bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a prognostic nomogram for predicting overall survival in patients with primary bladder sarcoma: a SEER-based retrospective study
Authors: Li Shijie , Liu Xuefeng , Chen Xiaonan 
Published: November 2021

Abstract
Background
Primary bladder sarcoma (PBS) is a rare malignant tumor of the bladder with a poor prognosis, and its disease course is inadequately understood. Therefore, our study aimed to establish a prognostic model to determine individualized prognosis of patients with PBS.

Patients and Methods
Data of 866 patients with PBS, registered from 1973 to 2015, were extracted from the surveillance, epidemiology, and end result (SEER) database. The patients included were randomly split into a training (n = 608) and a validation set (n = 258). Univariate and multivariate Cox regression analyses were employed to identify the important independent prognostic factors. A nomogram was then established to predict overall survival (OS). Using calibration curves, receiver operating characteristic curves, concordance index (C-index), decision curve analysis (DCA), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), the performance of the nomogram was internally validated. We compared the nomogram with the TNM staging system. The application of the risk stratification system was tested using Kaplan–Meier survival analysis.

Results
Age at diagnosis, T-stage, N-stage, M-stage, and tumor size were identified as independent predictors of OS. C-index of the training cohort were 0.675, 0.670, 0.671 for 1-, 3- and 5-year OS, respectively. And that in the validation cohort were 0.701, 0.684, 0.679, respectively. Calibration curves also showed great prediction accuracy. In comparison with TNM staging system, improved net benefits in DCA, evaluated NRI and IDI were obtained. The risk stratification system can significantly distinguish the patients with different survival risk.

Conclusion
A prognostic nomogram was developed and validated in the present study to predict the prognosis of the PBS patients. It may assist clinicians in evaluating the risk factors of patients and formulating an optimal individualized treatment strategy.
Triple-negative apocrine carcinoma as a rare cause of a breast lump in a Syrian female: a case report and review of the literature
Authors: Ismail Sawsan , Kherbek Haidara , Skef Jana , Zahlouk Nadim , Abdulal Rafik , Alshehabi Zuheir 
Published: November 2021

Abstract
Background
Apocrine carcinoma is a rare tumor that constitutes < 4% of all breast malignancies, characterized by the proliferation of large atypical cells with strictly defined borders, abundant eosinophilic cytoplasm, large nuclei, and prominent nucleoli in more than 90% of tumor cells. Triple-negative apocrine carcinoma is a rare molecular subtype that constitutes less than 1% of triple-negative breast cancers and is characterized by negative expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor, with positive expression of androgen receptor.

Case presentation
We report a case of a 45-year-old Syrian female who presented to our hospital due to a painless palpable mass in her left breast. Following physical and radiological examinations, an excisional biopsy was performed. Microscopic examination of the specimen followed by immunohistochemical staining revealed the diagnosis of a triple-negative apocrine carcinoma.

Conclusion
Triple-negative apocrine carcinoma is an extremely rare neoplasm that must be considered in the differential diagnoses of breast lesions through detailed clinical, histological, and immunohistochemical correlations. In our manuscript, we aimed to present the first case report of a Syrian female who was diagnosed with a triple-negative apocrine carcinoma, aiming to highlight the importance of detailed clinical, histological and immunohistochemical correlations with a detailed review of diagnostic criteria, molecular characteristics, and treatment recommendations.
Contribution of a positive psychology-based conceptual framework in reducing physician burnout and improving well-being: a systematic review
Authors: Bazargan-Hejazi Shahrzad , Shirazi Anaheed , Wang Andrew , Shlobin Nathan A. , Karunungan Krystal , Shulman Joshua , Marzio Robert , Ebrahim Gul , Shay William , Slavin Stuart 
Published: November 2021

AbstractBackgroundThe PERMA Model, as a positive psychology conceptual framework, has increased our understanding of the role of Positive emotion, Engagement, Relationships, Meaning, and Achievements in enhancing human potentials, performance and wellbeing. We aimed to assess the utility of PERMA as a multidimensional model of positive psychology in reducing physician burnout and improving their well-being.MethodsEligible studies include peer-reviewed English language studies of randomized control trials and non-randomized design. Attending physicians, residents, and fellows of any specialty in the primary, secondary, or intensive care setting comprised the study population. Eligible studies also involved positive psychology interventions designed to enhance physician well-being or reduce physician burnout. Using free text and the medical subject headings we searched CINAHL, Ovid PsychINFO, MEDLINE, and Google Scholar (GS) electronic bibliographic databases from 2000 until March 2020. We use keywords for a combination of three general or block of terms (Health Personnel OR Health Professionals OR Physician OR Internship and Residency OR Medical Staff Or Fellow) AND (Burnout) AND (Positive Psychology OR PERMA OR Wellbeing Intervention OR Well-being Model OR Wellbeing Theory).ResultsOur search retrieved 1886 results (1804 through CINAHL, Ovid PsychINFO, MEDLINE, and 82 through GS) before duplicates were removed and 1723 after duplicates were removed. The final review included 21 studies. Studies represented eight countries, with the majority conducted in Spain (n = 3), followed by the US (n = 8), and Australia (n = 3). Except for one study that used a bio-psychosocial approach to guide the intervention, none of the other interventions in this review were based on a conceptual model, including PERMA. However, retrospectively, ten studies used strategies that resonate with the PERMA components.ConclusionConsideration of the utility of PERMA as a multidimensional model of positive psychology to guide interventions to reduce burnout and enhance well-being among physicians is missing in the literature. Nevertheless, the majority of the studies reported some level of positive outcome regarding reducing burnout or improving well-being by using a physician or a system-directed intervention. Albeit, we found more favorable outcomes in the system-directed intervention. Future studies are needed to evaluate if PERMA as a framework can be used to guide system-directed interventions in reducing physician burnout and improving their well-being.
Analysis of the potential inappropriate use of medications in pediatric outpatients in China
Authors: Cui Jing , Zhao Lei , Liu Xianghong , Liu Mengyujie , Zhong Lihong 
Published: November 2021

Abstract
Background
The appropriate use of medications is essential in children. Yet, detailed information on how drugs are being prescribed and dispensed to pediatric populations is not documented in China.

Aim
The study objective was to analyze the details of medicine use and categorize the types of inappropriate use of medications on children.

Methods
A retrospective cross-sectional study was conducted on the prescriptions of pediatric outpatients aged < 18 years from 2019 to 2020 at a major Chinese tertiary academic center. Each age group’s demographic and clinical characteristics were collected, and the ratios of inappropriate prescriptions were analyzed.

Results
The total number of pediatric outpatients was 652,152, and 49.37% (322000) were prescribed medications, in which the most widely used medicines were respiratory, anti-infectives, and Traditional Chinese Medicines (TCMs). The prevalence rate of inappropriate prescriptions reached 20.49%, and in 2019 it was higher (21.71%) than that in 2020 (18.36%). The top three common inappropriate categories were indication-related off-label drug use, improper administration frequency, and overdosing, accounting for 67.93, 17.80 and 11.06% of all inappropriate prescriptions, respectively. The inappropriate prescriptions were more likely seen in patients aged 2–5 years and respiratory medicines.

Conclusions
The study findings indicate that inappropriate drug use in pediatric outpatients is still common, and great attention needs to be paid. More prospective trials are required to identify the effectiveness, safety, and necessity of off-label drug use of medicines in children.
Monkeying around with venom: an increased resistance to α-neurotoxins supports an evolutionary arms race between Afro-Asian primates and sympatric cobras
Authors: Harris Richard J. , Nekaris K. Anne-Isola , Fry Bryan G. 
Published: November 2021

Abstract
Background
Snakes and primates have a multi-layered coevolutionary history as predators, prey, and competitors with each other. Previous work has explored the Snake Detection Theory (SDT), which focuses on the role of snakes as predators of primates and argues that snakes have exerted a selection pressure for the origin of primates’ visual systems, a trait that sets primates apart from other mammals. However, primates also attack and kill snakes and so snakes must simultaneously avoid primates. This factor has been recently highlighted in regard to the movement of hominins into new geographic ranges potentially exerting a selection pressure leading to the evolution of spitting in cobras on three independent occasions.

Results
Here, we provide further evidence of coevolution between primates and snakes, whereby through frequent encounters and reciprocal antagonism with large, diurnally active neurotoxic elapid snakes, Afro-Asian primates have evolved an increased resistance to α-neurotoxins, which are toxins that target the nicotinic acetylcholine receptors. In contrast, such resistance is not found in Lemuriformes in Madagascar, where venomous snakes are absent, or in Platyrrhini in the Americas, where encounters with neurotoxic elapids are unlikely since they are relatively small, fossorial, and nocturnal. Within the Afro-Asian primates, the increased resistance toward the neurotoxins was significantly amplified in the last common ancestor of chimpanzees, gorillas, and humans (clade Homininae). Comparative testing of venoms from Afro-Asian and American elapid snakes revealed an increase in α-neurotoxin resistance across Afro-Asian primates, which was likely selected against cobra venoms. Through structure-activity studies using native and mutant mimotopes of the α-1 nAChR receptor orthosteric site (loop C), we identified the specific amino acids responsible for conferring this increased level of resistance in hominine primates to the α-neurotoxins in cobra venom.

Conclusion
We have discovered a pattern of primate susceptibility toward α-neurotoxins that supports the theory of a reciprocal coevolutionary arms-race between venomous snakes and primates.
Diagnostic accuracy of pooling urine, anorectal, and oropharyngeal specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae: a systematic review and meta-analysis
Authors: Aboud Lily , Xu Yangqi , Chow Eric P. F. , Wi Teodora , Baggaley Rachel , Mello Maeve B. , Fairley Christopher K. , Ong Jason J. 
Published: November 2021

Abstract
Background
Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at genital and extragenital sites is needed for most key populations, but molecular diagnostic tests for CT/NG are costly. We aimed to determine the accuracy of pooled samples from multiple anatomic sites from one individual to detect CT/NG using the testing of a single sample from one anatomic site as the reference.

Methods
In this systematic review and meta-analysis, we searched five databases for articles published from January 1, 2000, to February 4, 2021. Studies were included if they contained original data describing the diagnostic accuracy of pooled testing compared with single samples, resource use, benefits and harms of pooling, acceptability, and impact on health equity. We present the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. The study protocol is registered in PROSPERO, an international database of prospectively registered systematic reviews (CRD42021240793). We used GRADE to evaluate the quality of evidence.

Results
Our search yielded 7814 studies, with 17 eligible studies included in our review. Most studies were conducted in high-income countries (82.6%, 14/17) and focused on men who have sex with men (70.6%, 12/17). Fourteen studies provided 15 estimates for the meta-analysis for CT with data from 5891 individuals. The pooled sensitivity for multisite pooling for CT was 93.1% [95% confidence intervals (CI) 90.5–95.0], I2=43.3, and pooled specificity was 99.4% [99.0–99.6], I2=52.9. Thirteen studies provided 14 estimates for the meta-analysis for NG with data from 6565 individuals. The pooled sensitivity for multisite pooling for NG was 94.1% [95% CI 90.9–96.3], I2=68.4, and pooled specificity was 99.6% [99.1–99.8], I2=83.6. Studies report significant cost savings (by two thirds to a third).

Conclusion
Multisite pooled testing is a promising approach to improve testing coverage for CT/NG in resource-constrained settings with a small compromise in sensitivity but with a potential for significant cost savings.
Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway
Authors: Liu Xingyun , Yang Jia , Yang Chengwei , Huang Xiang , Han Mingming , Kang Fang , Li Juan 
Published: November 2021

Abstract
Background
Morphine, a µ-opioid receptor (MOR) agonist, has been shown to be related to the activity of cancer cells, and a higher morphine dosage reduces the survival time of patients with lung cancer. However, the effect of morphine on the malignant behavior of lung cancer cells remains unclear. The aim of this study was to investigate the specific molecular mechanism by which morphine regulates the malignant biological behavior of non-small cell lung cancer.

Methods
Immunofluorescence staining and Western blot analyses were performed to detect MOR expression. H460 non-small cell lung cancer cells were used in this study, and cell proliferation, the cell cycle and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Cell migration and invasion were detected using wound healing and Transwell assays. The effect of morphine on lung cancer development in vivo was examined by performing a xenograft tumor assay following morphine treatment.

Results
Morphine promoted the growth of H460 cells both in vivo and in vitro. Morphine enhanced cell migration and invasion, modified cell cycle progression through the S/G2 transition and exerted an antiapoptotic effect on H460 cells. Additionally, morphine increased Rous sarcoma oncogene cellular homolog (Src) phosphorylation and activated the phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Treatment with the MOR antagonist methylnaltrexone (MNTX) and the Src inhibitor protein phosphatase 1 (PP1) reduced the phosphorylation induced by morphine. Furthermore, MNTX, PP1, and the PI3K/AKT inhibitor deguelin reversed the antiapoptotic effect of morphine on lung cancer cells.

Conclusion
Morphine promotes the malignant biological behavior of H460 cells by activating the MOR and Src/mTOR signaling pathways.
Analysis of pir gene expression across the Plasmodium life cycle
Authors: Little Timothy S. , Cunningham Deirdre A. , Vandomme Audrey , Lopez Carlos Talavera , Amis Sarah , Alder Christopher , Addy John W. G. , McLaughlin Sarah , Hosking Caroline , Christophides George , Reid Adam J. , Langhorne Jean 
Published: November 2021

Abstract
Background
Plasmodium interspersed repeat (pir) is the largest multigene family in the genomes of most Plasmodium species. A variety of functions for the PIR proteins which they encode have been proposed, including antigenic variation, immune evasion, sequestration and rosetting. However, direct evidence for these is lacking. The repetitive nature of the family has made it difficult to determine function experimentally. However, there has been some success in using gene expression studies to suggest roles for some members in virulence and chronic infection.

Methods
Here pir gene expression was examined across the life cycle of Plasmodium berghei using publicly available RNAseq data-sets, and at high resolution in the intraerythrocytic development cycle using new data from Plasmodium chabaudi.

Results
Expression of pir genes is greatest in stages of the parasite which invade and reside in red blood cells. The marked exception is that liver merozoites and male gametocytes produce a very large number of pir gene transcripts, notably compared to female gametocytes, which produce relatively few. Within the asexual blood stages different subfamilies peak at different times, suggesting further functional distinctions. Representing a subfamily of its own, the highly conserved ancestral pir gene warrants further investigation due to its potential tractability for functional investigation. It is highly transcribed in multiple life cycle stages and across most studied Plasmodium species and thus is likely to play an important role in parasite biology.

Conclusions
The identification of distinct expression patterns for different pir genes and subfamilies is likely to provide a basis for the design of future experiments to uncover their function.
Accumulation of LDL/ox-LDL in the necrotic region participates in osteonecrosis of the femoral head: a pathological and in vitro study
Authors: Wang Xin-Yuan , Ma Tian-Le , Chen Kang-Ning , Pang Zhi-Ying , Wang Hao , Huang Jun-Ming , Qi Guo-Bin , Wang Chen-Zhong , Jiang Zeng-Xin , Gong Lin-Jing , Wang Zhe , Jiang Chang , Yan Zuo-Qin 
Published: November 2021

Abstract
Background
Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH.

Methods
Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments.

Results
In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes.

Conclusions
The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.
MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS
Authors: Barutta Federica , Corbetta Beatrice , Bellini Stefania , Guarrera Simonetta , Matullo Giuseppe , Scandella Michela , Schalkwijk Casper , Stehouwer Coen D. , Chaturvedi Nish , Soedamah-Muthu Sabita S. , Durazzo Marilena , Gruden Gabriella 
Published: November 2021

AbstractBackgroundMicroRNA-146a-5p (miR-146a-5p) is a key regulator of inflammatory processes. Expression of miR-146a-5p is altered in target organs of diabetic complications and deficiency of miR-146a-5p has been implicated in their pathogenesis. We investigated if serum miR-146a-5p levels were independently associated with micro/macrovascular complications of type 1 diabetes (DM1).MethodsA nested case–control study from the EURODIAB PCS of 447 DM1 patients was performed. Cases (n = 294) had one or more complications of diabetes, whereas controls (n = 153) did not have any complication. Total RNA was isolated from all subjects and miR-146a-5p levels measured by qPCR. Both the endogenous controls U6 snRNA and the spike (Cel-miR-39) were used to normalize the results. Logistic regression analysis was carried out to investigate the association of miR-146a-5p with diabetes complications.ResultsMiR-146a-5p levels were significantly lower in cases [1.15 (0.32–3.34)] compared to controls [1.74 (0.44–6.74) P = 0.039]. Logistic regression analysis showed that levels of miR-146a-5p in the upper quartile were inversely associated with reduced odds ratio (OR) of all complications (OR 0.34 [95% CI 0.14–0.76]) and particularly with cardiovascular diseases (CVD) (OR 0.31 [95% CI 0.11–0.84]) and diabetic retinopathy (OR 0.40 [95% CI 0.16–0.99]), independently of age, sex, diabetes duration, A1c, hypertension, AER, eGFR, NT-proBNP, and TNF-α.ConclusionsIn this large cohort of DM1 patients, we reported an inverse and independent association of miR-146a-5p with diabetes chronic complications and in particular with CVD and retinopathy, suggesting that miR-146a-5p may be a novel candidate biomarker of DM1 complications.