KMT2D might be a novel candidate driver gene and be considered as a diagnostic biomarker for PA. Meanwhile, CDC73 mutations might be an early developmental event from PA to PC. The results provided insights into elucidating the pathogenesis of parathyroid tumorigenesis and a certain basis for clinical diagnosis and treatment.
Systemic Activation of the Kynurenine Pathway in Graves Disease With and Without Ophthalmopathy
Authors: Ueland Hans Olav , Ulvik Arve , Løvås Kristian , Wolff Anette S B , Breivik Lars Ertesvåg , Stokland Ann-Elin Meling , Rødahl Eyvind , Nilsen Roy Miodini , Husebye Eystein , Ueland Grethe Åstrøm 
Published: January 2023

Abstract

Context
Graves disease (GD) is one of the most common autoimmune disorders. Recent literature has shown an immune response involving several different inflammatory related proteins in these patients.

Objective
This work aimed to characterize the kynurenine pathway, activated during interferon-γ (IFN-γ)–mediated inflammation and cellular (T-helper type 1 [Th1] type) immunity, in GD patients with and without thyroid eye disease (TED).

Methods
We analyzed 34 biomarkers by mass spectrometry in serum samples from 100 patients with GD (36 with TED) and 100 matched healthy controls. The analytes included 10 metabolites and 3 indices from the kynurenine pathway, 6 microbiota-derived metabolites, 10 B-vitamers, and 5 serum proteins reflecting inflammation and kidney function.

Results
GD patients showed significantly elevated levels of 7 biomarkers compared with healthy controls (omega squared [ω2] &gt; 0.06; P &lt; .01). Of these 7, the 6 biomarkers with the strongest effect size were all components of the kynurenine pathway. Factor analysis showed that biomarkers related to cellular immunity and the Th1 responses (3-hydroxykynurenine, kynurenine, and quinolinic acid with the highest loading) were most strongly associated with GD. Further, a factor mainly reflecting acute phase response (C-reactive protein and serum amyloid A) showed weaker association with GD by factor analysis. There were no differences in biomarker levels between GD patients with and without TED.

Conclusion
This study supports activation of IFN-γ inflammation and Th1 cellular immunity in GD, but also a contribution of acute-phase reactants. Our finding of no difference in systemic activation of the kynurenine pathway in GD patients with and without TED implies that the local Th1 immune response in the orbit is not reflected systemically.
Longitudinal Trajectory and Early Life Determinant of Childhood Adipokines: Findings From a Racially Diverse Birth Cohort
Authors: Makker Kartikeya , Zhang Mingyu , Wang Guoying , Hong Xiumei , Aziz Khyzer , Brady Tammy M , Wang Xiaobin 
Published: January 2023

Abstract

Context
Leptin and adiponectin play important roles in systemic metabolic homeostasis, beginning in utero. Limited data exist on the levels and trajectories of these 2 hormones at birth and in childhood and their biological and social determinants.

Objective
We examined the longitudinal trajectories of leptin and adiponectin from birth to early childhood, along with influential prenatal and infancy factors, and whether the trajectories and risk factors differ by preterm birth status.

Methods
We included mother-infant pairs in the Boston Birth Cohort, a predominantly Black, indigenous, and people of color (BIPOC) study population. We measured infant plasma leptin and adiponectin levels at birth and in early childhood. We examined longitudinal trajectories and the associated prenatal maternal and infancy factors. We analyzed 716 infants (158 preterm) who had leptin and adiponectin measured at birth and in early childhood (mean corrected age 2.18 years [interquartile range, 0.4-10.4]).

Results
Cord leptin was higher in term infants (40 230 vs 20 481 in preterm, P &lt; 0.0001) but childhood leptin did not differ by prematurity (4123 in term vs 4181 in preterm, P = 0.92). Adiponectin was higher in term infants at birth (18 416 vs 11 223, P &lt; 0.0001) and in childhood (12 108 vs 10532, P = 0.04). In stepwise regression, Black race was associated with higher childhood leptin and lower childhood adiponectin. Female sex was associated with higher childhood leptin levels and lower childhood adiponectin levels in multivariable regression models.

Conclusion
Our results highlight preterm status, race, and biological sex as predictors of adipokine trajectory throughout childhood. These findings raise the possibility that early life programming of adipokines may contribute to higher metabolic risk in life, especially among Black children born preterm.
Suppression of Insulin Receptor Substrate 1 Inhibits Breast Cancer Growth In Vitro and in Female Athymic Mice
Authors: Zhang Xihong , Varma Sidhant , Yee Douglas 
Published: January 2023

Abstract
Targeting the type I insulin-like growth factor receptor (IGF-IR) has not been successful in breast cancer. Data suggest the highly homologous insulin receptor (IR) may be an alternate growth stimulatory pathway used by cancer cells. Since both receptors phosphorylate the insulin receptor substrate 1 (IRS-1) protein as an immediate consequence of ligand binding, disruption of both receptors could be accomplished by suppression of IRS-1. IRS-1 gene deletion by CRISPR/Cas9 editing resulted in suppression of IGF-I, insulin, and estrogen-stimulated growth in hormone-dependent MCF-7L breast cancer cells. A doxycycline-inducible IRS-1 shRNA lentiviral construct was also used to infect MCF-7L breast cancer cells. IRS-1 shRNA downregulation resulted in decreased responses to IGF-I, insulin, and estradiol in monolayer and anchorage-independent growth assays. Decreased IRS-1 levels also suppressed estradiol-stimulated gene expression and estrogen receptor binding to DNA. Xenograft growth was also inhibited by induction of IRS-1 shRNA. These data show that IRS-1 is a critical regulator of endocrine responsive breast cancer. Efforts to target this adaptor protein could have broader growth inhibitory effects and receptor targeting.