bluuebunny/crossref_metadata_2025 huggingface dataset:
WGS based study of the population structure of Salmonella enterica serovar Infantis
Authors: Gymoese Pernille , Kiil Kristoffer , Torpdahl Mia , Østerlund Mark T. , Sørensen Gitte , Olsen John E. , Nielsen Eva M. , Litrup Eva
Published: November 2019

Background

SalmonellaInfantis (S. Infantis) is one of the most frequentSalmonellaserovars isolated from human cases of salmonellosis and the most detected serovar from animal and food sources in Europe. The serovar is commonly associated with poultry and there is increasing concern over multidrug resistant clones spreading worldwide, as the dominating clones are characterized by presence of large plasmids carrying multiple resistance genes. Increasing the knowledge of theS. Infantis population and evolution is important for understanding and preventing further spread.

In this study, we analysed a collection of strains representing different decades, sources and geographic locations. We analysed the population structure and the accessory genome, in particular we identified prophages with a view to understand the role of prophages in relation to the evolution of this serovar.

Results

We sequenced a global collection of 100 S. Infantis strains. A core-genome SNP analysis separated five strains in e-Burst Group (eBG) 297 with a long branch. The remaining strains, all in eBG31, were divided into three lineages that were estimated to have separated approximately 150 years ago. One lineage contained the vast majority of strains. In five of six clusters, no obvious correlation with source or geographical locations was seen. However, one cluster contained mostly strains from human and avian sources, indicating a clone with preference for these sources. The majority of strains within this cluster harboured a pESI-like plasmid with multiple resistance genes. Another lineage contained three genetic clusters with more rarely isolated strains of mainly animal origin, possibly less sampled or less infectious clones.

Conserved prophages were identified in all strains, likely representing bacteriophages which integrated into the chromosome of a common ancestor toS. Infantis. We also saw that some prophages were specific to clusters and were probably introduced when the clusters were formed.

Conclusions

This study analysed a globalS. Infantis population and described its genetic structure. We hypothesize that the population has evolved in three separate lineages, with one more successfully emerging lineage. We furthermore detected conserved prophages present in the entire population and cluster specific prophages, which probably shaped the population structure.
Candidate genes for grape white rot resistance based on SMRT and Illumina sequencing
Authors: Su Kai , Guo Yinshan , Zhao Yuhui , Gao Hongyan , Liu Zhendong , Li Kun , Ma Li , Guo Xiuwu
Published: November 2019

Background

White rot is one of the most dangerous fungal diseases and can considerably affect grape berry production and quality. However, few studies have focused on this disease, and thus, finding candidate white rot resistance genes is of great importance for breeding resistant grapevine cultivars. Based on field observations and indoor experiments, the cultivars “Victoria” and “Zhuosexiang” showed significant differences in white rot resistance. For understanding the molecular mechanisms behind it, different phenotypes of grapevine leaves were used for RNA sequencing via Illumina and single-molecule real-time (SMRT) sequencing technology.

Results

A transcript library containing 53,906 reads, including known and novel transcripts, was constructed following the full-length transcriptome sequencing of the two grapevine cultivars. Genes involved in salicylic acid (SA) and jasmonic acid (JA) synthesis pathways showed different expression levels. Furthermore, four key transcription factors (TFs), NPR1, TGA4, Pti6, and MYC2, all involved in the SA and JA signal pathways were identified, and the expression profile revealed the different regulation of the pathogenesis related protein1 (PR1) resistance gene, as mediated by the four TFs.

Conclusions

Full-length transcript sequencing can substantially improve the accuracy and integrity of gene prediction and gene function research in grapevine. Our results contribute to identify candidate resistance genes and improve our understanding of the genes and regulatory mechanisms involved in grapevine resistance to white rot.
Attitudes of primary care physicians toward prescribing buprenorphine: a narrative review
Authors: Louie Dexter L. , Assefa Mehret T. , McGovern Mark P.
Published: November 2019

Background

The opioid epidemic is a major public health issue associated with significant overdose deaths. Effective treatments exist, such as the medication buprenorphine, but are not widely available. This narrative review examines the attitudes of primary care providers (PCPs) toward prescribing buprenorphine.

Methods

Narrative review of 20 articles published after the year 2000, using the Consolidated Framework for Implementation Research (CFIR) to organize the findings.

Results

Three of the five CFIR domains (“Intervention Characteristics,” “Outer Setting,” “Inner Setting”) were strongly represented in our analysis. Providers were concerned about the clientele associated with buprenorphine, diversion, and their self-efficacy in prescribing the medication. Some believed that buprenorphine does not belong in the discipline of primary care. Other barriers included philosophical objections and stigma toward substance use disorders. Notably, two studies reported a shift in attitudes once physicians prescribed buprenorphine to actual patients.

Conclusions

Negative attitudes toward buprenorphine encompassed multi-layered concerns, ranging from skepticism about the medication itself, the behaviors of patients with opioid use disorders, and beliefs regarding substance use disorders more generally. We speculate, however, that negative attitudes may be improved by tailoring support strategies that address providers’ self-efficacy and level of knowledge.
Application value of nomogram and prognostic factors of gastric cancer patients who underwent D2 radical lymphadenectomy
Authors: Mu Guang-Chuan , Huang Yuan , Liu Zhi-Ming , Wu Xiang-Hua , Qin Xin-Gan , Chen Zhi-Bai
Published: November 2019

Background

The aim of this study was to explore the prognostic factors and establish a nomogram to predict the long-term survival of gastric cancer patients.

Methods

The clinicopathological data of 421 gastric cancer patients, who were treated with radical D2 lymphadenectomy by the same surgical team between January 2009 and March 2017, were collected. The analysis of long-term survival was performed using Cox regression analysis. Based on the multivariate analysis results, a prognostic nomogram was formulated to predict the 5-year survival rate probability.

Results

In the present study, the total overall 3-year and 5-year survival rates were 58.7 and 45.8%, respectively. The results of the univariate Cox regression analysis revealed that tumor staging, tumor location, Borrmann type, the number of lymph nodes dissected, the number of lymph node metastases, positive lymph nodes ratio, lymphocyte count, serum albumin, CEA, CA153, CA199, BMI, tumor size, nerve invasion, and vascular invasion were prognostic factors for gastric cancer (all,P < 0.05). However, merely tumor staging, tumor location, positive lymph node ratio, CA199, BMI, tumor size, nerve invasion, and vascular invasion were independent risk factors, based on the results of the multivariate Cox regression analysis (all,P < 0.05). The nomogram based on eight independent prognostic factors revealed a well-degree of differentiation with a concordance index of 0.76 (95% CI: 0.72–0.79,P < 0.001), which was better than the AJCC-7 staging system (concordance index = 0.68).

Conclusion

The present study established a nomogram based on eight independent prognostic factors to predict long-term survival in gastric cancer patients. The nomogram would be beneficial for more accurately predicting the prognosis of gastric cancer, and provide important basis for making individualized treatment plans following surgery.
Adding trans-abdominal elastography to the diagnostic tool for an ileal gastrointestinal stromal tumor: a case report
Authors: Lien Wan-Ching , Lee Po-Chu , Lin Min-Tsan , Chang Chih-Heng , Wang Hsiu-Po
Published: November 2019

Background

Diagnosis of gastrointestinal stromal tumors (GISTs) in the distal small intestine is difficult by endoscopic ultrasound. This is the first reported case of an ileal GIST, which is diagnosed by transabdominal sonography and strain elastography.

Case presentation

A 75 y/o woman presented with tarry stool and dizziness. No definite bleeder could be identified by esophagogastroduodenoscopy and colonoscopy. The transabdominal sonography revealed a large heterogeneous tumor involving the muscular layer of the ileum. Strain elastography showed the strain ratio was 6.51. Strain histogram was skewed to the blue side, and mean color value was 230.5, signifying a stiff tumor. GIST was highly suspected. The patient underwent laparoscope-assisted tumor excision and the histological examination confirmed a malignant GIST. The patient was discharged without postoperative event.

Conclusion

Transabdominal strain elastography could play a role to discriminate small bowel GISTs and other submucosal tumors, especially in the location with difficulty in endoscopic ultrasound.
Desmopressin and bleeding risk after percutaneous kidney biopsy
Authors: Athavale Ambarish , Kulkarni Hemant , Arslan Cagil D. , Hart Peter
Published: November 2019

Background

Desmopressin is used to reduce bleeding after kidney biopsy but evidence supporting its use is weak, especially in patients with elevated creatinine. The present study was undertaken to evaluate efficacy of desmopressin in reducing bleeding after percutaneous kidney biopsy.

Methods

Retrospective cohort study. 269 of 322 patients undergoing percutaneous kidney biopsy between January 1, 2014 and January 31, 2018 were included. Patients had normal bleeding time, platelet count and coagulation profile. Primary outcome was defined as composite of hemoglobin drop ≥1 g/dL, hematoma on post biopsy ultrasound, gross hematuria, erythrocyte transfusion or angiography to stop bleeding. Association of desmopressin with outcomes was assessed using linear (for continuous variables) and logistic (for binary variables) regression models. Propensity score was used to minimize potential confounding.

Results

Desmopressin was administered to 100/269 (37.17%) patients. After propensity score adjustment patients who received desmopressin had increased odds of post biopsy bleeding [OR 3.88 (1.95–7.74), p < 0.001]. Creatinine at time of biopsy influenced bleeding risk; gender, emergent vs elective biopsy, obesity, AKI, diabetes, hypertension or bleeding time did not influence bleeding risk. Administration of desmopressin to patients with serum creatinine ≥1.8 mg/dL decreased bleeding risk [OR 2.11 (95% CI 0.87–5.11), p = 0.09] but increased bleeding risk when serum creatinine was < 1.8 mg/dL (OR 9.72 (95% CI 2.95–31.96), p < 0.001).

Conclusion

Desmopressin should not be used routinely prior to percutaneous kidney biopsy in patients at low risk for bleeding but should be reserved for patients who are at high risk for bleeding.
Classification and management of epilepsy and epileptic syndromes in a cohort of 202 school children- a 2 year follow up study- Sudan
Authors: Mohamed Inaam N. , Elseed Maha A. , Mohamed Somia , Alsir Ali , Hamid Emtinan K. , Omer Ilham M. , Elsadig Sara M. , Gerais Yasmin M. , Osman Abdelgadir H. , Bakhiet Aisha M. , Hamed Ahlam A.
Published: November 2019

Background

In this paper, seizure types, and epilepsy syndromes are elucidated as per ILAE (2010) classification. A brief outline of the antiepileptic drug regimens used and the outcome of seizure control in a two -year period is presented. The applicability of the ILAE classification in resource limited countries has been revisited.

Methods

This is a descriptive prospective study, in which 202 patients were enrolled. The Cohort group was seen and evaluated by a pediatric neurologist at the Pediatric neurology Outpatients Department (OPD). Epilepsy was classified using the International League Against Epilepsy (ILAE) classification (2005–2009) report. All patients had an Electroencephalogram (EEG) at the start of the study, and this was repeated as deemed appropriate. Brain imaging (MRI) was done to patients when indicated. Treatment decisions were made by pediatric neurologists. Outcomes were categorized into four groups: fully recovered, well controlled, partially controlled and uncontrolled.

Results

The mean age is 10.5 + 2.7 years. Male to female ratio was 1.7: 1. Thirty five (17.3%) patients had generalized onset seizures, 46(22.8%) had focal onset seizures, 104(51.5%) had a specific epilepsy syndrome, and 17(8.4%) patients were unclassified. 170 (84.2%) patients were on mono-therapy on their initial visit, 30(14.8%) were on two Antiepileptic Drugs (AEDs) while two (1.0%) patients were on poly-therapy. After 2 years; 155(76.7%) patients were on mono-therapy, 36(17.8%) on two AEDs while ten were (4.0%) on polytherapy. One eighty (88.2%) patients were controlled. Fifteen (7.4%) of them were off medication after being seizure free for 2 years. Twenty (9.8%) have partial control, while two (1.0%) patients were uncontrolled. Patients with focal epilepsy, those on polytherapy and those with abnormal imaging had poor prognosis.

Conclusions

The ILAE classification can be used in resource limited countries. Childhood epilepsies have a good prognosis provided they are well classified and treated.
Efficacy, safety and feasibility of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric patients receiving moderately and highly emetogenic chemotherapy – results of a non-interventional observation study
Authors: Willier Semjon , Cabanillas Stanchi Karin Melanie , von Have Martina , Binder Vera , Blaeschke Franziska , Feucht Judith , Feuchtinger Tobias , Döring Michaela
Published: November 2019

Background

Chemotherapy-induced nausea and vomiting (CINV) belong among the most burdensome side effects in hemato-oncology. Mostly, a combination of ondansetron and dexamethasone is used as antiemetic prophylaxis in pediatric patients undergoing emetogenic chemotherapy. However, dexamethasone is prohibited in different pediatric chemotherapy protocols. Currently, data on the use of ondansetron with the new antiemetic agent fosaprepitant without dexamethasone is not available for pediatric patients.

Methods

In this non-interventional observation study, 79 pediatric patients with a median age of 8.0 years (range 0.5–17.9 years) who received a CINV prophylaxis regimen with either fosaprepitant (4 mg/kg; maximum 150 mg) and ondansetron (as 24-h continuous infusion) (n = 40; fosaprepitant group/FG) or ondansetron only (n = 39; control group/CG) during moderately or highly emetogenic chemotherapy were analyzed. The groups were analyzed and compared for frequency of vomiting, administered doses of on-demand antiemetic dimenhydrinate and adverse events during the acute (0-24 h after chemotherapy administration) and delayed (> 24 h–120 h) CINV phases.

Results

A total of 112 and 116 chemotherapy blocks were analyzed in the fosaprepitant and the control group, respectively. The emetogenic potential of the administered chemotherapy did not significantly differ (p = 0.8812) between the two cohorts. In the acute CINV phase, the percentage of patients experiencing vomiting (n = 26 patients) and the vomiting events were significantly higher (p = 0.0005 and p < 0.0001, respectively) in the CG (n = 26 patients (66.7%); 88 events) compared with the FG (n = 10 patients (25.0%); 37 events). In the delayed CINV phase, the percentage of patients experiencing vomiting and the vomiting events were also significantly higher (p = 0.0017 and p < 0.0001, respectively) in the CG (n = 31 patients (79.5%); 164 events) compared with the FG (n = 17 patients (42.5%); 103 events). Additionally, significantly more dimenhydrinate doses were administered in the CG compared with the FG patients (n = 322/n = 198; p < 0.0001). The occurrence of adverse events did not significantly differ between the two groups (p > 0.05).

Conclusion

Fosaprepitant (4.0 mg/kg) in addition to ondansetron, without application of dexamethasone, was well tolerated, safe, effective and superior to ondansetron only as CINV prophylaxis in pediatric patients during moderately and highly emetogenic chemotherapy.
Gastrointestinal stromal tumor with intracranial metastasis: case presentation and systematic review of literature
Authors: Prablek Marc , Srinivasan Visish M. , Srivatsan Aditya , Holdener Stephanie , Oneissi Mazen , Heck Kent A. , Jalali Ali , Mandel Jacob , Viswanathan Ashwin , Patel Akash J.
Published: November 2019

Background

Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms “‘gastrointestinal stromal tumor’ AND brain AND metastasis”” was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included.

Case presentation

A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day).

Conclusions

Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.
Wearable systems for shoulder kinematics assessment: a systematic review
Authors: Carnevale Arianna , Longo Umile Giuseppe , Schena Emiliano , Massaroni Carlo , Lo Presti Daniela , Berton Alessandra , Candela Vincenzo , Denaro Vincenzo
Published: November 2019

Background

Wearable sensors are acquiring more and more influence in diagnostic and rehabilitation field to assess motor abilities of people with neurological or musculoskeletal impairments. The aim of this systematic literature review is to analyze the wearable systems for monitoring shoulder kinematics and their applicability in clinical settings and rehabilitation.

Methods

A comprehensive search of PubMed, Medline, Google Scholar and IEEE Xplore was performed and results were included up to July 2019. All studies concerning wearable sensors to assess shoulder kinematics were retrieved.

Results

Seventy-three studies were included because they have fulfilled the inclusion criteria. The results showed that magneto and/or inertial sensors are the most used. Wearable sensors measuring upper limb and/or shoulder kinematics have been proposed to be applied in patients with different pathological conditions such as stroke, multiple sclerosis, osteoarthritis, rotator cuff tear. Sensors placement and method of attachment were broadly heterogeneous among the examined studies.

Conclusions

Wearable systems are a promising solution to provide quantitative and meaningful clinical information about progress in a rehabilitation pathway and to extrapolate meaningful parameters in the diagnosis of shoulder pathologies. There is a strong need for development of this novel technologies which undeniably serves in shoulder evaluation and therapy.
A cross-sectional study of environmental, dog, and human-related risk factors for positive canine leptospirosis PCR test results in the United States, 2009 to 2016
Authors: Smith Amanda M. , Arruda Andréia Gonçalves , Evason Michelle D. , Weese J. S. , Wittum Thomas E. , Szlosek Donald , Stull Jason W.
Published: November 2019

Background

Canine leptospirosis is a reemerging zoonotic disease concern in North America, and a better understanding of its epidemiology is needed. Wide-scale use and subsequent analyses of polymerase chain reaction (PCR) testing may provide additional insight into leptospirosis. This study aimed to describe temporal trends, to descriptively map, and to identify environmental, dog, and human-level factors associated with positive canine leptospirosis PCR test results in the United States.

Results

Data obtained from IDEXX Laboratories, Inc. on 40,118 canine leptospirosis PCR tests run in the United States between 2009 and 2016 were evaluated. Climate and socioeconomic (e.g. urban influence, income) data were obtained from public databases. Choropleth maps were created to identify high test-positive proportion areas and a cross-sectional analysis was completed with generalized (univariable, followed by multivariable) mixed logistic regression models accounting for county within state to identify significant predictors for a positive test. Overall test-positive proportion was 5.4% across the United States, with the regional point estimate highest in the southwest (8.1%). In the final multivariable model, the odds of a positive test were greater for male dogs (Odds Ratio [OR] = 1.28) and dogs 0–4 years of age (ORs ranged from 0.35–0.71 for the other age groups). The odds of a positive test were greater for dogs living in areas with wet environmental conditions (OR = 1.24). Season and temperature, as well as the interaction between them, were significant predictors of a positive test. Dogs had a greater probability of testing positive during cool temperatures (< 4 °C) compared to the other temperature categories in the fall season.

Conclusions

These findings based on PCR testing allow for an improved understanding of factors influencing a positive canine leptospirosis PCR test and will assist targeted education and prevention efforts.
Classification of glioma based on prognostic alternative splicing
Authors: Li Yaomin , Ren Zhonglu , Peng Yuping , Li Kaishu , Wang Xiran , Huang Guanglong , Qi Songtao , Liu Yawei
Published: November 2019

Background

Previously developed classifications of glioma have provided enormous advantages for the diagnosis and treatment of glioma. Although the role of alternative splicing (AS) in cancer, especially in glioma, has been validated, a comprehensive analysis of AS in glioma has not yet been conducted. In this study, we aimed at classifying glioma based on prognostic AS.

Methods

Using the TCGA glioblastoma (GBM) and low-grade glioma (LGG) datasets, we analyzed prognostic splicing events. Consensus clustering analysis was conducted to classified glioma samples and correlation analysis was conducted to characterize regulatory network of splicing factors and splicing events.

Results

We analyzed prognostic splicing events and proposed novel splicing classifications across pan-glioma samples (labeled pST1–7) and across GBM samples (labeled ST1–3). Distinct splicing profiles between GBM and LGG were observed, and the primary discriminator for the pan-glioma splicing classification was tumor grade. Subtype-specific splicing events were identified; one example is AS of zinc finger proteins, which is involved in glioma prognosis. Furthermore, correlation analysis of splicing factors and splicing events identified SNRPB and CELF2 as hub splicing factors that upregulated and downregulated oncogenic AS, respectively.

Conclusion

A comprehensive analysis of AS in glioma was conducted in this study, shedding new light on glioma heterogeneity and providing new insights into glioma diagnosis and treatment.
Diabetes mellitus and other cardiovascular risk factors in lower-extremity peripheral artery disease versus coronary artery disease: an analysis of 1,121,359 cases from the nationwide databases
Authors:   the J-EVT and J-PCI investigators, Takahara Mitsuyoshi , Iida Osamu , Kohsaka Shun , Soga Yoshimitsu , Fujihara Masahiko , Shinke Toshiro , Amano Tetsuya , Ikari Yuji
Published: November 2019

Background

Lower-extremity peripheral artery disease (LE-PAD) and coronary artery disease (CAD) are both pathologically rooted in atherosclerosis, and their shared clinical features regarding the exposure to cardiovascular risk factors have been emphasized. However, comparative data of the two cardiovascular diseases (CVDs) were so far lacking. The purpose of this study was to directly compare the clinical profile between cases undergoing endovascular therapy (EVT) for LE-PAD and those undergoing percutaneous coronary intervention (PCI).

Methods

Data were extracted from the nationwide procedural databases of EVT and PCI in Japan (J-EVT and J-PCI) between 2012 and 2017. A total of 1,121,359 cases (103,887 EVT cases for critical limb ischemia [CLI] or intermittent claudication and 1,017,472 PCI cases for acute coronary syndrome [ACS] or stable angina) were analyzed. Heterogeneity in clinical profile between CVDs was evaluated using the C statistic of the logistic regression model for which dependent variable was one CVD versus another, and explanatory variables were clinical profile. When two CVDs were completely discriminated from each other by the developed model, the C statistic (discrimination ability) of the model would be equal to 1, indicating that the two CVDs were completely different in clinical profile. On the other hand, when two CVDs were identical in clinical profile, the developed model would not discriminate them at all, with the C statistic equal to 0.5.

Results

Mean age was 73.5 ± 9.3 years in LE-PAD patients versus 70.0 ± 11.2 years in CAD patients (P < 0.001). The prevalence of diabetes mellitus and end-stage renal disease was 1.96- and 6.39-times higher in LE-PAD patients than in CAD patients (both P < 0.001). The higher prevalence was observed irrespective of age group. The exposure to other cardiovascular risk factors and the likelihood of cardiovascular risk clustering also varied between the diseases. The between-disease heterogeneity in patient profile was particularly evident between CLI and ACS, with the C statistic equal to 0.833 (95% CI 0.831–0.836).

Conclusions

The current study, an analysis based on nationwide procedural databases, confirmed that patient profiles were not identical but rather considerably different between clinically significant LE-PAD and CAD warranting revascularization.
Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion
Authors: Eerola Sini K. , Santio Niina M. , Rinne Sanni , Kouvonen Petri , Corthals Garry L. , Scaravilli Mauro , Scala Giovanni , Serra Angela , Greco Dario , Ruusuvuori Pekka , Latonen Leena , Rainio Eeva-Marja , Visakorpi Tapio , Koskinen Päivi J.
Published: November 2019

Background

Progression of prostate cancer from benign local tumors to metastatic carcinomas is a multistep process. Here we have investigated the signaling pathways that support migration and invasion of prostate cancer cells, focusing on the role of the NFATC1 transcription factor and its post-translational modifications. We have previously identified NFATC1 as a substrate for the PIM1 kinase and shown that PIM1-dependent phosphorylation increases NFATC1 activity without affecting its subcellular localization. Both PIM kinases and NFATC1 have been reported to promote cancer cell migration, invasion and angiogenesis, but it has remained unclear whether the effects of NFATC1 are phosphorylation-dependent and which downstream targets are involved.

Methods

We used mass spectrometry to identify PIM1 phosphorylation target sites in NFATC1, and analysed their functional roles in three prostate cancer cell lines by comparing phosphodeficient mutants to wild-type NFATC1. We used luciferase assays to determine effects of phosphorylation on NFAT-dependent transcriptional activity, and migration and invasion assays to evaluate effects on cell motility. We also performed a microarray analysis to identify novel PIM1/NFATC1 targets, and validated one of them with both cellular expression analyses and in silico in clinical prostate cancer data sets.

Results

Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells. We observed that also PIM2 and PIM3 can phosphorylate NFATC1, and identified several novel putative PIM1/NFATC1 target genes. These include the ITGA5 integrin, which is differentially expressed in the presence of wild-type versus phosphorylation-deficient NFATC1, and which is coexpressed with PIM1 and NFATC1 in clinical prostate cancer specimens.

Conclusions

Based on our data, phosphorylation of PIM1 target sites stimulates NFATC1 activity and enhances its ability to promote prostate cancer cell migration and invasion. Therefore, inhibition of the interplay between PIM kinases and NFATC1 may have therapeutic implications for patients with metastatic forms of cancer.

Graphical abstract
GPR110 (ADGRF1) mediates anti-inflammatory effects of N-docosahexaenoylethanolamine
Authors: Park Taeyeop , Chen Huazhen , Kim Hee-Yong
Published: November 2019

Background

Neuroinflammation is a widely accepted underlying condition for various pathological processes in the brain. In a recent study, synaptamide, an endogenous metabolite derived from docosahexaenoic acid (DHA, 22:6n-3), was identified as a specific ligand to orphan adhesion G-protein-coupled receptor 110 (GPR110, ADGRF1). Synaptamide has been shown to suppress lipopolysaccharide (LPS)-induced neuroinflammation in mice, but involvement of GPR110 in this process has not been established. In this study, we investigated the possible immune regulatory role of GPR110 in mediating the anti-neuroinflammatory effects of synaptamide under a systemic inflammatory condition.

Methods

For in vitro studies, we assessed the role of GPR110 in synaptamide effects on LPS-induced inflammatory responses in adult primary mouse microglia, immortalized murine microglial cells (BV2), primary neutrophil, and peritoneal macrophage by using quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) as well as neutrophil migration and ROS production assays. To evaluate in vivo effects, wild-type (WT) and GPR110 knock-out (KO) mice were injected with LPS intraperitoneally (i.p.) or TNF intravenously (i.v.) followed by synaptamide (i.p.), and expression of proinflammatory mediators was measured by qPCR, ELISA, and western blot analysis. Activated microglia in the brain and NF-kB activation in cells were examined microscopically after immunostaining for Iba-1 and RelA, respectively.

Results

Intraperitoneal (i.p.) administration of LPS increased TNF and IL-1β in the blood and induced pro-inflammatory cytokine expression in the brain. Subsequent i.p. injection of the GPR110 ligand synaptamide significantly reduced LPS-induced inflammatory responses in wild-type (WT) but not in GPR110 knock-out (KO) mice. In cultured microglia, synaptamide increased cAMP and inhibited LPS-induced proinflammatory cytokine expression by inhibiting the translocation of NF-κB subunit RelA into the nucleus. These effects were abolished by blocking synaptamide binding to GPR110 using an N-terminal targeting antibody. GPR110 expression was found to be high in neutrophils and macrophages where synaptamide also caused a GPR110-dependent increase in cAMP and inhibition of LPS-induced pro-inflammatory mediator expression. Intravenous injection of TNF, a pro-inflammatory cytokine that increases in the circulation after LPS treatment, elicited inflammatory responses in the brain which were dampened by the subsequent injection (i.p.) of synaptamide in a GPR110-dependent manner.

Conclusion

Our study demonstrates the immune-regulatory function of GPR110 in both brain and periphery, collectively contributing to the anti-neuroinflammatory effects of synaptamide under a systemic inflammatory condition. We suggest GPR110 activation as a novel therapeutic strategy to ameliorate inflammation in the brain as well as periphery.
Long-term follow-up outcomes for patients undergoing primary total hip arthroplasty with uncemented versus cemented femoral components: a retrospective observational study with a 5-year minimum follow-up
Authors: Liu Tiejian , Hua Xiaoxiao , Yu Weiguang , Lin Jinluan , Zhao Mingdong , Liu Jun , Zeng Xianshang
Published: November 2019

Background

This retrospective analysis compared the long-term outcomes for patients with a femoral neck fracture (AO/OTA type 31B) treated with a primary unilateral total hip arthroplasty with uncemented or cemented femoral components (UTHA or CTHA, respectively).

Methods

We conducted a retrospective cohort study using the South China Hip Arthroplasty Database. We identified 422 patients with femoral neck fracture (AO/OTA type 31B) who were previously treated with primary unilateral UTHA or CTHA between 2007 and 2015, with follow-up until 2019. Follow-up occurred 1, 3, 6 and 12 months postoperatively and yearly thereafter. The primary outcome was the Harris hip score (HHS). The secondary outcome was the orthopaedic complication rate.

Results

In total, 324 patients (UTHA n = 160, mean age 68.61 ± 7.49 years; CTHA n = 164, mean age 68.75 ± 7.04 years) were evaluated for study eligibility. The median follow-up was 73.3 months (range, 11.6–89.2 months). At the final follow-up, HHS was 74.09 ± 6.23 vs 79.01 ± 10.21 (UTHA vs CTHA, p = 0.012). Significant differences were detected in the incidence of prosthetic revision, loosening, and periprosthetic fracture between the UTHA and CTHA groups (7.5% for UTHA vs 1.8% for CTHA, p = 0.015; 17.5% for UTHA vs 8.5% for CTHA, p = 0.016; 11.9% for UTHA vs 4.9% for CTHA, p = 0.021, respectively).

Conclusion

In this setting, CTHA demonstrated superiority to UTHA by improving functional outcomes and decreasing complication rates.
Multilevel instrumented posterolateral lumbar spine fusion with an allogeneic cellular bone graft
Authors: Hall John F. , McLean Julie B. , Jones Savannah M. , Moore Mark A. , Nicholson Michelle D. , Dorsch Kimberly A.
Published: November 2019

Background

Low back pain (LBP) is the leading cause of absence from work, disability, and impaired quality of life. Fusion surgery may be indicated when non-operative treatments have failed to provide relief. Surgery may include the use of fusion-enhancing implants, such as cellular bone allografts (CBAs). The purpose of this retrospective study was to evaluate efficacy and safety of one CBA (V-CBA) in patients who underwent instrumented posterolateral fusion (IPLF).

Methods

Retrospective data were collected from 150 consecutive patients who had undergone IPLF surgery between January 1, 2015, and March 31, 2018, in which V-CBA was used. All surgeries were performed by one surgeon. V-CBA was mixed with local autograft bone. Patient diagnoses included degenerative disc disease, spondylosis, spondylolisthesis, or spondylolysis with or without stenosis. Standing anteroposterior (AP) and lateral images were collected prior to surgery and again at the terminal visit, which took place between 6 and 33 months post-operatively. De-identified images were assessed radiologically. Adverse events were documented. The primary composite endpoint of fusion status was dependent upon two main criteria: bridging bone per the Lenke scale (classified as “A” definitely solid or “B” possibly solid) and posterior hardware status (intact). Lenke scale C or D were categorized as pseudarthrosis.

Results

Eighty-seven male and 63 female patients (613 levels total) underwent IPLF in which V-CBA was implanted. An average of 4.1 levels was treated, with 59.3% of patients having undergone treatment for more than 3 levels. Twenty-nine percent of patients had diabetes. Fifty-two percent of patients had previously used nicotine products, and 12% were current smokers. Sixteen serious adverse events were recorded and included lumbar seroma, cerebrospinal fluid leak, wound dehiscence, pneumonia, urinary tract infection, and myocardial infarction. Successful fusion (Lenke scale “A” or “B”) was recorded in 148 out of 150 patients (98.7%), or 608 out of 613 levels. The total pseudarthrosis rate was 0.8%.

Conclusions

The use of V-CBA combined with local autograft in multilevel IPLF resulted in successful fusions in 98.7% of patients. These results are particularly robust given the complex nature of many of these cases: 89 patients had 4 or more surgical levels, and many patients had multiple comorbidities.

Level of evidence

IV
A meta-analysis comparing tenotomy or tenodesis for lesions of the long head of the biceps tendon with concomitant reparable rotator cuff tears
Authors: Na Yuyan , Zhu Yong , Shi Yuting , Ren Yizhong , Zhang Ting , Liu Wanlin , Han Changxu
Published: November 2019

Background

The best treatment for lesions of the long head of the biceps tendon (LHBT) with concomitant reparable rotator cuff tears is still controversial. The purpose of the meta-analysis was to compare clinical outcomes of biceps tenotomy and tenodesis for LHBT lesions.

Methods

A literature retrieval was conducted in MEDLINE, Embase, and Cochrane Library from 1979 to March 2018. Comparative studies (level of evidence I or II) comparing tenotomy and tenodesis for LHBT lesions with concomitant reparable rotator cuff tears were included. Risk of bias for all included studies was assessed using the Cochrane Collaboration’s risk of bias tool. Clinical outcomes compared were Popeye sign, Constant score, VAS pain score, cramping pain, elbow flexion and forearm supination strength, and re-tear of the rotator cuff.

Results

Two randomized controlled trials (RCTs) and five prospective cohort studies (PCS) with 288 biceps tenotomy patients and 303 biceps tenodesis patients were included in this review. Tenotomy resulted in significantly greater rates of Popeye sign (RR, 2.70 [95% CI, 1.80 to 4.04]; P < 0.01) and a less favorable Constant score (MD, − 1.09 [95% CI, − 1.90 to − 0.28]; P < 0.01) compared to tenodesis. No significant heterogeneity was found between the two groups across all parameters except forearm supination strength.

Conclusions

The current evidence indicates that biceps tenodesis for LHBT lesions with concomitant reparable rotator cuff tears results in decreased rate of Popeye sign and improved Constant score compared to biceps tenotomy.

Trial registration

PROSPERO, CRD42018105504. Registered on 13 August 2018.
Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study
Authors: Miesbach Wolfgang , Menne Jan , Bommer Martin , Schönermarck Ulf , Feldkamp Thorsten , Nitschke Martin , Westhoff Timm H. , Seibert Felix S. , Woitas Rainer , Sousa Rui , Wolf Michael , Walzer Stefan , Schwander Björn
Published: November 2019

Background

Acquired thrombotic thrombocytopenic Purpura (aTTP) is a life-threatening ultra-orphan disease with a reported annual incidence between 1.5 and 6.0 cases per million in Europe and mainly affecting otherwise young and healthy adults aged 40 years on average. The goal of this study was to assess the incidence of aTTP in Germany.

Methods

A systematic review was performed to determine the published evidence on the aTTP epidemiology in Germany. To obtain additional evidence on the proportion of aTTP cases within the national Thrombotic Microangiopathy (TMA) population a hospital-level study was performed, using a retrospective data collection approach. Diagnosis of aTTP was confirmed if ADAMTS13 level were < 10% and/or the medical records explicitly mentioned aTTP diagnosis. The aggregated hospital data were then projected to the national level using logistic regression techniques.

Results

The systematic literature search did not provide incidence estimates of aTTP in Germany. Eight centers (≈27% of the top 30 TMA hospitals) delivered data according to a predefined data collection form. On average (year 2014–2016) a total number of 172 aTTP episodes per year was projected (95% confidence interval [95%CI]: 132–212). The majority were newly diagnosed aTTP cases (n = 121; 95%CI: 105–129), and 51 were recurrent aTTP cases (95%CI: 27–84). The average annual projected incidence (year 2014–2016) of aTTP episodes was 2.10 per million inhabitants in Germany (95%CI: 1.60–2.58).

Conclusions

The determined annual incidence of newly diagnosed aTTP cases and the overall annual incidence of aTTP episodes in Germany confirm the ultra-orphan character of aTTP. An external validation against international registries (France, UK and USA) shows that our findings are quite comparable with those international incidence rates.
Socio-cultural change in conflict and post conflict settings: five decades of giving birth in Cambodia
Authors: Ros Bandeth , Lê Gillian , Fustukian Suzanne , McPake Barbara
Published: November 2019

Background

This paper explores the changing experience of giving birth in Cambodia over a 53-year period. During this time, Cambodian people experienced armed conflict, extreme privation, foreign invasion, and civil unrest.

Methods

An historical perspective was used to explore the changing place and nature of birth assistance given to Cambodian women between 1950 and 2013. Twenty-four life histories of poor and non-poor Cambodians aged 40–74 were gathered and analysed using a grounded thematic approach.

Results

In the early lives of the respondents, almost all births occurred at home and were assisted by Traditional Birth Attendants. In modern times, towards the end of their lives, the respondents’ grand-children and great grand-children are almost universally born in institutions in which skilled birth attendants are available. Respondents recognise that this is partly due to the availability of modern health care facilities but also describe the process by which attitudes to institutional and homebirth changed over time. Interviews can also chart the increasing awareness of the risks of homebirth, somewhat influenced by the success of health education messages transmitted by public health authorities.

Conclusions

The life histories provide insight into the factors driving the underlying cultural change: a modernising supply side; improving transport and communications infrastructure. In addition, a step-change occurred in the aftermath of the conflict with significant influence of extensive contact with the Vietnamese recognised.

Trial registration

None.
Identification of urban particulate matter-induced disruption of human respiratory mucosa integrity using whole transcriptome analysis and organ-on-a chip
Authors: Byun Junhyoung , Song Boa , Lee Kyungwoo , Kim Byoungjae , Hwang Hae Won , Ok Myung-Ryul , Jeon Hojeong , Lee Kijeong , Baek Seung-Kuk , Kim Sang-Heon , Oh Seung Ja , Kim Tae Hoon
Published: November 2019

Background

Exposure to air particulate matter (PM) is associated with various diseases in the human respiratory system. To date, most in vitro studies showing cellular responses to PM have been performed in cell culture using a single cell type. There are few studies considering how multicellular networks communicate in a tissue microenvironment when responding to the presence of PM. Here, an in vitro three-dimensional (3D) respiratory mucosa-on-a-chip, composed of human nasal epithelial cells, fibroblasts, and endothelial cells, is used to recapitulate and better understand the effects of urban particulate matter (UPM) on human respiratory mucosa.

Results

We hypothesized that the first cells to contact with UPM, the nasal epithelial cells, would respond similar to the tissue microenvironment, and the 3D respiratory mucosa model would be a suitable platform to capture these events. First, whole transcriptome analysis revealed that UPM induced gene expression alterations in inflammatory and adhesion-related genes in human nasal epithelial cells. Next, we developed an in vitro 3D respiratory mucosa model composed of human nasal epithelial cells, fibroblasts, and endothelial cells and demonstrated that the model is structurally and functionally compatible with the respiratory mucosa. Finally, we used our model to expose human nasal epithelial cells to UPM, which led to a disruption in the integrity of the respiratory mucosa by decreasing the expression of zonula occludens-1 in both the epithelium and endothelium, while also reducing vascular endothelial cadherin expression in the endothelium.

Conclusions

We demonstrate the potential of the 3D respiratory mucosa model as a valuable tool for the simultaneous evaluation of multicellular responses caused by external stimuli in the human respiratory mucosa. We believe that the evaluation strategy proposed in the study will move us toward a better understanding of the detailed molecular mechanisms associated with pathological changes in the human respiratory system.
SEQdata-BEACON: a comprehensive database of sequencing performance and statistical tools for performance evaluation and yield simulation in BGISEQ-500
Authors: Zhou Yanqiu , Liu Chen , Zhou Rongfang , Lu Anzhi , Huang Biao , Liu Liling , Chen Ling , Luo Bei , Huang Jin , Tian Zhijian
Published: November 2019

Background

The sequencing platform BGISEQ-500 is based on DNBSEQ technology and provides high throughput with low costs. This sequencer has been widely used in various areas of scientific and clinical research. A better understanding of the sequencing process and performance of this system is essential for stabilizing the sequencing process, accurately interpreting sequencing results and efficiently solving sequencing problems. To address these concerns, a comprehensive database, SEQdata-BEACON, was constructed to accumulate the run performance data in BGISEQ-500.

Results

A total of 60 BGISEQ-500 instruments in the BGI-Wuhan lab were used to collect sequencing performance data. Lanes in paired-end 100 (PE100) sequencing using 10 bp barcode were chosen, and each lane was assigned a unique entry number as its identification number (ID). From November 2018 to April 2019, 2236 entries were recorded in the database containing 65 metrics about sample, yield, quality, machine state and supplies information. Using a correlation matrix, 52 numerical metrics were clustered into three groups signifying yield-quality, machine state and sequencing calibration. The distributions of the metrics also delivered information about patterns and rendered clues for further explanation or analysis of the sequencing process. Using the data of a total of 200 cycles, a linear regression model well simulated the final outputs. Moreover, the predicted final yield could be provided in the 15th cycle of the early stage of sequencing, and the corresponding R2 of the 200th and 15th cycle models were 0.97 and 0.81, respectively. The model was run with the test sets obtained from May 2019 to predict the yield, which resulted in an R2 of 0.96. These results indicate that our simulation model was reliable and effective.

Conclusions

Data sources, statistical findings and application tools provide a constantly updated reference for BGISEQ-500 users to comprehensively understand DNBSEQ technology, solve sequencing problems and optimize run performance. These resources are available on our website http://seqBEACON.genomics.cn:443/home.html.