bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recessive myotonia congenita caused by a homozygous splice site variant in CLCN1 gene: a case report
Authors: Sparber Peter , Sharova Margarita , Filatova Alexandra , Shchagina Olga , Ivanova Evgeniya , Dadali Elena , Skoblov Mikhail 
Published: October 2020

Abstract
Background
Myotonia congenita is a rare neuromuscular disease, which is characterized by a delay in muscle relaxation after evoked or voluntary contraction. Myotonia congenita can be inherited in a dominant (Thomsen disease) and recessive form (Becker disease) and both are caused by pathogenic variants in the CLCN1 gene. Noncanonical splice site variants are often classified as variants of uncertain significance, due to insufficient accuracy of splice-predicting tools. Functional analysis using minigene plasmids is widely used in such cases. Moreover, functional analysis is very useful in investigation of the disease pathogenesis, which is necessary for development of future therapeutic approaches. To our knowledge only one noncanonical splice site variant in the CLCN1 gene was functionally characterized to date. We further contribute to this field by evaluation the molecular mechanism of splicing alteration caused by the c.1582 + 5G > A in a homozygous state.

Case presentation
We report a clinical case of an affected 6-y.o boy with athletic appearance due to muscle hypertrophy, calf muscle stiffness, cramping and various myotonic signs in a consanguineous family with no history of neuromuscular disorders. The neurological examination showed percussion-activated myotonia in the hands and legs. Plasma creatine kinase enzyme and transaminases levels were normal. Electromyography at the time of examination shows myotonic runs in the upper and lower extremities.

Conclusions
Functional analysis of the variant in a minigene system showed alteration of splicing leading to loss of function, thereby confirming that the variant is pathogenic.
The art of balancing: the facilitator’s role in briefing in simulation-based learning from the perspective of nursing students – a qualitative study
Authors: Solli Hilde , Haukedal Thor Arne , Husebø Sissel Eikeland , Reierson Inger Åse 
Published: October 2020

Abstract
Background
Facilitators plays a key role in nursing student’s learning when briefing them for simulation scenarios. However, few studies have explored the importance of the facilitator’s role in preparing students from the students’ perspective. The aim of this study was to explore undergraduate nursing students’ perspectives of the facilitator’s role in briefing.

Methods
An explorative, qualitative approach was used. Four focus group interviews with a total of 30 nursing students constituted the data source. Data collection took place in December 2017 and in May 2018. The data was analysed using systematic text condensation.

Results
Two main categories were identified: “The importance of framing the subsequent scenario” and “The importance of instructing students how to execute nursing actions in the subsequent scenario”. The first category consisted of three subcategories: providing predictability, providing emotional support and providing challenges. The second main category also consisted of three subcategories: providing information about medical and technical equipment, providing a demonstration of the monitor and providing a demonstration of the manikin.

Conclusion
A briefing is more than a general introduction to a simulation scenario, learning objectives, roles, simulation environment and medical equipment. The information provided in a briefing is important for nursing students’ understanding of what they will encounter in the simulation scenario and what is being simulated, as well as possibly being a prerequisite for mastery. The facilitator’s role in the briefing is complex and requires a high level of educational expertise to balance the diversity of students’ learning approaches. Students have to learn how to simulate before the briefing. Therefore, we suggest separating the concepts of prebriefing and presimulation from the concept of briefing, introducing prebriefing and presimulation preparation before briefing, and possibly dividing students into groups based on their learning approach. Such interventions will make it possible for facilitators to balance between students’ needs and the time available for briefing.
PHOSPHO1 is a skeletal regulator of insulin resistance and obesity
Authors: Suchacki Karla J. , Morton Nicholas M. , Vary Calvin , Huesa Carmen , Yadav Manisha C. , Thomas Benjamin J. , Turban Sophie , Bunger Lutz , Ball Derek , Barrios-Llerena Martin E. , Guntur Anyonya R. , Khavandgar Zohreh , Cawthorn William P. , Ferron Mathieu , Karsenty Gérard , Murshed Monzur , Rosen Clifford J. , MacRae Vicky E. , Millán Jose Luis , Farquharson Colin 
Published: October 2020

AbstractBackgroundThe classical functions of the skeleton encompass locomotion, protection and mineral homeostasis. However, cell-specific gene deletions in the mouse and human genetic studies have identified the skeleton as a key endocrine regulator of metabolism. The bone-specific phosphatase, Phosphatase, Orphan 1 (PHOSPHO1), which is indispensable for bone mineralisation, has been recently implicated in the regulation of energy metabolism in humans, but its role in systemic metabolism remains unclear. Here, we probe the mechanism underlying metabolic regulation by analysing Phospho1 mutant mice.ResultsPhospho1−/−mice exhibited improved basal glucose homeostasis and resisted high-fat-diet-induced weight gain and diabetes. The metabolic protection inPhospho1−/−mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated fromPhospho1−/−mice were enriched for genes associated with energy metabolism and diabetes;Phospho1both directly and indirectly interacted with genes associated with glucose transport and insulin receptor signalling. Canonical thermogenesis via brown adipose tissue did not underlie the metabolic protection observed in adultPhospho1−/−mice. However, the decreased serum choline levels inPhospho1−/−mice were normalised by feeding a 2% choline rich diet resulting in a normalisation in insulin sensitivity and fat mass.ConclusionWe show that mice lacking the bone mineralisation enzyme PHOSPHO1 exhibit improved basal glucose homeostasis and resist high-fat-diet-induced weight gain and diabetes. This study identifies PHOSPHO1 as a potential bone-derived therapeutic target for the treatment of obesity and diabetes.
Molecular detection of hemotropic mycoplasmas (hemoplasmas) in domestic cats (Felis catus) in Romania
Authors: Imre Mirela , Văduva Cristina , Dărăbuș Gheorghe , Morariu Sorin , Herman Viorel , Plutzer Judit , Suici Tijana , Lait Philippa J P , Imre Kálmán 
Published: October 2020

Abstract
Background
The hemotropic mycoplasmas (hemoplasmas) of the genus Mycoplasma are recognized as important bacteria that parasitize red blood cells, causing hemolytic anemia in many mammalian species, including cats. No information is available concerning the presence of feline hemoplasma infections in cats in Romania. Thus, the objective of the present study was to provide data on the occurrence and molecular characterization of hemotropic mycoplasmas in client-owned cats in Romania.

Methods
Blood samples from 51 unhealthy cats, originating from Timişoara Municipality, Romania, were screened for the presence of hemoplasmas using conventional polymerase chain reaction (PCR) targeting the 16S rRNA gene and sequencing assays. PCR-positive samples were subsequently analyzed by phylogenetic and population genetic analysis.

Results
Molecular analysis revealed 11 (21.6%) positive samples, consisting of 8 (72.7%) Candidatus Mycoplasma haemominutum and 3 (27.3%) Mycoplasma haemofelis confirmed positives. Candidatus Mycoplasma turicensis was not detected, and no co-infections were registered. No significant associations (p > 0.05) were found between the hemoplasma infection status and age, gender, breed, presence of ectoparasites, feline leukemia virus/feline immunodeficiency virus positivity of cats, or the sampling season. However, outdoor access was positively associated (p = 0.049) with infection and could be considered a risk factor (OR = 4.1) in acquiring feline hemotropic mycoplasmas. Phylogenetic analysis revealed that our sequences clustered with those selected from the GenBank database in two distinct clades. The registered population genetic indices were strongly supportive of the great variance in sequences between the recorded Mycoplasma species.

Conclusions
The findings support the occurrence of feline hemoplasma infections in previously uninvestigated territories of Europe, providing useful information for small animal practitioners. To our knowledge, the present survey is the first reported molecular evidence of feline hemoplasma infections in Romania.
Distinct non-ischemic myocardial late gadolinium enhancement lesions in patients with type 2 diabetes
Authors: Bojer Annemie Stege , Sørensen Martin Heyn , Vejlstrup Niels , Goetze Jens P. , Gæde Peter , Madsen Per Lav 
Published: October 2020

Abstract
Background
Cardiovascular magnetic resonance imaging (CMR) have described localised non-ischemic late gadolinium enhancement (LGE) lesions of prognostic importance in various non-ischemic cardiomyopathies. Ischemic LGE lesions are prevalent in diabetes (DM), but non-ischemic LGE lesions have not previously been described or systematically studied in DM.

Methods
296 patients with type 2 DM (T2DM) and 25 sex-matched control subjects underwent echocardiography and CMR including adenosine-stress perfusion, T1-mapping and LGE.

Results
264 patients and all control subjects completed the CMR protocol. 78.4% of patients with T2DM had no LGE lesions; 11.0% had ischemic LGE lesions only; 9.5% had non-ischemic LGE lesions only; and 1.1% had both one ischemic and one non-ischemic lesion. The non-ischemic LGE lesions were situated mid-myocardial in the basal lateral or the basal inferolateral part of the left ventricle and the affected segments showed normal to high wall thickness and normal contraction. Patients with non-ischemic LGE lesions in comparison with patients without LGE lesions had increased myocardial mass (150 ± 34 vs. 133 ± 33 g, P = 0.02), average E/e’(9.9 IQR8.7–12.6 vs. 8.8 IQR7.4–10.7, P = 0.04), left atrial maximal volume (102 IQR84.6–115.2 vs. 91 IQR75.2–100.0 mL, P = 0.049), NT-proBNP (8.9 IQR5.9–19.7 vs. 5.9 IQR5.9–10.1 µmol/L, P = 0.02) and high-sensitive troponin (15.6 IQR13.0–26.1 vs. 13.0 IQR13.0–14.6 ng/L, P = 0.007) and a higher prevalence of retinopathy (48 vs. 25%, P = 0.009) and autonomic neuropathy (52 vs. 30.5%, P = 0.005).

Conclusion
A specific LGE pattern with lesions in the basal lateral or the basal inferolateral part of the left ventricle was found in patients with type 2 diabetes.
Trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT02684331.
China’s mental health support in response to COVID-19: progression, challenges and reflection
Authors: Ju Yumeng , Zhang Yan , Wang Xiaoping , Li Weihui , Ng Roger M. K. , Li Lingjiang 
Published: October 2020

AbstractThe continued spread of the coronavirus disease 2019 (COVID-19) has a serious impact on everyone across the globe, both physically and psychologically. In addition to proactive measures addressing physical survival needs and health protection, China has launched a mental health support system to cope with the widespread psychological stress during the pandemic and its aftermath. In this debate, the authors attempted to depict and reflect upon the overall framework of China’s mental health support, with particular reference to the psychological intervention in response to COVID-19 over the last few months. Although a lot of effort has been made to meet the mental health needs, the accessibility, acceptability and effectiveness of the support system still have much room for improvement. Therefore, it is very important to re-think the predicament and challenge on ways of enhancing public mental health emergency responses in China. The concepts of universality, timeliness and scientific rigour were proposed as a possible reform in preparation for large-scale natural or man-made disasters in the coming future.
Pyruvate dehydrogenase complex deficiency: updating the clinical, metabolic and mutational landscapes in a cohort of Portuguese patients
Authors: Pavlu-Pereira Hana , Silva Maria João , Florindo Cristina , Sequeira Sílvia , Ferreira Ana Cristina , Duarte Sofia , Rodrigues Ana Luísa , Janeiro Patrícia , Oliveira Anabela , Gomes Daniel , Bandeira Anabela , Martins Esmeralda , Gomes Roseli , Soares Sérgia , Tavares de Almeida Isabel , Vicente João B. , Rivera Isabel 
Published: October 2020

Abstract
Background
The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible decarboxylation of pyruvate into acetyl-CoA. PDC deficiency can be caused by alterations in any of the genes encoding its several subunits. The resulting phenotype, though very heterogeneous, mainly affects the central nervous system. The aim of this study is to describe and discuss the clinical, biochemical and genotypic information from thirteen PDC deficient patients, thus seeking to establish possible genotype–phenotype correlations.

Results
The mutational spectrum showed that seven patients carry mutations in the PDHA1 gene encoding the E1α subunit, five patients carry mutations in the PDHX gene encoding the E3 binding protein, and the remaining patient carries mutations in the DLD gene encoding the E3 subunit. These data corroborate earlier reports describing PDHA1 mutations as the predominant cause of PDC deficiency but also reveal a notable prevalence of PDHX mutations among Portuguese patients, most of them carrying what seems to be a private mutation (p.R284X). The biochemical analyses revealed high lactate and pyruvate plasma levels whereas the lactate/pyruvate ratio was below 16; enzymatic activities, when compared to control values, indicated to be independent from the genotype and ranged from 8.5% to 30%, the latter being considered a cut-off value for primary PDC deficiency. Concerning the clinical features, all patients displayed psychomotor retardation/developmental delay, the severity of which seems to correlate with the type and localization of the mutation carried by the patient. The therapeutic options essentially include the administration of a ketogenic diet and supplementation with thiamine, although arginine aspartate intake revealed to be beneficial in some patients. Moreover, in silico analysis of the missense mutations present in this PDC deficient population allowed to envisage the molecular mechanism underlying these pathogenic variants.

Conclusion
The identification of the disease-causing mutations, together with the functional and structural characterization of the mutant protein variants, allow to obtain an insight on the severity of the clinical phenotype and the selection of the most appropriate therapy.
The psychosocial profile of family caregivers of children with chronic diseases: a cross-sectional study
Authors: Toledano-Toledano Filiberto , Luna David 
Published: October 2020

Abstract
Background
A family caregiver is defined as a person who has a significant emotional bond with the patient; this caregiver is a family member who is a part of the patient’s family life cycle; offers emotional-expressive, instrumental, and tangible support; and provides assistance and comprehensive care during the chronic illness, acute illness, or disability of a child, adult, or elderly person. The objectives of this study were to identify the psychosocial profiles of family caregivers of children with chronic diseases and to establish the relationship between these profiles and sociodemographic variables.

Methods
A cross-sectional study was conducted involving 401 family caregivers of children with chronic diseases at the National Institute of Health in Mexico City. The participants responded to the Sociodemographic Variables Questionnaire (Q-SV) for research on family caregivers of children with chronic disease and a battery of 7 instruments that examined anxiety, caregiver burden, family support, depression, resilience, parental stress, and the World Health Organization Well-Being Index.

Results
A hierarchical cluster analysis and its confirmation through a nonhierarchical cluster analysis confirmed two profiles of caregivers of pediatric patients with chronic diseases. Profile 1, called Vulnerability of family caregivers, is characterized by high levels of anxiety, depression, parental stress and caregiver burden, accompanied by low levels of family support, resilience, and well-being. Profile 2, called Adversity of family caregivers, shows an inverse pattern, with high levels of family support, resilience, and well-being and low levels of anxiety, depression, parental stress and caregiver burden. The sociodemographic characteristics are similar for both profiles, with the exception of the caregiver’s family type. Profile 1 shows more single-parent caregivers, while profile 2 includes more caregivers with a nuclear family. However, the type of family did not reach significance for predicting the caregiver’s profile in a bivariate logistic regression model.

Conclusions
The psychosocial profile of family caregivers of children with chronic diseases can be structured according to their psychosocial characteristics. Although no causal factors were detected that define criteria for belonging to one or another profile, the characteristics identified for each indicate the need for specific and differentiated intervention strategies for families facing adversity, risk and vulnerability during a child’s disease.
Gravitational distribution of regional opening and closing pressures, hysteresis and atelectrauma in ARDS evaluated by electrical impedance tomography
Authors: Scaramuzzo Gaetano , Spinelli Elena , Spadaro Savino , Santini Alessandro , Tortolani Donatella , Dalla Corte Francesca , Pesenti Antonio , Volta Carlo Alberto , Grasselli Giacomo , Mauri Tommaso 
Published: October 2020

Abstract
Background
The physiological behavior of lungs affected by the acute respiratory distress syndrome (ARDS) differs between inspiration and expiration and presents heterogeneous gravity-dependent distribution. This phenomenon, highlighted by the different distribution of opening/closing pressure and by the hysteresis of the pressure–volume curve, can be studied by CT scan, but the technique expose the patient to radiations, cannot track changes during time and is not feasible at the bedside. Electrical impedance tomography (EIT) could help in assessing at the bedside regional inspiratory and expiratory mechanical properties. We evaluated regional opening/closing pressures, hysteresis and atelectrauma during inspiratory and expiratory low-flow pressure–volume curves in ARDS using electrical impedance tomography.

Methods
Pixel-level inspiratory and expiratory PV curves (PVpixel) between 5 and 40 cmH2O were constructed integrating EIT images and airway opening pressure signal from 8 ARDS patients. The lower inflection point in the inspiratory and expiratory PVpixel were used to find opening (OPpixel) and closing (CPpixel) pressures. A novel atelectrauma index (AtI) was calculated as the percentage of pixels opening during the inspiratory and closing during the expiratory PV curves. The maximal hysteresis (HysMax) was calculated as the maximal difference between normalized expiratory and inspiratory PV curves. Analyses were conducted in the global, dependent and non-dependent lung regions.

Results
Gaussian distribution was confirmed for both global OPpixel (r2 = 0.90) and global CPpixel (r2 = 0.94). The two distributions were significantly different with higher values for OPpixel (p < 0.0001). Regional OPpixel and CPpixel distributions were Gaussian, and in the dependent lung regions, both were significantly higher than in the non-dependent ones (p < 0.001). Both AtI and the HysMax were significantly higher in the dependent regions compared to the non-dependent ones (p < 0.05 for both).

Conclusions
Gravity impacts the regional distribution of opening and closing pressure, hysteresis and atelectrauma, with higher values in the dorsal lung. Regional differences between inspiratory and expiratory lung physiology are detectable at the bedside using EIT and could allow in-depth characterization of ARDS phenotypes and guide personalized ventilation settings.

Graphic abstract
Compromised browning plasticity of primary subcutaneous adipocytes derived from overweight Chinese adults
Authors: Qiu Yao , Sun Lizhi , Hu Xiaolin , Zhao Xin , Shi Hongyan , Liu Zhao , Yin Xiao 
Published: October 2020

Abstract
Purpose
People with obesity have a compromised browning capacity of adipose tissue when faced with sympathetic stimuli. This study aimed to determine whether norepinephrine treatment can enhance the induction of precursor cells from human white adipose tissue to differentiate into adipocytes that express key markers of beige adipocytes, and if there is a difference in this capacity between normal weight and overweight individuals.

Methods
Stromal vascular cells derived from subcutaneous white adipose tissue of normal weight and overweight groups were induced to differentiation, with or without norepinephrine, into adipocytes. Oxygen consumption rate, lipolysis, the expression of uncoupling protein 1 and other thermogenic genes were compared between different adiposity and treatment groups.

Results
Peroxisome proliferator activated receptor γ- coactivator-1 alpha (PGC-1 α) and uncoupling protein 1 gene expression increased significantly in the normal weight group, but not in the overweight group, with norepinephrine treatment. The increments of lipolysis and oxygen consumption rate were also higher in adipocytes from the normal weight group with norepinephrine treatment, as compared with those of the overweight group. PR domain containing protein 16 (PRDM 16) gene expression was higher in the normal weight group compared with that in the overweight group, while there were no significant changes found with norepinephrine treatment in either the normal weight or overweight group.

Conclusions
Adipogenic precursor cells derived from overweight individuals were less prone to differentiate into beige-like adipocytes when facing sympathetic stimuli than normal weight ones, resulting in the compromised sympathetic-induced browning capacity in subcutaneous white adipose tissue in overweight individuals, which occurred before the onset of overt obesity.