bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urgent call for guidance supporting gene-based drug dosing in children and adolescents
Authors: Scodellaro Sierra , Cohn Ronald D , Cohn Iris 
Published: June 2023

Abstract
In the past decade, there have been tremendous advancements in the field of genomics that have led to significant progress in redefining the concept of precision medicine. Pharmacogenetics (PGx) is one of the most promising areas of precision medicine and is the ‘low hanging fruit’ of this individualized approach to medication dosing and selection. Although a variety of regulatory health agencies and professional consortia have established PGx clinical practice guidelines, implementation has been slow given numerous barriers faced by health care professionals. Many lack the training needed to interpret PGx and there are no paediatric specific guidelines. As the field of PGx continues to grow, an emphasis on collaborative inter-professional education, coupled with ongoing efforts to increase accessibility to advancing testing technology are necessary to translate this branch of precision medicine from the bench to the bedside.
Rethinking Political Polarization
Authors: Schedler Andreas 
Published: June 2023

Abstract
The comparative study of political polarization has been central to current debates on the global crisis of democracy. It has been built on uncertain conceptual foundations, though. Established uses of the concept lack a distinctive semantic core as multiple meanings compete against each other. On the basis of a broad reading of the comparative literature, I seek to circumscribe the use and reconstruct the core of political polarization as an instance of extraordinary democratic conflict. In a first step, I delineate the basic parameters of debate by distinguishing between cluster-analytic and conflict-analytic approaches and by specifying the generic type of political conflict that characterizes the polarization of democratic polities. In a second step, I argue for political intolerance as the defining trait of both ideological and social polarization. In a final step, I introduce a third, democratic dimension into the debate: the breakdown of basic democratic trust that leads actors to view their adversaries as “enemies of democracy.” Such perceptions spell the end of democratic consolidation. When played among “democratic enemies,” democracy stops being “the only game in town.”
The current existence of ChatGPT in education: a double-edged sword?
Authors: Situmorang Dominikus David Biondi , Salim Rose Mini Agoes , Ifdil Ifdil , Liza Ledya Oktavia , Rusandi M Arli , Hayati Isnaria Rizki , Amalia Rizki , Muhandaz Ramon , Fitriani Arbania 
Published: June 2023

Abstract
The authors in this article would like to invite related parties to carry out updates in the world of education, that the existence of ChatGPT can provide new enthusiasm for all of us to improve in a better direction.
Causal associations and genetic overlap between COVID-19 and intelligence
Authors: Cao Hongbao , Baranova Ancha , Song Yuqing , Chen Jian-Huan , Zhang Fuquan 
Published: June 2023

Summary

Objective
COVID-19 might cause neuroinflammation in the brain, which could decrease neurocognitive function. We aimed to evaluate the causal associations and genetic overlap between COVID-19 and intelligence.

Methods
We performed Mendelian randomization (MR) analyses to assess potential associations between three COVID-19 outcomes and intelligence (N = 269 867). The COVID phenotypes included severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (N = 2 501 486), hospitalized COVID-19 (N = 1 965 329) and critical COVID-19 (N = 743 167). Genome-wide risk genes were compared between the genome-wide association study (GWAS) datasets on hospitalized COVID-19 and intelligence. In addition, functional pathways were constructed to explore molecular connections between COVID-19 and intelligence.

Results
The MR analyses indicated that genetic liabilities to SARS-CoV-2 infection (odds ratio [OR]: 0.965, 95% confidence interval [CI]: 0.939–0.993) and critical COVID-19 (OR: 0.989, 95% CI: 0.979–0.999) confer causal effects on intelligence. There was suggestive evidence supporting the causal effect of hospitalized COVID-19 on intelligence (OR: 0.988, 95% CI: 0.972–1.003). Hospitalized COVID-19 and intelligence share 10 risk genes within 2 genomic loci, including MAPT and WNT3. Enrichment analysis showed that these genes are functionally connected within distinct subnetworks of 30 phenotypes linked to cognitive decline. The functional pathway revealed that COVID-19-driven pathological changes within the brain and multiple peripheral systems may lead to cognitive impairment.

Conclusions
Our study suggests that COVID-19 may exert a detrimental effect on intelligence. The tau protein and Wnt signaling may mediate the influence of COVID-19 on intelligence.
Realization of regularity coefficients for flows
Authors: Barreira Luis , Valls Claudia 
Published: June 2023

Abstract
We establish sharp relations between several regularity coefficients for flows generated by non-autonomous differential equations. We verify that these relations are sharp by showing that all possible values of the regularity coefficients satisfying these relations are attained by some linear equation with bounded piecewise-continuous coefficient matrix. In addition, we introduce two new regularity coefficients and we obtain sharp relations between these and other coefficients.
Development of a computed tomography calcium scoring technique for assessing calcinosis distribution, pattern and burden in dermatomyositis
Authors: Cervantes Briana A , Gowda Prateek , Rider Lisa G , Miller Frederick W , Chen Marcus Y , Schiffenbauer Adam 
Published: June 2023

Abstract

Objectives
To utilize whole-body CT imaging and calcium scoring techniques as tools for calcinosis assessment in a prospective cohort of patients with adult and juvenile dermatomyositis (DM and JDM, respectively).

Methods
Thirty-one patients (14 DM and 17 JDM) who fulfilled Bohan and Peter Classification criteria as probable or definite DM, the EULAR-ACR criteria for definite DM, and with calcinosis identified by physical examination or prior imaging studies were included. Non-contrast whole-body CT scans were obtained using low-dose radiation procedures. Scans were read qualitatively and quantitated. We calculated the sensitivity and specificity of calcinosis detection of physician physical exam against CT. We quantified calcinosis burden using the Agatston scoring technique.

Results
We identified five distinct calcinosis patterns: Clustered, Disjoint, Interfascial, Confluent and Fluid-filled. Novel locations of calcinosis were observed, including the cardiac tissue, pelvic and shoulder bursa, and the spermatic cord. Quantitative measures using Agatston scoring for calcinosis were used in regional distributions across the body. Physician physical exams had a sensitivity of 59% and a specificity of 90% compared with CT detection. A higher calcium score correlated with higher Physician Global Damage, Calcinosis Severity scores, and disease duration.

Conclusion
Whole-body CT scans and the Agatston scoring metric define distinct calcinosis patterns and provide novel insights relating to calcinosis in DM and JDM patients. Physicians’ physical examinations underrepresented the presence of calcium. Calcium scoring of CT scans correlated with clinical measures, which suggests that this method may be used to assess calcinosis and follow its progression.
Organizing family philanthropy: mobilizing resources and setting up governance for impact
Authors: Eichenberger Etienne , Smulowitz Malgorzata , Vogel Peter 
Published: June 2023

Abstract
Based on their research and experience, the authors find that “best practice” philanthropists adopt a pragmatic and rigorous approach to organizing their philanthropy. That is, they tend to run their philanthropic organizations as efficiently and effectively as possible, with clear structures, roles and responsibilities, as well as goals. The total resources and engagement of a family and wider network determine the setup and governance of one’s giving. In this article, the authors show how philanthropic families can organize their resources and governance to achieve the desired impact across generations. The authors conclude that mobilizing resources and structuring governance in a harmonized and holistic way helps philanthropists to achieve their desired impact.
The Knowledge Intensification of Agriculture
Authors: Vincelli Paul 
Published: June 2023

Federal funding for agricultural sciences was initiated with the passage of the Morrill Act in 1862. Since then, the need for science-based information to support our knowledge-intensive agricultural and food systems has grown substantially, and continues to grow, in all farm and food systems. Transformative developments in the disciplines of plant microbiology and plant pathology have led to an increased pace in research and application of knowledge in soil ecosystems and phytobiomes, precision agriculture, and more sophisticated tools for the manipulation of plant genetics. Appropriate federal support remains critical to our robust farming and food systems. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Myocardin‐related transcription factor contributes to renal fibrosis through the regulation of extracellular microenvironment surrounding fibroblasts
Authors: Yamamura Yuta , Sakai Norihiko , Iwata Yasunori , Lagares David , Hara Akinori , Kitajima Shinji , Toyama Tadashi , Miyagawa Taro , Ogura Hisayuki , Sato Koichi , Oshima Megumi , Nakagawa Shiori , Tamai Akira , Horikoshi Keisuke , Matsuno Takahiro , Yamamoto Naoki , Hayashi Daiki , Toyota Yoshitada , Kaikoi Daichi , Shimizu Miho , Tager Andrew M. , Wada Takashi 
Published: June 2023

AbstractFibroblast accumulation and extracellular matrix (ECM) deposition are common critical steps for the progression of organ fibrosis, but the precise molecular mechanisms remain to be fully investigated. We have previously demonstrated that lysophosphatidic acid contributes to organ fibrosis through the production of connective tissue growth factor (CTGF) via actin cytoskeleton‐dependent signaling, myocardin‐related transcription factor family (MRTF) consisting of MRTF‐A and MRTF‐B‐serum response factor (SRF) pathway. In this study, we investigated the role of the MRTF‐SRF pathway in the development of renal fibrosis, focusing on the regulation of ECM‐focal adhesions (FA) in renal fibroblasts. Here we showed that both MRTF‐A and ‐B were required for the expressions of ECM‐related molecules such as lysyl oxidase family members, type I procollagen and fibronectin in response to transforming growth factor (TGF)‐β1. TGF‐β1‐MRTF‐SRF pathway induced the expressions of various components of FA such as integrin α subunits (αv, α2, α11) and β subunits (β1, β3, β5) as well as integrin‐linked kinase (ILK). On the other hand, the blockade of ILK suppressed TGF‐β1‐induced MRTF‐SRF transcriptional activity, indicating a mutual relationship between MRTF‐SRF and FA. Myofibroblast differentiation along with CTGF expression was also dependent on MRTF‐SRF and FA components. Finally, global MRTF‐A deficient and inducible fibroblast‐specific MRTF‐B deficient mice (MRTF‐AKOBiFBKO mice) are protected from renal fibrosis with adenine administration. Renal expressions of ECM‐FA components and CTGF as well as myofibroblast accumulation were suppressed in MRTF‐AKOBiFBKO mice. These results suggest that the MRTF‐SRF pathway might be a therapeutic target for renal fibrosis through the regulation of components forming ECM‐FA in fibroblasts.
COGNITIVE IMPAIRMENT AND CARDIOVASCULAR RISK FACTORS: FINDINGS FROM THE PURE-COLOMBIA COHORT
Authors: Tiga-Loza Diana Carolina , Calderon-Ardila Ariel , Cohen Daniel , Otero Johanna , Perez Maritza , Rosa Andrea De La , Giraldo Juan Carlos , Vega Karol , Lopez-Lopez Jose , Lopez-Jaramillo Patricio 
Published: June 2023

Objective:
To estimate the prevalence of cognitive impairment and its association with cardiovascular risk factors in the cohort population of the Prospective Urban and Rural Epidemiological Study (PURE) for the fifteenth year of follow-up in some departments of Colombia.

Design and method:
Cross-sectional study nested in the PURE cohort in participants with Mini-Cog test for cognitive screening, with a cut-off point of < = 2 points to screen cognitive impairment. We evaluate behavioral cardiovascular factors such as smoking, pathological history such as arterial hypertension, and measurements of blood pressure, weight, height, waist/hip ratio, glucose, triglycerides, cholesterol, hdl, ldl, and creatinine. We stimate The prevalence ratios for cognitive impairment using a generalized linear model with binomial family and link log.

Results:
In 707 participants whose mean age is 64.9 (SD 9.2) years, 66.8% are women, we found that 26.8% with indicators of cognitive impairment, with complete difficulty for the clock sub-test in 24.5% and 3.9% on the memory subtest. A higher prevalence of cognitive impairment was found among hypertensives compared to non-hypertensives (63.7% vs. 41.8%, Prevalence Ratio = 1.51, 95% CI 1.17; 1.93, p = <0.001). In addition, systolic blood pressure was 9 mmHg, higher in participants with cognitive impairment (median 138mmHg vs 129mmHg, p = 0.0001)
Also, the proportion of people with deterioration was higher in those who had a cholesterol greater than 200mg/dL (PR = 1.38 95% CI = 1.11;1.72 p = 0.004) and with an increase in the waist-hip ratio (PR = 3.27 95% CI = 1.21; 8.8 p = 0.019) the above adjusted for age, sex and educational level.

Conclusions:
More than a quarter of the participants in the PURE cohort presented indicators of cognitive impairment, its prevalence was significantly higher in hypertensive patients, in people with high cholesterol and with a significantly higher waist/hip ratio, which indicates the importance of preventing and controlling the Cardiovascular risk factors in older adults with cognitive alterations.
BLOOD PRESSURE, HIGH-SENSITIVITY C-REACTIVE PROTEIN, INTERLEUKIN-6 AND WHITE BLOOD CELLS IN THE COMMUNITY-DWELLING OLDER ADULTS
Authors: Sulicka-Grodzicka Joanna , Wizner Barbara , Zdrojewski Tomasz , Mossakowska Malgorzata , Puzianowska-Kuznicka Monika , Chudek Jerzy , Wiecek Andrzej , Guzik Tomasz 
Published: June 2023

Objective:
Increasing evidence indicates an association between blood pressure (BP) and vascular inflammation, although these relationship remains unknown in older adults. Understanding this association in this population is particularly important in the context of increased prevalence of hypertension, as well as role of inflammatory responses in age related comorbidities.

Design and method:
We examined the relationship between BP, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and white blood cells (WBC) among 3571 older (aged > = 65 years) and 587 middle-aged (57 ± 1 years old) adults recruited as a part of the PolSenior health survey .

Results:
BP levels differed in relation to hs-CRP and WBC quartiles in older patients. In particular, systolic BP were 145 ± 22 mmHg and 149 ± 24 mmHg, in the first and fourth quartile of hs-CRP (P = 0.002), and 145 ± 20 mmHg and 150 ± 23 mmHg, respectively for the WBC (P < 0.001). In contrast, systolic BP did not differ between IL-6 quartiles (146 ± 21 mmHg and 145 ± 22 mmHg, P = 0.8). Moreover, the age, gender and body mass index (BMI) adjusted odds ratio (OR) for high BP in subjects with hs-CRP > = 3.7 mg/L was 1.29 (95% CI, 1.05-1.58, P = 0.01) compared with those with hs-CRP < 1 mg/L; in patients with WBC> = 7.1 x 109/L OR was 1.42 (95% CI, 1.16-1.75, P < 0.001) compared with those with WBC < 5.2 x 109/L. Interestingly, in subjects with IL-6 > = 3.4 pg/mL adjusted OR was 0.84 (95% CI, 0.68-1.04, P = 0.11) compared with those with IL-6 < 1.4 pg/mL. In the fully-adjusted model applied in older adults, higher hs-CRP remained associated with high BP, independently of age, gender, BMI, IL-6 and WBC (adjusted OR = 1.12, 95% CI, 1.03 to 1.22, P = 0.008).

Conclusions:
CRP and WBC, but not IL-6, are positively associated with high blood pressure in the population of community-dwelling older adults, independently of age, gender, and BMI. Results of our study may suggest an important role of inflammation in the pathogenesis of increased blood pressure, also in the older population.
REPRODUCIBILITY AND PREDICTIVE VALUE OF WHITE COAT HYPERTENSION IN YOUNG TO MIDDLE AGE SUBJECTS
Authors: Saladini Francesca , Mos Lucio , Vriz Olga , Mazzer Adriano , Zanata Giuseppe , Fania Claudio , Rattazzi Marcello , Palatini Paolo 
Published: June 2023

Objective:
The reproducibility and the prognostic value of white-coat hypertension (WCH) is still debated. The aim of the study was to investigate the reproducibility of WCH assessed twice within 3 months and its predictive capacity for development of hypertension needing antihypertensive treatment (HT) in young-to-middle-age subjects screened for stage 1 hypertension.

Design and method:
We investigated 1096, 18-to-45-year old subjects from the HARVEST. Office BP and 24hour BP were measured at baseline and after 3 months. On the basis of BPs measured after 3 months, 132 participants were classified as normotensive, 159 as WCH, 195 as masked hypertensive and 610 as sustained hypertensive. The reproducibility of WCH, office hypertension, and ambulatory hypertension was evaluated with Kappa statistics. The predictive capacity of WCH defined with a single assessment or with double assessment was tested in multivariate Cox models (N = 1054).

Results:
Baseline WCH was confirmed at 3-month assessment in only 33.3% of participants, whereas 31.6% became normotensive, 8.8% masked hypertensive and 26.3% sustained hypertensive. Reproducibility evaluated with weighted Kappa was fair (0.27, 95%CI 0.20 - 0.37) for WCH, poor (0.14, 95%CI 0.09 - 0.19) for office Hypertension (BP> = 140/90 mmHg), and moderate (0.47, 95%CI 0.41 - 0.53) for ambulatory Hypertension (24hBP> = 130/80 mmHg). During 17.4 years of follow-up, 80.5% of participants developed HT. WCH assessed either at baseline (p = 0.86) or after 3 months (p = 0.16) was not a significant predictor of future HT. However, participants who had WCH both at baseline and after 3 months (N = 76) had an increased risk of HT compared to the normotensives (Hazard ratio, 1.50, 95%CI 1.06 - 2.13, p = 0.022). HRs were 1.35 (95%CI 1.02 - 1.80, p = 0.037) in participants with masked hypertension and 1.52 (95%CI 1.19 - 1.95, p < 0.001) in those with sustained hypertension.

Conclusions:
These results show that in young-to-middle-age individuals, WCH was confirmed in only one third of people at repeat assessment. This was mainly due to a poor reproducibility of office hypertension. WCH diagnosed with two but not with one BP assessment showed an increased risk of future HT. Our data indicate that people with WCH at first assessment should undergo a second set of ambulatory and office BP measurements before clinical decisions are made.
ABSENT VASOREACTIVE RESPONSE TO HIGH SODIUM INTAKE COINCIDES WITH SALT SENSITIVITY IN CKD PATIENTS
Authors: Duin Robert van , Oppelaar Jetta , Schijndel Emma Van , Born Bert -Jan van den , Engberink Rik Olde , Vogt Liffert 
Published: June 2023

Objective:
Chronic kidney disease (CKD) patients are advised to limit salt intake, because of its detrimental effects on blood pressure (BP) and albuminuria. The salt-sensitive BP response in CKD is classically attributed to impaired renal ability to excrete sodium (Na+) resulting in fluid overload. Yet, BP sensitivity to salt is also linked to vasodysfuction, and may even be fluid independent. We aimed to investigate which factor contributes to BP sensitivity to salt in CKD.

Design and method:
In this randomized crossover study, CKD patients (KDIGO stage G2-3A, proteinuria >0.5 g/d) and healthy controls (HC) followed a 7-day low sodium diet (LSD, <50mmol/d) and high sodium diet (HSD, >200mmol/d), respectively. After each diet, assessment of the hemodynamic profile included daytime BP (Mobil-O-Graph) and cardiac output (CO) measurements (using NexfinTM), by which SVR was calculated accordingly. Extracellular fluid volume (ECV) change was assessed with multi-frequency body impedance spectroscopy (FHCresenius).

Results:
We included 16 HC (median age 36.0 yrs) and 8 CKD patients (median age 49.5 yrs, and median (IQR) proteinuria 0.6 (0.5-1.1) g/d and plasma creatinine 144 (103 - 167) μmol/l. Dietary salt intervention was successful with median difference in urine Na+ excretion of 242.2 vs 224.6 mmol/day in HC and CKD respectively (p = 0.74). After HSD, the median (IQR) change in systolic BP of patients with CKD was 14 mmHg (4 - 18; p = 0.04), while systolic BP change (4 mmHg (-3 - 8)) in HC was not significant (Fig 1A). After HSD, we observed a significant ECV expansion in both CKD and HC subjects (Fig 1B), but no effect on CO. No associations between HSD-induced BP changes and both ECV and CO were found. Systolic BP increase was correlated with SVR decline in HC, but not in CKD patients (Fig 1C).

Conclusions:
In contrast to healthy persons, BP salt sensitivity in CKD does not associate with vasodilation. Regarding the absence of differences with ECV and CO between healthy and CKD persons, our data indicate that the incapacity for vasodilation might explain salt sensitivity in CKD.
ASSOCIATION BETWEEN PEAK EXPIRATORY FLOW AND INCIDENT HEART FAILURE AND MORTALITY IN MIDDLE-AGED AND OLDER CHINESE ADULTS
Authors: Chen Chao -Lei , Feng Ying -Qing 
Published: June 2023

Objective:
Previous studies have suggested that pulmonary dysfunction predicts incident cardiovascular disease, posing the question of whether peak expiratory flow, one of the most direct measurements of lung function, could present a modifiable risk factor. In the present study, we aimed to evaluate associations of peak expiratory flow with incident heart failure, cardiovascular death, and all-cause death.

Design and method:
This study included 93,161 participants from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project in Southern China who had lung function measurements at baseline (year 2016-2017) and were annually followed-up to December 2020. The composite endpoints included hospitalization for heart failure, cardiovascular death, and all-cause death. Hospitalization for heart failure were ascertained by linking to the Inpatient Registry and confirmation of death was based on information from local government vital statistics offices. The relationship between peak expiratory flow and all outcomes was assessed using multivariable Cox regression adjusting for age, sex, education, annual income, insurance, residence, occupation, current smoking, current drinking, body mass index, hypertension, diabetes, coronary heart disease, and stroke at baseline.

Results:
The mean age was 54.2 years, and 60.7% were women. At 3.4 ± 0.9 years of follow-up, heart failure occurred in 1361 (1.5%), cardiovascular death in 365 (0.4%), all-cause death in 1346 (1.4%), and the composite in 2490 (2.7%). Compared with the lowest quartile, the HR (95% CI) of the highest quartile in peak expiratory flow was 0.66 (0.55 - 0.78) for incident heart failure, 0.70 (0.51 - 0.95) for cardiovascular death, 0.54 (0.46 - 0.64) for all-cause death, and 0.54 (0.47 - 0.61) for the composite. The restricted cubic spline showed significantly negative relationships of peak expiratory flow with all outcomes. In addition, the association between peak expiratory flow and incident heart failure was not significantly changed after mortality was treated as competing risks in the Fine–Gray proportional sub-distribution hazards models (HR [95% CI]: 0.87 [0.81 - 0.93]).

Conclusions:
Higher peak expiratory flow was significantly associated with decreased risks of incident heart failure, cardiovascular death, and all-cause death in middle aged and elderly Chinese adults, independent of and to a similar extent as major known cardiovascular risk factors.