bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender, reproductive output covariation and their role on gene diversity of Pinus koraiensis seed orchard crops
Authors: Kang Kyu-Suk , Park Ji-Min , Kang Hye-In , Yeom Da-Bin , El-Kassaby Yousry A. , Lee Kyung-Mi
Published: May 2020

Background: Gender and fertility variation have an impact on mating dynamics in a population because they affect the gene exchange among parental members and the genetic composition of the resultant seed crops. Fertility is the proportional gametic contribution of parents to their progeny. An effective number of parents, derivative of effective population size, is the probability that two alleles randomly chosen from the gamete gene pool originated from the same parent. The effective number of parents is directly related to the fertility variation among parents, which should be monitored for manipulating gene diversity of seed crops. We formulated a fundamental equation of estimating the effective number of parents and applied it to a seed production population.Results: Effective number of parents (Np) was derived from fertility variation (Y) considering covariance (correlation coefficient, r) between maternal and paternal fertility. The Y was calculated from the coefficient of variation in reproductive outputs and divided into female (yf) and male (ym) fertility variation in the population under study. The Np was estimated from the parental Y estimated by the fertility variation of maternal (yf) and paternal (ym) parents. The gene diversity of seed crops was monitored by Y and Np. in a 1.5 generation Pinus koraiensis seed orchard as a case of monoecious species. A large variation of female and male strobili production was observed among the studied 52 parents for four consecutive years, showing statistically significant across all studied years. Parental balance curve showed greater distortion in paternal parents than maternal parents. The Y ranged from 1.879 to 4.035 with greater ym than yf, and the Np varied from 14.8 to 36.8. When pooled, the relative effective number of parents was improved as 80.0% of the census number. Conclusions: We recommend the use of fertility variation (i.e., CV, Y), Person’s product-moment correlation (r) and effective number of parents (Np) as tools for gauging gene diversity of seed crops in production populations. For increasing Np and gene diversity, additional management options such as mixing seed-lots, equal cone harvest and application of supplemental-mass-pollination are recommended.
Inter-limb differences in total hip arthroplasty patients four to five years after surgery: a cross-sectional study
Authors: John Stefanie , Weizel David , Heumann Anna Sophie , Fischer Anja , Orlowski Katja , Mrkor Kai-Uwe , Edelmann-Nusser Jürgen , Witte Kerstin
Published: May 2020

BackgroundːTotal hip arthroplasty (THA) is a successful method to reduce pain in end-stage hip osteoarthritis (OA) patients. If the pre-operatively existing deficits in the affected limb are persisting years after THA has not been thoroughly researched. Therefore, the aim of the study was to investigate potential side-to-side differences in long-time THA patients.MethodsːSixteen patients (age: 65.20 ± 5.32 years), who had undergone unilateral THA four to five years ago and ten, healthy, age-matched controls (age = 60.85 ± 7.57 years) were examined for maximum isometric hip muscle strength, range of motion (ROM) of the hip joint, balance and gait on both limbs. Paired t-testes were used to assess the inter-limb differences in THA patients and controls and unpaired t-tests were applied to investigate differences between the two groups.ResultsːIn THA patients, significant deficits on the operated side were found for the center of pressure (COP) length, hip abduction torque and ROM of hip extension with small to medium effects. Compared to the controls, THA patients demonstrated highly significantly reduced hip strength in flexion, extension, abduction and adduction as well as limited ROM in hip flexion and abduction.ConclusionsːA few side-to-side difference were present in THA patients four to five years after the surgery, although the general hip muscle weakness and restricted hip ROM compared to the controls was more severe. Postoperative training focusing on strengthening hip muscles should be continued months and years after the surgery in order to compensate persisting deficits.Trial registrationːDRKS, DRKS00016945. Registered 12 March 2019 – Retrospectively registered, http://www.drks.de/DRKS00016945
Uncovering the genomic potential of the Amazon River microbiome to degrade rainforest organic matter
Authors: Júnior Célio Dias Santos , Sarmento Hugo , de Miranda Fernando Pellon , Henrique-Silva Flávio , Logares Ramiro
Published: May 2020

Background The Amazon River is one of the largest in the world and receives huge amounts of terrestrial organic matter (TeOM) from the surrounding rainforest. Despite this TeOM is typically recalcitrant (i.e. resistant to degradation), only a small fraction of it reaches the ocean, pointing to a substantial TeOM degradation by the river microbiome. Yet, microbial genes involved in TeOM degradation in the Amazon River were barely known. Here, we examined the Amazon River microbiome by analyzing 106 metagenomes from 30 sampling points distributed along the river.Results We constructed the Amazon River basin Microbial non-redundant Gene Catalogue (AMnrGC) that includes ~ 3.7 million non-redundant genes, affiliating mostly to bacteria. We found that the Amazon River microbiome contains a substantial gene-novelty compared to other relevant known environments (rivers and rainforest soil). Genes encoding for proteins potentially involved in lignin degradation pathways were correlated to tripartite tricarboxylates transporters and hemicellulose degradation machinery, pointing to a possible priming effect. Based on this, we propose a model on how the degradation of recalcitrant TeOM could be modulated by labile compounds in the Amazon River waters. Our results also suggest changes of the microbial community and its genomic potential along the river course.Conclusions Our work contributes to expand significantly our comprehension of the world’s largest river microbiome and its potential metabolism related to TeOM degradation. Furthermore, the produced gene catalogue (AMnrGC) represents an important resource for future research in tropical rivers.
Pediatric NTRK fusion sarcomas
Authors: Kang Jeongwan , Park Jin Woo , Won Jae-Kyung , Bae Jeong Mo , Yun Hongseok , Kim Seung-Ki , Choi Jung Yoon , Kang Hyoung Jin , Shin Joo Heon , Park Sung-Hye
Published: May 2020

Background
While ETV6-NTRK3 fusion is common in infantile fibrosarcoma, NTRK1 fusion in pediatric sarcoma is extremely rare and consequently not well known. Herein, we evaluated NTRK1 fusion pediatric sarcomas to determine their clinicopathological nature and differential diagnosis from classic ETV6-NTRK3 fusion infantile fibrosarcoma.
Methods
We retrieved and reviewed eight NTRK-fusion pediatric sarcomas confirmed by fluorescence in situ hybridization and/or next-generation sequencing from Seoul National University Hospital between 2002 and 2019.
Results
The NTRK1 fusion-positive tumors included one case of TPR-NTRK1 fusion in a 12-year-old boy with an intracranial extra-axial high-grade undifferentiated sarcoma and an LMNA-NTRK1 fusion in a 3-year-old boy with a low-grade infantile fibrosarcoma of the forehead. Six cases of infantile fibrosarcoma with ETV6-NTRK3 fusion were identified (median age: 2.6 months, range: 1.6–5.6 months, M: F = 5:1). The TPR-NTRK1 fusion sarcoma showed nuclear Trk expression, robust CD34/nestin expression (S100 protein-negative), and high mitoses. The LMNA-NTRK1 fusion sarcoma showed nuclear membrane Trk expression, CD34/S100 protein/nestin/CD10 coexpression, and a low mitotic rate. The six cases of infantile fibrosarcoma with ETV6-NTRK3 fusion showed S100 protein (3/6)/nestin(6/6)/CD10 (4/5) coexpression and both cytoplasmic and nuclear Trk expression but were CD34-negative.
Conclusions
All cases of NTRK1 and NTRK3 fusion-positive pediatric sarcomas robustly expressed the Trk protein. A Trk immunopositive pattern and CD34/S100/nestin/CD10 immunohistochemical profile may suggest NTRK fusion partner genes. TPR-NTRK1 and LMNA-NTRK1 fusions might be surrogate markers for pediatric mesenchymal tumors, while LMNA-NTRK1 fusion sarcoma might be a low-grade infantile fibrosarcoma subtype. More than half of the infantile fibrosarcoma cases were S100 protein and CD10-positive. The cases of infantile fibrosarcoma showed good prognoses regardless of tumor cellularity, Ki-67 index, and mitoses.
A novel magnetic field generating machine with a wide range of tunable parameters to study in vitro cells
Authors: Nezamtaheri Maryam sadat , Shariatpanahi Seyed Peyman , Goliaei Bahram , Ansari Alireza Madjid
Published: May 2020

Background Extremely low-frequency magnetic field (ELF-MF) significantly induces apoptosis in cancer cells. To study the biological effects of the ELF-MF on tumor cells, we have designed and constructed a new exposure system that provides a uniform magnetic field with negligible temperature fluctuations during the exposure. Additionally, it provides ideal physiological conditions for live cells inside the incubator. This ELF-MF exposure system eliminates several limitations and disadvantages of other low frequency magnetic field systems; it generates a magnetic field with a frequency of 0 to 70 Hz with a maximum magnetic flux density of 150 mT. Methods The capabilities of the setup were examined using a 1 Hz, 100 mT magnetic field, at various exposure times, to induce apoptosis-mediated cell death in the MC4-L2 cell line. After exposure, apoptosis was assessed by flow cytometry. Results A biphasic response was observed in cells exposed to ELF-MF: at first a decreasing apoptotic rate during 2-12 hours exposure time was detected, after which apoptosis gradually increased during 24-120 hours of exposure. Conclusions We show that ELF-MF exposure with a frequency of 1 Hz and intensity of 100 mT induces apoptosis in MC4-L2 cancer cells in a time-dependent manner. These results show the significance of the long term studies of the ELF exposure effects.
Optimal cumulative dose of cisplatin for concurrent chemoradiotherapy among patients with locally advanced nasopharyngeal carcinoma: a multicenter analysis in Thailand
Authors: Ngamphaiboon Nuttapong , Dechaphunkul Arunee , Setakornnukul Jiraporn , Dechaphunkul Tanadech , Jiratrachu Rungarun , Suktitipat Bhoom , Jiarpinitnun Chuleeporn , Pattaranutaporn Poompis , Danchaivijitr Pongwut
Published: May 2020

IntroductionChemoradiotherapy (CRT) with high cumulative doses (CDs) of cisplatin has been considered the standard of care for locally advanced nasopharyngeal carcinoma (LA-NPC). However, given most patients’ inability to tolerate high CDs due to cisplatin-related toxicities, the optimal CD of cisplatin during CRT remains undetermined.MethodsPatients with LA-NPC who received CRT with cisplatin between 2007 and 2017 were identified through the Thai head and neck cancer multicenter database and then categorized according to cisplatin CD (mg/m2) received. All complications and cisplatin-related toxicities during CRT were recorded.ResultsWe identified 779 LA-NPC patients receiving low (£150; n=97), intermediate (151–250; n=411), and high (>250; n=271) CDs of cisplatin. Low CD patients had significantly lower mean actual radiation dose (p<0.001) and more radiotherapy delay (p=0.010), while intermediate CD patients had the least hospitalization (p<0.001). Overall, 39.3% of the patients experienced cisplatin-related toxicity, which was associated with poor overall survival (OS) (p=0.001). Acute kidney injury was observed in 7% in all patients, which was highest among low CD patients (15.5%; p=0.002). Intermediate CD patients had significantly longer median OS than the low and high groups (64 vs. 49.8 vs. 53.2, respectively; p=0.015). Univariate, but not multivariate, analysis showed that CD of cisplatin was significantly associated with OS.ConclusionCD of cisplatin during CRT was not an independent prognostic factor for OS. An intermediate CD induced minimal toxicity without compromising survival and should be considered the optimal CD. Nonetheless, a randomized phase 3 study evaluating the optimal CD of cisplatin is warranted.
Somatic mutation detection efficiency in EGFR: A comparison between High Resolution Melting Analysis and Sanger Sequencing
Authors: Joy Reenu Anne , Thelakkattusserry Sukrishna Kamalasanan , Vikkath Narendranath , Bhaskaran Renjitha , Vasudevan Damodaran , Krishnan Sajitha , Ariyannur Prasanth S.
Published: May 2020

Background: The current study focuses on comparing the mutation detection efficiency of High-Resolution Melt Analysis (HRM) with Sanger Sequencing in EGFR gene.Methods: The minor allele frequency of somatic mutations was titrated against total DNA concentration using Sanger sequencing and HRM. Somatic mutation detection efficiency, for exons 19 & 21 of the EGFR gene, was compared in 116 formalin fixed paraffin embedded tumor tissues, after screening 275 tumor tissues by Sanger sequencing.Results: The limit of detection of minor allele fraction of exon 19 mutation was 1% with Sequencing, and 0.25% with HRM, whereas for exon 21 mutation, 0.25% MAF was detected using both methods. Mutation positive samples detected by Sanger sequencing, and wild-type samples detected by HRM were corresponding to each other. About 28% cases in exon 19 and 40% in exon 21, detected as mutated in HRM, was not detected by sequencing. Overall, sensitivity and specificity of HRM were found to be 100% and 67% respectively, and the negative predictive value was 100%, while positive predictive value was 80%.Conclusion: The comparative series study suggests that HRM is a modest initial screening test for somatic mutation detection of EGFR, which must further be confirmed by Sanger sequencing.
Association between serum bone biomarker levels and ultrasonographic response in abatacept-treated rheumatoid arthritis patients
Authors: Kawashiri Shin-Ya , Endo Yushiro , Nishino Ayako , Okamoto Momoko , Tsuji Sosuke , Takatani Ayuko , Shimizu Toshimasa , Sumiyoshi Remi , Koga Tomohiro , Iwamoto Naoki , Ichinose Kunihiro , Tamai Mami , Nakamura Hideki , Origuchi Tomoki , Aramaki Toshiyuki , Ueki Yukitaka , Yoshitama Tamami , Eiraku Nobutaka , Matsuoka Naoki , Okada Akitomo , Fujikawa Keita , Hamada Hiroaki , Nagano Shuji , Tada Yoshifumi , Maeda Takahiro , Kawakami Atsushi
Published: May 2020

Background

To evaluate the effect of treatment on bone biomarkers and explore whether bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept.
Methods

We enrolled 59 RA patients treated with abatacept from a multicenter prospective ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients' clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. 'Power Doppler (PD) responder' was defined as a patient whose Δtotal PD score over 6 months was greater than the median change.
Results

Abatacept significantly improved clinical disease activity as well as the MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the introduction of abatacept (p = 0.016). The ΔSOST and ΔOPG values were negatively correlated with the Δtotal PD score (rs = − 0.31, p < 0.05 and rs = − 0.34, p < 0.01, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) compared to the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, p = 0.043) was an independent predictor of PD responder status.
Conclusion

Serum levels of bone biomarkers may be useful for predicting RA patients' ultrasonographic response to abatacept.
Medical students’ perceptions of nutrition in medical education and future practice
Authors: Fenwick Peri , Colborne Alyson , Theou Olga , Cahill Leah
Published: May 2020

Background: Physicians are relied upon as knowledgeable sources of nutrition information; however, many report low nutrition knowledge.Objective: The present study assessed first and second-year medical students’ perceptions of nutrition education within the medical curriculum, in terms of their attitudes, learned body of knowledge, and satisfaction.Methods: An online questionnaire was administered to Dalhousie University medical students completing their first or second years (N=125). Mann-Whitney U tests compared the responses of first-year to second-year students and those with and without previous nutrition education.Results: 97.6% of respondents agreed that nutritional counselling can positively influence patient outcomes, with 91.2% agreeing that physicians play a key role in nutritional counselling. Compared to second-year students, first-year students had greater self-perceived knowledge of basic nutrition concepts (p<0.001) and nutrition in the treatment of disease (p=0.005), as did students with previous nutrition education compared to those without (p=0.019 and 0.018 respectively). Satisfaction was <30% agreement, with first-year students more satisfied with their nutrition education than second-year students (p<0.05).Conclusions: First and second-year medical students regard nutrition as an important component of medical practice that can positively impact patient outcomes. However, low satisfaction with their nutrition education suggests that additional nutrition curriculum would better prepare them for future practice.
Increased salt tolerance in Zymomonas mobilis strain generated by adaptative evolution
Authors: Fuchino Katsuya , Bruheim Per
Published: May 2020

BackgroundEthanologenic alphaproteobacterium Zymomonas mobilis has been acknowledged as a promising biofuel producer. There have been numerous efforts to engineer this species applicable for an industrial-scale bioethanol production. Although Z. mobilis is robustly resilient to certain abiotic stress such as ethanol, the species is known to be sensitive to saline stress at a mild concentration, which hampers its industrial use as an efficient biocatalyst. To overcome this issue, we implemented laboratory adaptive evolution approach to obtain salt tolerant Z. mobilis strain.ResultsDuring an adaptive evolution, we biased selection by cell morphology to exclude stressed cells. The evolved strains significantly improved growth and ethanol production in the medium supplemented with 0.225 M NaCl. Furthermore, comparative metabolomics revealed that the evolved strains did not accumulate prototypical osmolytes, such as proline, to counter the stress during their growth. The sequenced genomes of the studied strains suggest that disruption of ZZ6_1149 encoding carboxyl peptidase was likely responsible for the improved phenotype.ConclusionsThe present work successfully generated the strains able to grow and ferment glucose under saline condition that severely perturbs parental strain physiology. Our approach to generate strains, cell shape-based diagnosis and selection, might be applicable to other kind of strain engineering in Z. mobilis.
Source model for the Mw 6.0 earthquake in Jiashi, China on 19 January 2020 from Sentinel-1A InSAR data
Authors: Yu Pengfei , Qiao Xuejun , Xiong Wei , Chen Wei , Nie Zhaosheng , Wang Dijin , Jia Zhige , Li Jie
Published: May 2020

On January 19, 2020, an Mw 6.0 earthquake occurred in Jiashi, Western China. The epicenter was located at the basin-mountain boundary between the southern Tian Shan and the Tarim Basin. Many strong earthquakes occurred in this region, such as the 1997 Jiashi strong earthquake swarm. In this study, Interferometric Synthetic Aperture Radar (InSAR) was used to obtain the coseismic deformation field from the ascending and descending Sentinel-1A satellite data of the European Space Agency. The results showed that the coseismic deformation was distributed along the Kalpingtag fault and the Ozgertaou fault. The earthquake produced significant deformation over an area of approximately 40 km by 30 km. The long axis of the deformation was near the east-west direction. The maximum and minimal displacements along the line of sight (LOS) were 5.3 cm, 7.2 cm and -4.2 cm, -3 cm for the ascending and descending interferograms, respectively. The slip model inverted by the steepest descent method demonstrated that the rupture process of this earthquake is dominated by a thrust fault. The slips were concentrated in a depth of 3.5 ~ 6.5 km. The maximum slip was 0.29 m. The estimated total seismic moment was 1.728×1018 Nm, corresponding to a magnitude of Mw 6.09. The inversion revealed that the coseismic rupture was located at the transition zone between the shallow high-dip fault and the deep detachment fault. The geometry of the coseismic rupture is direct evidence of the deep attitude of the Kalping fault, indicating the possibility of independent earthquakes at the shallow ramp-to-flat transition zone of an orogenic belt. The coseismic Coulomb stress changes have enhanced the stress on the deep margin of the Jiashi earthquake rupture area, indicating that there is still the possibility of another strong earthquake in this region in the future.
The Effect of Cognitive Behavioral Therapy for Insomnia in People with Type 2 Diabetes Mellitus, Pilot RCT Part II: Diabetes Health Outcomes
Authors: Alshehri Mohammed , Alothman Shaima A. , Alenazi Aqeel M. , Rucker Jason L. , Phadnis Milind A. , Miles John M. , Siengsukon Catherine F. , Kluding Patricia M.
Published: May 2020

Background: Previous studies have shown the negative impact of sleep disturbances, specifically insomnia symptoms, on glucose metabolism for people with type 2 diabetes (T2D). People with insomnia symptoms are at risk of poor glycemic control and suboptimal diabetes self-care behavior (DSCB). Investigating the impact of a safe and effective intervention for individuals with T2D and insomnia symptoms on diabetes health outcomes is needed. Therefore, the aim of this exploratory study is to examine the effect of Cognitive Behavioral Therapy for Insomnia (CBT-I) on glycemic control, DSCB, and fatigue. Methods: Twenty-eight participants with T2D and insomnia symptoms after passing an eligibility criteria at a medical research center were randomly assigned to CBT-I (n=14) or Health Education (HE; n=14). The CBT-I and HE groups received 6 weekly one-hour sessions. This Randomized Controlled Trial (RCT) will be using a non-inferiority framework to test the effectiveness of CBT-I. Validated assessments were administered at baseline and post-intervention to assess glycemic control, DSCB, and fatigue. A Wilcoxon signed-rank test was utilized to compare within-group changes from baseline to post-intervention. A Mann-Whitney test was utilized to measure the between-group differences. Linear regression was used to assess the association between blood glucose level and number of days in the CBT-I group. Results: The recruitment duration was from October 2018 to May 2019. A total of 13 participants completed the interventions in each group and included in the final analysis. No adverse events due to being a part of this RCT were reported. CBT-I participants showed significantly greater improvement in glycemic control, DSCB, and fatigue. There significant association between the number of days in the CBT-I intervention with blood glucose level before bedtime (B=-0.56, p=.009) and after awakening in the morning (B=-0.57, p=.007). Conclusions: This study demonstrated a clinically meaningful effect of CBT-I on glycemic control in people with T2D and insomnia symptoms. Also, CBT-I positively impacted daytime functioning, including DSCB and fatigue. Future research is needed to investigate the long-term effect of CBT-I on laboratory tests of glycemic control and to understand the underlying mechanisms of any improvements.Trial registration: Clinical Trials Registry (NCT03713996). Registered 22 October 2018, https://clinicaltrials.gov/ct2/show/NCT03713996
Transcriptome profilings reveal the candidate genes, pathways and transcription factors related to nitrogen utilization and excessive nitrogen stress in perennial ryegrass.
Authors: Li Yinruizhi , Wang Mengdi , Teng Ke , Dong Di , Liu Zhuocheng , Zhang Tiejun , Chao Yuehui , Han Liebao
Published: May 2020

Background：Lolium perenne L. is a kind of high quality forage grass, which can provide a good nutritional basis for herbivorous livestock. However, how to improve the nitrogen utilization rate of ryegrass and avoid the nitrate toxicity caused by excessive nitrogen has been troubling people for a long time. Up to now, the molecular response mechanism of ryegrass to nitrogen is not clear, especially under the condition of excessive nitrogen. Based on this, we tried to obtain a new insight into molecular response of ryegrass in nitrogen utilization and excessive nitrogen stress, providing the molecular theoretical basis for solving this problem.Results: In this study, the transcription of perennial ryegrass at different nitrogen levels was identified by high-throughput next-generation DNA sequencing. Phenotypic characterizations investigated that ryegrass in treatment N0.5 has a better growth state than the other three groups. The treatment N1 and N10 contained excessive nitrogen, which had a stress effect on plant growth. Analysis of differentially expressed genes indicated that 345, 105 genes are considered to involve in the regulation of nitrogen utilization and excessive nitrogen stress, respectively. GO enrichment analysis revealed that plant response to nitrogen mainly enrich in two categories, including “biological process” and “molecular function”. KEGG enrichment analysis suggested that “Photosynthesis-antenna proteins” may respond positively to nitrogen under appropriate nitrogen conditions, whereas “steroid biosynthesis”, “carotenoid biosynthesis” and “C5-branched dibasic acid metabolism” had been identified as top significant enrichment pathways response to excessive nitrogen. Transcription factors analysis showed that 21 TFs related to nitrogen utilization were classified into 10 transcription factor families, especially AP2-EREBP and MYB TF families. 4 TFs related to excessive nitrogen stress were identified, which belonged to 4 transcription factor families including LOB, NAC, AP2-EREBP and HB. The expression patterns of these selected genes above were also analyzed. Conclusions: These results made a contribution to comprehend the molecular mechanism of perennial ryegrass response to nitrogen. It provides new ideas for guiding the production practice and variety improvement of forage and even food crops from the perspective of molecular biology.
Reduced intensity of induction does not increase the risk of relapse in childhood acute lymphoblastic leukemia - A multi-centric clinical study of GD-2008-ALL protocol
Authors: Li Xin-Yu , Li Jia-Qiang , Luo Xue-Qun , Wu Xue-Dong , Sun Xin , Xu Hong-Gui , Li Chang-Gang , Liu Ri-Yang , Sun Xiao-Fei , Chen Hui-Qin , Lin Yu-Deng , LI Chi-Kong , Fang Jian-Pei
Published: May 2020

Background The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70%-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong(GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity in terms of duration in ALL chemotherapy on chemotherapy related mortality. The study was designed to elucidate weather the reduced intensity of induction is effective and safe for children with ALL, compared with Berlin-Frankfurt-Münster (BFM) backbone treatment. Methods The clinical data was obtained from February 28, 2008 to June 30, 2016. A total of 1,765 childhood ALL cases from 9 medical centers were collected and data was retrospectively analyzed. Bone marrow morphology, prednisone response, age, genotype, and karyotype information was evaluated for the stratification of chemotherapy intensity. Patients were stratified into 3 groups: standard risk (SR), intermediate risk (IR) and high risk (HR). The dose of cyclophosphamide (CTX), Cytarabine (Ara-c) and 6-mercaptopurine (6-MP) during induction for the SR group was half that of the BFM backbone treatment. Results The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2 %) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day33 positive group (n=7) was 28.6%, while the incidence of relapse in the MRD Day33 negative group (n=67) was 7.5% (p=0.129).Conclusions The results of GD-2008-ALL protocol are outstanding for reducing treatment related mortality in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.
Comparison of regional and local anesthesia for arteriovenous fistula creation in end-stage renal disease: a systematic review and meta-analysis
Authors: Gao Chen , Weng Chunyan , He Chenghai , Xu Jingli , Yu Liqiang
Published: May 2020

Background Arteriovenous fistulae (AVF) are the hemodialysis access modality of choice for patients with end-stage renal disease. However, they have a high early failure rate. Good vascular access is essential to manage long-term hemodialytic treatment, but some anesthesia techniques directly affect venous diameter as well as intra- and post- operative blood flow. The main purpose of this meta-analysis was to compare the results of regional and local anesthesia for arteriovenous fistula creation in end-stage renal disease.Methods: We conducted a systematic review and meta-analysis to synthesize evidence from 7 randomized controlled trials (565 patients) and 2 observational studies (524 patients) aim to evaluate the safety and efficacy of regional anesthesia (RA) versus local anesthesia (LA) in AVF surgical construction.Results: Pooled data showed that RA was associated with higher primary patency rates than LA (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.24 - 2.84; P = 0.003; I 2 = 31%; Figure 2a). Additionally, brachial artery diameter was significantly increased in the RA versus LA group (mean difference [MD] = 0.83; 95% CI: 0.75 - 0.92; P < 0.001; I 2 = 97%) and the need for intra- as well as post- operative pain killers was significantly less (RA, p = 0.0363; LA, p = 0.0318). Moreover, operation duration was significantly reduced in the RA (67.5 ± 8.9 min) versus LA (134.7 ± 14.8 min) group (p = 0.0007).Conclusions: In conclusion, compared with LA, RA shows higher primary patency rates and it also associated with significantly better intra- as well as post- operative pain control, reduced operative times, which are extremely important in patients with end-stage renal disease and severe comorbidities.
Local Use of Dexamethasone in the Treatment of Ocular Myasthenia Gravis
Authors: Shi Minghua , Ye Yingjia , Zhou Junping , Qin Aijiao , Cheng Jing , Ren Hongxing
Published: May 2020

Background At present, patients with ocular myasthenia gravis (OMG) are typically treated with systemic drugs. We investigated the use of dexamethasone injected in the peribulbar region or extraocular muscle to treat patients with OMG. Methods Patients with OMG were given dexamethasone via peribulbar injection or direct injection into the main paralyzed extraocular muscles, once a week, for 4-6 weeks. The severity of diplopia, blepharoptosis, eye position, and eye movement were evaluated before and after treatment. The duration of follow-up time was ≥6 months. Results Among the 14 patients with OMG who received this treatment, mean age was 38.7 ± 29.7 years. After treatment, symptoms had resolved in 12 patients; symptoms had improved in 1 patient; treatment had failed in 1 patient. Two of the 12 patients in whom symptoms had resolved experienced symptom recurrence during the follow-up period. Conclusions Dexamethasone peribulbar or extraocular muscle injection is effective in the treatment of patients with OMG and may replace systemic drug therapy
Thymosin alpha-1 Protected T Cells from Excessive Activation in Severe COVID-19
Authors: Yu Kuai , Wu Yongjian , He Jingjing , Liu Xuefei , Wei Bo , Wen Wen , Wen Xiaofeng , Xu Wenxiong , Dong Xingjun , Yan Yue , Li Shuo , Liao Shuangye , Gao Chenqi , Zhong Bei , Jiang Yongliang , Li Min , Bian Chaochao , Li Xiang , Li You , Liu Haiping , Chen Xiangqi , Zhao Qingyu , Xia Xiaojun , Liang Juanran , Zou Bin , Lin Bingliang , Xie Baosong , Wei Lai , Zuo Zhixiang , Zhou Haibo , Huang Xi , Zhou Penghui
Published: May 2020

Two typical features of uncontrolled inflammation, cytokine storm and lymphopenia, are associated with the severity of coronavirus disease 2019 (COVID-19), demonstrating that both innate and adaptive immune responses are involved in the development of this disease. Recent studies have explored the contribution of innate immune cells to the pathogenesis of the infection. However, the impact of adaptive immunity on this disease remains unknown. In order to clarify the role of adaptive immune response in COVID-19, we characterized the phenotypes of lymphocytes in PBMCs from patients at different disease stages using single-cell RNA sequencing (scRNA-seq) technology. Dynamics of the effector cell levels in lymphocytes revealed dysregulated adaptive immune responses in patients with severe disease. A new cluster of excessively activated CD8 T cells (Tea) was further identified, which displayed exhausted phenotypes and diminished function of antigen recognition. Interestingly, expression of PTMA, the proprotein of Tα1, was significantly increased in a group of highly proliferating CD8 T cells with memory stem cell features. We further showed that Tα1 significantly promoted the proliferation of activated T cells in vitro and relieved the lymphopenia in COVID-19 patients. Our data suggest that protection of T cells from excessive activation might be critical for the prevention of severe COVID-19.
Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report.
Authors: Firstenberg Michael S , Stahel Philip F. , Hanna Jennifer , Kotaru Chakradhar , Crossno Joseph , Forrester Joseph
Published: May 2020

Background: The value of extracorporeal membrane oxygenation (ECMO) for patients suffering from novel coronavirus disease 2019 (COVID-19) as a rescue therapy for respiratory failure remains controversial and associated with high mortality rates of 50% to 82% in early reports from Wuhan, China. We hypothesized that patient outcomes would be improved at our tertiary cardiothoracic surgery referral center with a protocolized team-approach for ECMO treatment of patients with severe COVID-19 disease. Case Presentation: A 51-year-old healthy female developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) bilateral pneumonia while vacationing in Colorado with her family. She was transferred to our facility for a higher level of care. Her respiratory status continued to deteriorate despite maximized critical care, including prone positioning ventilation and nitric oxide inhalation therapy. Veno-venous ECMO was initiated on hospital day 7 in conjunction with a 10-day course of compassionate use antiviral treatment with remdesivir. The patient’s condition improved significantly and she was decannulated from ECMO on hospital day 17 (ECMO day 11). She was successfully extubated and eventually discharged to rehabilitation on hospital day 28.Conclusion: This case report demonstrates that the judicious application of ECMO for respiratory failure due to SARS-CoV-2 pneumonia in conjunction with compassionate use antiviral treatment (remdesivir) resulted in a positive outcome in a young patient with a high predicted mortality from COVID-19. Future prospective multi-center studies are needed to validate these findings in a larger cohort of patients.
Compartmentalized mathematical model to predict future number of active cases and deaths of COVID-19
Authors: Neto Osmar Pinto , Reis José Clark , Brizzi Ana Carolina Brisola , Zambrano Gustavo José , Souza Joabe Marcos de , Amorim Wellington Pedroso Estevam de , Pedreiro Rodrigo Cunha de Mello , Brizzi Bruno de Matos , Abinader Ellysson Oliveira , Zangaro Renato Amaro
Published: May 2020

In December 2019, China reported a series of atypical pneumonia cases caused by a new Coronavirus, called COVID-19. In response to the rapid global dissemination of the virus, on the 11th of Mars, the World Health Organization (WHO) has declared the outbreak a pandemic. In light of this situation, this paper intends to analyze and improve the current SEIR models to better represent the behavior of the COVID-19 and accurately predict the outcome of the pandemic in a given social, economic and political scenario. We present a novel generalized Susceptible-Exposed-Infected-Recovered (SEIR) compartmental model and test it using a global optimization algorithm with data collected from the WHO. Our main results were: (a) our model was able to accurately fit the data of all countries tested (b) it is possible to predict values for one week ahead with errors in the order of 15% for the number of cases and 30% in the number of deaths for all countries; (c) predictions are better for countries where the active cases curve already reached the maximum; the error being in the order of 10% in the number of cases and 20% in the number of deaths; (d) for countries where the active curve is still growing, different optimization solutions can be found that fit the data; so, to predict future behavior in this scenarios some of the model coefficients should be estimated from outside sources or based on generalized results from other countries according to their health policies of social distance, quarantining and case test and tracing.
A case report of an undiagnosed COVID-19 infection
Authors: Wu zhiqian , Xia haibo , zhu ronghui , Cao Jing
Published: May 2020

Background: A very serious new type of coronavirus infection has recently erupted in China. For new viruses, data and information in all aspects need to be improved.Case Presentations: During the early COVID-19 outbreak, a 38-year-old man experienced COVID-19 infection in Shenzhen (nonendemic area-related personnel) and underwent SARS-CoV-2 nucleic acid screening multiple times due to an initial positive COVID-19 screening at the beginning of the disease. The results of these additional tests were negative, and the initial SARS-CoV-2 nucleic acid screening result for this patient was suspected as being a false positive.Diagnosis: After nearly 17 days of hospitalization in two hospitals, a variety of tests were performed to diagnosis this new coronavirus infection (due to the positive results of the initial screening).Intervention: Early in the onset of the disease, treatment was given to maintain water and electrolyte balance, and antibiotics and proprietary Chinese medicines were given as the treatment. The symptoms were controlled at an early stage.Outcomes: The patient developed symptoms on the first day and had pneumonia in the lungs, as shown by a chest CT examination on the 7th day of onset. The subsequent prognosis was good. The family members living with this patient did not show similar symptoms.Conclusion: The diagnostic process of COVID-19 needs to be improved, and the development of SARS-CoV-2 diagnostic reagents needs to be strengthened under certain conditions. Screening should be performed at an early stage when a COVID-19 infection is suspected and should distinguish between patients with a COVID-19 infection and with a non-COVID-19 infection. Patients are more conducive to controlling the COVID-19 epidemic.
A novel Monte Carlo simulation procedure for modelling COVID-19 spread over time
Authors: Xie Gang
Published: May 2020

The coronavirus disease 2019 (COVID-19) has now spread throughout most countries in the world causing heavy life losses and damaging social-economic impacts. Following a stochastic point process modelling approach, a Monte Carlo simulation model was developed to represent the COVID-19 spread dynamics. First the simulation study was to examine various expected properties of the simulation model performance based on a number of arbitrarily defined scenarios. Then the simulation studies were performed in analysis of the real COVID-19 data reported for Australia and United Kingdom (UK). Given the initial number of active cases before 1 March were around 10 for both countries, the model estimated that the number of active COVID-19 cases was to peak around 30 March in Australia (≈ 1630 cases) and around 11 April in UK (≈ 24600 cases); ultimately the total confirmed cases could sum to 6610 for Australia in about 70 days and 136000 for UK in about 90 days. The analysis results also confirmed the reproduction number ranges as reported in the literature. This simulation model was considered as an effective and adaptable decision making/what-if analysis tool in battling COVID-19 in the immediate need, and in battling any other infectious diseases in the future.
Epidemiological characteristics and the effectiveness of countermeasures to control coronavirus disease 2019 in Ningbo City, China
Authors: Lao Xuying , Luo Li , Lei Zhao , Fang Ting , Chen Yi , Liu Yuhui , Ding Keqin , Zhang Dongliang , Wang Rong , Zhao Zeyu , Rui Jia , Zhu Yuanzhao , Xu Jingwen , Wang Yao , Yang Meng , Yi Bo , Chen Tianmu
Published: May 2020

Background: A novel coronavirus (SARS-CoV-2) has spread widely and led to high disease burden around the world. This study aimed to explore key parameters of SARS-CoV-2 infection and to assess the effectiveness of interventions to control the coronavirus disease 2019 (COVID-19).Methods: A susceptible – exposed – infectious – asymptomatic – recovered (SEIAR) model was developed for the assessment. Data of symptomatic and asymptomatic infection of SARS-CoV-2 were collected to calculate the key parameters of the model in Ningbo City, China.Results: A total of 157 confirmed COVID-19 cases (including 51 imported cases and 106 secondary cases) and 30 asymptomatic infections were reported in Ningbo City. The proportion of asymptomatic has an increasing trend. The proportion of asymptomatic of elder people was lower than younger people, and the difference was statistical significant (Fisher’s Exact Test, P = 0.034). There were 22 clusters associated with 167 SARS-CoV-2 infections, among which 29 cases were asymptomatic, with a proportion of 17.37%. We found that the secondary attack rate of asymptomatic was almost the same as that of symptomatic cases, and no significance was observed (χ2 = 1.350, P = 0.245) by Kruskal-Wallis test. The effective reproduction number (Reff) was 1.43 which revealed that the transmissibility of SARS-CoV-2 was moderate. If the interventions were not strengthened, the duration of the outbreak would last about 16 months with a simulated attack rate of 44.15%. The total attack rate and duration of the outbreak would increase along with the increasing delay of intervention.Conclusions: SARS-CoV-2 had moderate transmissibility in Ningbo City, China. Asymptomatic infection has the same transmissibility as symptomatic. The integrated interventions were implemented at different stages during the outbreak, which found to be exceedingly effective in China.
Severe coronavirus disease 2019: CT changes based on prognosis
Authors: Liang Bin , Xie Lingli , Yang Fan , Makamure Joyman , Zhang Lijie , Pang Ran , Du Peng , Fan Wenhui , Zheng Chuansheng
Published: May 2020

Purpose: To determine the characteristics of CT changes in patients with severe coronavirus disease 2019 (COVID-19) based on prognosis.Method: Serial CT scans in 47 patients with severe COVID-19 were reviewed. The patterns, distribution and CT score of lung abnormalities were assessed. Scans were classified according to duration in weeks after onset of symptoms. These CT abnormalities were compared between discharged and dead patients.Results: Twenty-six patients were discharged, whereas 21 passed away. Discharged patients were characterized by a rapid rise in CT score in the first 2 weeks followed by a slow decline, presence of reticular and mixed patterns from the second week, and prevalence of subpleural distribution of opacities in all weeks. In contrast, dead patients were characterized by a progressive rise in CT score, persistence of ground-glass opacity and consolidation patterns in all weeks, and prevalence of diffuse distribution from the second week. CT scores of death group were significantly higher than those of discharge group ( P < .05). Significant differences were also noted in abnormality pattern ( P < .05) and opacity distribution (P < .05) between groups.Conclusions: The severe COVID-19 patients presented with characteristic CT changes and the CT changes varied with prognosis.Authors Bin Liang, Lingli Xie contributed equally to this work.
PSYCHOHISTORY DALAM KAJIAN SELF-ESTEEM TEKS DEKLARASI NU 1983 TENTANG HUBUNGAN PANCASILA DAN ISLAM
Authors: Jamil Robit Nurul , Joebagio Hermanu , Djono Djono
Published: May 2020

Special concern on the sources of Islamic history contributes to the thoughts and identity of Indonesian Muslims. Muslim self-esteem can be formed from these historical sources. The formation of Muslim self-esteem gives the right decision so that it does not come out of the context of religion and humanity. The historical source used in this study is the text of the 1983 Nahdlatul Ulama Declaration (NU). The concept of Islam Nusantara (NU) 2015 is an implication of the values of the text of the declaration. The purpose of this study is to provide new insights regarding the 2015 NU's concept of Islam Nusantara by analyzing the historical sources of the text of the 1983 NU Declaration and exploring the values of self-esteem contained in the text of the declaration. The study used a qualitative method with psychohistory approach. This study produced two discussions: 1) The 2015 NU's concept of Islam Nusantara. 2) Psychohistory self-esteem in the historical source of the text of the 1983 NU Declaration. This study concluded that the conception of Islam Nusantara 2015 was mandated by the 1983 NU declaration, in its implementation provides Islamic self-esteem that can hinder the process of radicalization.