bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and ultrasound characteristics of virilizing ovarian tumors in pre- and postmenopausal patients: a single tertiary center experience
Authors: Zou Mi , Chen Rong , Wang Yahong , He Yonglan , Wang Ying , Dong Yifan , Li Jianchu 
Published: October 2021

Abstract
Background
A virilizing ovarian tumor (VOT) is a rare cause of hyperandrogenism in pre- and postmenopausal women. Although transvaginal ultrasound is considered as the first-line imaging method for ovarian tumors, it is examiner-dependent. We aimed to summarize the clinical and ultrasound manifestations of VOTs to help establish the diagnosis with emphasis on those causing diagnostic difficulty.

Method
We retrospectively identified 31 patients with VOTs who underwent surgery at Peking Union Medical College Hospital.

Results
Patients with VOTs were predominantly premenopausal. All patients showed androgenic manifestations with serum testosterone levels elevated to varying degrees. The tumor size of VOTs was significantly correlated with age (P < 0.001). The VOTs in the postmenopausal group were significantly smaller than those in the premenopausal group (median 1.8 cm [range, 1.3–4.8 cm] vs 4.5 cm [range, 0.7–11.9 cm]; P = 0.018). Twenty-seven out of 31 VOTs were successfully identified by ultrasound. On ultrasound, VOTs are mostly solid and hypoechoic masses with enhanced vascularity. Four VOTs (0.7–1.5 cm) were radiologically negative, and they were the smallest among all patients.

Conclusion
Patients with VOTs showed androgenic manifestations with varying degrees of hyperandrogenemia. Older patients tend to have smaller VOTs. Ultrasound is an effective method for the detection of VOTs. Some VOTs can be very small and difficult to visualize radiologically, especially in postmenopausal patients. Examiners must remain vigilant about very small VOTs on the basis of endocrine symptoms.
The impact of demographic and clinical characteristics on the trajectories of health-related quality of life among patients with Fabry disease
Authors: Sigurdardottir Solrun , Bjerkely Birgitte , Jenssen Trond G. , Mathisen Per , von der Lippe Charlotte , Ørstavik Kristin , Heimdal Ketil , Dahle Dag Olav , Weedon-Fekjær Mina Susanne , Solberg Olga , Pihlstrøm Hege K. 
Published: October 2021

Abstract
Background
Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by multiorgan dysfunction. Since individuals with FD usually experience progressive clinical disease manifestations, their health-related quality of life (HRQOL) is expected to change over time. However, there is limited longitudinal research examining HRQOL outcomes in individuals with FD. We aimed to: assess longitudinal outcomes in HRQOL in adults with FD; examine the physical- and mental HRQOL trajectories at the initial registration (baseline), 3–5 year, and 7–13 year follow-ups; and evaluate the possible associations of age, sex and medical complications with the physical- and mental HRQOL trajectories.

Methods
Forty-three individuals with FD (53% female) who were aged 18 to 81 years at baseline attended clinical follow-up visits between 2006 and 2020. Medical records were extracted retrospectively. Demographics and the 36-item Short-Form Health Survey (SF-36) were recorded at scheduled visits, except for the last data collection which was prospectively obtained in 2020. The physical (PCS) and mental (MCS) composite scores (SF-36) were chosen as outcome measures.

Results
The eight SF-36 domain scores were stable over a span of 13 years, and only physical- and social functioning domains worsened clinically over this follow-up period. Mean baseline SF-36 domain scores were all significantly lower (decreased HRQOL) in the FD sample compared with Norwegian population norms. Two hierarchical linear models were run to examine whether demographics and medical complications (measured at the last clinical visit) predicted physical and mental HRQOL trajectories. Age above 47 years (p < 0.001), male sex (p = 0.027), small fibre neuropathy (p < 0.001), renal dysfunction (p < 0.001), and cerebrovascular events (p = 0.003) were associated with lower HRQOL over time. No significant interactions were found between the time of follow up and the abovementioned predictors of HRQOL.

Conclusions
Overall HRQOL trajectories remained stable between baseline, 3–5 year, and 7–13 year follow-ups, with the majority of individuals reporting decreased physical and mental HRQOL. Medical complications in combination with older age and male sex are important predictors of lower HRQOL in FD. Awareness of this relationship is valuable both for health care providers and for patients. The findings provide indicators that can guide treatment decisions to improve physical and mental HRQOL outcomes.
Association between psychosocial functioning, health status and healthcare access of asylum seekers and refugee children: a population-based cross-sectional study in a German federal state
Authors: Costa Diogo , Biddle Louise , Bozorgmehr Kayvan 
Published: October 2021

Abstract
Background
The mental health condition and healthcare needs of asylum seeking and refugee (ASR) children may go unrecognized if barriers to healthcare access exist accompanied by exclusive focus on somatic illness. We analysed the relationship between psychosocial functioning, health status and healthcare access of ASR children.

Methods
During 2018, 560 ASR adults in 58 collective accommodations in Germany’s 3rd largest federal state were randomly sampled and assessed. The parent-reported Strengths and Difficulties Questionnaire (SDQ) was used to assess child psychosocial functioning. SDQ dimensions (Emotional, Conduct, Peer, Hyperactivity, Prosocial, Total) were compared by demographics (sex, age, region of origin, time since arrival, subjective social status), health status (long-lasting illness, physical limitation, pain) and healthcare access (utilization: paediatrician, specialist, dentist, psychologist, hospital/emergency department, prescribed medicines; and unmet needs: for paediatrician/specialist, reduced spending to cover healthcare cost). Age and sex-adjusted odds ratios (AOR, 95%CI-Confidence Intervals) for scoring in borderline/abnormal ranges in SDQ dimensions were estimated through logistic regression depending on children’ health status and healthcare access.

Results
We analysed parents’ answers pertaining to 90 children aged 1–17 years old, 57% of which were girls and 58% with (Eastern or Western) Asian nationality. Scoring in the borderline/abnormal range of the SDQ Total Difficulties score was associated with feeling bodily pain (compared to no pain, AOR, 95%CI = 3.14, 1.21–8.10) and with an unmet need for a specialist during the previous year (4.57, 1.09–19.16). Borderline/abnormal SDQ Emotional scores were positively associated with a long-lasting illness (5.25, 1.57–17.55), physical limitation (4.28, 1.49–12.27) and bodily pain (3.00, 1.10–8.22), and negatively associated with visiting a paediatrician (0.23, 0.07–0.78), specialist (0.16, 0.04–0.69), and the emergency department (0.27, 0.08–0.96).

Conclusion
Poor psychosocial functioning among ASR children is associated with somatic problems, unmet medical needs, and lower healthcare utilisation. Somatic clinical encounters with ASR should include children’ mental health symptomatology assessment, especially in those with worst physical health conditions.
L1CAM promotes ovarian cancer stemness and tumor initiation via FGFR1/SRC/STAT3 signaling
Authors: Giordano Marco , Decio Alessandra , Battistini Chiara , Baronio Micol , Bianchi Fabrizio , Villa Alessandra , Bertalot Giovanni , Freddi Stefano , Lupia Michela , Jodice Maria Giovanna , Ubezio Paolo , Colombo Nicoletta , Giavazzi Raffaella , Cavallaro Ugo 
Published: October 2021

Abstract
Background
Cancer stem cells (CSC) have been implicated in tumor progression. In ovarian carcinoma (OC), CSC drive tumor formation, dissemination and recurrence, as well as drug resistance, thus contributing to the high death-to-incidence ratio of this disease. However, the molecular basis of such a pathogenic role of ovarian CSC (OCSC) has been elucidated only to a limited extent. In this context, the functional contribution of the L1 cell adhesion molecule (L1CAM) to OC stemness remains elusive.

Methods
The expression of L1CAM was investigated in patient-derived OCSC. The genetic manipulation of L1CAM in OC cells provided gain and loss-of-function models that were then employed in cell biological assays as well as in vivo tumorigenesis experiments to assess the role of L1CAM in OC cell stemness and in OCSC-driven tumor initiation. We applied antibody-mediated neutralization to investigate L1CAM druggability. Biochemical approaches were then combined with functional in vitro assays to study the molecular mechanisms underlying the functional role of L1CAM in OCSC.

Results
We report that L1CAM is upregulated in patient-derived OCSC. Functional studies showed that L1CAM promotes several stemness-related properties in OC cells, including sphere formation, tumor initiation and chemoresistance. These activities were repressed by an L1CAM-neutralizing antibody, pointing to L1CAM as a druggable target. Mechanistically, L1CAM interacted with and activated fibroblast growth factor receptor-1 (FGFR1), which in turn induced the SRC-mediated activation of STAT3. The inhibition of STAT3 prevented L1CAM-dependent OC stemness and tumor initiation.

Conclusions
Our study implicate L1CAM in the tumorigenic function of OCSC and point to the L1CAM/FGFR1/SRC/STAT3 signaling pathway as a novel driver of OC stemness. We also provide evidence that targeting this pathway can contribute to OC eradication.
An SETD1A/Wnt/β-catenin feedback loop promotes NSCLC development
Authors: Wang Rui , Liu Jian , Li Kai , Yang Ganghua , Chen Sisi , Wu Jie , Xie Xinming , Ren Hong , Pang Yamei 
Published: October 2021

AbstractBackgroundSETD1A, a member of SET1/MLL family H3K4 methyltransferases, is involved in the tumorigenesis of numerous cancers. However, the biological role and mechanism of SETD1A in non-small cell lung cancer (NSCLC) remain to be elucidated.MethodsThe expression of SETD1A, NEAT1, EZH2, and β-catenin in NSCLC tissues and cell lines was detected by qRT-PCR, immunohistochemistry and western blotting. The regulatory mechanisms were validated by chromatin immunoprecipitation, co-immunoprepitation and luciferase reporter assay. The self-renewal, cisplatin sensitivity and tumorigenesis of NSCLC cells were analyzed using sphere formation, CCK-8, colony formation assays and xenograft tumor models.ResultsSETD1A expression was significantly increased in NSCLC and its overexpression predicted a poor prognosis of patients with NSCLC. Functional experiments showed that SETD1A positively regulated cancer stem cell property and negatively regulated cisplatin sensitivity in NSCLC cells via the Wnt/β-catenin pathway. Next, we found that SETD1A positively regulated the Wnt/β-catenin pathway via interacting with and stabilizing β-catenin. The SET domain is dispensable for the interaction between SETD1A and β-catenin. Furthermore, we identified that SETD1A bound to the promoters of NEAT1 and EZH2 to activate gene transcription by inducing H3K4me3 enrichment. Rescue experiments showed that SETD1A promoted the Wnt/β-catenin pathway and exerted its oncogenic functions in NSCLC, at least, partly through NEAT1 and EZH2 upregulation. In addition, SETD1A was proven to be a direct target of the Wnt/β-catenin pathway, thus forming a positive feedback loop in NSCLC cells.ConclusionSETD1A and Wnt/β-catenin pathway form a positive feedback loop and coordinately contribute to NSCLC progression.
Exosomal miR-30d-5p of neutrophils induces M1 macrophage polarization and primes macrophage pyroptosis in sepsis-related acute lung injury
Authors: Jiao Yang , Zhang Ti , Zhang Chengmi , Ji Haiying , Tong Xingyu , Xia Ran , Wang Wei , Ma Zhengliang , Shi Xueyin 
Published: October 2021

Abstract
Background
Polymorphonuclear neutrophils (PMNs) play an important role in sepsis-related acute lung injury (ALI). Accumulating evidence suggests PMN-derived exosomes as a new subcellular entity acting as a fundamental link between PMN-driven inflammation and tissue damage. However, the role of PMN-derived exosomes in sepsis-related ALI and the underlying mechanisms remains unclear.

Methods
Tumor necrosis factor-α (TNF-α), a key regulator of innate immunity in sepsis-related ALI, was used to stimulate PMNs from healthy C57BL/6J mice in vitro. Exosomes isolated from the supernatant were injected to C57BL/6J wild-type mice intraperitoneally (i.p.) and then examined for lung inflammation, macrophage (Mϕ) polarization and pyroptosis. In vitro co-culture system was applied where the mouse Raw264.7 macrophages or bone marrow-derived macrophages (BMDMs) were co-cultured with PMN-derived exosomes to further confirm the results of in vivo animal study and explore the potential mechanisms involved.

Results
Exosomes released by TNF-α-stimulated PMNs (TNF-Exo) promoted M1 macrophage activation after in vivo i.p. injection or in vitro co-culture. In addition, TNF-Exo primed macrophage for pyroptosis by upregulating NOD-like receptor 3 (NLRP3) inflammasome expression through nuclear factor κB (NF-κB) signaling pathway. Mechanistic studies demonstrated that miR-30d-5p mediated the function of TNF-Exo by targeting suppressor of cytokine signaling (SOCS-1) and sirtuin 1 (SIRT1) in macrophages. Furthermore, intravenous administration of miR-30d-5p inhibitors significantly decreased TNF-Exo or cecal ligation and puncture (CLP)-induced M1 macrophage activation and macrophage death in the lung, as well as the histological lesions.

Conclusions
The present study demonstrated that exosomal miR-30d-5p from PMNs contributed to sepsis-related ALI by inducing M1 macrophage polarization and priming macrophage pyroptosis through activating NF-κB signaling. These findings suggest a novel mechanism of PMN-Mϕ interaction in sepsis-related ALI, which may provide new therapeutic strategies in sepsis patients.
Glutamine involvement in nitrogen regulation of cellulase production in fungi
Authors: Pang Ai-Ping , Zhang Funing , Hu Xin , Luo Yongsheng , Wang Haiyan , Durrani Samran , Wu Fu-Gen , Li Bing-Zhi , Zhou Zhihua , Lu Zuhong , Lin Fengming 
Published: October 2021

Abstract
Background
Cellulase synthesized by fungi can environment-friendly and sustainably degrades cellulose to fermentable sugars for producing cellulosic biofuels, biobased medicine and fine chemicals. Great efforts have been made to study the regulation mechanism of cellulase biosynthesis in fungi with the focus on the carbon sources, while little attention has been paid to the impact and regulation mechanism of nitrogen sources on cellulase production.

Results
Glutamine displayed the strongest inhibition effect on cellulase biosynthesis in Trichoderma reesei, followed by yeast extract, urea, tryptone, ammonium sulfate and l-glutamate. Cellulase production, cell growth and sporulation in T. reesei RUT-C30 grown on cellulose were all inhibited with the addition of glutamine (a preferred nitrogen source) with no change for mycelium morphology. This inhibition effect was attributed to both l-glutamine itself and the nitrogen excess induced by its presence. In agreement with the reduced cellulase production, the mRNA levels of 44 genes related to the cellulase production were decreased severely in the presence of glutamine. The transcriptional levels of genes involved in other nitrogen transport, ribosomal biogenesis and glutamine biosynthesis were decreased notably by glutamine, while the expression of genes relevant to glutamate biosynthesis, amino acid catabolism, and glutamine catabolism were increased noticeably. Moreover, the transcriptional level of cellulose signaling related proteins ooc1 and ooc2, and the cellular receptor of rapamycin trFKBP12 was increased remarkably, whose deletion exacerbated the cellulase depression influence of glutamine.

Conclusion
Glutamine may well be the metabolite effector in nitrogen repression of cellulase synthesis, like the role of glucose plays in carbon catabolite repression. Glutamine under excess nitrogen condition repressed cellulase biosynthesis significantly as well as cell growth and sporulation in T. reesei RUT-C30. More importantly, the presence of glutamine notably impacted the transport and metabolism of nitrogen. Genes ooc1, ooc2, and trFKBP12 are associated with the cellulase repression impact of glutamine. These findings advance our understanding of nitrogen regulation of cellulase production in filamentous fungi, which would aid in the rational design of strains and fermentation strategies for cellulase production in industry.
Coinfection of Clostridium perfringens and Escherichia coli in gas-producing perianal abscess diagnosed by 16S rDNA sequencing: a case report
Authors: Sun Yang , Bai Haotian , Qu Ji , Liu Jichao , Wang Jincheng , Du Zhenwu , Feng Linlin 
Published: October 2021

Abstract
Background
Gas-producing perianal abscess raises the possibility of clostridial infection, with Clostridium perfringens being the most common causative agent, which is highly lethal if untreated timely. As the treatment of clostridial infections often differs from that of non-clostridial infections, which they may closely resemble, the importance of accurate pathogenic organism identification cannot be overemphasized. The 16S rDNA of bacteria is highly conserved within a species and among species of the same genus but demonstrates substantial variation between different species, thus making it a suitable genomic candidate for bacterial detection and identification.

Case presentation
Here, we report the case of a 53-year-old patient who was admitted to the hospital for a gas-producing perianal abscess. The patient was managed with ceftizoxime and ornidazole and then received debridement and drainage at the lesion on the second day after admission. The bacterial cultures of the patient isolates from the debridement showed a coinfection of Escherichia coli and Enterococcus faecium. Although perianal redness and swelling subsided obviously after the surgery, the patient was febrile to 38.3℃ with his left upper thigh red and swollen, aggravated with tenderness and crepitus. Considering insufficient debridement and the risk of incorrect identification of pathogens, a second debridement and drainage were performed 4 days after the primary operation, and 16S rDNA sequencing of the isolates implicated Clostridium perfringens infection. Given the discrepancies in diagnostic results and the treatment outcomes, Enterococcus faecium was identified as sample contamination, and a diagnosis of coinfection of Clostridium perfringens and Escherichia coli in gas-producing perianal abscess was confirmed. The patient was then successfully treated with meropenem and vancomycin and was discharged at 27 days of admission.

Conclusions
This case represents the first report of coinfection of both clostridial and non-clostridial organisms in gas-producing perianal abscess and the first case reporting the use of 16S rDNA sequencing in the diagnosis of perianal abscess. Timely pathogen identification is critical for treating gas-producing perianal abscess and an antibiotic regimen covering both aerobic and anaerobic organisms is recommended before true pathogens are identified.
Comparative genomic characterization of multidrug-resistant Citrobacter spp. strains in Fennec fox imported to China
Authors: Qin Jie , Zhao Yishu , Wang Aifang , Chi Xiaohui , Wen Peipei , Li Shuang , Wu Lingjiao , Bi Sheng , Xu Hao 
Published: October 2021

Abstract
Background
To investigate the antimicrobial profiles and genomic characteristics of MDR-Citrobacter spp. strains isolated from Fennec fox imported from Sudan to China.

Methods
Four Citrobacter spp. strains were isolated from stool samples. Individual fresh stool samples were collected and subsequently diluted in phosphate buffered saline as described previously. The diluted fecal samples were plated on MacConkey agar supplemented with 1 mg/l cefotaxime and incubated for 20 h at 37 °C. Matrix-assisted laser desorption/ionization–time of flight mass spectrometry (MALDI–TOF–MS) was used for identification. Antimicrobial susceptibility testing was performed using the broth microdilution method. Whole-genome sequencing was performed on an Illumina Novaseq-6000 platform. Acquired antimicrobial resistance genes and plasmid replicons were detected using ResFinder 4.1 and PlasmidFinder 1.3, respectively. Comparative genomic analysis of 277 Citrobacter genomes was also performed.

Results
Isolate FF141 was identified as Citrobacter cronae while isolate FF371, isolate FF414, and isolate FF423 were identified as Citrobacter braakii. Of these, three C. braakii isolates were further confirmed to be extended-spectrum β-lactamases (ESBL)-producer. All isolates are all multidrug resistance (MDR) with resistance to multiple antimicrobials. Plasmid of pKPC-CAV1321 belong to incompatibility (Inc) group. Comparative genomics analysis of Citrobacter isolates generated a large core-genome. Genetic diversity was observed in our bacterial collection, which clustered into five main clades. Human, environmental and animal Citrobacter isolates were distributed into five clusters.

Conclusions
To our knowledge, this is the first investigation of MDR-Citrobacter from Fennec Fox. Our phenotypic and genomic data further underscore the threat of increased ESBL prevalence in wildlife and emphasize that increased effort should be committed to monitoring the potentially rapid dissemination of ESBL-producers with one health perspective.
Superior training efficacy of beginning movement load training for the baseball throwers
Authors: Chou Wen-Yi , Ko Jih-Yang , Chen Shu-Fang , Wu Chia-Feng , Wu Kuan-Ting , Jhan Shun-Wun 
Published: October 2021

Abstract
Background
Superior shoulder motion with rotator cuff activation are essential for the performance of the throwing athletes. The present study compared the novel beginning movement load training (BMLT) and popular throwers ten program regarding the training efficacy of baseball throwers. We hypothesized that the BMLT contributed the superior training efficacy than popular throwers ten program.

Methods
Forty adult baseball players were randomized into study group and control group equally. In study group, the cyclic shoulder motion was repeatedly operated 3 days in a week and lasted for 6 weeks using three different BMLT training machines. As for control group, three popular cyclic training in the throwers ten program were adopted for the shoulder trainings as the same protocol in study group. The evaluations before and after training included the static range of motion (ROM), the maximal voluntary isometric contraction (MVICs) of the target muscle (pectoralis major, middle deltoid and supraspinatus) and throwing velocity.

Result
After 6-week course, study group had significant wider static ROM in saggital adduction (p = 0.002), coronal internal rotation (p = 0.018) and external rotation (p = 0.044) than in control group. The maximal voluntary isometric contraction (MVIC) ratio of middle deltoid/supraspinatus was significant lower in study group (Study:Control = 1.14 ± 0.76:3.56 ± 5.57, p = 0.049) which indicated the enhanced supraspinatus maximal contraction in the study group after training. In addition, the study group had significant improvement in throwing speed (117 ± 10 vs. 109 ± 10 km/h, p = 0.040).

Conclusion
The BMLT contributed the superiority in range of motion, recruitment of supraspinatus and throwing velocity than the popular thrower’s ten program. It could be a favourable training for the overhead activity.