bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of deep learning artificial intelligence technique to the classification of clinical orthodontic photos
Authors: Ryu Jiho , Lee Yoo-Sun , Mo Seong-Pil , Lim Keunoh , Jung Seok-Ki , Kim Tae-Woo
Published: October 2022

Background

Taking facial and intraoral clinical photos is one of the essential parts of orthodontic diagnosis and treatment planning. Among the diagnostic procedures, classification of the shuffled clinical photos with their orientations will be the initial step while it was not easy for a machine to classify photos with a variety of facial and dental situations. This article presents a convolutional neural networks (CNNs) deep learning technique to classify orthodontic clinical photos according to their orientations.

Methods

To build an automated classification system, CNNs models of facial and intraoral categories were constructed, and the clinical photos that are routinely taken for orthodontic diagnosis were used to train the models with data augmentation. Prediction procedures were evaluated with separate photos whose purpose was only for prediction.

Results

Overall, a 98.0% valid prediction rate resulted for both facial and intraoral photo classification. The highest prediction rate was 100% for facial lateral profile, intraoral upper, and lower photos.

Conclusion

An artificial intelligence system that utilizes deep learning with proper training models can successfully classify orthodontic facial and intraoral photos automatically. This technique can be used for the first step of a fully automated orthodontic diagnostic system in the future.
Early prediction of patient discharge disposition in acute neurological care using machine learning
Authors: Mickle Charles F. , Deb Debzani
Published: October 2022

Background

Acute neurological complications are some of the leading causes of death and disability in the U.S. The medical professionals that treat patients in this setting are tasked with deciding where (e.g., home or facility), how, and when to discharge these patients. It is important to be able to predict potential patient discharge outcomes as early as possible during the patient’s hospital stay and to know what factors influence the development of discharge planning. This study carried out two parallel experiments: A multi-class outcome (patient discharge targets of ‘home’, ‘nursing facility’, ‘rehab’, ‘death’) and binary class outcome (‘home’ vs. ‘non-home’). The goal of this study is to develop early predictive models for each experiment exploring which patient characteristics and clinical variables significantly influence discharge planning of patients based on the data that are available only within 24 h of their hospital admission. 

Method

Our methodology centers around building and training five different machine learning models followed by testing and tuning those models to find the best-suited predictor for each experiment with a dataset of 5,245 adult patients with neurological conditions taken from the eICU-CRD database.

Results

The results of this study show XGBoost to be the most effective model for predicting between four common discharge outcomes of ‘home’, ‘nursing facility’, ‘rehab’, and ‘death’, with 71% average c-statistic. The XGBoost model was also the best-performer in the binary outcome experiment with a c-statistic of 76%. This article also explores the accuracy, reliability, and interpretability of the best performing models in each experiment by identifying and analyzing the features that are most impactful to the predictions.

Conclusions

The acceptable accuracy and interpretability of the predictive models based on early admission data suggests that the models can be used in a suggestive context to help guide healthcare providers in efforts of planning effective and equitable discharge recommendations.
An asparagine metabolism-based classification reveals the metabolic and immune heterogeneity of hepatocellular carcinoma
Authors: Bai Jianguo , Tang Ruifeng , Zhou Keyu , Chang Jialei , Wang Hongyue , Zhang Qixin , Shi Jiahui , Sun Chao
Published: October 2022

Introduction and objectives

hepatocellular carcinoma (HCC) is the major form of liver cancer with a poor prognosis. Amino acid metabolism has been found to alter in cancers and contributes to malignant progression. However, the asparagine metabolism status and relevant mechanism in HCC were barely understood.

Methods

By conducting consensus clustering and the least absolute shrinkage and selection operator regression of HCC samples from three cohorts, we classified the HCC patients into two subtypes based on asparagine metabolism level. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analyses and Gene Set Enrichment Analysis of the differentially expressed genes between two subgroups were conducted. Immune cell infiltration was evaluated using CIBERSORT algorithm. The prognostic values of genes were analyzed by univariate and multivariate cox regression, ROC curve and Kaplan–Meier survival estimate analyses. Cell types of sing-cell RNA sequencing (scRNA-seq) data were clustered utilizing UMAP method.

Results

HCC patients with higher asparagine metabolism level have worse prognoses. Moreover, we found the distinct energy metabolism patterns, DNA damage response (DDR) pathway activating levels, drug sensitivities to DDR inhibitors, immune cell compositions in the tumor microenvironment and responses to immune therapy between two subgroups. Further, we identified a potential target gene, glutamic-oxaloacetic transaminase 2 (GOT2). GOT2 downregulation was associated with worse HCC prognosis and increased infiltration of T regulatory cells (Tregs). ScRNA-seq revealed the GOT2 downregulation in cancer stem cells compared with HCC cells.

Conclusions

Taken together, HCC subtype which is more reliant on asparagine and glutamine metabolism has a worse prognosis, and a core gene of asparagine metabolism GOT2 is a potential prognostic marker and therapeutic target of HCC. Our study promotes the precision therapy of HCC and may improve patient outcomes.
Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome
Authors: Wang Zheng , Waldman Michelle F. , Basavanhally Tara J. , Jacobs Aviva R. , Lopez Gonzalo , Perichon Regis Y. , Ma Johnny J. , Mackenzie Elyse M. , Healy James B. , Wang Yixin , Hersey Sarah A.
Published: October 2022

Background

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease.

Methods

In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity’s 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method.

Results

Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives).

Conclusions

Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.
Development of a multicellular in vitro model of the meningeal blood-CSF barrier to study Neisseria meningitidis infection
Authors: Endres Leo M. , Jungblut Marvin , Divyapicigil Mustafa , Sauer Markus , Stigloher Christian , Christodoulides Myron , Kim Brandon J. , Schubert-Unkmeir Alexandra
Published: October 2022

Background

Bacterial meningitis is a life-threatening disease that occurs when pathogens such as Neisseria meningitidis cross the meningeal blood cerebrospinal fluid barrier (mBCSFB) and infect the meninges. Due to the human-specific nature of N. meningitidis, previous research investigating this complex host–pathogen interaction has mostly been done in vitro using immortalized brain endothelial cells (BECs) alone, which often do not retain relevant barrier properties in culture. Here, we developed physiologically relevant mBCSFB models using BECs in co-culture with leptomeningeal cells (LMCs) to examine N. meningitidis interaction.

Methods

We used BEC-like cells derived from induced pluripotent stem cells (iBECs) or hCMEC/D3 cells in co-culture with LMCs derived from tumor biopsies. We employed TEM and structured illumination microscopy to characterize the models as well as bacterial interaction. We measured TEER and sodium fluorescein (NaF) permeability to determine barrier tightness and integrity. We then analyzed bacterial adherence and penetration of the cell barrier and examined changes in host gene expression of tight junctions as well as chemokines and cytokines in response to infection.

Results

Both cell types remained distinct in co-culture and iBECs showed characteristic expression of BEC markers including tight junction proteins and endothelial markers. iBEC barrier function as determined by TEER and NaF permeability was improved by LMC co-culture and remained stable for seven days. BEC response to N. meningitidis infection was not affected by LMC co-culture. We detected considerable amounts of BEC-adherent meningococci and a relatively small number of intracellular bacteria. Interestingly, we discovered bacteria traversing the BEC-LMC barrier within the first 24 h post-infection, when barrier integrity was still high, suggesting a transcellular route for N. meningitidis into the CNS. Finally, we observed deterioration of barrier properties including loss of TEER and reduced expression of cell-junction components at late time points of infection.

Conclusions

Here, we report, for the first time, on co-culture of human iPSC derived BECs or hCMEC/D3 with meningioma derived LMCs and find that LMC co-culture improves barrier properties of iBECs. These novel models allow for a better understanding of N. meningitidis interaction at the mBCSFB in a physiologically relevant setting.
Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry
Authors: Fujiwara Kenji , Shao Yingkuan , Niu Nan , Zhang Tengyi , Herbst Brian , Henderson Mackenzie , Muth Stephen , Zhang Pingbo , Zheng Lei
Published: October 2022

Background

Identifying T cell epitopes on pancreatic ductal adenocarcinoma (PDAC) associated antigens or neoantigens has been a challenge. In this study, we attempted to identify PDAC T cell epitopes by mass spectrometry (MS).

Methods

We isolated HLA class I (HLA-I) and HLA class II (HLA-II)-restricted peptides, respectively, from tissues of human PDAC by using the pan-HLA-I or pan-HLA-II affinity purification column and identified T cell epitopes by peptidome analysis with MS.

Results

Through peptidome analysis, we identified T cell epitopes shared by multiple patients with different HLA types and those containing sequences of both anti-HLA-I and HLA-II antibodies-affinity purified peptides. The identified epitopes bound non-matched HLA molecules and induced T cell response in peripheral T cells from both HLA-type matched and non-matched patients. Peptides containing both HLA class I and class II epitopes were able to induce polyfunctional cytokine responses in peripheral T cells.

Conclusions

T cell epitopes in PDAC can be discovered by the MS approach and can be designed into vaccine and TCR-T cell therapies for both HLA-type matched and non-matched patients.
Drugging KRAS: current perspectives and state-of-art review
Authors: Parikh Kaushal , Banna Giuseppe , Liu Stephen V. , Friedlaender Alex , Desai Aakash , Subbiah Vivek , Addeo Alfredo
Published: October 2022

After decades of efforts, we have recently made progress into targeting KRAS mutations in several malignancies. Known as the ‘holy grail’ of targeted cancer therapies, KRAS is the most frequently mutated oncogene in human malignancies. Under normal conditions, KRAS shuttles between the GDP-bound ‘off’ state and the GTP-bound ‘on’ state. Mutant KRAS is constitutively activated and leads to persistent downstream signaling and oncogenesis. In 2013, improved understanding of KRAS biology and newer drug designing technologies led to the crucial discovery of a cysteine drug-binding pocket in GDP-bound mutant KRAS G12C protein. Covalent inhibitors that block mutant KRAS G12C were successfully developed and sotorasib was the first KRAS G12C inhibitor to be approved, with several more in the pipeline. Simultaneously, effects of KRAS mutations on tumour microenvironment were also discovered, partly owing to the universal use of immune checkpoint inhibitors. In this review, we discuss the discovery, biology, and function of KRAS in human malignancies. We also discuss the relationship between KRAS mutations and the tumour microenvironment, and therapeutic strategies to target KRAS. Finally, we review the current clinical evidence and ongoing clinical trials of novel agents targeting KRAS and shine light on resistance pathways known so far.
B3GALT4 remodels the tumor microenvironment through GD2-mediated lipid raft formation and the c-met/AKT/mTOR/IRF-1 axis in neuroblastoma
Authors: Sha Yong-Liang , Liu Yun , Yang Jia-Xing , Wang Yang-Yang , Gong Bao-Cheng , Jin Yan , Qu Tong-Yuan , Xia Fan-Tong , Han Lei , Zhao Qiang
Published: October 2022

Background

Beta-1,3-galactosyltransferase-4 (B3GALT4) plays a critical regulatory role in tumor biology. However, the role of B3GALT4 in modulating the tumor microenvironment (TME) of neuroblastoma (NB) remains unknown.

Methods

Public datasets and clinical NB samples were collected to evaluate the expression and clinical significance of GD2 and B3GALT4 in NB patients. CCK-8, colony formation, and transwell assays and experiments in tumor-bearing mouse models were conducted to investigate the function of B3GALT4. Flow cytometry, ELISA, immunohistochemistry, immunofluorescence, western blotting, and chemotaxis assays were conducted to ascertain the immunomodulatory mechanism of B3GALT4. The combined therapeutic effect of the lipid raft inhibitor MβCD and anti-GD2 mAb was validated in a murine model of NB.

Results

GD2 was overexpressed in NB tissues and high expression of GD2 was associated with poor prognosis in NB patients. B3GALT4 was downregulated in NB tissues, and low expression of B3GALT4 indicated poor prognosis in NB patients. Silencing B3GALT4 significantly enhanced tumor progression both in vitro and in vivo. Meanwhile, the overexpression of B3GALT4 increased the recruitment of CD8+ T lymphocytes via the chemokines CXCL9 and CXCL10. Additionally, B3GALT4 regulated NB-cell GD2 expression and lipid raft formation. Mechanistically, B3GALT4 regulated the expression of CXCL9 and CXCL10 via the c-Met signaling in the lipid rafts and the downstream AKT/mTOR/IRF-1 pathway. The lipid raft inhibitor, MβCD, attenuated B3GALT4 deficiency-induced tumor progression and immune evasion. Last, MβCD combined with anti-GD2 mAb treatment significantly enhanced the antitumor effect and the infiltration of CD8+ T cells.

Conclusions

Upregulation of B3GALT4 promotes the secretion of CXCL9 and CXCL10 to recruit CD8+ T lymphocytes via the GD2-mediated lipid rafts and the c-Met/AKT/mTOR/IRF-1 pathway. Moreover, lipid raft inhibitors may enhance the efficacy of anti-GD2 immunotherapy for NB.
Toe Grip strength declines earlier than hand grip strength and knee extension strength in community‐dwelling older men: a cross sectional study
Authors: Miura Sayo , Seko Toshiaki , Himuro Nobuaki , Koyama Masayuki , Saitoh Shigeyuki , Ohnishi Hirofumi
Published: October 2022

Background

The aim of this study is to examine the age‐related changes in the toe grip strength and its differences from hand grip strength and knee extension strength using cross‐sectional data.

Methods

Of participants aged 65 years over who underwent health checkups for lifestyle‐related diseases in 2018, 307 men and women met the criteria. Toe grip strength, hand grip strength, and knee extension strength were also measured as optional tests. The participants were divided into five groups categorized by every 5 years of age (Group 65–85). The data were analyzed with multiple comparisons using the linear mixed multilevel model to examine the following categories: association between age and muscle strength, differences in the pattern of change, and gender, using the 65–69 years group as a reference.

Results

In men, there were interaction effects between the factors of age and muscle, but in women there were not. Toe grip strength was significantly lower in Group 70, 75, 80, and 85 in men, lower in Group 85 than in 65 in women. Hand grip strength was significantly lower in Group 85 than in 65 in both men and women. There was no significant difference in knee extension strength among the age groups for both men and women.

Conclusions

The decline in toe grip strength may occur earlier and in a different pattern from hand grip strength and knee extension strength in men.
Comparison of continuous versus intermittent enteral feeding in critically ill patients: a systematic review and meta-analysis
Authors: Heffernan Aaron J. , Talekar C. , Henain M. , Purcell L. , Palmer M. , White H.
Published: October 2022

Background

The enteral route is commonly utilised to support the nutritional requirements of critically ill patients. However, there is paucity of data guiding clinicians regarding the appropriate method of delivering the prescribed dose. Continuous enteral feeding is commonly used; however, a bolus or intermittent method of administration may provide several advantages such as minimising interruptions. The purpose of this meta-analysis is to compare a continuous versus an intermittent or bolus enteral nutrition administration method.

Methods

A systematic review and meta-analysis were performed with studies identified from the PubMed, EMBASE, Cochrane Library and Web of Science databases. Studies were included if they compared a continuous with either an intermittent or bolus administration method of enteral nutrition in adult patients admitted to the intensive care unit. Study quality was assessed using the PEDro and Newcastle–Ottawa scoring systems. Review Manager was used for performing the random-effects meta-analysis on the outcomes of mortality, constipation, diarrhoea, increased gastric residuals, pneumonia, and bacterial colonisation.

Results

A total of 5546 articles were identified, and 133 were included for full text review. Fourteen were included in the final analysis. There was an increased risk of constipation with patients receiving continuous enteral nutrition (relative risk 2.24, 95% confidence interval 1.01–4.97,p = 0.05). No difference was identified in other outcome measures. No appreciable bias was identified.

Conclusion

The current meta-analysis has not identified any clinically relevant difference in most outcome measures relevant to the care of critically ill patients. However, there is a paucity of high-quality randomised controlled clinical trials to guide this decision. Therefore, clinicians may consider either dosing regimen in the context of the patient’s care requirements.
Reliability and validity of the Japanese movement imagery questionnaire-revised second version
Authors: Nakano Hideki , Tachibana Mizuki , Fujita Nao , Sawai Shun , Fujikawa Shoya , Yamamoto Ryosuke , Murata Shin
Published: October 2022

Objective

Developing a Japanese version of the Movement Imagery Questionnaire-Revised Second Version (MIQ-RS) is essential for widespread evaluation and treatment based on motor imagery in physically disabled persons and patients in rehabilitation. This study aimed to investigate the reliability and validity of the Movement Imagery Questionnaire-Revised Second Version (MIQ-RS), which assesses motor imagery ability, by translating it into Japanese.

Results

This study enrolled twenty healthy participants (10 men and 10 women, mean age 21.17 ± 1.10 years). Reliability was examined for internal consistency using Cronbach’s alpha coefficient. Spearman’s rank correlation coefficient was used to examine the criterion-related validity of the MIQ-RS and the Kinesthetic and Visual Imagery Questionnaire (KVIQ-20). Results showed that Cronbach’s alpha coefficients for the MIQ-RS were 0.81 and 0.82 for visual and kinesthetic imagery, respectively. Significant positive correlations were found between each visual and kinesthetic imagery score, and each total on the MIQ-RS and KVIQ-20 scores (r = 0.73, p < 0.01; r = 0.84, p < 0.01; r = 0.80, p < 0.01, respectively). This study suggests that the Japanese version of the MIQ-RS is a reliable and valid method of assessing motor imagery ability.
HPV infection and 5mC/5hmC epigenetic markers in penile squamous cell carcinoma: new insights into prognostics
Authors: Santos Renan da Silva , Hirth Carlos Gustavo , Pinheiro Daniel Pascoalino , Bezerra Maria Júlia Barbosa , Silva-Fernandes Isabelle Joyce de Lima , Paula Dayrine Silveira de , Alves Ana Paula Negreiros Nunes , Moraes Filho Manoel Odorico de , Moura Arlindo de Alencar Araripe , Lima Marcos Venício Alves , Pessoa Claudia do Ó , Furtado Cristiana Libardi Miranda
Published: October 2022

Background

Penile cancer is one of the most aggressive male tumors. Although it is preventable, the main etiologic causes are lifestyle behaviors and viral infection, such as human papillomavirus (HPV). Long-term epigenetic changes due to environmental factors change cell fate and promote carcinogenesis, being an important marker of prognosis. We evaluated epidemiological aspects of penile squamous cell carcinoma (SCC) and the prevalence of HPV infection using high-risk HPV (hrHPV) and p16INK4A expression of 224 participants. Global DNA methylation was evaluated through 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC).

Results

The incidence of HPV was 53.2% for hrHPV and 22.32% for p16INK4a. hrHPV was not related to systemic or lymph node metastasis and locoregional recurrence, nor influenced the survival rate. P16INK4a seems to be a protective factor for death, which does not affect metastasis or tumor recurrence. Lymph node and systemic metastases and locoregional recurrence increase the risk of death. An increased 5mC mark was observed in penile SCC regardless of HPV infection. However, there is a reduction of the 5hmC mark for p16INK4a + (P = 0.024). Increased 5mC/5hmC ratio (> 1) was observed in 94.2% of penile SCC, irrespective of HPV infection. Despite the increase in 5mC, it seems not to affect the survival rate (HR = 1.06; 95% CI 0.33–3.38).

Conclusions

P16INK4a seems to be a good prognosis marker for penile SCC and the increase in 5mC, an epigenetic mark of genomic stability, may support tumor progression leading to poor prognosis.
Efficient depolymerization of polyethylene terephthalate (PET) and polyethylene furanoate by engineered PET hydrolase Cut190
Authors: Kawai Fusako , Furushima Yoshitomo , Mochizuki Norihiro , Muraki Naoki , Yamashita Mitsuaki , Iida Akira , Mamoto Rie , Tosha Takehiko , Iizuka Ryo , Kitajima Sakihito
Published: October 2022

The enzymatic recycling of polyethylene terephthalate (PET) can be a promising approach to tackle the problem of plastic waste. The thermostability and activity of PET-hydrolyzing enzymes are still insufficient for practical application. Pretreatment of PET waste is needed for bio-recycling. Here, we analyzed the degradation of PET films, packages, and bottles using the newly engineered cutinase Cut190. Using gel permeation chromatography and high-performance liquid chromatography, the degradation of PET films by the Cut190 variant was shown to proceed via a repeating two-step hydrolysis process; initial endo-type scission of a surface polymer chain, followed by exo-type hydrolysis to produce mono/bis(2-hydroxyethyl) terephthalate and terephthalate from the ends of fragmented polymer molecules. Amorphous PET powders were degraded more than twofold higher than amorphous PET film with the same weight. Moreover, homogenization of post-consumer PET products, such as packages and bottles, increased their degradability, indicating the importance of surface area for the enzymatic hydrolysis of PET. In addition, it was required to maintain an alkaline pH to enable continuous enzymatic hydrolysis, by increasing the buffer concentration (HEPES, pH 9.0) depending on the level of the acidic products formed. The cationic surfactant dodecyltrimethylammonium chloride promoted PET degradation via adsorption on the PET surface and binding to the anionic surface of the Cut190 variant. The Cut190 variant also hydrolyzed polyethylene furanoate. Using the best performing Cut190 variant (L136F/Q138A/S226P/R228S/D250C-E296C/Q123H/N202H/K305del/L306del/N307del) and amorphous PET powders, more than 90 mM degradation products were obtained in 3 days and approximately 80 mM in 1 day.

Graphical Abstract
Recombinant acetylxylan esterase of Halalkalibacterium halodurans NAH-Egypt: molecular and biochemical study
Authors: Embaby Amira M. , Mahmoud Hoda E.
Published: October 2022

Acetylxylan esterase plays a crucial role in xylan hydrolysis as the acetyl side-groups restrict endoxylanase action by stearic hindrance. In this study, an acetylxylan esterase (AXE-HAS10: 960 bp & 319 a.a) putative ORF from Halalkalibacterium halodurans NAH-Egypt was extensively studied through heterologous overexpression in Escherichia coli, biochemical characterization, and structural modeling. The AXE-HAS10 tertiary structure was predicted by the Local Meta Threading Server. AXE-HAS10 belongs to the carbohydrate esterase Family 7. Purified to homogeneity AXE-HAS10 showed specific activity (36.99 U/mg), fold purification (11.42), and molecular mass (41.39 kDa). AXE-HAS10 showed optimal pH (8.5) and temperature (40 oC). After 15 h of incubation at pH 7.0–9.0, AXE-HAS10 maintained 100% activity. After 120 min at 35 and 40 oC, the retained activity was 80 and 50%, respectively. At 10 mM Mn2+, Fe3+, K+, and Ca2+ after 30 min, retained activity was 329 ± 15, 212 ± 5.2, 123 ± 1.4, and 120 ± 3.0%, respectively. After 30 min of preincubation with triton x-100, SDS, and CTAB at 0.1% (v/v), the retained activity was 150 ± 19, 88 ± 4, and 82 ± 7%, respectively. At 6.0 M NaCl after 30 min, retained activity was 58%. A 1.44-fold enhancement of beechwood xylan hydrolysis was achieved by AXE-HAS10 and Penicillium chrysogenum DSM105774 β-xylanase concurrently. Present data underpins AXE-HAS10 as a promising AXE for industrial exploitation.
Housekeeping gene gyrA, a potential molecular marker for Bacillus ecology study
Authors: Liu Yan , Štefanič Polonca , Miao Youzhi , Xue Yansheng , Xun Weibing , Zhang Nan , Shen Qirong , Zhang Ruifu , Xu Zhihui , Mandic-Mulec Ines
Published: October 2022

Bacillus is a genus of microorganisms (bacteria) and contains many important commercial species used in industry, agriculture and healthcare. Many different Bacilli are relatively well understood at the single-cell level; however, molecular tools that determine the diversity and ecology of Bacillus community are limited, which limits our understanding of how the Bacillus community works. In the present study, we investigated the potential of the housekeeping gene gyrA as a molecular marker for determining the diversity of Bacillus species. The amplification efficiency for Bacillus species diversity could be greatly improved by primer design. Therefore, we designed a novel primer pair gyrA3 that can detect at least 92 Bacillus species and related species. For B. amyloliquefaciens, B. pumilus, and B. megaterium, we observed that the high variability of the gyrA gene allows for more detailed clustering at the subspecies level that cannot be achieved by the 16S rRNA gene. Since gyrA provides better phylogenetic resolution than 16S rRNA and informs on the diversity of the Bacillus community, we propose that the gyrA gene may have broad application prospects in the study of Bacillus ecology.
Association of variants in the KIF1A gene with amyotrophic lateral sclerosis
Authors: Liao Panlin , Yuan Yanchun , Liu Zhen , Hou Xiaorong , Li Wanzhen , Wen Jin , Zhang Kexuan , Jiao Bin , Shen Lu , Jiang Hong , Guo Jifeng , Tang Beisha , Zhang Zhuohua , Hu Zhonghua , Wang Junling
Published: October 2022

Background

Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease that affects neurons in the central nervous system and the spinal cord. As in many other neurodegenerative disorders, the genetic risk factors and pathogenesis of ALS involve dysregulation of cytoskeleton and neuronal transport. Notably, sensory and motor neuron diseases such as hereditary sensory and autonomic neuropathy type 2 (HSAN2) and spastic paraplegia 30 (SPG30) share several causative genes with ALS, as well as having common clinical phenotypes. KIF1A encodes a kinesin 3 motor that transports presynaptic vesicle precursors (SVPs) and dense core vesicles and has been reported as a causative gene for HSAN2 and SPG30.

Methods

Here, we analyzed whole-exome sequencing data from 941 patients with ALS to investigate the genetic association of KIF1A with ALS.

Results

We identified rare damage variants (RDVs) in the KIF1A gene associated with ALS and delineated the clinical characteristics of ALS patients with KIF1A RDVs. Clinically, these patients tended to exhibit sensory disturbance. Interestingly, the majority of these variants are located at the C-terminal cargo-binding region of the KIF1A protein. Functional examination revealed that the ALS-associated KIF1A variants located in the C-terminal region preferentially enhanced the binding of SVPs containing RAB3A, VAMP2, and synaptophysin. Expression of several disease-related KIF1A mutants in cultured mouse cortical neurons led to enhanced colocalization of RAB3A or VAMP2 with the KIF1A motor.

Conclusions

Our study highlighted the importance of KIF1A motor-mediated transport in the pathogenesis of ALS, indicating KIF1A as an important player in the oligogenic scenario of ALS.
Synergetic Influence of Microcrystalline Quartz and Alkali Content in Aggregate on Deterioration of Concrete Railroad Ties Used for 15 Years in High-Speed Railways
Authors: Jeon Dongho , Yu Juan , Kim Jihwan , Yoon Seyoon , Bae Younghoon , Oh Jae Eun
Published: October 2022

This study investigated the deteriorations of precast prestressed concrete (PSC) ties that were used for 15 years in high-speed railways in Korea and its damaging mechanism. The collected PSC ties with longitudinal cracks on sides and map cracks on surfaces exhibited strength degradation. The deteriorations were likely related to alkali-silica reaction (ASR) and delayed ettringite formation (DEF) together, given that the presence of massive ettringite crystals and the decomposition of ASR gel were found from microstructural analyses. Although there were no typical reactive siliceous aggregates for ASR in this study, ASR cracks were generated in the PSC ties. This is because the aggregates in the PSC ties with cracks were potentially reactive, and its high alkali-silica reactivity was likely attributable to the presence of microcrystalline quartz, supplying reactive SiO2 to trigger ASR. Furthermore, the alkali content in aggregates was associated with the deterioration of the PSC ties. The alkali-bearing minerals in aggregates (i.e., alkali feldspars) likely supplied enough alkalis for ASR. Besides, micas in aggregates could promote ASR due to their porous structure, which helps easy water ingress.
Multi-light photogrammetric survey applied to the complex documentation of engravings in Palaeolithic rock art: the Cova de les Meravelles (Gandia, Valencia, Spain)
Authors: Cantó Ana , Lerma José Luis , Martínez Valle Rafael , Villaverde Valentín
Published: October 2022

The new phase of study and revision of the Palaeolithic art of the Cova de les Meravelles, as well as the advances made in the field of 3D documentation in recent years, have motivated a new documentation campaign on the main panel full of tiny engraved motifs. The difficulties involved in acquiring and processing data executed using fine and thin engraving techniques indoors, have been solved through a multi-light photogrammetric survey, photographing the main panel surface with five lighting directions, and applying principal component analysis (PCA). This procedure has allowed us to obtain a large corpus of two and three-dimensional data and to improve the documentation base produced 17 years ago after its discovery. In this paper, we present the procedure followed, the enhanced engraving results in the new documentation campaign, its most significant contributions to the complex archaeological survey, and the limits we have found along the procedure.
The influence of genetics on epilepsy syndromes in infancy and childhood
Authors: Yozawitz Elissa , Moshé Solomon L.
Published: October 2022

Genetics is rapidly evolving and is actively playing a role in how we diagnose and manage epilepsy. The definition of an epilepsy syndrome has changed throughout the years. The International League Against Epilepsy (ILAE) has developed a classification of the epilepsies and has recently described specific epilepsy syndromes taking into account emerging genetic information which is rapidly evolving as well as etiology-specific syndromes. Understanding genetics can help clarify the syndrome and its treatment. This review provides a history of the definition of a syndrome, and the evolving contribution of genetic information that is part of the syndromic classification. We provide few examples of several phenotypes/genotypes of epilepsy syndromes in infancy and childhood and treatment issues that may arise from the available genetic information. Epilepsy syndromes and their genetics have been rapidly changing as new gene technologies are being developed. Understanding genetics can help clarify the syndrome, its treatment, and will help change the field of epilepsy to improve patients qualify of life by creating new means of preventing, controlling, and curing epilepsy.
Psychological adverse effects of COVID-19 pandemic on health service providers: an online survey
Authors: Somi Mohammad Hossein , Fakhari Ali , Azizi Hosein , Barzegar Habibeh , Norouzi Sanaz , Aslrahimi Vahab , Farahbakhsh Mostafa
Published: October 2022

Background

In the current situation of the COVID-19 pandemic, health service providers (HCPs) suffered from mental health consequences such as depression, anxiety, fear, and post-traumatic stress disorder (PTSD). The study aimed to evaluate the adverse psychological impacts of the COVID-19 pandemic on HSPs at the Tabriz University of Medical Science, North West of Iran. An online survey was conducted to assess the psychological adverse effects of COVID-19 during the pandemic of COVID-19 from May 2021 to February 2022. Psychological adverse effects including depression, anxiety, PTSD, and fear were measured using valid instruments. Overall, 298 HSPs responded to the questionnaires. Descriptive and multiple logistic regression analyses with crude and adjusted ORs were used to estimate mental health adverse effects.

Results

The overall prevalence of depressive symptoms, major depression disorder (MDD), anxiety, and probable PTSD were 58%, 9.1%, 61.7%, and 15%, respectively. The fear of COVID-19 scale (mean) was 17.6± 6.2. We found mental health adverse effects were higher in HSPs who worked in the treatment and health sections than HSPs in the support section. Having a history of mental disorder, HSP type (health and treatment), and female sex had a statistically significant association with MDD and depressive symptoms.

Conclusions

Mental health problems were high in HSPs. The study highlights the demand for support systems and appropriate interventions for improving HSPs’ mental health and well-being during the COVID-19 pandemic.
Self-efficacy as a mediator of the relationship between pain and disability in chronic pain patients: a narrative review
Authors: Raman Saikripa , Sharma Priyanshu
Published: October 2022

Self-efficacy is an important indicator of psychological wellness, devoted to prescribed medications, along with pain-coping strategies in individuals who have chronic pain, a psychological concept described as one’s confidence in performing a specific activity. Poor self-efficacy is an impediment to rehabilitation and predicts long-term impairment. Higher self-efficacy can improve function and prolong physical well-being in people who have chronic pain. Recent findings show that coping mechanisms play a major role in chronic pain adaptation. SE beliefs are a significant determinant of coping habits. This article reviews the theory of SE, the importance of application of SE in treating chronic pain and disability.
Heart Rate Variability
Authors: Cooper Emily , Franklin Barry A.
Published: October 2022

Apply It!

This article will help readers to:

• understand the physiology behind heart rate variability (HRV)

• learn more about the favorable effect that regular exercise and resonance breathing have on HRV

• improve performance

• reduce stress and anxiety
Cognitive and Behavioral Outcomes in Male and Female NCAA Soccer Athletes across Multiple Years: A CARE Consortium Study
Authors: CACCESE JACLYN B. , BRYK KELSEY N. , PORFIDO TARA , BRETZIN ABIGAIL C. , PEEK KERRY , KAMINSKI THOMAS W. , KONTOS ANTHONY P. , CHRISMAN SARA P. D. , PUTUKIAN MARGOT , BUCKLEY THOMAS A. , BROGLIO STEVEN P. , MCALLISTER THOMAS W. , MCCREA MICHAEL A. , PASQUINA PAUL F. , ESOPENKO CARRIE ,   the CARE Consortium Investigators
Published: October 2022

Purpose

The purpose of this study was to determine changes in neurocognitive, psychosocial, and balance functioning in collegiate male and female soccer players across three consecutive years of baseline testing compared with a control group of noncontact athletes.

Methods

Generalized estimating equations were used to compare changes in annual, preseason baseline measures of neurocognitive function, neurobehavioral and psychological symptoms, and postural stability between collegiate soccer players (n = 75; 51 [68%] female soccer players) and noncontact athletes (n = 210; 133 [63%] female noncontact athletes) across three consecutive years.

Results

Among all participants, the group–time interaction was not significant for any outcome measures. Overall, soccer players reported lower (better) Brief Symptom Inventory 18 Depression (P = 0.004, Exp(B) = 0.36, 95% confidence interval [CI] = 0.18–0.73), Global Severity Index (P = 0.006, Exp(B) = 0.53, 95% CI = 0.33–0.84), and Post-Concussion Symptom Scale Symptom Severity (P < 0.001, Exp(B) = 0.45, 95% CI = 0.22–0.95) scores than noncontact athletes. No other outcome measures were different between soccer players and noncontact athletes.

Conclusions

Among collegiate athletes, soccer players report similar or better psychosocial functioning and symptom scores than noncontact athletes. Importantly, neurocognitive functioning, neurobehavioral and psychological symptoms, and postural stability do not worsen over time in collegiate soccer players relative to their noncontact counterparts. Our findings suggest that despite possible exposure to repetitive head impacts, collegiate soccer players do not exhibit changes in observable function and symptoms across multiple seasons.
Vulnerability and Clientelism
Authors: Bobonis Gustavo J. , Gertler Paul J. , Gonzalez-Navarro Marco , Nichter Simeon
Published: October 2022

This study argues that economic vulnerability causes citizens to participate in clientelism, a phenomenon with various pernicious consequences. To examine how reduced vulnerability affects citizens’ participation in clientelism, we employ two exogenous shocks to vulnerability. First, we designed a randomized control trial to reduce household vulnerability: our development intervention constructed residential water cisterns in drought-prone areas of Brazil. Second, we exploit rainfall shocks. We find that reducing vulnerability significantly decreases requests for private goods from politicians, especially among citizens likely to be in clientelist relationships. Moreover, reducing vulnerability decreases votes for incumbent mayors, who typically have more resources for clientelism. (JEL D72, H41, I38, O12, O17, Q54)
TNT Express: os desafios de alinhar interesses e integrar culturas organizacionais em um processo de joint venture
Authors: Porteiro Giovana Guardia Kill , Fernandes Gustavo Andrey de Almeida Lopes
Published: October 2022

O caso apresenta a situação da empresa TNT, que deseja estruturar seu programa de expansão para a América Latina e abrir o capital da empresa. Para tanto, a TNT decide estabelecer uma sociedade (joint venture) com um fundo internacional de private equity (“Fundo Internacional Mudar” – FIM). As origens culturais da TNT e do FIM são díspares, e as lógicas de atuação, distintas, apesar dos interesses supostamente convergentes. No decorrer dos planos, surgem conflitos e dilemas éticos que resultam na dissolução da sociedade. O protagonista do caso é o Sr. Silva, presidente interino que terá que testemunhar no processo de arbitragem.
Factors associated with scientific production of professors working at a private university in Peru: An analytical cross-sectional study
Authors: Rivera-Lozada Oriana , RIVERA-LOZADA ISABEL CRISTINA , Bonilla-Asalde Cesar Antonio
Published: October 2022

Objective: To estimate the association between the academic, personal, and work characteristics and scientific production of professors at a private university of Lima, Peru, in 2021. Methods: We undertook an observational, analytical, and cross-sectional study. The sample included 322 professors through simple random sampling. Two questionnaires were administered. The first gathered personal, academic, and work characteristics; while the second evaluated scientific production. The chi-squared test was used, with a significance level of p<0,05, to evaluate the association between the different characteristics and scientific production. A multiple logistic regression was analyzed through the Stepwise method to evaluate the relationship between the variables of exposure and scientific production. We calculated prevalence ratios (PRs) with their respective 95% confidence intervals (95% CI). Results: We analyzed 322 professors, 59,6% were male. Scientific production was associated with being registered in Renacyt (PR = 5,52; 95% CI: 2,14 to 4,23; p = <0.001), having a doctoral degree (PR = 2,45; 95% CI: 1,60 to 3,85; p = <0.001), having been a thesis advisor (PR = 3,83; 95% CI: 1,45 to 5,66; p = <0.001), having facilities to conduct research at the workplace (PR = 1,58; 95% CI: 1,12 to 2,47; p = 0.006), and having received training by the university (PR = 1,99; 95% CI: 1,55 to 2,56; p = 0,001). Conclusions: Scientific production was associated with being registered in Renacyt, having a doctoral degree, having been a thesis advisor, having facilities to conduct research at the workplace, and having being trained in research by the university. Hence, evaluation systems and the monitoring of university quality standards should be strengthened. In addition, it is necessary to undertake wider scope studies in order to enhance the strategies that promote professors’ research.
Effect of Antigravity Treadmill Training on Gait and Balance in Patients with Diabetic Polyneuropathy: A Randomized Controlled Trial
Authors: Abdelaal Ashraf , El-Shamy Shamekh
Published: October 2022

Background: Diabetic polyneuropathy (DPN) is the most prevalent consequence of diabetes mellitus, and it has a significant impact on the patient's health. This study aims to evaluate effects of antigravity treadmill training on gait and balance in patients with DPN. Methods: The study included 45 males with type 2 diabetes who were randomly assigned to one of two groups: the experimental group (n=23) or the control group (n=22). For a period of 12 weeks, the experimental group received antigravity treadmill training (75% weight bearing, 30 min per session, three times per week) combined with traditional physical therapy. During the same time period, the control group received only traditional physical therapy. The Biodex Balance System was used to assess postural stability indices, while the GAITRite Walkway System was used to assess spatiotemporal gait parameters. All measurements were obtained before and at the end of the study after 12 weeks of treatment. Results: The mean values of all measured variables improved significantly in both groups (P<0.05), with the experimental group showing significantly greater improvements than the control group. The post-treatment gait parameters (i.e., step length, step time, double support time, velocity, and cadence) were 61.3 cm, 0.49 sec, 0.25 sec, 83.09 cm/sec, and 99.78 steps/min as well as 56.14 cm, 0.55 sec, 0.29 sec, 75.73 cm/sec, and 88.14 steps/min for the experimental and control group, respectively. The post-treatment overall stability index was 0.32 and 0.70 for the experimental and control group, respectively. Conclusions: Antigravity treadmill training in combination with traditional physical therapy appears to be superior to traditional physical therapy alone in terms of gait and balance training. As a result, the antigravity treadmill has been found to be an effective device for the rehabilitation of DPN patients.