bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limb-specific thalamocortical tracts are impaired differently in hemiplegic and diplegic subtypes of cerebral palsy
Authors: Jaatela Julia , Aydogan Dogu Baran , Nurmi Timo , Vallinoja Jaakko , Mäenpää Helena , Piitulainen Harri 
Published: August 2023

AbstractThalamocortical pathways are considered crucial in the sensorimotor functioning of children with cerebral palsy (CP). However, previous research has been limited by non-specific tractography seeding and the lack of comparison between different CP subtypes. We compared limb-specific thalamocortical tracts between children with hemiplegic (HP, N = 15) or diplegic (DP, N = 10) CP and typically developed peers (N = 19). The cortical seed-points for the upper and lower extremities were selected (i) manually based on anatomical landmarks or (ii) using functional magnetic resonance imaging (fMRI) activations following proprioceptive-limb stimulation. Correlations were investigated between tract structure (mean diffusivity, MD; fractional anisotropy, FA; apparent fiber density, AFD) and sensorimotor performance (hand skill and postural stability). Compared to controls, our results revealed increased MD in both upper and lower limb thalamocortical tracts in the non-dominant hemisphere in HP and bilaterally in DP subgroup. MD was strongly lateralized in participants with hemiplegia, while AFD seemed lateralized only in controls. fMRI-based tractography results were comparable. The correlation analysis indicated an association between the white matter structure and sensorimotor performance. These findings suggest distinct impairment of functionally relevant thalamocortical pathways in HP and DP subtypes. Thus, the organization of thalamocortical white matter tracts may offer valuable guidance for targeted, life-long rehabilitation in children with CP.
Inhibition of galectin-3 post-infarction impedes progressive fibrosis by regulating inflammatory profibrotic cascades
Authors: Wang Xiaoyin , Gaur Meenakshi , Mounzih Khalid , Rodriguez Hilda J , Qiu Huiliang , Chen Ming , Yan Liqiu , Cooper Brian A , Narayan Shilpa , Derakhshandeh Ronak , Rao Poonam , Han Daniel D , Nabavizadeh Pooneh , Springer Matthew L , John Constance M 
Published: August 2023

Abstract

Aims
Acute myocardial infarction (MI) causes inflammation, collagen deposition, and reparative fibrosis in response to myocyte death and, subsequently, a pathological myocardial remodelling process characterized by excessive interstitial fibrosis, driving heart failure (HF). Nonetheless, how or when to limit excessive fibrosis for therapeutic purposes remains uncertain. Galectin-3, a major mediator of organ fibrosis, promotes cardiac fibrosis and remodelling. We performed a preclinical assessment of a protein inhibitor of galectin-3 (its C-terminal domain, Gal-3C) to limit excessive fibrosis resulting from MI and prevent ventricular enlargement and HF.

Methods and results
Gal-3C was produced by enzymatic cleavage of full-length galectin-3 or by direct expression of the truncated form in Escherichia coli. Gal-3C was intravenously administered for 7 days in acute MI models of young and aged rats, starting either pre-MI or 4 days post-MI. Echocardiography, haemodynamics, histology, and molecular and cellular analyses were performed to assess post-MI cardiac functionality and pathological fibrotic progression. Gal-3C profoundly benefitted left ventricular ejection fraction, end-systolic and end-diastolic volumes, haemodynamic parameters, infarct scar size, and interstitial fibrosis, with better therapeutic efficacy than losartan and spironolactone monotherapies over the 56-day study. Gal-3C therapy in post-MI aged rats substantially improved pump function and attenuated ventricular dilation, preventing progressive HF. Gal-3C in vitro treatment of M2-polarized macrophage-like cells reduced their M2-phenotypic expression of arginase-1 and interleukin-10. Gal-3C inhibited M2 polarization of cardiac macrophages during reparative response post-MI. Gal-3C impeded progressive fibrosis post-MI by down-regulating galectin-3-mediated profibrotic signalling cascades including a reduction in endogenous arginase-1 and inducible nitric oxide synthase (iNOS).

Conclusion
Gal-3C treatment improved long-term cardiac function post-MI by reduction in the wound-healing response, and inhibition of inflammatory fibrogenic signalling to avert an augmentation of fibrosis in the periinfarct region. Thus, Gal-3C treatment prevented the infarcted heart from extensive fibrosis that accelerates the development of HF, providing a potential targeted therapy.
C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway
Authors: Liu Aiting , Chen Zhenwei , Li Xiaoxue , Xie Chen , Chen Yanlian , Su Xiaoyan , Chen Ying , Zhang Mengbi , Chen Jie , Yang Tiecheng , Shen Jiangang , Huang Hui 
Published: August 2023

Abstract

Aims
Vascular calcification (VC) predicts the morbidity and mortality in cardiovascular diseases. Vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation is the crucial pathological basis for VC. To date, the molecular pathogenesis is still largely unclear. Notably, C5a-C5aR1 contributes to the development of cardiovascular diseases, and its closely related to physiological bone mineralization which is similar to VSMCs osteogenic transdifferentiation. However, the role and underlying mechanisms of C5a-C5aR1 in VC remain unexplored.

Methods and results
A cross-sectional clinical study was utilized to examine the association between C5a and VC. Chronic kidney diseases mice and calcifying VSMCs models were established to investigate the effect of C5a-C5aR1 in VC, evaluated by changes in calcium deposition and osteogenic markers. The cross-sectional study identified that high level of C5a was associated with increased risk of VC. C5a dose-responsively accelerated VSMCs osteogenic transdifferentiation accompanying with increased the expression of C5aR1. Meanwhile, the antagonists of C5aR1, PMX 53, reduced calcium deposition, and osteogenic transdifferentiation both in vivo and in vitro. Mechanistically, C5a-C5aR1 induced endoplasmic reticulum (ER) stress and then activated PERK-eIF2α-ATF4 pathway to accelerated VSMCs osteogenic transdifferentiation. In addition, cAMP-response element-binding protein 3-like 1 (CREB3L1) was a key downstream mediator of PERK-eIF2α-ATF4 pathway which accelerated VSMCs osteogenic transdifferentiation by promoting the expression of COL1α1.

Conclusions
High level of C5a was associated with increased risk of VC, and it accelerated VC by activating the receptor C5aR1. PERK-eIF2α-ATF4-CREB3L1 pathway of ER stress was activated by C5a-C5aR1, hence promoting VSMCs osteogenic transdifferentiation. Targeting C5 or C5aR1 may be an appealing therapeutic target for VC.
Outcomes Following Acute Severe Colitis at Initial Presentation: A Multi-centre, Prospective, Paediatric Cohort Study
Authors: Dhaliwal Jasbir , Tertigas Dominique , Carman Nicholas , Lawrence Sally , Debruyn Jennifer C , Wine Eytan , Church Peter C , Huynh Hien Q , Rashid Mohsin , El-Matary Wael , Deslandres Colette , Critch Jeffrey , Ricciuto Amanda , Carroll Matthew W , Benchimol Eric I , Muise Aleixo , Jacobson Kevan , Otley Anthony R , Vallance Bruce , Mack David R , Walters Thomas D , Surette Michael G , Griffiths Anne M 
Published: August 2023

Abstract

Aim
To assess contemporary outcomes in children with acute severe ulcerative colitis [ASUC] at initial presentation.

Methods
Between April 2014 and January 2019, children aged &lt;17 years, with new onset ASUC (Paediatric Ulcerative Colitis Activity Index [PUCAI ≥65) were prospectively followed in a Canadian inception cohort study. 16S rRNA amplicon sequencing captured microbial composition of baseline faecal samples. Primary endpoint was corticosteroid-free clinical remission with intact colon at 1 year [PUCAI &lt;10, no steroids ≥4 weeks].

Results
Of 379 children with new onset UC/IBD-unclassified, 105 [28%] presented with ASUC (42% male; median [interquartile range; [IQR]) age 14 [11-16] years; extensive colitis in all). Compared with mild UC, gut microbiome of ASUC patients had lower α-diversity, decreased beneficial anaerobes, and increased aerobes; 54 [51%] children were steroid-refractory and given infliximab [87% intensified regimen]. Corticosteroid-free remission at 1 year was achieved by 62 [61%] ASUC cohort (by 34 [63%] steroid-refractory patients, all on biologics; by 28 [55%] steroid responders,13 [25%] on 5- aminosalicylic acid [5-ASA], 5 [10%] on thiopurines, 10 [20%] on biologics). By 1 year, 78 [74%] escalated to infliximab including 24 [47%] steroid-responders failed by 5-ASA and/or thiopurines. In multivariable analysis, clinical predictors for commencing infliximab included hypoalbuminaemia, greater PUCAI, higher age, and male sex. Over 18 months, repeat corticosteroid course[s] and repeat hospitalisation were less likely among steroid-refractory versus -responsive but -dependent patients (adjusted odds ratio [aOR] 0.71 [95% CI 0.57-0.89] and 0.54 [95% CI 0.45-0.66], respectively).

Conclusion
The majority of children presenting with ASUC escalate therapy to biologics. Predictors of need for advanced therapy may guide selection of optimal maintenance therapy.
A novel approach to hypophysitis: outcomes using non-glucocorticoid immunosuppressive therapy
Authors: Vakharia Janaki D , Muhammed Maged , Remba-Shapiro Ilan , Marsiglia Marcela , Hadaway Natalia , Chwalisz Bart K , Nachtigall Lisa B 
Published: August 2023

Abstract

Objective
To determine pituitary function before and after nonglucocorticoid immunosuppressive therapy (NGIT) in subjects with hypophysitis and evaluate their clinical and radiologic outcomes.

Design
Retrospective, longitudinal study.

Methods
We reviewed a large database, selected subjects with hypophysitis treated with NGIT, and collected information on the duration of therapy, and clinical, hormonal, and radiologic outcomes.

Results
Twelve subjects met the inclusion criteria. Five subjects had primary hypophysitis (PH), while seven had secondary hypophysitis (SH) due to an underlying systemic inflammatory disease. Mean age ± SD was 48.0 ± 15.7 years and 40.9 ± 13.0 years, for PH and SH, respectively. The majority were female (PH 60% and SH 86%). BMI ± SD at presentation was 25.2 ± 2.5 kg/m2 and 26.8 ± 6.7 kg/m2 for PH and SH, respectively. The most common symptom at presentation was fatigue (75%). All PH subjects (100%) and 2 (28.6%) SH subjects had polyuria/polydipsia. There was a significant decrease in mean pituitary stalk thickness after NGIT (P = .0051) (mean duration 16.5 ± 4.8 months). New hormone loss or recovery occurred rarely. Mycophenolate mofetil was the most used NGIT: adverse effects prompted discontinuation in 2 out of 7 subjects.

Conclusions
Subjects with hypophysitis receiving NGIT had stable or improved brain/pituitary magnetic resonance imaging findings with a significant decrease in pituitary stalk thickness. NGITs did not improve anterior pituitary function. Our findings suggest that NGIT may be considered as an alternative therapy for patients with hypophysitis who require immunosuppression.
Time on the crossing: emigrant voyages across the Atlantic, 1853–1913
Authors: Hatton Timothy J 
Published: August 2023

Abstract
I provide a new series of the average duration of emigrant voyages from Liverpool to New York from 1853 to 1913. Time on the crossing fell by 80 percent, from about 40 days to just eight, most of which occurred in the first 2 decades and was associated with the transition from sail to steam. The standard deviation of voyage durations also dramatically decreased. Although average transatlantic fares did not fall, if foregone earnings during the voyage are included, the total cost declined until the early 1900s, and especially so when measured in terms of the number of weeks’ work.
Lending a hand: help banks in the Netherlands, 1848–1898
Authors: de Vicq Amaury , van Bochove Christiaan 
Published: August 2023

Abstract
Households and small businesses are often confronted with funding gaps due to small-scale lending problems. Whereas existing research focused primarily on how rural areas addressed such problems, this paper determines what contributed to the success of urban help banks in the Netherlands (1848–1898). It considers how help banks’ lending mechanism, corporate governance mechanism, and historical circumstances lowered operating costs. The latter was crucial and depended on elites with philanthropic and practical considerations, who housed, staffed, and funded help banks at modest costs. This mix provides guidance to small-scale lenders, including microcredit institutions, to address funding gaps and tailor their services.
Educational achievement of children with selected major congenital anomalies and associated factors: a Finnish registry-based study
Authors: Roustaei Zahra , Heino Anna , Kiuru-Kuhlefelt Sonja , Morris Joan K , Glinianaia Svetlana V , Garne Ester , Loane Maria , Rankin Judith , Gissler Mika 
Published: August 2023

Abstract

Background
Children with major congenital anomalies may be at risk of poor educational outcomes. We aimed to evaluate the educational achievement of children born with major congenital anomalies compared with children without major congenital anomalies in relation to sociodemographic factors.

Methods
We performed a registry-based study including 401 544 children in Finland, graduates of the compulsory school who applied to secondary education. We used health data from the Finnish Register of Congenital Malformations for children born from 1995 to 2002 linked with education data from the Finnish Ministry of Education and Culture. We used generalized linear regression to compare the mean grade differences of children with specific major congenital anomalies and ‘All anomalies’ subgroup (major congenital anomalies, chromosomal syndromes, and multiple anomalies) with reference children.

Results
Children with major congenital anomalies were less likely to apply for further education than reference children (88.0% vs. 96.8%; odds ratio = 4.13; 95% confidence interval, 3.92–4.36). For most non-chromosomal congenital anomalies, children born with congenital anomalies had similar educational achievement to the reference children. For the ‘All anomalies’ subgroup, children with congenital anomalies had lower educational achievement than reference children. Among children with congenital anomalies, male sex, lower maternal educational levels and younger maternal age were associated with lower educational achievement.

Conclusions
For children applying to further education, most non-chromosomal congenital anomalies were not associated with lower educational achievement. Nevertheless, efforts are needed to improve educational achievement in children with major congenital anomalies associated with maternal sociodemographic background.
Genomic mechanisms and consequences of diverse postzygotic barriers between monkeyflower species
Authors: Sotola V Alex , Berg Colette S , Samuli Matthew , Chen Hongfei , Mantel Samuel J , Beardsley Paul A , Yuan Yao-Wu , Sweigart Andrea L , Fishman Lila 
Published: August 2023

Abstract
The evolution of genomic incompatibilities causing postzygotic barriers to hybridization is a key step in species divergence. Incompatibilities take 2 general forms—structural divergence between chromosomes leading to severe hybrid sterility in F1 hybrids and epistatic interactions between genes causing reduced fitness of hybrid gametes or zygotes (Dobzhansky–Muller incompatibilities). Despite substantial recent progress in understanding the molecular mechanisms and evolutionary origins of both types of incompatibility, how each behaves across multiple generations of hybridization remains relatively unexplored. Here, we use genetic mapping in F2 and recombinant inbred line (RIL) hybrid populations between the phenotypically divergent but naturally hybridizing monkeyflowers Mimulus cardinalis and M. parishii to characterize the genetic basis of hybrid incompatibility and examine its changing effects over multiple generations of experimental hybridization. In F2s, we found severe hybrid pollen inviability (&lt;50% reduction vs parental genotypes) and pseudolinkage caused by a reciprocal translocation between Chromosomes 6 and 7 in the parental species. RILs retained excess heterozygosity around the translocation breakpoints, which caused substantial pollen inviability when interstitial crossovers had not created compatible heterokaryotypic configurations. Strong transmission ratio distortion and interchromosomal linkage disequilibrium in both F2s and RILs identified a novel 2-locus genic incompatibility causing sex-independent gametophytic (haploid) lethality. The latter interaction eliminated 3 of the expected 9 F2 genotypic classes via F1 gamete loss without detectable effects on the pollen number or viability of F2 double heterozygotes. Along with the mapping of numerous milder incompatibilities, these key findings illuminate the complex genetics of plant hybrid breakdown and are an important step toward understanding the genomic consequences of natural hybridization in this model system.
Safety, Effectiveness, and Treatment Persistence of Subcutaneous Vedolizumab in IBD: A Multicenter Study From the United Kingdom
Authors: Lim Samuel Hsiang , Gros Beatriz , Sharma Esha , Lehmann Anouk , Lindsay James O , Caulfield Louise , Gaya Daniel R , Taylor Jo , Limdi Jimmy , Kwok Jon , Shuttleworth Elinor , Dhar Anjan , Burdge Gemma , Selinger Christian , Cococcia Sara , Murray Charles , Balendran Karthiha , Raine Tim , George Becky , Walker Gareth , Aldridge Robin , Irving Peter , Lees Charlie W , Samaan Mark 
Published: August 2023

Abstract

Background and Aims
Despite intravenous (IV) vedolizumab being established for treatment of inflammatory bowel disease (IBD), the novel subcutaneous (SC) route of administration may provide numerous incentives to switch. However, large-scale real-world data regarding the long-term safety and effectiveness of this strategy are lacking.

Methods
IBD patients on IV vedolizumab across 11 UK sites agreed to transition to SC injections or otherwise continued IV treatment. Data regarding clinical disease activity (Simple Clinical Colitis Activity Index, partial Mayo score, and modified Harvey-Bradshaw Index), biochemical markers (C-reactive protein and calprotectin), quality of life (IBD control), adverse events, treatment persistence, and disease-related outcomes (namely corticosteroid use, IBD-related hospitalization, and IBD-related surgery) were retrospectively collected from prospectively maintained clinical records at baseline and weeks 8, 24, and 52.

Results
Data from 563 patients (187 [33.2%] Crohn’s disease, 376 [66.8%] ulcerative colitis; 410 [72.8%] SC, 153 [27.2%] IV) demonstrated no differences in disease activity, remission rates, and quality of life between the SC and IV groups at all time points. Drug persistence at week 52 was similar (81.1% vs 81.2%; P = .98), as were rates of treatment alteration due to either active disease (12.2% vs 8.9%; P = .38) or adverse events (3.3% vs 6.3%; P = .41). At week 52, there were equivalent rates of adverse events (9.8% vs 7.8%; P = .572) and disease-related outcomes. IBD control scores were equivalent in both IV-IV and IV-SC groups.

Conclusions
Switching to SC vedolizumab appears as effective, safe, and well tolerated as continued IV treatment and maintains comparable disease control and quality of life as IV treatment at 52 weeks.
Floating offshore wind farms in Mediterranean marine protected areas: a cautionary tale
Authors: Lloret Josep , Wawrzynkowski Paul , Dominguez-Carrió Carlos , Sardá Rafael , Molins Climent , Gili Josep Maria , Sabatés Ana , Vila-Subirós Josep , Garcia Laura , Solé Jordi , Berdalet Elisa , Turiel Antonio , Olivares Alberto 
Published: August 2023

Abstract
As offshore wind energy expands in Europe, maritime planners increasingly need to consider the potential effects of these activities on the different types of marine protected areas (MPAs), including Natura 2000 sites. The aim of this article is to critically review the initial development of offshore wind energy inside and/or in the vicinity of Mediterranean Natura 2000 sites and other types of MPAs. The western Mediterranean Sea is taken as an example as this is where most of the offshore wind developments have been proposed. In order to open up discussion of offshore wind energy policy and guide ecological research that supports holistic decisions regarding offshore wind farm (OWF) installation in the region, we (i) outline the context of Natura 2000 and other MPA policy in the Mediterranean for OWF development, (ii) summarize the potential impacts of OWF on EU-protected habitats and species, (iii) assess the interactions of OWFs, the Natura 2000 sites, and other MPAs, and (iv) propose recommendations to approach OWF development in the Mediterranean in order to safeguard the Natura 2000 sites and other MPAs. After documenting the potential overlaps between OWFs and MPAs in the western Mediterranean, we recommend OWFs be placed outside Natura 2000 and other MPA sites, including their buffer zones. We also advocate for rigorous and independent Appropriate Assessments to be carried out for OWF proposals that could affect protected areas.
Association of Prolactin, Oxytocin, and Homocysteine With the Clinical and Cognitive Features of a First Episode of Psychosis Over a 1-Year Follow-Up
Authors: Hidalgo-Figueroa Maria , Salazar Alejandro , Romero-López-Alberca Cristina , MacDowell Karina S , García-Bueno Borja , Bioque Miquel , Bernardo Miquel , Parellada Mara , González-Pinto Ana , García-Portilla M Paz , Lobo Antonio , Rodriguez-Jimenez Roberto , Berrocoso Esther , Leza Juan C ,   FLAMM-PEPs study,   CIBERSAM
Published: August 2023

Abstract

Background
The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics.

Methods
We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features.

Results
At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients.

Conclusion
This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind.