bluuebunny/crossref_metadata_2025 huggingface dataset:
GeneSetCluster: a tool for summarizing and integrating gene-set analysis results
Authors: Ewing Ewoud , Planell-Picola Nuria , Jagodic Maja , Gomez-Cabrero David
Published: October 2020

Background

Gene-set analysis tools, which make use of curated sets of molecules grouped based on their shared functions, aim to identify which gene-sets are over-represented in the set of features that have been associated with a given trait of interest. Such tools are frequently used in gene-centric approaches derived from RNA-sequencing or microarrays such as Ingenuity or GSEA, but they have also been adapted for interval-based analysis derived from DNA methylation or ChIP/ATAC-sequencing. Gene-set analysis tools return, as a result, a list of significant gene-sets. However, while these results are useful for the researcher in the identification of major biological insights, they may be complex to interpret because many gene-sets have largely overlapping gene contents. Additionally, in many cases the result of gene-set analysis consists of a large number of gene-sets making it complicated to identify the major biological insights.

Results

We present GeneSetCluster, a novel approach which allows clustering of identified gene-sets, from one or multiple experiments and/or tools, based on shared genes. GeneSetCluster calculates a distance score based on overlapping gene content, which is then used to cluster them together and as a result, GeneSetCluster identifies groups of gene-sets with similar gene-set definitions (i.e. gene content). These groups of gene-sets can aid the researcher to focus on such groups for biological interpretations.

Conclusions

GeneSetCluster is a novel approach for grouping together post gene-set analysis results based on overlapping gene content. GeneSetCluster is implemented as a package in R. The package and the vignette can be downloaded at https://github.com/TranslationalBioinformaticsUnit
ESCRT machinery plays a role in microautophagy in yeast
Authors: Morshed Shamsul , Tasnin Most Naoshia , Ushimaru Takashi
Published: October 2020

Background

Microautophagy, which degrades cargos by direct lysosomal/vacuolar engulfment of cytoplasmic cargos, is promoted after nutrient starvation and the inactivation of target of rapamycin complex 1 (TORC1) protein kinase. In budding yeast, microautophagy has been commonly assessed using processing assays with green fluorescent protein (GFP)-tagged vacuolar membrane proteins, such as Vph1 and Pho8. The endosomal sorting complex required for transport (ESCRT) system is proposed to be required for microautophagy, because degradation of vacuolar membrane protein Vph1 was compromised in ESCRT-defective mutants. However, ESCRT is also critical for the vacuolar sorting of most vacuolar proteins, and hence reexamination of the involvement of ESCRT in microautophagic processes is required.

Results

Here, we show that the Vph1-GFP processing assay is unsuitable for estimating the involvement of ESCRT in microautophagy, because Vph1-GFP accumulated highly in the prevacuolar class E compartment in ESCRT mutants. In contrast, GFP-Pho8 and Sna4-GFP destined for vacuolar membranes via an alternative adaptor protein-3 (AP-3) pathway, were properly localized on vacuolar membranes in ESCRT-deficient cells. Nevertheless, microautophagic degradation of GFP-Pho8 and Sna4-GFP after TORC1 inactivation was hindered in ESCRT mutants, indicating that ESCRT is indeed required for microautophagy after nutrient starvation and TORC1 inactivation.

Conclusions

These findings provide evidence for the direct role of ESCRT in microautophagy induction.
Symbiotic microbiome Staphylococcus aureus from human nasal mucus modulates IL-33-mediated type 2 immune responses in allergic nasal mucosa
Authors: Jeon Yung Jin , Gil Chan Hee , Won Jina , Jo Ara , Kim Hyun Jik
Published: October 2020

Background

The host-microbial commensalism can shape the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models.

Results

Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, ovalbumin-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice.

Conclusion

Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.
Genome-wide characterization, evolution and expression profiling of UDP-glycosyltransferase family in pomelo (Citrus grandis) fruit
Authors: Wu Boping , Liu Xiaohong , Xu Kai , Zhang Bo
Published: October 2020

Background

Pomelo is one of the three major species of citrus. The fruit accumulates a variety of abundant secondary metabolites that affect the flavor. UDP-glycosyltransferases (UGTs) are involved in the glycosylation of secondary metabolites.

Results

In the present study, we performed a genome-wide analysis of pomelo UGT family, a total of 145 UGTs was identified based on the conserved plant secondary product glycosyltransferase (PSPG) motif. These UGT genes were clustered into 16 major groups through phylogenetic analysis of these genes with other plant UGTs (A-P). Pomelo UGTs were distributed unevenly among the chromosomes. At least 10 intron insertion events were observed in these UGT genome sequences, and I-5 was identified to be the highest conserved one. The expression profile analysis of pomelo UGT genes in different fruit tissues during development and ripening was carried out by RNA-seq.

Conclusions

We identified 145 UGTs in pomelo fruit through transcriptome data and citrus genome database. Our research provides available information on UGTs studies in pomelo, and provides an important research foundation for screening and identification of functional UGT genes.
Impact of low skeletal muscle mass index and perioperative blood transfusion on the prognosis for HCC following curative resection
Authors: Bekki Tomoaki , Abe Tomoyuki , Amano Hironobu , Hattori Minoru , Kobayashi Tsuyoshi , Nakahara Masahiro , Ohdan Hideki , Noriyuki Toshio
Published: October 2020

Background

This study aimed to assess the prognostic factors including low skeletal muscle mass index (SMI) and perioperative blood transfusion for patients with hepatocellular carcinoma (HCC) following curative surgery.

Methods

This study included 139 patients with HCC who underwent hepatectomy between 2005 and 2016. Univariate and multivariate analyses were performed to identify variables associated with overall survival (OS) and recurrence-free survival (RFS).

Results

Low SMI was significantly related with poor OS, while blood transfusion had a strong impact on RFS. The male ratio and body mass index in the low SMI group were significantly higher than those in the high SMI group. There were no significant differences in age, virus etiology, laboratory data, liver function, tumor makers, and operative variables between the groups. Tumor factors such as tumor diameter, tumor number, poor differentiation, and intrahepatic metastasis (IM) did not significantly differ between the two groups. Operation time, intraoperative blood loss volume, and recurrence ratio were significantly higher in the blood transfusion group than in the non-transfusion group. IM was associated with poor OS and RFS.

Conclusions

Low SMI and blood transfusion were independently related with long-term prognosis in patients with HCC following curative surgery.
Three-tube method and covered metallic stent for the treatment of anastomotic leakage after esophagectomy
Authors: Bi Yonghua , Wu Zhengyang , Yi Mengfei , Han Xinwei , Ren Jianzhuang
Published: October 2020

Background

Anastomotic leakage is common and life-threatening complication after esophagectomy. The management of esophageal anastomotic leakage remains challenging. We aimed to determine the safety, feasibility and efficacy of three-tube method and covered metallic stent placement for the management of anastomotic leakage.

Methods

Twenty-six consecutive patients with anastomotic leakage were treated using three-tube method and covered metallic stent and the medical records were retrospectively assessed. All patients received placement of abscess drainage tube, jejunal feeding tube and gastrointestinal decompression tube as well as esophageal covered stent, followed by continue abscess drainage, nutritional support and anti-inflammatory treatment. Tubes and esophageal stents will be removed once anastomotic leakage heals.

Results

The procedure was technically successful in 23 patients (95.8%). A total of 31 covered stents were used. Esophageal stents and abscess drainage tubes were successfully removed from 14 patients. The median retention duration was 2.3 months and 2.6 months for stent and abscess drainage tubes, respectively. No perioperative death, esophageal rupture, massive hemorrhage, or other severe complications were observed during procedures. The abscess cavity had markedly decreased in 8 patients or disappeared in 16 cases. During follow-up, 8 patients died of cancer recurrence and 2 patients died of severe pulmonary infection. The 1-, 3-, 5-year survival rates were 60.1, 51.5 and 51.5%, respectively.

Conclusion

Three-tube method and covered metallic stent placement is safe, feasible and efficacious for treatment of anastomotic leakage after esophagectomy.
Challenges of transferring rural adults with chronic HCV infection for further HCV RNA confirmation and free DAAs treatment: a success story of the interdisciplinary collaboration approach
Authors: Li Wei , Chang Te-Sheng , Chang Shu-Zhi , Chen Ching-Hwa , Chen Mei-Yen
Published: October 2020

Background

Chronic hepatitis C virus (HCV), which is a concern in many countries, is the leading cause of liver cancer around the world. Since Taiwan launched its national health insurance system in 1995, it has managed to extend health coverage to 99% of the Taiwanese population, providing free but limited antiviral treatment each year since 2017. However, many people in rural areas are unaware that they have chronic HCV; nor do they realize that new drugs with high cure rates could drastically reduce their health burden. The aim of this study is to explore the implementation facilitators of and barriers to inviting potentially infected patients in rural areas to be transferred for HCV ribonucleic acid (RNA) confirmation and new drug treatment.

Methods

A descriptive and prospective study design with an interdisciplinary collaboration approach was implemented. After five elements of referral were developed, telephone counseling was conducted between August 2018 and May 2019 in Yunlin, Taiwan. The elements of referral developed by the research team were: (1) forming and coordinating physicians’ schedules, (2) recruiting and training volunteers, (3) training the nursing staff, (4) raising funds or resources, and (5) connecting with village leaders. Thereafter, we collaborated with two district health centers, a private local hospital, and health clinics. Based on the medical records provided by these agencies, community adults that were HCV antibody (anti-HCV) positive were invited to join the program.

Results

Of the 1795 adults who were serum anti-HCV positive, 1149 (64%) accepted transfer to a qualified hospital; of these, 623 (54.2%) had an HCV infection. 552 (88.6%) of those infected started receiving direct-acting antivirals (DAAs) treatment. The top four barriers to accepting transfer were: (1) they perceived themselves to be healthy (n = 98, 32.3%); (2) mistrust of treatment/healthcare (n = 60, 20.2%); (3) limited transportation to the hospital (n = 52, 17.5%); and (4) work conflict (n = 30, 10.1%).

Conclusion

An interdisciplinary collaboration approach significantly contributed to the invitation of CHC patients, as well as their acceptance of HCV RNA confirmation and free DAAs treatment. Using anti-HCV data from previous medical records for case-finding and collaborating with a hospital and health clinics proved to be an efficient strategy.
Chest palpitations in a teenager as an unusual presentation of Lyme disease: case report
Authors: Myers Faith , Mishra Pooja E. , Cortez Daniel , Schleiss Mark R.
Published: October 2020

Background

The incidence of Lyme disease (LD) in North America has increased substantially in the past two decades. Concomitant with the increased incidence of infection has been an enhancement in the recognition of LD complications. Here, we report a case of Lyme carditis complicated by heart block in a pediatric patient admitted to our children’s hospital. What is unique about this case is that the complaint of chest palpitations is an infrequent presentation of LD, and what it adds to the scientific literature is an improved understanding of LD in the pediatric population.

Case presentation

The patient was a 16-year-old male who presented with the main concerns of acute onset of palpitations and chest pain. An important clinical finding was Erythema migrans (EM) on physical exam. The primary diagnoses were LD with associated Lyme carditis, based on the finding of 1st degree atrioventricular heart block (AVB) and positive IgM and IgG antibodies to Borrelia burgdorferi. Interventions included echocardiography, electrocardiography (EKG), and intravenous antibiotics. The hospital course was further remarkable for transition to 2nd degree heart block and transient episodes of complete heart block. A normal sinus rhythm and PR interval were restored after antibiotic therapy and the primary outcome was that of an uneventful recovery.

Conclusions

Lyme carditis occurs in < 5% of LD cases, but the “take-away” lesson of this case is that carditis can be the presenting manifestation of B. burgdorferi infection in pediatric patients. Any patient with suspected Lyme carditis manifesting cardiac symptoms such as syncope, chest pain, or EKG changes should be admitted for parenteral antibiotic therapy and cardiac monitoring. The most common manifestation of Lyme carditis is AVB. AVB may manifest as first-degree block, or may present as high-grade second or third-degree block. Other manifestations of Lyme carditis may include myopericarditis, left ventricular dysfunction, and cardiomegaly. Resolution of carditis is typically achieved through antibiotic administration, although pacemaker placement should be considered if the PR interval fails to normalize or if higher degrees of heart block, with accompanying symptoms, are encountered. With the rising incidence of LD, providers must maintain a high level of suspicion in order to promptly diagnose and treat Lyme carditis.
Retrospective analysis of the etiology, clinical characteristics and outcomes of community-acquired bacterial meningitis in the University Infectious Diseases Centre in Lithuania
Authors: Matulyte E. , Kiveryte S. , Paulauskiene R. , Liukpetryte E. , Vaikutyte R. , Matulionyte R.
Published: October 2020

Background

The morbidity and mortality in community-acquired bacterial meningitis (CABM) remain substantial, and the etiology, clinical characteristics, treatment outcomes and predictors of poor prognosis must be assessed regularly. The aim of this study was to identify the distribution of etiological agents and their relationship with clinical characteristics, treatment and outcomes in this cohort of patients with CABM.

Methods

Our retrospective chart review analyzed the causative microorganisms, clinical characteristics, laboratory findings, treatment and outcomes of 159 adults with CABM hospitalized in the Infectious Diseases Centre of Vilnius University Hospital from January 1, 2009 to December 31, 2016. A Glasgow Outcome Scale (GOS) score ≤ 3 was defined as unfavorable outcome. Predictors of an unfavorable outcome were identified through logistic regression analysis.

Results

The median patient age was 36 (IQR 24–56), and 51.6% were male. Microbiologically confirmed causative agents were identified in 80 (50.3%) patients: N. meningitidis in 55 (34.6%) patients with serotype B accounting for 85% of cases, S. pneumoniae in 15 (9.4%), L. monocytogenes in 5 (3.1%) and other in 5 (3.1%). The clinical triad of fever, neck stiffness and a change in mental status was present in 59.1% of patients. Coexisting conditions and comorbidities were similar in all groups stratified by etiology. Initial antimicrobial treatment consisted of penicillin in 78 patients (49.1%) and ceftriaxone in 72 patients (45.3%). The median time in which antibiotic treatment was started was 40 min (IQR 30.0–90.0). The outcome was unfavorable in 15.7% of episodes and death occurred in 5.7% of cases and did not differ according to the causative agent. Risk factors for an unfavorable outcome were age > 65 years, coexisting pneumonia and a platelet count <150x10e9/l.

Conclusions

The most common causative agent of CABM was N. meningitidis, with serotype B clearly dominant. Causative agents did not influence the disease outcome. The strongest risk factors for an unfavorable outcome were older age, pneumonia and a low platelet count. Since the introduction of routine vaccination against meningococcus B for infants in Lithuania in 2018, the national vaccination policy may hopefully contribute to a decrease in the incidence of serogroup B meningococcal disease in the Lithuanian population.
The potential impact of a recent measles epidemic on COVID-19 in Samoa
Authors: MacIntyre Chandini Raina , Costantino Valentina , Heslop David J.
Published: October 2020

Background

The pandemic of COVID-19 has occurred close on the heels of a global resurgence of measles. In 2019, an unprecedented epidemic of measles affected Samoa, requiring a state of emergency to be declared. Measles causes an immune amnesia which can persist for over 2 years after acute infection and increases the risk of a range of other infections.

Methods

We modelled the potential impact of measles-induced immune amnesia on a COVID-19 epidemic in Samoa using data on measles incidence in 2018–2019, population data and a hypothetical COVID-19 epidemic.

Results

The young population structure and contact matrix in Samoa results in the most transmission occurring in young people < 20 years old. The highest rate of death is the 60+ years old, but a smaller peak in death may occur in younger people, with more than 15% of total deaths in the age group under 20 years old. Measles induced immune amnesia could increase the total number of cases by 8% and deaths by more than 2%.

Conclusions

Samoa, which had large measles epidemics in 2019–2020 should focus on rapidly achieving high rates of measles vaccination and enhanced surveillance for COVID-19, as the impact may be more severe due to measles-induced immune paresis. This applies to other severely measles-affected countries in the Pacific, Europe and elsewhere.
Impact of serum phosphate changes on in-hospital mortality
Authors: Thongprayoon Charat , Cheungpasitporn Wisit , Hansrivijit Panupong , Thirunavukkarasu Sorkko , Chewcharat Api , Medaura Juan , Mao Michael A. , Kashani Kianoush B.
Published: October 2020

Background

Fluctuations in serum phosphate levels increased mortality in end-stage renal disease patients. However, the impacts of serum phosphate changes in hospitalized patients remain unclear. This study aimed to test the hypothesis that serum phosphate changes during hospitalization were associated with in-hospital mortality.

Methods

We included all adult hospitalized patients from January 2009 to December 2013 that had at least two serum phosphate measurements during their hospitalization. We categorized in-hospital serum phosphate changes, defined as the absolute difference between the maximum and minimum serum phosphate, into 5 groups: 0–0.6, 0.7–1.3, 1.4–2.0, 2.1–2.7, ≥2.8 mg/dL. Using serum phosphate change group of 0–0.6 mg/dL as the reference group, the adjusted odds ratio of in-hospital mortality for various serum phosphate change groups was obtained by multivariable logistic regression analysis.

Results

A total of 28,149 patients were studied. The in-hospital mortality in patients with serum phosphate changes of 0–0.6, 0.7–1.3, 1.4–2.0, 2.1–2.7, ≥2.8 mg/dL was 1.5, 2.0, 3.1, 4.4, and 10.7%, respectively (p < 0.001). When adjusted for confounding factors, larger serum phosphate changes were associated with progressively increased in-hospital mortality with odds ratios of 1.35 (95% 1.04–1.74) in 0.7–1.3 mg/dL, 1.98 (95% CI 1.53–2.55) in 1.4–2.0 mg/dL, 2.68 (95% CI 2.07–3.48) in 2.1–2.7 mg/dL, and 5.04 (95% CI 3.94–6.45) in ≥2.8 mg/dL compared to serum phosphate change group of 0–0.6 mg/dL. A similar result was noted when we further adjusted for either the admission or mean serum phosphate during hospitalization.

Conclusion

Greater serum phosphate changes were progressively associated with increased in-hospital mortality.
Increased canonical NF-kappaB signaling specifically in macrophages is sufficient to limit tumor progression in syngeneic murine models of ovarian cancer
Authors: Hoover Alyssa A. , Hufnagel Demetra H. , Harris Whitney , Bullock Kennady , Glass Evan B. , Liu Esther , Barham Whitney , Crispens Marta A. , Khabele Dineo , Giorgio Todd D. , Wilson Andrew J. , Yull Fiona E.
Published: October 2020

Background

New treatment options for ovarian cancer are urgently required. Tumor-associated macrophages (TAMs) are an attractive target for therapy; repolarizing TAMs from M2 (pro-tumor) to M1 (anti-tumor) phenotypes represents an important therapeutic goal. We have previously shown that upregulated NF-kappaB (NF-κB) signaling in macrophages promotes M1 polarization, but effects in the context of ovarian cancer are unknown. Therefore, we aimed to investigate the therapeutic potential of increasing macrophage NF-κB activity in immunocompetent mouse models of ovarian cancer.

Methods

We have generated a transgenic mouse model, termed IKFM, which allows doxycycline-inducible overexpression of a constitutively active form of IKK2 (cIKK2) specifically within macrophages. The IKFM model was used to evaluate effects of increasing macrophage NF-κB activity in syngeneic murine TBR5 and ID8-Luc models of ovarian cancer in two temporal windows: 1) in established tumors, and 2) during tumor implantation and early tumor growth. Tumor weight, ascites volume, ascites supernatant and cells, and solid tumor were collected at sacrifice. Populations of macrophages and T cells within solid tumor and/or ascites were analyzed by immunofluorescent staining and qPCR, and soluble factors in ascitic fluid were analyzed by ELISA. Comparisons of control versus IKFM groups were performed by 2-tailed Mann-Whitney test, and a P-value < 0.05 was considered statistically significant.

Results

Increased expression of the cIKK2 transgene in TAMs from IKFM mice was confirmed at the mRNA and protein levels. Tumors from IKFM mice, regardless of the timing of doxycycline (dox) administration, demonstrated greater necrosis and immune infiltration than control tumors. Analysis of IKFM ascites and tumors showed sustained shifts in macrophage populations away from the M2 and towards the anti-tumor M1 phenotype. There were also increased tumor-infiltrating CD3+/CD8+ T cells in IKFM mice, accompanied by higher levels of CXCL9, a T cell activating factor secreted by macrophages, in IKFM ascitic fluid.

Conclusions

In syngeneic ovarian cancer models, increased canonical NF-κB signaling in macrophages promoted anti-tumor TAM phenotypes and increased cytotoxic T cell infiltration, which was sufficient to limit tumor progression. This may present a novel translational approach for ovarian cancer treatment, with the potential to increase responses to T cell-directed therapy in future studies.
Risk of HPV-related extra-cervical cancers in women treated for cervical intraepithelial neoplasia
Authors: Preti Mario , Rosso Stefano , Micheletti Leonardo , Libero Carola , Sobrato Irene , Giordano Livia , Busso Paola , Gallio Niccolò , Cosma Stefano , Bevilacqua Federica , Benedetto Chiara
Published: October 2020

Background

The aim was to estimate the risk of subsequent extra-cervical Human Papillomavirus (HPV) related cancer in patients surgically treated for high grade cervical intraepithelial neoplasia (CIN 2–3). This is the first study in Italy investigating the occurrence of extra-cervical tumors in this cohort of patients.

Methods

3184 patients surgically treated for CIN2–3 since 1992 at the Department of Surgical Sciences of University of Torino were considered. The risk of HPV-related cancer was calculated as Standardized Incidence Ratio (SIR), using as expected values tumour age specific incidence of resident population.

Results

173 second primary cancer (SCPs) were identified. SIR to develop cancer after treatment for CIN2–3 was 2.2 (CI 95% 1.89–2.50). Among these occurrences, 10 are in HPV related sites: 1 anus (SIR = 1.8; 0.04–10.0), 3 vagina (SIR = 12.4; 2.56–36.3), 1 vulva (SIR = 1.7; 0.04–9.59), 5 oropharynx (SIR = 8.5; 2.76–19.8).

Significant risk has been also recorded for pulmonary (SIR = 3.1; 0.70–5.27) and bladder (SIR = 4.05; 1.10–10.56), with smoking as possible cofactor. We also found increased risk for breast (SIR = 2.4; 2.07–2.84) and ovarian cancers (SIR = 2.1; 1.13–3.49), probably due to an higher adherence to spontaneous and programmed screening programs.

Conclusions

Our study supports the hypothesis of an increased risk of HPV-related tumours for CIN treated patients, mostly for CIN3. It is conceivable the need of early diagnosis for these cancers in this higher-risk populations.
An audit tool for longitudinal assessment of the health-related characteristics of urban neighborhoods: implementation methods and reliability results
Authors: Ghosh-Dastidar Madhumita , Hunter Gerald P. , Sloan Jennifer C. , Collins Rebecca L. , Richardson Andrea S. , Troxel Wendy , Colabianchi Natalie , Dubowitz Tamara
Published: October 2020

Background

Improving the neighborhood environment may help address chronic disease and mortality. To identify neighborhood features that are predictors of health, objective assessments of the environment are used. Multiple studies have reported on cross-sectional assessments of health-related neighborhood features using direct observation. As study designs expand to better understand causation and predictors of change, there is a need to test whether direct observation methods are adequate for longitudinal assessment. To our knowledge, this is the first study to report on the reliability of repeated measurements of the neighborhood environment, and their stability, over time.

Methods

The Pittsburgh Hill/Homewood Research on Neighborhood Change and Health (PHRESH) study conducted longitudinal assessments in two low-income, African American neighborhoods at three waves (years 2012, 2015, 2017). The PHRESH audit tool is a modification of earlier validated tools, with an emphasis on environment features relevant for physical activity, sleep, and obesogenic behaviors. Trained data-collector pairs conducted direct observations of a 25% sample of street segments in each neighborhood. At each wave, we audited a sub-sample of street segments twice and assessed reliability using percentage inter-observer agreement and krippendorf’s alpha statistics. Stability of these items was assessed as exhibiting moderate or high agreement at every time point.

Results

Across waves, a majority (81%) of the items consistently demonstrated moderate to high agreement except for items such as public/communal space, amount of shade, sidewalk features, number of traffic lanes, garden/flower bed/planter, art/statue/monument, amount of trash, and physical disorder. The list of items with poor agreement includes features that are easy to miss (e.g. flower bed/planter), hard to assess from outside (e.g. public/communal space), or may change quickly (e.g. amount of trash).

Conclusion

In this paper, we have described implementation methods, reliability results and lessons learned to inform future studies of change. We found the use of consistent methods allowed us to conduct reliable, replicable longitudinal assessments of the environment. Items that did not exhibit stability are less useful for detecting real change over time. Overall, the PHRESH direct observation tool is an effective and practical instrument to detect change in the neighborhood environment.
Employment transitions for spouses of stroke survivors: evidence from Swedish national registries
Authors: Persson Josefine , Hensing Gunnel , Bonander Carl
Published: October 2020

Background

The sudden occurrence of stroke often leads to impaired physical, emotional, and cognitive abilities. Many stroke survivors therefore require support from their family members. However, little is known about the effects of a stroke event on the spouses’ employment transition probabilities. The aim of this study was twofold 1) to investigate whether a first ever stroke has an effect on employment transition probabilities for employed and unemployed spouses and 2) to analyze whether heterogeneity with respect to age, gender, education and comorbidities influence the size of the effect.

Method

Data for this population-based cohort study were extracted from Swedish national registries from 2005 to 2016. The national sample consisted of 1818 spouses of first ever stroke survivors during 2010 and 2011, and 7399 matched controls that were employed or unemployed during 5 years prior stroke onset. Effects of stroke on spousal employment transitions were analyzed using linear regression, stratified by employment status prior to stroke onset.

Results

Employed spouses prior stroke onset reduced their employment by − 1.3 percentage points (95% CI, − 2.4, − 0.2). The data also indicated that employed spouses with lower age, comorbid conditions, and low educational attainment may be at even greater risk of transitioning to unemployment. On the other hand, stroke events appear to have limited impact on spouses that were unemployed prior to stroke onset.

Conclusion

The risk of transitioning to unemployment appears to increase after stroke onset for spouses of stroke survivors, and disadvantaged groups may be at even greater risk. Thus, it is important for policy-makers to implement interventions to ensure that these groups of spouses have the possibilities to combine their caregiving role and remaining in the labor market.
Transurethral resection of a bladder trigone leiomyoma: a rare case report
Authors: Zachariou Athanasios , Filiponi Maria , Dimitriadis Fotios , Kaltsas Aris , Sofikitis Nikolaos
Published: October 2020

Background

Bladder leiomyomas are rare and benign tumors of the bladder. They account for 0.43% of all bladder tumors, and only 250 cases have been reported in English literature. Based on the size and localization of the lesion, their symptoms vary considerably. Women seem to be more affected, and obstructive symptoms predominate. Surgical treatment is almost always highly effective, leaving a low recurrence rate.

Case presentation

We present a clinical case of a 52-year old man with macroscopic hematuria and obstructive lower urinary tract symptoms due to a large bladder trigone leiomyoma. CT and MRI showed a well-defined large bladder leiomyoma and cystoscopy established the initial findings. The patient underwent successful transurethral resection of the lesion, and pathology findings confirmed the diagnosis.

Conclusions

This case report demonstrates that transurethral resection of a large bladder trigone leiomyoma is a feasible and successful procedure. Long term follow-up proves that there is neither scarring distortion of the bladder trigone area nor damage in the ureteral orifices, even though there was a thorough removal of the trigone wall.
Creation of Golden Gate constructs for gene doctoring
Authors: Thomson Nicholas M. , Zhang Chuanzhen , Trampari Eleftheria , Pallen Mark J.
Published: October 2020

Background

Gene doctoring is an efficient recombination-based genetic engineering approach to mutagenesis of the bacterial chromosome that combines the λ-Red recombination system with a suicide donor plasmid that is cleaved in vivo to generate linear DNA fragments suitable for recombination. The use of a suicide donor plasmid makes Gene Doctoring more efficient than other recombineering technologies. However, generation of donor plasmids typically requires multiple cloning and screening steps.

Results

We constructed a simplified acceptor plasmid, called pDOC-GG, for the assembly of multiple DNA fragments precisely and simultaneously to form a donor plasmid using Golden Gate assembly. Successful constructs can easily be identified through blue-white screening. We demonstrated proof of principle by inserting a gene for green fluorescent protein into the chromosome of Escherichia coli. We also provided related genetic parts to assist in the construction of mutagenesis cassettes with a tetracycline-selectable marker.

Conclusions

Our plasmid greatly simplifies the construction of Gene Doctoring donor plasmids and allows for the assembly of complex, multi-part insertion or deletion cassettes with a free choice of target sites and selection markers. The tools we developed are applicable to gene editing for a wide variety of purposes in Enterobacteriaceae and potentially in other diverse bacterial families.
Isolation of endophytic bacteria from the leaves of Anredera cordifolia CIX1 for metabolites and their biological activities
Authors: Nxumalo Celiwe Innocentia , Ngidi Londeka Sibusisiwe , Shandu Jabulani Siyabonga Emmanuel , Maliehe Tsolanku Sidney
Published: October 2020

Background

Endophytes, especially those that are found from ethnopharmacologically noteworthy medicinal plants have attracted attention due to their diverse bioactive metabolites of pharmacological importance.

Methods

This study aimed at isolating endophytic bacterium from the leaves of Anredera cordifolia CIX1 for its bioactive metabolites. The endophytic isolates were identified by 16S rRNA sequence and investigated for antibiotic sensitivity using different antibiotics. The secondary metabolites were evaluated for antibacterial activity against four bacterial strains. The 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis (3- ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods were used to assess their scavenging activities. The chemical components were analysed by gas chromatography-mass spectrometry (GC-MS).

Results

Out of 13 isolates, Isolate 1 was identified as Pseudomonas aeruginosa CP043328.1. It was resistant to clindamycin, ertapenem, penicillin G, amoxicillin, cephalothin and kanamycin but sensitive to imipenem, meropenem, and gentamycin. Its extract demonstrated antibacterial activity with minimum inhibitory concentration value of 0.098 against Bacillus cereus (ATCC 10102) and Staphylococcus aureus (ATCC 25925) and 0.391 mg/ml against Escherichia coli (ATCC 25922) and Proteus mirabilis (ATCC 25933). The extract revealed DPPH and ABTS scavenging activities with half maximal inhibitory concentration value of 0.650 mg/ml and 0.15 mg/ml, respectively. The GC-MS revealed a total of 15 compounds with diisooctyl phthalate (50.51%) and [1, 2, 4] oxadiazole, 5-benzyl-3 (10.44%) as major components.

Conclusions

P. aeruginosa CP043328.1 produced secondary metabolites with antibacterial and antioxidant activities.
What is the impact of the COVID-19 pandemic on emergency medicine residency training: an observational study
Authors: Lo Hsiang-Yun , Lin Shen-Che , Chaou Chung-Hsien , Chang Yu-Che , Ng Chip-Jin , Chen Shou-Yen
Published: October 2020

Background

The coronavirus disease 2019 (COVID-19) pandemic has engendered difficulties for health systems globally; however, the effect of the pandemic on emergency medicine (EM) residency training programs is unknown. The pandemic has caused reduced volumes of emergency department (ED) patients, except for those with COVID-19 infections, and this may reduce the case exposure of EM residents. The primary objective of this study was to compare the clinical exposure of EM residents between the prepandemic and pandemic periods.

Methods

This was a retrospective study of EM resident physicians’ training in a tertiary teaching hospital with two branch regional hospitals in Taiwan. We retrieved data regarding patients seen by EM residents in the ED between September 1, 2019, and April 30, 2020. The first confirmed COVID-19 case in Taiwan was reported on January 11, so the pandemic period in our study was defined as spanning from February 1, 2020, to April 30, 2020. The number and characteristics of patients seen by residents were recorded. We compared the data between the prepandemic and pandemic periods.

Results

The mean number of patients per hour (PPH) seen by EM residents in the adult ED decreased in all three hospitals during the pandemic. The average PPH of critical area of medical ED was 1.68 in the pre-epidemic period and decreased to 1.33 in the epidemic period (p value < 0.001). The average number of patients managed by residents decreased from 1.24 to 0.82 in the trauma ED (p value = 0.01) and 1.56 to 0.51 in the pediatric ED (p value = 0.003) during the pandemic, respectively. The severity of patient illness did not change significantly between the periods.

Conclusions

The COVID-19 pandemic engendered a reduced ED volume and decreased EM residents’ clinical exposure. All portion of EM residency training were affected by the pandemic, with pediatric EM being the most affected. The patient volume reduction may persist and in turn reduce patients’ case exposure until the pandemic subsides. Adjustment of the training programs may be necessary and ancillary methods of learning should be used to ensure adequate EM residency training.
Clinicopathological and imaging features of pulmonary alveolar microlithiasis in a dog – a case report
Authors: Sousa Ana Canadas , Santos Joana C. , Landolt Clara , Gomes Catarina , Dias-Pereira Patrícia , Baptista Cláudia S.
Published: October 2020

Background

The aetiology of pulmonary alveolar microlithiasis (PAM) in animals is still unknown. In humans, this pulmonary disorder is a rare autosomal recessive disorder triggered by a mutation in the gene SLC34A2, which causes deposition and aggregation of calcium and phosphate in the pulmonary parenchyma with formation of microliths. Although histopathological examination is required for a definite diagnosis, in humans, imaging modalities such as computed tomography can demonstrate typical patterns of the disease. This is the first description of the computed tomographic (CT) features of a histologically confirmed PAM in dogs.

Case presentation

The following report describes a case of a 7-year-old female Boxer dog evaluated for paroxysmal loss of muscle tone and consciousness with excitement. The main differential diagnoses considered were syncope, seizures, and narcolepsy-cataplexy. The results of the complete blood count, serum biochemistry panel, urinalysis, arterial blood pressure, echocardiography, abdominal ultrasound, Holter monitoring, and ECG were all within normal limits. Additional exams included thoracic radiographs, head and thorax CT, bronchoalveolar lavage (BAL), and CT-guided cytology. Thoracic radiographs revealed micronodular calcifications in the lungs, with sandstorm appearance. Computed tomography of the thorax showed the presence of numerous mineralized high-density agglomerates of multiple sizes throughout the pulmonary parenchyma, a reticular pattern with ground glass opacity and intense mineralized fibrosis of the pleural lining. Head CT was unremarkable. BAL and CT-guided cytology were inconclusive, but imaging features strongly suggest the diagnosis of PAM, which was histologically confirmed after necropsy.

Conclusions

This case report contributes to the clinicopathological and imaging characterization of pulmonary alveolar microlithiasis in dogs. In this species, the diagnosis of PAM should be considered when CT features evidence a reticular pattern with ground glass opacity and the presence of an elevated number and size of calcifications.
Longitudinal [18F]FDG-PET/CT analysis of the glucose metabolism in ApoE-deficient mice
Authors: Kuhla Angela , Meuth Lou , Stenzel Jan , Lindner Tobias , Lappe Chris , Kurth Jens , Krause Bernd J. , Teipel Stefan , Glass Änne , Kundt Guenther , Vollmar Brigitte
Published: October 2020

Background

Strong line of evidence suggests that the increased risk to develop AD may at least be partly mediated by cholesterol metabolism. A key regulator of cholesterol transport is the Apolipoprotein E4 (ApoE4), which plays a fundamental role in neuronal maintenance and repair. Impaired function of ApoE4 may contribute to altered cerebral metabolism leading to higher susceptibility to neurodegeneration.

Methods

To determine a possible link between ApoE function and alterations in AD in the brain of Apolipoprotein E-deficient mice (ApoE−/−) in a longitudinal manner metabolic and neurochemical parameters were analyzed. Cortical metabolism was measured by 2-deoxy-2-[18F]fluoroglucose ([18F]FDG)-PET/CT and proton magnetic resonance spectroscopy (1H-MRS) served to record neurochemical status.

Results

By using [18F]FDG-PET/CT, we showed that brain metabolism declined significantly stronger with age in ApoE−/− versus wild type (wt) mice. This difference was particularly evident at the age of 41 weeks in almost each analyzed brain region. In contrast, the 1H-MRS-measured N-acetylaspartate to creatine ratio, a marker of neuronal viability, did not decline with age and did not differ between ApoE−/− and wt mice.

Conclusion

In summary, this longitudinal in vivo study shows for the first time that ApoE−/− mice depict cerebral hypometabolism without neurochemical alterations.
Optimization of unmanned aerial vehicle augmented ultra-dense networks
Authors: Zamani Alireza , Kämmer Robert , Hu Yulin , Schmeink Anke
Published: October 2020

In this paper, we study the integration of unmanned aerial vehicle small cells (UAV-SCs) for the purpose of augmenting or temporarily restoring service to an ultra-dense cellular network. The aim is to minimize the overall power consumption of the network by jointly optimizing the number of UAV-SCs, their placement, associations, and the power allocation, subject to user QoS (quality of service), transmit power, and fronthaul capacity constraints. As the resulting optimization problem is non-convex and computationally inefficient to solve, we investigate lower complexity alternatives. By reformulating the original problem, a linear structure can be obtained that is efficiently solved by off-the-shelf solvers. Furthermore, we also propose a meta-heuristic method that is based on particle swarm optimization. The performance of the proposed methods is evaluated via simulation studies and compared to state-of-the-art techniques. The results illustrate that the proposed methods consistently outperform conventional techniques by deploying fewer UAV-SCs and also lowering the transmit powers. Furthermore, considerable power savings were observed particularly for low QoS demands and dense scenarios.
Time-ResNeXt for epilepsy recognition based on EEG signals in wireless networks
Authors: Wang Shaoqiang , Wang Shudong , Zhang Song , Wang Yifan
Published: October 2020

To automatically detect dynamic EEG signals to reduce the time cost of epilepsy diagnosis. In the signal recognition of electroencephalogram (EEG) of epilepsy, traditional machine learning and statistical methods require manual feature labeling engineering in order to show excellent results on a single data set. And the artificially selected features may carry a bias, and cannot guarantee the validity and expansibility in real-world data. In practical applications, deep learning methods can release people from feature engineering to a certain extent. As long as the focus is on the expansion of data quality and quantity, the algorithm model can learn automatically to get better improvements. In addition, the deep learning method can also extract many features that are difficult for humans to perceive, thereby making the algorithm more robust. Based on the design idea of ResNeXt deep neural network, this paper designs a Time-ResNeXt network structure suitable for time series EEG epilepsy detection to identify EEG signals. The accuracy rate of Time-ResNeXt in the detection of EEG epilepsy can reach 91.50%. The Time-ResNeXt network structure produces extremely advanced performance on the benchmark dataset (Berne-Barcelona dataset) and has great potential for improving clinical practice.
TMaR: a two-stage MapReduce scheduler for heterogeneous environments
Authors: Maleki Neda , Faragardi Hamid Reza , Rahmani Amir Masoud , Conti Mauro , Lofstead Jay
Published: October 2020

In the context of MapReduce task scheduling, many algorithms mainly focus on the scheduling of Reduce tasks with the assumption that scheduling of Map tasks is already done. However, in the cloud deployments of MapReduce, the input data is located on remote storage which indicates the importance of the scheduling of Map tasks as well. In this paper, we propose a two-stage Map and Reduce task scheduler for heterogeneous environments, called TMaR. TMaR schedules Map and Reduce tasks on the servers that minimize the task finish time in each stage, respectively. We employ a dynamic partition binder for Reduce tasks in the Reduce stage to lighten the shuffling traffic. Indeed, TMaR minimizes the makespan of a batch of tasks in heterogeneous environments while considering the network traffic. The simulation results demonstrate that TMaR outperforms Hadoop-stock and Hadoop-A in terms of makespan and network traffic and achieves by an average of 29%, 36%, and 14% performance using Wordcount, Sort, and Grep benchmarks. Besides, the power reduction of TMaR is up to 12%.