bluuebunny/crossref_metadata_2025 huggingface dataset:
Tauroursodeoxycholic acid in patients with amyotrophic lateral sclerosis: The TUDCA-ALS trial protocol
Authors: Albanese Alberto , Ludolph Albert Christian , McDermott Christopher J. , Corcia Philippe , Van Damme Philip , Van den Berg Leonard H. , Hardiman Orla , Rinaldi Gilberto , Vanacore Nicola , Dickie Brian ,   TUDCA-ALS Study Group
Published: September 2022

Background

Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative rare disease that affects motor neurons in the brain, brainstem, and spinal cord, resulting in progressive weakness and atrophy of voluntary skeletal muscles. Although much has been achieved in understanding the disease pathogenesis, treatment options are limited, and in Europe, riluzole is the only approved drug. Recently, some other drugs showed minor effects.

Methods

The TUDCA-ALS trial is a phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The study aims to enroll 320 patients in 25 centers across seven countries in Europe. Enrolled patients are randomized to one of two treatment arms: TUDCA or identical placebo by oral route. The study measures disease progression during the treatment period and compares it to natural progression during a no-treatment run-in phase. Clinical data and specific biomarkers are measured during the trial. The study is coordinated by a consortium composed of leading European ALS centers.

Conclusion

This trial is aimed to determine whether TUDCA has a disease-modifying activity in ALS. Demonstration of TUDCA efficacy, combined with the validation of new biomarkers, could advance ALS patient care.

Clinical trial registration

ClinicalTrials.gov, identifier: NCT03800524.
Recurrent Vertigo of Childhood: Clinical features and prognosis
Authors: Dunker Konstanze , Schnabel Lutz , Grill Eva , Filippopulos Filipp Maximilian , Huppert Doreen
Published: September 2022

Introduction

“Recurrent Vertigo of Childhood” (RVC) has recently replaced the term “Benign Paroxysmal Vertigo of Childhood” and was defined as recurrent spells of vertigo without evidence of a vestibular migraine of childhood (VMC). RVC and VMC are considered the most frequent causes of vertigo and dizziness in children below 18 years of age. Diagnosis might be challenging since clinical features of RVC and VMC may overlap.

Objective

This study aims to characterize clinical and instrument-based findings in patients with RVC and to evaluate the course of the disorder.

Methods

We prospectively collected clinical and instrument-based data of children/adolescents younger than 18 years, who presented at the German Center for Vertigo and Balance Disorders (DSGZ) at the LMU University Hospital in Munich. All patients underwent a comprehensive neurological, ocular motor, vestibular and cochlear examination. Furthermore, findings from follow-up examinations were analyzed.

Results

Overall 42 children (24 male and 18 female) with RVC were included in the study. The mean age at diagnosis was 7 ± 3.6 years with a mean onset of symptoms at the age of 5.6 ± 3.4 years. Attack duration ranged between 1 min and 4 h. The most common accompanying symptoms included nausea, vomiting, expression of fear, and falls. Non-migrainous headaches were reported by 11 patients during initial presentation, 7 of whom were later diagnosed with migraine. Female patients showed a higher age at symptom onset, a higher attack frequency, and attack duration. Eleven of the 24 patients seen at a 3.5 year follow-up reported a complete cessation of attacks. Patients still experiencing vertigo attacks had a significantly reduced attack frequency, especially those who implemented at least one prophylactic measure.

Conclusion

A precise characterization of symptoms is essential for diagnosing children with RVC. Age at symptom onset does not exceed the age of 12. Gender-specific differences should be considered and may further support the evidence of an association with migraine. The disease course of RVC is benign, nevertheless implementing prophylactic measures such as regular exercise, increased fluid intake, sleep hygiene, and relaxation exercises, can improve attack frequency.
Comparative efficacy of 5 non-pharmacological therapies for adults with post-stroke cognitive impairment: A Bayesian network analysis based on 55 randomized controlled trials
Authors: Li Zhendong , Yang Lei , Qiu Hangjian , Wang Xiaoqian , Zhang Chengcheng , Zhang Yuejuan
Published: September 2022

Background

As a common sequela after stroke, cognitive impairment negatively impacts patients' activities of daily living and overall rehabilitation. Non-pharmacological therapies have recently drawn widespread attention for their potential in improving cognitive function. However, the optimal choice of non-pharmacological therapies for post-stroke cognitive impairment (PSCI) is still unclear. Hence, in this study, we compared and ranked 5 non-pharmacological therapies for PSCI with a Bayesian Network Meta-analysis (NMA), to offer a foundation for clinical treatment decision-making.

Methods

PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Chinese Biomedical Medicine, China National Knowledge Infrastructure, Wangfang Database, and China Science and Technology Journal Database were searched from database inception to December 31, 2021, to collect Randomized Controlled Trials for PSCI. All of the studies were assessed (according to Cochrane Handbook for Systematic Reviews) and then data were extracted by two researchers separately. Pairwise meta-analysis for direct comparisons was performed using Revman. NMA of Bayesian hierarchical model was performed by WinBUGS and ADDIS. STATA was used to construct network evidence plots and funnel plots.

Results

A total of 55 trials (53 Two-arm trials and 2 Three-arm trials) with 3,092 individuals were included in this study. In the pair-wise meta-analysis, Transcranial Magnetic Stimulation (TMS), Virtual Reality Exposure Therapy (VR), Computer-assisted cognitive rehabilitation (CA), Transcranial Direct Current Stimulation (tDCS), and Acupuncture were superior to normal cognition training in terms of MoCA, MMSE, and BI outcomes. Bayesian NMA showed that the MoCA outcome ranked Acupuncture (84.7%) as the best therapy and TMS (79.7%) as the second. The MMSE outcome ranked TMS (76.1%) as the best therapy and Acupuncture as the second (72.1%). For BI outcome, TMS (89.1%) ranked the best.

Conclusions

TMS and Acupuncture had a better effect on improving cognitive function in post-stroke patients according to our Bayesian NMA. However, this conclusion still needs to be confirmed with large sample size and high-quality randomized controlled trials.

Registration

https://inplasy.com (No. INPLASY202260036).
Accurate segmentation of neonatal brain MRI with deep learning
Authors: Richter Leonie , Fetit Ahmed E.
Published: September 2022

An important step toward delivering an accurate connectome of the human brain is robust segmentation of 3D Magnetic Resonance Imaging (MRI) scans, which is particularly challenging when carried out on perinatal data. In this paper, we present an automated, deep learning-based pipeline for accurate segmentation of tissues from neonatal brain MRI and extend it by introducing an age prediction pathway. A major constraint to using deep learning techniques on developing brain data is the need to collect large numbers of ground truth labels. We therefore also investigate two practical approaches that can help alleviate the problem of label scarcity without loss of segmentation performance. First, we examine the efficiency of different strategies of distributing a limited budget of annotated 2D slices over 3D training images. In the second approach, we compare the segmentation performance of pre-trained models with different strategies of fine-tuning on a small subset of preterm infants. Our results indicate that distributing labels over a larger number of brain scans can improve segmentation performance. We also show that even partial fine-tuning can be superior in performance to a model trained from scratch, highlighting the relevance of transfer learning strategies under conditions of label scarcity. We illustrate our findings on large, publicly available T1- and T2-weighted MRI scans (n = 709, range of ages at scan: 26–45 weeks) obtained retrospectively from the Developing Human Connectome Project (dHCP) cohort.
A data-driven approach to clinical decision support in tinnitus retraining therapy
Authors: Tarnowska Katarzyna A. , Ras Zbigniew W. , Jastreboff Pawel J.
Published: September 2022

Background

Tinnitus, known as “ringing in the ears”, is a widespread and frequently disabling hearing disorder. No pharmacological treatment exists, but clinical management techniques, such as tinnitus retraining therapy (TRT), prove effective in helping patients. Although effective, TRT is not widely offered, due to scarcity of expertise and complexity because of a high level of personalization. Within this study, a data-driven clinical decision support tool is proposed to guide clinicians in the delivery of TRT.

Methods

This research proposes the formulation of data analytics models, based on supervised machine learning (ML) techniques, such as classification models and decision rules for diagnosis, and action rules for treatment to support the delivery of TRT. A knowledge-based framework for clinical decision support system (CDSS) is proposed as a UI-based Java application with embedded WEKA predictive models and Java Expert System Shell (JESS) rule engine with a pattern-matching algorithm for inference (Rete). The knowledge base is evaluated by the accuracy, coverage, and explainability of diagnostics predictions and treatment recommendations.

Results

The ML methods were applied to a clinical dataset of tinnitus patients from the Tinnitus and Hyperacusis Center at Emory University School of Medicine, which describes 555 patients and 3,000 visits. The validated ML classification models for diagnosis and rules: association and actionable treatment patterns were embedded into the knowledge base of CDSS. The CDSS prototype was tested for accuracy and explainability of the decision support, with preliminary testing resulting in an average of 80% accuracy, satisfactory coverage, and explainability.

Conclusions

The outcome is a validated prototype CDS system that is expected to facilitate the TRT practice.
Machine learning for autism spectrum disorder diagnosis using structural magnetic resonance imaging: Promising but challenging
Authors: Bahathiq Reem Ahmed , Banjar Haneen , Bamaga Ahmed K. , Jarraya Salma Kammoun
Published: September 2022

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects approximately 1% of the population and causes significant burdens. ASD’s pathogenesis remains elusive; hence, diagnosis is based on a constellation of behaviors. Structural magnetic resonance imaging (sMRI) studies have shown several abnormalities in volumetric and geometric features of the autistic brain. However, inconsistent findings prevented most contributions from being translated into clinical practice. Establishing reliable biomarkers for ASD using sMRI is crucial for the correct diagnosis and treatment. In recent years, machine learning (ML) and specifically deep learning (DL) have quickly extended to almost every sector, notably in disease diagnosis. Thus, this has led to a shift and improvement in ASD diagnostic methods, fulfilling most clinical diagnostic requirements. However, ASD discovery remains difficult. This review examines the ML-based ASD diagnosis literature over the past 5 years. A literature-based taxonomy of the research landscape has been mapped, and the major aspects of this topic have been covered. First, we provide an overview of ML’s general classification pipeline and the features of sMRI. Next, representative studies are highlighted and discussed in detail with respect to methods, and biomarkers. Finally, we highlight many common challenges and make recommendations for future directions. In short, the limited sample size was the main obstacle; Thus, comprehensive data sets and rigorous methods are necessary to check the generalizability of the results. ML technologies are expected to advance significantly in the coming years, contributing to the diagnosis of ASD and helping clinicians soon.
Zein-based nano-delivery systems for encapsulation and protection of hydrophobic bioactives: A review
Authors: Yan Xiaojia , Li Moting , Xu Xingfeng , Liu Xuebo , Liu Fuguo
Published: September 2022

Zein is a kind of excellent carrier materials to construct nano-sized delivery systems for hydrophobic bioactives, owing to its unique interfacial behavior, such as self-assembly and packing into nanoparticles. In this article, the chemical basis and preparation methods of zein nanoparticles are firstly reviewed, including chemical crosslinking, emulsification/solvent evaporation, antisolvent, pH-driven method, etc., as well as the pros and cons of different preparation methods. Various strategies to improve their physicochemical properties are then summarized. Lastly, the encapsulation and protection effects of zein-based nano-sized delivery systems (e.g., nanoparticles, nanofibers, nanomicelles and nanogels) are discussed, using curcumin as a model bioactive ingredient. This review will provide guidance for the in-depth development of hydrophobic bioactives formulations and improve the application value of zein in the food industry.
The reasonable therapeutic modality for biliary duct-to-duct anastomotic stricture after liver transplantation: ERCP or PTC?
Authors: Bowen Hu , Wenzhi Guo , Peihao Wen , Jihua Shi , Shuijun Zhang
Published: September 2022

Objective

To compare the initial success rate, feasibility, and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) versus percutaneous transhepatic cholangiography (PTC) for anastomotic biliary stricture after liver transplantation (LT).

Methods

We retrospectively analyzed the data collected during January 2015 to December 2021 from liver transplantation recipients who developed anastomotic biliary stricture after liver transplantation and treated by ERCP and/or PTC. The success rate, complications and patients’ survival rate of ERCP and PTC procedures was evaluated.

Results

Forty-eight patients who underwent LT and were confirmed to have the anastomotic biliary stricture were enrolled. Overall, 48/48 patients underwent single or multiple ERCP procedures as the first line therapy; 121 therapeutic ERCPs (3.36 ± 2.53 ERCPs per patient) were performed in 36/48 patients successfully. All the 12 patients who failed ERCP tend to have special bile duct conditions such as overlong, angle shaped, and/or extremely narrowed bile duct and underwent PTC as an alternative treatment. The initial success rate of ERCP was 75% (36/48) while the success rate of ERCP for the 12 patients with special bile duct was 0% (0/12). PTC was an effective second-line treatment for those 12 patients who failed ERCP, and 58.33% (7 of 12 cases) were treated successfully. The average procedure time in PTC group was significantly lower than ERCP group (t=2.292, P=0.027). The feasibility of ERCP was associated with the anatomical shape of bile duct and the severity of the stricture site. Finally, the cumulative survival rate was 100% (12/12) in PTC group compared to 86.11% (31/36) in ERCP group (χ2 =0.670, P=0.413).

Conclusion

ERCP is the gold standard method for the diagnosis and effective intervention for the management of biliary complications after LT. However, its use in certain types of biliary complications (e.g., patients with severe anastomotic biliary stricture and those with overlong and angle shaped bile ducts) is not promising and associated with significant risk of complications. PTC and other interventions should be studied along with ERCP for patients for whom ERCP may not work. The feasibility and efficacy of primary management can be predicted by the noninvasive imaging examinations like Magnetic Resonance Cholangiopancreatography (MRCP) before the procedure, which may help with the choice of the most reasonable therapeutic modality and avoiding unnecessary financial burden and complications.
Nomograms for the prediction of lateral lymph node metastasis in papillary thyroid carcinoma: Stratification by size
Authors: Feng Jia-Wei , Ye Jing , Hong Li-Zhao , Hu Jun , Wang Fei , Liu Sheng-Yong , Jiang Yong , Qu Zhen
Published: September 2022

Background

Lateral lymph node metastasis (LLNM) is a risk factor of poor prognosis in papillary thyroid cancer (PTC). We aimed to determine predictive factors and develop the nomograms for LLNM in patients with papillary thyroid microcarcinoma (PTMC) and macro-PTC.

Methods

We reviewed the medical records of 1,106 patients who underwent surgery between January 2019 and January 2022. Patients were divided into a PTMC and a macro-PTC group. We developed preoperative and postoperative nomograms for predicting LLNM based on results of multivariate analysis. Internal calibration was performed for these models.

Results

The number of metastatic lymph nodes in lateral compartment was higher in macro-PTC patients. LLNM was independently associated with gender, the number of foci, location, shape, and central lymph node metastasis (CLNM) in PTMC patients. For macro-PTC patients, chronic lymphocytic thyroiditis, the number of foci, location, margin, CLNM, and central lymph node ratio were all independent predictors for LLNM. All the above factors were incorporated into nomograms, which showed the perfect discriminative ability.

Conclusion

The diameter of the tumor has an impact on the rate of LLNM. Separate predictive systems should be used for PTMC and macro-PTC patients for more accurate clinical assessment of lateral lymph node status. Through these nomograms, we can not only detect high-risk patients with occult LLNM preoperatively, but also form appropriate treatment protocols for postoperative management of PTC patients with different risks.
Ultrasound-based deep learning using the VGGNet model for the differentiation of benign and malignant thyroid nodules: A meta-analysis
Authors: Zhu Pei-Shan , Zhang Yu-Rui , Ren Jia-Yu , Li Qiao-Li , Chen Ming , Sang Tian , Li Wen-Xiao , Li Jun , Cui Xin-Wu
Published: September 2022

Objective

The aim of this study was to evaluate the accuracy of deep learning using the convolutional neural network VGGNet model in distinguishing benign and malignant thyroid nodules based on ultrasound images.

Methods

Relevant studies were selected from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases, which used the deep learning-related convolutional neural network VGGNet model to classify benign and malignant thyroid nodules based on ultrasound images. Cytology and pathology were used as gold standards. Furthermore, reported eligibility and risk bias were assessed using the QUADAS-2 tool, and the diagnostic accuracy of deep learning VGGNet was analyzed with pooled sensitivity, pooled specificity, diagnostic odds ratio, and the area under the curve.

Results

A total of 11 studies were included in this meta-analysis. The overall estimates of sensitivity and specificity were 0.87 [95% CI (0.83, 0.91)] and 0.85 [95% CI (0.79, 0.90)], respectively. The diagnostic odds ratio was 38.79 [95% CI (22.49, 66.91)]. The area under the curve was 0.93 [95% CI (0.90, 0.95)]. No obvious publication bias was found.

Conclusion

Deep learning using the convolutional neural network VGGNet model based on ultrasound images performed good diagnostic efficacy in distinguishing benign and malignant thyroid nodules.

Systematic Review Registration

https://www.crd.york.ac.nk/prospero, identifier CRD42022336701.
Health-related quality of life in breast cancer patients in Asia: A meta-analysis and systematic review
Authors: Chen Xinyu , Wu Chenxi , Bai Dingxi , Gao Jing , Hou Chaoming , Chen Tingting , Zhang Lulu , Luo Huan
Published: September 2022

Objectives

The primary purposes of this meta-analysis and systematic review were to evaluate the health-related quality of life (HRQoL) of Asian breast cancer (BC) patients to understand their holistic HRQoL level and provide medical and nursing recommendations to improve and preserve their quality of life.

Methods

A comprehensive literature search was conducted to find cross-sectional studies published in Chinese and English concerning HRQoL in BC patients from the inceptions of databases to 14 March 2022. The databases consulted were PubMed, Web of Science, Embase, Cochrane, PsyclNFO, CINAHL, and CNKI. Literature screening, data extraction, risk bias assessment, and data synthesis were independently carried out by two researchers. The Endnote X9 and Stata 15.0 software programs were used during the meta-analysis process.

Results

Out of the 8,563 studies identified, 23 cross-sectional studies involving 3,839 Asian BC patients were included in this meta-analysis. Two tools, namely, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and Quality of Life Questionnaire Breast Cancer module 23 (EORTC QLQ-BR23)—were used to evaluate the HRQoL of BC patients in Asia. The pooled mean of the global health status of Asian BC patients was 58.34 (95% confidence interval [CI]: 53.66–63.02). According to functional subscales of EORTC QLQ-C30 and EORTC QLQ-BR23, Asian BC patients suffered from the worst emotional functioning (pooled mean=66.38; 95% CI: 59.66–73.11) and sexual enjoyment (pooled mean=49.31; 95% CI: 31.97–63.36). In addition, fatigue (pooled mean=42.17; 95% CI: 34.46–49.88) and being upset by hair loss (pooled mean=48.38; 95% CI: 36.64–60.12) were the most obvious symptoms that Asian BC patients experienced according to the meta-analysis results of the EORTC QLQ-C30 and EORTC QLQ-BR23 symptom subscales.

Conclusion

Asian BC patients experience a relatively low HRQoL due to the prominent decline in their body functions, as well as the unpleasant experiences caused by their symptoms. It is suggested that timely, appropriate, and targeted intervention should be provided in relation to the physical, psychological, and social aspects of Asian BC patients’ lives to enhance their ability to function, relieve them of adverse symptoms, and improve their overall HRQoL.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022321165.
The association between biomarkers of acrylamide and cancer mortality in U.S. adult population: Evidence from NHANES 2003-2014
Authors: Gu Wenbo , Zhang Jiacheng , Ren Chunling , Gao Yang , Zhang Tongfang , Long Yujia , Wei Wei , Hou Shaoying , Sun Changhao , Wang Changhong , Jiang Wenbo , Zhao Junfei
Published: September 2022

The association between acrylamide (AA) and the development of cancer has been extensively discussed but the results remained controversial, especially in population studies. Large prospective epidemiological studies on the relationship of AA exposure with cancer mortality were still lacking. Therefore, we aimed to assess the association between AA biomarkers and cancer mortality in adult population from National Health and Nutrition Examination Survey (NHANES) 2003-2014. We followed 3717 participants for an average of 10.3 years. Cox regression models with multivariable adjustments were performed to determine the relationship of acrylamide hemoglobin adduct (HbAA) and glycidamide hemoglobin adduct (HbGA) with cancer mortality. Mediation analysis was conducted to demonstrate the mediated role of low-grade inflammation score (INFLA-score) in this correlation. Compared with the lowest quintile, participants with the highest quintile of HbAA, HbGA and HbAA+HbGA had increased cancer mortality risk, and the hazard ratios(HRs) were 2.07 (95%CI:1.04-4.14) for HbAA, 2.39 (95%CI:1.29-4.43) for HbGA and 2.48 (95%CI:1.28-4.80) for HbAA+HbGA, respectively. And there was a considerable non-linearity association between HbAA and cancer mortality (pfor non-linearity = 0.0139). We further found that increased INFLA-score significantly mediated 71.67% in the effect of HbGA exposure on increased cancer mortality risk. This study demonstrates that hemoglobin biomarkers of AA are positively associated with cancer mortality in adult American population and INFLA-score plays a mediated role in this process. Our findings can raise public awareness of environmental and dietary exposure to acrylamide and remind people to refrain from smoking or having acrylamide-rich foods.
Intracranial solitary fibrous tumor/hemangiopericytoma: Role and choice of postoperative radiotherapy techniques
Authors: Gou Qiheng , Xie Yuxin , Ai Ping
Published: September 2022

Background

Intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a novel rare disease after the 2016 WHO reclassification. Surgery is the main treatment. Postoperative adjuvant radiotherapy is often used, but the effects of different radiotherapy techniques are still unclear. The purpose of this study was to analyze the effects of postoperative radiotherapy (PORT) and different radiotherapy methods on the efficacy of patients with intracranial SFT/HPC.

Materials and methods

We retrospectively analyzed 42 patients with intracranial SFT/HPC who underwent surgical treatment from 2008 to 2022, 20 of whom were treated with postoperative intensity-modulated radiotherapy (IMRT) and 22 with postoperative stereotactic radiosurgery (SRS). The Kaplan–Meier method was used to analyze the disease-free survival (DFS) of all the 42 patients receiving postoperative radiotherapy and the time to progression (TTP) of 22 of these patients experiencing recurrence. A multivariate Cox proportional hazards model was used to detect prognostic factors of survival.

Results

In the analysis of PORT patients, the median DFS was 8.33 years for PORT IMRT patients and 3.04 years for PORT SRS patients. The 10-year DFS incidence was 46.0% in the PORT IMRT group and 27.5% in the SRS group. Among the 22 patients who relapsed, the median TTP of other patients was 1.25 years, of which 3 received radiotherapy alone and 1 received symptomatic treatment, while the median TTP of surgical and surgical combined with radiotheray patients were 1.83 and 2.49 years, respectively (p=0.035).

Conclusion

PORT IMRT could prolong DFS compared with PORT SRS. It indicated that PORT IMRT radiotherapy technology was a feasible option for SFT/HPC. Moreover, TTP results of relapsed patients showed that, surgery and surgery combined with radiotherapy treatments have no significant difference on TTP in relapsed patients, but both of them were better than other treatments.
Impact of COVID-19 on glaucoma management: A review
Authors: Yadav Manoj , Tanwar Mukesh
Published: September 2022

Glaucoma is the leading cause of irreversible vision loss and the second leading cause of blindness worldwide. The rapid transmission of SARS-CoV-2virus compelled governments to concentrate their efforts on emergency units to treat the large number of cases that arose due to the Covid-19 outbreak. As a result, many chronically ill patients were left without access to medical care. The progression of glaucoma in previously diagnosed cases has been accelerated; due to this, some have lost their vision. Evaluation of Covid-19’s effect on glaucoma treatment was one goal of this study. We used search phrases like “COVID-19,” “telemedicine,” and “glaucoma” to find published papers on COVID-19 and glaucoma. Artificial Intelligence (AI) may be the answer to the unanswered questions that arose due to this pandemic crisis. The benefits and drawbacks of AI in the context of teliglaucoma have been thoroughly examined. These AI-related ideas have been floating around for some time. We hope that Covid-19’s enormous revisions will provide them with the motivation to move forward and significantly improve services. Despite the devastation the pandemic has caused, we are hopeful that eye care services will be better prepared and better equipped to avoid the loss of sight due to glaucoma in future.
Quantifying lung aeration in neonatal lambs at birth using lung ultrasound
Authors: Pryor Emily J. , Blank Douglas A. , Hooper Stuart B. , Crossley Kelly J. , Badurdeen Shiraz , Pollock James A. , Stainsby Andrew V. , Croton Linda C. P. , O’Connell Dylan W. , Hall Christopher J. , Maksimenko Anton , Hausermann Daniel , Davis Peter G. , Kitchen Marcus J.
Published: September 2022

Background

Lung ultrasound (LUS) is a safe and non-invasive tool that can potentially assess regional lung aeration in newborn infants and reduce the need for X-ray imaging. LUS produces images with characteristic artifacts caused by the presence of air in the lung, but it is unknown if LUS can accurately detect changes in lung air volumes after birth. This study compared LUS images with lung volume measurements from high-resolution computed tomography (CT) scans to determine if LUS can accurately provide relative measures of lung aeration.

Methods

Deceased near-term newborn lambs (139 days gestation, term ∼148 days) were intubated and the chest imaged using LUS (bilaterally) and phase contrast x-ray CT scans at increasing static airway pressures (0–50 cmH2O). CT scans were analyzed to calculate regional air volumes and correlated with measures from LUS images. These measures included (i) LUS grade; (ii) brightness (mean and coefficient of variation); and (iii) area under the Fourier power spectra within defined frequency ranges.

Results

All LUS image analysis techniques correlated strongly with air volumes measured by CT (p < 0.01). When imaging statistics were combined in a multivariate linear regression model, LUS predicted the proportion of air in the underlying lung with moderate accuracy (95% prediction interval ± 22.15%, r2 = 0.71).

Conclusion

LUS can provide relative measures of lung aeration after birth in neonatal lambs. Future studies are needed to determine if LUS can also provide a simple means to assess air volumes and individualize aeration strategies for critically ill newborns in real time.
Genetic and pharmacological tools to study the role of discoidin domain receptors in kidney disease
Authors: Borza Corina M. , Bolas Gema , Pozzi Ambra
Published: September 2022

Following injury the kidney undergoes a repair process, which results in replacement of the injured tissue with little evidence of damage. However, repetitive injuries or inability of the kidney to stop the repair process result in abnormal deposition of extracellular matrix (ECM) components leading to fibrosis and organ dysfunction. The synthesis/degradation of ECM components is finely regulated by several factors, including discoidin domain receptors (DDRs). These are receptor tyrosine kinases that are activated by collagens. Upon activation, DDRs control several cell functions that, when exacerbated, contribute to kidney injury and fibrosis. DDRs are undetectable in healthy kidney, but become rapidly upregulated in several kidney fibrotic conditions, thus making them attractive anti-fibrotic targets. DDRs contribute to kidney injury and fibrosis by promoting apoptosis of injured kidney cells, stimulating the production of pro-inflammatory cytokines, and regulating the production of ECM components. They achieve these effects by activating canonical intracellular molecules or by directly interacting with nuclear chromatin and promoting the transcription of pro-fibrotic genes. The goal of this review is to highlight canonical and non-canonical mechanisms whereby DDRs contribute to kidney injury/fibrosis. This review will summarize key findings obtained using cells and mice lacking DDRs and it will discuss the discovery and development of targeted DDR small molecule- and antisense-based inhibitors. Understanding the molecular mechanisms whereby DDRs control kidney injury and fibrosis might enable us to not only develop more selective and potent inhibitors, but to also determine when DDR inhibition needs to be achieved to prevent and/or halt the development of kidney fibrosis.
Sagacious confucius’ pillow elixir ameliorates Dgalactose induced cognitive injury in mice via estrogenic effects and synaptic plasticity
Authors: Zhao De-Ping , Lei Xia , Wang Yue-Ying , Xue Ao , Zhao Chen-Yu , Xu Yan-Ming , Zhang Yue , Liu Guo-Liang , Geng Fang , Xu Hong-Dan , Zhang Ning
Published: September 2022

Alzheimer’s disease (AD) is a growing concern in modern society, and there is currently a lack of effective therapeutic drugs. Sagacious Confucius’ Pillow Elixir (SCPE) has been studied for the treatment of neurodegenerative diseases such as AD. This study aimed to reveal the key components and mechanisms of SCPE’s anti-AD effect by combining Ultra-high Performance Liquid Chromatography-electrostatic field Orbitrap combined high-resolution Mass Spectrometry (UPLC-LTQ/Orbitrap-MS) with a network pharmacology approach. And the mechanism was verified byin vivoexperiments. Based on UPLC-LTQ/Orbitrap-MS technique identified 9 blood components from rat serum containing SCPE, corresponding to 113 anti-AD targets, and 15 of the 113 targets had high connectivity. KEGG pathway enrichment analysis showed that estrogen signaling pathway and synaptic signaling pathway were the most significantly enriched pathways in SCPE anti-AD, which has been proved byin vivoexperiments. SCPE can exert estrogenic effects in the brain by increasing the amount of estrogen in the brain and the expression of ERα receptors. SCPE can enhance the synaptic structure plasticity by promoting the release of brain-derived neurotrophic factor (BDNF) secretion and improving actin polymerization and coordinates cofilin activity. In addition, SCPE also enhances synaptic functional plasticity by increasing the density of postsynaptic densified 95 (PSD95) proteins and the expression of functional receptor AMPA. SCPE is effective for treatment of AD and the mechanism is related to increasing estrogenic effects and improving synaptic plasticity. Our study revealed the synergistic effect of SCPE at the system level and showed that SCPE exhibits anti-AD effects in a multi-component, multi-target and multi-pathway manner. All these provide experimental support for the clinical application and drug development of SCPE in the prevention and treatment of AD.
Active membrane recycling induced morphology changes in vesicles
Authors: Sachin Krishnan T. V. , Sunil Kumar P. B.
Published: September 2022

Membranes of organelles in the intracellular trafficking pathway continuously undergo recycling through fission and fusion processes. The effect of these recycling processes on the large-scale morphology of organelles is not well understood. Using a dynamically triangulated surface model, we developed a membrane morphology simulator that allows for membrane trafficking, and analyzed the steady state shape of vesicles subjected to such active remodeling. We study a two-component vesicle composed of 1) active species which can have nonzero spontaneous curvature and participate in the recycling and 2) inactive species which do not participate in the recycling. We obtain a plethora of steady state morphologies as a function of the activity rate, spontaneous curvature, and the strength of interaction between species. We observe that morphology changes, as a function of rate of activity, are diametrically opposite for the two signs of the spontaneous curvature, but only have a weak effect on its magnitude. The interplay between the in-plane diffusion, the activity rate, and the spontaneous curvature are shown to determine the vesicle morphology at the steady state. It is shown that the spontaneous curvature and activity inhibits the formation of clusters of active species on the surface. We carry out linear stability analysis of a continuum model and show that the spherical shape of a vesicle is indeed unstable when subjected to active membrane recycling above a certain activity rate.
Estimating the stopping power distribution during proton therapy: A proof of concept
Authors: Ferrero Veronica , Werner Julius , Cerello Piergiorgio , Fiorina Elisa , Vignati Anna , Pennazio Francesco , Rafecas Magdalena
Published: September 2022

Objective: We introduce a new treatment verification technique to estimate the primary particle’s stopping power from prompt gamma timing measurements in proton therapy.

Approach: The starting point is the Spatio-temporal Emission Recostruction technique, which provides the time-depth distribution of the emitted prompt photons with a multiple Prompt-Gamma Timing detector setup based on Lanthanum Bromide crystals. A dedicated formalism based on an analytical approximation of the stopping power is developed to obtain the desired information. Its performance is evaluated in a proof of concept configuration via Monte Carlo simulations of monochromatic proton beams impinging on a homogeneous PMMA phantom.

Main Results: Results indicate stopping power estimations as good as 3.8% with respect to NIST values, and range estimations within 0.3 cm (standard deviation), when considering 250 ps FWHM timing resolution.

Significance: The current study shows, for the first time, the feasibility of evaluating the stopping power of primary beams with a technique that can be performed in-vivo, opening up new possibilities in the field of treatment verification and therapy optimization.
Does vitamin D supplementation improve bone health, body composition and physical performance beyond endurance exercise in patients with type 2 diabetes: A secondary analysis of randomized controlled trial
Authors: Sun Xiaomin , Xiao Wenjuan , Li Zhongying , Zhou Sirui , Dong Mengyue , Huang Cong , Ma Yan , Gou Bo
Published: September 2022

This study aimed to assess the effects of a 12-week vitamin D and endurance exercise intervention on bone health, body composition and physical performance among patients with type 2 diabetes. Totally, 61 patients were randomly assigned to vitamin D (VDG), exercise (EG), vitamin D and exercise intervention (VEG), and control (CG) groups. Bone health (bone mineral density, BMD; bone mineral content, BMC), body composition and physical performance were measured before and after the intervention. Dual energy X-ray absorptiometry was used to assess bone health and body composition. There were no additive effects of vitamin D beyond exercise were observed. Vitamin D supplementation had significant effects on maintaining bone health compared with their counterpart Total (BMC, EG + CG: 2,719.9 ± 70.0 vs. 2,670.1 ± 65.6; VDG + VEG: 2,610.9 ± 88.2 vs. 2,605.3 ± 84.8; trunk BMC, 870.2 ± 26.8 vs. 836.3 ± 23.7; 824.8 ± 29.5 vs. 822.1 ± 27.8; spine BMD, 1.15 ± 0.03 vs. 1.11 ± 0.02; 1.09 ± 0.03 vs. 1.09 ± 0.02) were observed. Exercise had a main effect on the reduction of total and trunk BF%. Patients in EG had a decreased BMC, while it was alleviated in VEG after intervention. Although no additive effect of vitamin D supplementation beyond exercise training, the supplementation had a potential effect on the prevention of bone loss induced by exercise only.
Mapping of a novel clubroot disease resistance locus in Brassica napus and related functional identification
Authors: Jiang Xuefei , Su Ying , Wang Maolin
Published: September 2022

Clubroot disease, caused by Plasmodiophora brassicae, is a devastating disease that results in substantial yield loss in Brassicaceae crops worldwide. In this study, we identified a clubroot disease resistance (CR) Brassica napus, “Kc84R,” which was obtained by mutation breeding. Genetic analysis revealed that the CR trait of “Kc84R” was controlled by a single dominant locus. We used the bulked segregant analysis sequencing (BSA-seq) approach, combined with genetic mapping based on single nucleotide polymorphism (SNP) markers to identify CR loci from the F2 population derived from crossing CR “Kc84R” and clubroot susceptible “855S.” The CR locus was mapped to a region between markers BnSNP14198336 and BnSNP14462201 on the A03 chromosome, and this fragment of 267 kb contained 68 annotated candidate genes. Furthermore, we performed the CR relation screening of candidate genes with the model species Arabidopsis. An ERF family transcriptional activator, BnERF034, was identified to be associated with the CR, and the corresponding Arabidopsis homozygous knockout mutants exhibited more pronounced resistance compared with the wild-type Col-0 and the transgenic lines of BnERF034 in response to P. brassicae infection. Additionally, the expression analysis between resistant and susceptible materials indicated that BnERF034 was identified to be the most likely CR candidate for the resistance in Kc84R. To conclude, this study reveals a novel gene responsible for CR. Further analysis of BnERF034 may reveal the molecular mechanisms underlying the CR of plants and provide a theoretical basis for Brassicaceae resistance breeding.
Integrated analyses of transcriptome and metabolome provides new insights into the primary and secondary metabolism in response to nitrogen deficiency and soil compaction stress in peanut roots
Authors: Yang Liyu , Wu Qi , Liang Haiyan , Yin Liang , Shen Pu
Published: September 2022

Peanut (Arachis hypogaea L.) is an important oil crop globally because of its high edible and economic value. However, its yield and quality are often restricted by certain soil factors, especially nitrogen (N) deficiency, and soil compaction. To explore the molecular mechanisms and metabolic basis behind the peanut response to N deficiency and soil compaction stresses, transcriptome and metabolome analyses of peanut root were carried out. The results showed that N deficiency and soil compaction stresses clearly impaired the growth and development of peanut's aboveground and underground parts, as well as its root nodulation. A total of 18645 differentially expressed genes (DEGs) and 875 known differentially accumulated metabolites (DAMs) were identified in peanut root under differing soil compaction and N conditions. The transcriptome analysis revealed that DEGs related to N deficiency were mainly enriched in “amino acid metabolism”, “starch and sucrose metabolism”, and “TCA cycle” pathways, while DEGs related to soil compaction were mainly enriched in “oxidoreductase activity”, “lipids metabolism”, and “isoflavonoid biosynthesis” pathways. The metabolome analysis also showed significant differences in the accumulation of metabolisms in these pathways under different stress conditions. Then the involvement of genes and metabolites in pathways of “amino acid metabolism”, “TCA cycle”, “lipids metabolism”, and “isoflavonoid biosynthesis” under different soil compaction and N deficiency stresses were well discussed. This integrated transcriptome and metabolome analysis study enhances our mechanistic knowledge of how peanut plants respond to N deficiency and soil compaction stresses. Moreover, it provides new leads to further investigate candidate functional genes and metabolic pathways for use in improving the adaptability of peanut to abiotic stress and accelerating its breeding process of new stress-resistant varieties.
A novel function of the key nitrogen-fixation activator NifA in beta-rhizobia: Repression of bacterial auxin synthesis during symbiosis
Authors: Bellés-Sancho Paula , Liu Yilei , Heiniger Benjamin , von Salis Elia , Eberl Leo , Ahrens Christian H. , Zamboni Nicola , Bailly Aurélien , Pessi Gabriella
Published: September 2022

Rhizobia fix nitrogen within root nodules of host plants where nitrogenase expression is strictly controlled by its key regulator NifA. We recently discovered that in nodules infected by the beta-rhizobial strain Paraburkholderia phymatum STM815, NifA controls expression of two bacterial auxin synthesis genes. Both the iaaM and iaaH transcripts, as well as the metabolites indole-acetamide (IAM) and indole-3-acetic acid (IAA) showed increased abundance in nodules occupied by a nifA mutant compared to wild-type nodules. Here, we document the structural changes that a P. phymatum nifA mutant induces in common bean (Phaseolus vulgaris) nodules, eventually leading to hypernodulation. To investigate the role of the P. phymatum iaaMH genes during symbiosis, we monitored their expression in presence and absence of NifA over different stages of the symbiosis. The iaaMH genes were found to be under negative control of NifA in all symbiotic stages. While a P. phymatum iaaMH mutant produced the same number of nodules and nitrogenase activity as the wild-type strain, the nifA mutant produced more nodules than the wild-type that clustered into regularly-patterned root zones. Mutation of the iaaMH genes in a nifA mutant background reduced the presence of these nodule clusters on the root. We further show that the P. phymatum iaaMH genes are located in a region of the symbiotic plasmid with a significantly lower GC content and exhibit high similarity to two genes of the IAM pathway often used by bacterial phytopathogens to deploy IAA as a virulence factor. Overall, our data suggest that the increased abundance of rhizobial auxin in the non-fixing nifA mutant strain enables greater root infection rates and a role for bacterial auxin production in the control of early stage symbiotic interactions.
Exploring English for medical purposes (EMP) teacher cognition in the Chinese context
Authors: Cao Zhongkai , Zhang Zaihong , Liu Ya , Pu Liping
Published: September 2022

It has been a growing trend in Chinese universities to shift from English for general purposes (EGP) to English for specific purposes (ESP) teaching. Against this background, large groups of teachers previously engaged in teaching EGP have become or are becoming ESP teachers, which means a complex process of learning for subject-specific information, transforming teaching practices and constructing new identities. Despite this, very little has been written about the ESP teacher cognition (TC) of language teaching or the factors influencing this shift in teaching. This study involved English for Medical Purposes (EMP) teachers in Chinese universities as participants, and a scale of EMP TC with 31 items was developed on the basis of questionnaire results. Data from exploratory factor analysis revealed six dimensions of the scale, namely, teacher attitude, teacher belief, teacher learning, teacher support, role identification, and teacher practice—that combine to constitute and influence EMP TC. While the identity factor has attracted wide attention in ESP teacher research, other factors have largely been neglected. Thus, this research highlights the importance of more factors in shaping and changing the language teaching cognition of EMP or ESP teachers in large, especially the teacher belief factor. In addition, results of independent samplest-tests indicated significant difference in EMP teacher learning in terms of gender, differences in EMP teacher attitude and teacher support in terms of EMP teaching experience. Suggestions for enhancing EMP TC are offered on the basis of the conclusions of this research.