bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular cloning of SLC35D3 and analysis of its role during porcine intramuscular preadipocyte differentiation
Authors: Li Wentong , Wu Keliang , Liu Ying , Yang Yalan , Wang Wenwen , Li Xiuxiu , Zhang Yanmin , Zhang Qin , Zhou Rong , Tang Hui
Published: February 2020

Background

Solute carrier family 35 (SLC35) is one of a large number of membrane transporter protein families. Member D3 of this family is thought to be involved in adipose deposition and metabolic control.

Results

We obtained 2238 bp cDNA of porcine SLC35D3, it contains a 1272 bp ORF, encoding a 423 amino acid polypeptide, and a 966 bp 3′ UTR. BLAST results revealed that the amino acid sequence of porcine SLC35D3 had the closest phylogenetic relationship with members of the genus Ovis aries. Further bioinformatics analysis showed that the SLC35D3 protein contains 8 transmembrane domains, and that there is no signal peptide structure. The secondary structure of the protein mainly contains 37.12% α-helixes, 7.8% in β-folds, and 33.57% random coils. mRNA expression analysis showed that SLC35D3 is expressed in lung, liver, heart, spleen, kidney, longissimus dorsi muscle (LDM), leaf fat (LF), and subcutaneous adipose tissue (SAT). To examine the effects of SLC35D3 expression on fat synthesis and catabolism, SLC35D3-siRNA was transfected into cultured intramuscular adipocytes. SLC35D3 silenced cells showed increased expression of genes related to fat synthesis, and increased deposition of intramuscular fat (IMF), abundance of lipid droplets, and the level of free fatty acid (FFA) in the culture medium. In contrast, the siRNA decreased the expression genes involved in fat catabolism.

Conclusions

Our results demonstrate that silenced SLC35D3 results in increased adipogenic processes in pig intramuscular adipocytes. These data represent the first exploration of SLC35D3 expression in swine, and provide valuable insights into the functions of SLC35D3 in adipocyte differentiation.
Inferring B cell specificity for vaccines using a Bayesian mixture model
Authors: Fowler Anna , Galson Jacob D. , Trück Johannes , Kelly Dominic F. , Lunter Gerton
Published: February 2020

Background

Vaccines have greatly reduced the burden of infectious disease, ranking in their impact on global health second only after clean water. Most vaccines confer protection by the production of antibodies with binding affinity for the antigen, which is the main effector function of B cells. This results in short term changes in the B cell receptor (BCR) repertoire when an immune response is launched, and long term changes when immunity is conferred. Analysis of antibodies in serum is usually used to evaluate vaccine response, however this is limited and therefore the investigation of the BCR repertoire provides far more detail for the analysis of vaccine response.

Results

Here, we introduce a novel Bayesian model to describe the observed distribution of BCR sequences and the pattern of sharing across time and between individuals, with the goal to identify vaccine-specific BCRs. We use data from two studies to assess the model and estimate that we can identify vaccine-specific BCRs with 69% sensitivity.

Conclusion

Our results demonstrate that statistical modelling can capture patterns associated with vaccine response and identify vaccine specific B cells in a range of different data sets. Additionally, the B cells we identify as vaccine specific show greater levels of sequence similarity than expected, suggesting that there are additional signals of vaccine response, not currently considered, which could improve the identification of vaccine specific B cells.
Biased visibility in Hi-C datasets marks dynamically regulated condensed and decondensed chromatin states genome-wide
Authors: Chandradoss Keerthivasan Raanin , Guthikonda Prashanth Kumar , Kethavath Srinivas , Dass Monika , Singh Harpreet , Nayak Rakhee , Kurukuti Sreenivasulu , Sandhu Kuljeet Singh
Published: February 2020

Background

Proximity ligation based techniques, like Hi-C, involve restriction digestion followed by ligation of formaldehyde cross-linked chromatin. Distinct chromatin states can impact the restriction digestion, and hence the visibility in the contact maps, of engaged loci. Yet, the extent and the potential impact of digestion bias remain obscure and under-appreciated in the literature.

Results

Through analysis of 45 Hi-C datasets, lamina-associated domains (LADs), inactive X-chromosome in mammals, and polytene bands in fly, we first established that the DNA in condensed chromatin had lesser accessibility to restriction endonucleases used in Hi-C as compared to that in decondensed chromatin. The observed bias was independent of known systematic biases, was not appropriately corrected by existing computational methods, and needed an additional optimization step. We then repurposed this bias to identify novel condensed domains outside LADs, which were bordered by insulators and were dynamically associated with the polycomb mediated epigenetic and transcriptional states during development.

Conclusions

Our observations suggest that the corrected one-dimensional read counts of existing Hi-C datasets can be reliably repurposed to study the gene-regulatory dynamics associated with chromatin condensation and decondensation, and that the existing Hi-C datasets should be interpreted with cautions.
Metabolic alterations provide insights into Stylosanthes roots responding to phosphorus deficiency
Authors: Luo Jiajia , Liu Yunxi , Zhang Huikai , Wang Jinpeng , Chen Zhijian , Luo Lijuan , Liu Guodao , Liu Pandao
Published: February 2020

Background

Phosphorus (P) deficiency is one of the major constraints limiting plant growth, especially in acid soils. Stylosanthes (stylo) is a pioneer tropical legume with excellent adaptability to low P stress, but its underlying mechanisms remain largely unknown.

Results

In this study, the physiological, molecular and metabolic changes in stylo responding to phosphate (Pi) starvation were investigated. Under low P condition, the growth of stylo root was enhanced, which was attributed to the up-regulation of expansin genes participating in root growth. Metabolic profiling analysis showed that a total of 256 metabolites with differential accumulations were identified in stylo roots response to P deficiency, which mainly included flavonoids, sugars, nucleotides, amino acids, phenylpropanoids and phenylamides. P deficiency led to significant reduction in the accumulation of phosphorylated metabolites (e.g., P-containing sugars, nucleotides and cholines), suggesting that internal P utilization was enhanced in stylo roots subjected to low P stress. However, flavonoid metabolites, such as kaempferol, daidzein and their glycoside derivatives, were increased in P-deficient stylo roots. Furthermore, the qRT-PCR analysis showed that a set of genes involved in flavonoids synthesis were found to be up-regulated by Pi starvation in stylo roots. In addition, the abundances of phenolic acids and phenylamides were significantly increased in stylo roots during P deficiency. The increased accumulation of the metabolites in stylo roots, such as flavonoids, phenolic acids and phenylamides, might facilitate P solubilization and cooperate with beneficial microorganisms in rhizosphere, and thus contributing to P acquisition and utilization in stylo.

Conclusions

These results suggest that stylo plants cope with P deficiency by modulating root morphology, scavenging internal Pi from phosphorylated metabolites and increasing accumulation of flavonoids, phenolic acids and phenylamides. This study provides valuable insights into the complex responses and adaptive mechanisms of stylo roots to P deficiency.
The viral prescription pad - a mixed methods study to determine the need for and utility of an educational tool for antimicrobial stewardship in primary health care
Authors: Lee Christine , Jafari Maryam , Brownbridge Regan , Phillips Casey , Vanstone Jason R.
Published: February 2020

Background

In order to combat rising rates of antimicrobial resistant infections, it is vital that antimicrobial stewardship become embedded in primary health care (PHC). Despite the high use of antimicrobials in PHC settings, there is a lack of data regarding the integration of antimicrobial stewardship programs (ASP) in non-hospital settings. Our research aimed to determine which antimicrobial stewardship interventions are optimal to introduce into PHC clinics beginning to engage with an ASP, as well as how to optimize those interventions. This work became focused specifically around management of viral upper respiratory tract infections (URTIs), as these infections are one of the main sources of inappropriate antibiotic use.

Methods

This mixed methods study of sequential explanatory design was developed through three research projects over 3 years in Regina, Saskatchewan, Canada. First, a survey of PHC providers was performed to determine their perceived needs from a PHC-based ASP. From this work, a “viral prescription pad” was developed to provide a tool to help PHC providers engage in patient education regarding appropriate antimicrobial use, specifically for URTIs. Next, interviews were performed with family physicians to discuss their perceived utility of this tool. Finally, we performed a public survey to determine preferences for the medium by which information is received regarding symptom management for viral URTIs.

Results

The majority of PHC providers responding to the initial survey indicated they were improperly equipped with tools to aid in promoting conversations with patients and providing education about the appropriate use of antimicrobials. Following dissemination of the viral prescription pad and semi-structured interviews with family physicians, the viral prescription pad was deemed to be a useful educational tool. However, about half of the physicians interviewed indicated they did not actually provide a viral prescription to patients when providing advice on symptom management for viral URTIs. When asked about their preferences, 76% of respondents to the public survey indicated they would prefer to receive written or a combination of verbal and written information in this circumstance.

Conclusions

PHC providers indicated a need for educational tools to promote conversations with patients and provide education about the appropriate use of antimicrobials. Viral prescription pads were regarded by family physicians and patients as useful tools in facilitating discussion on the appropriate use of antimicrobials. PHC providers should exercise caution in opting out of providing written forms of information, as many respondents to the general public survey indicated their preference in receiving both verbal and written information.
Profile of American tegumentary leishmaniasis in transmission areas in the state of Minas Gerais, Brazil, from 2007 to 2017
Authors: Pinto Mariana Olímpia Köhler Marra , de Oliveira Tiago Mendonça , de Assis Aguiar Andreza Nayla , Pinto Paulo Eustáquio Marra , Barbosa David Soeiro , de Araújo Diniz Soraia , Silva Marcos Xavier
Published: February 2020

Background

American tegumentary leishmaniasis (ATL) is a widespread anthropozoonosis caused by protozoa of the genus Leishmania and is considered a serious public health problem. The aim of this study was to provide a descriptive analysis of confirmed ATL cases and evaluate the spatial distribution of ATL in high-risk transmission areas from the state of Minas Gerais, Brazil.

Methods

An ecological, analytical, and retrospective study of the confirmed cases of ATL in Minas Gerais from 2007 to 2017 was conducted. To characterize these cases, multiple correspondence analysis and georeferencing of the ATL prevalence rates in the municipalities were conducted based on variables obtained at Sistema Nacional de Agravos de Notificação and Instituto Brasileiro de Geografia e Estatística databases.

Results

There were 13,025 confirmed cases of ATL from 74.4% (635) municipalities of Minas Gerais, corresponding to a prevalence rate of 66.5 cases for every 100,000 inhabitants. Males aged 20 to 59 years and individuals who attended elementary school were most affected with ATL. Multiple correspondence analysis presented an accumulated qui-squared value of 44.74%, proving that there was a relationship between the variables, including ethnicity, age, pregnancy status, zone of infection, and number of cases.

Conclusion

We confirmed that ATL is endemic to Minas Gerais, and there is high risk of infection within the municipalities due to a high rate of parasite transmission. The occurrence of infection in children, pregnant women, and the indigenous population demonstrates the need for the government to expand social policies aimed at vulnerable groups.
Computational MHC-I epitope predictor identifies 95% of experimentally mapped HIV-1 clade A and D epitopes in a Ugandan cohort
Authors: Bugembe Daniel Lule , Ekii Andrew Obuku , Ndembi Nicaise , Serwanga Jennifer , Kaleebu Pontiano , Pala Pietro
Published: February 2020

Background

Identifying immunogens that induce HIV-1-specific immune responses is a lengthy process that can benefit from computational methods, which predict T-cell epitopes for various HLA types.

Methods

We tested the performance of the NetMHCpan4.0 computational neural network in re-identifying 93 T-cell epitopes that had been previously independently mapped using the whole proteome IFN-γ ELISPOT assays in 6 HLA class I typed Ugandan individuals infected with HIV-1 subtypes A1 and D. To provide a benchmark we compared the predictions for NetMHCpan4.0 to MHCflurry1.2.0 and NetCTL1.2.

Results

NetMHCpan4.0 performed best correctly predicting 88 of the 93 experimentally mapped epitopes for a set length of 9-mer and matched HLA class I alleles. Receiver Operator Characteristic (ROC) analysis gave an area under the curve (AUC) of 0.928. Setting NetMHCpan4.0 to predict 11-14mer length did not improve the prediction (37–79 of 93 peptides) with an inverse correlation between the number of predictions and length set. Late time point peptides were significantly stronger binders than early peptides (Wilcoxon signed rank test: p = 0.0000005). MHCflurry1.2.0 similarly predicted all but 2 of the peptides that NetMHCpan4.0 predicted and NetCTL1.2 predicted only 14 of the 93 experimental peptides.

Conclusion

NetMHCpan4.0 class I epitope predictions covered 95% of the epitope responses identified in six HIV-1 infected individuals, and would have reduced the number of experimental confirmatory tests by > 80%. Algorithmic epitope prediction in conjunction with HLA allele frequency information can cost-effectively assist immunogen design through minimizing the experimental effort.
Vancomycin-resistant Enterococcus faecium pneumonia in a uremic patient on hemodialysis: a case report and review of the literature
Authors: Li Fengqin , Wang Yonglan , Sun Linlin , Wang Xiaoxia
Published: February 2020

Background

Even though enterococci can cause serious infections in multiple sites, they are a rare cause of pneumonia. We reported a uremic patient with vancomycin-resistant E. faecium (VRE-fm) pneumonia, possibly related to epileptic seizures.

Case presentation

A 57-year old man with uremia on hemodialysis was admitted to the hospital with complaint of recurrent epileptic seizures, followed by a two-week history of recurrent fever and cough with purulent sputum. Chest CT demonstrated multiple exudation of both lungs. He was diagnosed as community acquired pneumonia. Despite antibiotic combination therapy, abnormal chest shadows aggravated. Sputum and blood cultures were initially negative, but later blood culture grew VRE-fm. We suspected aspiration of gastrointestinal content induced by epilepsy as the most likely mechanism. The patient was successfully treated with a four-week course of linezolid according to the antibiotic susceptibility testing.

Conclusions

Physicians should consider multi-drug resistant organisms such as VRE in uremic patients with pneumonia that fails to resolve with broad-spectrum antibiotics, especially in the cases with aspiration induced by epilepsy, immunocompromised conditions, and repeated or prolonged hospitalizations.
Suspension microarray-based comparison of oropharyngeal swab and bronchoalveolar lavage fluid for pathogen identification in young children hospitalized with respiratory tract infection
Authors: Ma Zhan-Ying , Deng Hua , Hua Li-Dong , Lei Wen , Zhang Chang-Bin , Dai Qi-Qiang , Tao Wei-Jing , Zhang Liang
Published: February 2020

Background

Respiratory tract infection (RTI) in young children is a leading cause of morbidity and hospitalization worldwide. There are few studies assessing the performance for bronchoalveolar lavage fluid (BALF) versus oropharyngeal swab (OPS) specimens in microbiological findings for children with RTI. The primary purpose of this study was to compare the detection rates of OPS and paired BALF in detecting key respiratory pathogens using suspension microarray.

Methods

We collected paired OPS and BALF specimens from 76 hospitalized children with respiratory illness. The samples were tested simultaneously for 8 respiratory viruses and 5 bacteria by suspension microarray.

Results

Of 76 paired specimens, 62 patients (81.6%) had at least one pathogen. BALF and OPS identified respiratory pathogen infections in 57 (75%) and 49 (64.5%) patients, respectively (P > 0.05). The etiology analysis revealed that viruses were responsible for 53.7% of the patients, whereas bacteria accounted for 32.9% and Mycoplasma pneumoniae for 13.4%. The leading 5 pathogens identified were respiratory syncytial virus, Streptococcus pneumoniaee, Haemophilus influenzae, Mycoplasma pneumoniae and adenovirus, and they accounted for 74.2% of etiological fraction. For detection of any pathogen, the overall detection rate of BALF (81%) was marginally higher than that (69%) of OPS (p = 0.046). The differences in the frequency distribution and sensitivity for most pathogens detected by two sampling methods were not statistically significant.

Conclusions

In this study, BALF and OPS had similar microbiological yields. Our results indicated the clinical value of OPS testing in pediatric patients with respiratory illness.
Implementation of the FilmArray ME panel in laboratory routine using a simple sample selection strategy for diagnosis of meningitis and encephalitis
Authors: Pfefferle Susanne , Christner Martin , Aepfelbacher Martin , Lütgehetmann Marc , Rohde Holger
Published: February 2020

Background

Infectious meningitis is a serious disease and patient outcome relies on fast and reliable diagnostics. A syndromic panel testing approach like the FilmArray ME can accelerate diagnosis and therefore decrease the time to pathogen specific therapy. Yet, its clinical utility is controversial, mainly because of a remaining uncertainty in correct interpretation of results, limited data on its performance on clinical specimens and its relatively high costs. The aim of this study was to analyze clinical performance of the assay in a real life setting at a tertiary university hospital using a pragmatic and simple sample selection strategy to reduce the overall cost burden.

Methods

Over a period of 18 months we received 4623 CSF samples (2338 hospitalizations, 1601 individuals). FilmArray ME analysis was restricted to CSF-samples with a high pretest probability of infectious meningitis, e.g. positive Gram-stain, samples in which leukocytes and/or bacteria were evident or urgent suspicion of infection was communicated by clinicians. N = 171 samples matched to our risk criteria and were subjected to FilmArray ME analysis. Those samples were also analyzed by reference methods: culture only (n = 45), PCR only (n = 20) or both methods (n = 106).

Results

56/171 (32.75%) were FilmArray ME positive. Bacterial pathogens were detected in 30/56 (53.57%), viral pathogens were detected in 27/56 (48.21%) and yeast DNA was detected in 1/56 (1.79%) of positive samples. Double detection occurred in 2/56 samples. In 52/56 (92.86%) FilmArray ME positive samples, results could be confirmed by the reference assays (sensitivity = 96.30%, specificity =96.58%).

Conclusion

The FilmArray ME assay is a fast and reliable diagnostic tool for the management of infectious meningitis and can easily be implemented in routine diagnostic workflows. However, correlation of test results and underlying clinical symptoms requires experienced users and the awareness of potentially false negative or false positive results. Moreover, considering the need for antimicrobial susceptibility testing, the use of molecular tests as a stand-alone diagnostic cannot be recommended.
Oral Sucrosomial® iron versus intravenous iron for recovering iron deficiency anaemia in ND-CKD patients: a cost- minimization analysis
Authors: Riccio Eleonora , Sabbatini Massimo , Capuano Ivana , Pellegrino Angela Maria , Petruzzelli Luigi Annicchiarico , Pisani Antonio
Published: February 2020

Background

Oral iron is recommended as first line treatment of anemia in non-dialysis chronic kidney disease (ND-CKD) patients. Sucrosomial® iron, a new generation oral iron with high absorption and bioavailability and a low incidence of side effects, has shown to be not inferior to intravenous (IV) iron in the replacement of iron deficiency anemia in patients with ND-CKD. Besides the clinical benefit, it is also important to determine the comparative total costs of oral versus IV iron administrations. The aim of this study was to perform a cost-minimization analysis of oral Sucrosomial iron, compared with IV iron gluconate from an Italian societal perspective.

Methods

Cost analysis was performed on the 99 patients with ND-CKD and iron-deficiency anemia of the randomized trial by Pisani et al. Human and material resources utilization was recorded during each iron administration. According to study perspective, direct and indirect costs were considered. Costs for each resource unit were taken from official Italian sources. Probabilistic sensitivity analyses were carried out to test the robustness of the results.

Results

The base case analysis showed an average cost/cycle per patient of € 111 for oral iron and € 1302 for IV iron. Thus, the potential saving was equal to € 1191 per patient/cycle. The sensitivity analysis showed that the most sensitive driver is the time loss by patient and caregivers for the therapy and related-care, followed by the minutes of nursing care and the number of kilometres travelled to reach the referral centre.

Discussion

This study showed that oral Sucrosomial® iron could offer specific advantages in terms of potential savings, and allowed identifying some implications for future research. Such advantages still persist with the new single dose IV iron formulation available in the market, although to a lesser extent.
Association of peripheral neutrophil count with intracranial atherosclerotic stenosis
Authors: Zhang Xing , Hou Xiao-He , Ma Ya-Hui , Shen Xue-Ning , Cao Xi-Peng , Song Jing-Hui , Tan Lan , Yu Jin-Tai
Published: February 2020

Background

Inflammation plays an important role in atherosclerosis but the contribution of neutrophils to this process is unclear. We sought to assess whether neutrophil count is associated with intracranial atherosclerotic stenosis (ICAS).

Methods

A total of 2847 individuals were included in our study, including 1363 with acute ischemic stroke and 1484 normal controls without stroke. The presence of ICAS was confirmed by magnetic resonance angiography. The association between neutrophil count and ICAS was evaluated by multivariable logistic regression analysis.

Results

Among 2847 individuals included in this study, individuals with ICAS had higher neutrophil counts than those without ICAS in groups with and without stroke (P <  0.0001 for stroke group, P = 0.0097 for group without stroke). The multivariable logistic regression analysis showed that the third and fourth quartiles were independent predictors of ICAS in all the subjects (Q3: OR 1.81, 95% CI 1.39–2.37, Q4: OR 2.29, 95% CI 1.70–3.10) and patients in the fourth quartile had a higher risk for the occurrence of ICAS in stroke group (Q4: OR 2.82, 95% CI 1.79–4.48). However, there was no significant association between neutrophil count and ICAS in the group without stroke.

Conclusions

The levels of circulating neutrophils were associated with the presence of ICAS. Our findings suggest that neutrophils may play a role in the pathogenesis of stroke related to ICAS and emphasize the need to develop proper strategies to control neutrophil response for the treatment of ICAS.
Patterns of recurrence after surgery and efficacy of salvage therapy after recurrence in patients with thoracic esophageal squamous cell carcinoma
Authors: Ni Wenjie , Yang Jinsong , Deng Wei , Xiao Zefen , Zhou Zongmei , Zhang Hongxing , Chen Dongfu , Feng Qinfu , Liang Jun , Lv Jima , Wang Xiaozhen , Wang Xin , Zhang Tao , Bi Nan , Deng Lei , Wang Wenqing
Published: February 2020

Background

Information on the optimal salvage regimen for recurrent esophageal cancer is scarce. We aimed to assess the patterns of locoregional failure, and evaluate the therapeutic efficacy of salvage therapy along with the prognostic factors in recurrent thoracic esophageal squamous cell carcinoma (TESCC) after radical esophagectomy.

Methods

A total of 193 TESCC patients who were diagnosed with recurrence after radical surgery and received salvage treatment at our hospital were retrospectively reviewed from 2004 to 2014. The patterns of the first failure were assessed. The post-recurrence survival rate was determined using the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model.

Results

The median time of failure was 7.0 months. Among the 193 patients, 163 exhibited isolated locoregional lymph node (LN) recurrence and 30 experienced locoregional LN relapse with hematogenous metastasis. Among the 193 patients, LN recurrence was noted at 302 sites; the most common sites included the supraclavicular (25.8%; 78/302) and mediastinal LNs (44.4%; 134/302), particularly stations 1 to 6 for the mediastinal LNs (36.4%; 110/302). The median overall survival (OS) was 13.1 months after recurrence. In those treated with salvage chemoradiotherapy, with radiotherapy, and without radiotherapy, the 1-year OS rates were 68.5, 55.0, and 28.6%; the 3-year OS rates were 35.4, 23.8, and 2.9%; and the 5-year OS rates were 31.8, 17.2, 2.9%, respectively (P < 0.001). Furthermore, patient survival in those who received salvage chemoradiotherapy was significantly better than those treated with salvage radiotherapy alone (P = 0.044). Multivariate analysis showed that the pathological TNM stage and salvage treatment regimen were independent prognostic factors.

Conclusions

Supraclavicular and mediastinal LN failure were the most common types of recurrence after R0 surgery in TESCC patients. Salvage chemoradiotherapy or radiotherapy could significantly improve survival in esophageal cancer with locoregional LN recurrence.
Unphosphorylated STAT3 in heterochromatin formation and tumor suppression in lung cancer
Authors: Dutta Pranabananda , Zhang Lin , Zhang Huijun , Peng Qin , Montgrain Phillippe R. , Wang Yingxiao , Song Yuanlin , Li Jinghong , Li Willis X.
Published: February 2020

Background

Aberrant JAK/STAT activation has been detected in many types of human cancers. The role of JAK/STAT activation in cancer has been mostly attributed to direct transcriptional regulation of target genes by phosphorylated STAT (pSTAT), while the unphosphorylated STAT (uSTAT) is believed to be dormant and reside in the cytoplasm. However, several studies have shown that uSTATs can be found in the nucleus. In addition, it has been shown that tissue-specific loss of STAT3 or STAT5 in mice promotes cancer growth in certain tissues, and thus these STAT proteins can act as tumor suppressors. However, no unifying mechanism has been shown for the tumor suppressor function of STATs to date. We have previously demonstrated a non-canonical mode of JAK/STAT signaling for Drosophila STAT and human STAT5A, where a fraction of uSTAT is in the nucleus and associated with Heterochromatin Protein 1 (HP1); STAT activation (by phosphorylation) causes its dispersal, leading to HP1 delocalization and heterochromatin loss.

Methods

We used a combination of imaging, cell biological assays, and mouse xenografts to investigate the role of STAT3 in lung cancer development.

Results

We found that uSTAT3 has a function in promoting heterochromatin formation in lung cancer cells, suppressing cell proliferation in vitro, and suppressing tumor growth in mouse xenografts.

Conclusions

Thus, uSTAT3 possesses noncanonical function in promoting heterochromatin formation, and the tumor suppressor function of STAT3 is likely attributable to the heterochromatin-promoting activity of uSTAT3 in the non-canonical JAK/STAT pathway.
Ab interno implantation of glaucoma drainage devices tubes in the posterior chamber
Authors: Moreno-Montañés Javier , Guirao-Navarro Concepción , Argüeso Francisco
Published: February 2020

Background

Glaucoma drainage device (GDD) implantation in the anterior chamber are associated with corneal complications. We describe a novel technique to implant GDD tubes in the posterior chamber of pseudophakic eyes.

Methods

Ten patients with glaucoma who required GDD tube implantation were included.

Results

The new technique begins with the passage of one of two straight needles existing at each end of a 10–0 Polypropylene suture through the GDD tube. A 23-gauge needle then is inserted at an angle 180° away and passed from the anterior to the posterior chamber and finally through the sclera. The two suture straight needles from the 10–0 Polypropylene suture are positioned in the lumen of the 23-gauge needle. The 23-gauge needle is then extracted from the eye by passing the 2 needles through the lumen. The suture remains inside the posterior chamber, and the tube is inserted into the posterior chamber by pulling on the suture from the other side. No intra-operative complications were found such as bleeding, vitreous tube placement, bent tubes, etc.

Conclusions

This surgical procedure to implant a tube into the posterior chamber of the pseudophakic eyes is uncomplicated and facilitates the insertion of the flexible tube into the posterior chamber. This eliminates the tendency of the tube to enter the vitreous as the tube is always placed in the posterior chamber away from the cornea.

Trial registration

Current Controlled Trials ISRCTN14276553 (31th May, 2019) Retrospectively registered.
Prevalence of depression and its associated factors among patients with diabetes mellitus at Tirunesh-Beijing general hospital, Addis Ababa, Ethiopia
Authors: Engidaw Nigus Alemnew , Wubetu Abate Dargie , Basha Elyas Admasu
Published: February 2020

Background

Depression is one of the common and overwhelming mental disorder in diabetic patients. A little is known about the prevalence and associated factors of depression among diabetic patients at general hospitals. Therefore, this study aimed to assess the prevalence and associated factors of depression among patients with diabetes mellitus at Tirunesh-Beijing General Hospital, Addis Ababa, Ethiopia.

Methods

An institution-based cross-sectional study was conducted from February 8 to April 8, 2019. A systematic random sampling technique was used to select 403 participants. Depression was assessed by using patient health questionnaire-9 (PHQ-9). Oslo 3 social support scale was used to assess social support. The data were entered into Epidata version 3.1 and analyzed by the statistical package for social science version 23 software. We computed bivariate and multivariate binary logistic regressions to assess factors associated with depression. Statistical significance was declared at P-value < 0.05.

Results

A total of 403 study participants were interviewed with a response rate of 99%. The prevalence of depression among diabetic patients was 21.3%. In the final multivariate analysis, diagnosed with type II diabetes mellitus, being physically disabled and having poor social support were independent predictors of depression.

Conclusions

Type II diabetes mellitus, poor social support and physical disability were factors associated with depression. An early depression-focused regular screening for diabetic patient should be carried out by trained health professionals. Linkage with mental health service providers also needs to be considered. Clinicians needs to give emphasis to diabetic patients with physically disable and poor social support.
Minimally invasive comprehensive treatment for granulomatous lobular mastitis
Authors: Wang Yaohuai , Song Junlong , Tu Yi , Chen Chuang , Sun Shengrong
Published: February 2020

Objective

To describe a minimally invasive comprehensive treatment for granulomatous lobular mastitis (GLM) and compare its effect with the existing methods, particularly in terms of its recurrence rate and esthetic outcomes.

Methods

This retrospective study reviewed 69 GLM patients receiving the minimally invasive comprehensive treatment. Patients’ information, including age, clinical features, image characteristics, histopathological findings, mastitis history, treatment process, operative technique, recurrence, and esthetic effect, was evaluated.

Results

All patients were female with a median age of 32 (range 17–55) years. Hospital stays ranged from 2 to 34 days, with a median of 6 days. The shortest time for complete rehabilitation was 2 days and the longest time was 365 days, with a median of 30 days. After a median follow-up of 391 days (range 162–690), 7 patients (10.14%) relapsed. The average cosmetic score was 2.62 ± 0.57 points and was mainly related to the past treatment, especially the surgical history.

Conclusion

Minimally invasive comprehensive treatment is a new method for the treatment of GLM, ensuring a therapeutic effect while maintaining breast beauty.
Medical students’ experiences with sexual discrimination and perceptions of equal opportunity: a pilot study in Germany
Authors: Jendretzky Konstantin , Boll Lukas , Steffens Sandra , Paulmann Volker
Published: February 2020

Background

Data is available on sexual discrimination and subjective perceptions of equal opportunity in medical education for many countries. Surveys focussing on sexual harassment have not yet been conducted at German medical schools.

Methods

A student initiative surveyed all medical students at the Hannover Medical School (MHH) using an anonymous online questionnaire on equal opportunity and sexual discrimination to identify potential problems in education.

Results

A total of 343 students (15%) participated in the survey. Over 50% reported having either witnessed sexual harassment or experienced it themselves. Female students indicated having experienced sexual harassment three times more often than their male peers; verbal forms of sexual discrimination predominate. These observations and experiences of sexual harassment demonstrated significant influences on many perceptions regarding equal opportunity and equal treatment in the MHH undergraduate medical education at MHH.

Conclusion

This blind spot in medical education in the German-speaking countries should be scrutinized more closely. The experience of sexism in the context of undergraduate medical education, which has negative effects on students, should no longer be ignored in empirical education research.
Factors affecting the implementation of a whole school mindfulness program: a qualitative study using the consolidated framework for implementation research
Authors: Hudson Kristian G. , Lawton Rebecca , Hugh-Jones Siobhan
Published: February 2020

Background

Preventing the onset of poor mental health in adolescence is an international public health priority. Universal, whole school preventative approaches are valued for their reach, and anti-stigmatising and resilience building principles. Mindfulness approaches to well-being have the potential to be effective when delivered as a whole school approach for both young people and staff. However, despite growing demand, there is little understanding of possible and optimal ways to implement a mindfulness, whole school approach (M-WSA) to well-being. This study aimed to identify the determinants of early implementation success of a M-WSA. We tested the capacity of the Consolidated Framework for Implementation Research (CFIR), to capture the determinants of the implementation of a mental health intervention in a school setting.

Methods

Key members of school staff (n = 15) from five UK secondary schools attempting to implement a M-WSA were interviewed at two-time points, 6 months apart, generating a total of 30 interviews. Interviews explored participants’ attitudes, beliefs and experiences around implementing a M-WSA. Interview data were coded as CFIR constructs or other (non CFIR) factors affecting implementation. We also mapped school-reported implementation activity and perceived success over 30 months.

Results

The CFIR captured the implementation activities and challenges well, with 74% of CFIR constructs identifiable in the dataset. Of the 38 CFIR constructs, 11 appeared to distinguish between high and low implementation schools. The most essential construct was school leadership. It strongly distinguished between high and low implementation schools and appeared inter-related with many other distinguishing constructs. Other strongly distinguishing constructs included relative priority, networks and communications, formally appointed implementation leaders, knowledge and beliefs about the intervention, and executing.

Conclusions

Our findings suggest key implementation constructs that schools, commissioners and policy makers should focus on to promote successful early implementation of mental health programs. School leadership is a key construct to target at the outset. The CFIR appears useful for assessing the implementation of mental health programs in UK secondary schools.
Disabled and immigrant, a double minority challenge: a qualitative study about the experiences of immigrant parents of children with disabilities navigating health and rehabilitation services in Norway
Authors: Arfa Shahrzad , Solvang Per Koren , Berg Berit , Jahnsen Reidun
Published: February 2020

Background

Immigrants and their Norwegian-born children make up approximately 18% of the total population in Norway. While several studies have been conducted on immigrants’ utilization of healthcare services, immigrant families are systematically underrepresented in international studies of children with disabilities. By focusing on experiences of immigrant parents of children with disabilities navigating health and rehabilitation services in Norway, this study generated knowledge of how accessible and tailored the services were from their point of view.

Methods

This study took a qualitative approach, using semi-structured interviews to explore the experiences of immigrant parents of children with disabilities from non-Western countries. The interviews were transcribed, coded, and analyzed via an inductive thematic analytic approach.

Results

The findings show how the “immigrant experience” influenced the way the parents looked at, experienced, and even praised the services. The parents appreciated the follow-up services provided by the pediatric rehabilitation centers, which they experienced as predictable and well-organized. While navigating the services, they experienced several challenges, including the need for information, support, and timely help. They felt exhausted because of years of struggle in the healthcare system to access the help and services they needed. They expressed how this struggle had affected their own health. The feeling of being treated differently from the majority was another challenge they experienced while navigating the services. The findings also show how parents’ experiences of communication with healthcare providers were influenced not only by their own language and communication skills but also by the healthcare providers’ intercultural communication skills and dominant organizational culture.

Conclusions

The parents’ experiences show that there is still a gap between the public ideal of equal healthcare services and the reality of the everyday lives of immigrant families of children with disabilities. By exploring immigrant parents’ experiences, this study highlights the importance of mobilization at both the individual and systemic levels to fill the current gap and provide tailored and accessible services to the entire population.
Genomic-based identification of environmental and clinical Listeria monocytogenes strains associated with an abortion outbreak in beef heifers
Authors: Whitman Katherine J. , Bono James L. , Clawson Michael L. , Loy John D. , Bosilevac Joseph M. , Arthur Terrance M. , Ondrak Jeff D.
Published: February 2020

Background

In a beef cattle facility an outbreak of abortions occurred over a 36-day period and included samples from two aborted (non-viable) fetuses and 21 post-abortion clinical cases. There are numerous etiologies, including clinical listeriosis. At the species level,Listeria monocytogenesis ubiquitous in cattle production environments, including soil, feed, and occasionally water sources, and is a common enteric resident of cattle and other mammals. There are four genetically distinct lineages ofL. monocytogenes(I-IV), with most lineage III and IV isolates obtained from ruminants. Definitive diagnosis ofL. monocytogenesas a causative agent in disease outbreaks relies upon case identification, appropriate sample collection, and laboratory confirmation. Furthermore, clearly establishing a relationship between a pathogen source and clinical disease is difficult.

Results

Of the two fetal and 21 clinical case submissions, 19 were positive forL. monocytogenes. Subsequent culture forL. monocytogenesfrom water and silage sources identified both as potential origins of infection. Using whole-genome sequencing and phylogenetic analyses, clinical, water and silageL. monocytogenesstrains grouped into two of four lineages. All water and silage strains, plus 11 clinical strains placed in lineage III, with identical or nearly identical genomic sequences. The remaining eight clinical strains placed in lineage I, with seven having nearly identical sequences and one distinctly different.

Conclusion

Three genetically distinct strains within two lineages ofL. monocytogenescaused the abortion outbreak. The etiology of abortion in 11 cases was directly linked to water and silage contamination from a lineage IIIL. monocytogenesstrain. The source of infection for the remaining abortion cases with two different strains from lineage I is unknown. This is the first report ofL. monocytogenesgenomics being used as part of an outbreak investigation of cattle abortion.
neoANT-HILL: an integrated tool for identification of potential neoantigens
Authors: Coelho Ana Carolina M. F. , Fonseca André L. , Martins Danilo L. , Lins Paulo B. R. , da Cunha Lucas M. , de Souza Sandro J.
Published: February 2020

Background

Cancer neoantigens have attracted great interest in immunotherapy due to their capacity to elicit antitumoral responses. These molecules arise from somatic mutations in cancer cells, resulting in alterations on the original protein. Neoantigens identification remains a challenging task due largely to a high rate of false-positives.

Results

We have developed an efficient and automated pipeline for the identification of potential neoantigens. neoANT-HILL integrates several immunogenomic analyses to improve neoantigen detection from Next Generation Sequence (NGS) data. The pipeline has been compiled in a pre-built Docker image such that minimal computational background is required for download and setup. NeoANT-HILL was applied in The Cancer Genome Atlas (TCGA) melanoma dataset and found several putative neoantigens including ones derived from the recurrent RAC1:P29S and SERPINB3:E250K mutations. neoANT-HILL was also used to identify potential neoantigens in RNA-Seq data with a high sensitivity and specificity.

Conclusion

neoANT-HILL is a user-friendly tool with a graphical interface that performs neoantigens prediction efficiently. neoANT-HILL is able to process multiple samples, provides several binding predictors, enables quantification of tumor-infiltrating immune cells and considers RNA-Seq data for identifying potential neoantigens. The software is available through github at https://github.com/neoanthill/neoANT-HILL.
Neighbourhood-level deprivation indices and postpartum women’s health: results from the Community Child Health Network (CCHN) multi-site study
Authors:   for the Community Child Health Network (CCHN) of Eunice Kennedy Shriver National Institute of Child Health and Human Development, Kaufman-Shriqui Vered , O’Campo Patricia , Misir Vachan , Schafer Peter , Morinis Julia , Vance Maxine , Dunkel Schetter Christine , Raju Tonse N. K. , Hillemeier Marianne M. , Lanzi Robin , Chinchilli Vernon M.
Published: February 2020

Background

Area-level socioeconomic characteristics have been shown to be related to health status and mortality however, little is known about the association between residential community characteristics in relation to postpartum women’s health.

Methods

Data from the longitudinal, multi-site Community Child Health Network (CCHN) study were used. Postpartum women (n = 2510), aged 18–40 were recruited from 2008 to 2012 within a month of delivery. Socioeconomic data was used to create deprivation indices. Census data were analysed using principal components analysis (PCA) and logistic regression to assess the association between deprivation indices (DIs) and various health indicators.

Results

PCA resulted in two unique DIs that accounted for 67.5% of the total variance of the combined all-site area deprivation. The first DI was comprised of variables representing a high percentage of Hispanic or Latina, foreign-born individuals, dense households (more than one person per room of residence), with less than a high-school education, and who spent more than 30% of their income on housing costs. The second DI was comprised of a high percentage of African-Americans, single mothers, and high levels of unemployment. In a multivariate logistic regression model, using the quartiles of each DI, women who reside in the geographic area of Q4-Q2 of the second DI, were almost twice as likely to have more than three adverse health conditions compared to those who resided in the least deprived areas. (Q2vs.Q1:OR = 2.09,P = 0.001,Q3vs.Q1:OR = 1.89,P = 0.006,Q4vs.Q1:OR = 1.95,P = 0.004 respectively).

Conclusions

Our results support the utility of examining deprivation indices as predictors of maternal postpartum health.