bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractProtein 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

AbstractIn 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

Abstract
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

AbstractEnergy 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

Abstract
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

AbstractIn 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

Abstract
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

Abstract
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

Abstract
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.
Practical approaches to improve vancomycin-related patient outcomes in pediatrics- an alternative strategy when AUC/MIC is not feasible
Authors: Hussain Kashif , Salat Muhammad Sohail , Rauf Shahzad , Rathi Manoj , Khan Midhat , Naz Fizzah , Khan Wasif Ahmed , Ikram Rahila , Ambreen Gul 
Published: August 2022

Abstract
Background
Anecdotal experience and studies have shown that most pediatric patients fail to reach target therapeutic vancomycin trough levels (VTLs) and required higher total daily doses (TDD). This retrospective study aims to evaluate the frequency of hospitalized children who achieved target VTLs with a vancomycin (VNCO) dosing regimen of 40-60 mg/kg/d q6h and to assess the VNCO-TDD required to attain the target and their effects on clinical outcomes in pediatric patients.

Methods
After ethical approval, patients of 3 month-12 years were evaluated in this chart review study who received ≥ 3 intravenous-VNCO doses and appropriately drawn blood samples of VTLs between October 2019 to June 2020. Data were retrieved for demographic and clinical characteristics, culture reports, VNCO-regimen, subsequent steady-state VTLs, concomitant nephrotoxic medications, and serum creatinine. Clinical pharmacists made interventions in VNCO therapy and higher VNCO-TDD were used. Safety of higher vs standard daily doses and their clinical impact on duration of therapy, hospital stay, and survival were evaluated.

Results
A total of 89 (39.1%) patients achieved target VTLs (SD-group). The smallest proportion (18.2%) of 2–6 years patients achieved target VTLs and reported the lowest mean value of 10.1 ± 0.2 mg/L which was a significant difference (p < 0.05) from all subgroups. Subtherapeutic VTLs were observed in 139 (60.9%) cases (HD-group), who received higher VNCO-TDD of 72 ± 8.9 mg/kg/d q6h to achieve the targets. Duration of therapy in culture-proven septic patients was significantly (p = 0.025) longer in SD-group [18.4 ± 12.2 days] than HD-group [15.1 ± 8.9 days]. Nephrotoxicity and electrolyte imbalance were comparable in groups. Length of hospital stay was significantly (p = 0.011) longer [median 22 (range 8–55) days] in SD-group compared to HD-group [median 16 (range 8–37) days]. Number of patients survived in HD-group were significantly (p = 0.008) higher than SD-group [129 (92.8%) vs 75 (84.3%)].

Conclusion
Initial Vancomycin doses of 72 ± 8.9 mg/kg/day q6h are required to achieve therapeutic target in 3 months to 12 years patients. High doses are not associated with higher nephrotoxicity than reported with low doses. In addition, efficient pharmacist intervention for the use of higher VNCO-TDD may improve clinical outcomes in terms of duration of therapy, hospital stay, and survival.
DPP-4 inhibitors and GLP-1RAs: cardiovascular safety and benefits
Authors: Razavi Michael , Wei Ying-Ying , Rao Xiao-Quan , Zhong Ji-Xin 
Published: August 2022

AbstractGlucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors are commonly used treatments for patients with type 2 diabetes mellitus (T2DM). Both anti-diabetic treatments function by playing key modulatory roles in the incretin system. Though these drugs have been deemed effective in treating T2DM, the Food and Drug Administration (FDA) and some members of the scientific community have questioned the safety of these therapeutics relative to important cardiovascular endpoints. As a result, since 2008, the FDA has required all new drugs for glycemic control in T2DM patients to demonstrate cardiovascular safety. The present review article strives to assess the safety and benefits of incretin-based therapy, a new class of antidiabetic drug, on the health of patient cardiovascular systems. In the process, this review will also provide a physiological overview of the incretin system and how key components function in T2DM.