bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiota regulation of T lymphocyte subsets during systemic lupus erythematosus
Authors: Lian Fen-Ping , Zhang Fen , Zhao Chun-Miao , Wang Xu-Xia , Bu Yu-Jie , Cen Xing , Zhao Gui-Fang , Zhang Sheng-Xiao , Chen Jun-Wei
Published: July 2024

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes.

Methods

A total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann–Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation.

Results

Compared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P < 0.05). In the correlation analysis of SLE, Tregs were positively correlated with Ruminococcus2 (P = 0.042), Th17 cells were positively correlated with Megamonas (P = 0.009), γδT cells were positively correlated with Megamonas (P = 0.003) and Streptococcus (P = 0.004), Tfh cells were positively correlated with Bacteroides (P = 0.040), and Th1 cells were negatively correlated with Bifidobacterium (P = 0.005). As for clinical indicators, the level of Tregs was negatively correlated with ESR (P = 0.031), but not with C3 and C4, and the remaining cells were not significantly correlated with ESR, C3 and C4.

Conclusion

Gut microbiota and T lymphocyte subsets of SLE changed and related to each other, which may break the immune balance and affect the occurrence and development of SLE. Therefore, it is necessary to pay attention to the changes of gut microbiota and provide new ideas for the treatment of SLE.
LCP1 correlates with immune infiltration: a prognostic marker for triple-negative breast cancer
Authors: Pan Shuaikang , Wan Mengting , Jin Hongwei , Ning Ran , Zhang Jinguo , Han Xinghua
Published: July 2024

Objective

Triple-Negative Breast Cancer (TNBC) is known for its aggressiveness and treatment challenges due to the absence of ER, PR, and HER2 receptors. Our work emphasizes the prognostic value of LCP1 (Lymphocyte cytosolic protein 1), which plays a crucial role in cell processes and immune cell activity, to predict outcomes and guide treatments in TNBC.

Methods

We explored LCP1 as a potential biomarker in TNBC and investigated the mRNA and protein expression levels of LCP1. We investigated different databases, including GTEX, TCGA, GEO, cBioPortal and Kaplan-Meier Plotter. Immunohistochemistry on TNBC and benign tumor samples was performed to examine LCP1's relationship with patient clinical characteristics and macrophage markers. We also assessed survival rates, immune cell infiltration, and drug sensitivity related to LCP1 using various bioinformatics tools.

Results

The results indicated that LCP1 expression was higher in TNBC tissues compared to adjacent normal tissues. However, high expression of LCP1 was significantly associated with favorable survival outcomes in patients with TNBC. Enrichment analysis revealed that genes co-expressed with LCP1 were significantly enriched in various immune processes. LCP1 showed a positive correlation with the infiltration of resting dendritic cells, M1 macrophages, and memory CD4 T cells, and a negative correlation with M2 macrophages. Further analysis suggested a link between high levels of LCP1 and increased survival outcomes in cancer patients receiving immunotherapy.

Conclusion

LCP1 may serve as a potential diagnostic and prognostic biomarker for TNBC, which was closely associated with immune cell infiltration, particularly M1 and M2 macrophages. Our findings may provide valuable insights into immunotherapeutic strategies for TNBC patients.
Evaluating the effects of temperature and agitation on biofilm formation of bacterial pathogens isolated from raw cow milk
Authors: Alabdullatif Meshari
Published: July 2024

Objectives

To study the effect of agitation and temperature on biofilm formation (cell aggregates embedded within a self-produced matrix) by pathogenic bacteria isolated from Raw cow milk (RCM).

Methods

A 40 RCM samples were gathered from eight dairy farms in Riyadh, Saudi Arabia. After bacterial culturing and isolation, gram staining was performed, and all pathogenic, identified using standard criteria established by Food Standards Australia New Zealand (FSANZ), and non-pathogenic bacteria were identified using VITEK-2 and biochemical assays. To evaluate the effects of temperature and agitation on biofilm formation, isolated pathogenic bacteria were incubated for 24 h under the following conditions: 4 °C with no agitation (0 rpm), 15 °C with no agitation, 30 °C with no agitation, 30 °C with 60 rpm agitation, and 30 °C with 120 rpm agitation. Then, biofilms were measured using a crystal violet assay.

Results

Of the eight farm sites, three exhibited non-pathogenic bacterial contamination in their raw milk samples. Of the total of 40 raw milk samples, 15/40 (37.5%; from five farms) were contaminated with pathogenic bacteria. Overall, 346 bacteria were isolated from the 40 samples, with 329/346 (95.1%) considered as non-pathogenic and 17/346 (4.9%) as pathogenic. Most of the isolated pathogenic bacteria exhibited a significant (p < 0.01) increase in biofilm formation when grown at 30 °C compared to 4 °C and when grown with 120 rpm agitation compared to 0 rpm.

Conclusion

Herein, we highlight the practices of consumers in terms of transporting and storing (temperature and agitation) can significantly impact on the growth of pathogens and biofilm formation in RCM.
Genomic characterization of multi drug resistant ESBL-producing Escherichia coli isolates from patients and patient environments in a teaching hospital in Ghana
Authors: Asare Yeboah Esther Eyram , Agyepong Nicholas , Mbanga Joshua , Amoako Daniel Gyamfi , Abia Akebe Luther King , Ismail Arshad , Owusu-Ofori Alexander , Essack Sabiha Yusuf
Published: July 2024

Background

ESBL-producing Escherichia coli pose a growing health risk in community and healthcare settings. We investigated the resistome, virulome, mobilome, and genetic relatedness of multidrug-resistant (MDR) E. coli isolates from patients and their environment in a Ghanaian teaching hospital.

Materials and methods

Twenty-three MDR ESBL-producing or carbapenem-resistant E. coli isolates from a collection of MDR Gram-negative bacteria (GNB) from patients and environments were selected for genomic analyses. Whole genome sequencing and bioinformatics tools were used to analyze genomic characteristics and phylogeny.

Results

The prevalence and incidence of rectal carriage of ESBL E. coli among patients were 13.65% and 11.32% respectively. The β-lactamase genes, blaTEM−1B (10 isolates) and blaCTX−M−15 (12 isolates) were commonly associated with IncFIB plasmid replicons and co-occurred with aminoglycoside, macrolide, and sulfamethoxazole/trimethoprim resistance. Insertion sequences, transposons, and class I integrons were found with blaCTX−M−15. Carriage and environmental isolates carried multiple virulence genes, with terC being the most prevalent in 21 isolates. Seventeen sequence types (STs) were identified, including a novel ST (ST13846). Phylogenetic analysis grouped the isolates into four main clusters, with one outlier. High genetic relatedness was observed between two carriage isolates of ST940 and between a carriage isolate and an environmental isolate of ST648. Isolates with different STs, collected at different times and locations, also showed genetic similarities.

Conclusion

We identified ESBL-producing E. coli with diverse genomic characteristics circulating in different hospital directorates. Clonal relatedness was observed among isolates from patients and the environment, as well as between different patients, suggesting transmission within and between sources.
Proposal and validation of a new approach in tele-rehabilitation with 3D human posture estimation: a randomized controlled trial in older individuals with sarcopenia
Authors: He Shichun , Meng Deyu , Wei Meiqi , Guo Hongzhi , Yang Guang , Wang Ziheng
Published: July 2024

Objective

Through a randomized controlled trial on older adults with sarcopenia, this study compared the training effects of an AI-based remote training group using deep learning-based 3D human pose estimation technology with those of a face-to-face traditional training group and a general remote training group.

Methods

Seventy five older adults with sarcopenia aged 60–75 from community organizations in Changchun city were randomly divided into a face-to-face traditional training group (TRHG), a general remote training group (GTHG), and an AI-based remote training group (AITHG). All groups underwent a 3-month program consisting of 24-form Taichi exercises, with a frequency of 3 sessions per week and each session lasting 40 min. The participants underwent Appendicular Skeletal Muscle Mass Index (ASMI), grip strength, 6-meter walking pace, Timed Up and Go test (TUGT), and quality of life score (QoL) tests before the experiment, during the mid-term, and after the experiment. This study used SPSS26.0 software to perform one-way ANOVA and repeated measures ANOVA tests to compare the differences among the three groups. A significance level of p < 0.05 was defined as having significant difference, while p < 0.01 was defined as having a highly significant difference.

Results

(1) The comparison between the mid-term and pre-term indicators showed that TRHG experienced significant improvements in ASMI, 6-meter walking pace, and QoL (p < 0.01), and a significant improvement in TUGT timing test (p < 0.05); GTHG experienced extremely significant improvements in 6-meter walking pace and QoL (p < 0.01); AITHG experienced extremely significant improvements in ASMI, 6-meter walking pace, and QoL (p < 0.01), and a significant improvement in TUGT timing test (p < 0.05). (2) The comparison between the post-term and pre-term indicators showed that TRHG experienced extremely significant improvements in TUGT timing test (p < 0.01); GTHG experienced significant improvements in ASMI and TUGT timing test (p < 0.05); and AITHG experienced extremely significant improvements in TUGT timing test (p < 0.01). (3) During the mid-term, there was no significant difference among the groups in all tests (p > 0.05). The same was in post-term tests (p > 0.05).

Conclusion

Compared to the pre-experiment, there was no significant difference at the post- experiment in the recovery effects on the muscle quality, physical activity ability, and life quality of patients with sarcopenia between the AI-based remote training group and the face-to-face traditional training group. 3D pose estimation is equally as effective as traditional rehabilitation methods in enhancing muscle quality, functionality and life quality in older adults with sarcopenia.

Trial registration

The trial was registered in ClinicalTrials.gov (NCT05767710).
MR–CT image fusion method of intracranial tumors based on Res2Net
Authors: Chen Wei , Li Qixuan , Zhang Heng , Sun Kangkang , Sun Wei , Jiao Zhuqing , Ni Xinye
Published: July 2024

Background

Information complementarity can be achieved by fusing MR and CT images, and fusion images have abundant soft tissue and bone information, facilitating accurate auxiliary diagnosis and tumor target delineation.

Purpose

The purpose of this study was to construct high-quality fusion images based on the MR and CT images of intracranial tumors by using the Residual-Residual Network (Res2Net) method.

Methods

This paper proposes an MR and CT image fusion method based on Res2Net. The method comprises three components: feature extractor, fusion layer, and reconstructor. The feature extractor utilizes the Res2Net framework to extract multiscale features from source images. The fusion layer incorporates a fusion strategy based on spatial mean attention, adaptively adjusting fusion weights for feature maps at each position to preserve fine details from the source images. Finally, fused features are input into the feature reconstructor to reconstruct a fused image.

Results

Qualitative results indicate that the proposed fusion method exhibits clear boundary contours and accurate localization of tumor regions. Quantitative results show that the method achieves average gradient, spatial frequency, entropy, and visual information fidelity for fusion metrics of 4.6771, 13.2055, 1.8663, and 0.5176, respectively. Comprehensive experimental results demonstrate that the proposed method preserves more texture details and structural information in fused images than advanced fusion algorithms, reducing spectral artifacts and information loss and performing better in terms of visual quality and objective metrics.

Conclusion

The proposed method effectively combines MR and CT image information, allowing the precise localization of tumor region boundaries, assisting clinicians in clinical diagnosis.
Rash caused by lurasidone in old chinese patient with bipolar disorder: case-based review
Authors: Yang Wenjuan , Hu Danhong , Zheng Bei , Han Bing , Feng Pingping , Zhou Yongcan , Wang Weixin , Li Gonghua , Zhang Meiling
Published: July 2024

Background

Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone.

Case presentation

A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic.

Conclusions

In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.
Strategies to promote treatment compliance: a grounded theory study with relatives of people with a serious mental health condition
Authors: Hempeler Christin , Potthoff Sarah , Scholten Matthé , Juckel Georg , Gather Jakov
Published: July 2024

Background

Treatment pressures encompass communicative strategies that influence mental healthcare service users’ decision-making to increase their compliance with recommended treatment. Persuasion, interpersonal leverage, inducements, and threats have been described as examples of treatment pressures. Research indicates that treatment pressures are exerted not only by mental healthcare professionals but also by relatives. While relatives play a crucial role in their family member’s pathway to care, research on the use of treatment pressures by relatives is still scarce. Likewise, little is known about other strategies relatives may use to promote the treatment compliance of their family member with a serious mental health condition. In particular, no study to date has investigated this from the perspective of relatives of people with a serious mental health condition.

Aim

The aim of this study was to answer the following research questions: Which types of treatment pressures do relatives use? Which other strategies do relatives use to promote the treatment compliance of their family member with a serious mental health condition? How do treatment pressures relate to these other strategies?

Methods

Eleven semi-structured interviews were conducted with relatives of people with a serious mental health condition in Germany. Participants were approached via relatives’ self-help groups and flyers in a local psychiatric hospital. Inclusion criteria were having a family member with a psychiatric diagnosis and the family member having experienced formal coercion. The data were analyzed using grounded theory methodology.

Results

Relatives use a variety of strategies to promote the treatment compliance of their family member with a serious mental health condition. These strategies can be categorized into three general approaches: influencing the decision-making of the family member; not leaving the family member with a choice; and changing the social or legal context of the decision-making process. Our results show that the strategies that relatives use to promote their family member’s treatment compliance go beyond the treatment pressures thus far described in the literature.

Conclusion

This qualitative study supports and conceptually expands prior findings that treatment pressures are not only frequently used within mental healthcare services but also by relatives in the home setting. Mental healthcare professionals should acknowledge the difficulties faced and efforts undertaken by relatives in seeking treatment for their family member. At the same time, they should recognize that a service user’s consent to treatment may be affected and limited by strategies to promote treatment compliance employed by relatives.
Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and kidney stone: evidence from NHANES 2007–2018
Authors: Chen Tao , Cheng Yu , Song Zheng , Zhang Gan , Zeng Tao , Chao Haichao
Published: July 2024

Background

As an innovative lipid parameter, NHHR (the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol) can serve as a valuable tool for assessing cardiovascular disease risk. Nevertheless, the relationship between NHHR and the risk of kidney stones remains unexplored.

Methods

A cross-sectional survey utilized data from the National Health and Population Survey (NHANES) database in the United States spanning from 2007 to 2018. Distinct statistical analyses were applied, including weighted logistic regression, stratified and interaction analysis and restricted cubic spline curve (RCS) models, to examine the correlation between NHHR and the incidence of kidney stones.

Results

This analysis encompassed 24,664 participants, with 9.63% reporting incidents of kidney stones. Following multivariate logistic regression and comprehensive adjustments, participants in NHHR quartile 4 (OR 1.34; 95% CI 1.12, 1.60, P < 0.01) exhibited a significantly increased risk of kidney stones compared to those in NHHR quartile 1 (Q1). The RCS result further illustrated a non-linear correlation between NHHR and the incidence of kidney stones. The result of subgroup analysis manifested that participants without diabetes had a higher risk of kidney stones when measured high NHHR levels compared those with diabetes (p for interaction < 0.05).

Conclusion

Elevated NHHR levels were found to be associated with an increased risk of kidney stones. Based on these findings, NHHR appears to be a promising predictive indicator for the occurrence of kidney stones.
Effects of exercise on depression and anxiety in postmenopausal women: a pairwise and network meta-analysis of randomized controlled trials
Authors: Han Bing , Duan Yaya , Zhang Peizhen , Zeng Liqing , Pi Peng , Chen Jiping , Du Guoli
Published: July 2024

Background

Exercise has been identified as a promising non-pharmacological therapy for the management of depression, but there is still controversy over which type is most effective. We aimed to compare and rank the types of exercise that improve depression in postmenopausal women by quantifying information from randomized controlled trials (RCTs).

Methods

The PubMed, Web of Science, SPORTDiscus, CNKI, The Cochrane Library, PsycINFO, EMBASE, and CINAHL Plus databases were searched to identify articles published from inception to 1 March 2024 reporting RCTs that examined the effectiveness of exercise on depression in postmenopausal women. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for RCTs. The quality of the evidence for each comparison was graded using the online confidence in network meta-analysis tool (CINeMA). Standardized mean differences (SMDs) were calculated using the mean and standard deviation of pre-to-post intervention changes and then pooled using a random effects model in a pairwise meta-analysis using Review Manager 5.4. Then, a frequentist network meta-analysis was conducted using a random effects model was conducted to evaluate the efficacy of different exercise types using the network package of Stata 15.

Results

This study included 26 studies involving 2,170 participants. The pairwise meta-analysis revealed that exercise had a significant positive effect on depression in postmenopausal women (SMD = -0.71, 95% confidence interval [CI] = -0.94 to -0.48; I2 = 78%). The network meta-analysis revealed that mind-body exercise (SMD = -0.97, 95% CI = -1.28 to -0.67), aerobic exercise (SMD = -0.58, 95% CI = -0.88 to -0.27) and multicomponent exercise (SMD = -0.57, 95% CI = -1.15 to -0.002) significantly reduced depression compared to the control intervention. Mind-body exercise had the highest probability of being the most effective intervention. Exercise interventions also showed positive effects on anxiety. Most studies were judged to have some concerns regarding their risk of bias, and the confidence in evidence was often very low according to CINeMA.

Conclusion

For postmenopausal women, there is very low to moderate quality evidence that exercise interventions are an effective antidepressant therapy, with mind-body exercise most likely being the optimal type.

Trial registration

This meta-analysis was prospectively registered with PROSPERO (registration number: CRD42024505425).
Machine learning models to predict systemic inflammatory response syndrome after percutaneous nephrolithotomy
Authors: Zhang Tianwei , Zhu Ling , Wang Xinning , Zhang Xiaofei , Wang Zijie , Xu Shang , Jiao Wei
Published: July 2024

Objective

The objective of this study was to develop and evaluate the performance of machine learning models for predicting the possibility of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL).

Methods

We retrospectively reviewed the clinical data of 337 patients who received PCNL between May 2020 and June 2022. In our study, 80% of the data were used as the training set, and the remaining data were used as the testing set. Separate prediction models based on the six machine learning algorithms were created using the training set. The predictive performance of each machine learning model was determined by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity using the testing set. We used coefficients to interpret the contribution of each variable to the predictive performance.

Results

Among the six machine learning algorithms, the support vector machine (SVM) delivered the best performance with accuracy of 0.868, AUC of 0.942 (95% CI 0.890–0.994) in the testing set. Further analysis using the SVM model showed that prealbumin contributed the most to the prediction of the outcome, followed by preoperative urine culture, systemic immune-inflammation (SII), neutrophil to lymphocyte ratio (NLR), staghorn stones, fibrinogen, operation time, preoperative urine white blood cell (WBC), preoperative urea nitrogen, hydronephrosis, stone burden, sex and preoperative lymphocyte count.

Conclusion

Machine learning-based prediction models can accurately predict the possibility of SIRS after PCNL in advance by learning patient clinical data, and should be used to guide surgeons in clinical decision-making.
Subgroups of relational job characteristics and their differences in turnover intention and subjective well-being among nurses: a latent profile analysis
Authors: Chen Yi-ping , Li Yifei , Zhang Jie , Li Juan , Yang Xiu-fen , Xiong Lile , Xia Guili , Zhang Jingping
Published: July 2024

Objective

Relational job characteristics include perceived social worth and perceived social influence. Good relational job characteristics mean that nurses have high prosocial behavior. The purpose of this study was to explore the potential profile of nurses’ relational job characteristics, influencing factors and their differences in turnover intention and subjective well-being, thus finding the most suitable clinical relationship job characteristics.

Methods

A cross-sectional survey was conducted among 1013 clinical nurses using the general demographic data questionnaire, Relational Job Characteristics scale, Turnover Intention Questionnaire and Campbell index of well-being. A latent profile analysis was performed to explore relational job characteristics latent profiles. Multinomial logistic regression analysis was conducted to examine the predictors of profile membership, and a one-way analysis of variance was applied to compare the turnover intention and subjective well-being in each latent profile.

Results

Five latent profiles were identified and labeled ‘High prosocial job characteristics’ profile (20.7%), ‘Moderate prosocial job characteristics’ profile (41.7%), ‘High social worth-low social impact perceived’ profile (6.3%), ‘Low social worth‐high social impact perceived’ profile (18.8%) and ‘Low prosocial job characteristics’ profile (12.5%). Factors affecting the different types of nurse relationship job characteristics include age, marital status, hospital department, nursing years, professional title and hospital position. Among them, chief nurse, nurses with more than 20 years of nursing experience and obstetrics and gynecology nurses were more likely to be ‘high prosocial job characteristics’ profile. The turnover intention of nurses in ‘high prosocial job characteristics’ profile was significantly lower than that of other profiles, and their subjective well-being was significantly higher than that of other profiles.

Conclusion

Improving nurses’ perception of social worth and social impact on clinical work can improve nurses’ prosocial behavior and subjective well-being, and reduce their turnover intention. Nursing managers or policy makers can formulate targeted intervention measures according to the influencing factors of potential profiles.
Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome
Authors: Wang Duocai , Pan Meize , Li Hang , Li Minchun , Li Ping , Xiong Fu , Xiao Hongbo
Published: July 2024

Background

Alport syndrome (AS) is an inherited nephropathy caused by mutations in the type IV collagen genes. It is clinically characterized by damage to the eyes, ears and kidneys. Diagnosis of AS is hampered by its atypical clinical picture, particularly when the typical features, include persistent hematuria and microscopic changes in the glomerular basement membrane (GBM), are the only clinical manifestations in the patient.

Methods

We screened 10 families with suspected AS using whole exome sequencing (WES) and analyzed the harmfulness, conservation, and protein structure changes of mutated genes. In further, we performed in vitro functional analysis of two missense mutations in the COL4A5 gene (c.2359G > C, p.G787R and c.2605G > A, p.G869R).

Results

We identified 11 pathogenic variants in the type IV collagen genes (COL4A3, COL4A4 and COL4A5). These pathogenic variants include eight missense mutations, two nonsense mutations and one frameshift mutation. Notably, Family 2 had digenic mutations in the COL4A3 (p.G1170A) and UMOD genes (p.M229K). Family 3 had a digenic missense mutation (p.G997E) in COL4A3 and a frameshift mutation (p.P502L fs*151) in COL4A4. To our knowledge, four of the 11 mutations are novel mutations. In addition, we found that COL4A5 mutation relation mRNA levels were significantly decreased in HEK 293 T cell compared to control, while the cellular localization remained the same.

Conclusions

Our research expands the spectrum of COL4A3-5 pathogenic variants, which is helpful for clinical and scientific research.
A case of Ph+ acute lymphoblastic leukemia and EGFR mutant lung adenocarcinoma synchronous overlap: may one TKI drug solve two diseases?
Authors: Zhang Qi , Zhou Jing-dong , Ding Hao , Yang Lei , Lu Chao , Chu Ming-qiang , Qian Jun , Zhang Ting-juan
Published: July 2024

Background

Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) refers to ALL patients with t(9;22) cytogenetic abnormalities, accounting for about 25% of ALL. Lung adenocarcinoma (LUAD) is the most common pathological type of non-small-cell lung cancer, which has a frequency of approximately 45% cases with mutations in EGFR. Both Ph+ ALL and EGFR mutant LUAD are involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway. Although the second primary hematological malignancy after the treatment of solid tumors is common in clinics, the synchronous multiple primary malignant tumors of hematological malignancy overlap solid tumors are uncommon, even both tumors involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway are extremely rare.

Case presentation

An 84-year-old man with fatigue and dizziness was diagnosed with Ph+ ALL. Meanwhile, a chest CT indicated a space-occupying lesions, characterized by the presence of void, in the right lower lope with the enlargement of mediastinal lymph node and right pleural effusion. After a few weeks, the patient was diagnosed with LUAD with EGFR exon 19 mutation. Both tyrosine kinase inhibitors (TKI) (Flumatinib) and EGFR-TKI (Oxertinib) was used for the patients, and finally have controlled both diseases.

Conclusion

As far as we know, we for the first time reported a case of Ph+ ALL and EGFR mutant LUAD synchronous overlap, of which pathogenesis is related to abnormal tyrosine kinase activation. This patient was successfully treated with two different TKIs without serious adverse events.
Trends in direct health care costs among US adults with atherosclerotic cardiovascular disease with and without diabetes
Authors: Shah Chintal H. , Fonarow Gregg C. , Echouffo-Tcheugui Justin B.
Published: July 2024

Objective

Population-based national data on the trends in expenditures related to coexisting atherosclerotic cardiovascular diseases (ASCVD) and diabetes is scarce. We assessed the trends in direct health care expenditures for ASCVD among individuals with and without diabetes, which can help to better define the burden of the co-occurrence of diabetes and ASCVD.

Methods

We used 12-year data (2008–2019) from the US national Medical Expenditure Panel Survey including 28,144 U.S individuals aged ≥ 18 years. Using a two-part model (adjusting for demographics, comorbidities and time), we estimated mean and adjusted incremental medical expenditures by diabetes status among individuals with ASCVD. The costs were direct total health care expenditures (out-of-pocket payments and payments by private insurance, Medicaid, Medicare, and other sources) from various sources (office-based visits, hospital outpatient, emergency room, inpatient hospital, pharmacy, home health care, and other medical expenditures).

Results

The total direct expenditures for individuals with ASCVD increased continuously by 30% from $14,713 (95% confidence interval (CI): $13,808–$15,619) in 2008–2009 to $19,145 (95% CI: $17,988–$20,301) in 2008–2019. Individuals with diabetes had a 1.5-fold higher mean expenditure that those without diabetes. A key driver of the observed increase in direct costs was prescription drug costs, which increased by 37% among all individuals with ASCVD. The increase in prescription drug costs was more pronounced among individuals with ASCVD and diabetes, in whom a 45% increase in costs was observed, from $5184 (95% CI: $4721–$5646) in 2008–2009 to $7501 (95% CI: $6678–$8325) in 2018–2019. Individuals with ASCVD and diabetes had $5563 (95% CI: $4643–$6483) higher direct incremental expenditures compared with those without diabetes, after adjusting for demographics and comorbidities. Among US adults with ASCVD, the estimated adjusted total direct excess medical expenditures were $42 billion per year among those with diabetes vs. those without diabetes.

Conclusions

In the setting of ASCVD, diabetes is associated with significantly increased health care costs, an increase that was driven by marked increase in medication costs.
Fitness costs of Tn1546-type transposons harboring the vanA operon by plasmid type and structural diversity in Enterococcus faecium
Authors: Kim Dokyun , Kang Da Young , Choi Min Hyuk , Hong Jun Sung , Kim Hyun Soo , Kim Young Ree , Kim Young Ah , Uh Young , Shin Kyeong Seob , Shin Jeong Hwan , Kim Soo Hyun , Shin Jong Hee , Jeong Seok Hoon
Published: July 2024

Background

This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon.

Methods

All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments.

Results

Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P < 0.001), and reduction in growth rate under vancomycin pressure was significantly larger in isolates harboring putative linear plasmids than in those harboring circular plasmids (P = 0.020).

Conclusions

The possession of vanA operon was costly to bacterial hosts in antimicrobial-free environment, which provide evidence for the importance of reducing vancomycin pressure for prevention of VREfm dissemination. Fitness burden to bacterial hosts was varied by type and size of the vanA operon-harboring plasmid.
Clinical data-based modeling of IVF live birth outcome and its application
Authors: Liu Liu , Liang Hua , Yang Jing , Shen Fujin , Chen Jiao , Ao Liangfei
Published: July 2024

Background

The low live birth rate and difficult decision-making of the in vitro fertilization (IVF) treatment regimen bring great trouble to patients and clinicians. Based on the retrospective clinical data of patients undergoing the IVF cycle, this study aims to establish classification models for predicting live birth outcome (LBO) with machine learning methods.

Methods

The historical data of a total of 1405 patients undergoing IVF cycle were first collected and then analyzed by univariate and multivariate analysis. The statistically significant factors were identified and taken as input to build the artificial neural network (ANN) model and supporting vector machine (SVM) model for predicting the LBO. By comparing the model performance, the one with better results was selected as the final prediction model and applied in real clinical applications.

Results

Univariate and multivariate analysis shows that 7 factors were closely related to the LBO (with P < 0.05): Age, ovarian sensitivity index (OSI), controlled ovarian stimulation (COS) treatment regimen, Gn starting dose, endometrial thickness on human chorionic gonadotrophin (HCG) day, Progesterone (P) value on HCG day, and embryo transfer strategy. By taking the 7 factors as input, the ANN-based and SVM-based LBO models were established, yielding good prediction performance. Compared with the ANN model, the SVM model performs much better and was selected as the final model for the LBO prediction. In real clinical applications, the proposed ANN-based LBO model can predict the LBO with good performance and recommend the embryo transfer strategy of potential good LBO.

Conclusions

The proposed model involving all essential IVF treatment factors can accurately predict LBO. It can provide objective and scientific assistance to clinicians for customizing the IVF treatment strategy like the embryo transfer strategy.
Physical activity, gut microbiota and the nexuses of metabolic and psychological disorders in children and adolescents
Authors: Ashaolu Joseph Opeolu , Sylvain Some Y. Marie , Otuechere Chiagoziem A. , Bamigboye Olufunke C. , Ashaolu Tolulope Joshua
Published: July 2024

The burden of health issues surrounding the children and adolescents (ChAds) population is of great concern. From metabolic disorders such as obesity, non-alcoholic fatty liver disease, diabetes, multiple sclerosis including mental and several other psychological disorders like attention deficit hyperactivity, internet addiction, autism spectrum, subthreshold mood symptoms and depression, and stress disorders, is a nexus of the gut microbiota (GM) profile and physical activity (PA), as they both play a crucial role in ameliorating these disorders. The aim of this review is to explore the disorders with regard to their association with ChAds’ GM and its health. We started with brief descriptions of PA and its connections with GM profile cum health in ChAds. In addition, the disorders in ChAds were broadly classified into metabolic and psychological. Observations from the discussed sections show that exercise and physical activity are efficient methods for enhancing physical, metabolic, and mental health, which are often GM-mediated, and thus might require certain levels of personalization. Furthermore, age, gender, genetics, baseline BMI, baseline exercise level, and diet are key parameters to be explored when proffering intervention of combative mechanisms against these disorders.
Impact of fish oil supplementation on plasma levels of highly unsaturated fatty acid-containing lipid classes and molecular species in American football athletes
Authors: Mullins Veronica Anne , Snider Justin M. , Michael Bryce , Porter Lydia Rose , Brinton Roberta Diaz , Chilton Floyd H.
Published: July 2024

Background

Previous studies have linked sports-related concussions and repeated subconcussive head impacts in contact sport athletes to elevated brain injury biomarkers. Docosahexaenoic acid (DHA), the primary omega-3 (n-3) highly unsaturated fatty acid (HUFA) in the brain, has shown neuroprotective effects in animal models after brain injury, but clinical research has shown mixed results.

Methods

We conducted a randomized, double-blind, placebo-controlled study on 29 Division 1 collegiate American football players, exploring the impact of DHA (2.5 g) and eicosapentaenoic acid (EPA) (1.0 g) supplied as ethyl esters, on levels of plasma lipids shown to cross the blood-brain barrier. Dietary intake data was collected using food frequency questionnaires (FFQ). Complex lipids and unesterified fatty acids were isolated from plasma, separated via reversed-phase liquid chromatography and analyzed by targeted lipidomics analysis.

Results

FFQ results indicated that participants had low dietary n-3 HUFA intake and high omega-6 (n-6):n-3 polyunsaturated fatty acids (PUFA) and HUFA ratios at baseline. After DHA + EPA supplementation, plasma lysophosphatidylcholine (LPC) containing DHA and EPA significantly increased at all timepoints (weeks 17, 21, and 26; p < 0.0001), surpassing placebo at Weeks 17 (p < 0.05) and 21 (p < 0.05). Phosphatidylcholine (PC) molecular species containing DHA or EPA, PC38:6 PC36:6, PC38:7, PC40:6, and PC40:8, increased significantly in the DHA + EPA treatment group at Weeks 17 (and 21. Plasma concentrations of non-esterified DHA and EPA rose post-supplementation in Weeks 17 and 21.

Conclusions

This study demonstrates that n-3 HUFA supplementation, in the form of ethyl esters, increased the DHA and EPA containing plasma lipid pools the have the capacity to enrich brain lipids and the potential to mitigate the effects of sports-related concussions and repeated subconcussive head impacts.

Trial Registration

All deidentified data are available at ClinicalTrials.gov #NCT0479207.
Application of 3D bioprinting technology apply to assessing Dangguiniantongtang (DGNT) decoctions in arthritis
Authors: Liang Zhichao , Han Yunxi , Chen Tao , Wang Jinwu , Lin Kaili , Yuan Luying , Li Xuefei , Xu Hao , Wang Tengteng , Liu Yang , Xiao Lianbo , Liang Qianqian
Published: July 2024

The aim of this study was to develop a three-dimensional (3D) cell model in order to evaluate the effectiveness of a traditional Chinese medicine decoction in the treatment of arthritis. Chondrocytes (ATDC5) and osteoblasts (MC3T3-E1) were 3D printed separately using methacryloyl gelatin (GelMA) hydrogel bioinks to mimic the natural 3D cell environment. Both cell types showed good biocompatibility in GelMA. Lipopolysaccharide (LPS) was added to the cell models to create inflammation models, which resulted in increased expression of inflammatory factors IL-1β, TNF-α, iNOS, and IL-6, and decreased expression of cell functional genes such as Collagen II (COLII), transcription factor SOX-9 (Sox9), Aggrecan, alkaline phosphatase (ALP), RUNX family transcription factor 2 (Runx2), Collagen I (COLI), Osteopontin (OPN), and bone morphogenetic protein-2 (BMP-2). The created inflammation model was then used to evaluate the effectiveness of Dangguiniantongtang (DGNT) decoctions. The results showed that DGNT reduced the expression of inflammatory factors and increased the expression of functional genes in the cell model. In summary, this study established a 3D cell model to assess the effectiveness of traditional Chinese medicine (TCM) decoctions, characterized the gene expression profile of the inflammatory state model, and provided a practical reference for future research on TCM efficacy evaluation for arthritis treatment.
Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer
Authors: Bahadar Noor , Bahadar Sher , Sajid Abdul , Wahid Muqeet , Ali Ghadir , Alghamdi Abdullah , Zada Hakeem , Khan Tamreez , Ullah Shafqat , Sun Qingjia
Published: July 2024

The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.
Survival, mortality and epidemic risk status of COVID-19: a population-based Study in Golestan province, Iran
Authors: Kashiri Fatemeh , Sarbakhsh Parvin , Mohammadpoorasl Asghar , Seyedghasemi Navisa Sadat , Bagheri Ali , Akbari Hossein
Published: July 2024

Background

Appreciating the various dimensions of the coronavirus disease 2019 (COVID-19) pandemic can improve health systems and prepare them to deal better with future pandemics and public health events. This study was conducted to investigate the association between the survival of hospitalized patients with COVID-19 and the epidemic risk stratification of the disease in Golestan province, Iran.

Methods

In this study, all patients with COVID-19 who were hospitalized in the hospitals of Golestan province of Iran from February 20, 2020, to December 19, 2022, and were registered in the Medical Care Monitoring Center (MCMC) system (85,885 individuals) were examined.The community's epidemic risk status (ERS) was determined based on the daily incidence statistics of COVID-19. The survival distribution and compare Survival in different subgroups was investigated using Kaplan–Meier and log-rank test and association between the survival and ERS by multiple Cox regression modeling.

Results

Out of 68,983 individuals whose data were correctly recorded, the mean age was 49 (SD = 23.98) years, and 52.8% were women. In total, 11.1% eventually died. The length of hospital stay was varying significantly with age, gender, ERS, underlying diseases, and COVID-19 severity (P < 0.001 for all). The adjusted hazard ratio of death for the ERS at medium, high, and very high-risk status compared to the low-risk status increased by 19%, 26%, and 56%, respectively (P < 0.001 for all).

Conclusions

Enhancing preparedness, facilitating rapid rises in hospital capacities, and developing backup healthcare capacities can prevent excessive hospital referrals during health crises and further deaths.