bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)
Authors: Griffiths-Jones Deborah J , Garcia Yvonne Sylvestre , Ryder W David , Pauling John D , Hall Frances , Lanyon Peter , Bhat Smita , Douglas Karen , Gunawardena Harsha , Akil Mohammed , Anderson Marina , Griffiths Bridget , Del Galdo Francesco , Youssef Hazem , Madhok Rajan , Arthurs Barbara , Buch Maya , Fligelstone Kim , Zubair Mohammed , Mason Justin C , Denton Christopher P , Herrick Ariane L 
Published: January 2023

Abstract

Objectives
Although the painful and disabling features of early diffuse cutaneous SSc (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate-dose prednisolone in early dcSSc.

Methods
PRedSS set out as a Phase II, multicentre, double-blind randomized controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomized to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the HAQ Disability Index (HAQ-DI) and modified Rodnan skin score (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients.

Results
Thirty-five patients were randomized (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was −0.10 (97.5% CI: −0.29, 0.10), P = 0.254, and in mRSS −3.90 (97.5% CI: −8.83, 1.03), P = 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (P = 0.027), anxiety (P = 0.018) and helplessness (P = 0.040) than control patients at 3 months. There were no renal crises, but sample size was small.

Conclusion
PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomized trial.

Trial registration
ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.
A Sustainable Solution or Just a Different Form of Humanitarian Assistance? Examining the Kalobeyei Integrated Socio-Economic Development Plan (KISEDP)
Authors: Fellesson Måns 
Published: January 2023

Abstract
This article contributes to the understanding of operational challenges linked to the implementation of the Global Compact on Refugees and the Comprehensive Refugee Response Framework . In the scope of the analysis is the operationalisation of the Kalobeyei Integrated Socio-Economic Development Plan in Kenya, aimed at promoting economic and social integration through greater opportunities for self-reliance, livelihood, and inclusion in national service systems for refugees and the host population alike. The article sheds light on the conditions and prospects for developing the Kalobeyei Integrated Socio-Economic Development Plan by examining key circumstances and interplays in two areas central to the idea of refugee/host integration – relevant national legal frameworks and the composition of grounding socio-economic factors. The results show the need for revisions to the Kalobeyei Integrated Socio-Economic Development Plan if its most grounding objectives are to materialise. As it stands, the implementation builds on an incompatible amalgamation of a grand development vision, speaking about inclusion, mobility, and economic development, to be carried out in a much restricted and economically challenging environment.
Longitudinal self-concept development in adolescence
Authors: van der Cruijsen Renske , Blankenstein Neeltje E , Spaans Jochem P , Peters Sabine , Crone Eveline A 
Published: January 2023

AbstractThis longitudinal behavioral neuroimaging study tested two hypotheses concerning self-concept development in adolescence: domain-specific self-concept and similarity between own (direct) and perceived peers’ (reflected) opinions of the self. Participants (N = 189; 10–24 years) evaluated their traits in academic, physical appearance and prosocial domains from direct and reflected perspectives in an functional magnetic resonance imaging session across three time points (TP1: n = 160; TP2: n = 151; TP3: n = 144). Behaviorally, we observed a mid-adolescent dip in self-concept positivity, which was strongest for the academic domain, showing domain differentiation in mid-adolescence. Self-evaluations were associated with activity in, e.g. medial prefrontal cortex (mPFC) and temporal–parietal junction (TPJ). mPFC showed an adolescent-emerging peak in activation, pronounced more for direct than reflected self-evaluations. TPJ activation was generally stronger for reflected self-evaluations, and activation linearly increased with age for both reflected and direct self-evaluations. Longitudinal prediction analyses showed that positivity of self-evaluations predicted increases in self-concept clarity and less fear of negative evaluation 1 and 2 years later, highlighting the developmental benefits of acquiring a positive self-concept. Together, we show that adolescent self-development is characterized by dissociable neural patterns underlying self-evaluations in different domains, and from reflected and direct perspectives, confirming adolescence as a formative phase for developing a coherent and positive self-concept.
Right amygdala–right precuneus connectivity is associated with childhood trauma in major depression patients and healthy controls
Authors: Fan Jie , Gao Feng , Wang Xiang , Liu Qian , Xia Jie , Han Yan , Yi Jinyao , Tan Changlian , Zhu Xiongzhao 
Published: January 2023

AbstractThe present study investigated the effect of childhood trauma (CT) on amygdala and hippocampus functional connectivity (FC) and the association with clinical presentations of major depressive disorder (MDD). Participants included 73 MDD patients (42 with moderate-to-severe CT and 31 with no or low CT) and 64 healthy controls (HC; 30 with moderate-to-severe CT and 34 with no or low CT). Seed-based whole-brain resting-state FC analyses were performed with seeds located in amygdala and hippocampus. Individuals with moderate-to-severe CT, irrespective of MDD diagnosis, had decreased right amygdala–right precuneus connectivity compared to those with no or low CT. Right amygdala–right precuneus connectivity was significantly correlated with physical and social trait anhedonia in MDD. Mediation effects of this FC on relationship between CT (specifically neglect but not abuse) and trait anhedonia in MDD were significant. MDD patients demonstrated increased right amygdala–left middle frontal gyrus FC, decreased right amygdala–right medial superior frontal gyrus (mSFG) FC and decreased right hippocampus–bilateral mSFG FC relative to HC. Findings highlight the effect of CT on right amygdala–right precuneus FC irrespective of MDD diagnosis. FC of right amygdala–right precuneus may be involved in the mechanism linking CT and depression through its association with trait anhedonia.
E-cigarettes Induce Dysregulation of Autophagy Leading to Endothelial Dysfunction in Pulmonary Arterial Hypertension
Authors: Liu Chen-wei , Le Hoai Huong Thi , Denaro Philip , Dai Zhiyu , Shao Ning-Yi , Ong Sang-Ging , Lee Won Hee 
Published: January 2023

Abstract
Given the increasing popularity of electronic cigarettes (e-cigs), it is imperative to evaluate the potential health risks of e-cigs, especially in users with preexisting health concerns such as pulmonary arterial hypertension (PAH). The aim of the present study was to investigate whether differential susceptibility exists between healthy and patients with PAH to e-cig exposure and the molecular mechanisms contributing to it. Patient-specific induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from healthy individuals and patients with PAH were used to investigate whether e-cig contributes to the pathophysiology of PAH and affects EC homeostasis in PAH. Our results showed that PAH iPSC-ECs showed a greater amount of damage than healthy iPSC-ECs upon e-cig exposure. Transcriptomic analyses revealed that differential expression of Akt3 may be responsible for increased autophagic flux impairment in PAH iPSC-ECs, which underlies increased susceptibility upon e-cig exposure. Moreover, knockdown of Akt3 in healthy iPSC-ECs significantly induced autophagic flux impairment and endothelial dysfunction, which further increased with e-cig treatment, thus mimicking the PAH cell phenotype after e-cig exposure. In addition, functional disruption of mTORC2 by knocking down Rictor in PAH iPSC-ECs caused autophagic flux impairment, which was mediated by downregulation of Akt3. Finally, pharmacological induction of autophagy via direct inhibition of mTORC1 and indirect activation of mTORC2 with rapamycin reverses e-cig-induced decreased Akt3 expression, endothelial dysfunction, autophagic flux impairment, and decreased cell viability, and migration in PAH iPSC-ECs. Taken together, these data suggest a potential link between autophagy and Akt3-mediated increased susceptibility to e-cig in PAH.
The effect of supplementation of essential amino acid combinations in a low crude protein diet on growth performance in weanling pigs
Authors: Wellington Michael O , Hulshof Tetske G , Resink Jan Wellim , Ernst Kristi , Balemans Anke , Page Greg I 
Published: January 2023

Abstract
The present study investigated the impact of providing different supplemental essential amino acids (EAA) in a low crude protein (CP) diet on growth performance in weanling pigs. A total of 324 mixed-sex 24-d weaned piglets (initial BW 6.9 ± 0.34 kg) were used in a 27-d growth trial with six dietary treatments immediately post-weaning. The first two treatments were a control standard CP (19%) diet (positive control; PC) and a negative control (NC) diet with low CP (16%) and reduced Ile, Leu, and histidine levels. The rest of the treatments had low CP with varied EAA types and levels; T1 had similar Ile, Leu, and His levels as PC but with low CP (16%), while T2 had low CP and 10% higher His, Thr, Trp, and Met+Cys compared to PC. The T3 was a low CP diet with 10% supplemental Leu, Ile, and Val compared to PC, while T4 was a low CP diet with 10% supplementation with all the EAA except Lys compared to PC. The initial body weight (BW) was not statistically different (P &gt; 0.05) among the treatments. Also, on d 6, no statistical differences in BW were observed among the treatments. The average BW recorded on d 13, 20, and 27 showed significant treatment differences where the PC had consistently higher BW than all the other treatments (P &lt; 0.05). The average daily gain (ADG) of the PC was higher than the rest of the treatments. Between d 13 and 20, the average daily feed intake (ADFI) for PC was not different from NC and T1 (P &gt; 0.05), but compared to T2, T3, and T4, the PC treatment showed a high ADFI (P &lt; 0.05). Overall (d 0–27), the ADFI for PC was not different from T1 and was significantly higher than all other treatments. Overall, results showed that the gain to feed (G:F) ratio was higher (P &lt; 0.05) for PC compared to other dietary treatments. In summary, although the treatments (T1–T4) consisted of varying levels of EAA above the recommended requirement levels for optimal performance, we did not see a significant impact on growth performance improvement, which may indicate that the targeted EAA (His, Val, Thr, lle, Leu, Trp, and Met) may not have been limiting in these diets. On the other hand, the phenylalanine (Phe) requirement may be limited in the current formulations, or perhaps the EAA: total N ratio in T1, T2, T3, and T4 may have been too high, resulting in the inefficiency of EAA utilization for growth.
Temporal asymmetries and interactions between dorsal and ventral visual pathways during object recognition
Authors: Ayzenberg Vladislav , Simmons Claire , Behrmann Marlene 
Published: January 2023

Abstract
Despite their anatomical and functional distinctions, there is growing evidence that the dorsal and ventral visual pathways interact to support object recognition. However, the exact nature of these interactions remains poorly understood. Is the presence of identity-relevant object information in the dorsal pathway simply a byproduct of ventral input? Or, might the dorsal pathway be a source of input to the ventral pathway for object recognition? In the current study, we used high-density EEG—a technique with high temporal precision and spatial resolution sufficient to distinguish parietal and temporal lobes—to characterise the dynamics of dorsal and ventral pathways during object viewing. Using multivariate analyses, we found that category decoding in the dorsal pathway preceded that in the ventral pathway. Importantly, the dorsal pathway predicted the multivariate responses of the ventral pathway in a time-dependent manner, rather than the other way around. Together, these findings suggest that the dorsal pathway is a critical source of input to the ventral pathway for object recognition.
Systematic evaluation of chromatin immunoprecipitation sequencing to study histone occupancy in dormancy transitions of grapevine buds
Authors: Hermawaty Dina , Cahn Jonathan , Lister Ryan , Considine Michael J 
Published: January 2023

Abstract
The regulation of DNA accessibility by histone modification has emerged as a paradigm of developmental and environmental programming. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a versatile tool to investigate in vivo protein–DNA interaction and has enabled advances in mechanistic understanding of physiologies. The technique has been successfully demonstrated in several plant species and tissues; however, it has remained challenging in woody tissues, in particular complex structures such as perennating buds. Here we developed a ChIP method specifically for mature dormant buds of grapevine (Vitis vinifera cv. Cabernet Sauvignon). Each step of the protocol was systematically optimized, including crosslinking, chromatin extraction, sonication and antibody validation. Analysis of histone H3-enriched DNA was performed to evaluate the success of the protocol and identify occupancy of histone H3 along grapevine bud chromatin. To our best knowledge, this is the first ChIP experiment protocol optimized for the grapevine bud system.
Risk Factors for Refractory Immune Checkpoint Inhibitor-related Pneumonitis in Patients With Lung Cancer
Authors: Tan Peixin , Huang Wei , He Xinyan , Lv Fengquan , Cui Yanhai , Du Shasha 
Published: January 2023

Checkpoint inhibitor-related pneumonitis (CIP) is one of the most important immune checkpoint inhibitors side effects, and it is rare but fatal. Identifying patients at risk of refractory CIP before the start of CIP therapy is important for controlling CIP. We retrospectively analyzed the clinical data of 60 patients with lung cancer who developed CIP. Refractory CIP was defined as CIP with poor response to corticosteroid treatment, including CIP not relieved with corticosteroid administration or CIP recurrence during the corticosteroid tapering period. We analyzed clinical characteristics, peripheral blood biomarkers, treatment, and outcomes in nonrefractory and refractory CIP. Risk factors associated with refractory CIP were assessed. Among 60 patients with CIP, 16 (26.7%) had refractory CIP. The median onset time for patients with nonrefractory and those with refractory CIP was 16.57 (interquartile range [IQR], 6.82–28.14) weeks and 7.43 (IQR, 2.71–19.1) weeks, respectively. The level of lactate dehydrogenase (LDH) was significantly higher in the refractory CIP group at baseline (255 [222, 418] vs. 216 [183, 252], P=0.031) and at CIP onset (321.5 [216.75, 487.5] vs. 219 [198. 241], P=0.019). An LDH level >320 U/L at CIP onset was an independent risk factor of refractory CIP (odds ratio [OR], 8.889; 95% confidence interval [CI]: 1.294–61.058; P=0.026). The incidence of refractory CIP is high among patients with CIP. An increased LDH level at CIP onset is independently associated with refractory CIP. Monitoring LDH levels during immune checkpoint inhibitors treatment is recommended.
Population Pharmacokinetic and Pharmacokinetic/Pharmacodynamic Target Attainment Analyses for Dalbavancin in Pediatric Patients
Authors: Carrothers Timothy J. , Lagraauw H. Maxime , Lindbom Lars , Riccobene Todd A. 
Published: January 2023

Background:
Dalbavancin, approved for the treatment of pediatric and adult patients with acute bacterial skin and skin structure infections, has a terminal half-life of >14 days allowing administration as a single-dose regimen.

Methods:
We developed a population pharmacokinetic (PK) model using 1124 dalbavancin concentrations from 211 pediatric patients, with allometric scaling of clearance and volume parameter exponents fixed at 0.75 and 1, respectively. Serum albumin was included as a covariate on all PK parameters; creatinine clearance or estimated glomerular filtration rate was a covariate on clearance. The final model, qualified by visual predictive checks and bootstrapping, was used to simulate 1000 PK profiles for a range of pediatric age groups. PK/pharmacodynamic target attainment (PTA) was calculated for targets associated with stasis, 1-log kill, and 2-log kill of Staphylococcus aureus (neutropenic murine thigh infection model).

Results:
Dalbavancin PK was well characterized by a three-compartment model. No additional significant covariates were identified. Simulations showed that single-dose (30-minute intravenous infusion) regimens of 22.5 mg/kg (patients <6 years) and 18 mg/kg (patients 6 years to <18 years) resulted in PTA ≥94% for minimal inhibitory concentrations ≤2 mg/L and ≤0.5 mg/L for the stasis and 2-log kill targets, respectively. PTA for pediatric patients was similar to adults with exposures within the range for adults administered 1500 mg dalbavancin.

Conclusion:
Dalbavancin PK in pediatric patients was well characterized by a three-compartment model. Simulations with the final model demonstrated adequate PTA across the entire age range for the approved pediatric dalbavancin doses.
Comparison of Epidemiologic and Clinical COVID-19 Profiles in Children in Argentina, During Circulation of Original and Variant (Alpha, Gamma and Lambda) Strains
Authors: Gentile Angela , Juárez María Del Valle , Romero Bollon Lucia , Aprea Valeria , Matteucci Erika , Falaschi Andrea , Brizuela Martin , Euliarte Cristina , Gregorio Gabriela , Della Latta Maria Paula , Russ Carlota , Ensinck Gabriela Nidia , Saraceni Liliana , Bruno Miriam , Garnero Analía , Cohen Arazi Laura , Melonari Pablo , Pebe Florian Victor , Bogdanowicz Elizabeth , Gaiano Alejandra , Bellone Luciana , Areso Maria Soledad ,   on behalf of the COVID-19 Pediatric Networka
Published: January 2023

Background:
Information on the impact of the different variants in children in Latin America is scarce. The objective of this study was to describe epidemiologic and clinical features of COVID-19 infection in children under 18 years of age in Argentina, comparing the periods before and after the circulation of new variants.

Methods:
Observational, cross-sectional, multicentric, analytical study. All patients under 18 years of age with confirmed SARS-CoV-2 infection admitted at 22 healthcare centers were included. Two study periods were established: Period 1 (EW10-2020 to EW12-2021) for the Wuhan strain; Period 2 (EW13 to EW35 2021) for Alpha, Gamma, Delta and Lambda variants.

Findings:
A total of 6330 confirmed cases were included. Period 1: 3575 (56.5%), period 2: 2755 (43.5%). During period 2, a lower number of asymptomatic cases was observed, while general, respiratory and neurologic signs and symptoms increased in all age groups. Oxygen therapy requirement was higher during the first period (36.7% vs 19.1%; P < 0.001). No significant differences were observed in the rates of severe or critical cases (6.3% vs 5,4%; P = 0.102), intensive care admission (2.1% vs 2%; P < 0.656) or case fatality (0.3% vs 0.5 %; P < 0.229). MIS-C cases occurred more frequently during the first period (1.9% vs 1.1%; P = 0.009)

Interpretation:
The clinical spectrum of COVID-19 in Argentina has evolved. With the emergence of new variants, although the number of asymptomatic cases declined, numbers of severe and critical cases, as well as case fatality rates in children, remained unchanged.
Increasing Prevalence of Pediatric Community-acquired UTI by Extended Spectrum β-Lactamase-producing E. coli: Cause for Concern
Authors: Collingwood Joshua D. , Yarbrough April H. , Boppana Suresh B. , Dangle Pankaj P. 
Published: January 2023

Background:
Antimicrobial resistance and emerging spectrum-β-lactamase (ESBL) infections are a rising concern in public health. Despite the increasing prevalence of community-acquired (CA) ESBL-E. coli UTIs, there is little data on the antibiotic resistance profiles of this bacterial strain in the pediatric population. We review antibiotic resistance profile and rising trend in pediatric ESBL-E. coli UTI presentation at our pediatric hospital.

Methods:
This retrospective study reviewed data drawn from the infectious disease database at our pediatric hospital for all patients whose urine culture grew ESBL-E. coli from 01/2015 to 01/2021. Demographic information and antimicrobial susceptibility test results for ESBL-E. coli isolates from CA-UTIs were collected. Annual changes in resistance to antimicrobial agents and average annual percent change in ESBL-E. coli UTI presentation over the study period are reported.

Results:
From 01/2015 to 01/2021, 6403 urine cultures at our hospital grew E. coli. Of these, 169 urine cultures from 135 children grew ESBL-E. coli. The study population was 57% male (77) with a mean age of 6.9 ± 6.2 years and multiethnic. CA-UTI by ESBL-producing E. coli accounted for 2.62% of total E. coli UTIs within the study period and increased from 0.97% in 2015 to 3.54% in 2020 by an average of 0.51% each year.

Conclusions:
These findings demonstrate an increase in CA-ESBL E. coli UTIs in children. We observed most isolates demonstrated multidrug resistance. As CA-ESBL E. coli UTIs are associated with prolonged hospitalization and increased morbidity, our findings highlight the rising trend in pediatric CA-ESBL E. coli UTI.