bluuebunny/crossref_metadata_2025_split huggingface dataset:
LONG-TERM OUTCOMES OF ENDOSCOPIC ULTRASOUND-GUIDED RADIOFREQUENCY ABLATION (EUS-RFA) FOR ADVANCED PANCREATIC AND PERIAMPULLARY ADENOCARCINOMA
Authors: Thosani Nirav , Cen Putao , Rowe Julie , Guha Sushovan , Bailey-Lundberg Jennifer , Bhakta Dimpal , Patil Prithvi , Rashtak Shahrooz , Davee Roy Tomas , Ramireddy Srinivas , Wray Curtis J. 
Published: December 2021

ABSTRACTBackgroundLong term prognosis for pancreatic adenocarcinoma (PDAC) remains especially poor with an overall 5-year survival rate less than 9%. Endoscopic ultrasound (EUS) guided RFA (EUS-RFA) is an emerging technology and limited data exist regarding long-term outcomes of EUS-RFA for PDAC. In addition to thermal-induced coagulative necrosis and tissue damage, radiofrequency ablation (RFA) has potential to stimulate the host’s antitumor immunity. The aim of this study is to report long-term outcomes of EUS-RFA for unresectable PDAC.MethodsRetrospective chart review of adult patients with an established diagnosis of locally-advanced or metastatic PDAC undergoing EUS-RFA between October 2016 to March 2018 with long term follow up (>30 months). Patients included in the review underwent a total of 1-4 RFA sessions using the Habib EUS-RFA radiofrequency catheter. All patients were concurrently undergoing standard of care chemotherapy.Results10 patients (median age 62 years, male 70%) underwent EUS-RFA (Table 1). Location of the primary PDAC was in the head (4), neck (2), body (2), and tail (2). A total of 22 RFA sessions were performed with a range of 1-4 RFA sessions per patient. RFA was technically successful in all RFA sessions (100%). There were no major adverse events (bleeding, perforation, infection, pancreatitis) in immediate (up to 72 hours) and short-term follow up (4 week). Mild worsening of existing abdominal pain was noted during post-procedure observation in 12/22 (55%) of RFA treatments. Follow-up imaging after RFA treatment was available in 8/10 patients. Tumor progression was noted in 2 patients, whereas tumor regression was noted in 6 patients (>50% reduction in size in 3 patients). Median survival for the cohort was 20.5 months (95% CI, 9.93 to 42.2 months). Currently, 2 patients remain alive at 53 and 73 months follow-up since initial diagnosis. One patient had 3 cm PDAC with encasement of the portal confluence, abutment of the celiac axis, common hepatic and superior mesenteric artery. This patient had significant reduction in tumor size and underwent standard pancreaticoduodenectomy.ConclusionIn our experience, EUS-RFA was safe, well-tolerated and could be concurrently performed with standard of care chemotherapy. In this select cohort, median survival (20.5 months) was improved when compared to published survival based upon SEER database and clinical trials. Future prospective trials are needed to understand the role of EUS-RFA in overall management of PDAC.
Social and labor stressors influencing disability in Adult Attention Deficit/Hyperactivity
Authors: Abramov Dimitri Marques , Baruzzi Marjorie Mastellaro , Alvim Renata Joviano , Peixoto Ana Carolina Moda Nunes , de Souza Mannarino Victor , Pacheco Loureiro Caroline Barros , Ferreira Danilla , Almeida Iara , Pinheiro Ingrid , Valentim Rosângela Marques 
Published: December 2021

AbstractAttention Deficit/Hyperactivity Disorder (ADHD) is a controversial issue. If ADH represents a mental disorder, it must be the cause of a primary dysfunctionality and maladaptation from childhood to adult life. We will look for evidence to substantiate this discussion. We conducted an online survey about economic and academic performances and maladaptation, following a screening for ADHD using Adult Self Report Scale (ASRS). The subjects were naive. There were 2173 participants, of which 28.06% were ADH(+). Even regarding only subjects with extreme ASRS scores (<1.0 and >2.5), ADH(+) and (−) groups did not shown difference in functionality. We grouped subjects by professional career. The highest ADH(+) prevalence was found in publicity, where almost no difference in subjective suffering between the groups was observed. Our results indicate that ADH(+) people can show equivalent functionality and adaptability than ADH(−) ones when they live in their preferred labor/social niches, arguing that ADHD can be a different cognitive style with dysfunctionality and mental suffering could be secondary to social stress.
Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac
Authors: Nantanee Rapisa , Aikphaibul Puneyavee , Jaru-Ampornpan Peera , Sodsai Pimpayao , Himananto Orawan , Theerawit Tuangtip , Sophonphan Jiratchaya , Tovichayathamrong Punyot , Manothummetha Kasama , Laohasereekul Tysdi , Hiransuthikul Narin , Hirankarn Nattiya , Puthanakit Thanyawee 
Published: December 2021

AbstractBackgroundCurrently, booster dose is needed after 2 doses of inactivated COVID-19 vaccine. With limited resource and shortage of COVID-19 vaccine, intradermal(ID) administration might be a potential dose-sparing strategy.ObjectiveTo determine antibody response and reactogenicity of ID ChAdOx1 nCoV-19 vaccine(AZD1222,Oxford/AstraZeneca) as a booster dose after completion of 2-dose CoronaVac(SV) in healthy adult.MethodsThis is a prospective cohort study of adult aged 18-59 years who received 2-dose SV at 14-35 days apart for more than 2 months. Participants received ID AZD1222 at fractional low dose(1×1010 viral particles,0.1ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against wild type and delta variant and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14 or 28, and day90 post booster. Solicited reactogenicity was collected during 7 days post-booster. Primary endpoint was the differences of sVNT against delta strain ≥80%inhibition at day14 and 90 compared with the parallel cohort study of 0.5-ml intramuscular(IM) route.ResultsFrom August2021, 100 adults with median(IQR) age of 46(41-52) years participated. At baseline, geometric means(GMs) of sVNT against delta strain prior to booster were 22.4%inhibition(95%CI 18.7-26.9) and of anti-S-RBD IgG were 109.3(95.4-125.1)BAU/ml. GMs of sVNT against delta strain were 92.9%inhibition(95%CI 87.7-98.3) at day14 and 73.1%inhibition(66.7-80.2) at day90 post ID booster. The differences of proportion of participants with sVNT to delta strain≥80%inhibition in ID recipients versus IM were +4.2%(95%CI-2.0to10.5) at day14, and -37.3%(−54.2to−20.3) at day90. Anti-S-RBD IgG GMs were 2037.1(95%CI1770.9-2343.2) at day14 and 744.6(650.1-852.9) BAU/ml at day90, respectively. Geometric mean ratios(GMRs) of anti-S-RBD IgG were 0.99(0.83-1.20) at day14, and 0.82(0.66-1.02) at day90. Only 18% reported feverish, compared with 37% of IM(p=0.003). Only 18% reported feverish, compared with 37% of IM(p=0.003). Common reactogenicity was erythema(55%) at injection site while 7% reported blister.ConclusionLow-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.HighlightsIntradermal AZD1222 booster vaccine gave comparable short-term immunogenicity but lower 90-day immunogenicity with conventional intramuscular vaccine.Lower systemic but higher local reactogenicity was found in intradermal AZD1222 booster vaccine.Blister and pruritus could be seen after intradermal AZD1222 booster vaccine.
Proposing Response Evaluation Criteria in Solid Tumors Based on Genomic Profiling or Genomic RECIST: A Retrospective Study on the Liquid Biopsy Results of 29 Cancer Patients
Authors: Yar Myint Khin Zay , Shimabuku Masamori , Kashihara Kenichi , Horio Ruriko , Kaneda Munehisa , Shimizu Yoko , Taguchi Junichi 
Published: December 2021

AbstractTumor response and disease progression are assessed using imaging technologies. However, these technologies fail to detect tumor responses at the molecular level and clonal evolution. A potential surrogate for such parameters is using circulating tumor DNA (ctDNA). This study aimed to examine the quantity and composition of the ctDNA results of 29 cancer patients before and after dendritic cell (DC) immunotherapy and develop criteria to evaluate the molecular response to treatment based on these results. We categorized the patients into four categories based on percent changes in the total ctDNA compared with the baseline ctDNA titers, and this response assessment was termed genomic response evaluation criteria in solid tumors or gRECIST. Even those who are clinically evaluated as having a good response might harbor unfavorable tumor responses at the molecular level. Newly formed ctDNA levels can be the most prognostic parameter in tumor progression or the treatment response, while ctDNA clearance and the decline or rise in existing ctDNA did not change significantly in genomic response categories (gRECIST). More research is needed to support the clinical use of ctDNA in precision oncology and personalized cancer treatment.
Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects on brain
Authors: Kember Rachel L. , Vickers-Smith Rachel , Xu Heng , Toikumo Sylvanus , Niarchou Maria , Zhou Hang , Hartwell Emily , Crist Richard C. , Rentsch Christopher T. ,   VA Million Veteran Program, Davis Lea K. , Justice Amy C. , Sanchez-Roige Sandra , Kampman Kyle M. , Gelernter Joel , Kranzler Henry R. 
Published: December 2021

AbstractDespite an estimated twin heritability of ∼50%, genome-wide association studies (GWAS) of opioid use disorder (OUD) have revealed few genome-wide significant (GWS) loci, with replicated findings only in European-ancestry individuals. To identify novel loci, including those in non-European ancestries, and improve our understanding of the biology of OUD, we conducted a cross-ancestry meta-analysis using the Million Veteran Program (MVP). OUD cases in MVP had at least 1 International Classification of Diseases (ICD)-9 or ICD-10 code for opioid abuse or dependence (N=31,473). Opioid-exposed controls (N=394,471) had one or more outpatient opioid prescription fills. We conducted GWAS for each major ancestral group in MVP: African Americans (AAs; N=88,498), European Americans (EAs; N=302,585), and Hispanic Americans (HAs; N=34,861), followed by a cross-ancestry meta-analysis. Ten loci were GWS in the cross-ancestry meta-analysis, 8 of them novel. In addition to the known coding variant rs1799971 in OPRM1, which was the lead SNP genome-wide (p=6.78×10−10), and a recently reported exonic variant in FURIN, we identified intronic variants in RABEPK, FBXW4, NCAM1, and KCNN1. Ancestry-specific analyses identified an additional novel locus for each of the 3 ancestry groups. A supplementary meta-analysis within EAs that included MVP and other samples identified a locus in TSNARE1, which was also GWS in the cross-ancestry meta-analysis of all datasets. Gene-based association analyses identified 1 gene in AAs (CHRM2) and 3 in EAs (OPRM1, DRD2, and FTO). Significant genetic correlations (rg’s) were identified for 127 traits, including positive correlations with schizophrenia, problematic alcohol use, and major depressive disorder. The most significantly enriched cell type group was the central nervous system with gene-expression enrichment identified in brain regions previously associated with substance use disorders. With a case sample 50% larger than that of the previous largest GWAS, we identified 14 loci for OUD, including 12 novel loci, some of which were ancestry-specific. These findings increase our understanding of the biological pathways involved in OUD, which can inform preventive, diagnostic, and therapeutic efforts and thereby help to address the opioid epidemic.
Comparisons of the risk of myopericarditis between COVID-19 patients and individuals receiving COVID-19 vaccines: a population-based study
Authors: Chou Oscar Hou In , Zhou Jiandong , Lee Teddy Tai Loy , Kot Thompson , Lee Sharen , Wai Abraham Ka Chung , Wong Wing Tak , Zhang Qingpeng , Cheng Shuk Han , Liu Tong , Vassiliou Vassilios S , Cheung Bernard Man Yung , Tse Gary 
Published: December 2021

AbstractBackgroundBoth COVID-19 infection and COVID-19 vaccines have been associated with the development of myopericarditis. The objective of this study is to 1) analyze the rates of myopericarditis after COVID-19 infection and COVID-19 vaccination in Hong Kong and 2) compare to the background rates, and 3) compare the rates of myopericarditis after COVID-19 vaccination to those reported in other countries.MethodsThis was a population-based cohort study from Hong Kong, China. Patients with positive RT-PCR test for COVID-19 between 1st January 2020 and 30th June 2021 or individuals who received COVID-19 vaccination until 31st August were included. The main exposures were COVID-19 positivity or COVID-19 vaccination. The primary outcome was myopericarditis.ResultsThis study included 11441 COVID-19 patients from Hong Kong, of whom four suffered from myopericarditis (rate per million: 350; 95% confidence interval [CI]: 140-900). The rate was higher than the pre-COVID-19 background rate in 2020 (rate per million: 61, 95% CI: 55-67) with a rate ratio of 5.73 (95% CI: 2.23-14.73. Compared to background rates, the rate of myopericarditis among vaccinated subjects in Hong Kong was substantially lower (rate per million: 8.6; 95% CI: 6.4-11.6) with a rate ratio of 0.14 (95% CI: 0.10-0.19). The rates of myocarditis after vaccination in Hong Kong are comparable to those vaccinated in the United States, Israel, and the United Kingdom.ConclusionsCOVID-19 infection is associated with a higher rate of myopericarditis whereas COVID-19 vaccination is associated with a lower rate of myopericarditis compared to the background.
Development of an explicit and implicit knowledge identification tool for the analysis of the decision-making process of traditional Asian medicine doctors
Authors: Park Musun , Kim Min Hee , Park So-young , Kang Minseo , Choi Inhwa , Kim Chang-Eop 
Published: December 2021

AbstractBackground and objectivesWhile pattern identification (PI) is an essential process for diagnosis and treatment in traditional Asian medicine (TAM), it is difficult to objectify since it relies heavily on implicit knowledge. Here, we propose a machine learning-based analysis tool to objectify and evaluate the clinical decision-making process of PI in terms of explicit and implicit knowledge.MethodsClinical data for the development of the analysis tool were collected using a questionnaire administered to allergic rhinitis (AR) patients and the diagnosis and prescription results of TAM doctors based on the completed AR questionnaires. Explicit knowledge and implicit knowledge were defined based on the explicit and implicit importance scores of the AR questionnaire, which were obtained through doctors’ explicit scoring and feature evaluations of machine learning models, respectively. The analysis tool consists of eight evaluation indicators used to compare, analyze and visualize the explicit and implicit knowledge of TAM doctors.ResultsThe analysis results for 8 doctors showed that our tool could successfully identify explicit and implicit knowledge in the PI process. We also conducted a postquestionnaire study with the doctors who participated to evaluate the applicability of our tool.ConclusionsThis study proposed a tool to evaluate and compare decision-making processes of TAM doctors in terms of their explicit and implicit knowledge. We identified the differences between doctors’ own explicit and implicit knowledge and the differences among TAM doctors. The proposed tool would be helpful for the clinical standardization of TAM, doctors’ own clinical practice, and intern/resident training.
An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome
Authors: Liu Shixuan , Ezran Camille , Wang Michael F. Z. , Li Zhengda , Awayan Kyle ,   The Tabula Microcebus Consortium, Long Jonathon Z. , De Vlaminck Iwijn , Wang Sheng , Epelbaum Jacques , Kuo Christin , Terrien Jeremy , Krasnow Mark A. , Ferrell James E. 
Published: December 2021

AbstractHormones mediate long-range cell communication in multicellular organisms and play vital roles in normal physiology, metabolism, and health. Using the newly-completed organism-wide single cell transcriptional atlas of a non-human primate, the mouse lemur (Microcebus murinus), we have systematically identified hormone-producing and -target cells for 84 classes of hormones, and have created a browsable atlas for hormone signaling that reveals previously unreported sites of hormone regulation and species-specific rewiring. Hormone ligands and receptors exhibited cell-type-dependent, stereotypical expression patterns, and their transcriptional profiles faithfully classified the molecular cell type identities, despite their comprising less than 1% of the transcriptome. Cells of similar cell types further display stage, subtype or organ-dependent specification of hormonal signaling, reflecting the precise control of global hormonal regulation. By linking ligand-expressing cells to the cells expressing the corresponding receptor, we constructed an organism-wide map of the hormonal cell communication network. This network was remarkably densely and robustly connected and included a myriad of feedback circuits. Although it includes classical hierarchical circuits (e.g. pituitary → peripheral endocrine gland → diverse cell types), the hormonal network is overall highly distributed without obvious network hubs or axes. Cross-species comparisons among humans, lemurs, and mice suggest that the mouse lemur better models human hormonal signaling, than does the mouse. Hormonal genes show a higher evolutionary conservation between human and lemur vs. human and mouse at both the genomic level (orthology-mapping and sequence identity) and the transcriptional level (cell type expression patterns). This primate hormone atlas provides a powerful resource to facilitate discovery of regulation on an organism-wide scale and at single-cell resolution, complementing the single-site-focused strategy of classical endocrine studies. The network nature of hormone regulation and the principles discovered here further emphasize the importance of a systems approach to understanding hormone regulation.
Morphological variation and phylogeny ofKarenia selliformis(Gymnodiniales, Dinophyceae) in an intensive cold-water algal bloom in eastern Hokkaido, Japan in September–November 2021
Authors: Iwataki Mitsunori , Lum Wai Mun , Kuwata Koyo , Takahashi Kazuya , Arima Daichi , Kuribayashi Takanori , Kosaka Yuki , Hasegawa Natsuki , Watanabe Tsuyoshi , Shikata Tomoyuki , Isada Tomonori , Orlova Tatiana Yu. , Sakamoto Setsuko 
Published: December 2021

AbstractHarmful algal blooms responsible for mass mortalities of marine organisms have so far been rare in Hokkaido, northern Japan, although fish killing blooms have been frequently reported from western Japanese coasts. In September–November 2021, a huge and prolonged cold-water bloom occurred along the Pacific coast of eastern Hokkaido, Japan, and was associated with intensive mortalities of sea urchin, fish, octopus, shellfish, etc. In this study, morphology and phylogeny of the dominant and co-occurred unarmored dinoflagellates of the Kareniaceae in the bloom were examined by using light microscopy, scanning electron microscopy and molecular phylogeny inferred from ITS and LSU rDNA (D1–D3) sequences. Morphological observation and molecular phylogeny showed that the dominant species wasKarenia selliformis, with co-occurrences of other kareniacean dinoflagellates,Kr. longicanalis,Kr. mikimotoi,Karlodiniumsp.,Takayamacf.acrotrocha,Takayama tuberculataandTakayamasp. The typical cell forms ofK. selliformisin the bloom were discoid, dorsoventrally flattened, and larger than the cell sizes in previous reports, 35.3–43.6 (39.4±2.1) μm in length. Transparent cells ofKr. selliformislacking or having several shrunken chloroplasts and oil droplets were also found. Cells ofKr. selliformishad morphological variation, but the species could be distinguished from other co-occurredKareniaspecies by its numerous (46–105) and small granular (2.9–4.6 μm in diameter) chloroplasts and the nucleus positioned in the hypocone. Cell density ofKr. selliformisexceeding 100 cells/mL was recorded in the range of temperature 9.8–17.6°C. The rDNA sequences determined fromKr. selliformisin the blooms of Hokkaido, Japan in 2021 were identical to those from another bloom in Kamchatka, Russia in 2020.HighlightsA marine fauna-destructive harmful algal bloom in the Pacific coast of eastern Hokkaido, Japan in September–November 2021 was dominated byKarenia selliformis.Cells ofKarenia selliformistypical in the bloom were discoid and possessing numerous small chloroplasts, approximately 70 in number.Cells ofKarenia selliformisshowed morphological variation in size and shape, and transparent motile cells lacking or having degraded chloroplasts were also present.Co-occurred kareniaceans in the bloom wereKarenia longicanalis,Karenia mikimotoi,Karlodiniumsp. andTakayamaspp.rDNA sequences ofKarenia selliformisin the blooms of Hokkaido in 2021 and Kamchatka in 2020 were identical, which belong to the group I ofKr. selliformis.
Myricetin allosterically inhibits Dengue NS2B-NS3 protease as studied by NMR and MD simulations
Authors: Dang Mei , Lim Liangzhong , Roy Amrita , Song Jianxing 
Published: December 2021

ABSTRACTDengue NS2B-NS3 protease existing in equilibrium between the active and inactive forms is essential for virus replication, thus representing a key drug target. Here Myricetin, a plant flavonoid, was characterized to non-competitively inhibit Dengue protease. Further NMR study identified the protease residues perturbed by binding to Myricetin, which were utilized to construct the Myricetin-protease complexes. Strikingly, in the active form Myricetin binds a new allosteric site (AS2) far away from the active site pocket and allosteric site (AS1) for binding Curcumin, while in the inactive form it binds both AS1 and AS2. To decipher the mechanism for the allosteric inhibition by Myricetin, we conducted molecular dynamics (MD) simulations on different forms of Dengue NS2B-NS3 protease. Unexpectedly, the binding of Myricetin to AS2 is sufficient to disrupt the active conformation by displacing the characteristic NS2B C-terminal β- hairpin from the active site pocket. By contrast, the binding of Myricetin to AS1 and AS2 results in locking the inactive conformation. Therefore Myricetin represents the first small molecule which allosterically inhibits Dengue protease by both disrupting the active conformation and locking the inactive conformation. The results enforce the notion that a global allosteric network exists in Dengue NS2B-NS3 protease, which is susceptible to allosteric inhibition by small molecules such as Myricetin and Curcumin. As Myricetin has been extensively used as a food additive, it might be directly utilized to fight the Dengue infections and as a promising starting for further design of potent allosteric inhibitors.Graphic Abstract