bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of an Atraumatic Uterine Cervical Traction Device: A Pilot Study
Authors: Legardeur Hélène , Masiello-Fonjallaz Gessica , Jacot-Guillarmod Martine , Mathevet Patrice
Published: December 2021

Introduction: Alignment of the uterine cervix with the vaginal canal is often required during insertion of an intrauterine contraceptive device (IUD). Currently available instruments are traumatic tenacula, which can cause pain and bleeding and represent an obstacle for certain patients to pursue their medical follow-up. A novel investigational cervical vacuum tenaculum, enables atraumatic traction of the cervix using a semi-circular suction pad, designed to conform to the anatomical shape of the external cervical os. Suction is generated by manually pulling out a sliding tube in a vacuum chamber.

Methods: We performed a single arm non-comparative pilot study to assess the safety and efficacy of the cervical vacuum tenaculum in 13 women receiving an IUD. Data on procedural efficacy, safety, patient-reported pain scores at specific time points during IUD insertion procedure and patient satisfaction were collected prospectively.

Results: Insertion of IUD was successful with use of the study device in 7 of the 13 enrolled patients (54%). No bleeding or only limited ecchymosis were caused by the device. No adverse events were reported. Participants reported very little pain (mean Visual Analog Scale <10) when applying the device. Participants who achieved IUD insertion with the device reported strong overall satisfaction with the procedure.

Conclusions: The suction-based atraumatic tenaculum can be used to manipulate the cervix during IUD insertion with satisfactory efficacy and safety. The results of this pilot study support further studies of this device in larger populations comparing with standard single-tooth tenaculum.

Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT 04441333.
Ameliorating Metabolic Profiles After Kidney Transplantation: A Protocol for an Open-Label, Prospective, Randomized, 3-Arm, Controlled Trial
Authors: Yin Saifu , Ma Ming , Huang Zhongli , Fan Yu , Wang Xianding , Song Turun , Lin Tao
Published: December 2021

Aim: High prevalence of metabolic disorders causes higher risk of cardiovascular diseases after kidney transplantation (KT), which remains the main burden impairing short-term and long-term survival. This open-label, prospective, randomized, 3-arm, controlled trial will evaluate the safety, tolerability and efficacy of metformin and empagliflozin in ameliorating metabolic profiles after KT.

Methods: After a screening assessment, eligible patients with an estimated glomerular filtration rate (eGFR) >45 mL/min/1.73m2 are randomly assigned to standard triple immunosuppression alone, standard immunosuppression plus metformin (500 mg twice daily), standard immunosuppression plus empagliflozin (25 mg once daily) from discharge. The primary endpoint is the differences in the visceral-to-subcutaneous fat area ratio over 12 months, evaluated by magnetic resonance imaging (MRI). Secondary outcomes include kidney graft function, glycometabolism, lipid metabolism, and inflammatory parameters. The trial will enroll 105 kidney transplant recipients, providing 90% power to detect the difference at 5% significance.
Relationship Between Patient Sex and Serum Tumor Necrosis Factor Antagonist Drug and Anti-drug Antibody Concentrations in Inflammatory Bowel Disease; A Nationwide Cohort Study
Authors: Shehab Mohammad , Alasfour Hajer , Abdullah Israa , Alhendi Ghadeer , Alhadab Anwar , Alfadhli Ahmad , Ziyab Ali H. , Battat Robert
Published: December 2021

Background: Anti-drug antibodies to infliximab (ATI) and adalimumab (ATA) are associated with loss of response to tumor necrosis factor antagonist (anti-TNF) therapy in inflammatory bowel disease (IBD). We evaluated the relationship between patient sex and serum TNF antagonist drug and antibody concentrations in inflammatory bowel disease.

Methods: A nationwide multicenter retrospective cohort study was conducted by evaluating patients' charts from July 2018 until September 2021. The effect of patient sex on anti-drug antibodies and serum drug concentration in patients with IBD across seven hospitals was investigated. A subgroup analysis also investigated the effect of anti-TNF combination therapy. Geometric means were calculated, and multiple linear regression was used to estimate the adjusted ratio of geometric means (RoGM) and their 95% confidence intervals (CI).

Results: In the total study sample (n = 1093), males receiving infliximab had higher anti-drug antibody concentrations (38.3 vs. 22.3 AU/ml; aRoGM = 1.72, 95% CI: 1.30–2.27, p < 0.001) compared to females. Additionally, infliximab serum drug concentrations among males were lower compared to females (2.6 vs. 4.1 ug/ml; aRoGM = 0.62, 95% CI: 0.44–0.88, p = 0.007). In the subgroup analysis (n = 359), male compared to female patients on combination therapy with infliximab and immunomodulators had similar anti-drug antibody concentrations (30.2 vs. 21.9 AU/ml; aRoGM = 1.38, 95% CI: 0.79–2.40, p = 0.254). There was no difference in the anti-drug antibody and serum drug concentrations among males and females on adalimumab.

Conclusion: In patients receiving infliximab, anti-drug antibodies were higher in males than females. Consistent with this, serum drug concentrations were lower in males than females on infliximab. There was no difference in anti-drug antibody and serum drug concentrations among males and females on adalimumab. In addition, no difference in anti-drug antibodies between males and females receiving anti-TNF combination therapy was observed.
Characterization of Carbapenem-Resistant Enterobacteriaceae Cultured From Retail Meat Products, Patients, and Porcine Excrement in China
Authors: Feng Jie , Xiang Qian , Ma Jiangang , Zhang Pei , Li Kun , Wu Ke , Su Mengru , Li Ruichao , Hurley Daniel , Bai Li , Wang Juan , Yang Zengqi
Published: December 2021

The emergence and dissemination of carbapenem-resistant Enterobacteriaceae (CRE) is a growing concern to animal and public health. However, little is known about the spread of CRE in food and livestock and its potential transmission to humans. To identify CRE strains from different origins and sources, 53 isolates were cultured from 760 samples including retail meat products, patients, and porcine excrement. Antimicrobial susceptibility testing was carried out, followed by phylogenetic typing, whole-genome sequencing, broth mating assays, and plasmids analyses. Forty-three Escherichia coli, nine Klebsiella pneumoniae, and one Enterobacter cloacae isolates were identified, each exhibiting multidrug-resistant phenotypes. Genetically, the main sequence types (STs) of E. coli were ST156 (n = 7), ST354 (n = 7), and ST48 (n = 7), and the dominant ST of K. pneumoniae is ST11 (n = 5). blaNDM–5 (n = 40) of E. coli and blaKPC–2 (n = 5) were the key genes that conferred carbapenem resistance phenotypes in these CRE strains. Additionally, the mcr-1 gene was identified in 17 blaNDM-producing isolates. The blaNDM–5 gene from eight strains could be transferred to the recipients via conjugation assays. Two mcr-1 genes in the E. coli isolates could be co-transferred along with the blaNDM–5 genes. IncF and IncX3 plasmids have been found to be predominantly associated with blaNDM gene in these strains. Strains isolated in our study from different sources and regions tend to be concordant and overlap. CRE strains from retail meat products are a reservoir for transition of CRE strains between animals and humans. These data also provide evidence of the dissemination of CRE strains and carbapenem-resistant genes between animal and human sources.
Gut-Lung Crosstalk in Sepsis-Induced Acute Lung Injury
Authors: Zhou Xin , Liao Youxia
Published: December 2021

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common acute and severe cases of the respiratory system with complicated pathogenesis and high mortality. Sepsis is the leading indirect cause of ALI/ARDS in the intensive care unit (ICU). The pathogenesis of septic ALI/ARDS is complex and multifactorial. In the development of sepsis, the disruption of the intestinal barrier function, the alteration of gut microbiota, and the translocation of the intestinal microbiome can lead to systemic and local inflammatory responses, which further alter the immune homeostasis in the systemic environment. Disruption of homeostasis may promote and propagate septic ALI/ARDS. In turn, when ALI occurs, elevated levels of inflammatory cytokines and the shift of the lung microbiome may lead to the dysregulation of the intestinal microbiome and the disruption of the intestinal mucosal barrier. Thus, the interaction between the lung and the gut can initiate and potentiate sepsis-induced ALI/ARDS. The gut–lung crosstalk may be a promising potential target for intervention. This article reviews the underlying mechanism of gut-lung crosstalk in septic ALI/ARDS.
Phylogenomic Reappraisal of Fatty Acid Biosynthesis, Mycolic Acid Biosynthesis and Clinical Relevance Among Members of the Genus Corynebacterium
Authors: Dover Lynn G. , Thompson Amy R. , Sutcliffe Iain C. , Sangal Vartul
Published: December 2021

The genus Corynebacterium encompasses many species of biotechnological, medical or veterinary significance. An important characteristic of this genus is the presence of mycolic acids in their cell envelopes, which form the basis of a protective outer membrane (mycomembrane). Mycolic acids in the cell envelope of Mycobacterium tuberculosis have been associated with virulence. In this study, we have analysed the genomes of 140 corynebacterial strains, including representatives of 126 different species. More than 50% of these strains were isolated from clinical material from humans or animals, highlighting the true scale of pathogenic potential within the genus. Phylogenomically, these species are very diverse and have been organised into 19 groups and 30 singleton strains. We find that a substantial number of corynebacteria lack FAS-I, i.e., have no capability for de novo fatty acid biosynthesis and must obtain fatty acids from their habitat; this appears to explain the well-known lipophilic phenotype of some species. In most species, key genes associated with the condensation and maturation of mycolic acids are present, consistent with the reports of mycolic acids in their species descriptions. Conversely, species reported to lack mycolic acids lacked these key genes. Interestingly, Corynebacterium ciconiae, which is reported to lack mycolic acids, appears to possess all genes required for mycolic acid biosynthesis. We suggest that although a mycolic acid-based mycomembrane is widely considered to be the target for interventions by the immune system and chemotherapeutics, the structure is not essential in corynebacteria and is not a prerequisite for pathogenicity or colonisation of animal hosts.
HomeCoRe for Telerehabilitation in Mild or Major Neurocognitive Disorders: A Study Protocol for a Randomized Controlled Trial
Authors: Bernini Sara , Panzarasa Silvia , Sinforiani Elena , Quaglini Silvana , Cappa Stefano F. , Cerami Chiara , Tassorelli Cristina , Vecchi Tomaso , Bottiroli Sara
Published: December 2021

Background: Given the limited effectiveness of pharmacological treatments for cognitive decline, non-pharmacological interventions have gained increasing attention. Evidence exists on the effectiveness of cognitive rehabilitation in preventing elderly subjects at risk of cognitive decline and in reducing the progression of functional disability in cognitively impaired individuals. In recent years, telerehabilitation has enabled a broader application of cognitive rehabilitation programs. The purpose of this study is to test a computer-based intervention administered according to two different modalities (at the hospital and at home) using the tools CoRe and HomeCoRe, respectively, in participants with Mild or Major Neurocognitive Disorders.

Methods: Non-inferiority, single-blind randomized controlled trial where 40 participants with Mild or Major Neurocognitive Disorders will be assigned to the intervention group who will receive cognitive telerehabilitation through HomeCoRe or to the control group who will receive in-person cognitive intervention through CoRe, with the therapist administering the same computer-based exercises. The rehabilitative program will last 6 weeks, with 3 sessions/week, each lasting ~45 min. All the participants will be evaluated on an exhaustive neuropsychological battery before (T0) and after (T1) the intervention; follow-up visits will be scheduled after 6 (T2) and 12 months (T3).

Discussion: The results of this study will inform about the comparability (non-inferiority trial) of HomeCoRe with CoRe. Their equivalence would support the use of HomeCoRe for at distance treatment, favoring the continuity of care.

Ethics and Dissemination: This study has been approved by the Local Ethics Committee and registered in https://clinicaltrials.gov (NCT04889560). The dissemination plan includes the scientific community through publication in open-access peer-reviewed scientific journals and presentations at national and international conferences.

Trial Registration:Clinicaltrials.govhttps://clinicaltrials.gov/ct2/show/NCT04889560 (registration date: May 17, 2021).
TReC: Transferred ResNet and CBAM for Detecting Brain Diseases
Authors: Xiao Yuteng , Yin Hongsheng , Wang Shui-Hua , Zhang Yu-Dong
Published: December 2021

Early diagnosis of pathological brains leads to early interventions in brain diseases, which may help control the illness conditions, prolong the life of patients, and even cure them. Therefore, the classification of brain diseases is a challenging but helpful task. However, it is hard to collect brain images, and the superabundance of images is also a great challenge for computing resources. This study proposes a new approach named TReC: Transferred Residual Networks (ResNet)-Convolutional Block Attention Module (CBAM), a specific model for small-scale samples, to detect brain diseases based on MRI. At first, the ResNet model, which is pre-trained on the ImageNet dataset, serves as initialization. Subsequently, a simple attention mechanism named CBAM is introduced and added into every ResNet residual block. At the same time, the fully connected (FC) layers of the ResNet are replaced with new FC layers, which meet the goal of classification. Finally, all the parameters of our model, such as the ResNet, the CBAM, and new FC layers, are retrained. The effectiveness of the proposed model is evaluated on brain magnetic resonance (MR) datasets for multi-class and two-class tasks. Compared with other state-of-the-art models, our model reaches the best performance for two-class and multi-class tasks on brain diseases.
Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer’s Disease Model Mice
Authors: Takasu Keiko , Niidome Kazuki , Hasegawa Minoru , Ogawa Koichi
Published: December 2021

The hippocampal gamma oscillation is important for cognitive function, and its deficit is related to cognitive impairment in Alzheimer’s disease (AD). Recently, it has been recognized that post-translational modification via histone acetylation is a fundamental molecular mechanism for regulating synaptic plasticity and cognitive function. However, little is known regarding the regulation of hippocampal gamma oscillation by histone acetylation. We investigated whether histone acetylation regulated kainate-induced gamma oscillations and their important regulator, fast-spiking interneurons, using acute hippocampal slices of AD model mice (PSAPP transgenic mice). We found a decrease in kainate-induced gamma oscillations in slices from PSAPP mice, accompanied with the increased activity of fast spiking interneurons in basal state and the decreased activity in activated state. The histone deacetylase (HDAC) inhibitor (SAHA, named vorinostat) restored deficits of gamma oscillation in PSAPP mice, accompanied with rescue of activity of fast spiking interneurons in basal and activated state. The effect of SAHA was different from that of the clinical AD drug donepezil, which rescued only function of fast spiking interneurons in basal state. Besides, activator of nuclear receptor family 4a (NR4a) receptor (cytosporone B), as one of the epigenetic modification related to HDAC inhibition, rescued the deficits in gamma oscillations in PSAPP mice. These results suggested a novel mechanism in which HDAC inhibition improved impairment of gamma oscillations in PSAPP mice by restoring the activity of fast spiking interneurons both in basal and activated state. The reversal of gamma oscillation deficits by HDAC inhibition and/or NR4a activation appears to be a potential therapeutic target for treating cognitive impairment in AD patients.
Situational Understanding in the Human and the Machine
Authors: Yufik Yan , Malhotra Raj
Published: December 2021

The Air Force research programs envision developing AI technologies that will ensure battlespace dominance, by radical increases in the speed of battlespace understanding and decision-making. In the last half century, advances in AI have been concentrated in the area of machine learning. Recent experimental findings and insights in systems neuroscience, the biophysics of cognition, and other disciplines provide converging results that set the stage for technologies of machine understanding and machine-augmented Situational Understanding. This paper will review some of the key ideas and results in the literature, and outline new suggestions. We define situational understanding and the distinctions between understanding and awareness, consider examples of how understanding—or lack of it—manifest in performance, and review hypotheses concerning the underlying neuronal mechanisms. Suggestions for further R&D are motivated by these hypotheses and are centered on the notions of Active Inference and Virtual Associative Networks.
Acrylamide Contents of Local Snacks in Singapore
Authors: Yeo Michelle Ting Yun , Bi Xinyan , Henry Christiani Jeyakumar
Published: December 2021

Acrylamide is a carcinogen that forms in foods processed at high temperatures. In this study, acrylamide contents of 30 local snacks commonly consumed by the three ethnic groups (Malay, Chinese, and Indian) in Singapore were analysed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). These snacks were chosen because they were consumed regularly by people of different classes and age groups in Singapore. Our results showed that the average content of acrylamide in Indian snacks (102.23 ng/g) was higher than those in Malay (75.14 ng/g) and Chinese snacks (70.78 ng/g). The high acrylamide levels in several snacks was probably due to the processing methods and the usage of acrylamide-inducing raw materials. Same snacks prepared by different manufacturers contained different levels of acrylamide, suggesting the possibility of acrylamide reduction in these snacks. This study provides an insight into the acrylamide levels of snacks commonly consumed by the three different ethnic groups in Singapore.
Boosting Vaccine-Elicited Respiratory Mucosal and Systemic COVID-19 Immunity in Mice With the Oral Lactobacillus plantarum
Authors: Xu Jianqing , Ren Zhihong , Cao Kangli , Li Xianping , Yang Jing , Luo Xuelian , Zhu Lingyan , Wang Xiangwei , Ding Longfei , Liang Junrong , Jin Dong , Yuan Tingting , Li Lianfeng , Xu Jianguo
Published: December 2021

Boosting and prolonging SARS-CoV-2 vaccine-elicited immunity is paramount for containing the COVID-19 pandemic, which wanes substantially within months after vaccination. Here we demonstrate that the unique strain of probiotic Lactobacillus plantarum GUANKE (LPG) could promote SARS-CoV-2-specific immune responses in both effective and memory phases through enhancing interferon signaling and suppressing apoptotic and inflammatory pathways. Interestingly, oral LPG administration promoted SARS-CoV-2 neutralization antibodies even 6 months after immunization. Furthermore, when LPG was given immediately after SARS-CoV-2 vaccine inoculation, specific neutralization antibodies could be boosted >8-fold in bronchoalveolar lavage (BAL) and >2-fold in sera, T-cell responses were persistent and stable for a prolonged period both in BAL and the spleen. Transcriptional analyses showed that oral application of LPG mobilized immune responses in the mucosal and systemic compartments; in particular, gut-spleen and gut-lung immune axes were observed. These results suggest that LPG could be applied in combination with SARS-CoV-2 vaccines to boost and prolong both the effective and memory immune responses in mucosal and systemic compartments, thereby improving the efficacy of SARS-CoV-2 vaccination.
Case Report: A Case of Sintilimab-Induced Cystitis/Ureteritis and Review of Sintilimab-Related Adverse Events
Authors: Tu Lingfang , Ye Yuan , Tang Xiaoping , Liang Zhen , You Qihan , Zhou Jianying , Pan Zhijie
Published: December 2021

Immune checkpoint inhibitors (ICIs) have been proven to be beneficial in multiple advanced malignancies. However, the widespread use of ICIs also occurred with various immune-related adverse events (irAEs). Here, we first report a case of sintilimab-related cystitis/ureteritis. A 53-year-old man with driver gene-negative pulmonary adenocarcinoma (cT1cN3M1c, Stage IVB) was being treated with sintilimab in combination of paclitaxel-albumin and bevacizumab as second-line treatment. He was hospitalized for haematuria, pollakiuria, painful micturition and low back pain after three courses. Urinalysis showed red blood cells (RBCs) and white blood cells (WBCs) were obviously increased, and serum creatinine (sCr) level was also significantly elevated. Urine culture and cytology were both negative, and cystoscopy revealed diffused redness of bladder mucosa. Urinary ultrasonography showed mild hydronephrosis and dilated ureter. The patient was diagnosed as immunotherapy-related cystitis/ureteritis after a multidisciplinary team (MDT) meeting. Once the diagnosis was made, corticosteroid therapy was given, which rapidly resolved the patient’s symptoms and signs. Computer tomography angiography (CTA) and CT urography (CTU) was conducted after sCr level was back to normal and demonstrated ureter dilation and hydroureter. Once symptoms relieved, bladder biopsy was performed and confirmed the bladder inflammation. The patient was subsequently switched to maintenance dose of methylprednisolone and tapered gradually. Since sintilimab has been used in advanced malignancies, we first reported a rare case of sintilimab-induced cystitis/ureteritis and summarized sintilimab-related adverse events to improve the assessment and management of irAEs.
Trends in Development of Novel Machine Learning Methods for the Identification of Gliomas in Datasets That Include Non-Glioma Images: A Systematic Review
Authors: Subramanian Harry , Dey Rahul , Brim Waverly Rose , Tillmanns Niklas , Cassinelli Petersen Gabriel , Brackett Alexandria , Mahajan Amit , Johnson Michele , Malhotra Ajay , Aboian Mariam
Published: December 2021

Purpose

Machine learning has been applied to the diagnostic imaging of gliomas to augment classification, prognostication, segmentation, and treatment planning. A systematic literature review was performed to identify how machine learning has been applied to identify gliomas in datasets which include non-glioma images thereby simulating normal clinical practice.

Materials and Methods

Four databases were searched by a medical librarian and confirmed by a second librarian for all articles published prior to February 1, 2021: Ovid Embase, Ovid MEDLINE, Cochrane trials (CENTRAL), and Web of Science-Core Collection. The search strategy included both keywords and controlled vocabulary combining the terms for: artificial intelligence, machine learning, deep learning, radiomics, magnetic resonance imaging, glioma, as well as related terms. The review was conducted in stepwise fashion with abstract screening, full text screening, and data extraction. Quality of reporting was assessed using TRIPOD criteria.

Results

A total of 11,727 candidate articles were identified, of which 12 articles were included in the final analysis. Studies investigated the differentiation of normal from abnormal images in datasets which include gliomas (7 articles) and the differentiation of glioma images from non-glioma or normal images (5 articles). Single institution datasets were most common (5 articles) followed by BRATS (3 articles). The median sample size was 280 patients. Algorithm testing strategies consisted of five-fold cross validation (5 articles), and the use of exclusive sets of images within the same dataset for training and for testing (7 articles). Neural networks were the most common type of algorithm (10 articles). The accuracy of algorithms ranged from 0.75 to 1.00 (median 0.96, 10 articles). Quality of reporting assessment utilizing TRIPOD criteria yielded a mean individual TRIPOD ratio of 0.50 (standard deviation 0.14, range 0.37 to 0.85).

Conclusion

Systematic review investigating the identification of gliomas in datasets which include non-glioma images demonstrated multiple limitations hindering the application of these algorithms to clinical practice. These included limited datasets, a lack of generalizable algorithm training and testing strategies, and poor quality of reporting. The development of more robust and heterogeneous datasets is needed for algorithm development. Future studies would benefit from using external datasets for algorithm testing as well as placing increased attention on quality of reporting standards.

Systematic Review Registration

www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020209938, International Prospective Register of Systematic Reviews (PROSPERO 2020 CRD42020209938).
Surgical Management of Non-Metastatic Pancreatic Cancer in the United Kingdom: Results of a Nationwide Survey on Current Practice
Authors: Gemenetzis Georgios , McKay Siobhan , Pathak Samir , Moir John , Laing Richard , Jamieson Nigel B. , Young Alastair L. , Chatzizacharias Nikolaos A. , Giovinazzo Francesco , Roberts Keith J.
Published: December 2021

Background

It is presently unclear what clinical pathways are followed for patients with non-metastatic PDAC in specialised centres for pancreatic surgery across the United Kingdom (UK).

Methods

Between August 2019 and August 2020 an electronic survey was conducted aiming at a national cohort of pancreatic surgeons in the UK. Participants replied to a list of standardised questions and clinical vignettes, and data were collected and analysed focusing on management preferences, resectability criteria, and contraindications to surgery.

Results

Within the study period, 65 pancreatic surgeons from 27 specialist centres in the UK (96%) completed the survey. Multidisciplinary team meetings are utilised universally for the management of patients with PDAC, however, different staging systems for resectability classification are being applied. In borderline resectable PDAC, most surgeons were keen to proceed with surgical exploration post NAT, but differences were noted in preferred chemotherapy regimens. Surgeons from standard volume institutions performed fewer vein resections annually and were more likely to deem patients with locally advanced PDAC as unresectable. Intra-institutional variability in patient management was also present and ranging between 20-80%.

Conclusions

Significant variability in the surgical management of non-metastatic PDAC was identified both on inter- and intra-institutional level.
The Role of Proteasome Inhibitors in Treating Acute Lymphoblastic Leukaemia
Authors: Sin Chun-fung , Man Pui-hei Marcus
Published: December 2021

Acute lymphoblastic leukaemia (ALL) is an aggressive haematolymphoid malignancy. The prognosis of ALL is excellent in paediatric population, however the outcome of relapse/refractory disease is dismal. Adult ALL has less favourable prognosis and relapse/refractory disease is not uncommonly encountered. Bortezomib is the first generation proteasome inhibitor licensed to treat plasma cell myeloma and mantle cell lymphoma with favourable side effect profile. Efficacy of bortezomib had been proven in other solid tumors. Clinical studies showed promising response for proteasome inhibitors in treating relapse/refractory ALL. Thus, proteasome inhibitors are attractive alternative agents for research in treating ALL. In the review article, we will introduce different proteasome inhibitors and their difference in pharmacological properties. Moreover, the mechanism of action of proteasome inhibitors on ALL will be highlighted. Finally, results of various clinical studies on proteasome inhibitors in both paediatric and adult ALL will be discussed. This review article provides the insights on the use of proteasome inhibitors in treating ALL with a summary of mechanism of action in ALL which facilitates future research on its use to improve the outcome of ALL.
The Chest Radiographic Thoracic Area Can Serve as a Prediction Marker for Morbidity and Mortality in Infants With Congenital Diaphragmatic Hernia
Authors: Weis Meike , Burhany Sosan , Perez Ortiz Alba , Nowak Oliver , Hetjens Svetlana , Zahn Katrin , Schoenberg Stefan , Schaible Thomas , Rafat Neysan
Published: December 2021

Objective: Valid postnatal prediction parameters for neonates with congenital diaphragmatic hernia (CDH) are lacking, but recently, the chest radiographic thoracic area (CRTA) was proposed to predict survival with high sensitivity. Here, we evaluated whether the CRTA correlated with morbidity and mortality in neonates with CDH and was able to predict these with higher sensitivity and specificity than prenatal observed-to-expected (O/E) lung-to-head ratio (LHR).

Methods: In this retrospective cohort study, all neonates with CDH admitted to our institution between 2013 and 2019 were included. The CRTA was measured using the software Horos (V. 3.3.5) and compared with O/E LHR diagnosed by fetal ultrasonography in relation to outcome parameters including survival, extracorporeal membrane oxygenation (ECMO) support, and chronic lung disease (CLD).

Results: In this study 255 neonates were included with a survival to discharge of 84%, ECMO support in 46%, and 56% developing a CLD. Multiple regression analysis demonstrated that the CRTA correlates significantly with survival (p = 0.001), ECMO support (p < 0.0001), and development of CLD (p = 0.0193). The CRTA displayed a higher prognostic validity for survival [area under the curve (AUC) = 0.822], ECMO support (AUC = 0.802), and developing a CLD (AUC = 0.855) compared with the O/E LHR.

Conclusions: Our data suggest that the postnatal CRTA might be a better prognostic parameter for morbidity and mortality than the prenatal O/E LHR.
Host Factor Interaction Networks Identified by Integrative Bioinformatics Analysis Reveals Therapeutic Implications in COPD Patients With COVID-19
Authors: Zheng Wenjiang , Wang Ting , Wu Peng , Yan Qian , Liu Chengxin , Wu Hui , Zhan Shaofeng , Liu Xiaohong , Jiang Yong , Zhuang Hongfa
Published: December 2021

Background: The COVID-19 pandemic poses an imminent threat to humanity, especially for those who have comorbidities. Evidence of COVID-19 and COPD comorbidities is accumulating. However, data revealing the molecular mechanism of COVID-19 and COPD comorbid diseases is limited.

Methods: We got COVID-19/COPD -related genes from different databases by restricted screening conditions (top500), respectively, and then supplemented with COVID-19/COPD-associated genes (FDR<0.05, |LogFC|≥1) from clinical sample data sets. By taking the intersection, 42 co-morbid host factors for COVID-19 and COPD were finally obtained. On the basis of shared host factors, we conducted a series of bioinformatics analysis, including protein-protein interaction analysis, gene ontology and pathway enrichment analysis, transcription factor-gene interaction network analysis, gene-microRNA co-regulatory network analysis, tissue-specific enrichment analysis and candidate drug prediction.

Results: We revealed the comorbidity mechanism of COVID-19 and COPD from the perspective of host factor interaction, obtained the top ten gene and 3 modules with different biological functions. Furthermore, we have obtained the signaling pathways and concluded that dexamethasone, estradiol, progesterone, and nitric oxide shows effective interventions.

Conclusion: This study revealed host factor interaction networks for COVID-19 and COPD, which could confirm the potential drugs for treating the comorbidity, ultimately, enhancing the management of the respiratory disease.
Thermal Strain During Open-Water Swimming Competition in Warm Water Environments
Authors: Chalmers Samuel , Shaw Gregory , Mujika Iñigo , Jay Ollie
Published: December 2021

Open-water swim racing in warm water is associated with significant physiological strain. However, existing international policy that governs safe participation during competition relies only on a fixed water temperature threshold for event cancellation and has an unclear biophysical rationale. The current policy does not factor other environmental factors or race distance, nor provide a stratification of risk (low, moderate, high, or extreme) prior to the threshold for cancellation. Therefore, the primary aim of this Perspectives article is to highlight considerations for the development of modernized warm-water competition policies. We highlight current accounts (or lack thereof) of thermal strain, cooling interventions, and performance in warm-water swimming and opportunities for advancement of knowledge. Further work is needed that systematically evaluate real-world thermal strain and performance during warm water competition (alongside reports of environmental conditions), novel preparatory strategies, and in-race cooling strategies. This could ultimately form a basis for future development of modernized policies for athlete cohorts that stratifies risk and mitigation strategies according to important environmental factors and race-specific factors (distance).
Prospective Study of Serum Uric Acid Levels and First Stroke Events in Chinese Adults With Hypertension
Authors: Hu Feng , Hu Longlong , Yu Rihua , Han Fengyu , Zhou Wei , Wang Tao , Zhu Linjuan , Huang Xiao , Bao Huihui , Cheng Xiaoshu
Published: December 2021

Objectives: We investigated the association between serum uric acid (SUA) levels and the risk of the first stroke in Chinese adults with hypertension.

Methods: A total of 11, 841 hypertensive patients were selected from the Chinese Hypertension Registry for analysis. The relationship between SUA levels and first stroke was determined using multivariable Cox proportional hazards regression, smoothing curve fitting, and Kaplan–Meier survival curve analysis.

Results: During a median follow-up of 614 days, 99 cases of the first stroke were occurred. Cox proportional hazards models indicated that SUA levels were not significantly associated with the first stroke event [adjusted-hazard ratio (HR) per SD increase: 0.98, 95% CI 0.76–1.26, P = 0.889]. In comparison to the group without hyperuricemia (HUA), there were no significantly higher risks of first stroke events (adjusted-HR: 1.22, 95% CI 0.79–1.90, P = 0.373) in the population with HUA. However, in the population less than 60 years old, subjects with HUA had a significantly higher risk of the first stroke than the population without HUA (adjusted-HR: 4.89, 95% CI 1.36–17.63, P = 0.015). In subjects older than 60 years, we did not find a significant relationship between HUA and first stroke (adjusted-HR: 0.97, 95% CI 0.60–1.56, P = 0.886). Survival analysis further confirmed this discrepancy (log-rank P = 0.013 or 0.899 for non-aging or aging group).

Conclusion: No significant evidence in the present study indicated that increased SUA levels were associated with the risk of first stroke in the Chinese adults with hypertension. Age played an interactive role in the relationship between HUA and the first stroke event.
Bioactive Nutrient Fortified Fertilizer: A Novel Hybrid Approach for the Enrichment of Wheat Grains With Zinc
Authors: Ali Muhammad Asif , Naeem Farrukh , Tariq Nadeem , Ahmed Ijaz , Imran Asma
Published: December 2021

Zinc (Zn) is a critical micronutrient that synergizes nutrient use efficiency, and improves plant growth and human health. Low Zn bioavailability in soils affects produce quality and agricultural productivity worldwide ultimately inducing deficiency in humans and animals. Zn deficiency is a leading cause of malnutrition in underdeveloped countries where a widespread population depends upon staple cereals for daily intake of calories. Modern cereal cultivars are inherently low in Zn, eventually, plants need to be enriched with soil application of ZnSO4, but due to higher fixation losses, it becomes an inefficient source. Rhizosphere microbiome contains Zn-solubilizing bacteria (ZSB) that improve Zn bioavailability, thus increase the root function, Zn uptake, and plant growth. Niha Corp developed a hybrid process of bioactive nutrient fortified fertilizer (BNFF), which has been used to formulate Zabardast Urea (ZU) by coating bioactive Zn (BAZ) and ZSB on urea. Data obtained for 15 wheat varieties from 119 farmer field demonstration plots and eight replicated trials on 42 locations across multi-environment conditions conclude that ZU significantly improved the plant biomass and yield by 12% over non-Zn control and produced grains with 57 μg/g Zn contents, which can meet a major part of the recommended dietary allowance (RDA) of humans. The study recommends that this microbe-mediated hybrid invention (ZU) is a feasible approach to boost Zn bioavailability and Zn use efficiency, with enhanced yield and quality that may contribute to improve human health. To the best of our knowledge, this is the first wide-scale field testing of Zn enrichment in the grains of bread wheat using an innovative BNFF Urea Z technology.
Seed Germination and Seedling Growth of Dendrocalumus brandisii in vitro, and the Inhibitory Mechanism of Colchicine
Authors: Lv Zhuo , Zhu Fangwei , Jin Diankun , Wu Yufang , Wang Shuguang
Published: December 2021

Bamboos seldom bloom and almost no seeds could be harvested, and, hence, few works are focused on germination physiology. Systematic research on the physiological effects of colchicine on germination and seedling growth of bamboo seeds is lacking. In this study, we finely recorded seed germination and seedling growth of Dendrocalamus brandisii in media supplemented with different colchicine concentrations. Physiological effects and mechanisms of colchicine were analyzed. The results showed that D. brandisii seeds were non-dormant, and seed lots achieved their highest germination rates on the 4th day and finished the whole germination period after 21 days. Colchicine inhibited seed germination and seedling growth but did not change its germination pattern. Seed germination and seedling growth decreased constantly with colchicine concentration. Colchicine showed more negative effects on seedling growth than on seed germination and root growth. High concentrations of colchicine retarded the development of plumules and even caused their aberrant development. Under tissue culture conditions, seed germination, and seedling growth relied mainly on the endogenous starch and soluble sugar degradation, in which α-amylase, STP, and SUSY played the key role. Colchicine inhibited seed germination and seedling growth by suppressing the α-amylase, STP, and SUSY activities. Colchicine showed more negative effects on sucrose degradation than on starch degradation during seed germination and seedling growth. This study provides new basic information on the seedling physiology for the genetic breeding of bamboo plants.
Personalized Online Learning Resource Recommendation Based on Artificial Intelligence and Educational Psychology
Authors: Wei Xin , Sun Shiyun , Wu Dan , Zhou Liang
Published: December 2021

The objective of the study is to explore an effective way for providing students with the appropriate learning resources in the remote education scenario. Artificial intelligence (AI) technology and educational psychology theory are applied for designing a personalized online learning resource recommendation scheme to improve students' learning outcomes. First, according to educational psychology, students' learning ability can be obtained by analyzing their learning behaviors. Their identities can be classified into three main groups. Then, features of learning resources such as difficulty degree are extracted, and a LinUCB-based learning resource recommendation algorithm is proposed. In this algorithm, a personalized exploration coefficient is carefully constructed according to student's ability and attention scores. It can adaptively adjust the ratio of exploration and exploitation during recommendation. Finally, experiments are conducted for evaluating the superior performance of the proposed scheme. The experimental results show that the proposed recommendation scheme can find appropriate learning resources which will match the student's ability and satisfy the student's personalized demands. Meanwhile, by comparing with existing state-of-the-art recommendation schemes, the proposed scheme can achieve accurate recommendations, so as to provide students with the most suitable online learning resources and reduce the risk brought by exploration. Therefore, the proposed scheme can not only control the difficulty degree of learning resources within the student's ability but also encourage their potential by providing suitable learning resources.
Top Management Team Intrapersonal Functional Diversity and Adaptive Firm Performance: The Moderating Roles of the CEO–TMT Power Gap and Severity of Threat
Authors: Ma Changlong , Ge Yuhui , Wang Jingwei
Published: December 2021

While usually argued to be improving firm performance, the effect of top management team (TMT) functional diversity on firm performance is mixed. Bridging the TMT diversity, team adaptation, and threat-rigidity literature, we present a contingency model in which the relationships between intrapersonal functional diversity (at both CEO and TMT levels) and adaptive firm performance depend on the CEO–TMT power gap and severity of threat. To test our hypotheses, 270 firms, which have been severely affected due to the COVID-19 pandemic, were selected from China's A-share listed companies. Multiple regression analyses have shown that a moderation of CEO intrapersonal functional diversity's effect on adaptive firm performance by the CEO–TMT power gap is moderated by the severity of threat. However, no significant main or interaction effect of TMT intrapersonal functional diversity was found. The findings of this study have implications for the recovery or improvement of firm performance in threat situations.
Likeability and Expert Persuasion: Dislikeability Reduces the Perceived Persuasiveness of Expert Evidence
Authors: Younan Mariam , Martire Kristy A.
Published: December 2021

With the use of expert evidence increasing in civil and criminal trials, there is concern jurors' decisions are affected by factors that are irrelevant to the quality of the expert opinion. Past research suggests that the likeability of an expert significantly affects juror attributions of credibility and merit. However, we know little about the effects of expert likeability when detailed information about expertise is provided. Two studies examined the effect of an expert's likeability on the persuasiveness judgments and sentencing decisions of 456 jury-eligible respondents. Participants viewed and/or read an expert's testimony (lower vs. higher quality) before rating expert persuasiveness (via credibility, value, and weight), and making a sentencing decision in a Capitol murder case (death penalty vs. life in prison). Lower quality evidence was significantly less persuasive than higher quality evidence. Less likeable experts were also significantly less persuasive than either neutral or more likeable experts. This “penalty” for less likeable experts was observed irrespective of evidence quality. However, only perceptions of the foundational validity of the expert's discipline, the expert's trustworthiness and the clarity and conservativeness of the expert opinion significantly predicted sentencing decisions. Thus, the present study demonstrates that while likeability does influence persuasiveness, it does not necessarily affect sentencing outcomes.
The Impact of COVID-19 on Sleep Quality in People Living With Disabilities
Authors: Heinze Nikki , Hussain Syeda F. , Castle Claire L. , Godier-McBard Lauren R. , Kempapidis Theofilos , Ftouni Suzanne , Espie Colin A. , Gomes Renata S. M.
Published: December 2021

Background: Research exploring the impact of the COVID-19 pandemic on sleep in people with disabilities has been scarce. This study provides a preliminary assessment of sleep in people with disabilities, across two timepoints during the pandemic, with a focus on those with visual impairment (VI).

Methods: Two online surveys were conducted between April 2020 and March 2021 to explore sleep quality using the Pittsburgh Sleep Quality Index (PSQI). A convenience sample of 602 participants completed the first survey and 160 completed the follow-up survey.

Results: Across both timepoints, participants with disabilities reported significantly poorer global sleep quality and higher levels of sleep disturbance, use of sleep medication and daytime dysfunction than those with no disabilities. Participants with VI reported significantly higher levels of sleep disturbance and use of sleep medication at both timepoints, poorer global sleep quality, sleep duration and latency at time 1, and daytime dysfunction at time 2, than those with no disabilities. Global sleep quality, sleep duration, sleep efficiency, and self-rated sleep quality deteriorated significantly in participants with no disabilities, but daytime dysfunction increased in all three groups. Disability and state anxiety were significant predictors of sleep quality across both surveys.

Conclusion: While sleep was consistently poorer in people with disabilities such as VI, it appears that the COVID-19 pandemic has had a greater impact on sleep in people with no disabilities. State anxiety and, to a lesser extent, disability, were significant predictors of sleep across both surveys, suggesting the need to address anxiety in interventions targeted toward improving sleep.