bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term imaging reveals behavioral plasticity during C. elegans dauer exit
Authors: Preusser Friedrich , Neuschulz Anika , Junker Jan Philipp , Rajewsky Nikolaus , Preibisch Stephan
Published: December 2022

Background

During their lifetime, animals must adapt their behavior to survive in changing environments. This ability requires the nervous system to undergo adjustments at distinct temporal scales, from short-term dynamic changes in expression of neurotransmitters and receptors to longer-term growth, spatial and connectivity reorganization, while integrating external stimuli. The nematode Caenorhabditis elegans provides a model of nervous system plasticity, in particular its dauer exit decision. Under unfavorable conditions, larvae will enter the non-feeding and non-reproductive stress-resistant dauer stage and adapt their behavior to cope with the harsh new environment, with active reversal under improved conditions leading to resumption of reproductive development. However, how different environmental stimuli regulate the exit decision mechanism and thereby drive the larva’s behavioral change is unknown. To fill this gap and provide insights on behavioral changes over extended periods of time, we developed a new open hardware method for long-term imaging (12h) of C. elegans larvae.

Results

Our WormObserver platform comprises open hardware and software components for video acquisition, automated processing of large image data (> 80k images/experiment) and data analysis. We identified dauer-specific behavioral motifs and characterized the behavioral trajectory of dauer exit in different environments and genetic backgrounds to identify key decision points and stimuli promoting dauer exit. Combining long-term behavioral imaging with transcriptomics data, we find that bacterial ingestion triggers a change in neuropeptide gene expression to establish post-dauer behavior.

Conclusions

Taken together, we show how a developing nervous system can robustly integrate environmental changes activate a developmental switch and adapt the organism’s behavior to a new environment. WormObserver is generally applicable to other research questions within and beyond the C. elegans field, having a modular and customizable character and allowing assessment of behavioral plasticity over longer periods.
LncRNA weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis
Authors: Liu Miao , Chen Man-Yun , Huang Jia-Meng , Liu Qian , Wang Lin , Liu Rong , Yang Nian , Huang Wei-Hua , Zhang Wei
Published: December 2022

Background

Most prostate cancer patients die from metastasis and lack accurate efficacious biomarkers to monitor the disease behavior, optimize treatment and assess prognosis. Herein, we aimed to identify meaningful lncRNA biomarkers associated with prostate cancer metastatic progression.

Methods

By repurposing microarray probes, 11,624 lncRNAs in prostate cancer were obtained from Gene Expression Omnibus  database (GSE46691, N = 545; GSE29079, N = 235; GSE94767, N = 130). Weighted gene co-expression network analysis was applied to determine the co-expression lncRNA network pertinent to metastasis. Hub lncRNAs were screened. RNA-seq and clinical data from the Cancer Genome Atlas prostate cancer (TCGA-PRAD) cohort (N = 531) were analyzed. Transwell assay and bioinformatic analysis were performed for mechanism research.

Results

The high expression levels of nine hub lncRNAs (FTX, AC005261.1, NORAD, LINC01578, AC004542.2, ZFAS1, EBLN3P, THUMPD3-AS1, GAS5) were significantly associated with Gleason score and increased probability of metastatic progression. Among these lncRNAs, ZFAS1 had the consistent trends of expression in all of the analysis from different cohorts, and the Kaplan-Meier survival analyses showed higher expression of ZFAS1 was associated with shorter relapse free survival. In-vitro studies confirmed that downregulation of ZFAS1 decreased prostate cancer cell migration.

Conclusion

We offered some new insights into discovering lncRNA markers correlated with metastatic progression of prostate cancer using the WGCNA. Some may serve as potential prognostic biomarkers and therapeutic targets for advanced metastatic prostate cancer.
Health-related quality of life by household income in Chile: a concentration index decomposition analysis
Authors: Severino Rodrigo , Espinoza Manuel , Cabieses Báltica
Published: December 2022

Background

Health inequities have a profound impact on all dimensions of people’s lives, with invariably worse results among the most disadvantaged, transforming them into a more fragile and vulnerable population. These unfair inequalities also affect dimensions focused on subjectivity, such as health-related quality of life (HRQoL), which has been positioned, in recent decades, as an important outcome in health decision-making. The main objective of this study is to estimate socioeconomic inequality in HRQoL of Chilean by household income. 

Methods

Secondary analysis of the National Health Survey (ENS 2016–2017, Chile). This survey includes a nationally representative, stratified, and multistage household sample of people aged 15 and above. Socioeconomic inequality in HRQoL (EQ5D) is estimated by the concentration index (CI) ranked by household income. Decomposition analysis is conducted to examine potential explanatory sociodemographic factors. 

Results

The CI for household income inequality in HRQoL was -0.063. The lower the household income, the worse the HRQoL reported by in Chile. The decomposition analysis revealed that socioeconomic position contributes 75,7% to inequality in the quality of life, followed by educational level (21.8%), female gender (17.3%), and type of Health Insurance (15%), age (-19.7%) and residence (-10.8%). Less than 1% corresponds to the unexplained residual component.

Conclusions

Our findings suggest the existence of a disproportionate concentration of worse HRQoL in the most disadvantaged socioeconomic groups in Chile. This inequality is largely, yet not completely, associated with household income. Other significant factors associated with this inequality are education, gender, and healthcare insurance. These results suggest the need of strengthening efforts to reducing socioeconomic gaps in health outcomes in Chile, as a means to achieve social justice and equity in health and healthcare.
Association of ADAMTS proteoglycanases downregulation with IVF-ET outcomes in patients with polycystic ovary syndrome: a systematic review and meta-analysis
Authors: Shi Yanbin , Shi Yang , He Guiyuan , Wang Guang , Liu Hongbo , Shao Xiaoguang
Published: December 2022

Background

A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) is involved in inflammation and fertility in women with polycystic ovary syndrome (PCOS). This study aims to assess the role of ADAMTS level in the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with PCOS, using a meta-analytic approach.

Methods

We systematically searched Web of Science, PubMed, EmBase, and the Cochrane library to identify potentially eligible studies from inception until December 2021. Study assess the role of ADAMTS levels in patients with PCOS was eligible in this study. The pooled effect estimates for the association between ADAMTS level and IVF-ET outcomes were calculated using the random-effects model.

Results

Five studies involving a total of 181 patients, were selected for final analysis. We noted that ADAMTS-1 levels were positively correlated to oocyte maturity (r = 0.67; P = 0.004), oocyte recovery (r = 0.74; P = 0.006), and fertilization (r = 0.46; P = 0.041) rates. Moreover, ADAMTS-4 levels were positively correlated to oocyte recovery (r = 0.91; P = 0.001), and fertilization (r = 0.85; P = 0.017) rates. Furthermore, downregulation of ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-9 was associated with elevated follicle puncture (ADAMTS-1: weighted mean difference [WMD], 7.24, P < 0.001; ADAMTS-4: WMD, 7.20, P < 0.001; ADAMTS-5: WMD, 7.20, P < 0.001; ADAMTS-9: WMD, 6.38, P < 0.001), oocytes retrieval (ADAMTS-1: WMD, 1.61, P < 0.001; ADAMTS-4: WMD, 3.63, P = 0.004; ADAMTS-5: WMD, 3.63, P = 0.004; ADAMTS-9: WMD, 3.20, P = 0.006), and Germinal vesicle oocytes levels (ADAMTS-1: WMD, 2.89, P < 0.001; ADAMTS-4: WMD, 2.19, P < 0.001; ADAMTS-5: WMD, 2.19, P < 0.001; ADAMTS-9: WMD, 2.89, P < 0.001). Finally, the oocytes recovery rate, oocyte maturity rate, fertilization rate, cleavage rate, good-quality embryos rate, blastocyst formation rate, and clinical pregnancy rate were not affected by the downregulation of ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-9 (P > 0.05).

Conclusions

This study found that the outcomes of IVF-EF in patients with PCOS could be affected by ADAMTS-1 and ADAMTS-4; further large-scale prospective studies should be performed to verify these results.
Chiropractic pediatric patient management and interdisciplinary collaboration: a descriptive cross-sectional study of chiropractors in Quebec
Authors: Doucet Chantale , Dubuc Élisa , Imbeau Camille , Pohlman Katherine A. , Blanchette Marc-André
Published: December 2022

Background

Worldwide, many patients, including minors, seek chiropractic care. The purpose of this study was to investigate the practice characteristics of chiropractors who treat pediatric patients in Quebec, Canada.

Methods

We conducted a web-based cross-sectional survey of all licensed chiropractors working in Quebec (Canada). Data were collected using an adapted questionnaire. Descriptive statistics were produced for all the variables collected.

Results

Among our 245 participants (response rate: 21%), 63% were women, and half defined themselves as general musculoskeletal (MSK) health care practitioners. Nearly all participants reported seeing 0–5 new pediatric patients/week, and the most common pediatric age group was 6–12 years old (57%). Pediatric patients were most commonly referred by family members and “word of mouth”. The respondents most frequently indicated that they strongly agreed with statements affirming their confidence in their own diagnostic capacities regarding MSK disorders with respect to all age groups as well as non-MSK disorders with regard to young teens. They reported a moderate level of agreement with similar statements concerning the diagnosis of non-MSK disorders in newborns, preschoolers, and children. Chiropractors rarely referred their pediatric patients to a nurse/family doctor or a pediatrician. When presented with potential pediatric red flags, the respondents commonly indicated that they would refer the patient to a physician in an emergency situation or for comanagement.

Conclusion

Chiropractors in Quebec are confident in their diagnoses of pediatric MSK conditions and refer patients to physicians in the rare event of a worrisome presentation. However, some chiropractors may have expectations that are unsupported by evidence regarding the diagnosis and management of non-MSK complaints.
Comprehensive genomic profiling of a unique liposarcoma arising in a patient with Li–Fraumeni syndrome and the novel detection of c-myc amplification: a case report
Authors: Watanabe Hirofumi , Fujishima Fumiyoshi , Motoi Toru , Aoyama Yayoi , Niihori Tetsuya , Takahashi Masanobu , Umegaki Sho , Oishi Hisashi , Tada Hiroshi , Ichinohasama Ryo , Sasano Hironobu
Published: December 2022

Background

Germline TP53 mutations have been frequently reported in patients with Li–Fraumeni syndrome (LFS), resulting in a predisposition to various malignancies. Mutations other than germline TP53 mutations can also cause LFS-associated malignancies, but their details remain unclear. We describe a novel c-myc amplification in a unique liposarcoma in a patient with LFS.

Case presentation

A female patient with LFS developed breast cancer twice at the age of thirty; both were invasive ductal carcinomas harboring HER2 amplifications. Computed tomography revealed an anterior mediastinal mass, which was surgically resected. Histological analysis revealed three different lesions corresponding to myxoid liposarcoma-, pleomorphic liposarcoma-, and well-differentiated liposarcoma-like lesions. Fluorescence in-situ hybridization (FISH) analysis did not detect MDM2 amplification, Rb1 deletion, break apart signals of EWS, FUS, DDIT3, or c-myc, or c-myc-IGH fusion signals, but it did detect more c-myc signals. Further FISH analysis and comprehensive genomic profiling revealed c-myc amplification. We considered two differential diagnoses, dedifferentiated liposarcoma lacking MDM2 amplification and myxoid pleomorphic liposarcoma (MPLPS), and determined that this case is most likely MPLPS. However, definite diagnosis could not be made because a clear-cut differentiation of the case from liposarcomas was not possible.

Conclusions

A previous study demonstrated that c-myc amplification could not be detected in various liposarcomas, but the present unique liposarcoma showed c-myc amplification, so the c-myc amplification may indicate that the present liposarcoma is an LFS-related tumor. The present case further clarifies the pathological features of MPLPS and LFS-related liposarcomas by broadening their histopathological and genetic diversities.
Association between age and the host response in critically ill patients with sepsis
Authors: Michels Erik H. A. , Butler Joe M. , Reijnders Tom D. Y. , Cremer Olaf L. , Scicluna Brendon P. , Uhel Fabrice , Peters-Sengers Hessel , Schultz Marcus J. , Knight Julian C. , van Vught Lonneke A. , van der Poll Tom ,   MARS consortium, de Beer Friso M. , Bos Lieuwe D. J. , Glas Gerie J. , Hoogendijk Arie J. , van Hooijdonk Roosmarijn T. M. , Horn Janneke , Huson Mischa A. , Schouten Laura R. A. , Straat Marleen , Wieske Luuk , Wiewel Maryse A. , Witteveen Esther , Bonten Marc J. M. , Cremer Olaf M. , Ong David S. Y. , Frencken Jos F. , Klouwenberg Peter M. C. Klein , Koster‐Brouwer Maria E. , van de Groep Kirsten , Verboom Diana M.
Published: December 2022

Background

The association of ageing with increased sepsis mortality is well established. Nonetheless, current investigations on the influence of age on host response aberrations are largely limited to plasma cytokine levels while neglecting other pathophysiological sepsis domains like endothelial cell activation and function, and coagulation activation. The primary objective of this study was to gain insight into the association of ageing with aberrations in key host response pathways and blood transcriptomes in sepsis.

Methods

We analysed the clinical outcome (n = 1952), 16 plasma biomarkers providing insight in deregulation of specific pathophysiological domains (n = 899), and blood leukocyte transcriptomes (n = 488) of sepsis patients stratified according to age decades. Blood transcriptome results were validated in an independent sepsis cohort and compared with healthy individuals.

Results

Older age was associated with increased mortality independent of comorbidities and disease severity. Ageing was associated with lower endothelial cell activation and dysfunction, and similar inflammation and coagulation activation, despite higher disease severity scores. Blood leukocytes of patients ≥ 70 years, compared to patients < 50 years, showed decreased expression of genes involved in cytokine signaling, and innate and adaptive immunity, and increased expression of genes involved in hemostasis and endothelial cell activation. The diminished expression of gene pathways related to innate immunity and cytokine signaling in subjects ≥ 70 years was sepsis-induced, as healthy subjects ≥ 70 years showed enhanced expression of these pathways compared to healthy individuals < 50 years.

Conclusions

This study provides novel evidence that older age is associated with relatively mitigated sepsis-induced endothelial cell activation and dysfunction, and a blood leukocyte transcriptome signature indicating impaired innate immune and cytokine signaling. These data suggest that age should be considered in patient selection in future sepsis trials targeting the immune system and/or the endothelial cell response.

Graphical abstract
Pathogen genomics study of an early medieval community in Germany reveals extensive co-infections
Authors: Bonczarowska Joanna H. , Susat Julian , Mühlemann Barbara , Jasch-Boley Isabelle , Brather Sebastian , Höke Benjamin , Brather-Walter Susanne , Schoenenberg Valerie , Scheschkewitz Jonathan , Graenert Gabriele , Krausse Dirk , Francken Michael , Jones Terry C. , Wahl Joachim , Nebel Almut , Krause-Kyora Ben
Published: December 2022

Background

The pathogen landscape in the Early European Middle Ages remains largely unexplored. Here, we perform a systematic pathogen screening of the rural community Lauchheim “Mittelhofen,” in present-day Germany, dated to the Merovingian period, between fifth and eighth century CE. Skeletal remains of individuals were subjected to an ancient DNA metagenomic analysis. Genomes of the detected pathogens were reconstructed and analyzed phylogenetically.

Results

Over 30% of the individuals exhibit molecular signs of infection with hepatitis B virus (HBV), parvovirus B19, variola virus (VARV), andMycobacterium leprae. Seven double and one triple infection were detected. We reconstructed four HBV genomes and one genome each of B19, VARV, andM. leprae. All HBV genomes are of genotype D4 which is rare in Europe today. The VARV strain exhibits a unique pattern of gene loss indicating that viruses with different gene compositions were circulating in the Early Middle Ages. TheM. lepraestrain clustered in branch 3 together with the oldest to-date genome from the UK.

Conclusions

The high burden of infectious disease, together with osteological markers of physiological stress, reflect a poor health status of the community. This could have been an indirect result of the climate decline in Europe at the time, caused by the Late Antique Little Ice Age (LALIA). Our findings suggest that LALIA may have created an ecological context in which persistent outbreaks set the stage for major epidemics of severe diseases such as leprosy and smallpox hundreds of years later.
Structural variant analysis of a cancer reference cell line sample using multiple sequencing technologies
Authors: Talsania Keyur , Shen Tsai-wei , Chen Xiongfong , Jaeger Erich , Li Zhipan , Chen Zhong , Chen Wanqiu , Tran Bao , Kusko Rebecca , Wang Limin , Pang Andy Wing Chun , Yang Zhaowei , Choudhari Sulbha , Colgan Michael , Fang Li Tai , Carroll Andrew , Shetty Jyoti , Kriga Yuliya , German Oksana , Smirnova Tatyana , Liu Tiantain , Li Jing , Kellman Ben , Hong Karl , Hastie Alex R. , Natarajan Aparna , Moshrefi Ali , Granat Anastasiya , Truong Tiffany , Bombardi Robin , Mankinen Veronnica , Meerzaman Daoud , Mason Christopher E. , Collins Jack , Stahlberg Eric , Xiao Chunlin , Wang Charles , Xiao Wenming , Zhao Yongmei
Published: December 2022

Background

The cancer genome is commonly altered with thousands of structural rearrangements including insertions, deletions, translocation, inversions, duplications, and copy number variations. Thus, structural variant (SV) characterization plays a paramount role in cancer target identification, oncology diagnostics, and personalized medicine. As part of the SEQC2 Consortium effort, the present study established and evaluated a consensus SV call set using a breast cancer reference cell line and matched normal control derived from the same donor, which were used in our companion benchmarking studies as reference samples.

Results

We systematically investigated somatic SVs in the reference cancer cell line by comparing to a matched normal cell line using multiple NGS platforms including Illumina short-read, 10X Genomics linked reads, PacBio long reads, Oxford Nanopore long reads, and high-throughput chromosome conformation capture (Hi-C). We established a consensus SV call set of a total of 1788 SVs including 717 deletions, 230 duplications, 551 insertions, 133 inversions, 146 translocations, and 11 breakends for the reference cancer cell line. To independently evaluate and cross-validate the accuracy of our consensus SV call set, we used orthogonal methods including PCR-based validation, Affymetrix arrays, Bionano optical mapping, and identification of fusion genes detected from RNA-seq. We evaluated the strengths and weaknesses of each NGS technology for SV determination, and our findings provide an actionable guide to improve cancer genome SV detection sensitivity and accuracy.

Conclusions

A high-confidence consensus SV call set was established for the reference cancer cell line. A large subset of the variants identified was validated by multiple orthogonal methods.
Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial
Authors: Snijders Romée J. A. L. M. , Stoelinga Anna E. C. , Gevers Tom J. G. , Pape Simon , Biewenga Maaike , Verdonk Robert C. , de Jonge Hendrik J. M. , Vrolijk Jan Maarten , Bakker Sjoerd F. , Vanwolleghem Thomas , de Boer Ynto S. , Pronk Martine A. M. C. Baven , Beuers Ulrich H. W. , van der Meer Adriaan J. , van Gerven Nicole M. F. , Sijtsma Marijn G. M. , Verwer Bart J. , Gisbertz Ingrid A. M. , Bartelink Maartje , van den Brand Floris F. , Sebib Korkmaz Kerem , van den Berg Aad P. , Guichelaar Maureen M. J. , Soufidi Khalida , Levens Amar D. , van Hoek Bart , Drenth Joost P. H. ,   on behalf of the Dutch Autoimmune Hepatitis Working Group
Published: December 2022

Background

Currently, the standard therapy for autoimmune hepatitis (AIH) consists of a combination of prednisolone and azathioprine. However, 15% of patients are intolerant to azathioprine which necessitates cessation of azathioprine or changes in therapy. In addition, not all patients achieve complete biochemical response (CR). Uncontrolled data indicate that mycophenolate mofetil (MMF) can induce CR in a majority of patients. Better understanding of first-line treatment and robust evidence from randomised clinical trials are needed. The aim of this study was to explore the potential benefits of MMF as compared to azathioprine, both combined with prednisolone, as induction therapy in a randomised controlled trial in patients with treatment-naive AIH.

Methods

CAMARO is a randomised (1:1), open-label, parallel-group, multicentre superiority trial. All patients with AIH are screened for eligibility. Seventy adult patients with AIH from fourteen centres in the Netherlands and Belgium will be randomised to receive MMF or azathioprine. Both treatment arms will start with prednisolone as induction therapy. The primary outcome is biochemical remission, defined as serum levels of alanine aminotransferase and immunoglobulin G below the upper limit of normal. Secondary outcomes include safety and tolerability of MMF and azathioprine, time to remission, changes in Model For End-Stage Liver Disease (MELD)-score, adverse events, and aspects of quality of life. The study period will last for 24 weeks.

Discussion

The CAMARO trial investigates whether treatment with MMF and prednisolone increases the proportion of patients in remission compared with azathioprine and prednisolone as the current standard treatment strategy. In addition, we reflect on the challenges of conducting a randomized trial in rare diseases.

Trial registration

EudraCT 2016-001038-91. Prospectively registered on 18 April 2016.

Graphical Abstract
Effect of positive event recording based on positive psychology on healthy behaviors and readmission rate of patients after PCI: a study protocol for a prospective, randomized controlled trial
Authors: Hu Yao-Yao , Jiang Xin , Mao Fang-Ying , Zhang Jing , Liu Lin , Gu Jie , Wu Qing , Li Chun
Published: December 2022

Background

Unhealthy behaviors of coronary heart disease (CHD) patients are closely related to the occurrence of major heart events, which increases the readmission rate and brings a heavy economic burden to families and society. Therefore, it is necessary for health care workers to take active preventive and therapeutic measures to keep or establish healthy behaviors of patients. Positive psychological intervention has been proved to be effective, but it has not been reported in the field of CHD in China. The purpose of this study is to explore the effects of positive event recording based on positive psychology on the healthy behaviors, readmission rate, and anxiety of patients with CHD, in order to provide new ideas for the development of secondary prevention strategies for CHD.

Methods

This is a prospective, single-center, randomized controlled trial (RCT). The subjects will be enrolled from the Department of Cardiology, the First Affiliated Hospital of Soochow University. There are 80 cases in total; according to the random number table, the subjects are randomly divided into the intervention group (n = 40) and the control group (n = 40). The patients in the intervention group will receive the intervention of recording positive events once a week for 3 months, while the patients in the control group receive conventional nursing. The primary outcomes will include healthy behaviors, readmission rate, and anxiety, and the secondary outcomes will include psychological capital, subjective well-being, and corresponding clinical laboratory indicators. The protocol was approved by the Medical Ethics Committee of Soochow University (approval no. SUDA20200604H01) and is performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. All participants provide written informed consent.

Discussion

This study will verify whether positive event recording based on positive psychology can make patients maintain healthy behaviors, reduce readmission rate, and improve anxiety after PCI. Then, this study will provide new ideas and references for the development of secondary prevention strategies for patients with CHD.

Trial registration

Chinese Clinical Trials Registry 2000034538. Registered on 10 July 2020.
Effect of B7-H4 downregulation induced by Toxoplasma gondii infection on dysfunction of decidual macrophages contributes to adverse pregnancy outcomes
Authors: Cui Lijun , Wang Yu , Ren Liqin , Li Zhidan , Jiang Yuzhu , Wang Chao , Liu Xianbing , Ren Yushan , Hu Xuemei
Published: December 2022

Background

Toxoplasma gondii infection during pregnancy can lead to fetal defect(s) or congenital complications. The inhibitory molecule B7-H4 expressed on decidual macrophages (dMφ) plays an important role in maternal–fetal tolerance. However, the effect of B7-H4 on the function of dMφ during T. gondii infection remains unclear.

Methods

Changes in B7-H4 expression on dMφ after T. gondii infection were explored both in vivo and in vitro. B7-H4-/- pregnant mice (pregnant mice with B7-H4 gene knockout) and purified primary human dMφ treated with B7-H4 neutralizing antibody were used to explore the role of B7-H4 signaling on regulating the membrane molecules, synthesis of arginine metabolic enzymes and cytokine production by dMφ with T. gondii infection. Also, adoptive transfer of dMφ from wild-type (WT) pregnant mice or B7-H4-/- pregnant mice to infected B7-H4-/- pregnant mice was used to examine the effect of B7-H4 on adverse pregnancy outcomes induced by T. gondii infection.

Results

The results illustrated that B7-H4-/- pregnant mice infected by T. gondii had poorer pregnancy outcomes than their wild-type counterparts. The expression of B7-H4 on dMφ significantly decreased after T. gondii infection, which resulted in the polarization of dMφ from the M2 toward the M1 phenotype by changing the expression of membrane molecules (CD80, CD86, CD163, CD206), synthesis of arginine metabolic enzymes (Arg-1, iNOS) and production of cytokines (IL-10, TNF-α) production. Also, we found that the B7-H4 downregulation after T. gondii infection increased iNOS and TNF-α expression mediated through the JAK2/STAT1 signaling pathway. In addition, adoptive transfer of dMφ from a WT pregnant mouse donor rather than from a B7-H4-/- pregnant mouse donor was able to improve adverse pregnancy outcomes induced by T. gondii infection.

Conclusions

The results demonstrated that the downregulation of B7-H4 induced by T. gondii infection led to the dysfunction of decidual macrophages and contributed to abnormal pregnancy outcomes. Moreover, adoptive transfer of B7-H4+ dMφ could improve adverse pregnancy outcomes induced by T. gondii infection.

Graphical Abstract
Molecular characterization and genetic authentication assay for Anopheles ‘hemocyte-like’ cell lines 4a-3A and 4a-3B
Authors: Eggleston Heather , Njoya Kimani , Anderson Cameron E. , Holm Inge , Eiglmeier Karin , Liang Jiangtao , Sharakhov Igor V. , Vernick Kenneth D. , Riehle Michelle M.
Published: December 2022

Background

Anopheles cell lines are used in a variety of ways to better understand the major vectors of malaria in sub-Saharan Africa. Despite this, commonly used cell lines are not well characterized, and no tools are available for cell line identification and authentication.

Methods

Utilizing whole genome sequencing, genomes of 4a-3A and 4a-3B ‘hemocyte-like’ cell lines were characterized for insertions and deletions (indels) and SNP variation. Genomic locations of distinguishing sequence variation and species origin of the cell lines were also examined. Unique indels were targeted to develop a PCR-based cell line authentication assay. Mitotic chromosomes were examined to survey the cytogenetic landscape for chromosome structure and copy number in the cell lines.

Results

The 4a-3A and 4a-3B cell lines are female in origin and primarily of Anopheles coluzzii ancestry. Cytogenetic analysis indicates that the two cell lines are essentially diploid, with some relatively minor chromosome structural rearrangements. Whole-genome sequence was generated, and analysis indicated that SNPs and indels which differentiate the cell lines are clustered on the 2R chromosome in the regions of the 2Rb, 2Rc and 2Ru chromosomal inversions. A PCR-based authentication assay was developed to fingerprint three indels unique to each cell line. The assay distinguishes between 4a-3A and 4a-3B cells and also uniquely identifies two additional An. coluzzii cell lines tested, Ag55 and Sua4.0. The assay has the specificity to distinguish four cell lines and also has the sensitivity to detect cellular contamination within a sample of cultured cells.

Conclusions

Genomic characterization of the 4a-3A and 4a-3B Anopheles cell lines was used to develop a simple diagnostic assay that can distinguish these cell lines within and across research laboratories. A cytogenetic survey indicated that the 4a-3A and Sua4.0 cell lines carry essentially normal diploid chromosomes, which makes them amenable to CRISPR/Cas9 genome editing. The presented simple authentication assay, coupled with screening for mycoplasma, will allow validation of the integrity of experimental resources and will promote greater experimental reproducibility of results.

Graphical abstract
A novel potential mechanism for the development of portal vein thrombosis in cirrhosis based on portal hemodynamics
Authors: Yan Yuling , Xiong Zhuxiang , Wang Xiaoze , Yang Li , Zheng Tinghui , Luo Xuefeng
Published: December 2022

Background

Marked changes in hemodynamics have been suggested to be a potential contributing factor to portal vein thrombosis (PVT) development. This study investigated the effect of portal hemodynamics based on the anatomical structure of the portal venous system on PVT development.

Methods

The morphological features of portal venous system in patients with PVT and those without PVT subgroups were compared. In addition, idealized PV models were established to numerically evaluate the effect of the variation in the angulation of superior mesenteric vein (SMV) and splenic vein (SV) on the hemodynamics of portal venous system.

Results

The angle α (angulation of SMV and SV) in patients with PVT was lower than that in patients without PVT (p < 0.0001), which was the only independent risk factor (odds ratio (OR), 0.90 (95% CI 0.84–0.95); p < 0.0001) for the presence of PVT. With the change in angle α, the flow pattern of blood flow changed greatly, especially the helical flow. When α = 80°, helical flow only appeared at the local PV near the intersection of SMV and SV. When α = 120°, most regions were occupied by the helical flow. In addition, the h2 gradually increased with increasing α, when α = 80°, h2 = 12.6 m/s2; when α = 120°, h2 = 29.3 m/s2.

Conclusions

The angulation of SV and SMV was closely associated with PVT development. Helical flow changed following the varying angulation of SV and SMV. Therefore, angulation of SV and SMV may help to identify high-risk cohorts for future PVT development earlier.
Dynamic edge computing empowered by reconfigurable intelligent surfaces
Authors: Di Lorenzo Paolo , Merluzzi Mattia , Calvanese Strinati Emilio , Barbarossa Sergio
Published: December 2022

In this paper, we propose a novel algorithm for energy-efficient low-latency dynamic mobile edge computing (MEC), in the context of beyond 5G networks endowed with reconfigurable intelligent surfaces (RISs). We consider a scenario where new computing requests are continuously generated by a set of devices and are handled through a dynamic queueing system. Building on stochastic optimization tools, we devise a dynamic learning algorithm that jointly optimizes the allocation of radio resources (i.e., power, transmission rates, sleep mode and duty cycle), computation resources (i.e., CPU cycles), and RIS reflectivity parameters (i.e., phase shifts), while guaranteeing a target performance in terms of average end-to-end delay. The proposed strategy enables dynamic control of the system, performing a low-complexity optimization on a per-slot basis while dealing with time-varying radio channels and task arrivals, whose statistics are unknown. The presence and optimization of RISs helps boosting the performance of dynamic MEC, thanks to the capability to shape and adapt the wireless propagation environment. Numerical results assess the performance in terms of service delay, learning, and adaptation capabilities of the proposed strategy for RIS-empowered MEC.
Use of digital technology to give and receive feedback in clinical training: a scoping review protocol
Authors: Singaram Veena S. , Bagwandeen Chauntelle I. , Abraham Reina M. , Baboolal Sandika , Sofika Dumisa N. A.
Published: December 2022

Background

Feedback is vital to improving trainee competencies in medical education. The challenges of the global COVID-19 pandemic related to social distancing to curb the spread of the virus ignited a rapid transition to online medical education. These changes highlight the need for digital feedback tools that enhance the efficacy and efficiency of feedback practices. This protocol is for a scoping review that aims to identify the different digital tools and applications in medical education as reported in the literature, as well as highlight gaps in the current literature and provide suggestions for future technological developments and research.

Methods and analysis

A review of the relevant literature will be guided using the Joanna Briggs Institute methodological framework for scoping studies. Using the search strategy developed by the authors, an electronic search of the following databases will be conducted: PubMed/MEDLINE, EBSCOhost (academic search complete, CINAHL with full text) Scopus, Google Scholar, Union Catalogue of Theses and Dissertations (UCTD) via SABINET Online and World Cat Dissertations and Theses via OCLC. Studies will be identified by searching literature from January 2010 to date of review. Using a validated data extraction form developed for the scoping review, the review team will screen eligible studies and import them onto an electronic library created specifically for this purpose. Data collection for the review will be documented through a PRISMA-P flowchart, and the scoping review will use a basic descriptive content analysis to analyse and categorise the extracted data. All review steps will involve two or more reviewers.

Dissemination

The review will provide a comprehensive list of digital tools and applications used to enhance feedback in clinical training and inform future technological developments. The findings will be disseminated through medical education conferences and publications.
Haptic feedback intervention decreases the spatial margin when older adults walk through a narrow space
Authors: Hakamata T. , Muroi D. , Kodama K. , Kondo Y. , Higuchi T.
Published: December 2022

Background

The ability to avoid obstacles efficiently and safely is important for older adults to prevent injuries from tripping and falling. It is important to find an optimal spatial margin between the body and an obstacle considering both safety and efficiency. One side of finding the optimal margin is to decrease the margin in terms of motor efficiency. In this study, we tested whether fingertip-contact intervention to obtain haptic feedback information to perceive the relationship between body and the environment could immediately improve spatial perception and collision avoidance behavior (an instantaneous effect).

Methods

Twenty-seven older adults (12 males and 15 females) participated in the experiment. In the intervention of the fingertip-contact group, they lightly touched the edge of a door with both fingertips while walking. The test task before and after the intervention involved grasping a horizontal bar and passing through a narrow opening. As dependent variables, we measured the spatial margin and the collision rate.

Results

The fingertip-contact group showed a significant decrease in the spatial margin after the intervention. On the other hand, there was no significant improvement in the collision rate after the intervention but rather a decrease only in the control group.

Conclusion

The results obtained in this study indicate that touching obstacles with the fingertips had an instantaneous effect, leading to efficient movement learning, although a possible side effect of an increased collision rated was also found. The proposed intervention might promote an efficiency-based strategy due to learning the spatial relationship between the body and the environment, and it may suppress the excessive avoidance of older adults.
High molar activity [18F]tetrafluoroborate synthesis for sodium iodide symporter imaging by PET
Authors: Soloviev Dmitry , Dzien Piotr , Mackintosh Agata , Malviya Gaurav , Brown Gavin , Lewis David
Published: December 2022

Background

Sodium iodide symporter (NIS) imaging by positron emission tomography (PET) is gaining traction in nuclear medicine, with an increasing number of human studies being published using fluorine-18 radiolabelled tetrafluoroborate ([18F]TFB). Clinical success of any radiotracer relies heavily on its accessibility, which in turn depends on the availability of robust radiolabelling procedures providing a radiotracer in large quantities and of high radiopharmaceutical quality.

Results

Here we publish an improved radiolabelling method and quality control procedures for high molar activity [18F]TFB. The use of ammonium hydroxide for [18F]fluoride elution, commercially available boron trifluoride-methanol complex dissolved in acetonitrile as precursor and removal of unreacted [18F]fluoride on Florisil solid-phase extraction cartridges resulted in the reliable production of [18F]TFB on SYNTHRA and TRACERLAB FXFN automated synthesizers with radiochemical yields in excess of 30%, radiochemical purities in excess of 98% and molar activities in the range of 34–217 GBq/µmol at the end of synthesis. PET scanning of a mouse lung tumour model carrying a NIS reporter gene rendered images of high quality and improved sensitivity.

Conclusions

A novel automated radiosynthesis procedure for [18F]tetrafluoroborate has been developed that provides the radiotracer with high molar activity, suitable for preclinical imaging of NIS reporter gene.
Reactive power optimization of a distribution network with high-penetration of wind and solar renewable energy and electric vehicles
Authors: Xu Biao , Zhang Guiyuan , Li Ke , Li Bing , Chi Hongyuan , Yao Yao , Fan Zhun
Published: December 2022

As high amounts of new energy and electric vehicle (EV) charging stations are connected to the distribution network, the voltage deviations are likely to occur, which will further affect the power quality. It is challenging to manage high quality voltage control of a distribution network only relying on the traditional reactive power control mode. If the reactive power regulation potentials of new energy and EVs can be tapped, it will greatly reduce the reactive power optimization pressure on the network. Keeping this in mind, our reasearch first adds EVs to the traditional distribution network model with new forms of energy, and then a multi-objective optimization model, with achieving the lowest line loss, voltage deviation, and the highest static voltage stability margin as its objectives, is constructed. Meanwihile, the corresponding model parameters are set under different climate and equipment conditions. Ultimately, the optimization model under specific scenarios is obtained. Furthermore, considering the supply and demand relationship of the network, an improved technique for order preference by similarity to an ideal solution decision method is proposed, which aims to judge the adaptability of different algorithms to the optimized model, so as to select a most suitable algorithm for the problem. Finally, a comparison is made between the constructed model and a model without new energy. The results reveal that the constructed model can provide a high quality reactive power regulation strategy.
Fault ride-through capability improvement in a DFIG-based wind turbine using modified ADRC
Authors: Mosayyebi Seyed Reza , Shahalami Seyed Hamid , Mojallali Hamed
Published: December 2022

In this paper, an overview of several strategies for fault ride-through (FRT) capability improvement of a doubly-fed induction generator (DFIG)-based wind turbine is presented. Uncertainties and parameter variations have adverse effects on the performance of these strategies. It is desirable to use a control method that is robust to such disturbances. Auto disturbance rejection control (ADRC) is one of the most common methods for eliminating the effects of disturbances. To improve the performance of the conventional ADRC, a modified ADRC is introduced that is more robust to disturbances and offers better responses. The non-derivability of the fal function used in the conventional ADRC degrades its efficiency, so the modified ADRC uses alternative functions that are derivable at all points, i.e., the odd trigonometric and hyperbolic functions (arcsinh, arctan, and tanh). To improve the efficiency of the proposed ADRC, fuzzy logic and fractional-order functions are used simultaneously. In fuzzy fractional-order ADRC (FFOADRC), all disturbances are evaluated using a nonlinear fractional-order extended state observer (NFESO). The performance of the suggested structure is investigated in MATLAB/Simulink. The simulation results show that during disturbances such as network voltage sag/swell, using the modified ADRCs leads to smaller fluctuations in stator flux amplitude and DC-link voltage, lower variations in DFIG velocity, and lower total harmonic distortion (THD) of the stator current. This demonstrates the superiority over conventional ADRC and a proportional-integral (PI) controller. Also, by changing the crowbar resistance and using the modified ADRCs, the peak values of the waveforms (torque and currents) can be controlled at the moment of fault occurrence with no significant distortion.
Tuberculosis treatment outcomes among pulmonary TB patients attending public hospitals in Kebbi State, Northern Nigeria: a four-year retrospective study
Authors: Danlami Mohammed Bashar , Basiru Aliyu , Tajjudeen Yahaya , Bazata Abbas Yusuf , Gulumbe Bashar Haruna , Mohammed Musa
Published: December 2022

Background

In Nigeria, effective case management and evaluation of pulmonary tuberculosis treatment outcomes are an integral part of controlling the spread of infectious diseases. The study reviewed the treatment outcomes of pulmonary tuberculosis and the factors associated with rates of successful and unsuccessful treatment outcomes in the 21 referral hospitals in Kebbi State, Nigeria.

Methods

Documented records of pulmonary tuberculosis patients from January 2018 to December 2021 in 21 Local Area Councils in Kebbi State, Northern Nigeria were reviewed. A structured questionnaire collated the socio-demographic and clinical data from the documented records. Descriptive statistics were used to compute and analyse the outcomes of successful and unsuccessful treatment. Logistic regression models were used to determine the association of socio-demographic and clinical data with the unsuccessful treatment outcomes.

Results

The study reviewed data from 6114 records of TB patients. 1161 (18.9%) started treatment, 963 (82.9%) were males and 198 (17.1%) were females. Of the 1161 patients, 985 (18.2%) had documented treatment outcomes. 932 of 985 (95.1%) had a pulmonary infection. 64 (5.8%) patients with documented treatment outcomes were HIV seropositive. 903 (91.7%) were successfully treated, and 82 (8.3%) failed. Of the patients with failed treatment outcomes, 15 (1.5%) were lost to follow-up, 43 (4.4%) defaulted and 24 (2.4%) died. In the logistic analysis, the odds of unsuccessful treatment outcomes were higher among elderly patients (AOR = 2.00, 95% CI 1.37–2.92), patients with extrapulmonary infections (AOR = 2.40, 95% CI 1.12–5.39), and with old cases of pulmonary TB (AOR = 3.03, 95% CI 1.47–7.19) when compared to their groups.

Conclusions

The study reported a treatment success rate of 91.7% among TB patients attending public hospitals in Kebbi State. The outcome was higher than the projected success rate of 85% set by the WHO. However, one-fourth of the total patients reviewed were not documented for treatment. Therefore, the need to design an appropriate recruitment strategy to identify and enrol those patients for an effective and successful TB control program in Nigeria.
The role of ghrelin peptide among a sample of Egyptian patients with first episode of major depressive disorder
Authors: Okasha Tarek A. , El-Gabry Dina Aly , Ali Marim H. , Gabrielle Fiby F.
Published: December 2022

Background

Major depressive disorder (MDD) is a prominent psychiatric disorder that significantly reduces living quality and increases the risk of suicide. Ghrelin influences the central nervous system (CNS) and impacts reward, inspiration, and signaling pathways in addition to acting as an appetite signal. This case-controlled comparative study focused on the association between serum ghrelin levels and MDD. The study was done during September 2021 and March 2022 on 25 people with MDD and 25 healthy controls. SCID-1 and the Ham-D 17 scales were used to evaluate the cases. The GHQ scale was used to evaluate the controls. The serum ghrelin levels of all samples were determined. The findings were presented, and statistically analyzed to perform an accurate assessment.

Results

There were 50 subjects: 25 cases of MDD and 25 healthy matched controls with non-statistically significant difference to cases as regard gender, marital status, residence, education, age, height, weight and body mass index (BMI). Total serum ghrelin levels among our cases showed a mean value of 4.152, while the controls showed markedly low values, with a mean value of 0.436, showing a statistically significant difference between both groups with p < 0.001. Furthermore, Post Hoc analysis by least significant difference showed a significant difference between mild-severe and moderate-severe groups, although there was no statistically significant difference between mild and moderate groups.

Conclusions

There was a significant indirect correlation between serum ghrelin level and severity of the illness. Further investigations via longitudinal studies and on larger samples are recommended to settle specific causal paths between the two variables.