bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression variations in ectodysplasin-A gene (eda) may contribute to morphological divergence of scales in haplochromine cichlids
Authors: Wagner Maximilian , Bračun Sandra , Duenser Anna , Sturmbauer Christian , Gessl Wolfgang , Ahi Ehsan Pashay 
Published: March 2022

Abstract
Background
Elasmoid scales are one of the most common dermal appendages and can be found in almost all species of bony fish differing greatly in their shape. Whilst the genetic underpinnings behind elasmoid scale development have been investigated, not much is known about the mechanisms involved in moulding of scales. To investigate the links between gene expression differences and morphological divergence, we inferred shape variation of scales from two different areas of the body (anterior and posterior) stemming from ten haplochromine cichlid species from different origins (Lake Tanganyika, Lake Malawi, Lake Victoria and riverine). Additionally, we investigated transcriptional differences of a set of genes known to be involved in scale development and morphogenesis in fish.

Results
We found that scales from the anterior and posterior part of the body strongly differ in their overall shape, and a separate look on scales from each body part revealed similar trajectories of shape differences considering the lake origin of single investigated species. Above all, nine as well as 11 out of 16 target genes showed expression differences between the lakes for the anterior and posterior dataset, respectively. Whereas in posterior scales four genes (dlx5, eda, rankl and shh) revealed significant correlations between expression and morphological differentiation, in anterior scales only one gene (eda) showed such a correlation. Furthermore, eda displayed the most significant expression difference between species of Lake Tanganyika and species of the other two younger lakes. Finally, we found genetic differences in downstream regions of eda gene (e.g., in the eda-tnfsf13b inter-genic region) that are associated with observed expression differences. This is reminiscent of a genetic difference in the eda-tnfsf13b inter-genic region which leads to gain or loss of armour plates in stickleback.

Conclusion
These findings provide evidence for cross-species transcriptional differences of an important morphogenetic factor, eda, which is involved in formation of ectodermal appendages. These expression differences appeared to be associated with morphological differences observed in the scales of haplochromine cichlids indicating potential role of eda mediated signal in divergent scale morphogenesis in fish.
De novo assembly and analysis of Polygonatum cyrtonema Hua and identification of genes involved in polysaccharide and saponin biosynthesis
Authors: Li Dandan , Wang Qing , Chen Songshu , Liu Hongchang , Pan Keqin , Li Jinling , Luo Chunli , Wang Hualei 
Published: March 2022

Abstract
Background
The investigation of molecular mechanisms involved in polysaccharides and saponin metabolism is critical for genetic engineering of Polygonatum cyrtonema Hua to raise major active ingredient content. Up to now, the transcript sequences are available for different tissues of P. cyrtonema, a wide range scanning about temporal transcript at different ages’ rhizomes was still absent in P. cyrtonema.

Results
Transcriptome sequencing for rhizomes at different ages was performed. Sixty-two thousand six hundred thirty-five unigenes were generated by assembling transcripts from all samples. A total of 89 unigenes encoding key enzymes involved in polysaccharide biosynthesis and 56 unigenes encoding key enzymes involved in saponin biosynthesis. The content of total polysaccharide and total saponin was positively correlated with the expression patterns of mannose-6-phosphate isomerase (MPI), GDP-L-fucose synthase (TSTA3), UDP-apiose/xylose synthase (AXS), UDP-glucose 6-dehydrogenase (UGDH), Hydroxymethylglutaryl CoA synthase (HMGS), Mevalonate kinase (MVK), 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (ispF), (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (ispG), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (ispH), Farnesyl diphosphate synthase (FPPS). Finally, a number of key genes were selected and quantitative real-time PCR were performed to validate the transcriptome analysis results.

Conclusions
These results create the link between polysaccharides and saponin biosynthesis and gene expression, provide insight for underlying key active substances, and reveal novel candidate genes including TFs that are worth further exploration for their functions and values.
Typhoid fever presenting with gastric ulcer bleeding
Authors: Jeon Hong Jae , Lee Jong Seo , Lee Byung Seok , Kim Seok Hyun , Lee Eaum Seok , Sung Jae Kyu , Moon Hee Seok , Kang Sun Hyung , Lee Hyun Seok , Choi Seongwoo , Sa-Kong Heon , Cheon Shinhye , Eun Hyuk Soo 
Published: March 2022

Abstract
Background
Enteric fever is a systemic disease caused by Salmonella enterica serovar Typhi or Salmonella enterica serovar Paratyphi, characterized by high fever and abdominal pain. Most patients with enteric fever improve within a few days after antibiotic treatment. However, some patients do not recover as easily and develop fatal life-threatening complications, including intestinal hemorrhage. Lower gastrointestinal bleeding has been reported in 10% of cases. However, upper gastrointestinal bleeding has rarely been reported in patients with enteric fever. We present a case of gastric ulcer hemorrhage caused by enteric fever.

Case presentation
A 32-year-old woman, complaining of fever lasting four days and right upper quadrant pain and melena that started one day before admission, consulted our hospital. Abdominal computed tomography revealed mild hepatomegaly and gastroscopy revealed multiple active gastric ulcers with flat black hemorrhagic spots. The melena of the patient stopped on the third day. On the fifth admission day, she developed hematochezia. At that time, Salmonella enterica serovar Typhi was isolated from the blood culture. The antibiotic regimen was switched to ceftriaxone. Her hematochezia spontaneously resolved the following day. Finally, the patient was discharged on the 12th admission day without clinical symptoms. However, her fever recurred one month after discharge, and she was readmitted and Salmonella enterica serovar Typhi was confirmed again via blood culture. She was treated with ceftriaxone for one month, and was discharged without complications.

Conclusion
Our case showed that although rare, active gastric ulcers can develop in patients with enteric fever. Therefore, upper and lower gastrointestinal bleeding should be suspected in patients with enteric fever, especially showing relapsing bacteremia.
The prevalence and clinical correlates of medical disorders comorbidities in patients with bipolar disorder
Authors: Wang Zhonggang , Li Tao , Li Shuhua , Li Kunkun , Jiang Xianfei , Wei Chen , Yang Lei , Cao Haiyan , Li Shen , Li Jie 
Published: March 2022

Abstract
Objective
Medical disorders in patients with bipolar disorder (BD) have attracted more and more attention. So far, there is still a lack of studies on this issue utilizing large sample sizes in the Chinese sample. Therefore, we conducted this study to explore the clinical characteristics of BD patients comorbid medical disorders in a relatively large Chinese sample.

Methods
This was a cross-sectional study including 1,393 BD patients (882 patients with medical disorders and 511 patients without medical disorders). Their demographic and clinical characteristics were obtained by the Hospital Information System and self-designed questionnaires.

Results
The comorbidity rate of medical disorders in BD was 63.32%. The average number of medical disorders for a BD patient was 2.69. The top five comorbid medical disorders in BD patients were circulatory system diseases (19%), nervous system diseases (18%), endocrine and metabolic diseases (17%), digestive system diseases (16%), and respiratory system diseases (8%). BD patients with comorbid medical disorders had an older average age, lower education level, longer illness course, later onset age, lower ratio of psychotic features, more admission numbers, higher ratio of smoking and drinking alcohol, more number of manic episodes (All P < 0.05). Smoking, numbers of depressive episode, onset age, and illness course were independent risk factors of comorbidities in BD patients (All P < 0.05).

Conclusions
Medical disorders in Chinese BD patients are highly prevalent. The smoking, number of depressive episodes, onset age, illness course, are correlated with BD patients comorbid medical disorders. Clinicians should pay attention to the medical disorders comorbidities in BD patients, and take effective measures to improve treatment outcome and reduce the suffering. The integrative approach should be the imperative in clinical practice.
Comparison of mortality hazard ratios associated with health behaviours in Canada and the United States: a population-based linked health survey study
Authors: Fisher Stacey , Bennett Carol , Hennessy Deirdre , Finès Philippe , Jessri Mahsa , Bader Eddeen Anan , Frank John , Robertson Tony , Taljaard Monica , Rosella Laura C. , Sanmartin Claudia , Jha Prabhat , Leyland Alastair , Manuel Douglas G. 
Published: March 2022

Abstract
Background
Modern health surveillance and planning requires an understanding of how preventable risk factors impact population health, and how these effects vary between populations. In this study, we compare how smoking, alcohol consumption, diet and physical activity are associated with all-cause mortality in Canada and the United States using comparable individual-level, linked population health survey data and identical model specifications.

Methods
The Canadian Community Health Survey (CCHS) (2003–2007) and the United States National Health Interview Survey (NHIS) (2000, 2005) linked to individual-level mortality outcomes with follow up to December 31, 2011 were used. Consistent variable definitions were used to estimate country-specific mortality hazard ratios with sex-specific Cox proportional hazard models, including smoking, alcohol, diet and physical activity, sociodemographic indicators and proximal factors including disease history.

Results
A total of 296,407 respondents and 1,813,884 million person-years of follow-up from the CCHS and 58,232 respondents and 497,909 person-years from the NHIS were included. Absolute mortality risk among those with a ‘healthy profile’ was higher in the United States compared to Canada, especially among women. Adjusted mortality hazard ratios associated with health behaviours were generally of similar magnitude and direction but often stronger in Canada.

Conclusion
Even when methodological and population differences are minimal, the association of health behaviours and mortality can vary across populations. It is therefore important to be cautious of between-study variation when aggregating relative effect estimates from differing populations, and when using external effect estimates for population health research and policy development.
A new tool to evaluate burnout: the Italian version of the BAT for Italian healthcare workers
Authors: Borrelli Ivan , Santoro Paolo Emilio , Fiorilli Caterina , Angelini Giacomo , Buonomo Ilaria , Benevene Paula , Romano Luciano , Gualano Maria Rosaria , Amantea Carlotta , Moscato Umberto 
Published: March 2022

Abstract
Background
Healthcare workers (HCWs) represents one of the highest-risk population to develop burnout symptoms. Recently, a new tool has been designed to measure several dimensions that capture an exhaustive expression of burnout symptoms by six dimensions (i.e., exhaustion; mental distance; cognitive impairment; emotional impairment; psychological distress; psychosomatic complaints).

Methods
The current study aims to adapt the Burnout Assessment Tool (BAT) to an Italian Healthcare workers’ sample confirming the original second-order factorial structure. Furthermore, we expected to find good indexes of reliability and validity tests. Participants were 697 Italian Health Care Workers (Female = 68.44%; mean age = 36.47; SD = 11.20). Data were collected by self-report questionnaires submitted by the snowball method.

Results
Findings show a good fit of the BAT’s structure, confirming the hypothesized second-order factorial model. Furthermore, good reliability has been established with the study’s measures.

Conclusions
The BAT for HCWs is eligible as a new tool to evaluate burnout in the at-risk HCWs as a multi-facet constellation of symptoms.
Targeting E2 ubiquitin-conjugating enzyme UbcH5c by small molecule inhibitor suppresses pancreatic cancer growth and metastasis
Authors: Qi Simin , Guan Xiaoqing , Zhang Jia , Yu Dehua , Yu Xuefei , Li Qinglin , Yin Wenjuan , Cheng Xiang-Dong , Zhang Weidong , Qin Jiang-Jiang 
Published: March 2022

Abstract
Background
Pancreatic cancer is one of the most lethal cancers worldwide. The IAPs function as E3 ubiquitin ligases and contribute to pancreatic cancer initiation, progression, and metastasis. Although IAP-targeted therapies have been developed and shown anticancer efficacy in preclinical settings, none of them has been approved yet.

Methods
Transcriptome data from public datasets were used to analyze the correlation of IAPs and E2s, and the biological function of E2 UbcH5c in pancreatic cancer. A structure-based virtual screen was used to identify UbcH5c inhibitor, and surface plasmon resonance analysis and cellular thermal shift assays were employed to evaluate the binding affinity. The anticancer activities were demonstrated through in vitro and in vivo assays, while the related mechanisms were explored through transcriptomic and proteomic analyses and confirmed by western blot, immunofluorescence, and qRT-PCR.

Results
UbcH5c is positively correlated with the expression of IAPs in pancreatic cancer. We further found that UbcH5c is overexpressed and associated with a poor prognosis in pancreatic cancer. We identified a small-molecule UbcH5c inhibitor, termed DHPO, which directly bound to UbcH5c protein. DHPO inhibited cell viability and colony formation, induced apoptosis, and suppressed migration and invasion of pancreatic cancer cells in vitro. The compound inhibited UbcH5c-mediated IκBα degradation and NF-κB activation, which is critical for its anticancer activity. Furthermore, DHPO suppressed the tumor growth and metastasis in two orthotopic pancreatic tumor mouse models.

Conclusions
These results indicated that inhibiting UbcH5c is a novel and effective strategy for treating pancreatic cancer and DHPO represents a new class of UbcH5c inhibitor and may be further developed as an anti-pancreatic cancer therapeutic agent.
Revision surgeries for tumor endoprostheses around the knee joint: a mid-long-term follow-up of 20 cases
Authors: Zan Pengfei , Wang Hongsheng , Cai Zhengdong , Shen Jiakang , Sun Wei 
Published: March 2022

Abstract
Background
Tumor endoprostheses of the knee joint after limb salvage surgery is associated with high rates of complications, which has introduced great challenges to a delayed revision surgery. The aim of the study was to summarize the failures, functional outcomes and prosthetic survival in revision tumor endoprostheses of the knee joint.

Methods
The clinical data of 20 patients with malignant tumors who received prosthetic revisions after limb salvage surgery from January, 2000 until January, 2018 were retrospectively reviewed. The cohort was constituted of 11 male and 9 female patients with a mean age of 34.1 years (range, 16 to 66 years). Infection cases received two-stage revisions after removing prostheses initially, while all other cases received one-stage revisions. Revision reasons and complications were well documented and analyzed.

Results
All patients received complete follow-up with a mean time of 64.7 months (range, 27 to 155 months). A total of 6 (6/20, 30.0%) patients experienced a second complication after revision surgery, of whom, one patient with deep infection experienced repeated infections after prosthetic revision and received amputation surgery; one patient revised of prosthetic fracture experienced an infection and received a second-stage infection revision; one case revised of prosthetic loosening had deep infection receiving anti-infective therapy with prostheses still in position; one case having wound complication healed after receiving two times of debridement surgery; one MBGCT patient experienced a second aseptic loosening 6 years after the initial loosening thus undergoing a second revision; a recurrent osteosarcoma patient died of pulmonary metastasis 3 years after revision surgery. Kaplan-Meier survival curve indicated a 5-year survival rate of initial prostheses was 75%. The Musculoskeletal Tumor Society (MSTS-93) score [20.9 (range, 15 to 27 scores)] at 1 year after revision surgeries was significantly improved (p < 0.001) when compared with the score [17.2 (range, 13 to 21 scores)] before revisions.

Conclusion
Prosthetic mechanical problems, aseptic loosening and infections were primary reasons for revisions after tumor endoprostheses of the knee joint. Although revision surgeries were complicated while still associated with high risk of failure, which remains the remedy strategy for limb salvage and functional recovery in those patients.
RUNX3-mediated circDYRK1A inhibits glutamine metabolism in gastric cancer by up-regulating microRNA-889-3p-dependent FBXO4
Authors: Liu Haofeng , Xue Qiu , Cai Hongzhou , Jiang Xiaohui , Cao Guangxin , Chen Tie , Chen Yuan , Wang Ding 
Published: March 2022

Abstract
Background
Targeting glutamine metabolism is previously indicated as a potential and attractive strategy for gastric cancer (GC) therapy. However, the underlying mechanisms responsible for the modification of glutamine metabolism in GC cells have not been fully elucidated. Accordingly, the current study sought to investigate the physiological mechanisms of RUNX3-mediated circDYRK1A in glutamine metabolism of GC.

Methods
Firstly, GC tissues and adjacent normal tissues were obtained from 50 GC patients to determine circDYRK1A expression in GC tissues. Next, the binding affinity among RUNX3, circDYRK1A, miR-889-3p, and FBXO4 was detected to clarify the mechanistic basis. Moreover, GC cells were subjected to ectopic expression and knockdown manipulations of circDYRK1A, miR-889-3p, and/or FBXO4 to assay GC cell malignant phenotypes, levels of glutamine, glutamic acid, and α-KG in cell supernatant and glutamine metabolism-related proteins (GLS and GDH). Finally, nude mice were xenografted with GC cells to explore the in vivo effects of circDYRK1A on the tumorigenicity and apoptosis.

Results
circDYRK1A was found to be poorly expressed in GC tissues. RUNX3 was validated to bind to the circDYRK1A promoter, and circDYRK1A functioned as a miR-889-3p sponge to up-regulate FBXO4 expression. Moreover, RUNX3-upregulated circDYRK1A reduced levels of glutamine, glutamic acid, and α-KG, and protein levels of GLS and GDH, and further diminished malignant phenotypes in vitro. Furthermore, in vivo experimentation substantiated that circDYRK1A inhibited the tumorigenicity and augmented the apoptosis in GC.

Conclusion
In conclusion, these findings highlighted the significance and mechanism of RUNX3-mediated circDYRK1A in suppressing glutamine metabolism in GC via the miR-889-3p/FBXO4 axis.
“The DEA would come in and destroy you”: a qualitative study of fear and unintended consequences among opioid prescribers in WV
Authors: Sedney Cara L. , Haggerty Treah , Dekeseredy Patricia , Nwafor Divine , Caretta Martina Angela , Brownstein Henry H. , Pollini Robin A. 
Published: March 2022

Abstract
Background
West Virginia has one of the highest rates of opioid overdose related deaths and is known as the epicenter of the opioid crisis in the United States. In an effort to reduce opioid-related harms, SB 273 was signed in 2018, and aimed to restrict opioid prescribing in West Virginia. SB 273 was enacted during a time when physician arrests and convictions had been increasing for years and were becoming more prevalent and more publicized. This study aims to better understand the impact of the legislation on patients and providers.

Methods
Twenty semi-structured interviews were conducted with opioid-prescribing primary care physicians and specialists practicing throughout West Virginia.

Results
Four themes emerged, 1. Fear of disciplinary action, 2. Exacerbation of opioid prescribing fear due to restrictive legislation, 3. Care shifts and treatment gaps, and 4. Conversion to illicit substances. The clinicians recognized the harms of inappropriate prescribing and how this could affect their patients. Decreases in opioid prescribing were already occurring prior to the law implementation. Disciplinary actions against opioid prescribers resulted in prescriber fear, which was then exacerbated by SB 273 and contributed to shifts in care that led to forced tapering and opioid under-prescribing. Providers felt that taking on patients who legitimately required opioids could jeopardize their career.

Conclusion
A holistic and patient-centered approach should be taken by legislative and disciplinary bodies to ensure patients are not abandoned when disciplinary actions are taken against prescribers or new legislation is passed.
Bittersweet: relevant amounts of the common sweet food additive, glycerol, accelerate the growth of PC3 human prostate cancer xenografts
Authors: DeGuzman Ariel , Lorenson Mary Y. , Walker Ameae M. 
Published: March 2022

Abstract
Objective
In a study of potential prostate cancer therapeutics, glycerol was used to increase the density of one solution. Glycerol alone was therefore one of the controls. Tumors of human PC3 castrate-resistant prostate cancer cells were initiated in male nude mice and grown for 12 days. Mice were then sorted such that mean tumor weights were the same in each group, and osmotic minipumps delivering 0.25 µL/h of either saline or glycerol were then implanted subcutaneously.

Results
Contrary to our initial assumption that glycerol would be without effect, tumors grew more rapidly in the glycerol group such that tumors were twice the size of those in the saline group after 4 weeks. Given the dose delivered, analysis of the literature suggests this effect was not via the conversion of glycerol to glucose but possibly via a reduction in oxidative damage in the growing tumor. Our data demonstrate that amounts of glycerol that could reasonably be derived from the diet promote the growth of these tumors. Given the increasing use of glycerol in foods and beverages, we present these data to stimulate interest in an epidemiological study in the human population examining glycerol consumption and the aggressiveness of prostate cancer.