bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of integrated full life cycle data management and application of the slab tracks
Authors: Ye Wenlong , Ren Juanjuan , Zhang Peng , Zhang Qi , Li Longxiang
Published: November 2022

The full life cycle data management and application of high-speed railway slab track has multiple benefits. While serving as the basis for scientific periodic and predictive maintenance, it is also the key to extending the service life of the track structure and improving train safety and smoothness. The paper provides a comprehensive review of the multi-source data collection methods, the integrated data management, and the multi-dimensional data applications for slab tracks from a full life cycle perspective. The data detection and monitoring methods across the design, construction, and O&M (Operation and Maintenance) phases of slab tracks are summarized, offering a potential direction for better refinement and intelligent data collection. In addition, the paper reviews the data management system at different life cycle stages of the slab track, and a integrated full life cycle data management framework is proposed. Also considered is the application of related complex mass data, in which we summarize the maintenance indexes to evaluate and predict the current and future quality of slab tracks. This study aims to lay a foundation for future scientific maintenance and repair strategies of slab tracks in high-speed railways.
High-precision magnetization vector inversion: application to magnetic data in the presence of significant remanent magnetization
Authors: Li Xiangdong , Liu Shuang , Liu Yunxiang , Ding Fufeng , Jian Xiange , Hu Xiangyun
Published: November 2022

Magnetization vector inversion is essential for obtaining magnetization vector information from subsurface rocks. To obtain focused inversion results that better match the true magnetization distributions, sparse constraints are considered to constrain the objective function. A compact magnetization vector inversion method is proposed that can provide accurate inversion results for magnetic data with significant remanent magnetization. Considering the sparse constraint and the correlation between the three magnetization components with different directions, the L1-norm is modified and introduced into the inversion algorithm to obtain compact results. Furthermore, to reduce the computational cost, a randomized singular value decomposition is used to replace the traditional singular value decomposition and iteratively minimize the proposed objective function. Two synthetic models with different magnetization directions are developed to verify the performance of the proposed method. The results of magnetization vectors obtained by the proposed method are focused and accurate. Finally, the proposed method is applied to igneous rocks with strong remanent magnetization in the Haba River area of northwestern China. The distributions, directions of total magnetization and remanent magnetization of the medium-base igneous rocks are revealed by the sparse magnetization vector inversion method, which provides a wealth of information about the concealed deposits in the area.
On the kinematic morphology around haloes
Authors: Luo Xiaolin , Xu Xiangling , Wang Xin
Published: November 2022

In this paper, we report an interesting kinematic phenomenon around the haloes’ edge related to the ‘splashback’ radius. After the shell-crossing, cosmic flow exhibits various rotational morphologies via stream-mixing. Vorticity is generated in a particular way that coincides with the large-scale structure. Notably, one specific flow morphology, which is spiralling inward and compressing in the third direction, concentrates around haloes. A detailed examination that reveals a sharp change in the logarithmic derivative of its volume fraction coincides with the location of the splashback radius Rsp defined as the outermost caustic structure. Such a feature encodes valuable phase-space information and provides a new perspective on understanding the dynamical evolution of haloes. As a volume-weighted quantity, the profile of flow morphology is purely kinematic. And unlike other related studies, the rotational flow morphologies capture the anisotropic phase structure in the multistream region.
Comprehensive comparison of gene expression diversity among a variety of human stem cells
Authors: Yamatani Yukiyo , Nakai Kenta
Published: November 2022

Several factors, including tissue origins and culture conditions, affect the gene expression of undifferentiated stem cells. However, understanding the basic identity across different stem cells has not been pursued well despite its importance in stem cell biology. Thus, we aimed to rank the relative importance of multiple factors to gene expression profile among undifferentiated human stem cells by analyzing publicly available RNA-seq datasets. We first conducted batch effect correction to avoid undefined variance in the dataset as possible. Then, we highlighted the relative impact of biological and technical factors among undifferentiated stem cell types: a more influence on tissue origins in induced pluripotent stem cells than in other stem cell types; a stronger impact of culture condition in embryonic stem cells and somatic stem cell types, including mesenchymal stem cells and hematopoietic stem cells. In addition, we found that a characteristic gene module, enriched in histones, exhibits higher expression across different stem cell types that were annotated by specific culture conditions. This tendency was also observed in mouse stem cell RNA-seq data. Our findings would help to obtain general insights into stem cell quality, such as the balance of differentiation potentials that undifferentiated stem cells possess.
Glioblastoma management in a lower middle-income country: Nationwide study of compliance with standard care protocols and survival outcomes in Ukraine
Authors: Rozumenko Artem , Kliuchka Valentyn , Rozumenko Volodymir , Daschakovskiy Andriy , Fedorenko Zoja
Published: November 2022

Background

The effective treatment of high-grade gliomas is a complex problem that requires ubiquitous implementation of sophisticated therapy protocols. The present study aimed to perform population-based analysis of glioblastoma management in lower-middle-income countries.

Methods

The National Cancer Registry of Ukraine was screened for the records of adult patients with primary glioblastomas diagnosed in 2015–2019. Survival analysis was performed using Kaplan–Meier method and a multivariable Cox model.

Results

A total of 2973 adult patients with histologically confirmed glioblastoma were included in the study. Mean age of patients was 55.6 ± 11.4 years, males slightly prevailed—1541 (51.8%) cases. The completed clinical protocol including surgery followed by chemoradiotherapy was applied only in 658 (19.0%) patients. The minority of patients 743 (25.0%) were treated at the academic medical centers, where patients were more likely to receive combined treatment 70.1% compared with 57.9% (P  = .0001) at the community hospitals. The overall median survival was 10.6 ± 0.2 months, and the 2-year survival rate was 17%. The number of utilized treatment modalities contributed to better survival rates and was associated with lower hazard ratio: Protocol with 2 modalities — 0.62 (P = .0001), 3 modalities — 0.48 (P = .0001).

Conclusions

The management of glioblastoma in lower-middle-income countries is characterized by insufficient availability of treatment in academic medical centers and low rates of advanced therapy application. Survival analysis showed similar prognostic risk factors and outcomes compared with high-income countries.
State Neutrality and Religion in Europe: What’s the Prospect?
Authors: Evans Malcolm
Published: November 2022

This article examines the jurisprudence under the European Convention on Human Rights concerning the role of the state in relation to matters of religious belief. The Court’s approach to this topic has changed markedly over the last 30 years and has become increasingly focussed on the idea of ‘neutrality’. This, it is suggested, is a significant error. The article highlights the shortcomings of the approaches it has adopted and argues that the essence of neutrality under the European Convention on Human Rights does not lie in the nature of the relationship between the state and religion or belief but in the manner in which the state approaches the exercise of the substantive right itself.
Scandinavian Surgical Society
Authors: Lindfors Nina C. , Svendsen Lars Bo , Glent John Christian F. , Glambek Inge , Haraldsdóttir Kristin H. , Andersen Per V. , Almquist Martin
Published: November 2022

Scandinavian Surgical Society (SSS), Nordisk Kirurgisk Förening, founded in 1893, is the oldest international surgical society in the world. The purpose of the society is to promote scientific and clinical work as well as education in the field of surgery in the Nordic countries; Denmark, Finland, Sweden, Norway and Iceland. Nordic co-operation has long traditions in the medical field. The surgical development through the surgical communities and the long-term co-operation between the Nordic surgeons have affected the patient care and development of surgery throughout the Nordic region. An overview and a historical glance of the surgical communities in the Nordic countries from the 18th century are described as well as activities in the SSS from the beginning of 1893 to these days.
The effect of medial only versus medial and lateral hamstring lengthening on transverse gait parameters in cerebral palsy
Authors: Bezuidenhout Louis , Church Chris , Henley John , Salazar-Torres Jose J. , Lennon Nancy , Shields Thomas , Miller Freeman , Shrader M. Wade
Published: November 2022

Benefits of hamstring lengthening surgery on the sagittal plane in children with cerebral palsy have been previously demonstrated, but there is limited information on its effects on the transverse plane. This study compared the effects of medial hamstring lengthening (MHL) with those of medial and lateral hamstring lengthening (MLHL) procedures in the transverse plane. Children with gross motor function classification system (GMFCS) levels I–III who had MHL or MLHL were included. Baseline, short- (1–2 years), and long-term (3+ years) postoperative three-dimensional gait analysis outcomes were compared using analysis of variance. Children were excluded if they had concurrent osteotomies or tendon transfers. One hundred fifty children (235 limbs) were included, with 110 limbs in the MHL group (age 8.5 ± 4.1 years, GMFCS I-27%, II-52%, and III-21%) and 125 limbs in the MLHL group (age 10.0 ± 4.0 years, GMFCS I-23%, II-41%, and III-37%). Time between surgery and short- and long-term follow-up gait analysis was 1.5 ± 0.6 years and 6.6 ± 2.9 years, respectively. Transmalleolar axis became more external after MHL at both short and long terms (P < 0.05), whereas there were only significant differences at long term in MLHL (P < 0.05). Although hamstring lengthening has a positive impact on stance phase knee extension in children with cerebral palsy, intact lateral hamstrings after MHL likely contribute to increased tibial external rotation after surgery. Significant increases in external rotation at the knee in the long term are likely related to a trend present with growth in children with cerebral palsy rather than a direct result of surgical intervention.
Radiologic, clinical, and functional evaluation of children with lateral humeral condyle fractures using the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire
Authors: Abusaq Ibrahim , Martins Antoine , Mansour Mounira , Samba Antoine , Dimeglio Alain , Canavese Federico
Published: November 2022

This study investigated the clinical and radiologic outcomes of lateral humeral condyle (LHC) fractures in children and evaluated the functional outcome of these injuries according to the type of treatment using the Quick DASH questionnaire. Data on consecutive children admitted to the Emergency Department for LHC fracture (01/11–12/18) were collected from their charts. Anterior-posterior and lateral radiographs of the injured elbow were used to classify each fracture according to Jakob’s classification, and to detect any other concomitant bone lesions. Data on pain, stiffness, impact on daily activities, skin lesions, surgical-site infection, and range of motion were retrieved. The Quick DASH questionnaire was used to evaluate functional outcome. Forty-eight children with a mean age at trauma of 6.06 ± 2.22 years (32 males; mean follow-up: 75 ± 25 months) were reviewed. The overall Quick DASH score was 4 (0–15.9); it was 2.69 ± 0.31 in Jakob-1 (n = 12; 25%), 3 ± 1.06 in Jakob-2 (n = 19; 39.6%), and 3.06 ± 1.56 in Jakob-3 fractures (n = 17; 35.4%). Functional outcomes were similar irrespective of the severity of displacement, type of treatment, length of postoperative immobilization, and presence of associated fracture (P > 0.05). Quick DASH scores in children less than 8 years (2.77 ± 0.44) and in those more than 8 years (3.47 ± 2.13) were similar (P > 0.05). Five out of 48 patients developed one complication (10.5%). Good functional and radiologic outcomes can be expected in children with LHC fractures irrespective of the amount of initial displacement, type of treatment, length of postoperative immobilization, and age at surgery. Families should be warned about potential complications although these are most often minor. Level of evidence: III.
The incidence of congenital pseudarthrosis of the clavicle and review of the literature
Authors: Rehm Andreas , Ashby Elizabeth , Thahir Azeem , Ngu Albert W.T. , Kobezda Tamás , Ong Joshua C.Y. , Granger Luke
Published: November 2022

The aim of this study was to identify the hitherto unknown incidence of congenital pseudarthrosis of the clavicle (CPC), based on a cohort of continuous livebirths born in our hospital, to review the literature and investigate if there is evidence supporting the published association between left-sided CPC and dextrocardia. From our electronic medical record and radiology databases, we identified all live births and patients with the diagnosis of CPC born from 2000 to 2016. We reviewed the imaging which included one or both clavicles to search for unrecorded CPC cases and reviewed all retrievable CPC publications listed in PubMed and publications quoted within these publications going back to 1910. We identified 87 407 livebirths of which 41 800 had radiological studies done, 14 885 showing one or both clavicles. We found five cases of CPC, two from the electronic database and three from our imaging review, giving an incidence of 1 of 17 481 livebirths. We identified 138 publications reporting paediatric and adult CPC cases and 12 review articles, including 429 patients (187 female; 159 male; 83 unknown) with 456 CPCs and a minimum of 24 additional patients from case reports for which we could not retrieve details. Two publications reported one case of left-sided CPC with dextrocardia, either not showing left/right marking or only showing the CPC with the aortic knob on the same side. We report the first CPC incidence of 0.0057%, provide the by far most inclusive CPC epidemiology based on 429 patients and could not find reliable proof that there has ever been a patient with left-sided CPC which was associated with dextrocardia.
The effect of the caudal insertion angle of pedicle screws on postoperative thoracic kyphosis in adolescent idiopathic scoliosis: a pilot study
Authors: Karami Mohsen , Eghbali Ahmad , Khaleghnejad Tabari Ahmad , Moradi Shahrbabak Mahdi , Keyhaninejad Nima
Published: November 2022

The study was a prospective analysis of collected data to compare the effect of the insertion angle (parallel or oblique relative to the upper-end plates) of thoracic pedicle screws on postoperative thoracic kyphosis in patients with idiopathic thoracic scoliosis. This study was conducted on idiopathic adolescent scoliosis (AIS) patients. Two groups of patients were defined according to the insertion angle of thoracic pedicle screws in relation to the upper-end plate of the corresponding vertebra, the insertion angles being either oblique or parallel. Seven consecutive AIS patients were compared in each group. Pre- and postoperative standing X-rays were obtained. Cobb’s angles, sagittal parameters such as thoracic kyphosis (TK) (T1–T12) and lumbar lordosis (LL) (L1–S1) were all measured. The average of the main curve or compensatory curve corrections showed no significant differences between the two groups. From a sagittal profile perspective, the mean TK in the oblique screw group was 39.3 ± 11.5 preoperatively, which was reduced to 30.9 ± 6.41 after surgery. The mean TK in the parallel group was 36.4 ± 14 preoperatively and 42.1 ± 13.9 postoperatively. There was a significant reduction in TK in the oblique screws group compared with the second group (P = 0.038). The insertion angle of pedicle screws had no significant effect on Cobb’s angle and lumbar lordosis changes. However, oblique insertion of thoracic screws decreased thoracic kyphosis postoperatively, which could be considered a negative point. As such, the insertion of thoracic screws in a caudal direction should not be routinely used because of its lordogenic effect.
Advanced sperm tests and impact on clinical male factor management
Authors: Nam Catherine S. , Mehta Akanksha
Published: November 2022

Purpose of review

Although semen analysis remains a cornerstone of male fertility evaluation, conventional semen analysis parameters do not assess for DNA integrity or functional capacity of sperm. Sperm DNA fragmentation (SDF) and sperm aneuploidy tests have been utilized as adjunct tools to distinguish fertile and infertile men and predict pregnancy outcomes. This review serves as an update on indications and utility of advanced sperm tests, as well as associated controversies and limitations.

Recent findings

Elevated SDF is associated with prolonged time to pregnancy, lower chance of spontaneous pregnancy, and lower live birth rates. Sperm aneuploidy is more frequent in infertile men, in male partners of couples experiencing recurrent pregnancy loss, and recurrent failure of assisted reproductive technology (ART). These tests can, therefore, provide important information to guide management and counseling of infertile couples to optimize reproductive outcomes.

We evaluated data surrounding SDF and sperm aneuploidy tests, which are utilized both within and beyond the scope of AUA/ASRM guidelines. While the tests at hand require further standardization and randomized controlled studies, the current data suggest strong associations with pregnancy outcomes and can be utilized to counsel and manage infertile males.
VALPROIC ACID INHIBITS CLASSICAL MONOCYTE-DERIVED TISSUE FACTOR AND ALLEVIATES HEMORRHAGIC SHOCK-INDUCED ACUTE LUNG INJURY IN RATS
Authors: Shao Lina , Wu Bing , Liu Chang , Chong Wei
Published: November 2022

Background: Monocytes and monocyte-derived tissue factor (TF) promote the development of sepsis-induced acute lung injury (ALI). Classical monocytes (C-Mcs) can be induced to express TF. Valproic acid (VPA) alleviates hemorrhagic shock (HS)–induced ALI (HS/ALI) and inhibits TF expression in monocytes. We hypothesized that C-Mcs and C-Mc–derived TF promoted HS/ALI and that VPA could inhibit C-Mc–derived TF expression and attenuate HS/ALI. Methods: Wistar rats and THP-1 cells were used to evaluate our hypothesis. Monocyte subtypes were analyzed by flow cytometry; mRNA expression was measured by fluorescence quantitative polymerase chain reaction; protein expression was measured by Western blotting, immunofluorescence, or immunohistology; inflammatory cytokines levels were measured by enzyme-linked immunosorbent assay; and ALI scores were used to determine the degree of ALI. Results: The blood %C-Mcs and C-Mcs/non–C-Mcs ratios, monocyte TF levels, serum and/or lung inflammatory cytokine levels, and ALI scores of HS rats were significantly increased (P < 0.05). After monocyte depletion and thrombin inhibition, the inflammatory cytokine levels and ALI scores were significantly decreased (P < 0.05). VPA reduced the %C-Mcs and C-Mc/non-C-Mc ratios, TF expression, inflammatory cytokine levels, and ALI scores during HS (P < 0.05) and inhibited HS-induced monocyte Egr-1 and p-ERK1/2 expression (P < 0.05). VPA inhibited hypoxia-induced TF expression in THP-1 cells by regulating the p-ERK1/2–Egr-1 axis. Conclusion: C-Mcs and C-Mc–derived TF accelerate the development of HS/ALI by increasing thrombin production. VPA inhibits HS-induced C-Mc production of TF by regulating the p-ERK1/2–Egr-1 axis and alleviates HS/ALI.
Prophage-encoded small protein YqaH counteracts the activities of the replication initiator DnaA in Bacillus subtilis
Authors: Ventroux Magali , Noirot-Gros Marie-Francoise
Published: November 2022

Bacterial genomes harbour cryptic prophages that are mostly transcriptionally silent with many unannotated genes. Still, cryptic prophages may contribute to their host fitness and phenotypes. In Bacillus subtilis, the yqaF-yqaN operon belongs to the prophage element skin, and is tightly repressed by the Xre-like repressor SknR. This operon contains several small ORFs (smORFs) potentially encoding small-sized proteins. The smORF-encoded peptide YqaH was previously reported to bind to the replication initiator DnaA. Here, using a yeast two-hybrid assay, we found that YqaH binds to the DNA binding domain IV of DnaA and interacts with Spo0A, a master regulator of sporulation. We isolated single amino acid substitutions in YqaH that abolished the interaction with DnaA but not with Spo0A. Then, using a plasmid-based inducible system to overexpress yqaH WT and mutant derivatives, we studied in

B. subtilis

the phenotypes associated with the specific loss-of-interaction with DnaA (DnaA_LOI). We found that expression of yqaH carrying DnaA_LOI mutations abolished the deleterious effects of yqaH WT expression on chromosome segregation, replication initiation and DnaA-regulated transcription. When YqaH was induced after vegetative growth, DnaA_LOI mutations abolished the drastic effects of YqaH WT on sporulation and biofilm formation. Thus, YqaH inhibits replication, sporulation and biofilm formation mainly by antagonizing DnaA in a manner that is independent of the cell cycle checkpoint Sda.
Potential for bias in (sero)prevalence estimates when not accounting for test sensitivity and specificity
Authors: Haile Sarah R , Kronthaler David
Published: November 2022

Background

The COVID-19 pandemic has led to many studies of seroprevalence. A number of methods exist in the statistical literature to correctly estimate disease prevalence or seroprevalence in the presence of diagnostic test misclassification, but these methods seem to be less known and not routinely used in the public health literature. We aimed to examine how widespread the problem is in recent publications, and to quantify the magnitude of bias introduced when correct methods are not used.

Methods

A systematic review was performed to estimate how often public health researchers accounted for diagnostic test performance in estimates of seroprevalence. Using straightforward calculations, we estimated the amount of bias introduced when reporting the proportion of positive test results instead of using sensitivity and specificity to estimate disease prevalence.

Results

Of the seroprevalence studies sampled, 78% (95% CI 72% to 82%) failed to account for sensitivity and specificity. Expected bias is often more than is desired in practice, ranging from 1% to 12%.

Conclusions

Researchers conducting studies of prevalence should correctly account for test sensitivity and specificity in their statistical analysis.
A draft genome of the ascomycotal fungal speciesPseudopithomyces maydicus(familyDidymosphaeriaceae)
Authors: Arumugam Krithika , Ho Sherilyn , Bessarab Irina , Goh Falicia Q. Y. , Haryono Mindia A. S. , Santillan Ezequiel , Wuertz Stefan , Chow Yvonne , Williams Rohan B. H.
Published: November 2022

We report a draft genome of the ascomycotal fungal species Pseudopithomyces maydicus (isolate name SBW1) obtained using a culture isolate from brewery wastewater. From a 22 contig assembly, we predict 13502 protein coding gene models, of which 4389 (32.5%) were annotated to KEGG Orthology and identify 39 biosynthetic gene clusters.
Single-cell Mendelian randomisation identifies cell-type specific genetic effects on human brain disease and behaviour
Authors: Haglund Alexander , Zuber Verena , Yang Yifei , Abouzeid Maya , Feleke Rahel , Ko Jeong Hun , Nott Alexi , Babtie Ann C. , Mills James D. , Muhammed Louwai , Laaniste Liisi , Gveric Djordje O. , Clode Daniel , Pagni Susanna , Bellampalli Ravishankara , Somani Alyma , McDade Karina , Anink Jasper J. , Mesarosova Lucia , Aronica Eleonora , Thom Maria , Sisodiya Sanjay M. , Srivastava Prashant K. , Malhotra Dheeraj , Bryois Julien , Bottolo Leonardo , Johnson Michael R.
Published: November 2022

Translating genome-wide association loci to therapies requires knowledge of the causal genes, their directionality of effect and the cell-types in which they act. To infer these relationships in the human brain, we implemented Mendelian randomisation using single cell-type expression quantitative trait loci (eQTLs) as genetic anchors. Expression QTLs were mapped across 8 major cell-types in brain tissue exclusively ascertained from donors with no history of brain disease. We report evidence for a causal association between the change in expression of 118 genes and one or more of 16 brain phenotypes, revealing candidate targets for risk mitigation and opportunities for shared preventative therapeutic strategies. We highlight key causal genes for neurodegenerative and neuropsychiatric disease and for each, we report its cellular context and the therapeutic directionality required for risk mitigation. Our use of control samples establishes a new resource for the causal interpretation of GWAS risk alleles for human brain phenotypes.
CiliaMiner: an integrated database for Ciliopathy Genes and Ciliopathies
Authors: Turan Merve Gül , Orhan Mehmet Emin , Cevik Sebiha , Kaplan Oktay I.
Published: November 2022

Cilia are found in eukaryotic species ranging from single-celled organisms, such asChlamydomonas reinhardtii, to humans, but not in plants. The ability to respond to repellents and/or attractants, regulate cell proliferation and differentiation, and provide cellular mobility are just a few examples of how crucial cilia are to cells and organisms. Over 30 distinct rare disorders generally known as ciliopathy are caused by abnormalities or functional impairments in cilia and cilia-related compartments. Because of the complexity of ciliopathies and the rising number of ciliopathies and ciliopathy genes, a ciliopathy-oriented and up-to-date database is required. In addition, disorders not yet known as ciliopathy but have genes that produce cilia localizing proteins have yet to be classified. Here we present CiliaMiner, a manually curated ciliopathy database that includes ciliopathy lists collected from articles and databases. Analysis reveals that there are 55 distinct disorders likely related to ciliopathy, with over 4000 clinical manifestations. Based on comparative symptom analysis and subcellular localization data, diseases are classified as primary, secondary, or atypical ciliopathies. CiliaMiner provides easy access to all of these diseases and disease genes, as well as clinical features and gene-specific clinical features, as well as subcellular localization of each protein. Additionally, the orthologs of disease genes are also provided for mice, zebrafish, Xenopus, Drosophila, andC. elegans. CiliaMiner (https://kaplanlab.shinyapps.io/ciliaminer) aims to serve the cilia community with its comprehensive content, and highly enriched interactive heatmaps, and will be continually updated.
Targeted and Explorative Profiling of Kallikrein Proteases and Global Proteome Biology of Pancreatic Ductal Adenocarcinoma, Chronic Pancreatitis, and Normal Pancreas Highlights Disease-Specific Proteome Remodelling
Authors: Werner Janina , Bernhard Patrick , Cosenza-Contreras Miguel , Pinter Niko , Fahrner Matthias , Pallavi Prama , Eberhard Johannes , Bronsert Peter , Rückert Felix , Schilling Oliver
Published: November 2022

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive and lethal malignancies worldwide with an urgent need for new diagnostic and therapeutic strategies. One major risk factor for PDAC is the pre-indication of chronic pancreatitis (CP), which represents highly inflammatory pancreatic tissue. Kallikreins (KLKs) are secreted serine proteases that play an important role in various cancers as components of the tumor microenvironment. Previous studies of KLKs in solid tumors largely relied on either transcriptomics or immunodetection. We present one of the first targeted mass spectrometry profiling of kallikrein proteases in PDAC, CP, and normal pancreas. We show that KLK6 and KLK10 are significantly upregulated in PDAC (n=14) but not in CP (n=7) when compared to normal pancreas (n=21), highlighting their specific intertwining with malignancy. Additional explorative proteome profiling identified 5936 proteins in our pancreatic cohort and observed disease-specific proteome rearrangements in PDAC and CP. As such, PDAC features an enriched proteome motif for extracellular matrix (ECM) and cell adhesion while there is depletion of mitochondrial energy metabolism proteins, reminiscent of the Warburg effect. Although often regarded as a PDAC hallmark, the ECM fingerprint was also observed in CP, alongside with a prototypical inflammatory proteome motif as well as with an increased wound healing process and proteolytic activity, thereby possibly illustrating tissue autolysis. Proteogenomic analysis based on publicly accessible data sources identified 112 PDAC-specific and 32 CP-specific single amino acid variants, which among others affect KRAS and ANKHD1. Our study emphasizes the diagnostic potential of kallikreins and provides novel insights into proteomic characteristics of PDAC and CP.
Highly potent antisense oligonucleotides (ASOs) targeting the SARS-CoV-2 RNA genome
Authors: Dauksaite V. , Tas A. , Wachowius F. , Spruit A. , van Hemert M.J. , Snijder E.J. , van der Veer E.P. , van Zonneveld A.J.
Published: November 2022

Currently the world is dealing with the third outbreak of the human-infecting coronavirus with potential lethal outcome, cause by a member of the Nidovirus family, the SARS-CoV-2. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused the last worldwide pandemic. Successful development of vaccines highly contributed to reduce the severeness of the COVID-19 disease. To establish a control over the current and newly emerging coronaviruses of epidemic concern requires development of substances able to cure severely infected individuals and to prevent virus transmission. Here we present a therapeutic strategy targeting the SARS-CoV-2 RNA using antisense oligonucleotides (ASOs) and identify locked nucleic acid gapmers (LNA gapmers) potent to reduce by up to 96% the intracellular viral loadin vitro. Our results strongly suggest promise of our preselected ASOs for further development as therapeutic or prophylactic anti-viral agents.

One sentence summary

ASOs (LNA gapmers) targeting the SARS-CoV-2 RNA genome have been effective in viral RNA (load) reductionin vitro.
Fast protein structure searching using structure graph embeddings
Authors: Greener Joe G , Jamali Kiarash
Published: November 2022

Comparing and searching protein structures independent of primary sequence has proved useful for remote homology detection, function annotation and protein classification. Fast and accurate methods to search with structures will be essential to make use of the vast databases that have recently become available, in the same way that fast protein sequence searching underpins much of bioinformatics. We train a simple graph neural network using supervised contrastive learning to learn a low-dimensional embedding of protein structure. The method, called Progres, is available as software athttps://github.com/greener-group/progresand as a web server athttps://progres.mrc-lmb.cam.ac.uk. It has accuracy comparable to the best current methods and can search the AlphaFold database TED domains in a tenth of a second per query on CPU.
Characterization of a novel deep-intronic variant inDYNC2H1identified by whole-exome sequencing in a patient with a lethal form of a short-rib thoracic dysplasia type III
Authors: Buchh Muqsit , Gillespie Patrick J. , Treat Kayla , Abreu Marco A. , Schwantes-An Tae-Hwi Linus , Helm Benjamin M. , Fang Fang , Xuei Xiaoling , Mantcheva Lili , Suhrie Kristen R. , Graham Brett H. , Conboy Erin , Vetrini Francesco
Published: November 2022

Biallelic pathogenic variants inDYNC2H1are the cause of short-rib thoracic dysplasia type III with or without polydactyly (OMIM #613091), a skeletal ciliopathy characterized by thoracic hypoplasia due to short ribs. In this report, we review the case of a patient who was admitted to the Neonatal Intensive Care Unit (NICU) of Indiana University Health (IUH) for respiratory support after experiencing respiratory distress secondary to a small, narrow chest causing restrictive lung disease. Additional phenotypic features include postaxial polydactyly, short proximal long bones, and ambiguous genitalia were noted. Exome sequencing (ES) revealed a maternally inherited likely pathogenic variant c.10322C > T p.(Leu3448Pro) in theDYNC2H1gene. However, there was no variant found on the paternal allele. Microarray analysis to detect deletion or duplication inDYNC2H1was normal. Therefore, there was insufficient evidence to establish a molecular diagnosis. To further explore the data and perform additional investigations, the patient was subsequently enrolled in the Undiagnosed Rare Disease Clinic (URDC) at Indiana University School of Medicine (IUSM). The investigators at the URDC performed a reanalysis of the ES raw data, which revealed a paternally inheritedDYNC2H1deep-intronic variant c.10606-14A > G predicted to create a strong cryptic acceptor splice site. Additionally, the RNA sequencing of fibroblasts demonstrated partial intron retention predicted to cause a premature stop codon and nonsense-mediated mRNA decay (NMD). Droplet digital RT-PCR (RT-ddPCR) showed a drastic reduction by 74% ofDYNCH2H1mRNA levels. As a result, the intronic variant was subsequently reclassified as likely pathogenic resulting in a definitive clinical and genetic diagnosis for this patient. Reanalysis of ES and fibroblast mRNA experiments confirmed the pathogenicity of the splicing variants to supplement critical information not revealed in original ES or CMA reports. The NICU and URDC collaboration ended the diagnostic odyssey for this family; furthermore, its importance is emphasized by the possibility of prenatally diagnosing the mother's current pregnancy.
A dual-pathway model for examining the effects of customer mistreatment on an employee's customer-directed counterproductive work behavior: can job autonomy make a difference?
Authors: Lu Wenzhu , Sun Bo , Yu Shengxian , Liu Shanshi
Published: November 2022

Purpose

This research examined how customer mistreatment activates individual customer-directed counterproductive work behavior (CWBC) by investigating the mediating roles of negative work reflection and negative affect. It also explored whether job autonomy buffers the negative impact of customer mistreatment on CWBC.

Design/methodology/approach

The authors tested their predictions using an experience-sample method with a sample of data from 79 service workers across eight days. A multilevel structural equation model was used to test the hypotheses.

Findings

The authors found that negative work reflection and negative affect mediated the association between customer mistreatment and CWBC. In addition, job autonomy moderated the indirect impact of daily customer mistreatment on employees' CWBC through negative work reflection and negative affect.

Research limitations/implications

There are some concerns about a common method because all of the study variables were self-reported. Moreover, the study sample consisted of participants recruited exclusively from China, thus limiting this research's generality.

Practical implications

To eliminate the detrimental impact of customer mistreatment, supervisors can strive to improve the autonomy of those who interact with customers frequently to reduce their CWBC.

Originality/value

This study offers an integrative view to explain why service workers engage in CWBC when suffering customer mistreatment by testing the mediating mechanisms of negative reflection and negative affect in the association between daily customer mistreatment and CWBC. Second, the authors have broadened the study of customer mistreatment by introducing job autonomy as a critical condition, eliminating the indirect association between customer mistreatment and CWBC.
The coupling and coordination relationship of the digital economy and tourism industry from the perspective of industrial integration
Authors: Ye Xinliang , Wang Jing , Sun Ruihong
Published: November 2022

Purpose

The digital economy has become a key force supporting the high-quality development of tourism. This paper discusses the coupling coordination relationship and spatiotemporal evolution path of digital economy and tourism in China's provinces.

Design/methodology/approach

This paper uses the entropy method to measure the development level of digital economy and tourism, and establishes coupling coordination model and spatial autocorrelation model to study the interaction between the two industries.

Findings

Results show that the development levels of the two industries are rising, which spatially show a progressively decreasing pattern of east-middle-northeast-west. The coupling coordination degrees of the two industries have increased steadily, but the overall level is still near maladjusted. Spatially, the positive correlation is increasing, but the incongruity of spatial agglomeration is still significant. The coupling coordination evolution path in the provinces shows differentiated characteristics. The migration path is mainly concentrated in Zones I and II. The eastern region has an obvious trend of extending to Zone III, where the tourism industry was the most affected by the pandemic.

Practical implications

The study helps clarify the industrial coupling and coordination relationship in various regions and formulate regional tourism digital transformation strategies to promote the high-quality development of China's tourism industry.

Originality/value

This paper enriches the research on the relationship between digital economy and tourism from the perspective of industrial integration. The development commonality of China's tourism digital transformation summarized provides theoretical reference and demonstration for the coordinated development of China's tourism.
Mind the gap: a critical reflection on hotel employee turnover
Authors: Mohsin Asad , Brochado Ana , Rodrigues Helena
Published: November 2022

Purpose

This study aims to provide a critical reflection research that was carried out to understand more fully how employee turnover has been critical to hotel management’s strategies for constructing a better workplace. Human resources decisions need to be made carefully based on a clear grasp of their effects on hotels and their staff.

Design/methodology/approach

A critical review was conducted with a sample of 160 academic papers that reported findings on staff turnover intentions in hotels.

Findings

The results include a concept map that highlights the two main dimensions found by researchers: hotel staff turnover consequences (i.e. customer satisfaction and financial performance) and antecedents (i.e. individual, job-related, relationship, organisational and opportunities).

Research limitations/implications

The findings underline that staff retention strategies need to focus on managing job-related, organisational and relationship variables as hotel managers have little influence on individual and job opportunity factors.

Originality/value

This study examined 20 years of research summarised in an up-to-date conceptual map. The findings have cross-disciplinary implications.
Does a family-supportive supervisor reduce the effect of work-family conflict on emotional exhaustion and turnover intentions? A moderated mediation model
Authors: Gull Nida , Asghar Muhammad , Bashir Mohsin , Liu Xiliang , Xiong Zhengde
Published: November 2022

Purpose

This study aims to answer how family-supportive supervisor behavior (FSSB) reduces work–family conflict (WFC), family–work conflict (FWC) and employee turnover intention. Based on the conservation of resources theory, this study examines the direct and indirect effects of emotional exhaustion between WFC/FWC and turnover intention. Moreover, this study explores FSSB moderated the role relationship between WFC/FWC and emotional exhaustion.

Design/methodology/approach

This study draws time-lagged data from two phases of a survey of health-care workers working in Chinese hospitals. In the first phase, data on WFC/FWC and turnover were collected from 407 workers. In second round, 387 employees express their feeling about emotional exhaustion and supportive supervisor behavior toward support family members. The data was collected from health-care workers, and a moderated mediation technique was tested using structural equation model-AMOS.

Findings

The findings of this study show that the positive relation between WFC/FWC and emotional exhaustion is high for employees with lower family-supportive supervisors than those with higher family-supportive supervisors. This finding provides further insight into the mechanism of how family and work conflicts impact turnover intention.

Originality/value

To the best of the authors’ knowledge, this is the first empirical study based on the conservation of resources theory, the relationship between WFC/FWC and turnover intention, considering the mediating role of emotional exhaustion and the moderating effects of FSSB. This paper proposes that FSSB can reduce WFCs, addressing a significant research gap in the literature.
Is starting and staying unregistered longer beneficial for firms? The moderating role of institutional quality
Authors: Misganaw Bisrat A. , Assefa Dawit Z. , Colovic Ana
Published: November 2022

Purpose

This study examines the impact of initial informality years on subsequent firm performance and the moderating effect of institutional quality on this relationship.

Design/methodology/approach

The study draws on the World Bank Enterprises Survey (WBES) data covering 116 developing economies over the 2006–2018 period. The study also utilizes data from the Heritage Foundation, the World Bank World Development Indicators (WDI) and the Fraser Institute Economic Freedom Database.

Findings

The study demonstrates that firms that start operation without formal registration perform better than firms that start operation formally. However, contrary to prior studies that show a linear relationship between time spent unregistered and subsequent firm performance, this study finds a non-monotonic relationship between the two – taking an inverted–U shape form. The study further shows that institutional quality at country level moderates this relationship such that firms operating in countries marked by poorly functioning formal institutions benefit from remaining unregistered longer.

Originality/value

This study is the first to show a non-monotonic relationship between the time firms spend without registration and their subsequent performance. By doing so, it reconciles the contradicting findings in the extant literature regarding the relationship between the two variables. It also identifies one important boundary condition – institutional quality – that moderates this relationship.
Evaluation of a dementia prevention program to improve health and social care and promote human rights among older adults
Authors: Kaneko Keisuke , Sasamori Fumihito , Okuhara Masao , Maruo Suchinda Jarupat , Ashida Kazuki , Tabuchi Hisaaki , Akasaki Hisaki , Kobayashi Kazuki , Aoyagi Yuya , Watanabe Noriaki , Nishino Tomoyuki , Terasawa Koji
Published: November 2022

Purpose

This study aims to evaluate a human rights-informed dementia prevention program promoting better health and social care among older adults. In this study, the authors examined whether a dual-task training would improve cognition in healthy older adults.

Design/methodology/approach

Individuals attending the systematic health education program for older adults based in Japan were recruited for study inclusion, and divided into a dual-task training group (TG) and a control group (CG). The TG underwent 90 min of a weekly dual-task training for 12 weeks. Severity of dementia was measured using the Mini-Mental State Examination (MMSE) test. Brain function was assessed using a go/no-go task paradigm, during which cerebral blood flow was additionally measured using functional near-infrared spectroscopy to quantify oxyhemoglobin (oxy-Hb).

Findings

MMSE total score, number of errors in the go/no-go tasks and oxy-Hb values showed significant improvements in the TG.

Research limitations/implications

Owing to the small number of participants allocated to the CG, the results must be interpreted with caution. Replication and further validation based on large-scale, randomized-controlled trials is warranted.

Practical implications

This study highlights potential benefits of incorporating an early prevention training for dementia into a human rights-friendly health education program.

Social implications

This study suggests a potential means to reduce costs of social security and health care by introducing a human rights-informed dementia prevention program.

Originality/value

The results suggest that dual-task training may improve cognitive function in healthy older adults, thereby contributing to better health and improvement of social health care, based on a human rights-informed health education program for the prevention of dementia.
Applied engineering education for soft skills in the context of sustainability and mobility
Authors: Tell Joakim , Hoveskog Maya
Published: November 2022

Purpose

The purpose of this paper is to address the need to rethink the traditional approach to education in the university engineering curriculum. The paper examines two engineering projects led by university students in Sweden: the design and construction of a solar-powered car taking part in the Bridgestone World Solar Challenge and the creation of a business model for the ownership phase of an electric car together with Polestar.

Design/methodology/approach

An extensive literature review was conducted. Students were interviewed and surveyed on their impressions of their learning experience in the two projects and student logbooks reviewed. Problem-based learning (PBL), the Conceiving, Designing, Implementing and Operating approach and the ABCD procedure are used. Results are compared to theories from the literature.

Findings

PBL in real-world settings can increase engineering students’ technical knowledge and improve their technical skills as they solve complex problems or propose solutions to such problems. Such projects also strengthen students’ commitment, self-confidence and self-esteem as well as promote co-operation and creativity. These are soft skills largely absent from traditional engineering education.

Practical implications

Innovative, student-led learning in the applied engineering curriculum can foster students’ soft skills in ways that teacher-led, lecture-style learning does not.

Originality/value

This research offers a timely perspective on an issue of current interest in engineering education: student-led learning versus teacher-led learning. The paper also provides two illustrative student-led projects that focus on sustainability and mobility.