bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the severe respiratory insufficiency questionnaire for Chile
Authors: Andrade Marianela , Antolini Mónica , Canales Krishnna , Maquilon Cesar , Fuentes Mauricio , Mazzei Marinella 
Published: July 2022

Abstract
Background
Long-term home non-invasive ventilation (LTH-NIV) has an impact on the health-related quality of life of patients with chronic hypercapnic respiratory failure (CRF) of different causes. There are generic and specific questionnaires for respiratory diseases. In 2003 a specific questionnaire was developed for patients with CRF in LTH-NIV, called the Severe Respiratory Insufficiency (SRI) questionnaire, which has been shown to be reproducible and reliable and has been validated in several languages.

The aim of the study was to translate and culturally adapt the SRI questionnaire for adult Chilean patients under LTH-NIV, and to assess its psychometric properties.

Methods
The Chilean version of the SRI was obtained using the translation-back translation method, which was then applied by cross-sectional study to a non-probabilistic convenience sample of stable patients from five regions of Chile. The validated Chilean version of the SRI questionnaire and SF-36 (gold standard) questionnaire were applied, demographic and ventilatory data were collected. Reliability was analysed using Cronbach’s alpha and intraclass correlation (test–retest). Construct validity was tested using exploratory factor analysis (principal component extraction and equimax orthogonal rotation) and hypothesis testing (Mann–Whitney test). Convergent criterion validity was tested using Spearman’s rho.

Results
The sample comprised 248 patients, 132 women (53.2%), median age (IQR) was 62 years (51–75), 146 patients (58.9%) were 60 years or older, 40% had a low education level. The mean ± SD completion time of the questionnaire was 18.8 ± 9.1 min, and 100% of the items were answered. The questionnaire was self-applied by 46.8% of the sample. The validated Chilean version of the SRI questionnaire showed very good overall reliability (0.95) and by scales (> 0.7). It showed a good correlation with the SF-36, with equivalent scales, a rotated matrix with 8 factors and hypotheses that explain the underlying constructs.

Conclusions
The validated Chilean version of the SRI questionnaire has good psychometric properties. It is feasible, valid, and reliable for application to evaluate patients with CRF in LTH-NIV. It was found to be sensitive to assess the characteristics of the local population.
Estrogen alleviates post-traumatic osteoarthritis progression and decreases p-EGFR levels in female mouse cartilage
Authors: Lu Zhihua , Zhang Aihua , Wang Jingcheng , Han Kuijing , Gao Han 
Published: July 2022

Abstract
Objective
To investigate the effect of estrogen on the progression of post-traumatic osteoarthritis (PTOA) in mice and its possible mechanism.

Methods
Twelve-week-old ICR mice were divided into Group A (female control group), group B (ovariectomized(OVX) group), group C (OVX group supplemented with estrogen), and group D (male group) by destabilization of the medial meniscus (DMM)or sham operation. Safranin O staining was performed at 8 weeks and 12 weeks after operation, and the degree of articular cartilage lesion was evaluated using Mankin score. Twelve weeks after the operation, tissue sections were stained to analyze the matrix metalloproteinase 13(MMP13), phosphorylated epidermal growth factor receptor (p-EGFR) expression and apoptosis of chondrocytes.

Results
Decreased estrogen can significantly increase the weight of mice in female mice. The degree of cartilage damage in the knee joint on the DMM side of female mice was significantly severer than that on the Sham side. The DMM side also showed higher MMP13 expression and increased apoptotic chondrocytes. The degree of cartilage damage in the knee joint on the DMM side of female mice was significantly reduced after estrogen supplementation, and cartilage damage in the knee joint on the DMM side of female mice was less serious than that of male mice. As estrogen levels decreased, the severity of cartilage erosion in the knee joint on the DMM side was aggravated, and p-EGFR expression in the cartilage surface was also higher in female mice contrast to that in male mice. However, minimal changes in p-EGFR expression in the cartilage surface of bilateral knee joints of male mice were observe.

Conclusion
Estrogen has a regulatory effect on PTOA and its inhibits the expression of p-EGFR in cartilage on the knee joint surface and has a protective effect on articular cartilage in female mice.
Costs of multimorbidity: a systematic review and meta-analyses
Authors: Tran Phuong Bich , Kazibwe Joseph , Nikolaidis Georgios F. , Linnosmaa Ismo , Rijken Mieke , van Olmen Josefien 
Published: July 2022

Abstract
Background
Multimorbidity is a rising global phenomenon, placing strains on countries’ population health and finances. This systematic review provides insight into the costs of multimorbidity through addressing the following primary and secondary research questions: What evidence exists on the costs of multimorbidity? How do costs of specific disease combinations vary across countries? How do multimorbidity costs vary across disease combinations? What “cost ingredients” are most commonly included in these multimorbidity studies?

Methods
We conducted a systematic review (PROSPERO: CRD42020204871) of studies published from January 2010 to January 2022, which reported on costs associated with combinations of at least two specified conditions. Systematic string-based searches were conducted in MEDLINE, The Cochrane Library, SCOPUS, Global Health, Web of Science, and Business Source Complete. We explored the association between costs of multimorbidity and country Gross Domestic Product (GDP) per capita using a linear mixed model with random intercept. Annual mean direct medical costs per capita were pooled in fixed-effects meta-analyses for each of the frequently reported dyads. Costs are reported in 2021 International Dollars (I$).

Results
Fifty-nine studies were included in the review, the majority of which were from high-income countries, particularly the United States. (1) Reported annual costs of multimorbidity per person ranged from I$800 to I$150,000, depending on disease combination, country, cost ingredients, and other study characteristics. (2) Our results further demonstrated that increased country GDP per capita was associated with higher costs of multimorbidity. (3) Meta-analyses of 15 studies showed that on average, dyads which featured Hypertension were among the least expensive to manage, with the most expensive dyads being Respiratory and Mental Health condition (I$36,840), Diabetes and Heart/vascular condition (I$37,090), and Cancer and Mental Health condition in the first year after cancer diagnosis (I$85,820). (4) Most studies reported only direct medical costs, such as costs of hospitalization, outpatient care, emergency care, and drugs.

Conclusions
Multimorbidity imposes a large economic burden on both the health system and society, most notably for patients with cancer and mental health condition in the first year after cancer diagnosis. Whether the cost of a disease combination is more or less than the additive costs of the component diseases needs to be further explored. Multimorbidity costing studies typically consider only a limited number of disease combinations, and few have been conducted in low- and middle-income countries and Europe. Rigorous and standardized methods of data collection and costing for multimorbidity should be developed to provide more comprehensive and comparable evidence for the costs of multimorbidity.
Effects of ATLAS 2030 gait exoskeleton on strength and range of motion in children with spinal muscular atrophy II: a case series
Authors: Cumplido-Trasmonte C. , Ramos-Rojas J. , Delgado-Castillejo E. , Garcés-Castellote E. , Puyuelo-Quintana G. , Destarac-Eguizabal M. A. , Barquín-Santos E. , Plaza-Flores A. , Hernández-Melero M. , Gutiérrez-Ayala A. , Martínez-Moreno M. , García-Armada E. 
Published: July 2022

Abstract
Background
Children with spinal muscular atrophy (SMA) present muscle weakness and atrophy that results in a number of complications affecting their mobility, hindering their independence and the development of activities of daily living. Walking has well-recognized physiological and functional benefits. The ATLAS 2030 exoskeleton is a paediatric device that allows gait rehabilitation in children with either neurological or neuromuscular pathologies with gait disorders. The purpose is to assess the effects in range of motion (ROM) and maximal isometric strength in hips, knees and ankles of children with SMA type II after the use of ATLAS 2030 exoskeleton.

Methods
Three children (mean age 5.7 ± 0.6) received nine sessions bi-weekly of 60 min with ATLAS 2030. ROM was assessed by goniometry and strength by hand-held dynamometer. All modes of use of the exoskeleton were tested: stand up and sit down, forward and backward walking, and gait in automatic and active-assisted modes. In addition, different activities were performed during the gait session. A descriptive analysis of all variables was carried out.

Results
The average time of use was 53.5 ± 12.0 min in all sessions, and all participants were able to carry out all the proposed activities as well as to complete the study. Regarding isometric strength, all the measurements increased compared to the initial state, obtaining the greatest improvements for the hip flexors (60.2%) and extensors muscles (48.0%). The ROM increased 12.6% in hip and 34.1% in the ankle after the study, while knee ROM remained stable after the study.

Conclusion
Improvements were showed in ROM and maximal isometric strength in hips, knees and ankles after using ATLAS 2030 paediatric gait exoskeleton in all three children. This research could serve as a preliminary support for future clinical integration of ATLAS 2030 as a part of a long-term rehabilitation of children with SMA.
Trial registration: The approval was obtained (reference 47/370329.9/19) by Comunidad de Madrid Regional Research Ethics Committee with Medical Products and the clinical trial has been registered on Clinical Trials.gov: NCT04837157.
Changes of physico-chemical properties of nano-biomaterials by digestion fluids affect the physiological properties of epithelial intestinal cells and barrier models
Authors: Antonello Giulia , Marucco Arianna , Gazzano Elena , Kainourgios Panagiotis , Ravagli Costanza , Gonzalez-Paredes Ana , Sprio Simone , Padín-González Esperanza , Soliman Mahmoud G. , Beal David , Barbero Francesco , Gasco Paolo , Baldi Giovanni , Carriere Marie , Monopoli Marco P. , Charitidis Costas A. , Bergamaschi Enrico , Fenoglio Ivana , Riganti Chiara 
Published: July 2022

AbstractBackgroundThe widespread use of nano-biomaterials (NBMs) has increased the chance of human exposure. Although ingestion is one of the major routes of exposure to NBMs, it is not thoroughly studied to date. NBMs are expected to be dramatically modified following the transit into the oral-gastric-intestinal (OGI) tract. How these transformations affect their interaction with intestinal cells is still poorly understood. NBMs of different chemical nature—lipid-surfactant nanoparticles (LSNPs), carbon nanoparticles (CNPs), surface modified Fe3O4nanoparticles (FNPs) and hydroxyapatite nanoparticles (HNPs)—were treated in a simulated human digestive system (SHDS) and then characterised. The biological effects of SHDS-treated and untreated NBMs were evaluated on primary (HCoEpiC) and immortalised (Caco-2, HCT116) epithelial intestinal cells and on an intestinal barrier model.ResultsThe application of the in vitro SDHS modified the biocompatibility of NBMs on gastrointestinal cells. The differences between SHDS-treated and untreated NBMs could be attributed to the irreversible modification of the NBMs in the SHDS. Aggregation was detected for all NBMs regardless of their chemical nature, while pH- or enzyme-mediated partial degradation was detected for hydroxyapatite or polymer-coated iron oxide nanoparticles and lipid nanoparticles, respectively. The formation of a bio-corona, which contains proteases, was also demonstrated on all the analysed NBMs. In viability assays, undifferentiated primary cells were more sensitive than immortalised cells to digested NBMs, but neither pristine nor treated NBMs affected the intestinal barrier viability and permeability. SHDS-treated NBMs up-regulated the tight junction genes (claudin 3 and 5, occludin, zonula occludens 1) in intestinal barrier, with different patterns between each NBM, and increase the expression of both pro- and anti-inflammatory cytokines (IL-1β, TNF-α, IL-22, IL-10). Notably, none of these NBMs showed any significant genotoxic effect.ConclusionsOverall, the results add a piece of evidence on the importance of applying validated in vitro SHDS models for the assessment of NBM intestinal toxicity/biocompatibility. We propose the association of chemical and microscopic characterization, SHDS and in vitro tests on both immortalised and primary cells as a robust screening pipeline useful to monitor the changes in the physico-chemical properties of ingested NBMs and their effects on intestinal cells.
Genetic etiology and clinical challenges of phenylketonuria
Authors: Elhawary Nasser A. , AlJahdali Imad A. , Abumansour Iman S. , Elhawary Ezzeldin N. , Gaboon Nagwa , Dandini Mohammed , Madkhali Abdulelah , Alosaimi Wafaa , Alzahrani Abdulmajeed , Aljohani Fawzia , Melibary Ehab M. , Kensara Osama A. 
Published: July 2022

AbstractThis review discusses the epidemiology, pathophysiology, genetic etiology, and management of phenylketonuria (PKU). PKU, an autosomal recessive disease, is an inborn error of phenylalanine (Phe) metabolism caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene. The prevalence of PKU varies widely among ethnicities and geographic regions, affecting approximately 1 in 24,000 individuals worldwide. Deficiency in the PAH enzyme or, in rare cases, the cofactor tetrahydrobiopterin results in high blood Phe concentrations, causing brain dysfunction. Untreated PKU, also known as PAH deficiency, results in severe and irreversible intellectual disability, epilepsy, behavioral disorders, and clinical features such as acquired microcephaly, seizures, psychological signs, and generalized hypopigmentation of skin (including hair and eyes). Severe phenotypes are classic PKU, and less severe forms of PAH deficiency are moderate PKU, mild PKU, mild hyperphenylalaninaemia (HPA), or benign HPA. Early diagnosis and intervention must start shortly after birth to prevent major cognitive and neurological effects. Dietary treatment, including natural protein restriction and Phe-free supplements, must be used to maintain blood Phe concentrations of 120–360 μmol/L throughout the life span. Additional treatments include the casein glycomacropeptide (GMP), which contains very limited aromatic amino acids and may improve immunological function, and large neutral amino acid (LNAA) supplementation to prevent plasma Phe transport into the brain. The synthetic BH4 analog, sapropterin hydrochloride (i.e., Kuvan®, BioMarin), is another potential treatment that activates residual PAH, thus decreasing Phe concentrations in the blood of PKU patients. Moreover, daily subcutaneous injection of pegylated Phe ammonia-lyase (i.e., pegvaliase; PALYNZIQ®, BioMarin) has promised gene therapy in recent clinical trials, and mRNA approaches are also being studied.
Acute intestinal necrosis due to multiple thrombosis in COVID-19 patient. Report of a case
Authors: Morioka Hirotsugu , Goto Michitoshi , Tanaka Haruka , Momose Hirotaka , Fujino Kazuyoshi , Hagiwara Toshiaki , Aoki Jun , Orihata Michihiro , Kaneko Kotaro 
Published: July 2022

Abstract
Background
While thrombosis is a well-known complication of coronavirus disease 2019 (COVID-19) infection, reports on intestinal necrosis due to intestinal ischemia caused by thrombosis are extremely rare. We herein report a case of intestinal necrosis due to multiple thrombosis in a COVID-19 patient.

Case presentation
The patient was a 64-year-old man. He was admitted to hospital after being diagnosed with COVID-19, the severity was classified as moderate II. Nasal High Flow™ management was conducted along with treatment with tocilizumab, remdesivir, and dexamethasone. Heparin was also administered due to high D-dimer values. As abdominal pain appeared from the 6th day of hospitalization, contrast-enhanced CT was performed, which confirmed multiple thrombosis in the aorta. However, no obvious intestinal ischemia was found. On the 10th day of hospitalization, the patient’s abdominal pain was exacerbated. Upon re-evaluation by CT, he was diagnosed with perforative peritonitis due to ileal ischemic necrosis and emergency surgery was performed. Intraoperative examination revealed perforation due to necrosis at multiple sites in the ileum; thus, partial ileectomy was carried out. Pathological findings also revealed discontinuous multiple intestinal necrosis due to the frequent occurrence of thrombosis. Following surgery, the patient recuperated and was discharged after ventilator management and multimodal therapy at the ICU.

Conclusions
Thrombosis due to COVID-19 complications is rare in the intestinal tract, but also occur. Its initial symptoms might not be captured by CT images, therefore caution is required.
Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival
Authors: Choudhary Rishabh C. , Ahmed Umair , Shoaib Muhammad , Alper Eric , Rehman Abdul , Kim Junhwan , Shinozaki Koichiro , Volpe Bruce T. , Chavan Sangeeta , Zanos Stavros , Tracey Kevin J. , Becker Lance B. 
Published: July 2022

Abstract
Background
Vagus nerve stimulation (VNS) has shown therapeutic potential in a variety of different diseases with many ongoing clinical trials. The role of VNS in reducing ischemic injury in the brain requires further evaluation. Cardiac arrest (CA) causes global ischemia and leads to the injury of vital organs, especially the brain. In this study, we investigated the protective effects of customized threshold-adjusted VNS (tVNS) in a rat model of CA and resuscitation.

Methods
Sprague-Dawley rats underwent 12 min asphyxia-CA followed by resuscitation. Rats were assigned to either post-resuscitation tVNS for 2 h or no-tVNS (control). tVNS was applied by electrode placement in the left cervical vagus nerve. To optimize a threshold, we used animal’s heart rate and determined a 15–20% drop from baseline levels as the effective and physiological threshold for each animal. The primary endpoint was 72 h survival; secondary endpoints included neurological functional recovery, reduction in brain cellular injury (histopathology), cardiac and renal injury parameters (troponin I and creatinine levels, respectively).

Results
In comparison to the control group, tVNS significantly improved 72 h survival and brain functional recovery after 12 minutes of CA. The tVNS group demonstrated significantly reduced numbers of damaged neurons in the CA1 hippocampal region of the brain as compared to the control group. Similarly, the tVNS group showed decreased trend in plasma troponin I and creatinine levels as compared to the control group.

Conclusions
Our findings suggest that using tVNS for 2 h after 12 minutes of CA attenuates ischemia neuronal cell death, heart and kidney damage, and improves 72 h survival with improved neurological recovery.
Does liver diffusion tensor imaging (L-DTI) has a role in differentiation of hepatic focal lesions? Analytic study for assessment of the value of L-DTI in differentiating hepatic focal lesions according to LI-RADS
Authors: Mahmoud Bahaa Eldin , Metwally Lamiaa I. A. , Salama Rabab Maamoun , Yehia Mahmoud , Ibrahim Iman Mohamed Hamdy , Mikhael Hisham S. Wahba 
Published: July 2022

Abstract
Background
Magnetic resonance imaging (MRI) plays an important role in the differentiation of hepatic focal lesions and diagnosis of hepatic malignancy, especially hepatocellular carcinoma which is a major health problem worldwide. Diffusion imaging is a functional MRI technique that became an essential part of MRI study of the liver. Recently, diffusion tensor imaging (DTI) is diffusion variant that can provide more information than conventional diffusion imaging based on the tissue anisotropy. The aim of this study was to present the role of DTI in the assessment and differentiation between hepatic focal lesions.

Results
Fifty-one patients having 95 hepatic focal lesions who underwent dynamic MRI with conventional diffusion imaging and DTI acquisition were included in the study. A positive moderate significant correlation was found between Fractional anisotropy (FA) values and Liver Imaging Reporting and Data System (LI-RADS) category while substantial negative significant correlation and moderate negative significant correlation were found between DTI-ADC and DWI-ADC values, respectively, with the LI-RADS category. There was a significant negative correlation between DTI-ADC and FA values. DTI-ADC showed a significant role in differentiation of benign from malignant lesions with cut-off value 0.905 × 10−3 having 88.7% sensitivity and 88.3% specificity compared to 78.5% and 68.7% for DWI-ADC, respectively. Also, it was found that FA value had a significant role in differentiation between benign and malignant lesions with cut-off value 0.34 having 87.1% sensitivity and 73.9% specificity.

Conclusions
DTI can be included in liver MRI studies for better tissue characterization as it may perform better than conventional DWI with higher sensitivity and specificity of DTI-ADC and FA values than conventional DWI-ADC.
Lessons Learned from a Physically Active Learning Intervention: Texas I-CAN!
Authors: Bartholomew John B. , Jowers Esbelle M. , Golaszewski Natalie M. 
Published: July 2022

ABSTRACT
The Texas Initiatives for Children’s Activity and Nutrition (Texas I-CAN!) has focused on the development of interventions to provide physically active learning (PAL) to regular education, elementary classroom. This article provides an overview of our approach and the iterations through which we have progressed in the intervention. We adopt a framework that considers PAL along continuums of relatedness to and integration with the academic goals of the lessons. This provides a lens through which to view our iterations of I-CAN!, as we sought a version of PAL that is both acceptable to teachers and effective for physical activity and academic outcomes. As such, this provides an overview of the choices that must be made to translate theory to practice.