bluuebunny/crossref_metadata_2025 huggingface dataset:
FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression
Authors: Wang Jie , Wang Chunlin , Hu Anling , Yu Kunlin , Kuang Yi , Gajendran Babu , Zacksenhaus Eldad , Sample Klarke Michael , Xiao Xiao , Liu Wuling , Ben-David Yaacov
Published: March 2024

Background

FLI1 is an oncogenic transcription factor that promotes diverse malignancies through mechanisms that are not fully understood. Herein, FLI1 is shown to regulate the expression of Ubiquitin Associated and SH3 Domain Containing A/B (UBASH3A/B) genes. UBASH3B and UBASH3A are found to act as an oncogene and tumor suppressor, respectively, and their combined effect determines erythroleukemia progression downstream of FLI1.

Methods

Promoter analysis combined with luciferase assays and chromatin immunoprecipitation (ChIP) analysis were applied on the UBASH3A/B promoters. RNAseq analysis combined with bioinformatic was used to determine the effect of knocking-down UBASH3A and UBASH3B in leukemic cells. Downstream targets of UBASH3A/B were inhibited in leukemic cells either via lentivirus-shRNAs or small molecule inhibitors. Western blotting and RT-qPCR were used to determine transcription levels, MTT assays to assess proliferation rate, and flow cytometry to examine apoptotic index.

Results

Knockdown of FLI1 in erythroleukemic cells identified the UBASH3A/B genes as potential downstream targets. Herein, we show that FLI1 directly binds to the UBASH3B promoter, leading to its activation and leukemic cell proliferation. In contrast, FLI1 indirectly inhibits UBASH3A transcription via GATA2, thereby antagonizing leukemic growth. These results suggest oncogenic and tumor suppressor roles for UBASH3B and UBASH3A in erythroleukemia, respectively. Mechanistically, we show that UBASH3B indirectly inhibits AP1 (FOS and JUN) expression, and that its loss leads to inhibition of apoptosis and acceleration of proliferation. UBASH3B also positively regulates the SYK gene expression and its inhibition suppresses leukemia progression. High expression of UBASH3B in diverse tumors was associated with worse prognosis. In contrast, UBASH3A knockdown in erythroleukemic cells increased proliferation; and this was associated with a dramatic induction of the HSP70 gene, HSPA1B. Accordingly, knockdown of HSPA1B in erythroleukemia cells significantly accelerated leukemic cell proliferation. Accordingly, overexpression of UBASH3A in different cancers was predominantly associated with good prognosis. These results suggest for the first time that UBASH3A plays a tumor suppressor role in part through activation of HSPA1B.

Conclusions

FLI1 promotes erythroleukemia progression in part by modulating expression of the oncogenic UBASH3B and tumor suppressor UBASH3A.
Vacuum bell therapy for pectus excavatum: a retrospective study
Authors: Lei Weixuan , Shao Mengqi , Hu Yan , Cao Jieming , Han Wei , Wang Ruoyao , Fei Quanming , Zou Jian , Yi Junqi , Cheng Zheyu , Liu Wenliang
Published: March 2024

Background

Pectus excavatum, the most common chest wall deformity, is frequently treated with Nuss procedure. Here we will describe non-invasive procedure and analyze the variables associated vacuum bell therapy for patients with pectus excavatum.

Methods

Retrospective case–control study in a single center between July 2018 and February 2022, including patients with pectus excavatum treated with vacuum bell. Follow-up was continued to September 2022. The Haller index and Correction index was calculated before and after treatment to analysis the effectiveness of vacuum bell therapy.

Results

There were 98 patients enrolled in the treatment group, with 72 available for analysis, and the follow-up period ranged from 1.1 to 4.4 years (mean 3.3 years). When analyzing with the Haller Index, 18 patients (25.0%) showed excellent correction, 13 patients (18.1%) achieved good correction, and 4 patients (5.6%) had fair correction. The remaining patients had a poor outcome. Characteristics predicting a non-poor prognosis included initial age ≤ 11 years (OR = 3.94, p = 0.013) and patients with use over 24 consecutive months (OR = 3.95, p = 0.013). A total of 9 patients (12.5%) achieved a CI reduction below 10. Patients who started vacuum bell therapy at age > 11 had significantly less change compared to those who started at age ≤ 11 (P < 0.05). Complications included chest pain (5.6%), swollen skin (6.9%), chest tightness (1.4%) and erythema (15.3%).

Conclusions

A certain percentage of patients with pectus excavatum can achieve excellent correction when treated with pectus excavatum therapy. Variables predicting better outcome including initial age ≤ 11 years both in HI and CI and vacuum bell use over 24 consecutive months in HI. In summary, pectus excavatum is an emerging non-invasive therapy for pectus excavatum and will be widely performed in a certain group of patients.
The association of dietary carbohydrate quality and quantity with obesity among Iranian adolescents: a case-control study
Authors: Mohebati Shabnam , Shakeri Mahboobeh , Ranjbar Sara , Jalali Mohammad , Nouri Mehran , Faghih Shiva
Published: March 2024

Background

Adolescent obesity is considered as a major health concern worldwide which is closely linked to the quality of diet. The purpose of the present study was to assess the carbohydrate quality and quantity in relation to odds of overweight and obesity in adolescents.

Methods

This case-control study with a 1:1 ratio was conducted on 406 adolescents (14 to 18 years old) matched for age and gender. Participants were selected by multistage cluster random sampling method from March to October 2019 in Shiraz, Iran. Dietary intakes of the study population were assessed by a validated semi-quantitative food frequency questionnaire. Also anthropometric indices were measured using standard methods and demographic information was recorded via face to face interview. The relation between low carbohydrate diet score (LCDS) and carbohydrate quality index (CQI), and odds of obesity was evaluated by multiple Logistic regression.

Results

After adjusting the role of potential confounders, the participants in the third tertiles of LCDS (OR = 0.443, 95% CI = (0.260 to 0.755)) and CQI (OR = 0.005, 95% CI = (0.001 to 0.025)) had less odds of being overweight and obese compared to the first tertile.

Conclusion

The present study found an inverse relationship between dietary quantity and quality of carbohydrate intake and the odds of overweight and obesity in a sample of Iranian adolescents.
Modeling and mobile home monitoring of behavioral and psychological symptoms of dementia (BPSD)
Authors: Yuan Haihang , Yang Tianyi , Xie Qiaolian , Lledos Guilhem , Chou Wen-Huei , Yu Wenwei
Published: March 2024

With the increasing global aging population, dementia care has rapidly become a major social problem. Current diagnosis of Behavior and Psychological Symptoms of Dementia (BPSD) relies on clinical interviews, and behavioral rating scales based on a period of behavior observation, but these methods are not suitable for identification of occurrence of BPSD in the daily living, which is necessary for providing appropriate interventions for dementia, though, has been studied by few research groups in the literature. To address these issues, in this study developed a BPSD monitoring system consisting of a Psycho-Cognitive (PsyCo) BPSD model, a Behavior-Physio-Environment (BePhyEn) BPSD model, and an implementation platform. The PsyCo BPSD model provides BPSD assessment support to caregivers and care providers, while the BePhyEn BPSD model provides instantaneous alerts for BPSD enabled by a 24-hour home monitoring platform for early intervention, and thereby alleviation of burden to patients and caregivers. Data for acquiring the models were generated through extensive literature review and regularity determined. A mobile robot was utilized as the implementation platform for improving sensitivity of sensors for home monitoring, and elderly individual following algorithms were investigated. Experiments in a virtual home environment showed that, a virtual BPSD elderly individual can be followed safely by the robot, and BPSD occurrence could be identified accurately, demonstrating the possibility of modeling and identification of BPSD in home environment.
Histological, immunohistochemical and serological investigations of the ovary during follicular phase of estrous cycle in Saidi sheep
Authors: Abd-Elkareem Mahmoud , Khormi M. A. , Mohamed Ragab Hassan , Ali Fatma , Hassan Mervat S.
Published: March 2024

Background

Saidi sheep are the most abundant ruminant livestock species in Upper Egypt, especially in the Assiut governorate. Sheep are one of the most abundant animals raised for food in Egypt. They can convert low-quality roughages into meat and milk in addition to producing fiber and hides therefore; great opportunity exists to enhance their reproduction. Saidi breed is poorly known in terms of reproduction. So this work was done to give more information on some hormonal, oxidative, and blood metabolites parameters in addition to histological, histochemical and immunohistochemical investigations of the ovary during follicular phase of estrous cycle. The present study was conducted on 25 healthy Saidi ewes for serum analysis and 10 healthy ewes for histological assessment aged 2 to 5 years and weighted (38.5 ± 2.03 kg).

Results

The follicular phase of estrous cycle in Saidi sheep was characterized by the presence of ovarian follicles in different stages of development and atresia in addition to regressed corpus luteum. Interestingly, apoptosis and tissue oxidative markers play a crucial role in follicular and corpus luteum regression. The most prominent features of the follicular phase were the presence of mature antral (Graafian) and preovulatory follicles as well as increased level of some blood metabolites and oxidative markers. Here we give a new schematic sequence of ovarian follicles in Saidi sheep and describing the features of different types. We also clarified that these histological pictures of the ovary was influenced by hormonal, oxidative and blood metabolites factors that characterizes the follicular phase of estrous cycle in Saidi sheep.

Conclusion

This work helps to understanding the reproduction in Saidi sheep which assist in improving the reproductive outcome of this breed of sheep. These findings are increasingly important for implementation of a genetic improvement program and utilizing the advanced reproductive techniques as estrous synchronization, artificial insemination and embryo transfer.
Seroprevalence of contagious bovine pleuropneumonia (CBPP) in cattle from Karamoja region, North-eastern Uganda
Authors: Tweyongyere Robert , Nkamwesiga Joseph , Etiang Patrick , Mugezi Israel , Wamala Henry , Wasswa Auther Tamale , Kamusiime Maureen , Ainebyoona Solomon , Abizera Harriet , Mwiine Frank Norbert , Muhanguzi Dennis
Published: March 2024

Background

Contagious bovine pleuropneumonia [CBPP] is a transboundary animal disease of cattle caused by Mycoplasma mycoides subsp. mycoides [Mmm]. CBPP causes severe economic losses to livestock producers in sub-Saharan Africa mainly due to high mortality, morbidity, reduction in productivity as well as livestock trade restrictions. This study aimed at determining seroprevalence of Mmm in cattle from Karamoja region, north-eastern Uganda; data that are required to design and implement risk based CBPP control program.

Methods

We randomly collected blood samples from 2,300 cattle spread across Karamoja region. Serum was extracted and screened for antibodies against Mycoplasma mycoides subsp. mycoides [Mmm] using the competitive enzyme linked immunosorbent assay [cELISA].

Results

A quarter [25.4%; 95% CI: 23.7–27.3] of the screened cattle [n = 2,300] were sero-positive for Mmm. Amudat and Kaabong districts recorded the lowest [12.3%] and highest [30.7%] Mmm seroprevalence respectively. Increasing age, overnight stay in cattle kraals and location [certain districts, villages, herds and sub counties] of the cattle herds, the factors that promote animal commingling, were the most significant risk factors of seroconversion with Mmm.

Conclusion

Results from this study indicated a higher seroprevalence of Mmm in Karamoja region cattle herds. This could be due to the increased frequency of CBPP outbreaks in recent years. To be effective, CBPP vaccination programs should target high risk herds along the international borders and other hotspot areas [e.g., parishes or sub counties] where cattle commingling is high.
Attenuated vaccine PmCQ2Δ4555–4580 effectively protects mice against Pasteurella multocida infection
Authors: He Fang , Xiong Pan , Zhang Huihui , Yang Liu , Qiu Yangyang , Li Pan , Zhao Guangfu , Li Nengzhang , Peng Yuanyi
Published: March 2024

Pasteurella multocida type A (PmA) mainly causes respiratory diseases such as pneumonia in bovines, leading to great economic losses to the breeding industry. At present, there is still no effective commercial vaccine against PmA infection. In this study, a mutant strain (PmCQ2Δ4555–4580) with brand-new phenotypes was obtained after serially passaging at 42 °C. Whole genome resequencing and PCR analysis showed that PmCQ2Δ4555–4580 missed six genes, including PmCQ2_004555, PmCQ2_004560, PmCQ2_004565, PmCQ2_004570, PmCQ2_004575, and PmCQ2_004580. Importantly, the virulence of PmCQ2Δ4555–4580 was reduced by approximately 2.8 × 109 times in mice. Notably, live PmCQ2Δ4555–4580 could provide 100%, 100% and 40% protection against PmA, PmB and PmF, respectively; and inactivated PmCQ2Δ4555–4580 could provide 100% and 87.5% protection against PmA and PmB. Interestingly, immune protection-related proteins were significantly upregulated in PmCQ2Δ4555–4580 based on RNA-seq and bioinformatics analysis. Meaningfully, by in vitro expression, purification and in vivo immunization, 12 proteins had different degrees of immune protective effects. Among them, PmCQ2_008205, PmCQ2_010435, PmCQ2_008190, and PmCQ2_004170 had the best protective effect, the protection rates against PmA were 50%, 40%, 30%, and 30%, respectively, and the protective rates against PmB were 62.5%, 42.9%, 37.5%, and 28.6%, respectively. Collectively, PmCQ2Δ4555–4580 is a potential vaccine candidate for the prevention of Pasteurellosis involving in high expression of immune protective related proteins.
Associations between dietary fatty acids intake and abdominal aortic calcification: a national population-based study
Authors: Xiao Yan , Quan Yingping
Published: March 2024

Background

Abdominal aortic calcification (AAC) is a crucial indicator of cardiovascular health. This study aims investigates the associations between dietary fatty acid intake and AAC.

Methods

In this study, a cross-sectional assessment was performed on a group of 2,897 individuals aged 40 and above, utilizing data from the NHANES. The focus was on examining dietary consumption of various fatty acids, including Saturated (SFA), Monounsaturated (MUFA), Polyunsaturated (PUFA), as well as Omega-3 and Omega-6. The evaluation of AAC was done by applying the Kauppila AAC score to results obtained from dual-energy X-ray absorptiometry scans. For statistical analysis, weighted multivariate linear and logistic regression were employed, with adjustments for variables like gender, age, ethnicity, and overall health condition.

Results

Participants with higher intake of SFA and PUFA showed a positive association with AAC score, while higher levels of dietary Omega-3 and Omega-6 fatty acids was connected with a negative correlation. Subgroup analyses indicated consistent associations across different sexes and age groups. The study found that an increase in SFA and PUFA intake correlated with an increase in AAC score, whereas Omega-3 and Omega-6 intake correlated with a decrease.

Conclusion

This study underscores the importance of dietary fatty acid composition in the prevalence of AAC and its potential implications for dietary guidelines and cardiovascular disease prevention strategies.
Dyslipidemia versus obesity as predictors of ischemic stroke prognosis: a multi-center study in China
Authors: Ruan Hang , Ran Xiao , Li Shu-sheng , Zhang Qin
Published: March 2024

Background

This multicenter observational study aimed to determine whether dyslipidemia or obesity contributes more significantly to unfavorable clinical outcomes in patients experiencing a first-ever ischemic stroke (IS).

Methods

The study employed a machine learning predictive model to investigate associations among body mass index (BMI), body fat percentage (BFP), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC) with adverse outcomes in IS patients. Extensive real-world clinical data was utilized, and risk factors significantly linked to adverse outcomes were identified through multivariate analysis, propensity score matching (PSM), and regression discontinuity design (RDD) techniques. Furthermore, these findings were validated via a nationwide multicenter prospective cohort study.

Results

In the derived cohort, a total of 45,162 patients diagnosed with IS were assessed, with 522 experiencing adverse outcomes. A multifactorial analysis incorporating PSM and RDD methods identified TG (adjusted odds ratio (OR) = 1.110; 95% confidence interval (CI): 1.041–1.183; P <  0.01) and TC (adjusted OR = 1.139; 95%CI: 1.039–1.248; P <  0.01) as risk factors. However, BMI, BFP, and HDL showed no significant effect. In the validation cohort, 1410 controls and 941 patients were enrolled, confirming that lipid levels are more strongly correlated with the prognosis of IS patients compared to obesity (TC, OR = 1.369; 95%CI: 1.069–1.754; P <  0.05; TG, OR = 1.332; 95%CI: 1.097–1.618; P <  0.01).

Conclusion

This study suggests that dyslipidemia has a more substantial impact on the prognosis of IS patients compared to obesity. This highlights the importance of prioritizing dyslipidemia management in the treatment and prevention of adverse outcomes in IS patients.

Graphical abstract
UiO-66 nanoparticles combat influenza A virus in mice by activating the RIG-I-like receptor signaling pathway
Authors: Su Ruijing , Li Xinsen , Xiao Jin , Xu Jiawei , Tian Jijing , Liu Tianlong , Hu Yanxin
Published: March 2024

The Influenza A virus (IAV) is a zoonotic pathogen that infects humans and various animal species. Infection with IAV can cause fever, anorexia, and dyspnea and is often accompanied by pneumonia characterized by an excessive release of cytokines (i.e., cytokine storm). Nanodrug delivery systems and nanoparticles are a novel approach to address IAV infections. Herein, UiO-66 nanoparticles (NPs) are synthesized using a high-temperature melting reaction. The in vitro and in vivo optimal concentrations of UiO-66 NPs for antiviral activity are 200 μg mL−1 and 60 mg kg−1, respectively. Transcriptome analysis revealed that UiO-66 NPs can activate the RIG-I-like receptor signaling pathway, thereby enhancing the downstream type I interferon antiviral effect. These NPs suppress inflammation-related pathways, including the FOXO, HIF, and AMPK signaling pathways. The inhibitory effect of UiO-66 NPs on the adsorption and entry of IAV into A549 cells is significant. This study presents novel findings that demonstrate the effective inhibition of IAV adsorption and entry into cells via UiO-66 NPs and highlights their ability to activate the cellular RIG-I-like receptor signaling pathway, thereby exerting an anti-IAV effect in vitro or in mice. These results provide valuable insights into the mechanism of action of UiO-66 NPs against IAV and substantial data for advancing innovative antiviral nanomedicine.

Graphical Abstract
Identification and functional activity of Nik related kinase (NRK) in benign hyperplastic prostate
Authors: He Weixiang , Tian Zelin , Dong Bingchen , Cao Yitong , Hu Wei , Wu Peng , Yu Lei , Zhang Xinhua , Guo Shanshan
Published: March 2024

Objective

Benign prostatic hyperplasia (BPH) is common in elder men. The current study aims to identify differentially expressed genes (DEGs) in hyperplastic prostate and to explore the role of Nik related kinase (NRK) in BPH.

Methods

Four datasets including three bulk and one single cell RNA-seq (scRNA-seq) were obtained to perform integrated bioinformatics. Cell clusters and specific metabolism pathways were analyzed. The localization, expression and functional activity of NRK was investigated via RT-PCR, western-blot, immunohistochemical staining, flow cytometry, wound healing assay, transwell assay and CCK-8 assay.

Results

A total of 17 DEGs were identified by merging three bulk RNA-seq datasets. The findings of integrated single-cell analysis showed that NRK remarkably upregulated in fibroblasts and SM cells of hyperplasia prostate. Meanwhile, NRK was upregulated in BPH samples and localized almost in stroma. The expression level of NRK was significantly correlated with IPSS and Qmax of BPH patients. Silencing of NRK inhibited stromal cell proliferation, migration, fibrosis and EMT process, promoted apoptosis and induced cell cycle arrest, while overexpression of NRK in prostate epithelial cells showed opposite results. Meanwhile, induced fibrosis and EMT process were rescued by knockdown of NRK. Furthermore, expression level of NRK was positively correlated with that of α-SMA, collagen-I and N-cadherin, negatively correlated with that of E-cadherin.

Conclusion

Our novel data identified NRK was upregulated in hyperplastic prostate and associated with prostatic stromal cell proliferation, apoptosis, cell cycle, migration, fibrosis and EMT process. NRK may play important roles in the development of BPH and may be a promising therapeutic target for BPH/LUTS.
Incorporating genetic similarity of auxiliary samples into eGene identification under the transfer learning framework
Authors: Zhang Shuo , Jiang Zhou , Zeng Ping
Published: March 2024

Background

The term eGene has been applied to define a gene whose expression level is affected by at least one independent expression quantitative trait locus (eQTL). It is both theoretically and empirically important to identify eQTLs and eGenes in genomic studies. However, standard eGene detection methods generally focus on individual cis-variants and cannot efficiently leverage useful knowledge acquired from auxiliary samples into target studies.

Methods

We propose a multilocus-based eGene identification method called TLegene by integrating shared genetic similarity information available from auxiliary studies under the statistical framework of transfer learning. We apply TLegene to eGene identification in ten TCGA cancers which have an explicit relevant tissue in the GTEx project, and learn genetic effect of variant in TCGA from GTEx. We also adopt TLegene to the Geuvadis project to evaluate its usefulness in non-cancer studies.

Results

We observed substantial genetic effect correlation of cis-variants between TCGA and GTEx for a larger number of genes. Furthermore, consistent with the results of our simulations, we found that TLegene was more powerful than existing methods and thus identified 169 distinct candidate eGenes, which was much larger than the approach that did not consider knowledge transfer across target and auxiliary studies. Previous studies and functional enrichment analyses provided empirical evidence supporting the associations of discovered eGenes, and it also showed evidence of allelic heterogeneity of gene expression. Furthermore, TLegene identified more eGenes in Geuvadis and revealed that these eGenes were mainly enriched in cells EBV transformed lymphocytes tissue.

Conclusion

Overall, TLegene represents a flexible and powerful statistical method for eGene identification through transfer learning of genetic similarity shared across auxiliary and target studies.
Multi-omics analysis of the gut microbiome and metabolites associated with the psychoneurological symptom cluster in children with cancer receiving chemotherapy
Authors: Bai Jinbing , Eldridge Ronald , Houser Madelyn , Martin Melissa , Powell Christie , Sutton Kathryn S. , Noh Hye In , Wu Yuhua , Olson Thomas , Konstantinidis Konstantinos T. , Bruner Deborah W.
Published: March 2024

Background

Children with cancer receiving chemotherapy commonly report a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. The role of the gut microbiome and its functional metabolites in PNS is rarely studied among children with cancer. This study investigated the associations between the gut microbiome–metabolome pathways and PNS in children with cancer across chemotherapy as compared to healthy children.

Methods

A case–control study was conducted. Cancer cases were recruited from Children’s Healthcare of Atlanta and healthy controls were recruited via flyers. Participants reported PNS using the Pediatric Patient-Reported Outcomes Measurement Information System. Data for cases were collected pre-cycle two chemotherapy (T0) and post-chemotherapy (T1), whereas data for healthy controls were collected once. Gut microbiome and its metabolites were measured using fecal specimens. Gut microbiome profiling was performed using 16S rRNA V4 sequencing, and metabolome was performed using an untargeted liquid chromatography–mass spectrometry approach. A multi-omics network integration program analyzed microbiome–metabolome pathways of PNS.

Results

Cases (n = 21) and controls (n = 14) had mean ages of 13.2 and 13.1 years. For cases at T0, PNS were significantly associated with microbial genera (e.g., Ruminococcus, Megasphaera, and Prevotella), which were linked with carnitine shuttle (p = 0.0003), fatty acid metabolism (p = 0.001) and activation (p = 0.001), and tryptophan metabolism (p = 0.008). Megasphaera, clustered with aspartate and asparagine metabolism (p = 0.034), carnitine shuttle (p = 0.002), and tryptophan (p = 0.019), was associated with PNS for cases at T1. Gut bacteria with potential probiotic functions, along with fatty acid metabolism, tryptophan, and carnitine shuttle, were more clustered in cancer cases than the control network and this linkage with PNS needs further studies.

Conclusions

Using multi-omics approaches, this study indicated specific microbiome–metabolome pathways linked with PNS in children with cancer across chemotherapy. Due to limitations such as antibiotic use in cancer cases, these findings need to be further confirmed in a larger cohort.
High incidence of HPV infection in minors with oral squamous cell carcinoma
Authors: Wu Ningxiang , Li Yonghui , Ma Xiaokun , Huang Zhen , Chen Zhuoxuan , Chen Weihua , Zhang Ran
Published: March 2024

Background

Oral squamous cell carcinoma in minors is considered to be a distinct entity from OSCC in older patients, with an uncertain etiology. Human papillomavirus (HPV) infection may trigger the initiation and promote the progression of OSCC, but these roles have not been firmly established.We aimed to explore the correlation between HPV infection and the development of oral squamous cell carcinoma in minors and know the characteristics of OSCC in young patients more thoroughly.

Method

From January 2013 to December 2022,6 cases of OSCC aged < 15 years were selected from the Department of Oral Pathology, Peking University School of Stomatology, Beijing, China. All cases underwent testing for high-risk HPV mRNA infection using the RNA scope technique, and immunohistochemical staining was performed to investigate the expression of p16, pan-cytokeratin (CK), CK5/6, CK7, CK8/18, epidermal growth factor receptor (EGFR), p53, and Ki-67. Furthermore, we reviewed the literature on OSCC in patients aged < 21 years.

Conclusions

Minors OSCC is associated with HPV infection, and that p16 can serve as an immunohistochemical marker of HPV positivity.
Two-stage palatal repair in non-syndromic CLP patients using anterior to posterior closure is associated with minimal need for secondary palatal surgery
Authors: Kauffmann Philipp , Kolle Johanna , Quast Anja , Wolfer Susanne , Schminke Boris , Meyer-Marcotty Philipp , Schliephake Henning
Published: March 2024

Objective

The aim of the present study was to assess the need for secondary palatal corrective surgery in a concept of palate repair that uses a protocol of anterior to posterior closure of primary palate, hard palate and soft palate.

Methods

A data base of patients primarily operated between 2001 and 2021 at the Craniofacial and Cleft Care Center of the University Goettingen was evaluated. Cleft lips had been repaired using Tennison Randall and Veau-Cronin procedures in conjunction with alveolar cleft repair. Cleft palate repair in CLP patients was accomplished in two steps with repair of primary palate and hard palate first using vomer flaps at the age of 10–12 months and subsequent soft palate closure using Veau/two-flap procedures 3 months later. Isolated cleft palate repair was performed in a one-stage operation using Veau/two-flap procedures. Data on age, sex, type of cleft, date and type of surgery, occurrence and location of oronasal fistulae, date and type of secondary surgery performed for correction of oronasal fistula (ONF)and / or Velophyaryngeal Insufficiency (VPI) were extracted. The rate of skeletal corrective surgery was registered as a proxy for surgery induced facial growth disturbance.

Results

In the 195 patients with non-syndromic complete CLP evaluated, a total number of 446 operations had been performed for repair of alveolar cleft and cleft palate repair (Veau I through IV). In 1 patient (0,5%), an ONF occurred requiring secondary repair. Moreover, secondary surgery for correction of VPI was required in 1 patient (0,5%) resulting in an overall rate of 1% of secondary palatal surgery. Skeletal corrective surgery was indicated in 6 patients (19,3%) with complete CLP in the age group of 15 – 22 years (n = 31).

Conclusions

The presented data have shown that two-step sequential cleft palate closure of primary palate and hard palate first followed by soft palate closure has been associated with minimal rate of secondary corrective surgery for ONF and VPI at a relatively low need for surgical skeletal correction.
Suicide prevention for substance using youth experiencing homelessness: study protocol for a randomized controlled trial
Authors: Slesnick Natasha , Brakenhoff Brittany , Chavez Laura J. , Cuthbertson Caleb L. , Famelia Ruri , Feng Xin , Ford Jodi , Holowacz Eugene , Jaderlund Soren , Kelleher Kelly , Luthy Ellison , Mallory Allen M. , Pizzulo Alexis , Slesnick Tatiana D. , Yilmazer Tansel
Published: March 2024

Background

While research on substance using youth experiencing homelessness (YEH) is increasing, there is a dearth of information regarding effective prevention interventions for these youth. Suicide is the leading cause of death among YEH and most youth do not access services that may be available to them. Therefore, this study seeks to address this gap in the research literature with the goal to identify an effective suicide prevention intervention that can be readily adopted by communities that serve these youth.

Methods

Three hundred (N = 300) YEH with recent substance use and suicidal ideation or a recent suicide attempt will be recruited from the streets as well as a drop-in center serving YEH. After the baseline assessment, all youth will be randomly assigned to Cognitive Therapy for Suicide Prevention (CTSP) + Services as Usual (SAU) (N = 150) or to SAU alone (N = 150). SAU includes outreach, advocacy, and service linkage whereas YEH who receive CTSP will also receive ten CTSP sessions and an optional nine booster sessions. Follow-up assessments will be conducted at 3, 6, 9, and 12 months post-baseline. Theoretically derived mediators (e.g., cognitive distortions) will be tested to shed light on mechanisms associated with change, and the moderating effects of sex, race, sexual orientation, and baseline service connection will be examined. In order to ease future dissemination of the intervention to agencies serving YEH, we will rigorously assess acceptability, feasibility, fidelity, and cost associated with the delivery of our intervention approach using a mixed-methods approach.

Discussion

This study adds to a very small number of clinical trials seeking to prevent lethal suicide among a very high-risk group by addressing suicidal ideation directly rather than underlying conditions. It is hypothesized that youth receiving CTSP + SAU will show greater reductions in suicidal ideation (primary outcome), substance use, and depressive symptoms (secondary outcomes) over time compared to SAU alone, as well as improved risk and protective factors.

Trial registration

NCT05994612. Date of Registration: August 16, 2023.
Behavioral economic and wellness-based approaches for reducing alcohol use and consequences among diverse non-student emerging adults: study protocol for Project BLUE, a randomized controlled trial
Authors: Murphy James G. , Dennhardt Ashley A. , Tempchin Jacob , Colgonis Hannah E. , McDevitt-Murphy Meghan E. , Borsari Brian , Berlin Kristoffer S.
Published: March 2024

Background

Emerging adults (EAs) who are not 4-year college students nor graduates are at elevated risk for lifetime alcohol use disorder, comorbid drug use, and mental health symptoms, compared to college graduates. There is a need for tailored brief alcohol intervention (BAI) approaches to reduce alcohol risk and to facilitate healthy development in this high-risk population. Most BAIs include a single session focused on discussing risks associated with drinking and correcting normative beliefs about drinking rates. EAs may benefit from additional elements that enhance general wellness. The substance-free activity session (SFAS) aims to clarify life goals and values and increase goal-directed activities that provide alternatives to alcohol use, and the relaxation training (RT) session teaches relaxation and stress reduction skills.

Methods

The present study is a randomized 3-group (BAI + SFAS vs. RT + SFAS vs. education control) trial with 525 EAs (175 per group; estimated 50% women and 50% African American) who report recent risky drinking and who are not students or graduates of 4-year colleges. Participants will have the option of completing the intervention sessions in person or via a secure video teleconference. Levels of drinking and alcohol-related problems will be evaluated at baseline and 1, 3, 6, and 12 months post-intervention. The primary hypothesis is that both BAI + SFAS and RT + SFAS participants will report significantly greater reductions in alcohol use and problems relative to education control participants, with no differences in outcomes between the two active treatment conditions.

Discussion

The results of this study will inform alcohol prevention efforts for high-risk community dwelling emerging adults.

Trial registration

ClinicalTrials.gov Identifier: NCT04776278.
Enhancing enzymatic saccharification yields of cellulose at high solid loadings by combining different LPMO activities
Authors: Angeltveit Camilla F. , Várnai Anikó , Eijsink Vincent G. H. , Horn Svein J.
Published: March 2024

Background

The polysaccharides in lignocellulosic biomass hold potential for production of biofuels and biochemicals. However, achieving efficient conversion of this resource into fermentable sugars faces challenges, especially when operating at industrially relevant high solid loadings. While it is clear that combining classical hydrolytic enzymes and lytic polysaccharide monooxygenases (LPMOs) is necessary to achieve high saccharification yields, exactly how these enzymes synergize at high solid loadings remains unclear.

Results

An LPMO-poor cellulase cocktail, Celluclast 1.5 L, was spiked with one or both of two fungal LPMOs from Thermothielavioides terrestris and Thermoascus aurantiacus, TtAA9E and TaAA9A, respectively, to assess their impact on cellulose saccharification efficiency at high dry matter loading, using Avicel and steam-exploded wheat straw as substrates. The results demonstrate that LPMOs can mitigate the reduction in saccharification efficiency associated with high dry matter contents. The positive effect of LPMO inclusion depends on the type of feedstock and the type of LPMO and increases with the increasing dry matter content and reaction time. Furthermore, our results show that chelating free copper, which may leak out of the active site of inactivated LPMOs during saccharification, with EDTA prevents side reactions with in situ generated H2O2 and the reductant (ascorbic acid).

Conclusions

This study shows that sustaining LPMO activity is vital for efficient cellulose solubilization at high substrate loadings. LPMO cleavage of cellulose at high dry matter loadings results in new chain ends and thus increased water accessibility leading to decrystallization of the substrate, all factors making the substrate more accessible to cellulase action. Additionally, this work highlights the importance of preventing LPMO inactivation and its potential detrimental impact on all enzymes in the reaction.
Quality assessment of malaria microscopic diagnosis at the Aristide Le Dantec University Hospital of Dakar, Senegal, in 2020
Authors: Garba Mamane N. , Dème Awa B. , Diongue Khadim , Diédhiou Younousse , Mbaye Amadou M. , Dia NDèye M. , Seck N’Dèye A. , Zoumarou Daba , Ndiaye Lamine , Yade Mamadou S. , Dièye Baba , Sène Aita , Tine Abdoulaye , Touré Mariama , Gadiaga Nogaye , Fall Awa , Ngom Bassirou , Sow Djiby , Ndiaye Aliou , Keita Astou , Ndiaye Mame F. , Gomis Jules F. , Diop Nana F. , Diallo Guète , Ndiaye Ibrahima M. , Ba Elhadj M. , Bitèye Omar , Ndiaye Cheikh , Mbodji Fama S. D. , Ndiaye Pape O. , Ndiaye Tolla , Gaye Amy , Sy Mouhamad , Ndiaye Yaye D. , Seck Mame C. , Ndiaye Mouhamadou , Badiane Aida S. , Diallo Mamadou A. , Ndiaye Daouda
Published: March 2024

Background

Following WHO guidelines, microscopy is the gold standard for malaria diagnosis in endemic countries. The Parasitology-Mycology laboratory (LPM) is the National Reference Laboratory and is currently undergoing ISO 15189 accreditation. In this context, we assessed the performance of the laboratory by confirming the reliability and the accuracy of results obtained in accordance with the requirements of the ISO 15189 standards. This study aimed to verify the method of microscopic diagnosis of malaria at the LPM, in the Aristide Le Dantec hospital (HALD) in Dakar, Senegal.

Methods

This is a validation/verification study conducted from June to August 2020. Twenty (20) microscopic slides of thick/thin blood smear with known parasite densities (PD) selected from the Cheick Anta Diop University malaria slide bank in Dakar were used for this assessment. Six (6) were used to assess microscopists’ ability to determine PD and fourteen (14) slides were used for detection (positive vs negative) and identification of parasites. Four (4) LPM-HALD microscopists read and recorded their results on prepared sheets. Data analysis was done with Microsoft Excel 2010 software.

Results

A minimum threshold of 50% concordance was used for comparison. Of the twenty (20) slides read, 100% concordance was obtained on eight (8) detection (positive vs negative) slides. Four (4) out of the six (6) parasite density evaluation slides obtained a concordance of less than 50%. Thirteen (13) out of the fourteen (14) identification slides obtained a concordance greater than 50%. Only one (1) identification slide obtained zero agreement from the microscopists. For species identification a concordance greater than 80% was noted and the microscopists obtained scores between 0.20 and 0.4 on a scale of 0 to 1 for parasite density reading. The microscopists obtained 100% precision, sensitivity, specificity and both negative and positive predictive values.

Conclusion

This work demonstrated that the microscopic method of malaria diagnosis used in the LPM/HALD is in accordance with the requirements of WHO and ISO 15189. Further training of microscopists may be needed to maintain competency.
Prediction of conversion from mild cognitive impairment to Alzheimer’s disease and simultaneous feature selection and grouping using Medicaid claim data
Authors: Zhang Qi , Coury Ron , Tang Wenlong
Published: March 2024

Background

Due to the heterogeneity among patients with Mild Cognitive Impairment (MCI), it is critical to predict their risk of converting to Alzheimer’s disease (AD) early using routinely collected real-world data such as the electronic health record data or administrative claim data.

Methods

The study used MarketScan Multi-State Medicaid data to construct a cohort of MCI patients. Logistic regression with tree-guided lasso regularization (TGL) was proposed to select important features and predict the risk of converting to AD. A subsampling-based technique was used to extract robust groups of predictive features. Predictive models including logistic regression, generalized random forest, and artificial neural network were trained using the extracted features.

Results

The proposed TGL workflow selected feature groups that were robust, highly interpretable, and consistent with existing literature. The predictive models using TGL selected features demonstrated higher prediction accuracy than the models using all features or features selected using other methods.

Conclusions

The identified feature groups provide insights into the progression from MCI to AD and can potentially improve risk prediction in clinical practice and trial recruitment.
Primary extraskeletal intradural Ewing sarcoma with acute hemorrhage: a case report and review of the literature
Authors: Salama HusamEddin , Abu-Hilal Lila H. , Idkedek Mayar , Kharousha Abdalwahab , Abulihya Mohand , Nimer Hafez
Published: March 2024

Background

Spinal cord tumors present a challenge in diagnosis and treatment due to their varied histopathological characteristics. While Ewing sarcoma is a rare malignant tumor typically originating from skeletal bone, cases of primary intradural extraskeletal Ewing sarcoma are exceptionally rare. The similarity of its presentation to other spinal tumors further complicates its identification and management.

Case presentation

We report a case of a 58-year-old Palestinian male with intradural extraskeletal lumbar Ewing sarcoma. The patient initially presented with lower back pain and bilateral S1 radiculopathy, with more severe symptoms on the left side. Magnetic resonance imaging revealed a 7 cm oval-shaped mass with homogeneous contrast enhancement, obstructing the spinal canal from L3/L4 to L5/S1 levels. Initially, a myxopapillary ependymoma was suspected, but the patient’s sensory and motor functions suddenly deteriorated during hospitalization. Repeat magnetic resonance imaging indicated heterogeneous contrast enhancement, indicating acute intratumoral hemorrhage. Consequently, the patient underwent emergent L3–L5 laminotomy, with successful gross total resection of the tumor. Histopathological and immunohistochemical analyses confirmed the diagnosis of intradural extraskeletal Ewing sarcoma. Adjuvant therapy was administered to minimize the risk of local recurrence or distant metastasis. A systematic review of relevant literature, along with retrospective analysis of medical records, operative reports, radiological studies, and histopathological findings of similar cases, was also conducted.

Conclusions

Intradural extraskeletal Ewing sarcoma is an infrequently encountered condition in adult patients, emphasizing the importance of considering it in the differential diagnosis of spinal tumors. Surgeons must possess a comprehensive understanding of this rare entity to ensure accurate staging and optimal management, particularly in the early stages when prompt intervention may improve prognosis.
Single-cell transcriptome reveals a novel mechanism of C-Kit+-liver sinusoidal endothelial cells in NASH
Authors: Li Hui-Yi , Gao Yu-Xuan , Wu Jun-Cheng , Li Jing-Ze , Fu Seng-Wang , Xu Ming-Yi
Published: March 2024

Aim

To understand how liver sinusoidal endothelial cells (LSECs) respond to nonalcoholic steatohepatitis (NASH).

Methods

We profiled single-LSEC from livers of control and MCD-fed mice. The functions of C-Kit+-LSECs were determined using coculture and bone marrow transplantation (BMT) methods.

Results

Three special clusters of single-LSEC were differentiated. C-Kit+-LSECs of cluster 0, Msr1+-LSECs of cluster 1 and Bmp4+Selp+-VECs of cluster 2 were revealed, and these cells with diverse ectopic expressions of genes participated in regulation of endothelial, fibrosis and lipid metabolism in NASH. The number of C-Kit+-primary LSECs isolated from MCD mice was lower than control mice. Immunofluorescence co-staining of CD31 and C-KIT showed C-Kit+-LSECs located in hepatic sinusoid were also reduced in NASH patients and MCD mice, compared to AIH patients and control mice respectively. Interestingly, lipotoxic hepatocytes/HSCs cocultured with C-Kit+-LSECs or the livers of MCD mice receipting of C-Kit+-BMCs (bone marrow cells) showed less steatosis, inflammation and fibrosis, higher expression of prolipolytic FXR and PPAR-α, lower expression of TNF-α and α-SMA. Furthermore, coculturing or BMT of C-Kit+-endothelial derived cells could increase the levels of hepatic mitochondrial LC3B, decrease the degree of mitochondrial damage and ROS production through activating Pink1-mediated mitophagy pathway in NASH.

Conclusions

Hence, a novel transcriptomic view of LSECs was revealed to have heterogeneity and complexity in NASH. Importantly, a cluster of C-Kit+-LSECs was confirmed to recovery Pink1-related mitophagy and NASH progression.
Sudden cardiac death among workers: a systematic review and meta-analysis
Authors: Amantea Carlotta , Pilia Enrico , Rossi Maria Francesca , Corona Valerio Flavio , Amato Giuseppe , Ciccu Corrado , Gavi Filippo , Santoro Paolo Emilio , Borrelli Ivan , Ricciardi Walter , Gualano Maria Rosaria , Moscato Umberto
Published: March 2024

Objective

Sudden cardiac death (SCD) is a rare and yet unexplained condition. The most frequent cause is myocardial infarction, while a small proportion is due to arrhythmogenic syndromes (e.g., channelopathies). This systematic review and meta-analysis aimed to provide a comprehensive overview of the prevalence and risk factors associated with SCD in workers.

Material and methods

A search for eligible studies was performed utilizing three databases (PubMed, ISI Web of Knowledge, and Scopus). The inclusion criteria were fulfilled if sudden cardiac death due to channelopathy in workers was mentioned.

Results

Out of the 1408 articles found across three databases, 6 articles were included in the systematic review but the meta-analysis was conducted on 3 studies The total sample included was 23,450 participants. The pooled prevalence of channelopathies in employees was 0.3% (95% CI 0.07–0.43%), of sudden cardiac death in employees was 2.8% (95% CI 0.37–5.20%), and of sudden cardiac death in employees with a diagnosis of cardiac channelopathies was 0.2% (95% CI 0.02– 0.30%).

Conclusions

SCD is a serious and potentially preventable condition that can occur among workers. By identifying and addressing work-related risk factors, providing appropriate screening and interventions, and promoting healthy lifestyle behaviors, we can work to reduce the incidence of SCD and improve the cardiovascular health and well-being of workers.