bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the safety of Levilactobacillus brevis CNCM I-5321, a probiotic candidate strain isolated from pulque with anti-proliferative activities
Authors: Torres-Maravilla E. , Boucard A.-S. , Al Azzaz J. , Gontier S. , Kulakauskas S. , Langella P. , Bermúdez-Humarán L.G.
Published: September 2023

Gut dysbiosis has been strongly correlated with colorectal cancer (CRC) development and the use of probiotics to modulate this imbalance represents a potential and promising therapy to prevent and treat CRC. For this reason, the identification of novel probiotic strains from diverse origins has widely increased in recent years, including traditional fermented foods. In this work we describe a new strain previously isolated from pulque (a traditional Mexican beverage), Levilactobacillus brevis CNCM I-5321, which may represent an interesting probiotic candidate to prevent and treat cancer. Indeed, our results show that CNCM I-5321 displays significant and specific antiproliferative capacities in human intestinal cancer cell lines (HT-29, HTC-116 and Caco-2 cells), but not in normal cells (FH cells). In addition, CNCM I-5321 is able to induce: (1) a pro-inflammatory immune response through stimulation of interleukin (IL)-2, IL-6, IL-12 and IL-17 cytokines and (2) apoptosis via activation of caspase 8. On the other hand, a minimum inhibitory concentration (MIC) assay revealed phenotypic resistance of this strain to ampicillin and chloramphenicol. However, no known transferable determinants were found in the genome of CNCM I-5321, thus this probiotic candidate presents no risk of horizontal transfer to the intestinal bacterial population. Finally, the safety status of CNCM I-5321 was evaluated using an innovative model of chicken embryo chorioallantoic membrane (CAM) to assess undesirable and/or toxic effects. Overall, our results support that CNCM I-5321 strain is non-pathogenic and safe for potential use as an anti-cancer candidate in human and animal medicine.
On the Shared Structure of the Early to High Tang Gexing and the Seven-Character Short Poem with a Discussion of “Kayō Jūei” as a Japanese Seven-Character Short Poem Sequence
Authors: Liu Yi
Published: September 2023

The seven-character short poem [duan ge 短歌] is a distinct poetic form that originated in Han dynasty ballads and peaked during the Liang dynasty. It is closely related to the gexing 歌行 [song or song poem], a poetic form that also flourished during the Qi and Liang dynasties. The two forms differ in substance, with the former tending towards brevity and, the latter, length; however, they share fundamental principles of compositional method. At the start of the Tang dynasty, the seven-character short poem had not yet been eclipsed by the seven-character quatrain [jueju 絕句]; rather, it maintained its place among Early and High Tang poetic forms and continued to develop on its own terms. The “Ten Songs on Kayō [Kayō jūei 河陽十詠]” is a seven-character short poem sequence from the Heian period in Japan. Its formal elements are similar to those of the Chinese seven-character short poem, and it shares structural qualities with Qi-Liang style gexing composed by Heian poets. At the same, it also shares characteristics of the Heian topic poem. Its unique existence prompts us to look back to old poetic forms as precious source materials from which we may excavate long-overlooked stylistic phenomenon in poetry.
The Evolution of Money Culture and the Transformation of Narrative Culture in Pre-modern Chinese Fiction
Authors: Xu Jianping , Zhang Yaxin
Published: September 2023

The money culture of a given time and place can have a profound influence on literature, a medium that allows for the artistic expression of aesthetic taste. This article takes money culture as its analytical lens to explore the cultural transformation of literary concepts that were prevalent in Chinese novels. It will delve into the transition from agricultural production and lifestyles, which were focused on productive and consumptive survival, to industrialized production and lifestyles, which were centered on monetary survival. Additionally, it will trace the evolution from farming literature, which is rooted in Confucian morality, to commercial literature, which is characterized by themes of wealth, lust, and the search for novelty.
Effects of wind barriers on the aerodynamic characteristics of twin-separated parallel decks for a long-span rail-cum-road bridge
Authors: Liu Lulu , Yang Jiafeng , Zou Yunfeng , He Xuhui , Cai Chenzhi
Published: September 2023

The aerodynamic characteristics of twin-separated parallel decks for long-span rail-cum-road bridges with various wind barriers clamped at railway girder are more complicated because of aerodynamic interference. Experimental investigations on aerodynamic coefficient and wind pressure coefficients of twin girders under different incoming flow directions were conducted using wind tunnel tests. Three different heights ( H) varying from 2 m to 4 m and four different ventilation ratios ( R) varying from 20% to 50% for wind barriers were examined. Results indicated that the aerodynamic coefficients were affected significantly by the incoming wind direction, which must be considered, and the railway wind barrier affected the aerodynamic characteristics of the railway girder when it is located both upstream and downstream, but the laws are not the same. Due to the aerodynamic interference effect of the twin parallel girders, the aerodynamic characteristics of the adjacent highway girders were also affected by the wind barrier along the railway girder, especially when the highway girders were located downstream. While, the highway girders were less affected when located upstream. The influence of wind barrier height and ventilation ratios on the adjacent highway girders was completely different. Most importantly, the parameters optimization of wind barriers clamped at railway girders should be determined after a comprehensive evaluation of the aerodynamic characteristic of both the railway and highway girders.
Genetic analysis of 42 Y-STR loci in Han and Manchu populations from the three northeastern provinces in China
Authors: Song Wenqian , Zhou Shihang , Yu Weijian , Fan Yaxin , Liang Xiaohua
Published: September 2023

Background

Y-STR polymorphisms are useful in tracing genealogy and understanding human origins and migration history. This study aimed to fill a knowledge gap in the genetic diversity, structure, and haplogroup distribution of the Han and Manchu populations from the three northeastern provinces in China (Liaoning, Jilin, and Heilongjiang).

Methods

A total of 1,048 blood samples were collected from unrelated males residing in Dalian. Genotyping was performed using the AGCU Y37 + 5 Amplification Kit, and the genotype data were analyzed to determine allele and haplotype frequencies, genetic and haplotype diversity, discrimination capacity, and haplotype match probability. Population pairwise genetic distances (Fst) were calculated to compare the genetic relationships among Han and Manchu populations from Northeast China and other 23 populations using 27 Yfiler Plus loci set. Multi-dimensional scaling and phylogenetic analysis were employed to visualize the genetic relationships among the 27 populations. Moreover, haplogroups were predicted based on 27 Yfiler Plus loci set.

Results

The Han populations from Northeast China exhibited genetic affinities with both Han populations from the Central Plain and the Sichuan Qiang population, despite considerable geographical distances. Conversely, the Manchu population displayed a relatively large genetic distance from other populations. The haplogroup analysis revealed the prevalence of haplogroups E1b1b, O1b, O2, and Q in the studied populations, with variations observed among different ethnic groups.

Conclusion

The study contributes to our understanding of genetic diversity and history of the Han and Manchu populations in Northeast China, the genetic relationships between populations, and the intricate processes of migration, intermarriage, and cultural integration that have shaped the region’s genetic landscape.
RNA-Seq analysis of the pyloric caecum, liver, and muscle reveals molecular mechanisms regulating fillet color in rainbow trout
Authors: Ahmed Ridwan O. , Ali Ali , Leeds Tim , Salem Mohamed
Published: September 2023

Background

The characteristic pink-reddish color in the salmonids fillet is an important, appealing quality trait for consumers and producers. The color results from diet supplementation with carotenoids, which accounts for up to 20–30% of the feed cost. Pigment retention in the muscle is a highly variable phenotype. In this study, we aimed to understand the molecular basis for the variation in fillet color when rainbow trout (Oncorhynchus mykiss) fish families were fed an Astaxanthin-supplemented diet. We used RNA-Seq to study the transcriptome profile in the pyloric caecum, liver, and muscle from fish families with pink-reddish fillet coloration (red) versus those with lighter pale coloration (white).

Results

More DEGs were identified in the muscle (5,148) and liver (3,180) than in the pyloric caecum (272). Genes involved in lipid/carotenoid metabolism and transport, ribosomal activities, mitochondrial functions, and stress homeostasis were uniquely enriched in the muscle and liver. For instance, the two beta carotene genes (BCO1 and BCO2) were significantly under-represented in the muscle of the red fillet group favoring more carotenoid retention. Enriched genes in the pyloric caecum were involved in intestinal absorption and transport of carotenoids and lipids. In addition, the analysis revealed the modulation of several genes with immune functions in the pyloric caecum, liver, and muscle.

Conclusion

The results from this study deepen our understanding of carotenoid dynamics in rainbow trout and can guide us on strategies to improve Astaxanthin retention in the rainbow trout fillet.
Identification of apoptosis-related key genes and the associated regulation mechanism in thoracic aortic aneurysm
Authors: Ma Qi , Hu Long , Luo Yingwan , Wang Miao , Yu Shui , Lu Aidong , Zhang Leping , Zeng Huimin
Published: September 2023

Background

This study investigated the role of apoptosis-related genes in thoracic aortic aneurysms (TAA) and provided more insights into TAA's pathogenesis and molecular mechanisms.

Material/methods

Two gene expression datasets (GSE9106 and GSE26155) were retrieved from the Gene Expression Omnibus (GEO) database. Apoptosis-related genes were obtained from the KEGG apoptosis pathway (hsa04210). Differentially expressed apoptosis-related genes were identified by performing differential expression analysis using limma for TAA blood and tissue samples. GO and KEGG enrichment analysis of the differentially expressed apoptosis genes was performed using the Metascape web tool. The miRNA-mRNA regulatory network was reconstructed using the ENCORI and miRDB databases, and functional enrichment analysis was performed on the related miRNAs using the miEAA tool. The correlation between the expression levels of differentially expressed apoptosis-related genes and genes involved in immune infiltration in TAA was calculated using the CIBERSORT algorithm. The apoptosis modification patterns mediated by differentially expressed apoptosis-related genes were systematically assessed in TAA samples.

Results

A total of 9 differentially-expressed apoptosis-related genes were identified in TAA samples compared with normal samples. 150 miRNAs and 6 mRNAs regulatory networks were reconstructed using the ENCORI and miRDB databases. Immune infiltration analysis revealed that the GZMB had the strongest positive correlation with activated NK cells and the DFFA presented the strongest positive correlation with T cells follicular helper. 3 distinct apoptosis modification patterns mediated by 9 differentially-expressed apoptosis-related genes were identified. They differ in immune characteristics and drug sensitivity, and their biological functions in these subtypes were further studied.

Conclusions

This study identified key apoptosis-related genes related to TAA and evaluated the modification patterns of key apoptosis genes in TAA, providing insights into potential targets and mechanisms of TAA pathogenesis and progression.
Ensuring cross-cultural data comparability by means of anchoring vignettes in heterogeneous refugee samples
Authors: Menold Natalja , Biddle Louise , von Hermanni Hagen , Kadel Jasmin , Bozorgmehr Kayvan
Published: September 2023

Background

Configural, metric, and scalar measurement invariance have been indicators of bias-free statistical cross-group comparisons, although they are difficult to verify in the data. Low comparability of translated questionnaires or the different understanding of response formats by respondents might lead to rejection of measurement invariance and point to comparability bias in multi-language surveys. Anchoring vignettes have been proposed as a method to control for the different understanding of response categories by respondents (the latter is referred to as differential item functioning related to response categories or rating scales: RC-DIF). We evaluate the question whether the cross-cultural comparability of data can be assured by means of anchoring vignettes or by considering socio-demographic heterogeneity as an alternative approach.

Methods

We used the Health System Responsiveness (HSR) questionnaire and collected survey data in English (n = 183) and Arabic (n = 121) in a random sample of refugees in the third largest German federal state. We conducted multiple-group Confirmatory Factor Analyses (MGCFA) to analyse measurement invariance and compared the results when 1) using rescaled data on the basis of anchoring vignettes (non-parametric approach), 2) including information on RC-DIF from the analyses with anchoring vignettes as covariates (parametric approach) and 3) including socio-demographic covariates.

Results

For the HSR, every level of measurement invariance between the Arabic and English languages was rejected. Implementing rescaling or modelling on the basis of anchoring vignettes provided superior results over the initial MGCFA analysis, since configural, metric and – for ordered categorical analyses—scalar invariance could not be rejected. A consideration of socio-demographic variables did not show such an improvement.

Conclusions

Surveys may consider anchoring vignettes as a method to assess cross-cultural comparability of data, whereas socio-demographic variables cannot be used to improve data comparability as a standalone method. More research on the efficient implementation of anchoring vignettes and further development of methods to incorporate them when modelling measurement invariance is needed.
A rare case of periprosthetic joint infection of the hip due to Kocuria spp.
Authors: Koenemann Nora Anais , Sauerwald Fabian , Thimel Dierk , Mayr Edgar
Published: September 2023

Background

Kocuria spp. are ubiquitous bacteria that have gained recent attention as potential infectious agents. The most common bacteria in PJI are S. aureus und S. epidermidis.

Case presentation

We present the case of a 72-year-old woman who received total hip arthroplasty after a traumatic medial femoral neck fracture. Postoperatively, due to the clinical presentation of periprosthetic joint infection (PJI) revision surgery was performed twice. The microbiological tissue samples were positive for Kocuria spp. Initially, this was considered contamination and the patient was treated with various antibiotic regimens as well as prednisolone due to the differential diagnosis of pyoderma gangraenosum. However, a specialized histopathology lab performed further testing which substantiated the suspicion of a rare case of PJI due to Kocuria spp.

Conclusions

To our knowledge, this is the first reported case of a PJI caused by Kocuria spp. Further clinical research is necessary to assess whether Kocuria spp. are an underestimated cause of PJI.
Genotypic and phenotypic comparison of drug resistance profiles of clinical multidrug-resistant Mycobacterium tuberculosis isolates using whole genome sequencing in Latvia
Authors: Vīksna Anda , Sadovska Darja , Berge Iveta , Bogdanova Ineta , Vaivode Annija , Freimane Lauma , Norvaiša Inga , Ozere Iveta , Ranka Renāte
Published: September 2023

Background

Multidrug-resistant tuberculosis (MDR–TB) remains a major public health problem in many high tuberculosis (TB) burden countries. Phenotypic drug susceptibility testing (DST) take several weeks or months to result, but line probe assays and Xpert/Rif Ultra assay detect a limited number of resistance conferring gene mutations. Whole genome sequencing (WGS) is an advanced molecular testing method which theoretically can predict the resistance of M. tuberculosis (Mtb) isolates to all anti-TB agents through a single analysis.

Methods

Here, we aimed to identify the level of concordance between the phenotypic and WGS-based genotypic drug susceptibility (DS) patterns of MDR–TB isolates. Overall, data for 12 anti-TB medications were analyzed.

Results

In total, 63 MDR–TB Mtb isolates were included in the analysis, representing 27.4% of the total number of MDR–TB cases in Latvia in 2012–2014. Among them, five different sublineages were detected, and 2.2.1 (Beijing group) and 4.3.3 (Latin American-Mediterranean group) were the most abundant. There were 100% agreement between phenotypic and genotypic DS pattern for isoniazid, rifampicin, and linezolid. High concordance rate (> 90%) between phenotypic and genotypic DST results was detected for ofloxacin (93.7%), pyrazinamide (93.7%) and streptomycin (95.4%). Phenotypic and genotypic DS patterns were poorly correlated for ethionamide (agreement 56.4%), ethambutol (85.7%), amikacin (82.5%), capreomycin (81.0%), kanamycin (85.4%), and moxifloxacin (77.8%). For capreomycin, resistance conferring mutations were not identified in several phenotypically resistant isolates, and, in contrary, for ethionamide, ethambutol, amikacin, kanamycin, and moxifloxacin the resistance-related mutations were identified in several phenotypically sensitive isolates.

Conclusions

WGS is a valuable tool for rapid genotypic DST for all anti-TB agents. For isoniazid and rifampicin phenotypic DST potentially can be replaced by genotypic DST based on 100% agreement between the tests. However, discrepant results for other anti-TB agents limit their prescription based solely on WGS data. For clinical decision, at the current level of knowledge, there is a need for combination of genotypic DST with modern, validated phenotypic DST methodologies for those medications which did not showed 100% agreement between the methods.
Fatty liver is associated with significant liver inflammation and increases the burden of advanced fibrosis in chronic HBV infection
Authors: Dai Yi-Ning , Xu Cheng-Fu , Pan Hong-Ying , Chen Mei-Juan , Yu Chao-Hui
Published: September 2023

Background

Concurrent non-alcoholic fatty liver disease (NAFLD) is common in patients with chronic HBV infection. But the impact of fatty liver on the histologic progression of HBV infection remains controversial.

Methods

Consecutive HBV-infected patients who underwent liver biopsy between 2016 and 2021 were included. Alcohol consumption and other types of viral hepatitis were excluded. All biopsies were scored for grading and staging by Scheuer’s score, and the steatosis was scored as an estimate of the percentage of liver parenchyma replaced by fat. Logistic regression analyses were applied to assess the associated factors for significant liver inflammation (G ≥ 2), significant fibrosis (S ≥ 2) and advanced fibrosis (S ≥ 3).

Results

Among the 871 HBV-infected patients, hepatic steatosis was prevalent in 255 patients (29.28%). Significant liver inflammation was present in 461 patients (52.93%). Significant fibrosis was observed in 527 patients (60.51%), while advanced liver fibrosis was observed in 171 patients (19.63%). Patients with concomitant NAFLD were more likely to have significant liver inflammation and advanced fibrosis. Fatty liver was an independent risk factor for significant liver inflammation (OR: 2.117, 95% CI: 1.500-2.988), but it could not predict the development of fibrosis. Especially, in HBV-infected patients with persistent normal ALT (immune tolerant and inactive carrier phase), the presence of significant liver inflammation was higher in NAFLD than those without NAFLD. The prevalence of advanced liver fibrosis was higher in NAFLD than non-NAFLD only in the immune tolerant phase, while NAFLD did not increase fibrosis burden in other stages of HBV infection. We developed a predictive model for significant liver inflammation with the area under receiver operating characteristic curve (AUROC) of 0.825, and a model for significant fibrosis with the AUROC of 0.760.

Conclusions

NAFLD is independently associated with significant liver inflammation, and increases the burden of advanced liver fibrosis in HBV-infected patients. The influence of NAFLD on the degree of liver inflammation and fibrosis is different in distinct clinical phases of chronic HBV infection.
Treatment of idiopathic facial paralysis (Bell’s Palsy) and secondary facial paralysis with extracellular vesicles: a pilot safety study
Authors: Dreschnack Paul A. , Belshaku Ina
Published: September 2023

Background

Paralysis of the facial nerve (CN VII) is one of the most debilitating issues that any patient can encounter. Bell’s palsy is the most commonly seen mononeuropathy. Although usually self-limited, symptomatology can persist for decades in persistent cases. The non-surgical alternative therapies discussed in this study are successful without reconstruction and are regenerative.

Objective and design

We sought to determine a safe new treatment could be developed to restore facial nerve function using extracellular vesicles (EVs) in patients who have been unable to return to normal under a variety of conditions. We performed a pilot safety study of 7 patients with idiopathic and secondary facial paralysis to determine if any functional restoration was possible. Each patient had symptomology for varying periods of time, with diverse House-Brackmann scores. They were all treated with the same protocol of extracellular vesicles (EVs) over a 4-week period of time and were evaluated both before and after treatment.

Case presentations

All patients in this study received treatment by their private physicians prior to entering the study. A record review was completed, with independent physical examinations. House-Brackmann scores and Facial Disability Indices were obtained prior to, and after completing the study. EVs were injected into the area of the main trunk of the facial nerve on the affected side, and an intravenous drip of EVs on visits during weeks 1, 2, and 4.

Conclusions

All seven patients enrolled in the study improved with this treatment protocol. After the second week of treatment, we saw a progression of independent motion of the affected eyelid, brow motion, and commissure. Although all patients began at different House-Brackman starting points, almost all ended at the same endpoint on the scale over the same period of time – four weeks. No adverse effects were encountered.

Clearly, the duration of the treatment protocol needs to be longer than one month. The pathomechanism is still unknown. But it appears that the mechanism is reversible. At last, these patients can have hope.

Trial registration

The Institute of Regenerative and Cellular Medicine IRB approval number: IRCM-2021–304.
Developmental outcomes for survivors of placental laser photocoagulation for the management of twin-to-twin transfusion syndrome
Authors: Guzys Angela , Reid Susan M. , Bolch Christie , Reddihough Dinah S. , Teoh Mark , Palma-Dias Ricardo , Fung Alison , Cole Stephen , Hodges Ryan , Fahey Michael , Walker Susan P.
Published: September 2023

Background

Fetoscopic laser coagulation of placental anastomoses reverses the pathological process in twin-to-twin transfusion syndrome, thereby increasing survival, but there are a paucity of studies addressing long-term neurodevelopmental outcome of survivors. This study aimed to ascertain the presence of neurodevelopmental disabilities in child survivors of monochorionic pregnancies managed by placental laser photocoagulation in the Australian state of Victoria.

Methods

All pregnancies undergoing placental laser photocoagulation with the Victorian Fetal Therapy Service between 2006–2017 were included. Information on each surviving child, including demographics, perinatal course, and developmental progress was collected from parents, and consent was sought to complete the Child Behaviour Checklist. Interviewers evaluated whether this information was consistent with a diagnosis of any of 14 neurodevelopmental conditions. A three-tiered outcome measure was allocated for each child: (1) unimpaired or developmentally normal, (2) mild or moderate neurological impairment, or (3) severe neurological impairment. Clinical predictors for adverse outcome were identified.

Results

Of 116 pregnancies (113 twin, 3 triplet), 96 (83%) resulted in 1 + surviving fetuses. 57/113 (50%) twin pregnancies resulted in 2 survivors, 36 (32%) in 1 survivor, and 20 (18%) in no survivors. Of the 235 fetuses, 154 (65.5%) survived to follow-up. Survival increased from 59% in 2006–2008 to 73% in 2015–2017. 90/154 (58%) survivors were followed up at a mean age of 7.5 [SD 3.0] years. Based on parental interview and Child Behaviour Checklist data, 28/90 (31%) participants were assessed as having neurodevelopmental impairment, 27 of mild-moderate severity and 1 severe. Speech/language disorders, attention deficit (hyperactivity) disorders, and fine motor impairment were most common. Neonatal length of stay conferred the highest risk of impairment.

Conclusion

Substantial variation exists between fetal therapy services in the type and length of neonatal follow-up following fetoscopic laser coagulation, contributing to a lack of data on long-term outcomes. The findings from this study support increasingly urgent calls to undertake systematic and sustained follow-up of fetoscopic laser coagulation survivors until school age. Information from this study may assist parents in their decision-making when offered fetal surgery. Importantly, it highlights a group for targeted surveillance and early intervention.
Cancer survivorship challenges of rural older adults: a qualitative study
Authors: Arana-Chicas Evelyn , Prisco Laura M. Hincapie , Sharma Saloni , Stauffer Fiona , McGee Martha , Dauphin Serge , Ban-Hoefen Makiko , Navarette Jaime , Zittel Jason , Cupertino Ana Paula , Magnuson Allison , Mustian Karen M. , Mohile Supriya G.
Published: September 2023

Background

Although research has advanced the field of oncologic geriatrics with survivors to assess their cancer-related needs and devise patient-centered interventions, most of that research has excluded rural populations. This study aimed to understand the survivorship challenges and recommendations in the perspective of rural older adults.

Methods

This was a qualitative study that explored the survivorship challenges and recommendations of rural older adults who have completed curative intent chemotherapy for a solid tumor malignancy in the 12 months prior to enrollment in the present study.

Results

Twenty-seven older adult survivors from rural areas completed open-ended semi-structured interviews. The mean age was 73.4 (SD = 5.0). Most participants were non-Hispanic White (96.3%), female (59.3%), married (63.0%), and had up to a high school education (51.9%). Rural older survivors reported a general lack of awareness of survivorship care plans, communication challenges with healthcare team, transportation challenges, financial toxicity, psychological challenges, and diet and physical challenges. Rural older survivors recommend the provision of nutritional advice referral to exercise programs, and social support groups and for their healthcare providers to discuss their survivorship plan with them.

Conclusions

Although study participants reported similar survivorship challenges as urban older adult survivors, additional challenges reported regarding transportation and consideration of farm animals have not been previously reported. Heightened awareness of the survivorship needs of rural older adults may result in better survivorship care for this population.
ROR1-AS1 might promote in vivo and in vitro proliferation and invasion of cholangiocarcinoma cells
Authors: Li Xueliang , Sun Zhaowei , Wang Li , Wang Qinlei , Wang Maobing , Guo Jingyun , Li Haoran , Chen MenShou , Cao Guanghua , Yu Yanan , Zhong Haochen , Zou Hao , Ma Kai , Zhang Bingyuan , Wang Guolei , Feng Yujie
Published: September 2023

Long non-coding RNAs (lncRNAs) play important roles in many pathophysiological processes, including cancer progression. Namely, lncRNA Receptor-tyrosine-kinase-like orphan receptor-1 antisense 1 (ROR1-AS1) is crucial for cancer occurrence and progression in organs such as the liver or bladder. However, its expression and role in cholangiocarcinoma (CCA) have not been thoroughly explored.

Firstly, we assessed cell viability, proliferation, invasion, and migration using three cell lines (HuCCT-1, QBC399, and RBE) to explore the biological characteristics of ROR1-AS1 in CCA. Secondly, to determine the in vivo effect of ROR1-AS1 on tumor growth, ROR1-AS1 knockdown (KD) HuCCT-1 cells were subcutaneously injected into nude mice to evaluate tumor growth. Finally, we conducted a bioinformatic analysis to confirm the role of ROR1-AS1 in the prognosis and immunity of CCA.

In this study, we found that lncRNA ROR1-AS1 was increased in CCA samples and patients with higher ROR1-AS1 expression had a shorter overall survival period. siRNA-mediated KD of ROR1-AS1 significantly reduced cell proliferation and inhibited the migration of CCA cells. In addition, ROR1-AS1 KD HuCCT-1 cells injected into nude mice grew slower than normal CCA cells.

In summary, our results show that ROR1-AS1 can promote CCA progression and might serve as a new target for diagnosis and treatment of CCA.
Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system
Authors: Liu Yan , Li Hailong , Huang Liang , Wan Chaomin , Wang Huiqing , Jiao Xuefeng , Zeng Linan , Jia Zhijun , Cheng Guo , Zhang Lei , Zhang Wei , Zhang Lingli
Published: September 2023

Background

Evidence of drug-induced liver injury is abundant in adults but is lacking in children. Our aim was to identify suspected drug signals associated with pediatric liver injury.

Methods

Hepatic adverse events (HAEs) among children reported in the Food and Drug Administration Adverse Event Reporting System were analyzed. A descriptive analysis was performed to summarize pediatric HAEs, and a disproportionality analysis was conducted by evaluating reporting odds ratios (RORs) and proportional reporting ratios to detect suspected drugs.

Results

Here, 14,143 pediatric cases were reported, specifically 49.6% in males, 45.1% in females, and 5.2% unknown. Most patients (68.8%) were 6–18 years old. Hospitalization ranked first among definite outcomes (7,207 cases, 37.2%). In total, 264 disproportionate drug signals were identified. The top 10 drugs by the number of reports were paracetamol (1,365; ROR, 3.6; 95% confidence interval (CI), 3.4–3.8), methotrexate (878; ROR, 2.5; 95% CI, 2.3–2.7), vincristine (649; ROR, 3.0; 95% CI, 2.8–3.3), valproic acid (511; ROR, 3.2; 95% CI, 2.9–3.6), cyclophosphamide (490; ROR, 2.4; 95% CI, 2.2–2.6), tacrolimus (427; ROR, 2.4; 95% CI, 2.2–2.7), prednisone (416; ROR, 2.1; 95% CI, 1.9–2.3), prednisolone (401; ROR, 2.3; 95% CI, 2.1–2.5), etoposide (378; ROR, 2.3; 95% CI, 2.1–2.6), and cytarabine (344; ROR, 2.8; 95% CI, 2.5–3.2). After excluding validated hepatotoxic drugs, six were newly detected, specifically acetylcysteine, thiopental, temazepam, nefopam, primaquine, and pyrimethamine.

Conclusions

The hepatotoxic risk associated with 264 signals needs to be noted in practice. The causality of hepatotoxicity and mechanism among new signals should be verified with preclinical and clinical studies.
Patient outcome scores between 1,2- and 2,3-intercompartmental supra-retinacular artery (ICSRA) pedicled vascularised bone grafts (PVBGs) in the treatment of proximal pole scaphoid fracture non-union – a questionnaire study
Authors: Bugeja Mark , Calleja Jordan , Drew Tim , Poghosyan Gor
Published: September 2023

Background

Numerous studies have been published on the use of 1,2-intercompartmental supra-retinacular artery (ICSRA) as a pedicled vascularised bone graft (PVBG) in scaphoid fracture non-union, however, only very few studies have reported their results of 2,3-ICSRA. The aim of this study was to compare the patient-rated outcome scores between these two PVBGs in proximal pole scaphoid fracture non-union.

Methods

Nineteen patients who underwent surgery for scaphoid non-union between 2017 and 2021 at a single institution were recruited retrospectively in this study. All patients were operated by a one senior orthopaedic surgeon. A mailed questionnaire with the modified mayo wrist (MMW) and the patient rated wrist evaluation (PRWE) scores were sent to the patients.

Results

All patients were males with a mean age of 22.5 years. There was no statistically significant difference in the PRWE score between the two PVBGs. However, a statistically significant difference was found in the MMW score, with the 1,2-ICSRA PVBG having better scores.

Conclusion

Despite the 2,3-ICSRA having a longer arc of rotation, longer nutrient arteries, and is technically easier to incorporate in a PVBG, when compared with the 1,2-ICSRA it did not result in better patient-rated outcome scores.
Contact area and pressure changes of patellofemoral joint during stair ascent and stair descent
Authors: Wang Xiaomeng , Liu Huixin , Dong Zhenyue , Chen Xiaobo , Xu Chenyue , Ji Gang , Kang Huijun , Wang Fei
Published: September 2023

Purpose

To investigate the differences of patellofemoral joint pressure and contact area between the process of stair ascent and stair descent.

Methods

The finite element models of 9 volunteers without disorders of knee (9 males) to estimate patellar cartilage pressure during the stair ascent and the stair descent. Simulations took into account cartilage morphology from magnetic resonance imaging, joint posture from weight-bearing magnetic resonance imaging, and ligament model. The three-dimension models of the patella, femur and tibia were developed with the medical image processing software, Mimics 11.1. The ligament was established by truss element of the non-linear FE solver. The equivalent gravity direction (-z direction) load was applied to the whole end of femur (femoral head) according to the body weight of the volunteers, and the force of patella was observed. A paired-samples t-test or Wilcoxon rank sum test to make comparisons between stair ascent and stair descent. Statistical analyses were performed using SPSS 22.0 using a P value of 0.05 to indicate significance.

Results

During the stair descent (knee flexion at 30°), the contact pressure of the patella was 2.59 ± 0.06Mpa. The contact pressure of femoral trochlea cartilage was 2.57 ± 0.06Mpa. During the stair ascent (knee flexion at 60°), the contact pressure with patellar cartilage was 2.82 ± 0.08Mpa. The contact pressure of the femoral trochlea cartilage was 3.03 ± 0.11Mpa. The contact area between patellar cartilage and femoral trochlea cartilage was 249.27 ± 1.35mm2 during the stair descent, which was less than 434.32 ± 1.70mm2 during the stair ascent. The area of high pressure was located in the lateral area of patella during stair descent and the area of high pressure was scattered during stair ascent.

Conclusion

There are small change in the cartilage contact pressure between stair ascent and stair descent, indicating that the joint adjusts the contact pressure by increasing the contact area.
Association between a high triglyceride–glucose index and chronic kidney disease in adult patients with latent autoimmune diabetes
Authors: Fu Xiuli , Xu Zihui , Tan Qin , Wei Wei , Wang Zhongjing
Published: September 2023

Background

Insulin resistance (IR) is one of the risk factors for chronic kidney disease (CKD) and diabetes. The triglyceride–glucose (TyG) index is considered a reliable alternative marker of IR. We investigated the correlation between the TyG index and the severity of CKD in patients with latent autoimmune diabetes in adults (LADA).

Methods

This cross-sectional study included 288 patients with LADA in the department of endocrinology at our hospital between January 2018 and January 2022. The TyG index was calculated as Ln [TG (mg/dl) × fasting blood glucose (FBG) (mg/dl) / 2]. All individuals were divided into either a LADA + CKD group or a LADA + non-CKD group according to the presence or absence of CKD. A correlation analysis, logistic regression analysis and receiver operating characteristics curve analysis were performed.

Results

A total of 130 (45.1%) participants were identified as having CKD. Compared with the non-CKD group, the CKD group had a longer disease duration and a higher proportion of smokers; patients were more likely to have hypertension and higher serum creatinine, triglyceride, cholesterol, low-density lipoprotein cholesterol, FBG, uric acid estimated glomerular filtration rates (eGFR) and TyG levels as well as lower high-density lipoprotein cholesterol levels (all P < 0.05). The positive relationship between the TyG index and the urinary albumin/creatinine ratio was significant (r = 0.249, P = 0.010). There was also a significant correlation between the TyG index and the eGFR (r = − 0.211, P = 0.034) after adjusting for confounding factors. The area-under-the-curve value of the TyG index was 0.708 (95% confidence interval: 0.61–0.81, P < 0.001).

Conclusions

The TyG index is significantly associated with the severity of CKD in patients with LADA. This conclusion supports the clinical application of the TyG index for the assessment of kidney disease in patients with LADA.
The role of different educational programs in specialty preference among Chinese medical students: a cross-sectional study
Authors: Wang Shuangwen , Deng Xiaoqian
Published: September 2023

Background

The imbalanced supply of physicians in different specialties and the decreasing number of young doctors in China have made it important to understand specialty preference and influencing factors and to evaluate the role of different programs in specialty choice and career planning among Chinese medical students to help shape the social healthcare system and ensure adequate medical practitioners in each specialty.

Method

A cross-sectional study comprising medical students from 5-year and 8-year program was conducted online. Demographics, specialty preferences and influencing factors, and career planning situations were collected and analysed by the chi-square test. Binary logistic regression analysis was performed in each program to identify the association between influencing factors and each specialty.

Results

A total of 128 students (57.03% 5-year, 42.97% 8-year) responded to our survey. More 8-year students had a doctor in their household than 5-year students (25.45% vs. 10.96%, p < 0.05). The most preferred specialty among 5-year students was surgery, followed by others and internal medicine, while that most preferred by 8-year students was surgery, followed by internal medicine, obstetrics/gynecology and anesthesiology. Compared with 5-year students, more 8-year students considered ‘personal competencies’ (66.67% vs. 40.85%, p < 0.05), ‘the reputation of the specialty’ (18.52% vs. 7.04%, p ≤ 0.05), ‘fewer doctor‒patient disputes’ (27.78% vs. 11.27%, p < 0.05) and ‘advice from family members’ (24.07% vs. 7.04%, p < 0.05) influential. Among 5-year students, ‘personal competencies’ was positively associated with preference for surgery and ‘work-life balance’ was negatively associated. Among 8-year students, ‘personal competencies’ and ‘work-life balance’ were positively associated with internal medicine, while ‘interests in the specialty’ and ‘broad career prospects’ were negatively related. Many students need further career guidance, and personalized tutoring was the most wanted method.

Conclusions

There was no difference between 5-year and 8-year students regarding specialty preference, but bias existed, possibly due to the influence of the real-world situation. Improving the working environment and welfare might be beneficial for developing a balanced distribution of the workforce among different medical departments. It is necessary for medical schools to develop programs accordingly to help them better plan their future careers.
Training health care providers to administer VIA as a screening test for cervical cancer: a systematic review of essential training components
Authors: Brevik Thea Beate , da Matta Calegari Lara Rodrigues , Mosquera Metcalfe Isabel , Laake Petter , Maza Mauricio , Basu Partha , Todd Adam , Carvalho Andre L.
Published: September 2023

Background

Training health care providers to administer visual inspection after application of acetic acid (VIA) is paramount in improving cervical cancer screening services for women in low- and middle-income countries. The objective of this systematic review was to create a framework of essential VIA training components and provide illustrating examples of how VIA training programs can be carried out in different clinical settings.

Methods

A systematic review of PubMed, Embase, and Web of Science (from 2006 to 2021) was undertaken. Our inclusion criteria comprised articles reporting on implemented cervical cancer screening programs using VIA in a screen-and-treat approach. Trained health care providers with any level of health education were included, and the outcome of interest was the reporting of training components. Data were extracted by two reviewers, and a narrative synthesis of the training programs was performed. We developed a framework of seven essential training components and applied it to assess how training courses were conducted in different settings.

Results

13 primary studies were eligible for inclusion, including 2,722 trained health care providers and 342,889 screened women. Most training courses lasted 5–7 days and included theoretical education, practical skill development, and competence assessment. It was unclear how visual aids and training in client counselling and quality assessment were integrated in the training courses. After the training course, nearly all the VIA training programs made provisions for on-job training at the providers’ own clinical settings through supervision, feedback, and refresher training.

Conclusions

This study demonstrates the feasibility of implementing international training recommendations for cervical cancer screening in real-world settings and provides valuable examples of training program implementation across various clinical settings. The diverse reporting practices of quality indicators in different studies hinder the establishment of direct links between these data and training program effectiveness. To enhance future reporting, authors should emphasize specific training components, delivery methods, and contextual factors. Standardized reporting of quality indicators for effective evaluation of VIA training programs is recommended, fostering comparability, facilitating research, and enhancing reporting quality in this field.
Digital financial services for health in support of universal health coverage: qualitative programmatic case studies from Kenya and Rwanda
Authors: Wilson David Randolph , Haas Sherri , Van Gelder Sicco , Hitimana Regis
Published: September 2023

Background

This document describes two qualitative programmatic case studies documenting experiences implementing digital financial services (DFS) for health with a focus on expanding access to universal health coverage (UHC). The CBHI 3MS system in Rwanda and the i-PUSH and Medical Credit Fund programs in Kenya were selected because they represent innovative use of digital financing technologies to support UHC programs at scale.

Methods

These studies were conducted from April-August 2021 as part of a broader digital financial services landscape assessment that used a mixed methods process evaluation to answer three questions: 1) what was the experience implementing the program, 2) how was it perceived to influence health systems performance, and 3) what was the client/beneficiary experience? Qualitative interviews involved a range of engaged stakeholders, including implementers, developers, and clients/users from the examined programs in both countries. Secondary data were used to describe key program trends.

Results

Respondents agreed that DFS contributed to health system performance by making systems more responsive, enabling programs to implement changes to digital services based on new laws or client-proposed features, and improving access to quality data for better management and improved quality of services. Key informants and secondary data confirmed that both implementations likely contributed to increasing health insurance coverage; however, other changes in market dynamics were also likely to influence these changes. Program managers and some beneficiaries praised the utility of digital functions, compared to paper-based systems, and noted their effect on individual savings behavior to contribute to household resilience.

Discussion/Conclusions

Several implementation considerations emerged as facilitators or barriers to successful implementation of DFS for health, including the importance of multisectoral investments in general ICT infrastructure, the value of leveraging existing community resources (CHWs and mobile money agents) to boost enrollment and help overcome the digital divide, and the significance of developing trust across government and private sector organizations.

The studies led to the development of five main recommendations for the design and implementation of health programs incorporating DFS.
SQLE Knockdown inhibits bladder cancer progression by regulating the PTEN/AKT/GSK3β signaling pathway through P53
Authors: Zou Fan , Chen Wu , Song Tianbao , Xing Ji , Zhang Yunlong , Chen Kang , Hu Weimin , Li Linzhi , Ning Jinzhuo , Li Chenglong , Yu Weimin , Cheng Fan
Published: September 2023

Bladder cancer (BCa) is one of the most common malignancies worldwide. However, the lack of accurate and effective targeted drugs has become a major problem in current clinical treatment of BCa. Studies have demonstrated that squalene epoxidase (SQLE), as a key rate-limiting enzyme in cholesterol biosynthesis, is involved in cancer development. In this study, our analysis of The Cancer Genome Atlas, The Genotype-Tissue Expression, and Gene Expression Omnibus databases showed that SQLE expression was significantly higher in cancer tissues than it was in adjacent normal tissues, and BCa tissues with a high SQLE expression displayed a poor prognosis. We then confirmed this result in qRT-PCR and immunohistochemical staining experiments, and our vitro studies demonstrated that SQLE knockdown inhibited tumor cell proliferation and metastasis through the PTEN/AKT/GSK3β signaling pathway. By means of rescue experiments, we proved that that P53 is a key molecule in SQLE-mediated regulation of the PTEN/AKT/GSK3β signaling pathway. Simultaneously, we verified the above findings through a tumorigenesis experiment in nude mice. In conclusion, our study shows that SQLE promotes BCa growth through the P53/PTEN/AKT/GSK3β axis, which may serve as a therapeutic biological target for BCa.