bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between certolizumab pegol serum levels, anti-drug antibodies and treatment response in patients with inflammatory joint diseases: data from the NOR-DMARD study
Authors: Gehin Johanna Elin , Goll Guro Løvik , Warren David John , Syversen Silje Watterdal , Sexton Joseph , Strand Eldri Kveine , Kvien Tore Kristian , Bolstad Nils , Lie Elisabeth 
Published: November 2019

Abstract
Objectives
To identify a therapeutic target interval for certolizumab pegol drug levels and examine the influence of anti-drug antibodies in patients with inflammatory joint diseases.

Methods
Certolizumab pegol and anti-drug antibody levels were measured in serum samples collected after 3 months of certolizumab pegol treatment in 268 patients with inflammatory joint diseases (116 axial spondyloarthritis, 91 rheumatoid arthritis and 61 psoriatic arthritis) in the NOR-DMARD study. Treatment response was defined by Ankylosing Spondylitis Disease Activity Score Clinically important improvement in axial spondyloarthritis, European League Against Rheumatism good/moderate response in rheumatoid arthritis, and improvement in 28-joint Disease Activity Score of ≥ 0.6 in PsA. Serum drug levels and anti-drug antibodies were analysed using automated in-house assays.

Results
Certolizumab pegol serum levels varied considerably between individuals (median (IQR) 32.9 (17.3–43.9) mg/L). Certolizumab pegol level ≥ 20 mg/L was associated with treatment response for the total inflammatory joint disease population, with odds ratio (OR) 2.3 (95% CI 1.2–4.5, P = 0.01) and OR 1.9 (95% CI 1.0–3.5, P = 0.05) after 3 and 6 months of treatment, respectively. For individual diagnoses, this association was most consistent for axial spondyloarthritis, with OR 3.4 (95% CI 1.0–11.1, P < 0.05) and OR 3.3 (95% CI 1.0–10.8, P < 0.05), respectively. Certolizumab pegol level > 40 mg/L was not associated with any additional benefit for any of the diagnoses. Anti-drug antibodies were detected in 6.1% (19/310) of samples and were associated with low certolizumab pegol levels (P < 0.01).

Conclusions
Serum certolizumab pegol levels 20–40 mg/L were associated with treatment response in inflammatory joint diseases. Our study is the first to show this association in axial spondyloarthritis and psoriatic arthritis patients. The results suggest a possible benefit of therapeutic drug monitoring in patients with inflammatory joint disease on certolizumab pegol treatment.

Trial registration
NCT01581294, April 2012.
An alarming rise of non-albicans Candida species and uncommon yeasts in the clinical samples; a combination of various molecular techniques for identification of etiologic agents
Authors: Taei Monireh , Chadeganipour Mostafa , Mohammadi Rasoul 
Published: November 2019

Abstract
Objective
Yeasts are unicellular microorganisms may cause systemic infection in immunocompromised patients. The aim of this study was to identify yeast strains isolated from clinical specimens using molecular techniques.

Results
A total of 202 yeast strains isolated from 341 clinical samples between February 2017 and May 2019. All clinical isolates were identified using phenotypic and molecular tests including PCR–RFLP, duplex-PCR, multiplex-PCR, and PCR-sequencing. The most yeast fungal isolates were obtained from urine (66.8%), nail (9.4%), skin lesion (7.9%), bronchoalveolar lavage (5.9%), and blood (3.9%). One hundred and twenty-one Candida species were identified as non-albicans versus 76 Candida albicans. Trichosporon asahii, and Pichia terricola were uncommon non-Candida yeasts isolated from urine samples. For the first time, we isolated P. terricola as etiological agent of urinary tract infection in a pregnant female. Since Candida species show different levels of resistance to antifungal agents, precise identification of clinical isolates is critical for better treatment of infection.
Advanced primary urethral cancer: a case report
Authors: Chen Huan , Zou Li Li , Dong Chuan Jiang , Li Tao , Dong Zi Qiang 
Published: November 2019

Abstract
Background
Primary urethral cancer is exceedingly rare, resulting in a limitation in clinicians’ experience, and an accurate diagnosis is often delayed due to the non-specific clinical presentation. Here, we present this case report to show the treatment of a patient with primary urethral cancer. Our patient was diagnosed as having primary urethral cancer in the First Clinical Hospital of Yichang by cystoscopy and biopsy. Due to her age, poor physical tolerance, and economic condition, she refused radical operation. Since there is no definite guideline for the treatment process of primary urethral cancer in clinics, operation methods and postoperative adjuvant treatments vary in different hospitals, leading to diverse prognostic effects.

Case presentation
An 88-year-old Asian woman had difficulty in urinating for more than 6 months and the syndrome was aggravated for 1 month. She chose a relatively conservative treatment plan: primary tumor resection combined with bladder perfusion chemotherapy. Postoperative pathology revealed “urethra” high-grade urothelial carcinoma (sarcoma-like variants) with extensive necrosis. After treatment with intravesical chemotherapeutic drug (hydroxycamptothecin 40 mg), she was eventually released from our hospital in a stable condition. Postoperation follow-up was performed to observe to what extent this conservative treatment plan improved the quality of life and overall survival time of our patient.

Conclusions
She needed radical resection according to the actual situation. However, her age restricted her tolerance to general anesthesia; relatively conservative treatment options are available to ensure a high quality of life. The treatment of primary tumor resection combined with bladder perfusion chemotherapy is feasible. This case highlights the importance of the dissemination of new cases and optimizing primary urethral cancer diagnosis to obtain an effective treatment.
Diabetes drugs for nonalcoholic fatty liver disease: a systematic review
Authors: Blazina Ian , Selph Shelley 
Published: November 2019

Abstract
Background
Fatty liver is associated with obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. While there are no approved drugs for the treatment of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis, strategies to ameliorate fatty liver often target these related diseases. We sought to determine if any medications approved by the US Food and Drug Administration to treat diabetes are helpful in reducing weight and improving steatohepatitis in patients with NAFLD.

Methods
We conducted a systematic review of published and unpublished studies evaluating the comparative effectiveness and harms of diabetes medications for the treatment of NAFLD. We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials through 3rd quarter, 2019 using terms for included drugs and indications.

Results
We screened 1591 citations and included 18 trials of diabetes drugs to treat NAFLD. Studies of metformin found no difference from placebo in steatosis, fibrosis, NAFLD activity score, or resolution of NASH. While weight and glucose control were improved with metformin, it did not substantially impact liver disease. Studies of pioglitazone in NASH patients found benefits in liver function, liver fat, and NASH resolution, though significant increases in weight may be cause for concern. Evidence for other thiazolinediones was more limited and had somewhat mixed results, but findings were generally consistent with those for pioglitazone: liver fat and function and glucose measures improved, but weight also increased. We found some evidence that liraglutide improves liver fat, liver function, and HbA1c and is effective at resolving NASH and reducing weight. Exenatide performed less well but also resulted in significant reductions in liver fat and weight.

Conclusions
Consistent with existing clinical practice guidelines, which recommend lifestyle intervention and treatment for comorbidities related to fatty liver disease as first-line treatment, trial evidence supports the efficacy of some diabetes drugs (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with some diabetes drugs may warrant caution. Larger trials are needed to better characterize the efficacy and harms of diabetes pharmacotherapy in these patients.
Sites of synchronous distant metastases and prognosis in prostate cancer patients with bone metastases at initial diagnosis: a population‐based study of 16,643 patients
Authors: Zhao Feng , Wang Jili , Chen Meiqin , Chen Danni , Ye Sunyi , Li Xinke , Chen Xin , Ren Guoping , Yan Senxiang 
Published: November 2019

AbstractBackgroundBone is a preferential site for prostate cancer (PCa) metastasis. However, sites of synchronous distant metastases in PCa patients with bone metastases at initial diagnosis and their impacts on prognosis are still unclear, limiting our ability to better stratify and treat the patients. In this study, we examined the sites of synchronous extra‐skeletal metastases in de novo PCa patients with bone metastases and their associated prognoses.MethodsIn total, 16,643 de novo PCa patients with bone metastases from the SEER database were included. After stratification of metastatic sites (bone, lung, liver, and brain) and treatment modalities, overall survival (OS) and independent predictors of OS, were analyzed.ResultsLung was the most frequent site of synchronous metastases, followed by liver, while brain metastases were relatively uncommon. Patients with bone‐only metastases showed the longest mean survival time (35.87 months, p < 0.001), followed by patients with bone and lung metastases (30.74 months, p < 0.001). Patients with bone and liver metastases had the shortest mean survival time (17.39 months, p < 0.001). Age > 70 years, unmarried status, high tumor grade, prostate‐specific antigen (PSA) > 50 ng/ml, and Gleason score ≥ 8 were associated with poor OS (all p < 0.01). Asian or Pacific Islander ethnic background was associated with a favorable OS (all p < 0.01). Chemotherapy improved OS in patients without brain metastases (all p < 0.05). For patients with bone‐only metastases, radical prostatectomy (RP) (HR, 0.339; 95% CI 0.231–0.495; p < 0.001), brachytherapy (BT) (HR, 0.567; 95% CI 0.388–0.829; p = 0.003), and chemotherapy (HR, 0.850; 95% CI 0.781–0.924; p < 0.001) were associated with prolonged OS.ConclusionsAge, race, tumor grade, PSA, Gleason score, sites of synchronous extra‐skeletal metastases, as well as treatment modalities affected OS in newly diagnosed PCa patients with bone metastases. Synchronous liver metastases were associated with poor OS. Chemotherapy improved OS in patients without brain metastases. RP and BT improved OS in patients with bone‐only metastases. Further investigation is warranted to validate these findings.
Sodium valproate induced acute pancreatitis in a bipolar disorder patient: a case report
Authors: Huang Wanli , Ren Xin , Shen Fang , Xing Baoping 
Published: November 2019

Abstract
Background
Sodium valproate is one of the most widely used antiepileptics and mood stabilizers. However, this drug may induce acute pancreatitis. Few cases have been reported so far, mainly on the pediatric patients who underwent antiepileptic treatment. Hereby, we present a case of bipolar disorder with sodium valproate-induced acute pancreatitis.

Case presentation
The patient is a 54-year-old Chinese male. He was diagnosed with bipolar disorder for more than 39 years. Since the first onset of the disease, he had several relapses. The patient had had sodium valproate to stabilize mood swings for a year before the occurrence of acute pancreatitis. But he did vomit once during the inpatient care period. Then he was referred to another hospital following a notably high level of amylase. The results of computed tomography demonstrated an increased pancreatic volume and swollen peripancreatic fat tissue. As a result, the patient was diagnosed with acute pancreatitis. Unlike other cases reported in literatures, the high amylase level did not revert to normal after the withdrawal of medications. The patient was discharged from hospital with a high level of amylase, and was placed under follow-up observations.

Conclusion
Acute pancreatitis is considered as one of the idiosyncratic adverse reactions to antiepileptic drugs. Previous reports were mainly on the pediatric patients with increased propensity to idiosyncratic drug effects, or the adult chronic renal failure patients with sodium valproate-induced pancreatitis due to the retention of intermediate metabolites in their bodies. In this study, even though our patient exhibited no high risk of developing pancreatitis, he was treated for drug-induced acute pancreatitis in three hospitals. As rare as drug-induced acute pancreatitis can be, it should not be overlooked, Moreover, the mechanism of how sodium valproate induces acute pancreatitis remains unknown. Therefore, physicians need to consider the medical history of patients before prescribing this medication.
Strategic entrepreneurship, competitive advantage, and SMEs’ performance in the welding industry in Tanzania
Authors: Kiyabo Kibeshi , Isaga Nsubili 
Published: November 2019

AbstractThis study aimed at obtaining empirical evidence regarding the influence of strategic entrepreneurship on SMEs’ performance under the mediation of competitive advantage in the welding industry in Tanzania. Guided by the resource-based theory, this study adopted learning orientation, strategic resource management, and entrepreneurial orientation as strategic entrepreneurship components. Survey method with cross-sectional design was used to collect data from 300 owners-managers of welding industry SMEs located in Dar es Salaam, Morogoro, and Mbeya urban centers. Structural equation modelling technique was used to develop measurement and structural models. Findings suggest that learning orientation influences entrepreneurial orientation which influences strategic resource management to create competitive advantage that promotes SMEs’ performance. Findings of this study imply that the resource-based theory holds a better chance to describe the influence of strategic entrepreneurship components on SMEs’ performance under the mediation of competitive advantage than the individual resource-based view and knowledge-based view. It has been empirically demonstrated that knowledge is a unique resource that enables the acquisition of other resources and strategies. SMEs are urged to embrace learning orientation to create competitive advantage that leads to superior performance. The study has empirically verified that learning orientation, strategic resource management, and entrepreneurial orientation constructs adopted from entrepreneurship and strategic management literature are components of strategic entrepreneurship. Inclusion of strategic entrepreneurship components, competitive advantage, and SMEs’ performance with their composite measures in a single model distinguishes this study from past studies.
Long non-coding RNA MALAT1 enhances the apoptosis of cardiomyocytes through autophagy inhibition by regulating TSC2-mTOR signaling
Authors: Hu Hao , Wu Jiawei , Yu Xiaofan , Zhou Junling , Yu Hua , Ma Likun 
Published: November 2019

Abstract
Background
Our previous study showed that knockdown of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) attenuated myocardial apoptosis in mouse acute myocardial infarction (AMI). This study aims to explore whether MALAT1 enhanced cardiomyocyte apoptosis via autophagy regulation and the underlying mechanisms of MALAT1 regulating autophagy.

Methods
Cardiomyocytes were isolated from neonatal mice and then stimulated with hypoxia/reoxygenation (H/R) injury to mimic AMI. The autophagy level was assessed using GFP-LC3 immunofluorescence and western blot analysis of autophagy-related proteins. RNA pull-down and RNA immunoprecipitation (RIP) was performed to analyze the binding of MALAT1 and EZH2. Chromatin immunoprecipitation (ChIP) assay was performed to analyze the binding of TSC2 promoter and EZH2. The cell apoptosis was evaluated using TUNEL staining and western blot analysis of apoptosis-related proteins.

Results
H/R injury increased MALAT1 expression in cardiomyocytes. Furthermore, MALAT1 overexpression inhibited, whereas MALAT1 knockdown enhanced the autophagy of cardiomyocytes. Moreover, MALAT1 overexpression recruited EZH2 to TSC2 promoter regions to elevate H3K27me3 and epigenetically inhibited TSC2 transcription. Importantly, TSC2 overexpression suppressed mTOR signaling and then activated the autophagy. Further results showed that MALAT1 inhibited proliferation and enhanced apoptosis of cardiomyocytes through inhibiting TSC2 and autophagy.

Conclusion
These findings demonstrate that the increased MALAT1 expression induced by H/R injury enhances cardiomyocyte apoptosis through autophagy inhibition by regulating TSC2-mTOR signaling.
Pure pancreatic hepatoid carcinoma: a surgical case report and literature review
Authors: Tomino Takahiro , Ninomiya Mizuki , Matono Rumi , Narutomi Fumiya , Oshiro Yumi , Watanabe Kenji , Taniguchi Daisuke , Nishimura Sho , Zaitsu Yoko , Kajiwara Yuichiro , Yokota Tomoyuki , Minami Kazuhito , Nishizaki Takashi 
Published: November 2019

AbstractBackgroundHepatoid carcinoma (HC) is an extra-hepatic neoplasm that shares the morphological and immunohistochemical features of hepatocellular carcinoma. Pancreatic HC exists as either pure or combined type. Pure pancreatic HC is extremely rare, with only a few cases reported in the literature to date. Because of the rarity of pure pancreatic HC, its clinical features including incidence, behavior, and prognosis remain unclear. We herein report the case of a 56-year-old man who developed pure pancreatic HC treated with surgical resection. We also include a review of the existing literature.Case presentationA 56-year-old male patient was admitted to our hospital after a pancreatic cyst was identified by abdominal ultrasonography on a comprehensive medical examination. Endoscopic ultrasound revealed a cystic mass measuring 13 mm in size in the pancreatic head and a low-density mass measuring 16 mm in size in the pancreatic tail, which was partially enhanced on contrast-enhanced ultrasound. Contrast-enhanced computed tomography (CT) revealed a branch duct type intraductal papillary mucinous neoplasm in the pancreatic head and an early enhanced nodule measuring approximately 10 mm in size in the pancreatic tail. Endoscopic ultrasound-guided fine-needle aspiration of the hypervascular tumor was performed. The hypervascular tumor was suspected to be a solid pseudopapillary neoplasm. Laparoscopic spleen-preserving distal pancreatectomy was performed. Histology was identical to hepatocellular carcinoma of the liver. Immunohistochemically, the tumor cells were positive for hepatocyte paraffin 1, and a canalicular pattern was confirmed on the polyclonal carcinoembryonic antigen staining. The patient was diagnosed with a moderately differentiated pancreatic HC. The patient was followed up without adjuvant chemotherapy, and there was no evidence of recurrence at 6 months post-operatively.ConclusionsWe present a case of moderately differentiated pure pancreatic HC. For the accurate preoperative diagnosis of pure pancreatic HC, biopsy is preferred to cytology or preoperative imaging studies such as CT. The prognosis of pure pancreatic HC depends on its differentiation.
Histopathological study of invasive and non-invasive Entamoeba spp. in experimental rats
Authors: Al-Hilfi Athraa Abd-ulameer , Al-Malak Maha Khalil , Al-Tomah Muslim Abd-ulrahman 
Published: November 2019

Abstract
Background
The genus Entamoeba has many species that are invasive or non-invasive (E. histolytica, E. dispar, and E. moshkovskii).The invasive E. histolytica is the main pathogenic amoeba in human. Amoebiasis involves several stages starting with the adherence of the parasite to the intestinal epithelium, followed by degradation, tissue invasion, and distribution to other organs.

Results
The current study investigates the pathological changes of Entamoeba spp. infection in both rectum and cecum of experimental rats. The results showed the histological changes at the 7th, 14th, and 28th day post-infection for the three species. E. histolytica and E. moshkovskii infection showed less pathological changes compared to E. histolytica. These changes include the attachment of the trophozoites to the mucosal layer, significant surface epithelial changes such as dissociation and degeneration in the mucosal layer, and ulceration of the apical surface. Inflammatory cells infiltrate the varied regions, extending into the deep mucosa causing mild architectural alterations. These are features of amoebiasis.

Conclusion
The pathological changes reported in E. dispar and E. moshkovskii were less severe than E. histolytica.
The validity of HSG in infertility work up
Authors: Ahmed Shimaa Abdalla , Abo-taleb Hisham 
Published: November 2019

Abstract
Background
Our purpose was to evaluate the diagnostic accuracy of hysterosalpingography (HSG) in the diagnosis of the uterine cavity and tuboperitoneal abnormalities in infertile women. Reproducibility and consistency were also assessed. Two hundred infertile females underwent HSG, hysteroscopy, and/or laparoscopy as part of infertility workup. HSG examinations were retrospectively reviewed by three radiologists; we compared interobserver variability, and differences between the two results of reading the same examination after 3 months were compared to calculate intraobserver variability.
HSG sensitivity, specificity, PPV, NPV, and accuracy were calculated.

Results
The overall accuracy of HSG in diagnosing tubal, uterine cavity, and peritoneal abnormalities was 95.5%, 95%, and 89%, respectively (P value < 0.04).
HSG is reproducible in diagnosing normal versus abnormal examinations. Reproducibility in diagnosing uterine cavity, tubal, and peritoneal abnormalities was (ICC = 0.90), (ICC = 0.70), and (ICC = 0.31), respectively. Best agreement was seen in diagnosing luminal filling defect (sub mucous fibroid/polyp) (ICC = 0.90) (95% CI 0.86–0.98), whereas poorest agreement was found in diagnosing uterine adhesions (ICC = 0.13) (95% CI 0.10–0.13) and pelvic adhesions (ICC = 0.12) (95% CI 0.10–0.13) (P value < 0.03).
HSG consistency ranged from moderate to good (K = 0.49–0.79). It was highest in diagnosing normal versus abnormal examination (P value < 0.01); poorest in diagnosing pelvic adhesions.

Conclusion
HSG has high validity in negative results; it can minimize the use of invasive procedures. Laparoscopy is recommended in patients who had a pelvic disease or showing tubal obstruction on HSG.