bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal Cavernoma in an Infant: A Rare Pathological Entity with an Atypical Presentation
Authors: Gendle Chandrashekhar , Salunke Pravin , Karthigeyan Madhivanan , Gupta Kirti
Published: September 2020

Introduction: Cavernous malformation (CM) of the pediatric spine is uncommon, and its presentation especially in infancy is extremely rare. We report an unusual case of thoracolumbar intramedullary CM with hemorrhage in a 5-month-old male child. Case Presentation: The child presented with the predominant symptom of urinary retention, and the underlying neurological cause was initially overlooked. However, magnetic resonance imaging obtained after the onset of progressive limb weakness revealed a D11-L1 intramedullary lesion with features of intralesional bleed. Intraoperatively, the lesion showed evidence of hemorrhage and was completely excised. The final histopathology confirmed a cavernoma. Conclusion: Although rare, spinal CM can present with bleed in very young children. It is imperative to identify the subtle clinico-radiological findings and suspect such lesions, as an early treatment portends a good outcome.
Primary Tumor Resection Is Associated with a Better Outcome among Advanced EGFR-Mutant Lung Adenocarcinoma Patients Receiving EGFR-TKI Treatment
Authors: Tseng Jeng-Sen , Hsu Kuo-Hsuan , Zheng Zhe-Rong , Yang Tsung-Ying , Chen Kun-Chieh , Huang Yen-Hsiang , Su Kang-Yi , Yu Sung-Liang , Chang Gee-Chen
Published: September 2020

Objectives: The characteristics and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in advanced EGFR-mutant lung adenocarcinoma patients with primary tumor resection (PTR) is not yet clear. Methods: We enrolled advanced EGFR-mutant lung adenocarcinoma patients with EGFR-TKI as first-line therapy to access the impact of PTR on the outcomes. Results: A total of 466 patients were enrolled with 76 patients (16.3%) undergoing PTR; 59 patients recurred after curative surgery, while 17 patients underwent surgery as diagnostic purposes. PTR patients displayed a better performance status, a lower metastatic burden, and much less measurable diseases (30.3 vs. 97.4%, p < 0.001). PTR patients experienced a significantly longer progression-free survival (25.1 [95% CI 16.6–33.7] vs. 9.4 [95% CI 8.4–10.4] months; aHR 0.40 [95% CI 0.30–0.54], p < 0.001) and overall survival (56.8 [95% CI 36.3–77.2] vs. 31.8 [95% CI 28.2–35.4] months; aHR 0.57 [95% CI 0.39–0.84], p = 0.004). Survival advantage was still observed while comparing PTR patients with the better performance and lower metastatic burden subgroup found within the non-resection group. Moreover, the progression-free survival and overall survival of 11 patients who were found having pleural metastases during surgery and underwent PTR plus pleural biopsy, were also longer than those with pure N0--1/M1a-malignant pleural effusion disease in the non-resection group (n = 19) (p < 0.001 and p = 0.002, respectively). Conclusion: PTR was associated with significantly better outcomes in advanced lung adenocarcinoma patients treated with EGFR-TKI. Further studies are needed to evaluate the biological role of PTR among these patients.
Spectrum of Pathogenic Variants in SRD5A2 in Indian Children with 46,XY Disorders of Sex Development and Clinically Suspected Steroid 5α-Reductase 2 Deficiency
Authors: Kumar Anil , Sharma Rajni , Faruq Mohammed , Suroliya Varun , Kumar Manoj , Sharma Shilpa , Werner Ralf , Hiort Olaf , Jain Vandana
Published: September 2020

The aim of this study was to assess the prevalence of pathogenic variants in the SRD5A2 gene in children with 46,XY disorders of sex development (DSD) with normal to high serum testosterone levels and absence of Müllerian structures on imaging and to evaluate the genotype-phenotype correlation. Seventy-five patients with 46,XY DSD and probable clinical diagnosis of 5α-reductase 2 deficiency or androgen insensitivity syndrome were enrolled. Genetic analysis was done for pathogenic variants in SRD5A2, and the genotype-phenotype correlation was studied. As a result, 10 pathogenic or likely pathogenic biallelic variants in SRD5A2, either homozygous or compound heterozygous, were identified in 25 of 75 (33.3%) patients. The hCG stimulated testosterone: dihydrotestosterone (T:DHT) ratio was elevated in all patients with pathogenic variants in SRD5A2 and in nearly 90% of those without pathogenic variants in SRD5A2 in whom this was assessed. The missense pathogenic variant p.R246Q was a hotspot. One novel pathogenic variant p.Y178*, and a variant p.F194I, not previously reported in patients with 5α-reductase 2 deficiency, were identified. The missense variant p.F194I was predicted as deleterious and damaging by in silico analysis and as likely to reduce the enzyme activity by protein modeling. In conclusion, pathogenic variants in SRD5A2 can be detected in a wide spectrum of Indian patients with 46,XY DSD. Molecular genetic analysis should be considered as a first-line test as the T:DHT ratio lacks specificity and a hotspot variant is present in a vast majority.
Complete Clinical Response in Stage IVB Endometrioid Endometrial Carcinoma after First-Line Pembrolizumab Therapy: Report of a Case with Isolated Loss of PMS2 Protein
Authors: Carvalho Jesus Paula , Del Giglio Auro , Achatz Maria Isabel , Carvalho Filomena Marino
Published: September 2020

Endometrial cancer is the only gynecological cancer that is rising in incidence and associated mortality worldwide. Although most cases are diagnosed as early stage disease, with chances of cure after primary surgical treatment, those with advanced or metastatic disease have a poor prognosis because of the quality of treatment options that are currently available. Mismatch repair (MMR)-deficient cancers are susceptible to programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 inhibitors. The US Food and Drug Administration granted accelerated approval to pembrolizumab for MMR-deficient tumors, the first tumor-agnostic approval for a drug. We present a case of stage IV endometrioid endometrial carcinoma with isolated PMS2 protein loss, in which treatment with first-line pembrolizumab therapy achieved a complete clinical and pathological response of tumor.
Aspiration eines Perikardergusses mittels EUS-B-FNA bei Verdacht auf Lungentumoren
Authors: Christiansen Ida Skovgaard , Clementsen Paul Frost , Petersen Jesper Koefod , Fjaellegaard Katrine , Høegholm Asbjørn , Bodtger Uffe
Published: September 2020

Die ultraschallgestützte Feinnadelaspiration mit Zugang über den Ösophagus unter Verwendung eines endobronchialen Endoskops (EUS-B-FNA) wird von Pneumologen zunehmend für die Diagnose von Lungentumoren angewendet. Bislang liegen uns jedoch nur wenige Erfahrungen und Daten aus der Literatur über das Staging der Erkrankung vor. Wir stellen hier 2 Fälle einer EUS-B-gestützten Aspiration eines malignen Perikardergusses vor, die unter denselben Bedingungen wie eine Bronchoskopie und endobronchiale Ultraschalluntersuchung durchgeführt wurden. Es traten keine Komplikationen auf. Wir ziehen den Schluss, dass es sich bei der EUS-B-FNA vermutlich um ein sicheres und wirksames Verfahren zur Beurteilung eines Perikardergusses im Rahmen der Lungentumor-Diagnostik handelt. Somit könnte die EUS-B-FNA bei der diagnostischen Abklärung Zeit sparen, das Tumorstaging verbessern und eine transthorakale Perikardpunktion überflüssig machen.
Voltage harmonics reduction in single phase 9-level transistor clamped H-bridge inverter using nearest level control method
Authors: Mohd Said Nurul Ain , Ali Saleh Wail Ali , Abd Halim Wahidah
Published: September 2020

This paper proposes a nearest level control method based modulation scheme for a 9-level symmetrical Transistor Clamped H-bridge (TCHB) inverter. The topology has gained increasing research focus due to its advantages in obtaining high quality output while using a reduced number of electronic components. The device count for obtaining a 9-level output voltage is it uses 10 active switches as compared to the 16 being used in a conventional 9-level cascaded H-Bridge (CHB) inverter. The significant contribution of the research is the development of the NLC modulation technique that operates at the fundamental frequency, thus reducing switching losses, and able to reduce harmonic content significantly. The reduced harmonic content can lessen the power quality problem. The NLC modulation scheme, shows that the overall THD is reduced without the need for filtration. The 50 values of harmonic content will be count that follows the IEEE Standard 519. MATLAB/Simulink based simulations and experimental results obtained from the laboratory prototype of a single-phase TCHB inverter feeding a R load validate the theoretical analyses and effectiveness of the proposed modulation scheme.
A review of the gall midges (Diptera: Cecidomyiidae) of Indonesia: taxonomy, biology and adult key to genera
Authors: KOLESIK PETER , GAGNÉ RAYMOND J.
Published: September 2020

Forty-seven species in 25 genera of gall midges (Diptera: Cecidomyiidae: Cecidomyiinae) known from Indonesia are reviewed. Available historic types were examined, and taxa are revised. Leefmansiella Kolesik & Gagné gen. nov. is erected for Trishormomyia pandani Felt. Actilasioptera falcaria (Felt) is found to be a senior synonym of Actilasioptera tumidifolium Gagné. Apoasphondylia orientalis Felt is transferred to Bruggmanniella Tavares, new combination; Asphondylia bursaria Felt is changed to Bruggmanniella, new combination; Contarinia eragrostidis Felt to Stenodiplosis Reuter, new combination; the Australian Contarinia brevipalpis Harris to Stenodiplosis, new combination; Dasyneura tetrastigma Felt to Gephyraulus Rübsaamen, new combination; and the Philippine Itonida paederiae Felt to Eucalyptodiplosis Kolesik, new combination. For each species, type data, a description, the basic biology and the known geographical distribution are given. A key to Cecidomyiidae genera based on adults, with references to described species, is provided. Species of economic importance, as pests of cultivated plants or biological control agents of weeds and pest arthropods, are listed.
Comparative transcriptome analysis of the main beam and brow tine of sika deer antler provides insights into the molecular control of rapid antler growth
Authors: Yao Baojin , Wang Chaonan , Zhou Zhenwei , Zhang Mei , Zhao Daqing , Bai Xueyuan , Leng Xiangyang
Published: September 2020

Background

Deer antlers have become a valuable model for biomedical research due to the capacities of regeneration and rapid growth. However, the molecular mechanism of rapid antler growth remains to be elucidated. The aim of the present study was to compare and explore the molecular control exerted by the main beam and brow tine during rapid antler growth.

Methods

The main beams and brow tines of sika deer antlers were collected from Chinese sika deer (Cervus nippon) at the rapid growth stage. Comparative transcriptome analysis was conducted using RNA-Seq technology. Differential expression was assessed using the DEGseq package. Functional Gene Ontology (GO) enrichment analysis was accomplished using a rigorous algorithm according to the GO Term Finder tool, and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis was accomplished with the R function phyper, followed by the hypergeometric test and Bonferroni correction. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to verify the RNA levels for differentially expressed mRNAs.

Results

The expression levels of 16 differentially expressed genes (DEGs) involved in chondrogenesis and cartilage development were identified as significantly upregulated in the main beams, including transcription factor SOX-9 (Sox9), collagen alpha-1(II) chain (Col2a1), aggrecan core protein (Acan), etc. However, the expression levels of 17 DEGs involved in endochondral ossification and bone formation were identified as significantly upregulated in the brow tines, including collagen alpha-1(X) chain (Col10a1), osteopontin (Spp1) and bone sialoprotein 2 (Ibsp), etc.

Conclusion

These results suggest that the antler main beam has stronger growth capacity involved in chondrogenesis and cartilage development compared to the brow tine during rapid antler growth, which is mainly achieved through regulation of Sox9 and its target genes, whereas the antler brow tine has stronger capacities of endochondral bone formation and resorption compared to the main beam during rapid antler growth, which is mainly achieved through the genes involved in regulating osteoblast and osteoclast activities. Thus, the current research has deeply expanded our understanding of the intrinsic molecular regulation displayed by the main beam and brow tine during rapid antler growth.
A surveillance method to identify patients with sepsis from electronic health records in Hong Kong: a single centre retrospective study
Authors: Liu Ying Zhi , Chu Raymond , Lee Anna , Gomersall Charles David , Zhang Lin , Gin Tony , Chan Matthew T. V. , Wu William K. K. , Ling Lowell
Published: September 2020

Background

Currently there are only two population studies on sepsis incidence in Asia. The burden of sepsis in Hong Kong is unknown. We developed a sepsis surveillance method to estimate sepsis incidence from a population electronic health record (EHR) in Hong Kong using objective clinical data. The study objective was to assess our method’s performance in identifying sepsis using a retrospective cohort. We compared its accuracy to administrative sepsis surveillance methods such as Angus’ and Martin’s methods.

Method

In this single centre retrospective study we applied our sepsis surveillance method on adult patients admitted to a tertiary hospital in Hong Kong. Two clinicians independently reviewed the clinical notes to determine which patients had sepsis. Performance was assessed by sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of Angus’, Martin’s and our surveillance methods using clinical review as “gold standard.”

Results

Between January 1 and February 28, 2018, our sepsis surveillance method identified 1352 adult patients hospitalised with suspected infection. We found that 38.9% (95%CI 36.3–41.5) of these patients had sepsis. Using a 490 patient validation cohort, two clinicians had good agreement with weighted kappa of 0.75 (95% CI 0.69–0.81) before coming to consensus on diagnosis of uncomplicated infection or sepsis for all patients. Our method had sensitivity 0.93 (95%CI 0.89–0.96), specificity 0.86 (95%CI 0.82–0.90) and an AUC 0.90 (95%CI 0.87–0.92) when validated against clinician review. In contrast, Angus’ and Martin’s methods had AUCs 0.56 (95%CI 0.53–0.58) and 0.56 (95%CI 0.52–0.59), respectively.

Conclusions

A sepsis surveillance method based on objective data from a population EHR in Hong Kong was more accurate than administrative methods. It may be used to estimate sepsis population incidence and outcomes in Hong Kong.

Trial registration

This study was retrospectively registered at clinicaltrials.gov on October 3, 2019 (NCT04114214).
D6 blastocyst transfer on day 6 in frozen-thawed cycles should be avoided: a retrospective cohort study
Authors: Xu Huiling , Qiu Shumin , Chen Xiaojing , Zhu Suqin , Sun Yan , Zheng Beihong
Published: September 2020

Background

There is no definitive evidence about the suitable timing to transfer blastocysts formed and cryopreserved on day 6 (D6 blastocysts) in frozen-thawed embryo transfer (FET) cycles. This study aimed to investigate the suitable timing to transfer D6 blastocysts in FET cycles and to identify factors affecting clinical pregnancy rate (CPR) and early miscarriage rate (EMR) in FET cycles with blastocysts.

Methods

This retrospective cohort study included 1788 FET cycles with blastocysts. There were 518 cycles with D6 blastocysts, and 1270 cycles with blastocysts formed and cryopreserved on day 5 (D5 blastocysts) (D5 group). According to the blastocyst transfer timing, the cycles with D6 blastocysts were divided into cycles with D6 blastocysts transferred on day 5 (D6-on-D5 group, 103 cycles) and cycles with D6 blastocysts transferred on day 6 (D6-on-D6 group, 415 cycles). The chi-square test, independent t-test or Mann-Whitney test, and logistic regression analysis were used for data analysis.

Results

The CPR and implantation rate (IR) were significantly higher in the D6-on-D5 group than in the D6-on-D6 group (55.3% vs. 37.3%, 44.8% vs. 32.6%, P < 0.01). The CPR and IR were significantly higher in the D5 group than in the D6-on-D5 group (66.0% vs. 55.3%, 62.1% vs. 44.8%, P < 0.05), and the EMR was significantly lower in the D5 group than in the D6-on-D5 group (11.2% vs. 21.1%, P < 0.05). Logistic regression analysis demonstrated that transfer D6 blastocysts on day 5, instead of day 6, could significantly increase the CPR (odds ratio[OR]: 2.031, 95% confidence interval (CI): 1.296–3.182, P = 0.002). FET cycles with D6 blastocysts transferred on day 5 had a higher EMR than those with D5 blastocysts (OR: 2.165, 95% CI: 1.040–4.506, P = 0.039). Hormone replacement therapy (HRT) cycles exhibited a higher EMR than natural cycles (OR: 1.953, 95% CI: 1.254–3.043, P = 0.003), while no difference was observed in the CPR (P > 0.05).

Conclusions

These results indicate that the suitable timing to transfer D6 blastocysts in FET cycles may be day 5, and D6 blastocyst transfer on day 6 in FET cycles should be avoided. D6 blastocysts transfer and HRT cycles may be associated with a higher EMR.
Standardized herbal extract PM014 alleviates fine dust-induced lung inflammation in mice
Authors: Lee Ye-Seul , Min Daeun , Park Seon-Young , Lee Junyoung , Bae Hyunsu
Published: September 2020

Background

Fine dust penetrates deep into the human alveoli, and the fine dust accumulated in the bronchus and lungs can directly trigger various respiratory diseases. PM014 (HL301) is the herbal extract derived from the herbal medicine Chung-Sang-Bo-Ha-Tang which is used for the treatment of lung diseases.

Methods

To evaluate the effect of PM014 on the lung inflammation induced by fine dust, this study investigated inflammatory responses in the lung upon pm10 exposure by examining the infiltration of inflammatory cell profiles from bronchial alveolar lavage fluid (BALF), lung histology, and production of pro-inflammatory cytokines measured by RT-PCR and ELISA.

Results

PM014-treated mice exhibited reduced lung tissue damage and inflammatory cell infiltration. Bronchoalveolar lavage fluid (BALF) analysis showed significant decrease in the population of total cells, macrophages, eosinophils, and neutrophils in PM014-treated mice. PM014 treatment downregulated the pro-inflammatory cytokine expressions including IL-1b, IL-8, IL-6, TNF-alpha, IL-21 and IL-17. ELISA analysis also showed reduced production of IL-1b, IL-6 and IL-17 in PM014-treated mice.

Conclusion

PM014 suppressed the pm10-induced inflammatory response in mice. This study shows that PM014 is a possible therapeutic agent for lung inflammation induced by fine dust.
Bayesian variable selection for high dimensional predictors and self-reported outcomes
Authors: Gu Xiangdong , Tadesse Mahlet G , Foulkes Andrea S , Ma Yunsheng , Balasubramanian Raji
Published: September 2020

Background

The onset of silent diseases such as type 2 diabetes is often registered through self-report in large prospective cohorts. Self-reported outcomes are cost-effective; however, they are subject to error. Diagnosis of silent events may also occur through the use of imperfect laboratory-based diagnostic tests. In this paper, we describe an approach for variable selection in high dimensional datasets for settings in which the outcome is observed with error.

Methods

We adapt the spike and slab Bayesian Variable Selection approach in the context of error-prone, self-reported outcomes. The performance of the proposed approach is studied through simulation studies. An illustrative application is included using data from the Women’s Health Initiative SNP Health Association Resource, which includes extensive genotypic (>900,000 SNPs) and phenotypic data on 9,873 African American and Hispanic American women.

Results

Simulation studies show improved sensitivity of our proposed method when compared to a naive approach that ignores error in the self-reported outcomes. Application of the proposed method resulted in discovery of several single nucleotide polymorphisms (SNPs) that are associated with risk of type 2 diabetes in a dataset of 9,873 African American and Hispanic participants in the Women’s Health Initiative. There was little overlap among the top ranking SNPs associated with type 2 diabetes risk between the racial groups, adding support to previous observations in the literature of disease associated genetic loci that are often not generalizable across race/ethnicity populations. The adapted Bayesian variable selection algorithm is implemented in R. The source code for the simulations are available in the Supplement.

Conclusions

Variable selection accuracy is reduced when the outcome is ascertained by error-prone self-reports. For this setting, our proposed algorithm has improved variable selection performance when compared to approaches that neglect to account for the error-prone nature of self-reports.
The association between frailty and severe disease among COVID-19 patients aged over 60 years in China: a prospective cohort study
Authors: Ma Yao , Hou Lisha , Yang Xiufang , Huang Zhixin , Yang Xue , Zhao Na , He Min , Shi Yixin , Kang Yan , Yue Jirong , Wu Chenkai
Published: September 2020

Background

The coronavirus disease 2019 (COVID-19) has been a pandemic worldwide. Old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, whether frailty, a common geriatric syndrome of reduced reserve to stressors, is associated with poor prognosis among older COVID-19 patients is unknown. The aim of our study is to investigate the association between frailty and severe disease among COVID-19 patients aged ≥ 60 years.

Methods

A prospective cohort study of 114 hospitalized older patients (≥ 60 years) with confirmed COVID-19 pneumonia was conducted between 7 February 2020 and 6 April 2020. Epidemiological, demographic, clinical, laboratory, and outcome data on admission were extracted from electronic medical records. All patients were assessed for frailty on admission using the FRAIL scale, in which five components are included: fatigue, resistance, ambulation, illnesses, and loss of weight. The outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards models to identify the unadjusted and adjusted associations between frailty and severe illness. The significant variables in univariable analysis were included in the adjusted model.

Results

Of 114 patients, (median age, 67 years; interquartile range = 64–75 years; 57 [50%] men), 39 (34.2%), 39 (34.2%), and 36 (31.6%) were non-frail, pre-frail, and frail, respectively. During the 60 days of follow-up, 43 severe diseases occurred including eight deaths. Four of 39 (10.3%) non-frail patients, 15 of 39 (38.5%) pre-frail patients, and 24 of 36 (66.7%) frail patients progressed to severe disease. After adjustment of age, sex, body mass index, haemoglobin, white blood count, lymphocyte count, albumin, CD8+ count, D-dimer, and C-reactive protein, frailty (HR = 7.47, 95% CI 1.73–32.34, P = 0.007) and pre-frailty (HR = 5.01, 95% CI 1.16–21.61, P = 0.03) were associated with a higher hazard of severe disease than the non-frail.

Conclusions

Frailty, assessed by the FRAIL scale, was associated with a higher risk of developing severe disease among older COVID-19 patients. Our findings suggested that the use of a clinician friendly assessment of frailty could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.
Different hypothermic and cerebral perfusion strategies in extended arch replacement for acute type a aortic dissection: a retrospective comparative study
Authors: Dong Song-Bo , Xiong Jian-Xian , Zhang Kai , Zheng Jun , Xu Shang-Dong , Liu Yong-Min , Sun Li-Zhong , Pan Xu-Dong
Published: September 2020

Background

The optimal hypothermic level in total arch replacement with stented elephant trunk implantation for acute type A aortic dissection (aTAAD) has not been established, and the superiority of unilateral or bilateral cerebral perfusion remains a controversial issue. Therefore, we evaluated the application of moderate hypothermic circulatory arrest (MHCA) with a core temperature of 29 °C and bilateral selective antegrade cerebral perfusion in aTAAD treated by total arch replacement with stented elephant trunk implantation.

Methods

From July 2019 to January 2020, 25 aTAAD patients underwent total arch replacement with stented elephant trunk implantation via MHCA (29 °C) and bilateral selective antegrade cerebral perfusion (modified group). Thirty-six patients treated by the same procedure with MHCA (25 °C) and unilateral selective antegrade cerebral perfusion during this period were selected as controls.

Results

There were no differences between the two groups of patients in terms of age, sex, incidence of hypertension, malperfusion, and pericardial effusion, although the incidence of cardiac tamponade was higher in the modified group (control 2.8%, modified 20%; P = 0.038). The lowest mean circulatory arrest temperature was 24.6 ± 0.9 °C in the control group, and 29 ± 0.8 °C in the modified group (P <  0.001). In-hospital mortality was 4.9% (3/61) for the entire cohort (control 8.3%, modified 0; P = 0.262). The incidence of permanent neurologic deficit was 4.9% (control 8.3%, modified 0; P = 0.262). There were no significant differences in the occurrence of temporary neurological deficit, renal failure, and paraplegia between groups. The rate of major adverse events in the modified group was lower (30.6% vs. 4%, P = 0.019). A shorter duration of ventilation and ICU stay was identified in the modified group, as well as a reduced volume of drainage within the first 48 h and red blood cell transfusion.

Conclusions

The early results of MHCA (29 °C) and bilateral selective antegrade cerebral perfusion applied in total arch replacement with stented elephant trunk implantation for aTAAD were acceptable, providing similar inferior cerebral and visceral protection compared with that of the conventional strategy. A higher core temperature may account for the shorter duration of ventilation and ICU stay, as well as a reduced volume of drainage and red blood cell transfusion.
IFN-α confers epigenetic regulation of HBV cccDNA minichromosome by modulating GCN5-mediated succinylation of histone H3K79 to clear HBV cccDNA
Authors: Yuan Ying , Yuan Hongfeng , Yang Guang , Yun Haolin , Zhao Man , Liu Zixian , Zhao Lina , Geng Yu , Liu Lei , Wang Jiapei , Zhang Huihui , Wang Yufei , Zhang Xiao-dong
Published: September 2020

Background

Hepatitis B virus covalently closed circular DNA (HBV cccDNA) is assembled by histones and non-histones into a chromatin-like cccDNA minichromosome in the nucleus. The cellular histone acetyltransferase GCN5, displaying succinyltransferase activity, is recruited onto cccDNA to modulate HBV transcription in cells. Clinically, IFN-α is able to repress cccDNA. However, the underlying mechanism of IFN-α in the depression of cccDNA mediated by GCN5 is poorly understood. Here, we explored the effect of IFN-α on GCN5-mediated succinylation in the epigenetic regulation of HBV cccDNA minichromosome.

Results

Succinylation modification of the cccDNA minichromosome has been observed in HBV-infected human liver-chimeric mice and HBV-expressing cell lines. Moreover, histone H3K79 succinylation by GCN5 was identified in the system. Interestingly, the mutant of histone H3K79 efficiently blocked the replication of HBV, and interference with GCN5 resulted in decreased levels of HBV DNA, HBsAg, and HBeAg in the supernatant from de novo HBV-infected HepaRG cells. Consistently, the levels of histone H3K79 succinylation were significantly elevated in the livers of HBV-infected human liver-chimeric mice. The knockdown or overexpression of GCN5 or the mutant of GCN5 could affect the binding of GCN5 to cccDNA or H3K79 succinylation, leading to a change in cccDNA transcription activity. In addition, Southern blot analysis validated that siGCN5 decreased the levels of cccDNA in the cells, suggesting that GCN5-mediated succinylation of histone H3K79 contributes to the epigenetic regulation of cccDNA minichromosome. Strikingly, IFN-α effectively depressed histone H3K79 succinylation in HBV cccDNA minichromosome in de novo HepG2-NTCP and HBV-infected HepaRG cells.

Conclusions

IFN-α epigenetically regulates the HBV cccDNA minichromosome by modulating GCN5-mediated succinylation of histone H3K79 to clear HBV cccDNA. Our findings provide new insights into the mechanism by which IFN-α modulate the epigenetic regulation of HBV cccDNA minichromosome.
Unusual and delayed presentation of chronic uterine inversion in a young woman as a result of negligence by an untrained birth attendant: a case report
Authors: Garg Priyanka , Bansal Romi
Published: September 2020

Background

Uterine inversion is a rare but known complication following parturition and may prove fatal due to neurogenic shock or postpartum hemorrhage if not corrected immediately. The incidence is variable, occurring in 1 in 2000 to 1 in 50,000 deliveries, as reported in the past. Nowadays, the incidence is declining due to better antenatal care and increasing institutional deliveries. However, in a developing country such as India, due to cultural and financial reasons, most of the deliveries are still being conducted by untrained birth attendants (“dais”) who have sparse knowledge of oxytocic drugs. Hence, proper education and training should be imparted to the traditional birth attendants and local village health practitioners about the management of labor, placental delivery, timely diagnosis, and proper management of uterine inversion to avoid this grave complication. We report this case because only a limited number of such cases have been reported so far with delayed presentation of chronic uterine inversion 8 months after delivery as a result of the negligence of an untrained birth attendant.

Case presentation

We report a case of a patient with chronic uterine inversion presenting 8 months after childbirth as a result of ignorance at the time of delivery. A 22-year-old P1L1 (Para 1 Live 1) Asian woman of Punjabi ethnicity presented to our institute with a progressively increasing painless vaginal mass along with blood-stained vaginal discharge for the last 6 months and progressive dyspareunia (pain during intercourse) for the last 5 months that had worsened with time. She had experienced a full-term normal vaginal delivery at home 8 months earlier with the assistance of an untrained birth attendant (dai). Her history revealed that she had an unduly prolonged second stage of labor and was given aggressive fundal pressure due to inadequate bearing-down efforts and had collapsed after delivery but was managed conservatively by an untrained birth attendant. A provisional diagnosis of chronic uterine inversion was made on the basis of vaginal findings of a globular mass protruding from the cervix and approaching the vagina with thinning of the cervix around the mass, forming a tight constriction ring, in addition to ultrasound findings. The patient’s condition was corrected surgically using Haultain’s approach. She had a satisfactory outcome and was discharged symptom-free.

Conclusion

Awareness of this complication with timely diagnosis and prompt management can significantly minimize maternal morbidity and mortality, especially in a low- and middle-income country such as India, where 70–80% of deliveries still occur in a rural setting with untrained birth attendants.
Synovial membrane mesenchymal stem cells: past life, current situation, and application in bone and joint diseases
Authors: Li Na , Gao Jinfang , Mi Liangyu , Zhang Gailian , Zhang Liyun , Zhang Na , Huo Rongxiu , Hu Junping , Xu Ke
Published: September 2020

Mesenchymal stem cells (MSCs) can be isolated from not only bone marrow, but also various adult mesenchymal tissues such as periosteum, skeletal muscle, and adipose tissue. MSCs from different tissue sources have different molecular phenotypes and differentiation potential. Synovial membrane (SM) is an important and highly specific component of synovial joints. Previous studies have suggested that the synovium is a structure with a few cell layers thick and consists mainly of fibroblast-like synoviocytes (FLS), which forms a layer that lining the synovial membrane on the joint cavity and synovial fluid through cell-cell contact. In recent years, studies have found that there are also mesenchymal stem cells in the synovium, and as an important part of the mesenchymal stem cell family, it has strong capabilities of cartilage forming and tissue repairing. This article reviews the sources, surface markers, subtypes, influencing factors, and applications in inflammatory joints of synovial membrane mesenchymal stem cells (SM-MSCs) in recent years, aiming to clarify the research status and existing problems of SM-MSCs.
Spatiotemporal analysis of urban growth on forest and agricultural land using geospatial techniques and Shannon entropy method in the satellite town of Ethiopia, the western fringe of Addis Ababa city
Authors: Deribew Kiros Tsegay
Published: September 2020

Rapid conversion of conserved land and cropland to non-agricultural purposes is threatening the ecological areas and dominant agricultural activities that are the main sources of livelihood in urban fringe areas of Addis Ababa City. The combinations of government policy, socioeconomic, demographic dynamics, and biophysical triggers have driven such transformation. However, the recent fast urban expansion and infrastructural development could have accelerated the severity and rate at which urban growth impacts the ecosystem and fertile agricultural land. Yet, little attention is given about their impacts on forest and farming communities in the western fringe areas of Addis Ababa during the recent past. This study, therefore, aimed at quantifying and analyzing the trends of the urban growth and its impacts on flora and agricultural land in Sebeta-Awas town using an integrated GIS tool, remote sensing technique, and Shannon entropy method. Landsat TM of 1986, ETM+ of 2002, and OLI of 2019 were used to produce land use/land cover (LULC) classes. Object-based classification technique was carried out to generate the LULC and to measure the changes in the urban land-use class within the satellite town in the year 1986, 2002, and 2019. Shannon entropy method was applied to model study area’s urban sprawl, growth trend, and spatial change. Over the past three decades (1986–2019), Sebeta-Awas town has experienced severe urban sprawl following lack of proper development control and management. The annual urban growth rates of 1.2, 5.5, and ~15% for the periods of 1986, 2002, and 2019, respectively were obtained mainly at the expenses of agricultural land (25.48%) and forest land (16.6%), catalyzed urban sprawl which finally led to serious deforestation and reduction in rural farmland. The findings indicate that the average of entropy index increased from 0.02 in the year 1986 to 0.996 in the year 2019, indicating more dispersed urban growth to the outskirts, and spatially indicating anticlockwise shifting. In this regard, more than 90.2% of forest loss due to agricultural encroachment, built-up area expansion, and construction was widely observed in Sebeta and Alem Gena areas, of course, Northeast zone in this study. It is concluded that deforestation and continual evacuation of farming communities in the urban fringe areas due to rapid urban expansion in the name of investment and infrastructural development is expected to be worsened in the near future unless strong policy revision and management actions are undertaken.
Assessing the digital economy: aims, frameworks, pilots, results, and lessons
Authors: Hanna Nagy K.
Published: September 2020

The article discusses the motivations for a holistic assessment of the digital economy. It outlines the pilot assessment program initiated by the World Bank Group and describes the assessment frameworks, tools, and processes deployed in selected pilot countries. It identifies the common challenges faced and lessons learned from applying these assessments in different contexts. These challenges include prioritizing digital diagnosis objectives, addressing inequality and poverty issues, securing participation and partnership of stakeholders, addressing implementation challenges, and integrating digital transformation strategy into a country development strategy. Other challenges include harnessing digital innovation and entrepreneurship, mobilizing local demand for the new technologies, engaging business in digital diagnosis, and adopting multi-disciplinary and whole-of-society approaches. The article addresses the implications of these challenges and draws broad lessons and practical recommendations for developing countries and aid agencies.
The challenges ahead for patients with feeding and eating disorders during the COVID-19 pandemic
Authors: Khosravi Mohsen
Published: September 2020

The 2019 coronavirus disease (COVID-19) became a global pandemic only a few months after it emerged in China. Besides, this pandemic imposed adverse consequences on public health, particularly on the mental health status of individuals with serious mental illness. However, the adverse effects of the COVID-19 pandemic on the patients with feeding and eating disorders (FEDs) are at this stage unclear. In this letter, the author seeks to acknowledge the risks of worsening FEDs during this uncertain period.
An evaluation of the Caribbean regulatory system centralized assessment process for medicines submitted 2017–2018 using the OpERA methodology
Authors: Liberti Lawrence , Extavour Rian Marie , Patel Prisha , McAuslane Neil
Published: September 2020

Background

The Caribbean Regulatory System is a centralized medicine assessment procedure established to serve the needs of the Member States of the CARICOM region. In order to better understand the effectiveness and efficiency of the processes implemented by the Caribbean Regulatory System for the regulatory assessment of medicines for the region, the system has been participating in the Optimizing Efficiencies in Regulatory Agencies (OpERA) program, a multinational endeavor to characterize the assessment procedures and the corollary metrics associated with medicine review activities in regulatory agencies and regional regulatory initiatives.

Methods

The OpERA tool was used to collect process and specific milestone data for products approved by the Caribbean Regulatory System during 2017 (n = 10) and 2018 (n = 11).

Results

The median total approval time was 57.5 days (25th/75th percentiles: 54, 60) in 2017 and 148 days (120, 163) in 2018. The median time to conduct the scientific assessment of the dossier was 37 days (24, 42) in 2017 and 66 (40, 132) days in 2018, within the target of 90 days for this activity. The time increases observed in 2018 were due to staff manpower limitations that reduced the ability of the system to conduct the timely assessment of applications. Based on these observations, recommendations to optimize the effectiveness and efficiency of the Caribbean Regulatory System include a commitment from Member States and partner organizations to the use of the procedure to accelerate product availability, encouraging the use of the Caribbean Regulatory System for non-generic products approved by a reference agency, ensuring the establishment of policy and legal frameworks to facilitate the rapid uptake of Caribbean Regulatory System registrations as marketing authorizations in the Member States, and maintaining the sustainability of the process through a fee-based approach.

Conclusions

The observations obtained using the OpERA methodology indicate the Caribbean Regulatory System is an effective and efficient mechanism to provide recommendations to Member States for important medicines.
Objective pathogen monitoring in nursery and finisher pigs by monthly laboratory diagnostic testing
Authors: Goecke Nicole B. , Kobberø Maja , Kusk Thomas K. , Hjulsager Charlotte K. , Pedersen Ken Steen , Kristensen Charlotte S. , Larsen Lars E.
Published: September 2020

Background

Infectious diseases are of great economic importance in commercial pig production, causing both clinical and subclinical disease, with influence on welfare, productivity, and antibiotic use. The causes of these diseases are often multifactorial and laboratory diagnostics are seldom routinely performed. The aim of the present study was to explore the benefits of monthly pathogen monitoring in nursery and finisher herds and to examine association between laboratory results and observed clinical signs, including coughing and diarrhoea. Three monthly samplings were conducted in three different age groups in six nursery and four finisher production units. For each unit, two pens were randomly selected in each age group and evaluated for coughing and diarrhoea events. Furthermore, faecal sock and oral fluid samples were collected in the selected pens and analysed for 18 respiratory and enteric viral and bacterial pathogens using the high-throughput real-time PCR BioMark HD platform (Fluidigm, South San Francisco, USA).

Results

In total, 174 pens were sampled in which eight coughing events and 77 diarrhoeic events were observed. The overall findings showed that swine influenza A virus, porcine circovirus 2, porcine cytomegalovirus,Brachyspira pilosicoli,Lawsonia intracellularis,Escherichia colifimbria types F4 and F18 were found to be prevalent in several of the herds. Association between coughing events and the presence of swine influenza A virus, porcine cytomegalovirus (Cq ≤ 20) or a combination of these were found. Furthermore, an association between diarrhoeic events and the presence ofL. intracellularis(Cq ≤ 24) orB. pilosicoli(Cq ≤ 26) was found.

Conclusions

The use of high-throughput real-time PCR analysis for continuous monitoring of pathogens and thereby dynamics of infections in a pig herd, provided the veterinarian and farmer with an objective knowledge on the distribution of pathogens in the herd. In addition, the use of a high-throughput method in combination with information about clinical signs, productivity, health status and antibiotic consumption, presents a new and innovative way of diagnosing and monitoring pig herds and even to a lower cost than the traditional method.
Effect of hydro-methanol stem bark extract of Burkea africana on erythrocyte osmotic fragility and haematological parameters in acetaminophen-poisoned rats
Authors: Swem Terhemen Festus , Aba Patrick Emeka , Udem Samuel Chukwuneke
Published: September 2020

Background

Burkea africana is a widely used medicinal plant in folkloric medicine in many developing countries of the world. It is useful in the treatment of various ailments including hepatitis, jaundice, diarrhea, stomach aches, abscesses, oedema, epilepsy, bloody diarrhea, gonorrhea, syphilis, toothaches and poisoning. Nevertheless, there are little or no scientific evidence to substantiate this medicinal claim by traditional healers. Burkea africana stem bark was therefore, investigated for its protective or stabilizing effect on erythrocyte membrane in acetaminophen-treated rats. B. africana stem bark was extracted using 80% methanol. Erythrocyte stabilizing effect was studied using erythrocyte osmotic fragility (EOF) test. Thirty (30) male rats were randomly assigned into five (5) groups of six (6) rats each. Groups 1 and 2 served as normal control and negative control (acetaminophen-treated group) respectively. Groups 3, 4 and 5 were pretreated with methanol stem bark extract of Burkea africana (MSBEBA) at doses of 200, 400 and 600 mg/kg body weight respectively once daily for seven (7) days. Blood samples were collected from the animals in all the groups on the 8 day for evaluation of packed cell volume, haemoglobin, red blood cell, white blood cell counts, and differential white blood cell count as well as erythrocyte osmotic fragility.

Results

The erythrocyte osmotic fragility test showed that there was a significantly (p < 0.05) low percentage hemolysis in the groups pre-treated with the extract when compared with the negative control. The percentage hemolysis was least at 600 mg/kg body weight of the extract. There was also a significant (p < 0.05) increase in the packed cell volume, haemoglobin, red blood cell count at all the doses of the extract used. Neutrophils were significantly (p < 0.05) decreased while lymphocytes were significantly increased in the groups administered MSBEBA 400 and 600 mg/kg body weight.

Conclusion

Methanol stem bark extract of Burkea africana had protective effect on the red blood cells and also improved haematological parameters. This indicates that Burkea africana may be useful in the treatment of disease conditions that results in hemolytic anemia by stabilizing red erythrocyte membranes and enhancing erythropoiesis.
The role of cardiopulmonary exercise testing (CPET) in predicting mortality and morbidity in people with congenital heart disease: a systematic review and meta-analysis (Protocol)
Authors: Wadey Curtis A. , Weston Max E. , Dorobantu Dan Mihai , Taylor Rod S. , Pieles Guido E. , Barker Alan R. , Williams Craig A.
Published: September 2020

Background

Numerous studies have measured the prognostic associations between cardiorespiratory fitness and patient outcomes in congenital heart disease, but no systematic review has assessed these associations for all types of congenital heart disease. It is therefore a timely opportunity to syntheses all available data using a systematic review methodology. The aim of this study is to detail the protocol for a systematic review and meta-analysis.

Objectives

Within this paper we have developed a protocol for a prognostic factors systematic review and meta-analysis, to assess the role of cardiopulmonary exercise testing/cardiorespiratory fitness, in the prognosis of mortality and morbidity in congenital heart disease.

Methods

We have outlined, in detail, the process for this systematic review using the latest accepted methodological guidelines for prognostic factors research, such as the PICOTS system, CHARMS-PF data extraction, QUIPS risk of bias assessments and the prognostic GRADE guidelines (see list of abbreviations).

Conclusion

The implications of this review will aid future treatments, interventions and individual patient risk prediction. The publication of this protocol aims to improve scientific rigour by ensuring transparency in the systematic review and meta-analysis process.