bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congenital anomalies-associated Riga–Fede disease as an early manifestation of Lesch–Nyhan syndrome: rare entities in the same pediatric patient—a case report
Authors: Eita Aliaa Abdelmoniem Bedeir 
Published: February 2022

Abstract
Background
Riga–Fede disease is a rare begnin disorder of the oral tissues, it can be associated with congenital anomalies and neurological disturbances. Lesch–Nyhan syndrome is a rare X-linked recessive disorder characterized by neurological and behavioral manifestations. A patient can rarely be diagnosed with both diseases in a lifetime. Therefore, reporting manifestations from such disorders is important to avoid misdiagnosis and help in timely intervention.

Case presentation
This case report presents an 8-months-old male infant with traumatic oral ulcers from deciduous teeth. A diagnosis of Riga–Fede disease was made. Teeth grinding was performed and the oral lesions were healed. At the age of 2.5 years, the patient presented with neurological manifestations as well as facial tissue and premature teeth loss from self mutilation. Genetic sequencing revealed a variant of uncertain significance in the Hypoxanthine Phosphoribosyltransferase 1 gene. He was diagnosed with Lesch–Nyhan syndrome. Cleft palate, ventricular septal defect, congenitally undescended testis and ectopic left iliac kidney were also reported. The patient was scheduled on psychiatric treatment and after about six months of follow-up, both the behavioral and neurological symptoms were improved.

Conclusions
Riga–Fede disease can be an early manifestation of Lesch–Nyhan syndrome. To the best of our knowledge, this is the first reported case with the incidence of all the mentioned entities in one pediatric patient.
Efficacy of 3-day low dose quinine plus clindamycin versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children (CLINDAQUINE): an open-label randomized trial
Authors: Obonyo Charles O. , Juma Elizabeth A. , Were Vincent O. , Ogutu Bernhards R. 
Published: February 2022

Abstract
Background
The World Health Organization recommends quinine plus clindamycin as first-line treatment of malaria in the first trimester of pregnancy and as a second-line treatment for uncomplicated falciparum malaria when artemisinin-based drug combinations are not available. The efficacy of quinine plus clindamycin was compared with that of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in children below 5 years of age.

Methods
An open-label, phase 3, randomized trial was conducted in western Kenya. Children aged 6–59 months with uncomplicated falciparum malaria were randomly assigned (1:1) via a computer-generated randomization list to receive 3 days of twice a day treatment with either oral quinine (20 mg/kg/day) plus clindamycin (20 mg/kg/day) or artemether-lumefantrine (artemether 20 mg, lumefantrine 120 mg) as one (for those weighing 5–14 kg) or two (for those weighing 15–24 kg) tablets per dose. The primary outcome was a PCR-corrected rate of adequate clinical and parasitological response (ACPR) on day 28 in the per-protocol population.

Results
Of the 384 children enrolled, 182/192 (94.8%) receiving quinine plus clindamycin and 171/192 (89.1%) receiving artemether-lumefantrine completed the study. The PCR-corrected ACPR rate was 44.0% (80 children) in the quinine plus clindamycin group and 97.1% (166 children) in the artemether-lumefantrine group (treatment difference − 53.1%, 95% CI − 43.5% to − 62.7%). At 72 h after starting treatment, 50.3% (94 children) in the quinine plus clindamycin group were still parasitaemic compared with 0.5% (1 child) in the artemether-lumefantrine group. Three cases of severe malaria were recorded as serious adverse events in the quinine plus clindamycin group.

Conclusions
The study found no evidence to support the use of a 3-day low dose course of quinine plus clindamycin in the treatment of uncomplicated falciparum malaria in children under 5 years of age in Kenya, where artemether-lumefantrine is still effective.
Trial Registration: This trial is registered with the Pan-African Clinical Trials Registry, PACTR20129000419241.
Malaria prevention interventions beyond long-lasting insecticidal nets and indoor residual spraying in low- and middle-income countries: a scoping review
Authors: Nalinya Sarah , Musoke David , Deane Kevin 
Published: February 2022

Abstract
Background
Significant progress in malaria prevention during the past two decades has prompted increasing global dialogue on malaria elimination. Recent reviews on malaria strategies have focused mainly on long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), with little emphasis on other prevention methods. This article is a scoping review of literature on malaria prevention methods beyond LLINs and IRS in low- and middle-income countries (LMICs).

Methods
This scoping review found articles published between from 1994 to 2020. Studies were obtained from a search of the PubMed, the Cochrane Library and Social Science abstracts. Grey literature and manual search of secondary references was also done. The search strategy included all study designs but limited only to English. Three independent reviewers performed the selection and characterization of articles, and the data collected were synthesized qualitatively.

Results
A total of 10,112 studies were identified among which 31 met the inclusion criteria. The results were grouped by the 3 emerging themes of: housing design; mosquito repellents; and integrated vector control. Housing design strategies included closing eves, screening of houses including windows, doors and ceilings, while mosquito repellents were mainly spatial repellents, use of repellent plants, and use of plant-based oils. Integrated vector control included larvae source management. Evidence consistently shows that improving housing design reduced mosquito entry and malaria prevalence. Spatial repellents also showed promising results in field experiments, while evidence on repellent plants is limited and still emerging. Recent literature shows that IVM has been largely ignored in recent years in many LMICs. Some malaria prevention methods such as spatial repellents and IVM are shown to have the potential to target both indoor and outdoor transmission of malaria, which are both important aspects to consider to achieve malaria elimination in LMICs.

Conclusion
The scoping review shows that other malaria prevention strategies beyond LLINs and IRS have increasingly become important in LMICs. These methods have a significant role in contributing to malaria elimination in endemic countries if they are adequately promoted alongside other conventional approaches.
Association of HNF1A gene variants and haplotypes with metabolic syndrome: a case–control study in the Tunisian population and a meta-analysis
Authors: Dallali Hamza , Hechmi Meriem , Morjane Imane , Elouej Sahar , Jmel Haifa , Ben Halima Yosra , Abid Abdelmajid , Bahlous Afef , Barakat Abdelhamid , Jamoussi Henda , Abdelhak Sonia , Kefi Rym 
Published: February 2022

AbstractBackgroundVariants in the Hepatocyte Nuclear Factor 1 Alpha gene (HNF1A) are associated with lipoproteins levels and type 2 diabetes. In this study, we aimed to assess the association ofHNF1Agene and haplotypes with the metabolic syndrome (MetS) and its components through an association study in the Tunisian population as well as by a meta-analysis.MethodsA total of 594 Tunisian individuals were genotyped for three variants (rs1169288, rs2464196 and rs735396) located inHNF1Agene using KASPar technology. Statistical analyses were performed with R software. The association was furthermore evaluated through a meta-analysis of our results with those obtained in a Moroccan population.ResultsOur results showed no association betweenHNF1Avariants and MetS in the Tunisian population. However, a significant association was observed between the variant rs735396 and a higher waist circumference. The stratified analysis according to the sex highlighted a significant association between the variant rs1169288 and high cholesterol levels only in women. Similarly, Haplotype analysis showed an association between theHNF1Aminor haplotype and high total cholesterol mainly in women. Finally, our meta-analysis showed no association betweenHNF1Avariants and MetS.ConclusionsOur findings exclude the involvement of the threeHNF1Avariants rs1169288, rs2464196 and rs735396 in the susceptibility to MetS in our studied Tunisian population but emphasize the role of these variants in the cholesterol homeostasis with sex-specific differences, which may serve to rise clinical consideration to early statin therapy in women carrying these genetic variants.
Mesenchymal stem cells combined with autocrosslinked hyaluronic acid improve mouse ovarian function by activating the PI3K-AKT pathway in a paracrine manner
Authors: Jiao Wenlin , Mi Xin , Yang Yajuan , Liu Ran , Liu Qiang , Yan Tao , Chen Zi-Jiang , Qin Yingying , Zhao Shidou 
Published: February 2022

Abstract
Background
Declining ovarian function in advance-aged women and in premature ovarian insufficiency (POI) patients seriously affects quality of life, and there is currently no effective treatment to rescue ovarian function in clinic. Stem cell transplantation is a promising therapeutic strategy for ovarian aging, but its clinical application is limited due to the low efficiency and unclear mechanism. Here, a novel combination of umbilical cord-mesenchymal stem cells (UC-MSCs) and autocrosslinked hyaluronic acid (HA) gel is explored to rescue ovarian reserve and fecundity in POI and naturally aging mice.

Methods
To investigate HA prolonged the survival after UC-MSCs transplantation, PCR and immunofluorescence were performed to track the cells on day 1, 3, 7 and 14 after transplantation. The effects of HA on UC-MSCs were analyzed by CCK8 assay, RNA-sequencing and 440 cytokine array. In vivo experiments were conducted to evaluate the therapeutic effects of UC-MSCs combined with HA transplantation in 4-vinylcyclohexene diepoxide (VCD)-induced POI mice and naturally aging mice model. Ovarian function was analyzed by ovarian morphology, follicle counts, estrous cycle, hormone levels and fertility ability. To investigate the mechanisms of stem cell therapy, conditioned medium was collected from UC-MSCs and fibroblast. Both in vitro ovarian culture model and 440 cytokine array were applied to assess the paracrine effect and determine the underlying mechanism. Hepatocyte growth factor (HGF) was identified as an effective factor and verified by HGF cytokine/neutralization antibody supplementation into ovarian culture system.

Results
HA not only prolongs the retention of UC-MSCs in the ovary, but also boosts their secretory function, and UC-MSCs promote follicular survival by activating the PI3K-AKT pathway through a paracrine mechanism both in vitro and in vivo. More importantly, HGF is identified as the key functional cytokine secreted by MSCs.

Conclusions
The results show that HA is an excellent cell scaffold to improve the treatment efficiency of UC-MSCs for ovarian aging under both physiological and pathological conditions, and the therapeutic mechanism is through activation of the PI3K-AKT pathway via HGF. These findings will facilitate the clinical application of MSCs transplantation for ovarian disorders.
Path classification by stochastic linear recurrent neural networks
Authors: Boutaib Youness , Bartolomaeus Wiebke , Nestler Sandra , Rauhut Holger 
Published: February 2022

AbstractWe investigate the functioning of a classifying biological neural network from the perspective of statistical learning theory, modelled, in a simplified setting, as a continuous-time stochastic recurrent neural network (RNN) with the identity activation function. In the purely stochastic (robust) regime, we give a generalisation error bound that holds with high probability, thus showing that the empirical risk minimiser is the best-in-class hypothesis. We show that RNNs retain a partial signature of the paths they are fed as the unique information exploited for training and classification tasks. We argue that these RNNs are easy to train and robust and support these observations with numerical experiments on both synthetic and real data. We also show a trade-off phenomenon between accuracy and robustness.
Schizophyllum commune-derived β-glucan improves intestinal health demonstrating protective effects against constipation and common metabolic disorders
Authors: Vu Vuong , Muthuramalingam Karthika , Singh Vineet , Choi Changmin , Kim Young Mee , Unno Tatsuya , Cho Moonjae 
Published: February 2022

AbstractIt has been proven that β-glucan produced by Schizophyllum commune has beneficial effects on obesity, obesity-associated constipation, and colitis conditions; however, the protective effect of the compound on host at basal state is yet to be investigated. C57BL/6 J mice were fed with a normal diet (ND), normal diet supplemented with 3 g/kg (BG_low), and 5 g/kg (BG_high) of β-glucan (BG) for 12 weeks. Body weight, food and water intake and fecal status were monitored weekly. Intestine was stained by Periodic acid–Schiff (PAS) and Alcian Blue to evaluate the mucin layer thickness and goblet cell population. Morphological changes in internal organs and intestinal motility were also assessed, while serum biomarkers for liver injury and glucose level were analyzed. On the other hand, fecal microbiota and associated metabolic activities were also investigated. β-glucan bulked feces, decreased fecal moisture, and proliferated goblet cells resulted in a thickened lubricating mucin layer; however, the intestinal transit rate did not increase. The abundance of beneficial bacteria was increased while the harmful strains was decreased in a dose-dependent manner by the effect of β-glucan. Specific short chain fatty acid (SCFA)-producing strains, such as Roseburia, Ruminococcus, and Bifidobacteria, were selectively increased by β-glucan. In addition, consumption of β-glucan lowered level of obesity-associated biomarkers. Schizophyllum commune β-glucan showed an insignificant change in transit rate in healthy conditions when compared with obesity, despite similar effects on increasing mucus production and bulked feces. Nonetheless, the outcomes proposed protective effects against obesity, diabetes, inflammatory bowel diseases (IBD), and constipation, in which the modification of the gut microbiota by β-glucan is the largest contributor.
The transfer of heritage modelling from research to practice
Authors: Richards Jenny , Brimblecombe Peter 
Published: February 2022

Abstract
Heritage science is an inherently practice-oriented field that aims to support our understanding, and conservation, of heritage. Research is commonly undertaken using laboratory or field-based methodologies, but given the ethical and scale constraints, over time and space, of these approaches, process-based models should provide a tool for exploring practical solutions. Unlike other fields, such as climate science and ecology, there appears limited engagement with modelling within heritage science. The characteristics and use of processed-based models published in the field is examined to explore tensions in using models to transfer understanding between research and practice. By examining models that investigate interactions between heritage materials and environment, we find that, at best, model outputs may be used by other researchers or occasionally by heritage institutions; or more commonly, the model’s existence is used as a justification of research, yet without meaningful engagement within either the academic and heritage practitioner communities. Some models are unlikely to be used in practice as they have been developed at spatial or temporal scales incompatible with being truly applicable to objects or sites, or can seem to advance theory without engaging with practice. The uptake of models by researchers who rerun or change the code is rare. Models that seem to gain substantial use appear to benefit from graphical user interfaces that make them easy to run. Evidence of models in solving real-world conservation problems is hard to find. This may arise because practical applications are rarely reported in academic journal literature and open access publications. There is some evidence they are revealed in conferences and possibly internal heritage organisation reports, but this gray literature doesn’t readily feedback into the development and refinement of existing models. It is likely the use of models would increase if mechanisms were available to support the development of user interfaces, training workshops and the ability of practical use cases to be fed back to the modelling community.
An open-label prospective pilot trial of nucleus accumbens deep brain stimulation for children with autism spectrum disorder and severe, refractory self-injurious behavior: study protocol
Authors: Yan Han , Siegel Lauren , Breitbart Sara , Gorodetsky Carolina , Fasano Alfonso , Rahim Aliya , Loh Alvin , Kulkarni Abhaya V. , Ibrahim George M. 
Published: February 2022

Abstract
Background
Children and youth with autism spectrum disorder (ASD) may manifest self-injurious behaviors (SIB) that may become severe and refractory with limited pharmacologic or behavioral treatment options. Here, we present the protocol of a prospective, mixed-methods study to assess the safety and efficacy of deep brain stimulation (DBS) of the nucleus accumbens (NAcc) for children and youth with ASD and severe, refractory SIB.

Methods
This is a prospective, single-center, single-cohort, open-label, non-randomized pilot trial of 6 patients. Participants will be recruited through specialized behavioral clinics with persistent severe and refractory SIB following standard and intensive interventions. Following NAcc-DBS, participants will be enrolled in the study for 12 months. The primary objectives of the study are safety and feasibility, assessed by rate of recruitment and identification of factors impacting adherence to follow-up and study protocol. Potential treatment efficacy will be assessed by changes in the Children’s Yale-Brown Obsessive-Compulsive Scale in ASD (CYBOCS-ASD), the Behavior Problems Index (BPI), the Inventory of Statements about Self-Injury (ISAS) and the Repetitive Behavior Scale-Revised (RBS-R) questionnaires. Additional clinical outcomes will be assessed, including measures of participant and caregiver quality of life, actigraph measurements, and positron emission tomography (PET) changes following DBS.

Discussion
This study will be the first to evaluate the effect of DBS of the NAcc on a pediatric population in a controlled, prospective trial. Secondary outcomes will improve the understanding of behavioral, neuro-imaging, and electrophysiologic changes in children with ASD and SIB treated with DBS. This trial will provide an estimated effect size of NAcc-DBS for severe refractory SIB in children with ASD in preparation for future comparative trials.

Trial registration
Registration on ClinicalTrials.gov was completed on 12 June 2019 with the Identifier: NCT03982888.
Co-creating with patients an impact framework across the medicine’s life cycle: a qualitative study exploring patients’ experiences of involvement in and perceptions of impact measures
Authors: Gorbenko Oleks , Cavillon Pascale , Giles Rachel H. , Kolarova Teodora , Marks Muriël , Cardone Antonella , Bagga Sandeep , Nolan Claire 
Published: February 2022

Abstract
Background
The biopharmaceutical industry is challenged with efficiently delivering medicines that patients truly value. This can be addressed by engaging patients and caregivers throughout a medicine’s life cycle, ensuring that products meet the needs and expectations of those who take them. While isolated best practice examples of patient engagement exist, they remain relatively ad hoc and not fully embedded within Research & Development (R&D) practices. To encourage more patient engagement, the ‘impact’ of patient engagement projects (PEP) must be objectively measured and demonstrated. Some frameworks have been proposed; however, there is no evidence of widespread adoption, nor have patients’ perspectives been robustly explored. The objective of this qualitative study was therefore to understand patients’ perspectives of impact measurement that can be systematically applied within a biopharmaceutical company.

Methods
Semi-structured interviews were conducted with 13 patient organisation (PO) representatives exploring their experiences of engagement and reflections on 23 candidate patient engagement impact measures categorised into five groups: Medicines R&D Priorities; Clinical Trial Design; Regulatory & Market Access Submissions; Product Support & Information; and Disease Support & Information. Thematic analysis was undertaken and impact measures revised in line with interview participant feedback. Emerging themes and revisions to impact measures were validated at a joint workshop with 4 patient advisors representing 4 POs.

Results
The study revealed that PO representatives feel a deep sense of accomplishment and ownership when collaborating on PEPs with biopharmaceutical companies. They largely conceptualise ‘impact’ as positive, tangible and useful outcomes. The revisions made to the pre-defined patient engagement impact measures fell into three broad categories: (1) a requirement for greater context; (2) capturing the nature of patient influence; and (3) terminology changes. The greatest number of revisions concerned ‘requiring greater context’, for example, including additional descriptions, patient quotes, and satisfaction.

Conclusions
This study sheds light on how patient advocates view ‘impact’. Typically this means delivering ‘value’ important for them. Therefore, the authors of this paper created the term ‘value-impact’ to comprehensively characterise this conceptualisation, and propose a value-impact measurement plan, incorporating longitudinal data. Through this understanding and in light of other recently published work, wide-scale adoption and implementation of the measurement of value-impact across the biopharmaceutical industry can be realised.