bluuebunny/crossref_metadata_2025 huggingface dataset:
CHSY1 promotes CD8+ T cell exhaustion through activation of succinate metabolism pathway leading to colorectal cancer liver metastasis based on CRISPR/Cas9 screening
Authors: Sun Guangshun , Zhao Siqi , Fan Zhongguo , Wang Yuliang , Liu Hanyuan , Cao Hengsong , Sun Guoqiang , Huang Tian , Cai Hongzhou , Pan Hong , Rong Dawei , Gao Yun , Tang Weiwei
Published: September 2023

Background

The most common site of metastasis in colorectal cancer (CRC) is the liver and liver metastases occur in more than 50% of patients during diagnosis or treatment. The occurrence of metastasis depends on a series of events known as the invasive-metastasis cascade. Currently, the underlying genes and pathways regulating metastasis initiation in the liver microenvironment are unknown.

Methods

We performed systematic CRISPR/Cas9 screening using an in vivo mouse model of CRC liver metastasis to identify key regulators of CRC metastasis. We present the full results of this screen,which included a list of genes that promote or repress CRC liver colonization. By silencing these genes individually, we found that chondroitin sulfate synthase 1 (CHSY1) may be involved in CRC metastasis. We verified the function of CHSY1 and its involvement in liver metastasis of CRC through in vivo and in vitro experiments.

Result

The results of TCGA and CRISPR/Cas9 showed that CHSY1 was overexpressed in CRC primary and liver metastasis tissues and indicated a worse clinical prognosis. In vitro and in vivo experiments confirmed that CHSY1 facilitated the liver metastasis of CRC and CHSY1 induced CD8+ T cell exhaustion and upregulated PD-L1 expression. The metabolomic analysis indicated that CHSY1 promoted CD8+ T cell exhaustion by activating the succinate metabolism pathway leading to liver metastasis of CRC. Artemisinin as a CHSY1 inhibitor reduced liver metastasis and enhanced the effect of anti-PD1 in CRC. PLGA-loaded Artemisinin and ICG probe reduced liver metastasis and increased the efficiency of anti-PD1 treatment in CRC.

Conclusion

CHSY1 could promote CD8+ T cell exhaustion through activation of the succinate metabolic and PI3K/AKT/HIF1A pathway, leading to CRC liver metastasis. The combination of CHSY1 knockdown and anti-PD1 contributes to synergistic resistance to CRC liver metastasis. Artemisinin significantly inhibits CHSY1 activity and in combination with anti-PD1 could synergistically treat CRC liver metastases. This study provides new targets and specific strategies for the treatment of CRC liver metastases, bringing new hope and benefits to patients.
Palliative care for persons with late-stage Alzheimer’s and related dementias and their caregivers: protocol for a randomized clinical trial
Authors: Toles M. , Kistler C. , Lin F. C. , Lynch M. , Wessell K. , Mitchell S. L. , Hanson L. C.
Published: September 2023

Background

Limited access to specialized palliative care exposes persons with late-stage Alzheimer’s disease and related dementias (ADRD) to burdensome treatment and unnecessary hospitalization and their caregivers to avoidable strain and financial burden. Addressing this unmet need, the purpose of this study was to conduct a randomized clinical trial (RCT) of the ADRD-Palliative Care (ADRD-PC) program.

Methods

The study will use a multisite, RCT design and will be set in five geographically diverse US hospitals. Lead investigators and outcome assessors will be masked. The study will use 1:1 randomization of patient-caregiver dyads, and sites will enroll N = 424 dyads of hospitalized patients with late-stage ADRD with their family caregivers. Intervention dyads will receive the ADRD-PC program of (1) dementia-specific palliative care, (2) standardized caregiver education, and (3) transitional care. Control dyads will receive publicly available educational material on dementia caregiving. Outcomes will be measured at 30 days (interim) and 60 days post-discharge. The primary outcome will be 60-day hospital transfers, defined as visits to an emergency department or hospitalization ascertained from health record reviews and caregiver interviews (aim 1). Secondary patient-centered outcomes, ascertained from 30- and 60-day health record reviews and caregiver telephone interviews, will be symptom treatment, symptom control, use of community palliative care or hospice, and new nursing home transitions (aim 2). Secondary caregiver-centered outcomes will be communication about prognosis and goals of care, shared decision-making about hospitalization and other treatments, and caregiver distress (aim 3). Analyses will use intention-to-treat, and pre-specified exploratory analyses will examine the effects of sex as a biologic variable and the GDS stage.

Discussion

The study results will determine the efficacy of an intervention that addresses the extraordinary public health impact of late-stage ADRD and suffering due to symptom distress, burdensome treatments, and caregiver strain. While many caregivers prioritize comfort in late-stage ADRD, shared decision-making is rare. Hospitalization creates an opportunity for dementia-specific palliative care, and the study findings will inform care redesign to advance comprehensive dementia-specific palliative care plus transitional care.

Trial registration

ClinicalTrials.gov NCT04948866. Registered on July 2, 2021.
Effect of dexmedetomidine on postoperative delirium in patients undergoing awake craniotomies: study protocol of a randomized controlled trial
Authors: Li Muhan , Liu Minying , Cui Qianyu , Zeng Min , Li Shu , Zhang Liyong , Peng Yuming
Published: September 2023

Introduction

Postoperative delirium (POD) is a common complication, and it has a high incidence in neurosurgery patients. Awake craniotomy (AC) has been widely performed in patients with glioma in eloquent and motor areas. Most of the surgical procedure is frontotemporal craniotomy, and the operation duration has been getting longer. Patients undergoing AC are high-risk populations for POD. Dexmedetomidine (Dex) administration perioperatively might help to reduce the incidence of POD. The purpose of this study is to investigate the effect of Dex on POD in patients undergoing AC.

Methods

The study is a prospective, single-center, double-blinded, paralleled-group, randomized controlled trial. Patients undergoing elective AC will be randomly assigned to the Dex group and the control group. Ten minutes before urethral catheterization, patients in the Dex group will be administered with a continuous infusion at a rate of 0.2 µg/kg/h until the end of dural closure. In the control group, patients will receive an identical volume of normal saline in the same setting. The primary outcome will be the cumulative incidence and severity of POD. It will be performed by using the confusion assessment method in the first 5 consecutive days after surgery. Secondary outcomes include quality of intraoperative awareness, stimulus intensity of neurological examination, pain severity, quality of recovery and sleep, and safety outcomes.

Discussion

This study is to investigate whether the application of Dex could prevent POD in patients after undergoing AC and will provide strong evidence-based clinical practice on the impact of intraoperative interventions on preventing POD in AC patients.

Trial registration

ClinicalTrials.gov, NCT05195034. Registered on January 18, 2022.
Identification of candidate genes and chemicals associated with osteoarthritis by transcriptome-wide association study and chemical-gene interaction analysis
Authors: Mei Lin , Zhang Zhiming , Chen Ruiqi , Liu Zhongyue , Ren Xiaolei , Li Zhihong
Published: September 2023

Background

Osteoarthritis (OA) is a common degenerative joint disease and causes chronic pain and disability to the elderly. Several risk factors are involved, such as aging, obesity, genetic susceptibility, and environmental factors. We conducted a transcriptome-wide association study (TWAS) and chemical-related gene set enrichment analysis (CGSEA) to investigate the susceptibility genes and environmental factors.

Methods

TWAS analysis was conducted to identify the susceptibility genes by integrating the summary-level genome-wide association study data of knee OA (KOA) and hip OA (HOA) with the precomputed expression weights from the Genotype-Tissue Expression Project (Version 8). The FUSION software was used for both single-tissue and cross-tissue TWAS, which were combined using an aggregate Cauchy association test. The biological function and pathways of the TWAS genes were explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases, and the human cartilage mRNA expression profiles were utilized to validate the TWAS genes. CGSEA analysis was performed to scan the OA-associated chemicals by integrating the TWAS results with the chemical-related gene sets.

Results

There were 44 and 93 unique TWAS genes identified in 7 and 11 chromosomes for KOA and HOA, respectively, fourteen and four of which showed significantly differential expression in the mRNA profiles, such as CRHR1, LTBP1, WWP2, LMX1B, and PTHLH. OA-related pathways were found in the KEGG and GO analysis, such as TGF-beta signaling pathway, MAPK signaling pathway, hyaluronan metabolic process, and chondrocyte differentiation. Forty-five OA-associated chemicals were identified, including quercetin, bisphenol A, and cadmium chloride.

Conclusions

Several candidate OA-associated genes and chemicals were identified through TWAS and CGSEA analysis, which expanded our understanding of the relationship between genes, chemicals, and their impact on OA.
Automatic evaluation of atlantoaxial subluxation in rheumatoid arthritis by a deep learning model
Authors: Okita Yasutaka , Hirano Toru , Wang Bowen , Nakashima Yuta , Minoda Saki , Nagahara Hajime , Kumanogoh Atsushi
Published: September 2023

Background

This work aims to develop a deep learning model, assessing atlantoaxial subluxation (AAS) in rheumatoid arthritis (RA), which can often be ambiguous in clinical practice.

Methods

We collected 4691 X-ray images of the cervical spine of the 906 patients with RA. Among these images, 3480 were used for training the deep learning model, 803 were used for validating the model during the training process, and the remaining 408 were used for testing the performance of the trained model. The two-dimensional key points’ detection model of Deep High-Resolution Representation Learning for Human Pose Estimation was adopted as the base convolutional neural network model. The model inferred four coordinates to calculate the atlantodental interval (ADI) and space available for the spinal cord (SAC). Finally, these values were compared with those by clinicians to evaluate the performance of the model.

Results

Among the 408 cervical images for testing the performance, the trained model correctly identified the four coordinates in 99.5% of the dataset. The values of ADI and SAC were positively correlated among the model and two clinicians. The sensitivity of AAS diagnosis with ADI or SAC by the model was 0.86 and 0.97 respectively. The specificity of that was 0.57 and 0.5 respectively.

Conclusions

We present the development of a deep learning model for the evaluation of cervical lesions of patients with RA. The model was demonstrably shown to be useful for quantitative evaluation.
Development of a novel observed structured clinical exam to assess clinical ultrasound proficiency in undergraduate medical education
Authors: Kamilaris Andrew , Kramer Jeffrey A. , Baraniecki-Zwil Gwen , Shofer Frances , Moore Christy , Panebianco Nova , Chan Wilma
Published: September 2023

Objectives

A pilot study was performed to develop and test an observed structured clinical exam (OSCE) for clinical ultrasound in second-year medical students. The goal was to assess a longitudinal clinical ultrasound curriculum for medical students and to help determine readiness to perform ultrasound during clinical clerkships.

Methods

The OSCE contained 40 tasks over 30 min in a one-to-one examiner to examinee environment using standardized patients covering cardiac, pulmonary, and inferior vena cava (IVC) ultrasound exams along with 6 critical diagnoses. Examinees were assessed using a binary checklist approach. A two-way ANOVA analysis was performed to determine if there were differences between the day and session the OSCE was administered. Results are presented as mean ± standard deviation.

Results

One hundred fifty-two students were tested with an overall mean score of 64.9 ± 17.6%. Scores between the cardiac, IVC, and lung sections varied—67.8% ± 18.8%, 62.4% ± 26.2%, and 57.1% ± 20.6%, respectively. One hundred twenty-six (82.9%) answered at least one critical diagnosis incorrectly. Students in the late session performed better than the early session (1: 60% vs 2: 69%, p = .001).

Conclusions

Students performed better in later sessions. Additionally, the number of questions left blank at the end of the exam suggests that the length of the OSCE should be evaluated. Incorporating critical diagnoses was challenging for examinees. The proposed OSCE is a valuable assessment tool that could be adapted to assess student’s readiness to use clinical ultrasound prior to clerkships.
In vivo direct cell-penetrating peptide mediated protein transduction system in Acyrthosiphon pisum
Authors: Takenaka Aya , Konno Harutomo , Kikuta Shingo
Published: September 2023

Objective

The principal delivery method for CRISPR-based genome editing in insects is now based on microinjection into single cells or embryos. The direct protein transduction systems cannot be employed in aphids because oogenesis occurs without apparent vitellogenesis. Given the limited timing of injection into the embryonic stage in oviparous aphids, a protein delivery system from the hemolymph to the germline and embryos would be a useful tool for genome editing. This study reports a newly developed direct protein delivery system for aphids using cell-penetrating peptides (CPPs). CPPs are short peptides that translocate across the plasma membrane when bound to cargo proteins.

Results

Penetratin (PEN), a widely conserved CPP among insects, was identified in this study. We used mVenus, a recombinant fluorescent protein, as a visual marker for CPP availability assessments, and fused it with PEN by bacterial protein expression. The mVenus-PEN recombinant proteins were introduced into the hemolymph of adult unwinged Acyrthosiphon pisum females using a nanoinjector. Fluorescence emitted by mVenus-PEN was observed in various tissues, such as the gut, trachea, bacteriocytes, and their progeny. This study shows that PEN can deliver exogenously expressed proteins into tissues in vivo, indicating that CPPs are powerful tools for protein transduction.
Cost-effectiveness of physical activity interventions for prevention and management of cognitive decline and dementia—a systematic review
Authors: Li Weixin , Kim Kun-Woo Rafael , Zhang Donglan , Liu Bian , Dengler-Crish Christine M. , Wen Ming , Shi Lu , Pan Xi , Gu Yian , Li Yan
Published: September 2023

Background

Although increasing physical activity (PA) has been suggested to prevent and manage cognitive decline and dementia, its economic impact on healthcare systems and society is largely unknown. This study aimed to summarize evidence on the cost-effectiveness of PA interventions to prevent and manage cognitive decline and dementia.

Methods

Electronic databases, including PubMed/MEDLINE, Embase, and ScienceDirect, were searched from January 2000 to July 2023. The search strategy was driven by a combination of subject-heading terms related to physical activity, cognitive function, dementia, and cost-effectiveness. Selected studies were included in narrative synthesis, and extracted data were presented in narrative and tabular forms. The risk of bias in each study was assessed using the Consolidated Health Economic Evaluation Reporting Standards and Consensus on Health Economic Criteria list.

Results

Five of the 11 identified studies focused on individuals with existing dementia. Six of the 11 identified studies focused on individuals with no existing dementia, including 3 on those with mild cognitive impairment (MCI), and 3 on those with no existing MCI or dementia. PA interventions focused on individuals with no existing dementia were found to be cost-effective compared to the control group. Findings were mixed for PA interventions implemented in individuals with existing dementia.

Conclusions

PA interventions implemented before or during the early stage of cognitive impairment may be cost-effective in reducing the burden of dementia. More research is needed to investigate the cost-effectiveness of PA interventions in managing dementia. Most existing studies used short-term outcomes in evaluating the cost-effectiveness of PA interventions in the prevention and management of dementia; future research should consider adding long-term outcomes to strengthen the study design.
Subspecialisation in radiology in Europe, a survey of the accreditation council of imaging
Authors: Rupreht Mitja , Ricci Paolo , Prosch Helmut , Adriaensen Miraude E. A. P. M.
Published: September 2023

Background

To provide an overview of existing Subspecialty Exams and Diplomas in Radiology and their endorsement as well as to providing an insight into the status of subspecialisation in radiology in Europe. The European Training Curriculum for Subspecialisation in Radiology mentions thirteen fields of subspecialisation within radiology. The websites of the corresponding subspecialty societies were checked for Subspecialty Exams and Diplomas. In addition, we performed a survey among European radiologists regarding subspecialisation in radiology.

Results

Ten out of 13 European subspecialty societies offer a European subspecialty diploma. At least 7 out of the 10 European subspecialties societies in radiology offering a European subspecialty diploma obtained European Society of Radiology (ESR) endorsement. Two out of 10 obtained European Union of Medical Specialists—Council of European Specialist Medical Assessment endorsement. Survey among European radiologists who were ESR full members in March 2021 demonstrated that almost 20% of respondents indicated that they have no subspecialisation. Another 15% indicated that their area of subspecialisation is not recognised in their country of work. Eighty-four percent of respondents would like their area of subspecialisation in radiology to be officially recognised. According to the respondents, the major benefit of having their subspecialisation in radiology officially recognised is personal interest (45%).

Conclusions

There is a desire for more subspecialty recognition in radiology among European radiologists. Therefore, European subspecialty diplomas in radiology fulfil a need. Furthermore, there is room for further harmonisation and implementation on a European level regarding subspecialty training and recognition in radiology.

Critical relevance statement

As there is a desire for more subspecialty recognition in radiology among European radiologists, European subspecialty diplomas in radiology fulfil a need and there is still room for further harmonisation and implementation on a European level regarding subspecialty training in radiology.

Key points

• Radiology has 13 subspecialties as per the European Training Curriculum for Subspecialisation.

• Currently, 15 subspecialty diplomas are offered by European subspecialty societies in radiology

• Members of the European Society of Radiology seek greater recognition of radiology subspecialties.

Graphical Abstract
Label-set impact on deep learning-based prostate segmentation on MRI
Authors: Meglič Jakob , Sunoqrot Mohammed R. S. , Bathen Tone Frost , Elschot Mattijs
Published: September 2023

Background

Prostate segmentation is an essential step in computer-aided detection and diagnosis systems for prostate cancer. Deep learning (DL)-based methods provide good performance for prostate gland and zones segmentation, but little is known about the impact of manual segmentation (that is, label) selection on their performance. In this work, we investigated these effects by obtaining two different expert label-sets for the PROSTATEx I challenge training dataset (n = 198) and using them, in addition to an in-house dataset (n = 233), to assess the effect on segmentation performance. The automatic segmentation method we used was nnU-Net.

Results

The selection of training/testing label-set had a significant (p < 0.001) impact on model performance. Furthermore, it was found that model performance was significantly (p < 0.001) higher when the model was trained and tested with the same label-set. Moreover, the results showed that agreement between automatic segmentations was significantly (p < 0.0001) higher than agreement between manual segmentations and that the models were able to outperform the human label-sets used to train them.

Conclusions

We investigated the impact of label-set selection on the performance of a DL-based prostate segmentation model. We found that the use of different sets of manual prostate gland and zone segmentations has a measurable impact on model performance. Nevertheless, DL-based segmentation appeared to have a greater inter-reader agreement than manual segmentation. More thought should be given to the label-set, with a focus on multicenter manual segmentation and agreement on common procedures.

Critical relevance statement

Label-set selection significantly impacts the performance of a deep learning-based prostate segmentation model. Models using different label-set showed higher agreement than manual segmentations.

Key points

• Label-set selection has a significant impact on the performance of automatic segmentation models.

• Deep learning-based models demonstrated true learning rather than simply mimicking the label-set.

• Automatic segmentation appears to have a greater inter-reader agreement than manual segmentation.

Graphical Abstract
Human umbilical cord mesenchymal stem cells ameliorate colon inflammation via modulation of gut microbiota-SCFAs-immune axis
Authors: Liu Airu , Liang Xiaonan , Wang Wenxin , Wang Chen , Song Jia , Guo Jinbo , Sun Donglei , Wang Dong , Song Mei , Qian Jiaming , Zhang Xiaolan
Published: September 2023

Background

Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has emerged as a prospective novel tool for managing IBD, and which can also regulate the composition of gut microbiota. However, the functional significance of MSCs-induced changes in gut microbiome is poorly understood.

Methods

Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of human umbilical cord MSCs (HUMSCs) on DSS-induced colitis. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Spectrum antibiotic cocktail (ABX), fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) were employed to evaluate the protective effect of intestinal flora and its metabolites. Cytokine microarray, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry were conducted to assess the effect on CD4+T homeostasis.

Results

Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of MSCs on DSS-induced colitis. By performing gut microbiota depletion and fecal microbiota transplantation (FMT) experiments, we revealed that MSCs derived from human umbilical cord ameliorated colon inflammation and reshaped T-cells immune homeostasis via remodeling the composition and diversity of gut flora, especially up-regulated SCFAs-producing bacterial abundance, such as Akkermansia, Faecalibaculum, and Clostridia_UCG_014. Consistently, targeted metabolomics manifested the increased SCFAs production with MSCs administration, and there was also a significant positive correlation between differential bacteria and SCFAs. Meanwhile, combined with sterile fecal filtrate (SFF) gavage experiments, the underlying protective mechanism was further associated with the improved Treg/Th2/Th17 balance in intestinal mucosa mediated via the increased microbiota-derived SCFAs production.

Conclusion

The present study advances understanding of MSCs in the protective effects on colitis, providing evidence for the new role of the microbiome-metabolite-immune axis in the recovery of colitis by MSCs.
Meta-analysis on last ten years of clinical injection of bone marrow-derived and umbilical cord MSC to reverse cirrhosis or rescue patients with acute-on-chronic liver failure
Authors: Wang Huimin , Yao Weiqi , Wang Yuyan , Dong Haibo , Dong Tengyun , Zhou Wangyi , Cui Lingling , Zhao Lulu , Zhang Yu , Shi Lei , Jiang Yingan
Published: September 2023

Background

Recent studies have shown that mesenchymal stem cell (MSC) therapy has potential therapeutic effects for patients with end-stage liver diseases. However, a consensus on the efficacy and safety of MSCs has not been reached.

Methods

A systemic literature review was conducted by searching the Cochrane Library and PubMed databases for articles that evaluated the impact of MSC therapy on the outcomes among patients with end-stage liver disease. Various parameters, including pre- and post-treatment model of end-stage liver disease (MELD) score, serum albumin (ALB), total bilirubin (TB), coagulation function, aminotransferase, and survival rate, were evaluated.

Results

This meta-analysis included a final total of 13 studies and 854 patients. The results indicated improved liver parameters following MSC therapy at different time points, including in terms of MELD score, TB level, and ALB level, compared with conventional treatment. Furthermore, the MSC treatment increased the overall survival rate among patients with liver cirrhosis and acute-on-chronic liver failure (ACLF). The changes in transaminase level and coagulation function differed between the different therapies at various post-treatment time points, indicating that MSC therapy provided no significant benefits in this regard. The further subgroup analysis stratified by liver background revealed that patients with ACLF benefit more from MSC therapy at most time points with improved liver function, including in terms of MELD score, TB level, and ALB level. In addition, no serious side effects or adverse events were reported following MSC therapy.

Conclusions

The meta-analysis results suggest that MSC therapy is safe and results in improved liver function and survival rates among patients with end-stage liver disease. The subgroup analysis stratified by liver background indicated that patients with ACLF benefit more from MSC therapy than patients with liver cirrhosis at most time points.
Inflammation-inducible promoters to overexpress immune inhibitory factors by MSCs
Authors: Selich Anton , Fleischauer Jenni , Roepke Tina , Weisskoeppel Luisa , Galla Melanie , von Kaisenberg Constantin , Maus Ulrich A. , Schambach Axel , Rothe Michael
Published: September 2023

Background

Mesenchymal stromal cells (MSCs) are excessively investigated in the context of inflammation-driven diseases, but the clinical results are often moderate. MSCs are naturally activated by inflammatory signals, which lead to the secretion of immune inhibitory factors in inflamed tissues. Many work groups try to improve the therapeutic outcome of MSCs by genetic modification and the constitutive overexpression of immune modulatory transgenes. However, the ectopic secretion of immune inhibitory transgenes increases the chances of infections, and constitutive transgene expression is not necessary for chronic diseases undergoing different inflammatory stages.

Methods

We designed and tested inflammation-induced promoters to control transgene expression from integrating lentiviral vectors in human umbilical cord MSCs. Therefore, we investigated different combinations of general transcription factor elements to achieve a minimal promoter with low basal activity. The best candidates were combined with interferon-induced GAS or ISRE DNA motifs. The constructs with the highest transgene expression upon addition of pro-inflammatory cytokines were compared to vectorized promoters from inflammation-induced genes (CD317, CXCL9, CXCL10, CXCL11 and IDO1). Finally, we investigated IL10 as a potential immune inhibitory transgene by transcriptome analyses, ELISA and in an acute lung injury mouse model.

Results

The synthetic promoters achieved a high and specific transgene expression upon IFN-γ addition. However, the CXCL11 promoter showed synergistic activity upon IFN-γ, TNF-α and IL1-β treatment and surpassed the transgene expression height of all tested promoters in the study. We observed in transcriptome analyses that IL10 has no effect on MSCs and in ELISA that IL10 is only secreted by our genetically modified and activated CXCL11-IL10-MSCs. Finally, transplanted CXCL11-IL10-MSCs increased CD19+ and CD4+ lymphoid cells, and decreased CD11b+ Ly6g myeloid cells in an ALI mouse model.

Conclusion

These results provide new insights into MSC inflammatory activation and the subsequent translation into a tool for a tailored expression of transgenes in inflammatory microenvironments. The newly developed promoter elements are potentially interesting for other inflamed tissues, and can be combined with other elements or used in other cell types.
Probabilistic generative transformer language models for generative design of molecules
Authors: Wei Lai , Fu Nihang , Song Yuqi , Wang Qian , Hu Jianjun
Published: September 2023

Self-supervised neural language models have recently found wide applications in the generative design of organic molecules and protein sequences as well as representation learning for downstream structure classification and functional prediction. However, most of the existing deep learning models for molecule design usually require a big dataset and have a black-box architecture, which makes it difficult to interpret their design logic. Here we propose the Generative Molecular Transformer (GMTransformer), a probabilistic neural network model for generative design of molecules. Our model is built on the blank filling language model originally developed for text processing, which has demonstrated unique advantages in learning the “molecules grammars” with high-quality generation, interpretability, and data efficiency. Benchmarked on the MOSES datasets, our models achieve high novelty and Scaf compared to other baselines. The probabilistic generation steps have the potential in tinkering with molecule design due to their capability of recommending how to modify existing molecules with explanation, guided by the learned implicit molecule chemistry. The source code and datasets can be accessed freely at https://github.com/usccolumbia/GMTransformer
The optimization of the number of deployed antennas in large-scale CL-DAS for energy efficiency
Authors: Han Yonggue , Sim Dongkyu
Published: September 2023

We consider the deployment of a large-scale circular layout-distributed antenna system. To maximize energy efficiency, we define the optimization problem with the approximated analysis and find the number of deployed antennas as a closed-form solution. In simulation results, we verify that the analysis based on approximation is accurate and the closed-form solution can achieve near-optimal energy efficiency without an exhaustive search method.
The association of body mass index and weight waist adjustment index with serum ferritin in a national study of US adults
Authors: Han Hao , Ni Ping , Zhang Siqi , Ji Xiaojuan , Zhu Mingli , Ma Wanyu , Ge Hongfeng , Chu Hailiang
Published: September 2023

Background

Abnormal serum ferritin levels are associated with a variety of diseases. Meanwhile, abnormal serum ferritin is influenced by a variety of risk factors, but its correlation with obesity remains poorly described.

Objective

This study aimed to investigate the association of body mass index (BMI) and weight waist adjustment index (WWI) with serum ferritin in US adults.

Methods

Participants in this study took part in the National Health and Nutrition Examination Survey (NHANES) prior to the pandemic from 2017 to March 2020. Serum ferritin was used as the sole response variable and BMI and WWI were used as independent variables. Multiple linear regression was used to assess the relationship between serum ferritin and the independent variables, and smoothed curve fitting and threshold effects analysis were performed to assess the presence of non-linear relationships. To validate the sensitive individuals for the correlation between the independent and the dependent variables, a subgroup analysis was performed.

Results

A final total of 7552 participants were included in this study. Both independent variables had a positive relationship with serum ferritin, with effect values of (β = 0.68, 95% CI: 0.17–1.19) when BMI was the independent variable and (β = 8.62, 95% CI: 3.53–13.72) when WWI was the independent variable in the fully adjusted model. This positive association between the two obesity-related indexes and serum ferritin became more significant as BMI and WWI increased (P for trend < 0.001). In subgroup analyses, the positive association between the independent variables and serum ferritin was more pronounced in participants who were male, 40–59 years old, white, and had diabetes and hypertension. In addition, smoothed curve fitting and threshold effects analysis demonstrated a linear positive association of BMI and WWI with serum ferritin.

Conclusions

In the US adult population, while there was a linear positive association of WWI and BMI with serum ferritin, the effect values between WWI and serum ferritin were more significant. Male, 40–59 years old, white, participants with diabetes and hypertension should be cautious that higher WWI might entail a risk of higher serum ferritin levels.
The PTX3/TLR4 autocrine loop as a novel therapeutic target in triple negative breast cancer
Authors: Giacomini Arianna , Turati Marta , Grillo Elisabetta , Rezzola Sara , Ghedini Gaia Cristina , Schuind Ander Churruca , Foglio Eleonora , Maccarinelli Federica , Faletti Jessica , Filiberti Serena , Chambery Angela , Valletta Mariangela , Melocchi Laura , Gofflot Stephanie , Chiavarina Barbara , Turtoi Andrei , Presta Marco , Ronca Roberto
Published: September 2023

Background

The pattern recognition receptor long pentraxin-3 (PTX3) plays conflicting roles in cancer by acting as an oncosuppressor or as a pro-tumor mediator depending on tumor context. Triple negative breast cancer (TNBC) represents the most aggressive histotype of breast cancer, characterized by the lack of efficacious therapeutic targets/approaches and poor prognosis. Thus, the characterization of new molecular pathways and/or alternative druggable targets is of great interest in TNBC.

Methods

The expression of PTX3 in BC tumor samples and in BC cell lines has been analyzed using the Gene Expression-Based Outcome for Breast Cancer Online (GOBO), qPCR, Western blot and ELISA assay. The contribution of tumor and stromal cells to PTX3 production in TNBC was assessed by analyzing single cell RNA sequencing data and RNAscope performed on TNBC tumor samples. In order to investigate the effects of PTX3 in TNBC, different cell lines were engineered to knock-down (MDA-MB-231 and BT549 cells) or overexpress (MDA-MB-468 and E0771 cells) PTX3. Finally, using these engineered cells, in vitro (including gene expression profiling and gene set enrichment analyses) and in vivo (orthotopic tumor models in immune-compromised and immune competent mice) analyses were performed to assess the role and the molecular mechanism(s) exerted by PTX3 in TNBC.

Results

In silico and experimental data indicate that PTX3 is mainly produced by tumor cells in TNBC and that its expression levels correlate with tumor stage. Accordingly, gene expression and in vitro results demonstrate that PTX3 overexpression confers a high aggressive/proliferative phenotype and fosters stem-like features in TNBC cells. Also, PTX3 expression induces a more tumorigenic potential when TNBC cells are grafted orthotopically in vivo. Conversely, PTX3 downregulation results in a less aggressive behavior of TNBC cells. Mechanistically, our data reveal that PTX3 drives the activation of the pro-tumorigenic Toll-like receptor 4 (TLR4) signaling pathway in TNBC, demonstrating for the first time that the PTX3/TLR4 autocrine stimulation loop contributes to TNBC aggressiveness and that TLR4 inhibition significantly impacts the growth of PTX3-producing TNBC cells.

Conclusion

Altogether, these data shed light on the role of tumor-produced PTX3 in TNBC and uncover the importance of the PTX3/TLR4 axis for therapeutic and prognostic exploitation in TNBC.

Graphical abstract
A novel method for diaphragm-based electrode belt position of electrical impedance tomography by ultrasound
Authors: Yue Chaofu , He Huaiwu , Su Longxiang , Wang Jun , Yuan Siyi , Long Yun , Zhao Zhanqi
Published: September 2023

Background

This aim of study was to introduce a diaphragm-based EIT-belt placement method based on diaphragm position by ultrasound, and to evaluate the difference between diaphragm-based EIT-belt placement and conventional EIT-belt placement.

Method

The diaphragm position (L0) determined by ultrasound was taken as zero reference level. The direction of headward is defined as positive, and toward feet is negative. For EIT data collection, the electrode belt was placed at 7 different levels, respectively (denoted as L−2 cm, L0, L2cm, L4cm, L6cm, L8cm, L10cm) at supine position in healthy volunteers. The diaphragm-based EIT-belt level (Lxcm) was defined where highest tidal impedance variation (TV) was achieved. Subsequently, EIT measurements were conducted at diaphragm-based EIT-belt levels and traditional EIT-belt level in 50 critically ill patients under mechanical ventilation.

Result

The highest TV was achieved at L6cm and the smallest at L−2 cm., so the L6cm were taken as diaphragm-based EIT-belt level by ultrasound in 8 healthy volunteers. In 23 patients, the diaphragm-based EIT-belt plane agreed with the conventional planes (4th–6th ICS), which was defined as the Agreed group. Other patients were classified to the Disagreed group (above 4th ICS). The Disagreed group has a significantly higher BMI and lower global TV at the diaphragm-based EIT-belt plane compared to the Agreed group.

Conclusions

The diaphragm-based EIT-belt position by ultrasound was feasible and resulted in different belt positions compared to the conventional position in > 50% of the examined subjects, especially in patients with higher BMI. Further study is required to validate the impact on EIT images with this novel method on clinical management.
Characteristics and longitudinal extent of VLF quasi-periodic emissions using multi-point ground-based observations
Authors: Martinez-Calderon Claudia , Oonishi Tomoka , Shiokawa Kazuo , Manninen Jyrki K. , Oinats Alexey , Ozaki Mitsunori
Published: September 2023

Quasi-periodic (QP) emissions are a type of magnetospheric ELF/VLF waves characterized by a periodic intensity modulation ranging from tens of seconds to several minutes. Here, we present 63 QP events observed between January 2017 and December 2018. Initially detected at the VLF receiver in Kannuslehto, Finland (KAN, MLAT = 67.7°N, L = 5.5), we proceeded to check whether these events were simultaneously observed at other subauroral receivers. To do so we used the following PWING stations: Athabasca (ATH, MLAT = 61.2°N, L = 4.3, Canada), Gakona (GAK, MLAT = 63.6°N, L = 4.9, Alaska), Husafell (HUS, MLAT = 64.9°N, L = 5.6, Iceland), Istok (IST, MLAT = 60.6°N, L = 6.0, Russia), Kapuskasing (KAP, MLAT = 58.7°N, L = 3.8, Canada), Maimaga (MAM, MLAT = 58.0°N, L = 3.6, Russia), and Nain (NAI, MLAT = 65.8°N, L = 5.0, Canada). We found that: (1) QP emissions detected at KAN had a relatively longer observation time (1–10 h) than other stations, (2) 11.3% of the emissions at KAN were observed showing one-to-one correspondence at IST, and (3) no station other than IST simultaneously observed the same QP emission as KAN. Since KAN and IST are longitudinally separated by 60.6°, we estimate that the maximum meridional spread of conjugated QP emissions should be close to 60° or 4 MLT. Comparison with geomagnetic data shows half of the events are categorized as type II, while the rest are mixed (type I and II). This study is the first to clarify the longitudinal spread of QP waves observed on the ground by analyzing simultaneous observations over 2 years using multiple ground stations.

Graphical Abstract
The transition from cohabitation to marriage in Spain: differences and determinants in same-sex and different-sex couples
Authors: Caprinali Anna , Vitali Agnese , Cortina Clara
Published: September 2023

Same-sex households and non-heterosexual people’s living arrangements are an expanding area of research in family studies. This contribution focuses on the transition from cohabitation to marriage of same-sex couples in comparison to different-sex couples in Spain, i.e., one of the pioneer countries of same-sex marriage that was legalized in 2005. In this particular context, we investigate to what extent same-sex couples and different-sex couples present similar marriage risks. Employing Event History Analysis and using data from the 2018 Spanish Fertility Survey, we find that, overall, same-sex couples have a significantly lower hazard of transitioning from non-marital cohabitation to marriage than different-sex couples. When restricting the sample to currently co-residing couples, the difference in the hazard of marriage between the two couple types remains negative but becomes insignificant. We thus disprove that same-sex couples have a higher incentive for marriage. These results are discussed in light of the different composition of same-sex vs different-sex couples in terms of their socio-demographic profile and motivations for marriage.
Epidemiology, clinical presentation, and predictors of outcome in nontuberculous mycobacterial central nervous system infection: a systematic review
Authors: Meena Durga Shankar , Kumar Deepak , Meena Vasudha , Bohra Gopal Krishana , Tak Vibhor , Garg Mahendra Kumar
Published: September 2023

Background

CNS manifestations represent an emerging facet of NTM infection with significant mortality. Due to protean presentation and low index of suspicion, many cases are often treated erroneously as tubercular meningitis or fungal infections.

Objectives

Literature on NTM CNS disease is scarce, with most available data on pulmonary disease. This systematic review aimed to evaluate the epidemiology, clinical presentation, diagnostic modalities, and predictors of outcome in CNS NTM infection.

Methods

The literature search was performed in major electronic databases (PubMed, Google Scholar, and Scopus) using keywords “CNS,” “Central nervous system,” “brain abscess,” “meningitis,” “spinal,” “Nontuberculous mycobacteria,” “NTM”. All cases of CNS NTM infection reported between January 1980 and December 2022 were included.

Results

A total of 77 studies (112 cases) were included in the final analysis. The mean age of all patients was 38 years, with most patients male (62.5%). Mycobacterium avium complex (MAC) was the most common aetiology, followed by M. fortuitum and M. abscessus (34.8%, 21.4% and 15.2%, respectively). The disseminated disease was found in 33% of cases. HIV (33.9%) and neurosurgical hardware (22.3%) were the common risk factors. Intracranial abscess (36.6%) and leptomeningeal enhancement (28%) were the most prevalent findings in neuroimaging. The overall case fatality rate was 37.5%. On multivariate analysis, male gender (adjusted OR 2.4, 95% CI 1.2–7.9) and HIV (adjusted OR 3.7, 95% CI 1.8–6.1) were the independent predictors of mortality). M. fortuitum infection was significantly associated with increased survival (adjusted OR 0.18, 95% CI (0.08–0.45), p value 0.012).

Conclusions

Current evidence shows the emerging role of rapid-grower NTM in CNS disease. Male gender and HIV positivity were associated with significant mortality, while M fortuitum carries favourable outcomes.
Application of endophytic bacterium Bacillus velezensis BTR11 to control bacterial leaf blight disease and promote rice growth
Authors: Do Trung Quang , Nguyen Tri Trong , Dinh Van Mai
Published: September 2023

Background

Bacterial leaf blight (BLB) disease caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most destructive pathogens responsible for severe yield losses in rice. Application of bacterial biocontrol agent (BCA) with plant growth promotion (PGP) abilities is a promising method that alternates current conventional practices to manage BLB disease and increase crop yield. Hence, this study aimed to isolate and identify BCA with PGP abilities from internal plant tissues and rhizosphere soil of healthy and Xoo-infected rice and evaluate their antagonistic and PGP properties under greenhouse and field conditions.

Results

A total of 14 bacterial isolates were isolated and presented in vitro antagonistic ability against the Xoo. The rice endophytic bacterium strain Bacillius velezensis (BTR11) had the highest antagonistic activity against the Xoo, produced indole acetic acid (IAA), and mineralized nutrients (K and P). The greenhouse experiment revealed that culture broth of strain BTR11 had a high protective effect (72.1%) against the BLB when applied at the protective-fighting mode, i.e., before and after the Xoo infection. Preliminary results of the field experiment showed that a protective effect against the bacterial blight disease was obtained as high as 75–85%, if the strain was used as an additive to the soil for the seedlings in combination with spraying when the disease began in the field. In addition, using the strain BTR11 also increased the rice yield to about 12% more than the un-treatment control.

Conclusions

The study showed a significant potential for the application of endophytic bacteria in controlling BLB disease, while stimulating plant growth, thus reducing the use of agrochemicals in rice cultivation.
Removal of discal cyst using percutaneous full endoscopic via interlaminar route: a case report
Authors: Kasempipatchai Pawin , Kesornsak Withawin , Kuansongtham Verapan
Published: September 2023

Background

Discal cyst, a rare disease with unclear pathogenesis, exhibits symptoms similar to lumbar disk herniation. Currently, there is no consensus on the optimal treatment for this condition.

Case presentation

This report presents the clinical efficacy of the percutaneous endoscopic interlaminar approach surgery technique in patients diagnosed with lumbar 4–5 discal cyst. The patient exhibited sub-acute radiculopathy in the left leg accompanied by weakness of the extensor hallucis longus. Magnetic resonance imaging of the lumbar spine confirmed the presence of lumbar discal cysts, which exerted compression on the traversing nerve root. Surgical treatment involved performing percutaneous endoscopic interlaminar approach surgery without additional discectomy under general anesthesia. The symptoms were immediately alleviated following the removal of the discal cysts, and the weakness in the toe improved the day after the surgery. No recurrent symptoms or complications were observed during the 6-month follow-up period.

Conclusion

Based on our findings, we posit that percutaneous interlaminar endoscopic surgery represents a safe, minimally invasive, and appropriate approach for treating discal cysts.