bluuebunny/crossref_metadata_2025_split huggingface dataset:
JAK1 inactivation promotes proliferation and migration of endometrial cancer cells via upregulating the hypoxia-inducible factor signaling pathway
Authors: Lin Qin , Chen Zheng , Shi Wei , Lv Zeheng , Wan Xiaoping , Gao Kun 
Published: November 2022

Abstract
Background
Loss-of-function (LOF) mutations of JAK1, a member of the JAK kinase family, were frequently observed in EC, indicating that JAK1 may act as a tumor suppressor, at least in EC. However, the mechanism of JAK1 mediated regulation of tumorigenesis remains poorly understood.

Methods
The genetic alterations of JAK1 in EC using latest sequencing dataset of EC deposited in TCGA database. The RNA-Seq dataset of EC and normal endometrial tissues from TCGA cohort was analyzed. The expression of JAK1 in EC and normal endometrial tissues were investigated using immunohistochemistry. The expression levels of genes in endometrial cancer cells were detected by quantitative reverse transcription-PCR (RT-qPCR) and western blotting. JAK1 protein was efficiently depleted by the two shRNAs. HIF1/2-α protein was efficiently depleted by siRNAs. JAK1 overexpressed EC cells were generated by an expressing plasmid. The proliferation and migration ability of cancer cells were evaluated by CCK8, colony formation assays and transwell assays. The global transcriptomic changes in JAK1-depleted KLE cells were investigated using RNA-Seq. Gene Ontology (GO) Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to identify the most significant pathways that were altered in JAK1-depleted KLE cells. The physical association between HIF-1/2α and JAK1 using co-immunoprecipitation (co-IP) assays.

Results
In the present study, we found that JAK1 was frequently mutated and downregulated in EC. JAK1 knockdown promotes EC cell proliferation and migration. JAK1 overexpression reduces EC cell proliferation and migration. We examined the transcriptional profiling changes in JAK1-depleted EC cells and unexpectedly found that the hypoxia inducible factor (HIF) pathway was activated. Mechanistically, JAK1 interacts with HIF-1/2α, and reduces HIF1/2-α protein expression under hypoxia. HIF-1/2α knockdown reverses the JAK1 knockdown–induced growth and migration of EC cells under hypoxia. JAK1 knockdown or pharmacological inhibition of JAK1 kinase activity by Ruxolitinib upregulates transcription of HIF target genes under hypoxia. JAK1 overexpression downregulates transcription of HIF target genes under hypoxia.

Conclusions
These findings provide novel insights into the functional link between JAK1 LOF mutations and abnormal HIF pathway activation in EC and suggest that pharmacological inhibition of HIF1/2 represents a promising therapeutic strategy targeting JAK1-mutated ECs.
Epidemiological and genetic characteristics of porcine circovirus 3 in 15 provinces and municipalities of China between 2016 and 2020
Authors: Ku Xugang , Zhang Chengjun , Li Panpan , Yu Xuexiang , Sun Qi , Xu Fengqin , Qian Ping , He Qigai 
Published: November 2022

AbstractPorcine circovirus 3 (PCV3) is a newly emerging virus and has been found associated with porcine dermatitis and nephropathy syndrome in pigs. Compared with PCV2, research into PCV3 cap gene sequencing is deficient. To investigate the prevalence and genotype distribution of PCV3, we collected 1291 samples from 211 pig farms throughout 15 provinces and municipalities. 312 out of 1291 samples were tested positive by PCR. We further sequenced and analyzed 164 PCR-positive samples. The majority (61.8%) of isolates we sequenced belong to genotype PCV3c. PCV3c is also the dominant genotype in Hubei, Hunan, Hebei province and Chongqing city. We found 3 sites under positive selection and located in predicted epitope peptide, revealing that the pig’s immunity may be a reason those sites are undergoing highly positive selection.
AQP5 complements LGR5 to determine the fates of gastric cancer stem cells through regulating ULK1 ubiquitination
Authors: Zhao Rou , He Baoyu , Bie Qingli , Cao Jinghe , Lu Haoran , Zhang Zhixin , Liang Jing , Wei Li , Xiong Huabao , Zhang Bin 
Published: November 2022

Abstract
Background
Cancer stem cells (CSCs) are regarded as the "seed cells" for tumorigenesis, metastasis, recurrence and drug resistance. However, specific surface markers of CSCs of different origins have not been documented.

Methods
Single-cell sequencing was used to analyze the highly expressed genes in cancer stem cells of gastric cancer patients, and it was verified that AQP5 was specifically highly expressed in gastric cancer stem cells (GC-CSCs) in vivo and in vitro. The effect of AQP5-promoting LGR5 on the malignant biological function of GC-CSCs was investigated. The mechanism by which AQP5 affects GC-CSCs was explored through transcriptome sequencing, proteomic detection, mass spectrometry, etc.

Results
We report the identification and validation of AQP5 as a potentially specific surface marker of GC-CSCs. AQP5 was significantly upregulated in CSCs isolated from gastric cancer patients and in spheroid cells, and AQP5 was coexpressed with the canonical stem marker LGR5. Biologically, AQP5 promoted the sphere formation, proliferation, migration and invasion of GC cells in vitro and enhanced tumorigenesis in vivo. Furthermore, AQP5 coordinated with LGR5 and synergistically promoted the tumorigenesis of GC-CSCs. At the mechanistic level, AQP5 activated autophagy by inducing the LC3I/LC3II transformation in GC-CSCs, which was crucial for the biological functions of AQP5. Finally, we demonstrated that AQP5 recruited the E3 ligase TRIM21 to the key autophagy protein ULK1 and induced the K63-mediated ubiquitination of ULK1.

Conclusions
We elucidate a novel surface marker, AQP5, which is specifically expressed by GC-CSCs. Furthermore, our study creates a link between AQP5 and LGR5 and highlights the necessity of targeting both surface markers simultaneously as a promising approach for the treatment of gastric cancer patients.
Dual-labeled nanoparticles based on small extracellular vesicles for tumor detection
Authors: Santos-Coquillat Ana , Herreros-Pérez Desiré , Samaniego Rafael , González María Isabel , Cussó Lorena , Desco Manuel , Salinas Beatriz 
Published: November 2022

Abstract
Background
Small extracellular vesicles (sEVs) are emerging natural nanoplatforms in cancer diagnosis and therapy, through the incorporation of signal components or drugs in their structure. However, for their translation into the clinical field, there is still a lack of tools that enable a deeper understanding of their in vivo pharmacokinetics or their interactions with the cells of the tumor microenvironment. In this study, we have designed a dual-sEV probe based on radioactive and fluorescent labeling of goat milk sEVs.

Results
The imaging nanoprobe was tested in vitro and in vivo in a model of glioblastoma. In vitro assessment of the uptake of the dual probe in different cell populations (RAW 264.7, U87, and HeLa) by optical and nuclear techniques (gamma counter, confocal imaging, and flow cytometry) revealed the highest uptake in inflammatory cells (RAW 264.7), followed by glioblastoma U87 cells. In vivo evaluation of the pharmacokinetic properties of nanoparticles confirmed a blood circulation time of ~ 8 h and primarily hepatobiliary elimination. The diagnostic capability of the dual nanoprobe was confirmed in vivo in a glioblastoma xenograft model, which showed intense in vivo uptake of the SEV-based probe in tumor tissue. Histological assessment by confocal imaging enabled quantification of tumor populations and confirmed uptake in tumor cells and tumor-associated macrophages, followed by cancer-associated fibroblasts and endothelial cells.

Conclusions
We have developed a chemical approach for dual radioactive and fluorescent labeling of sEVs. This methodology enables in vivo and in vitro study of these vesicles after exogenous administration. The dual nanoprobe would be a promising technology for cancer diagnosis and a powerful tool for studying the biological behavior of these nanosystems for use in drug delivery.

Graphical Abstract
Prevalence of selected sexually transmitted infectious agents in a cohort of asymptomatic soldiers in Austria
Authors: Lesiak-Markowicz Iwona , Tscherwizek Claudia , Pöppl Wolfgang , Mooseder Gerhard , Walochnik Julia , Fürnkranz Ursula 
Published: November 2022

Abstract
Background
According to the World Health Organization (WHO), more than one million sexually transmitted infections (STIs) are acquired every day worldwide. Although STIs may be asymptomatic in many cases, they can cause severe symptoms and can also lead to adverse pregnancy outcomes and both male and female infertility. Asymptomatic carriers seem to play an important role in terms of the distribution of STIs; however, studies revealing the prevalence of STIs in asymptomatic individuals are rare.

Methods
In the current study, 654 leftovers of standard urine samples from healthy, asymptomatic Austrian soldiers were investigated for the prevalence of Trichomonas vaginalis, Chlamydia trachomatis, and genital mycoplasmas (Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, Ureaplasma parvum, and Candidatus Mycoplasma girerdii) by specific PCRs.

Results
We detected T. vaginalis, M. hominis, U. urealyticum, U. parvum, and C. trachomatis in the investigated samples with prevalence of 7.6%, 4%, 2.4%, 5.4%, and 3.2%, respectively; neither M. genitalium nor Ca. Mycoplasma girerdii was found in our sample collection.

Conclusions
Our study introduces data on STIs of a mainly male cohort, which are scarce because most of the available information on sexually transmitted infectious agents arises from fertility clinics (mainly women) or symptomatic patients.

Graphical abstract
Thelazia lacrymalis in horses from Romania: epidemiology, morphology and phylogenetic analysis
Authors: Cotuțiu Vlad-Dan , Ionică Angela Monica , Lefkaditis Menelaos , Cazan Cristina Daniela , Hașaș Alina Diana , Mihalca Andrei Daniel 
Published: November 2022

Abstract
Background
Equine thelaziosis is a neglected vector-borne parasitic disease in modern veterinary medicine, lacking recent reports. It is transmitted by Musca autumnalis, and potentially other Muscidae species, by ingesting the lachrymal secretions of its equine host. The distribution of both Thelazia lacrymalis and its intermediate hosts remains largely unknown throughout Europe, with most studies dating back 20 years. The aim of this study was to assess the presence, prevalence and distribution of T. lacrymalis in horses from Romania.

Methods
The eyes of 273 horses, slaughtered at two abattoirs from the Northwestern and Western regions of Romania, were examined for the presence of T. lacrymalis between March and November 2021. Upon detection, the nematodes were collected and morphologically identified using the keys from literature. Following identification, one specimen from each animal was selected for molecular analysis while the rest underwent detailed morphometric measurements. Mapping and distribution, according to ecoregions, was done using the QGis 3.20 software, while sequences obtained were compared to those available in GenBank through BLAST analysis using the MEGA X software.

Results
Of the 273 animals sampled, 12 (4.39%) were positive for Thelazia spp. infection. Eighty-seven nematodes were recovered, all morphologically identified as T. lacrymalis. The intensity of infestation varied between one and 33 nematodes/animal while five animals presented a bilateral infestation and seven a unilateral one. The highest prevalence was encountered in Pannonian ecoregion (12.12%) while the lowest was in the Alpine ecoregion (0%). Seventy-five intact specimens underwent detailed morphometric analysis, of the 18–20 parameters, resulting in notable differences in striation lengths compared to the data available in other reports. BLAST analysis identified a 96.46–98.60% similarity to the only other COI gene sequence available for T. lacrymalis.

Conclusions
The current study represents the first report of T. lacrymalis in horses in Romania. The low prevalence rates are probably linked to the wide use of macrocyclic lactones.

Graphic Abstract
Early gastric mixed neuroendocrine–non-neuroendocrine neoplasms with endoscopic findings of neuroendocrine cell carcinoma components exposed on the mucosal surface: a case report
Authors: Ito Yohei , Kimoto Yoshiaki , Sawada Rikimaru , Nagae Shinya , Furuta Koichi , Takeuchi Nao , Takayanagi Shunya , Kano Yuki , Ishii Rindo , Sakuno Takashi , Ono Kohei , Negishi Ryoju , Minato Yohei , Muramoto Takashi , Ohata Ken 
Published: November 2022

Abstract
Background
Gastric mixed neuroendocrine–non-neuroendocrine neoplasms are rare malignant tumors. The lack of specific findings makes it difficult to diagnose endoscopically. We report the case of early gastric mixed neuroendocrine–non-neuroendocrine neoplasms treated by endoscopic submucosal dissection.

Case presentation
An 81-year-old Japanese female underwent esophagogastroduodenoscopy for screening and was treated with endoscopic submucosal dissection for the diagnosis of early gastric cancer. Histopathologically, the lesion was diagnosed as mixed neuroendocrine–non-neuroendocrine neoplasms (tubular adenocarcinoma 2 60%, endocrine cell carcinoma 40%), pT1b(submucosa (SM) 900 μm), pUL(−), Ly(+), v(−), pHM0, pVM0. After additional surgical resection without adjuvant chemotherapy, she has had no recurrences or metastases for 3 years.

Conclusions
Comparing narrow-band imaging magnified endoscopic findings with pathological findings, the depressed area with a lack of surface structure was consistent with the neuroendocrine cell carcinoma component, while narrow-band imaging magnification findings showed non-network vessels. In this case, we examined endoscopic findings of early stage mixed neuroendocrine—non-neuroendocrine neoplasms in detail and compared it with the pathological findings. We believe that these endoscopic findings contribute to the diagnosis of mixed neuroendocrine–non-neuroendocrine neoplasms and can lead to its early detection.
Construction of a 10-gene prognostic score model of predicting recurrence for laryngeal cancer
Authors: Liu Yanan , Gao Zhiguang , Peng Cheng , Jiang Xingli 
Published: November 2022

AbstractWe constructed a prognostic score (PS) model to predict the recurrence risk in patients previously diagnosed with laryngeal cancer (LC). Here the training dataset, consisting of 82 LC samples, was downloaded from The Cancer Genome Atlas (TCGA). The PS model then divided the LC samples into high- and low-risk groups, which predicted well the survival time of LC in three datasets (TCGA dataset: AUC = 0.899; GSE27020: AUC = 0.719; and GSE25727: AUC = 0.662). Therefore, the PS model based on the 10 genes and its nomogram is proposed to help predict the recurrence risk in patients with LC.
Human targeted phenobarbital presents a poor substrate of gut microbiome deciphering new drug targets beyond pharmacokinetic curbs
Authors: Mukhtar Imran , Anwar Haseeb , Iftikhar Arslan , Hashem Heba E. , Ali Qasim , Siddique Farhan 
Published: November 2022

Abstract
Background
The gut microbiome, a new organ of the body, can potentially alter the pharmacokinetics of orally administered drugs through microbial enzymes. However, absorption of orally administered non-antibiotic drugs by the gut microbiome, during drug-microbiome interaction, is barely addressed. Structural homology studies confirm similar membrane transport proteins in gut epithelial cells and the gut microbiome of the host that may compete for drug substrates with the host itself for its absorbance. Therefore, it is hypothesized that orally administered human targeted phenobarbital may interact and/or be uptake by the gut microbiome during its transit through the small intestine.

Methods
In the current in vivo study, thirty-six male Wistar albino rats were divided into six groups including one control and 5 treatment groups, each having an equal number of rats (n = 6). Phenobarbital was administered orally (single dose of 15 mg/kg bw) to treatment groups. Animals were subsequently sacrificed to harvest microbial mass pallets residing in the small intestine after 2, 3, 4, 5, and 6 h of phenobarbital administration. Phenobarbital absorbance by the microbiome in the microbial lysate was estimated through RP-HPLC–UV at a wavelength of 207 nm.

Results
Maximum phenobarbital absorbance (149.0 ± 5.93 µg) and drug absorbance per milligram of microbial mass (1.19 ± 0.05 µg) were found significantly higher at 4 h of post-administration in comparison to other groups. Percent dose recovery of phenobarbital was 5.73 ± 0.19% at 4 h while the maximum intestinal transit time was 5 h till the drug was absorbed by the microbes. Such results pronounce the idea of the existence of structural homology between membrane transporters of the gut microbiome and intestinal enterocytes of the host that may competitively absorb orally administered phenobarbital during transit in the small intestine. The docking studies revealed that the phenobarbital is a poor substrate for the gut microbiome.

Conclusion
Gut microbiome may competitively absorb the non-antibiotics such as phenobarbital as novel substrates due to the presence of structurally homologous transporting proteins as in enterocytes. This phenomenon suggests the microbiome as a potential candidate that can significantly alter the pharmacokinetics of drugs.
Spatial analysis of provincial and district trends in stunting among children under five years in Nepal from 2001 to 2016
Authors: Nepali Sajama , Simkhada Padam , Thapa Balaram 
Published: November 2022

Abstract
Background
The average prevalence of stunting reported by the Nepal Demographic Health Survey from 2001 to 2016 only reports the prevalence of stunting at the national level and provincial and district level information is missing. Also, no previous study has reported a provincial trend in stunting from 2001 to 2016 in Nepal. This study for the first time presents the spatial trend of stunting among children under five years for 7 provinces and 77 districts of Nepal over 15 years using Demographic Health Survey Global Positioning System coordinates, Demographic Health Survey indicators, and geospatial covariates.

Methods
This is a secondary analysis of data from Nepal Demographic Health Survey from 2001 to 2016. The study population was children under five years. The outcome variable was stunting, which was analyzed as per districts and provinces. Sample weight was applied to calculate the percentage of stunting and 95% confidence interval for all survey years. The geographic dataset was used to provide information about the latitude and longitude of the survey cluster. Poisson-based model was used during the purely spatial analysis in SatScan for identification of clusters with stunting caseload.

Results
The reduction in the prevalence of stunting among children under five years has not been equal when disaggregated for district and provincial level data. In 2001, 57 districts had a prevalence of stunting among children above or equal to 50%, which has reduced over time except for districts in Karnali province. In 2016, 16 districts had a prevalence of stunting above or equal to 50%. Jumla (91.7%) and Kalikot (77.8%) still had the highest prevalence of stunting as of 2001. Among 7 provinces, the prevalence of stunting is found highest in Karnali for all subsequent survey years. Sudurpaschim and Madhesh provinces also had a high proportion of stunted children. The highest reduction in the prevalence of stunting was noted for Province Bagmati (by 30%) and Gandaki (by 28%).

Conclusion
The inequalities in childhood stunting persisted at the district and provincial levels although a good decline was noted at the national level. This calls for rigorous attention to be provided to districts and provinces with a high prevalence of stunting, and being prioritized for a targeted intervention.
Evaluation of nutrients in bread: a systematic review
Authors: Aghalari Zahra , Dahms Hans-Uwe , Sillanpää Mika 
Published: November 2022

Abstract
Background
A balanced and optimized amount of nutrients in bread, which is the main food in many countries, is necessary to maintain human health. Considering the importance of nutritional values of bread in the food basket of Iranian households, the purpose of this study was to determine the nutrients and their concentrations in breads consumed in Iran.

Methods
This systematic review study was performed to determine the types of nutrients in breads consumed in Iran by searching reputable international databases including Scopus and Google scholar, PubMed, Science direct, ISI (Web of Science). Data were collected according to inclusion and exclusion criteria and by searching for relevant keywords, emphasizing the types of nutrients in breads consumed in Iran. Qualitative data were collected using the standard PRISMA checklist (preferential reporting items for systematic reviews and meta-analysis). After verifying the quality of the articles, the information was entered into a checklist such as the name of the first author and year of publication of the research, type of study, number of samples, type of nutrition, type of bread and amount of nutrition measured.

Results
After reviewing the information and quality of articles, 10 articles were qualified for systematic review. The review of the articles showed that different breads were experimented, including: Sangak, Barbari, Taftoon, Lavash, French and local bread. The highest number of experimented bread samples was Sangak. Examination of the articles showed that 6 nutrients were experimented in different breads such as Fe, K, Mg, Ca, Cu and Zn. The highest number of experimented in breads was related to the amount of Zn (13 times) and Cu (10 times), respectively. The results of quality assessment of articles showed that most of the studies were of good quality. The results of articles on the amount of nutrients measured in different breads showed that only in two articles the amount of nutrients was reported to be desirable. In most articles, the amount of nutrients in breads was reported to be lower or higher than standard.

Conclusion
The results of this study showed that the concentration of nutrients in most articles was undesirable. It is suggested that optimal methods of enrichment of breads and flours be done with interdisciplinary cooperation between food hygiene, environmental health, nutrition, farmers and bakers. It is recommended that food hygiene and environmental health researchers investigate other nutrients (including phosphorus, selenium, manganese, boron and molybdenum) in breads and other staple foods used by people to constructive and practical measures to increase public health.