bluuebunny/crossref_metadata_2025 huggingface dataset:
Disclosing a diagnosis of autism spectrum disorder without intellectual disability to pediatric patients in Japan in early diagnostic stages and associated factors: a cross-sectional study
Authors: Sato Hiroyuki , Fujita Misao , Tsuchiya Atsushi , Hatta Taichi , Mori Katsumi , Nakazawa Eisuke , Takimoto Yoshiyuki , Akabayashi Akira
Published: August 2022

Background

With a recent increase in the prevalence of autism spectrum disorder (ASD), an important issue has emerged in clinical practice regarding when and how patients themselves should be given explanations following a diagnosis of ASD. The clinical guidelines of the UK National Institute for Health and Care Excellence state that children diagnosed with ASD should receive an explanation about what ASD is and how it affects their development and functioning—“if appropriate”. However, the guidelines do not provide any specifics regarding what constitutes “appropriate” situations

Methods

We conducted an anonymous self-administered postal questionnaire survey targeting all members of the Japanese Society for Child and Adolescent Psychiatry (n=1,995). The analysis included only physicians who had newly diagnosed pediatric patients with ASD in the past year. We imposed a limit of one year because diagnoses further back than that are difficult to recall; in other words, this would enhance the recall bias

Results

The recovery rate was 30.8%, and the rate of diagnosis disclosure to patients themselves without intellectual disability was 15.3%. We asked 361 physicians who responded that “deciding on a case-by-case basis” was the ideal way to disclose an ASD diagnosis about 20 items prioritized by physicians at the time of diagnosis disclosure and extracted three factors through exploratory factor analysis. Multiple logistic regression analysis was performed with physician attributes, awareness of ASD as a disorder or personality, and the three extracted factors as explanatory variables; diagnosis disclosure was the dependent variable. The patient age group and only one of the three factors (i.e., “factor related to readiness to accept diagnosis”) showed a significant association with disclosure of the diagnosis to the individual. Items included in the “factor related to readiness to accept diagnosis” were as follows: the degree of parental understanding, relationship of the patient with their parents/physician, agreement in opinion between parents, parental consent, “sufficient” patient understanding, symptom stabilization, and a guarantee of sufficient time required to explain the diagnosis to the patient

Conclusion

In clinical settings, disclosing an ASD diagnosis with the consideration of patient/parent readiness toward accepting the diagnosis could help to guide physicians in determining an ideal timing for disclosure. Future studies are needed to establish detailed and concrete guidelines regarding disclosure of an ASD diagnosis to patients.
The experience of bullying among adolescents receiving mental health care: an interpretative phenomenological analysis
Authors: Roques Marjorie , Spiers Solène , El Husseini Mayssa’ , Drieu Didier , Laimou Dimitra , de Kernier Nathalie , Mazoyer Anne-Valérie , Guénolé Fabian
Published: August 2022

Background

Bullying, the most prevalent form of abuse among adolescents, is associated with emotional and behavioural problems as well as psychiatric morbidity. Moreover, it has been shown that adolescents with previous mental health problems are at increased risk of being bullied and that the psychopathological repercussions of bullying are greatest among them. However, little is known about the experience of bullying in adolescents receiving treatment from mental health services. The aim of this study was to explore the subjective experience of bullying in adolescents receiving mental health care.

Methods

The study was developed in the context of a French multicentre research program and employed an exploratory phenomenological approach. A purposeful sampling strategy was used to select adolescents who had experienced bullying (according to the Olweus criteria) and who were able to relate their experiences clearly. In-depth, semistructured interviews with participants were conducted; written transcriptions of these interviews were analysed using thematic analysis.

Results

Twenty-one adolescents (age range: 12–17 years; 13 girls) participated in the study. The analysis indicated a three-axis structure: (1) negative emotions and violent feelings, describing adolescents’ fear, sadness, aggression against themselves, and generalized mistrust; (2) isolation and loneliness, underlining the need to take refuge within oneself and the experiences of rejection, helplessness, and secret-keeping; and (3) self and identity repercussions, including experiences of shame and lowered self-esteem, identity questions, and a vision of bullying as a life experience.

Conclusions

The results of this study may have practical implications for clinicians: (1) a situation of bullying should be sought when an adolescent is seen for unexplained externalized behavioural misconduct; (2) low levels of emotional expression in a bullied adolescent may warn about associated self-harm; (3) a bullied adolescent’s tendency to hide this situation from his or her parents may reflect underlying family-related vulnerability; and (4) the phenomenological analysis showed potential particularities in the assumptive world of these adolescents and suggested that relationality may play a crucial role in their experiences. These results suggest incentives to design specific individual and group therapeutic interventions for bullied adolescents with significant levels of social withdrawal, including family support. Additional research is necessary to improve our understanding of the psychopathological and intersubjective aspects of bullying in adolescents.
Toll-like receptors and their role in neuropathic pain and migraine
Authors: Liu Xuejiao , Yang Wenping , Zhu Chenlu , Sun Songtang , Wu Shouyi , Wang Longde , Wang Yonggang , Ge Zhaoming
Published: August 2022

Migraine is a complex neurological disease of unknown etiology involving both genetic and environmental factors. It has previously been reported that persistent pain may be mediated by the immune and inflammatory systems. Toll-like receptors (TLRs) play a significant role in immune and inflammatory responses and are expressed by microglia and astrocytes. One of the fundamental mechanisms of the innate immune system in coordinating inflammatory signal transduction is through TLRs, which protect the host organism by initiating inflammatory signaling cascades in response to tissue damage or stress. TLRs reside at the neuroimmune interface, and accumulating evidence has suggested that the inflammatory consequences of TLR activation on glia (mainly microglia and astrocytes), sensory neurons, and other cell types can influence nociceptive processing and lead to pain. Several studies have shown that TLRs may play a key role in neuropathic pain and migraine etiology by activating the microglia. The pathogenesis of migraine may involve a TLR-mediated crosstalk between neurons and immune cells. Innate responses in the central nervous system (CNS) occur during neuroinflammatory phenomena, including migraine. Antigens found in the environment play a crucial role in the inflammatory response, causing a broad range of diseases, including migraines. These can be recognized by several innate immune cells, including macrophages, microglia, and dendritic cells, and can be activated through TLR signaling. Given the prevalence of migraine and the insufficient efficacy and safety of current treatment options, a deeper understanding of TLRs is expected to provide novel therapies for managing chronic migraine. This review aimed to justify the view that TLRs may be involved in migraine.
Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial
Authors: Muti Paola , Sacconi Andrea , Pulito Claudio , Orlandi Giulia , Donzelli Sara , Morrone Aldo , Jiulian James , Cox Gerard P. , Kolb Martin , Pond Gregory , Kavsak Peter , Levine Mark Norman , Blandino Giovanni , Strano Sabrina
Published: August 2022

Background

Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set.

Methods

In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model.

Results

We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants.

Conclusions

We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma.

Trial registration

ClinicalTrials.gov, NCT02076672. Registered 03/03/2014.
Routine bacterial culture of proximal bone specimens during minor amputation in patients with diabetes‐related foot infections has little clinical utility in predicting re‐operation or ulcer healing
Authors: Voon Kimberly , Vo Uyen G. , Hand Robert , Hiew Jonathan , Ritter Jens Carsten , Hamilton Emma J. , Manning Laurens
Published: August 2022

Background

Trans‐phalangeal and trans‐metatarsal amputation, collectively termed ‘minor amputations' are important procedures for managing infections of diabetes‐related foot ulcers (DFU). Following minor amputation, international guidelines recommend a prolonged course of antibiotics if residual infected bone on intra‐operative bone samples are identified, but the quality of the evidence underpinning these guidelines is low. In this study, we examined the concordance of microbiological results from proximal bone cultures compared to results from superficial wound swabs in relation to patient outcomes; with the aim of determining the utility of routinely obtaining marginal bone specimens.

Methods

Data was retrospectively collected on 144 individuals who underwent minor amputations for infected DFU at a large Australian tertiary hospital. Concordance was identified for patients with both superficial wound swabs and intra‐operative bone samples available. Patient outcomes were monitored up to 6 months post‐amputation. The primary outcome was complete healing at 6 months; and secondary outcome measures included further surgery and death. Mann Whitney U testing was performed for bivariate analyses of continuous variables, Chi‐Squared testing used for categorical variables and a logistic regression was performed with healing as the dependent variable.

Results

A moderate‐high degree of concordance was observed between microbiological samples, with 38/111 (35%) of patients having discordant wound swab and bone sample microbiology. Discordant results were not associated with adverse outcomes (67.2% with concordant results achieved complete healing compared with 68.6% patients with discordant results; P = 0.89). Revascularisation during admission (0.37 [0.13–0.96], P = 0.04) and amputation of the 5th ray (0.45 [0.21–0.94], P = 0.03) were independent risk factors for non‐healing.

Conclusion

There was a moderate‐high degree of concordance between superficial wound swab results and intra‐operative bone sample microbiology in this patient cohort. Discordance was not associated with adverse outcomes. These results suggest there is little clinical utility in routinely collecting proximal bone as an adjunct to routine wound swabs for culture during minor amputation for an infected DFU.
Analysis of the risk factors and clinical features of Mycoplasma pneumoniae pneumonia with embolism in children: a retrospective study
Authors: Han Chunjiao , Zhang Tongqiang , Zheng Jiafeng , Jin Peng , Zhang Qi , Guo Wei , Xu Yongsheng
Published: August 2022

Background

Mycoplasmapneumoniae pneumonia (MPP) is a prevalent disease in community-acquired pneumonia among children. However, in addition to respiratory manifestations, it may also develop extra-pulmonary complications. Embolism is one of the uncommon extra-respiratory manifestations prone to severe sequelae and even death. This study aims to analyze the clinical features of MPP with embolism in children, and explore the associated risk factors of embolism in MPP patients.

Methods

A retrospective case–control analysis was performed on 48 children with MPP admitted to our hospital wards between January 2010 and December 2021. Embolism group comprised children with embolism by CTA or MRA results, whereas the non-embolism group comprised children with clinical suspicion of embolism but negative diagnostic imaging support. The clinical features, laboratory findings and imaging were analyzed to explore the risk factors for embolism in children with MPP.

Results

A total of 48 children with MPP were enrolled in the study (16 cases and 32 controls). In the embolism group, 10 patients (62.5%) had pulmonary embolism, 3 patients (18.75%) presented ventricle embolism, 2 patients (12.5%) presented cerebral and carotid artery embolism, one patient (6.25%) had a cerebral embolism, limb, and spleen, respectively. The univariate analysis revealed the maximum body temperature (Tmax), CRP, D-dimer (closest to CTA/MRA), the percentage of neutrophils (N%), pulmonary consolidation (⩾ 2/3 lobe), pleural effusion and atelectasis have significant differences between the embolism group and non-embolism group (P < 0.05). Multivariate logistic regression analysis showed that D-dimer (closest to CTA/MRA) > 3.55 mg/L [OR = 1.255 (95% CI: 1.025—1.537), P < 0.05], pulmonary consolidation (⩾ 2/3 lobe) [OR = 8.050 (95% CI: 1.341—48.327), P < 0.05], and pleural effusion [OR = 25.321 (95% CI: 2.738—234.205), P < 0.01] were independent risk factors for embolism in children with MPP.

Conclusion

In conclusion, MPP with embolism patients have more D-dimer values and severe radiologic manifestations.
Effectiveness and adherence to closed face shields in the prevention of COVID-19 transmission: a non-inferiority randomized controlled trial in a middle-income setting (COVPROSHIELD)
Authors: Varela Andrea Ramirez , Gurruchaga Alejandro Pacheco , Restrepo Silvia Restrepo , Martin Juan David , Landazabal Yessica Daniela Campaz , Tamayo-Cabeza Guillermo , Contreras-Arrieta Sandra , Caballero-Díaz Yuldor , Florez Luis Jorge Hernandez , González John Mario , Santos-Barbosa Juan Carlos , Pinzón José David , Yepes-Nuñez Juan José , Laajaj Rachid , Buitrago Gutierrez Giancarlo , Florez Martha Vives , Fuentes Castillo Janner , Quinche Vargas Gianni , Casas Andres , Medina Antonio , Behrentz Eduardo ,   on behalf of the CoVIDA Working Group, Guevara Yenny Paola Rueda , Sanchez Daniela Rodriguez , Guevara-Suarez Marcela , Hidalgo Marylin , Betancourt Paola
Published: August 2022

Background

The use of respiratory devices can mitigate the spread of diseases such as COVID-19 in community settings. We aimed to determine the effectiveness of closed face shields with surgical face masks to prevent SARS-CoV-2 transmission in working adults during the COVID-19 pandemic in Bogotá, Colombia.

Methods

An open-label non-inferiority randomized controlled trial that randomly assigned participants to one of two groups: the intervention group was instructed to wear closed face shields with surgical face masks, and the active control group was instructed to wear only surgical face masks. The primary outcome was a positive reverse transcription polymerase chain reaction test, IgG/IgM antibody test for SARS-CoV-2 detection, or both during and at the end of the follow-up period of 21 days. The non-inferiority limit was established at − 5%.

Results

A total of 316 participants were randomized, 160 participants were assigned to the intervention group and 156 to the active control group. In total, 141 (88.1%) participants in the intervention group and 142 (91.0%) in the active control group completed the follow-up. Primary outcome: a positive SARS-CoV-2 test result was identified in one (0.71%) participant in the intervention group and three (2.1%) in the active control group. In the intention-to-treat analysis, the absolute risk difference was − 1.40% (95% CI [− 4.14%, 1.33%]), and in the per-protocol analysis, the risk difference was − 1.40% (95% CI [− 4.20, 1.40]), indicating non-inferiority of the closed face shield plus face mask (did not cross the non-inferiority limit).

Conclusions

The use of closed face shields and surgical face masks was non-inferior to the surgical face mask alone in the prevention of SARS-CoV-2 infection in highly exposed groups. Settings with highly active viral transmission and conditions such as poor ventilation, crowding, and high mobility due to occupation may benefit from the combined use of masks and closed face shields to mitigate SARS-CoV-2 transmission.

Trial registration

ClinicalTrials.gov NCT04647305. Registered on November 30, 2020
Effect of high-flow nasal therapy on patient-centred outcomes in patients at high risk of postoperative pulmonary complications after cardiac surgery: a statistical analysis plan for NOTACS, a multicentre adaptive randomised controlled trial
Authors: Dawson Sarah N. , Chiu Yi-Da , Klein Andrew A. , Earwaker Melissa , Villar Sofia S.
Published: August 2022

Background

The NOTACS trial will assess the efficacy, safety and cost-effectiveness of high-flow nasal therapy (HFNT) compared to standard oxygen therapy (SOT) on the outcomes of patients after cardiac surgery.

Methods/design

NOTACS is an adaptive, international, multicentre, parallel-group, randomised controlled trial, with a pre-planned interim sample size re-estimation (SSR). A minimum of 850 patients will be randomised 1:1 to receive either HFNT or SOT. The primary outcome is days alive and at home in the first 90 days after the planned surgery (DAH90), with a number of secondary analyses and cost-effectiveness analyses also planned. The interim SSR will take place after a minimum of 300 patients have been followed up for 90 days and will allow for the sample size to increase up to a maximum of 1152 patients.

Results

This manuscript provides detailed descriptions of the design of the NOTACS trial, and the analyses to be undertaken at the interim and final analyses. The main purpose of the interim analysis is to assess safety and to perform a sample size re-estimation. The main purpose of the final analysis is to examine the safety, efficacy and cost-effectiveness of HFNT compared to SOT on the outcomes of patients after cardiac surgery.

Discussion

This manuscript outlines the key features of the NOTACS statistical analysis plan and was submitted to the journal before the interim analysis in order to preserve scientific integrity under an adaptive design framework. The NOTACS SAP closely follows published guidelines for the content of SAPs in clinical trials.

Trial registration

ISRCTN14092678. Registered on 13 May 2020.
Efficacy of manual acupuncture, electro-acupuncture, and warm acupuncture for knee osteoarthritis: study protocol for a randomized controlled trial
Authors: Chang Yiniu , Wu Nan , Zhang Zhenhua , Zhang Zhaoyang , Ren Binbin , Liu Feilai , Song Xiaolei , Wu Mingli , Feng Xiaodong , Yin Shuai
Published: August 2022

Background

Acupuncture is one of the most popular complementary and alternative treatments for knee osteoarthritis (KOA). There are many methods of acupuncture in the treatment of KOA, and the effects are different. According to our clinical observations and researches, it is found that manual acupuncture (MA), electro-acupuncture (EA), and warm acupuncture (WA) are used more frequently in the treatment of KOA, and the curative effects are satisfactory. However, there is currently a lack of efficacy comparison of efficacy between different acupuncture treatments, as well as a lack of standardized clinical research on the acupuncture treatment of KOA. Therefore, we will carry out a high-quality clinical randomized controlled trial to research the effect laws of MA, EA, and WA on KOA.

Methods/design

A total of 200 eligible participants with KOA will be randomly assigned to group A, B, C, or D in a ratio of 1:1:1:1. Patients in group A will receive MA, while those in group B, group C, and group D will be treated with EA, WA, and sham acupuncture (SA), respectively. Patients will be treated with acupuncture once a day, 30 min per session, 5 sessions per week for 4 weeks. The primary outcome is the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at week 4. The secondary outcomes include WOMAC, visual analog scale (VAS), Arthritis Quality of Life Measurement Scale Simplified Scale (AIMS2-SF), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Credibility/Expectancy Questionnaire. The evaluation will be performed at baseline and weeks 4, 8, and 12 respectively after randomization.

Discussion

This is a randomized controlled trial. We will observe the clinical effect of MA, EA, and WA on KOA to research the effect laws of these three acupuncture treatments on KOA and set up standardized treatment programs for acupuncture for KOA.

Trial registration

China Clinical Trials Registry ChiCTR2100049526. Registered on August 2, 2021
Mesenchymal stem cells and their microenvironment
Authors: Liu Jiaxi , Gao Jinfang , Liang Zixie , Gao Chong , Niu Qing , Wu Fengping , Zhang Liyun
Published: August 2022

Mesenchymal stem cells (MSCs), coming from a wide range of sources, have multi-directional differentiation ability. MSCs play vital roles in immunomodulation, hematopoiesis and tissue repair. The microenvironment of cells often refers to the intercellular matrix, other cells, cytokines and humoral components. It is also the place for cells’ interaction. The stability of the microenvironment is pivotal for maintaining cell proliferation, differentiation, metabolism and functional activities. Abnormal changes in microenvironment components can interfere cell functions. In some diseases, MSCs can interact with the microenvironment and accelerate disease progression. This review will discuss the characteristics of MSCs and their microenvironment, as well as the interaction between MSCs and microenvironment in disease.
Scaffold-based delivery of mesenchymal stromal cells to diabetic wounds
Authors: Du Shanshan , Zeugolis Dimitrios I. , O’Brien Timothy
Published: August 2022

Foot ulceration is a major complication of diabetes mellitus, which results in significant human suffering and a major burden on healthcare systems. The cause of impaired wound healing in diabetic patients is multifactorial with contributions from hyperglycaemia, impaired vascularization and neuropathy. Patients with non-healing diabetic ulcers may require amputation, creating an urgent need for new reparative treatments. Delivery of stem cells may be a promising approach to enhance wound healing because of their paracrine properties, including the secretion of angiogenic, immunomodulatory and anti-inflammatory factors. While a number of different cell types have been studied, the therapeutic use of mesenchymal stromal cells (MSCs) has been widely reported to improve delayed wound healing. However, topical administration of MSCs via direct injection has several disadvantages, including low cell viability and poor cell localization at the wound bed. To this end, various biomaterial conformations have emerged as MSC delivery vehicles to enhance cell viability and persistence at the site of implantation. This paper discusses biomaterial-based MSCs therapies in diabetic wound healing and highlights the low conversion rate to clinical trials and commercially available therapeutic products.
Immune recognition of syngeneic, allogeneic and xenogeneic stromal cell transplants in healthy retinas
Authors: Norte-Muñoz María , Gallego-Ortega Alejandro , Lucas-Ruiz Fernando , González-Riquelme María J. , Changa-Espinoza Yazmín I. , Galindo-Romero Caridad , Ponsaerts Peter , Vidal-Sanz Manuel , García-Bernal David , Agudo-Barriuso Marta
Published: August 2022

Background

Advanced therapies using adult mesenchymal stromal cells (MSCs) for neurodegenerative diseases are not effectively translated into the clinic. The cross talk between the transplanted cells and the host tissue is something that, despite its importance, is not being systematically investigated.

Methods

We have compared the response of the mouse healthy retina to the intravitreal transplantation of MSCs derived from the bone marrow in four modalities: syngeneic, allogeneic, xenogeneic and allogeneic with immunosuppression using functional analysis in vivo and histology, cytometry and protein measurementpost-mortem. Data were considered significant (p < 0.05) after nonparametric suitable statistical tests.

Results

Transplanted cells remain in the vitreous and are cleared by microglial cells a process that is quicker in allotransplants regardless of immunosuppression. All transplants cause anatomical remodelling which is more severe after xenotransplants. Xeno- and allotransplants with or without immunosuppression cause macro- and microglial activation and retinal functional impairment, being xenotransplants the most detrimental and the only ones that recruit CD45+Iba1−cells. The profile of proinflammatory cytokines changes in all transplantation settings. However, none of these changes affect the retinal ganglion cell population.

Conclusions

We show here a specific functional and anatomical retinal response depending on the MSC transplantation modality, an aspect that should be taken into consideration when conducting preclinical studies if we intend a more realistic translation into clinical practice.
Towards establishing human body-on-a-chip systems
Authors: Li Zhong Alan , Tuan Rocky S.
Published: August 2022

Body-on-a-chip (BoC) platforms are established from multiple organs-on-chips (OoCs) to recapitulate the interactions between different tissues. Recently, Vunjak-Novakovic and colleagues reported the creation of a BoC system comprising four fluidically linked OoCs. Herein, the major innovations in their BoC system are discussed, followed by our future perspectives on enhancing the physiological relevance and scalability of BoCs for applications in studying disease mechanisms, testing potential therapeutics, and developing personalized medicine.
Predicting the mutation effects of protein–ligand interactions via end-point binding free energy calculations: strategies and analyses
Authors: Yu Yang , Wang Zhe , Wang Lingling , Tian Sheng , Hou Tingjun , Sun Huiyong
Published: August 2022

Protein mutations occur frequently in biological systems, which may impact, for example, the binding of drugs to their targets through impairing the critical H-bonds, changing the hydrophobic interactions, etc. Thus, accurately predicting the effects of mutations on biological systems is of great interests to various fields. Unfortunately, it is still unavailable to conduct large-scale wet-lab mutation experiments because of the unaffordable experimental time and financial costs. Alternatively, in silico computation can serve as a pioneer to guide the experiments. In fact, numerous pioneering works have been conducted from computationally cheaper machine-learning (ML) methods to the more expensive alchemical methods with the purpose to accurately predict the mutation effects. However, these methods usually either cannot result in a physically understandable model (ML-based methods) or work with huge computational resources (alchemical methods). Thus, compromised methods with good physical characteristics and high computational efficiency are expected. Therefore, here, we conducted a comprehensive investigation on the mutation issues of biological systems with the famous end-point binding free energy calculation methods represented by MM/GBSA and MM/PBSA. Different computational strategies considering different length of MD simulations, different value of dielectric constants and whether to incorporate entropy effects to the predicted total binding affinities were investigated to provide a more accurate way for predicting the energetic change upon protein mutations. Overall, our result shows that a relatively long MD simulation (e.g. 100 ns) benefits the prediction accuracy for both MM/GBSA and MM/PBSA (with the best Pearson correlation coefficient between the predicted ∆∆G and the experimental data of ~ 0.44 for a challenging dataset). Further analyses shows that systems involving large perturbations (e.g. multiple mutations and large number of atoms change in the mutation site) are much easier to be accurately predicted since the algorithm works more sensitively to the large change of the systems. Besides, system-specific investigation reveals that conformational adjustment is needed to refine the micro-environment of the manually mutated systems and thus lead one to understand why longer MD simulation is necessary to improve the predicting result. The proposed strategy is expected to be applied in large-scale mutation effects investigation with interpretation.

Graphical Abstract
Reduced order multirate schemes in industrial circuit simulation
Authors: Bannenberg Marcus W. F. M. , Ciccazzo Angelo , Günther Michael
Published: August 2022

In this paper the industrial application of Reduced Order Multirate (ROMR) schemes is presented. This paper contains the mathematical foundations of the ROMR schemes and elaborates on the construction of these schemes using specific Model Order Reduction (MOR) techniques. Especially the Maximum Entropy Snapshot Sampling method for generating a reduced basis and reduction by Gauß–Newton with Approximated Tensors (GNAT). This basis generation method is also used for generating the basis for the gappy hyper-reduction method used for nonlinear function evaluation. For the multirate integration part, a Backward Differentation Formula approach to integration is used in conjunction with a coupled-slowest-first multirate approach. After introducing the numerical approach to industrial circuit simulation validation experiments are performed. First a simple academic model is used, and then an industrial test case is simulated as presented by STMicroelectronics. A significant speedup in simulation time is achieved whilst accuracy and convergence is kept.
Whole pulmonary assessment 1 year after paediatric acute respiratory distress syndrome: prospective multicentre study
Authors: Nève Véronique , Sadik Ahmed , Petyt Laurent , Dauger Stéphane , Kheniche Ahmed , Denjean André , Léger Pierre-Louis , Chalard François , Boulé Michèle , Javouhey Etienne , Reix Philippe , Canterino Isabelle , Deken Valérie , Matran Régis , Leteurtre Stéphane , Leclerc Francis
Published: August 2022

Background

Long-term pulmonary sequelae, including 1-year thoracic computed tomography (CT) sequelae of paediatric acute respiratory distress syndrome (ARDS) remain unknown. The purpose of the study was to determine pulmonary abnormalities in child survivors of pulmonary (p-ARDS) and extra-pulmonary ARDS (ep-ARDS) 1 year after paediatric intensive care unit discharge (PICUD).

Methods

Prospective multicentre study in four paediatric academic centres between 2005 and 2014. Patients with ARDS were assessed 1 year after PICUD with respiratory symptom questionnaire, thoracic CT and pulmonary function tests (PFT).

Results

39 patients (31 p-ARDS) aged 1.1–16.2 years were assessed. Respiratory symptoms at rest or exercise and/or respiratory maintenance treatment were reported in 23 (74%) of children with p-ARDS but in 1 (13%) of those with ep-ARDS. Thoracic CT abnormalities were observed in 18 (60%) of children with p-ARDS and 4 (50%) of those with ep-ARDS. Diffuse and more important CT abnormalities, such as ground glass opacities or mosaic perfusion patterns, were observed in 5 (13%) of children, all with p-ARDS. PFT abnormalities were observed in 30 (86%) of patients: lung hyperinflation and/or obstructive pattern in 12 (34%) children, restrictive abnormalities in 6 (50%), mild decrease in diffusing capacity in 2 (38%) and 6-min walking distance decrease in 11 (73%). Important PFT abnormalities were observed in 7 (20%) children, all with p-ARDS. Increasing driving pressure (max plateau pressure—max positive end-expiratory pressure) was correlated with increasing CT-scan abnormalities and increasing functional residual capacity (more hyperinflation) (p < 0.005).

Conclusions

Children surviving ARDS requiring mechanical ventilation present frequent respiratory symptoms, significant CT-scan and PFT abnormalities 1 year after PICUD. This highlights the need for a systematic pulmonary assessment of these children.

Trial registration The study was registered on Clinical Trials.gov PRS (ID NCT01435889)
Optimal energy-harvesting design for AF and DF two-way relay beamforming in 6G
Authors: Sun Hui , Han Fengxia , Zhao Shengjie , Deng Hao
Published: August 2022

Energy consumption is an important point which is crucial for green communications in 6G era, especially for those networks with limited life span or affected by dangerous environments where batteries are inconvenient to be changed. Therefore, energy harvesting (EH) has become a very attractive research field in recent years. In this paper, a new type of two-way EH relay beamforming system with two transceivers and many single-antenna relays is designed. All the transmit power of relay nodes is not restricted by the total quota or the personal quota and can be obtained entirely by energy harvesting. We use power splitting (PS) method for EH. We first establish a two-way system model for the amplify-and-forward and decode-and-forward relaying and then analyze the sum rate, and the gradient descent algorithm is used to solve the nonlinear joint PS factor optimization problem. Finally, the results of our analysis are verified by simulation, and they show that our method can not only optimize the PS factor efficiently, but also the model can improve the performance of the system.
Diagnostic accuracy of magnetic resonance imaging for nerve injury in obstetric brachial plexus injury: protocol for systematic review and meta-analysis
Authors: Hardie Claire , Brooks James , Wade Ryckie , Teh Irvin , Bourke Grainne
Published: August 2022

Background

Early and accurate clinical diagnosis of the extent of obstetric brachial plexus injury (OBPI) is challenging. The current gold standard for delineating the nerve injury is surgical exploration, and synchronous reconstruction is performed if indicated. Magnetic resonance imaging (MRI) is a non-invasive method of assessing the anatomy and severity of nerve injury in OBPI but the diagnostic accuracy is unclear.

The primary objective of this review is to determine the diagnostic accuracy of MRI in comparison to surgical brachial plexus exploration for detecting root avulsion in children under 5 with OBPI. The secondary objectives are to determine its’ diagnostic accuracy for detecting nerve abnormality and detecting pseudomeningocele(s) in this group.

Methods

This review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA).We will include studies reporting the accuracy of MRI (index test) compared to surgical exploration (reference standard) in detecting any of the three target conditions (root avulsion, any nerve abnormality and pseudomeningocele) in children under five with OBPI. Case reports and studies where the number of true positives, false positives, true negatives and false negatives cannot be derived will be excluded. We plan to search PubMed, Embase and CENTRAL for relevant studies from database inception to 15 June 2022. We will also search grey literature (medRxiv, bioRxiv and Google Scholar) and perform forward and backward citation chasing. Screening and full-text assessment of eligibility will be conducted by two independent reviewers, who will then both extract the relevant data. The QUADAS-2 tool will be used to assess methodological quality and risk of bias of included studies by two reviewers independently. The following test characteristics for the target conditions will be extracted: true positives, false positives, true negatives and false negatives. Estimates of sensitivity and specificity with 95% confidence intervals will be shown in forest plots for each study. If appropriate, summary sensitivities and specificities for target conditions will be obtained via meta-analyses using a bivariate model.

Discussion

This study will aim to clarify the diagnostic accuracy of MRI for detecting nerve injury in OBPI and define its clinical role.

Systematic review registration

PROSPERO CRD42021267629.
Numerical analysis of a linear second-order finite difference scheme for space-fractional Allen–Cahn equations
Authors: Wang Kai , Feng Jundong , Chen Hongbo , Xu Changling
Published: August 2022

In this paper, we construct a new linear second-order finite difference scheme with two parameters for space-fractional Allen–Cahn equations. We first prove that the discrete maximum principle holds under reasonable constraints on time step size and coefficient of stabilized term. Secondly, we analyze the maximum-norm error. Thirdly, we can see that the proposed scheme is unconditionally energy-stable by defining the modified energy and selecting the appropriate parameters. Finally, two numerical examples are presented to verify the theoretical results.
Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle
Authors: Luo Hanpeng , Hu Lirong , Brito Luiz F. , Dou Jinhuan , Sammad Abdul , Chang Yao , Ma Longgang , Guo Gang , Liu Lin , Zhai Liwei , Xu Qing , Wang Yachun
Published: August 2022

Background

The study of molecular processes regulating heat stress response in dairy cattle is paramount for developing mitigation strategies to improve heat tolerance and animal welfare. Therefore, we aimed to identify quantitative trait loci (QTL) regions associated with three physiological indicators of heat stress response in Holstein cattle, including rectal temperature (RT), respiration rate score (RS), and drooling score (DS). We estimated genetic parameters for all three traits. Subsequently, a weighted single-step genome-wide association study (WssGWAS) was performed based on 3200 genotypes, 151,486 phenotypic records, and 38,101 animals in the pedigree file. The candidate genes located within the identified QTL regions were further investigated through RNA sequencing (RNA-seq) analyses of blood samples for four cows collected in April (non-heat stress group) and four cows collected in July (heat stress group).

Results

The heritability estimates for RT, RS, and DS were 0.06, 0.04, and 0.03, respectively. Fourteen, 19, and 20 genomic regions explained 2.94%, 3.74%, and 4.01% of the total additive genetic variance of RT, RS, and DS, respectively. Most of these genomic regions are located in the Bos taurus autosome (BTA) BTA3, BTA6, BTA8, BTA12, BTA14, BTA21, and BTA24. No genomic regions overlapped between the three indicators of heat stress, indicating the polygenic nature of heat tolerance and the complementary mechanisms involved in heat stress response. For the RNA-seq analyses, 2627 genes were significantly upregulated and 369 downregulated in the heat stress group in comparison to the control group. When integrating the WssGWAS, RNA-seq results, and existing literature, the key candidate genes associated with physiological indicators of heat stress in Holstein cattle are: PMAIP1, SBK1, TMEM33, GATB, CHORDC1, RTN4IP1, and BTBD7.

Conclusions

Physiological indicators of heat stress are heritable and can be improved through direct selection. Fifty-three QTL regions associated with heat stress indicators confirm the polygenic nature and complex genetic determinism of heat tolerance in dairy cattle. The identified candidate genes will contribute for optimizing genomic evaluation models by assigning higher weights to genetic markers located in these regions as well as to the design of SNP panels containing polymorphisms located within these candidate genes.

Graphical Abstract
Experiences of eating difficulties in siblings of people with anorexia nervosa: a reflexive thematic analysis
Authors: Scutt Eleanor , Langdon-Daly Jasmin , Smithson Janet
Published: August 2022

Background

Siblings of people with anorexia nervosa (AN) have been found to experience strong emotions, changing family roles and poorer wellbeing as a consequence of experiencing the effects of the illness on their sibling and family system. These factors, combined with genetic influences, may put siblings at an increased risk of developing eating disorder psychopathology in addition to other mental health issues. This research aims to explore the experiences of siblings of people with AN who have had eating difficulties themselves and investigate issues that may be important to the development and prevention of eating difficulties in this population.

Methods

This qualitative study used a reflexive thematic analysis approach. Ten adults who had witnessed a sibling with AN and experienced eating difficulties themselves participated in semi-structured interviews.

Analysis

Participants’ own eating difficulties were affected by the specific experience of witnessing a sibling with AN through mealtimes becoming emotionally charged, an increased focus on body size and diet, and comparisons with their sibling. Difficult experiences, such as marital discord amongst parents were common, as was a difficulty in managing emotions. The onset of AN within the family caused participants to take on caring responsibilities for their sibling and to hide their own difficulties for fear of adding additional burden to their parents. This reduced their perceived ability to access support and for some increased a desire to restrict as a coping mechanism for the stress they were experiencing. Systemic beliefs regarding the value of thinness were prevalent and influential. Protective factors, such as not wanting to become as unwell as a sibling with AN and an understanding of the negative consequences of AN, aided recovery.

Conclusions

Eating difficulties in siblings of people with AN may be influenced by competition for slimness, increased focus on diet and body size, and a need to manage difficult emotions. The disruption to social connections and a difficulty finding emotional support that may be experienced by people when a sibling develops AN may further influence susceptibility to eating difficulties. Further research is needed into the best ways to support siblings of people with AN.
Depression, anxiety, and stress among Iranian nurses in COVID-19 care wards
Authors: Sharifi Azam , Fallahi-Khoshknab Masoud , Mohammadi Shamaneh , Zeraati Mashaallah , Jamshidi Zahra , Aghabeygi-Arani Mohsen , Mirzaei Nilofar , Fallahi-Khoshknab Negin , Rasooli Parisa
Published: August 2022

Background

Nurses are at the frontline of care provision to patients with coronavirus disease 2019 (COVID-19). The high communicability of COVID-19, high levels of stress associated with the disease, and challenges of care provision to afflicted patients faced nurses in Iran with problems such as depression, anxiety, and stress. The aim of the study was to assess depression, anxiety, and stress among Iranian nurses who provided care to patients with COVID-19.

Methods

This cross-sectional descriptive-analytical study was conducted in 2020–2021. Participants were 468 nurses purposively selected from university hospitals in Iran. They completed two online instruments, namely a demographic questionnaire and the 21-item Depression Anxiety Stress Scale. Data were analyzed using the SPSS software (v. 23.0).

Results

Most participants were female (75.9%) and married (73.4%) and held bachelor’s degree (88%). The means of participants’ age and work experience were 33.59 ± 6.40 years and 10.26 ± 6.61 years, respectively. The mean scores and the prevalence rates of depression, anxiety, and stress were 13.56 ± 5.37 and 74.1%, 13.21 ± 4.90 and 89.7%, and 15.13 ± 4.76 and 54.9%, respectively. The prevalence rates of moderate to severe depression, anxiety, and stress were 43.7%, 73%, and 24%, respectively. The mean scores of participants’ depression, anxiety, and stress had significant relationship with their employment status (p < 0.05). Besides, the mean scores of their anxiety had significant relationship with their educational level, employment status, and work shift (p < 0.05).

Conclusion

Most nurses who provide care to patients with COVID-19 suffer from depression, anxiety, and stress. Psychological support services may be needed for nurses in order to protect and promote their mental health.