bluuebunny/crossref_metadata_2025_split huggingface dataset:
An innovative pharmacology curriculum for medical students: promoting higher order cognition, learner-centered coaching, and constructive feedback through a social pedagogy framework
Authors: McHugh Douglas , Yanik Andrew J , Mancini Michael R 
Published: October 2020

Abstract
Background

Ongoing developments in medical education recognize the move to curricula that support self-regulated learning processes, skills of thinking, and the ability to adapt and navigate uncertain situations as much as the knowledge base of learners. Difficulties encountered in pursuing this reform, especially for pharmacology, include the tendency of beginner learners not to ask higher-order questions and the potential incongruency between creating authentic spaces for self-directed learning and providing external expert guidance. We tested the feasibility of developing, implementing, and sustaining an innovative model of social pedagogy as a strategy to address these challenges.

Methods

Constructivism, communities of practice, and networked learning theory were selected as lenses for development of the model. 365 first-year medical students participated between 2014-2018; they were introduced to pharmacodynamics and pharmacokinetics via 15 online modules that each included: learning objectives, a clinical vignette, teaching video, cumulative concept map, and small group wiki assignment. Five-person communities organized around the 15 wiki assignments were a key component where learners answered asynchronous, case-based questions that touched iteratively on Bloom’s cognitive taxonomy levels. The social pedagogy model’s wiki assignments were explored using abductive qualitative data analysis.

Results

Qualitative analysis revealed that learners acquired and applied a conceptual framework for approaching pharmacology as a discipline, and demonstrated adaptive mastery by evaluating and interacting competently with unfamiliar drug information. Learners and faculty acquired habits of self-directed assessment seeking and learner-centered coaching, respectively; specifically, the model taught learners to look outward to peers, faculty, and external sources of information for credible and constructive feedback, and that this feedback could be trusted as a basis to direct performance improvement.

Conclusions

This social pedagogy model is agnostic with regard to pharmacology and type of health professional learner; therefore, we anticipate its benefits to be transferable to other disciplines.
Hypofractionated proton beam radiotherapy in patients with unresectable liver tumors: multi-institutional prospective results from the Proton Collaborative Group
Authors: Parzen Jacob S , Hartsell William , Chang John , Apisarnthanarax Smith , Molitoris Jason , Durci Michael , Tsai Henry , Urbanic James , Ashman Jonathan , Vargas Carlos , Stevens Craig , Kabolizadeh Peyman 
Published: October 2020

Abstract
Background: Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton beam radiotherapy (PBT) provides the means to escalate radiation dose to the target volume while sparing the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated PBT for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).Methods: We evaluated the prospective registry of the Proton Collaborative Group for patients undergoing definitive PBT for liver tumors. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled.Results: To date, 63 patients have been treated at 9 institutions between 2013-2019. Thirty (48%) had HCC and 25 (40%) had ICC. The median dose and biological equivalent dose (BED) delivered was 58.05 GyE (range, 32.5-75) and 80.5 GyE (range, 53.6-100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ³3 toxicity. With median follow-up of 5.1 months (range, 0.1-40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC. The 1-year LC was significantly higher (95.7%) for patients receiving BED greater than 75.2 GyE than for patients receiving BED of 75.2 GyE or lower (84.6%, p = 0.029). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC. Conclusions: Hypofractionated PBT results in excellent LC, sparing of the uninvolved liver, and low toxicity, even in the setting of dose-escalation. Higher dose correlates with improved LC, highlighting the importance of PBT especially in patients with recurrent or bulky disease.
Ceiling Effect of Clomiphene Citrate on the Testosterone to Estradiol Ratio in Eugonadal Infertile Men
Authors: Liao Yian , Chang Hong-Chiang , WANG SHUO-MENG , CHANG YI-KAI 
Published: October 2020

Abstract
Background:
The testosterone to estradiol ratio (T/E2 ratio) reportedly exerts a stronger effect on semen quality and sexual desire than does testosterone alone. Clomiphene citrate is a selective estrogen receptor modulator that has long been used as an empirical treatment option in the management of idiopathic oligozoospermia. Clomiphene may change the hypothalamus–pituitary–gonad axis and result in the alteration of the T/E2 ratio. No reliable data are available regarding the change in the T/E2 ratio after clomiphene use in eugonadism.
Methods:
This study included 24 male patients who were diagnosed with idiopathic infertility with eugonadism. They all received clomiphene citrate (25 mg/day) as empirical treatment. Blood tests for serum testosterone, estradiol, prolactin, luteinizing hormone, and follicle stimulating hormone were performed before and after 4 weeks of clomiphene use. Paired t-tests were used to evaluate the significance of the hormone level change.
Results:
Overall, the patients’ T/E2 ratio did not increase significantly after clomiphene use. In the subgroup analysis, the T/E2 ratio of patients with a baseline ratio of < 0.2 increased significantly after clomiphene use.
Conclusions:
Clomiphene citrate may significantly increase the T/E2 ratio in eugonadal men under the premise of its ceiling effect (T/E2 ratio < 0.20), providing practitioners with guidance on the use of clomiphene in this demographic.
Waste Polystyrene Degradation in the World Oceans: Newly identified sources of Contamination
Authors: Saido Katsuhiko , Kodera Yoichi , Kimukai Hideki , Sato Hideto , Okabe Akifumi , Koizumi Koshiro , Takatama Kohei , Kwon Bum Gun , Chung Seon-Yong , Nishimura Masahiko , Mentese Sibel 
Published: October 2020

Abstract
Since 1970, lumps of plastic breakage into micro/nano pieces has been clearly shown a serious and large source of ocean pollution. To clarify in detail the course of this impact, thermoplastics were decomposed at natural conditions kinetically. And field surveys conducted on four thousand sand and water samples including these at deep-sea sites from around the world during the period, 2000 to 2015. All samples were found to contain styrene oligomers (SOs), that had been generated from drifting polystyrene (PS) degradation. Lumps of plastic not only break up into micro/nano-fragments but also degrade into their basic structure units of plastic. From 1950 to 2015, 4.2 billion metric tons (MT) of SOs were shown to be generated from drifting PS. The monomers are newly and highly significant source of pollution of marine ecosystem directly and global warming of planet and should be given the utmost serious attention.
Immune checkpoint inhibitor does not increase risks of poor outcomes in cancer patients with COVID-19 infection: A systematic review and meta-analysis
Authors: Lazarus Gilbert , Budiman Refael Alfa , Rinaldi Ikhwan 
Published: October 2020

Abstract
Background The association between prior exposure to immune checkpoint inhibitor (ICI) and outcomes of cancer patients with coronavirus disease 2019 (COVID-19) infection has yet to be systematically evaluated. As the current evidence remains equivocal, this meta-analysis aims to investigate the effects of ICI treatment on COVID-19 prognosis, including mortality, severity, and hospitalization.Methods Eligible studies published up to 14 September 2020 were included and assessed for risk of bias using the Quality in Prognosis Studies tool. A random-effects meta-analysis was conducted to estimate the pooled effect size along with 95% confidence intervals (CIs). The quality of body evidence was evaluated using the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Results Six studies involving a total of 1647 COVID-19-infected cancer patients were included in the systematic review. We discovered that prior ICI exposure was not associated with COVID-19 mortality (odds ratio [OR] 0.93 [95% CI: 0.37-2.36]; I2=30%), severity (OR 1.15 [95% CI: 0.40-3.28]; I2=0%), and hospitalization (OR 1.35 [95% CI: 0.64-2.87]; I2=51%). However, we discovered that prior exposure to chemoimmunotherapy predicted COVID-19 severity (OR 8.19 [95% CI: 2.67-25.08]; I2=0%), albeit with small sample size. GRADE assessments resulted in moderate-quality evidence for mortality, while the other outcomes yielded very low-to-low-quality evidenceConclusion Our findings indicated that ICI treatment should not be adjourned nor terminated during the current pandemic. Rather, COVID-19 vigilance should be increased, especially in patients receiving chemoimmunotherapy. Further studies with larger ICI cohorts are required to confirm our findingsTrial registration number: This project has been prospectively registered at PROSPERO (registration ID: CRD42020202142) on 4 August 2020.
WITHDRAWN: Comparative genome analyses highlight transposon-mediated genome expansion shapes the evolutionary architecture of 3D genomic folding in cotton
Authors: Wang Maojun , Li Jianying , Wang Pengcheng , Liu Zhenping , Liu Fang , Zhao Guannan , Xu Zhongping , Wang Kunbo , Zhang Xianlong 
Published: October 2020

Abstract
Transposable element (TE) amplification has been recognized as a driving force mediating genome size expansion and evolution, but the effect on shaping of 3D genomic architecture remains largely unknown in plants. Here, we report three reference-grade cotton genome assemblies of Gossypium rotundifolium (K2), G. arboreum (A2) and G. raimondii (D5) using Oxford Nanopore sequencing technology. Comparative genome analyses document the details of lineage-specific TE amplification contributing to three-fold change of genome size (K2, 2.44 Gb; A2, 1.62 Gb; D5, 750.19 Mb), and indicate a relatively conserved gene content and synteny relationship among genomes. We found that approximately 17% of syntenic genes exhibit chromatin status switching of A/B compartment, and active TE amplification increases the proportion of A compartment in gene regions in K2 and A2 relative to D5. We also found that only 42% of topologically associating domain (TAD) boundaries were conserved by comparing three genomes, and abundant TE amplification was linked to the organization of lineage-specific TADs. This study sheds light on the regulatory role of transposon-mediated genome expansion in the evolution of higher-order chromatin structure in plants.
SARS-CoV-2 direct cardiac damage through spike-mediated cardiomyocyte fusion
Authors: Schneider Jay , Pease David , Navaratnarajah Chanakha , Halfmann Peter , Clemens Daniel , Ye Dan , Kim Changsung , Barkhymer Alison , Cohle Stephen , Banks Aron , Mehta Arpit , Rantus Joseph , Emmerzaal Tim , Kozicz Tamas , Howell Kyle , Charlesworth Jon , Christensen Trace , Kawaoka Yoshihiro , Cooper Leslie , Ackerman Michael , Cattaneo Roberto 
Published: October 2020

Abstract
Viruses spread between hosts through particles, but within hosts, viral genomes can spread from cell to cell through fusion, evading antiviral defenses and obviating costly infectious virion production1-3. Billions of electromechanically coupled cardiomyocytes (CMs) make myocardium inherently vulnerable to pathological electromechanical short circuits caused by intercellular viral spread 4-6. Beyond respiratory illness, COVID-19 affects the heart7 and cardiac injury and arrhythmias are serious public health concerns8-12. By studying myocardium of a young woman who died suddenly, diagnosed postmortem with COVID-19, we discovered highly focal myocardial SARS-CoV-2 infection spreading from one CM to another through intercellular junctions identified by highly concentrated sarcolemmal t-tubule viral spike glycoprotein. SARS-CoV-2 permissively infected beating human induced pluripotent stem cell (hiPSC)-CMs building multinucleated cardiomyotubes (CMTs) through cell type-specific fusion driven by proteolytically-activated spike glycoprotein. Recombinant spike glycoprotein, co-localizing to sarcolemma and sarcoplasmic reticulum, produced multinucleated CMTs with pathological structure, electrophysiology and Ca2+ excitation-contraction coupling. Blocking cleavage, a peptide-based protease inhibitor neutralized SARS-CoV-2 spike glycoprotein pathogenicity. We conclude that SARS-CoV-2 spike glycoprotein, efficiently primed, activated and strategically poised during biosynthesis, can exploit the CM’s inherent membranous connectivities to drive heart damage directly, uncoupling clinically common myocardial injury from lymphocytic myocarditis, often suspected but rarely confirmed in COVID-19.
An Investigation on the Public's Acceptance of Prevention and Control Measures for COVID-19 in China
Authors: Zhang Ao , Wu Xiang , Gao Jingqi , Zhang Yongbao 
Published: October 2020

Abstract
Background: China has basically succeeded in controlling the COVID-19 epidemic, which is due to the cooperation and acceptance of epidemic prevention measures by the public. However, few studies have examined the measures China has taken to combat COVID-19 in order to reflect on its success in curbing the the spread of epidemic.Methods: In this study, the public acceptance questionnaire was designed based on the epidemic prevention measures adopted in China, to investigate the difference of public acceptance of epidemic prevention measures. The survey data was collected from 2,062 samples with different demographic characteristics from March 8, 2020 to April 9, 2020. And SPSS was used to analyze the data collected in the questionnaire, such as one-way variance, so as to draw conclusions.Results: The results show that age and educational level have a significant influence on public acceptance. In contrast gender and occupation field has no significant impact on it. The acceptance of the emergency prevention and control measures taken by the government during the epidemic period is generally high. With the development of the epidemic, the acceptability is increasing. And the public acceptance of traffic measures was highest. Conclusions: Rapid deployment of epidemic prevention measures and appropriate methods in transportation, economy and education are the key to China's effective containment of the epidemic. Measures such as shutting down cities and encouraging the wearing of masks deserve to be copied by other countries.This study summed up China's scientific experience in the fight against COVID-19 and differences in public acceptance. It can provide a positive reference for the development of epidemic prevention measures in other countries.
Bicelin (B-cell lymphoma 2 inhibitor) a Highly Safe DNA-based Anti-cancer Drug Showed No in vivo Cytopenia, Nephrotoxicity and/or Hepatotoxicity
Authors: Sheikhnejad Reza , Ashrafi Farzaneh , Talebi Ardeshir , Mazaheri Bahar , Moslemi Fatemeh , Nematbakhsh Mehdi 
Published: October 2020

Abstract
Background: Non-Hodgkin's lymphoma is the seventh most common cancer in clinic. Lymphoma could be treated with newly developed anti-apoptotic small molecule inhibitors of bcl-2 such as ABT-199 or venetoclax. However most small molecules present numerous side effects and cancer becomes resistance to them rapidly. PNT100 is a DNA-based bcl-2 inhibitor that has shown great efficacy and safety in treating non-Hodgkin's lymphoma tumors. However, liposomal carrier(smarticles) that was used to deliver PNT100 eventually failed to produce robust efficacy in the latest clinical trial conducted by ProNai Therapeutics (now called Sierra Technology). The high cost of liposomal carriers, makes this targeted drug less affordable. In addition, the liposomal components may also present some minor side effects as reported in pilot phase II trial [17-22]. In this study, we eliminated liposome and used a specific Epigenic modification to deliver this 24bp oligonucleotides (PNT100) without using additional chemicals and named it Bicelin. Methods: In this study, the safety of Bicelin was determined by evaluating the cytopenia, nephrotoxicity and hepatotoxicity effects of this drug in healthy animal model (Rats). The rats in experimental group were received Bicelin (20 mg/kg/day) for 5 days a week. The treatment was continued for 3 consecutive weeks. The blood and urine samples were collected for evaluation and the rats were then sacrificed. The kidneys and liver tissues were fixed in formalin 10% to perform histological investigation using H&E staining. Results: The in vitro and in vivo results clearly demonstrate that Bicelin is target specific and highly safe. We observed no cytopenia when blood tests were performed after 15 consecutive injection of Bicelin; Urine analysis revealed no significant differences between experimental and control group and there was no nephrotoxicity or hepatotoxicity when kidney and liver tissues were examined. Conclusion: based on our in vitro and in vivo safety studies, our bcl2 inhibitor, Bicelin is much safer and about 10-fold more effective than its liposomal form (PNT2258). Considering preclinical, phase I and II studies of PNT2258, Bicelin is expected to be very safe and effective in clinic.
Pacific Biosciences Single-molecule Real-time (SMRT) Sequencing Reveals High Diversity of Basal Fungal Lineages and Stochastic Processes Controlled Fungal Community Assembly in Mangrove Sediments
Authors: Zhang Zhi-Feng , Pan Yue-Ping , Liu Yue , Li Meng 
Published: October 2020

Abstract
Background: Mangrove wetlands are unique ecosystems with specific environmental characteristics, and are a hotspot of biodiversity. Although they probably harbor a variety of mangrove-specific fungi, the compositions of mangrove fungal community has been rarely investigated in detail, except for few published culture-based studies. In addition, the fungal community assembly and interaction patterns that impact the community composition in mangroves have not been explored to date. Results: We used the Pacific Biosciences single-molecule real-time sequencing approach targeting the entire internal transcribed spacer region, to systematically investigate the composition, biogeographical patterns, assembly processes, co-occurrence patterns and shaping factors of the fungal communities in sediments of seven representative mangroves across the Southeast China. We recovered 15 phyla, including some early diverging fungal lineages not previously reported in mangroves. Phylogenetic analysis revealed an incredibly high proportion of Rozellomycota and Chytridiomycota, as accounting for up to one-third of all fungal abundance. Although the neutral community model described a moderate portion of community variation, the similarity of fungal communities exhibited strong distance-decay patterns. Furthermore, the mean values and most beta nearest-taxon index fell between -2 to 2, with Bray–Curtis-based Raup–Crick value generally greater than 0.95, suggesting that stochastic processes strongly shape the fungal community composition. Consistently, nonmetric multidimensional scaling and permutational multivariate analysis of variance confirmed the geographical location as a crucial factor driving the distribution of both, the dominant and rare taxa of mangrove fungi. The db-RDA analyses indicated a minor role of environmental selections in shaping the fungal community. Network analyses revealed that the deep sediments harbor more complex fungal networks with highly connected taxa than surface sediments, and that rare fungal taxa might play important roles in microbial interactions and ecological functions in mangrove sediments.Conclusions: The investigation revealed high fungal diversity in mangrove sediments, with incredibly high numbers of basal fungal lineages, stochastic processes driving the assembly of fungal community, and geographic location strongly shaping fungal community composition in mangroves. These discoveries therefore spur further studies of the utilization and protection of fungal resources and communities in mangrove sediments.
Genome Wide Identification and Characterization of Light-Harvesting Chloro a/b Binding Genes Reveals their Potential Role in Enhancing Drought Tolerance in Gossypium hirsutum
Authors: Gereziher Teame , Xu Yanchao , Magwanga Richard Odongo , Kirungu Joy Nyangasi , Cai Xiaoyan , Hou Yuqing , Wang Yuhong , Wang Kunbo , Zhou Zhongli , Liu Fang 
Published: October 2020

Abstract
BackgroundCotton is an important commercial crop for its valuable source of natural fiber. Its production has undergone a sharp failure because of abiotic stress influences, of significance is drought. Moreover, plants have evolved self-defense mechanisms against the effects of several ways of abiotic factors like drought, salt, cold among others. The evolution of stress responsive transcription factors such as the trihelix, a nodule-inception-like protein (NLP), the late embryogenesis abundant (LEA) proteins among others have shown positive response in improving resistance to several forms of abiotic stress features.ResultsGenome wide identification and characterization of the effects of Light-Harvesting Chloro a/b binding (LHC) genes was carried out in cotton under drought stress conditions. A hundred and nine proteins encoded by the LHC genes were found in the cotton genome, with 55, 27, and 27 genes found to be distributed in Gossypium hirsutum, G. arboreum, and G. raimondii, respectively. The proteins encoded by the genes were unevenly distributed in various chromosomes. The Ka/Ks values were less than one, and an indication of negative selection of the gene family. differential expression arrangement of genes was showed with the majority of the genes being highly upregulated in the root tissues in relative to leave and stem tissues. Moreover, more genes were induced in M85 a relative drought tolerant germplasm.Conclusion:The results provide proof of the possible role of the LHC genes in improving drought stress tolerance, and can be explored by cotton breeders in releasing a more drought tolerant cotton germplasms.