bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Clinical And Non-Clinical Determinants of Intrapartum Stillbirths In Singletons In Six Public Hospitals In The Greater Accra Region of Ghana: A Retrospective Case-Control Study
Authors: Vanotoo Linda , Dwomoh Duah , Laar Amos , Kotoh Agnes , Adanu Richard
Published: December 2021

Background: The Greater Accra Region (GAR) of Ghana records 2000 stillbirths annually and 40 % of them occur intrapartum. An understanding of the contributing factors will facilitate the development of preventive strategies to reduce the huge numbers of intrapartum stillbirths. This study identified determinants of intrapartum stillbirths in GAR.Method: A retrospective 1:2 unmatched case-control study was conducted in six public hospitals in the Greater Accra Region of Ghana. A multivariable ordinary logistic regression model with robust standard error was used to quantify the effect of exposures on intrapartum stillbirth. The area under the receiver operating characteristics curve and the Brier scores were used to assess the predictive performance of the regression models. Results: The following maternal factors increased the odds of intrapartum stillbirths: pregnancy-induced hypertension (PIH) [adjusted Odds Ratio; aOR=3.72, 95% CI:1.71-8.10, p<0.001]; antepartum haemorrhage (APH) [aOR=3.28, 95% CI: 1.33-8.10, p<0.05] and premature rupture of membranes (PROM) [aOR=3.36, 95% CI: 1.20-9.40, p<0.05]. Conclusions: Improved management of PIH, APH, PROM, and preterm delivery will reduce intrapartum stillbirth. Hospitals should improve on the quality of monitoring women during labor. Auditing of intrapartum stillbirths should be mandatory for all hospitals and Ghana Health Service (GHS) should include fetal autopsy in stillbirth auditing to identify other causes of fetal deaths. Interventions to reduce intrapartum stillbirth must combine maternal, fetal, and service delivery factors to make them effective.
An Embeddable Molecular Code for Lewis X Modification Through Interaction with Fucosyltansferase 9
Authors: Saito Taiki , Yagi Hirokazu , Kuo Chu-Wei , Khoo Kay-Hooi , Kato Koichi
Published: December 2021

N-glycans are diversified by a panel of glycosyltransferases in the Golgi, which are supposed to modify various glycoproteins in promiscuous manners, resulting in unpredictable glycosylation profiles in general. In contrast, our previous study showed that fucosyltransferase 9 (FUT9) generates Lewis X glycotopes primarily on lysosome-associated membrane protein 1 (LAMP-1) in neural stem cells. Here, we demonstrate that a contiguous 29-amino acid sequence in the N-terminal domain of LAMP-1 is indispensable for FUT9-dependent Lewis X modification. Interestingly, Lewis X modification was induced on erythropoietin as a model glycoprotein both in vivo and in vitro, just by attaching this sequence to its C-terminus. Based on these results, we conclude that the amino acid sequence from LAMP-1 functions as a “Lewis X code”, which is deciphered by FUT9, and can be embedded into other glycoproteins to evoke a Lewis X modification, opening up new possibilities for protein engineering and cell engineering.
Decision Tool of Medical Endoscope Maintenance Service in Chinese Hospitals: A Conjoint Analysis
Authors: Zheng Jun , Wei Jingming , Xie Ying , Chen Siyao , Li Jun , Lou Ligang , Sun Jing , Feng Jingyi
Published: December 2021

Background: Quality and cost of medical device maintenance are dominant factors influencing hospitals’ decision in choosing medical endoscope products. Effective and efficient medical device maintenance are also paramount for providing cost-effective and high quality of medical care. This research aims to facilitate decision-making at hospitals in choosing the suitable endoscope device and the associated maintenance service; it also aims to facilitate decision-making at suppliers to develop the right products and services to fulfill customer demands.Methods: A cross-sectional survey was undertaken in 50 Chinese hospitals, including primary and tertiary hospitals. Moreover, 65 medical staff and 56 medical engineers were recruited from 50 Chinese hospitals. A comprehensive set of attributes were defined and investigated. Conjoint analysis and orthogonal design were used for survey design and statistical analysis. Results: Attribute importance and utility values of decision-making factors were analyzed at the aggregate, occupation, and medical institution levels. (1) At the aggregate level, the most critical factor is "maintenance response" and the least important one is "maintenance efficiency". (2) At the occupation level, medical staff paid more attention to "maintenance response" and medical engineers paid more attention to "maintenance quality". (3) At the medical institution level, Primary hospitals paid more attention to "maintenance price", while tertiary hospitals paid more attention to "maintenance quality". Conclusions: In general, this study provides a more scientific decision-making tool to both hospitals in choosing maintenance service of medical equipment such as endoscopy, and it also helps manufacturers and suppliers improve the after-sales service.
Susceptibility of Common Family Anatidae Bird Species to Clade 2.3.4.4e H5N6 High Pathogenicity Avian Influenza Virus: An Experimental Infection Study
Authors: Soda Kosuke , Tomioka Yukiko , Hidaka Chiharu , Matsushita Mayu , Usui Tatsufumi , Yamaguchi Tsuyoshi
Published: December 2021

Background: There were large outbreaks of high pathogenicity avian influenza (HPAI) caused by clade 2.3.4.4e H5N6 viruses in the winter of 2016–2017 in Japan, which caused large numbers of deaths among several endangered bird species including cranes, raptors, and birds in Family Anatidae. In this study, susceptibility of common Anatidae to a clade 2.3.4.4e H5N6 HPAI virus was assessed to evaluate their potential to be a source of infection for other birds. Eurasian wigeons (Mareca penelope), mallards (Anas platyrhynchos), and Northern pintails (Anas acuta) were intranasally inoculated with 106, 104, or 102 50% egg infectious dose (EID50) of clade 2.3.4.4e A/teal/Tottori/1/2016 (H5N6). Results: All birds survived for 10 days without showing any clinical signs of infection. Most ducks inoculated with ≥104 EID50 of virus seroconverted within 10 days post-inoculation (dpi). Virus was mainly shed via the oral route for a maximum of 10 days, followed by cloacal route in late phase of infection. Virus remained in the pancreas of some ducks at 10 dpi. Viremia was observed in some ducks euthanized at 3 dpi, and ≤106.3 EID50 of virus was recovered from systemic tissues and swab samples including eyeballs and conjunctival swabs. Conclusions: These results indicate that the subject duck species have a potential to be a source of infection of clade 2.3.4.4e HPAI virus to the environment and other birds sharing their habitats. Captive ducks should be reared under isolated or separated circumstances during the HPAI epidemic season to prevent infection and further viral dissemination.
Fremanezumab in the Prevention of High-Frequency Episodic and Chronic Migraine: A 12-Week, Multicenter, Real-Life, Cohort Study (The FRIEND Study).
Authors: Barbanti Piero , Egeo Gabriella , Aurilia Cinzia , d'Onofrio Florindo , Albanese Maria , Cetta Ilaria , Fiore Paola Di , Zucco Maurizio , Filippi Massimo , Bono Francesco , Altamura Claudia , Proietti Stefania , Bonassi Stefano , Vernieri Fabrizio
Published: December 2021

Background
Fremanezumab has demonstrated to be effective, safe, and tolerated in the prevention of episodic or chronic migraine (CM) in randomized, placebo-controlled trials (RCTs). Real-life studies are needed to explore drug effects in unselected patients in routine circumstances and to provide higher generalizability results. This study explores the effectiveness, safety, and tolerability of fremanezumab in a real-life population of individuals affected by high-frequency episodic (HFEM: 8-14 days/month) or CM.
Methods
This is a 12-week multicenter, prospective, cohort, real-life study. We considered all consecutive patients affected by HFEM or CM visited at 9 Italian headache centers from 28/07/2020 to 11/11/2020. Eligible patients were given subcutaneous fremanezumab at the doses of 225 mg monthly or 675 mg quarterly, according to their preference. Primary study endpoints were the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients at weeks 9-12 compared to baseline. Secondary endpoints encompassed variation in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), HIT-6 and MIDAS scores, and ≥50%, ≥75% and 100% responder rates at the same time intervals.
Results
67 migraine patients had received ≥1 subcutaneous fremanezumab dose and were considered for safety analysis, while 53 patients completed 12 weeks of treatment and were included also in the effectiveness analysis. Fremanezumab was effective in both HFEM and CM, inducing at week 12 a significant reduction in MMDs (-4.6, p<0.05), MHDs (-9.4, p<0.001), MAI (-5.7, p<0.05; -11.1, p<0.001), NRS (-3.1, p<0.001; -2.5, p<0.001), and MIDAS scores (-58.3, p<0.05; -43.7; p<0.001). HIT-6 was significantly reduced only in HFEM patients (-18.1, p<0.001). Remission from CM to episodic migraine and from MO to no-MO occurred in 75% and 67.7% of the patients. The ≥50%, ≥75% and 100% responder rates at week 12 were 76.5%, 29.4% and 9.9% in HFEM and 58.3%, 25% and 0% in CM. Younger age emerged as a positive response predictor (OR=0.91; 95% CI 0.85-0.98, p=0.013). Treatment-emergent adverse events were uncommon (5.7%) and mild. No patient discontinued fremanezumab for any reason.
Conclusions
Fremanezumab seems more effective in real-life than in RCTs. Younger age emerges as a potential response predictor.
Ferroelectric domain-wall logic units
Authors: Wang Jing , Ma Jing , Huang Houbing , Ma Ji , Jafri Hasnain , Chen Mingfeng , Liu Di , Fan Yuanyuan , Zhang Jinxing , Lin Yuan-Hua , Chen Long-Qing , Yi Di , Nan Ce-Wen
Published: December 2021

The electronic conductivities of ferroelectric domain walls have been extensively explored over the past decade for potential nanoelectronic applications. However, the realization of logic devices based on ferroelectric domain walls requires reliable and flexible control of the domain-wall configuration and conduction path. Here, we demonstrate electric-field-controlled stable and repeatable on-and-off switching of conductive domain walls within topologically confined vertex domains naturally formed in self-assembled ferroelectric nano-islands. Using a combination of piezoresponse force microscopy, conductive atomic force microscopy, and phase-field simulations, we show that on-off switching is accomplished through reversible transformations between charged and neutral domain walls via electric-field-controlled domain-wall reconfiguration. By analogy to logic processing, we propose programmable logic gates (such as NOT, OR, AND and their derivatives) and logic circuits (such as fan-out) based on reconfigurable conductive domain walls. Our work provides a potentially viable platform for programmable all-electric logic based on a ferroelectric domain-wall network with low energy consumption.
Age-Related Macular Degeneration Eyes Presenting with Cuticular Drusen and Reticular Pseudodrusen
Authors: Yoon Je Moon , Shin Dong Hoon , Kong Mingui , Ham Don-Il
Published: December 2021

This study aimed to describe the clinical characteristics of age-related macular degeneration (AMD) eyes with both cuticular drusen (CD) and reticular pseudodrusen (RPD). The clinical records of 13 eyes of seven patients diagnosed with CD and RPD were retrospectively reviewed. All patients underwent a complete ocular examination and multimodal imaging. The distribution patterns of CD (macular and diffuse type) and RPD (localized, intermediate, and diffuse type), presence of soft drusen, large drusen (> 200 µm), variant subretinal drusenoid deposits, and macular complications were investigated. The mean age at initial presentation was 71.4 ± 8.8 years and six patients were female. The mean subfoveal choroidal thickness was 143.8 ± 25.1 µm. The distribution of CD was of the macular type in all eyes. Distribution of RPD was localized in 11 eyes (84.6%) and intermediate in two eyes (15.4%). Soft drusen, large drusen, and variant subretinal drusenoid deposits were present in 13 (100%), 12 (92.3%) and, seven (53.8%) eyes, respectively. Macular neovascularization was observed in two eyes (15.4%). CD and RPD can coexist in eyes with AMD. Multimodal imaging should be used for AMD eyes with features suggestive of CD and RPD, considering the high likelihood of developing late AMD.
Reconstitution of Prenyltransferase Activity on Nanodiscs by Components of the Rubber Synthesis Machinery of the Para Rubber Tree and Guayule
Authors: Kuroiwa Fu , Nishino Akira , Mandal Yasuko , Honzawa Masataka , Suenaga-Hiromori Miki , Suzuki Kakeru , Takani Yukie , Miyagi-Inoue Yukino , Yamaguchi Haruhiko , Yamashita Satoshi , Takahashi Seiji , Tozawa Yuzuru
Published: December 2021

Natural rubber of the Para rubber tree (Hevea brasiliensis) is synthesized as a result of prenyltransferase activity. The proteins HRT1, HRT2, and HRBP have been identified as candidate components of the rubber biosynthetic machinery. To clarify the contribution of these proteins to prenyltransferase activity, we established a cell-free translation system for nanodisc-based protein reconstitution and measured the enzyme activity of the protein-nanodisc complexes. Co-expression of HRT1 and HRBP in the presence of nanodiscs yielded marked polyisoprene synthesis activity. By contrast, neither HRT1, HRT2, or HRBP alone nor a complex of HRT2 and HRBP manifested such activity. Similar analysis of guayule (Parthenium argentatum) proteins revealed that three HRT1 homologs (PaCPT1–3) manifested prenyltransferase activity only if co-expressed with PaCBP, the homolog of HRBP. Our results thus indicate that two heterologous subunits form the core prenyltransferase of the rubber biosynthetic machinery. A recently developed structure modeling program predicted the structure of such heterodimer complexes including HRT1/HRBP and PaCPT2/PaCBP. HRT and PaCPT proteins were also found to possess affinity for a lipid membrane in the absence of HRBP or PaCBP, and structure modeling implicated an amphipathic α-helical domain of HRT1 and PaCPT2 in membrane binding of these proteins.
Halo-Tolerant And Thermostable Mechanisms of An Endoglucanase From Marine Aspergillus Niger
Authors: Cai Li-Nian , Xu Sheng-Nan , Lu Tao , Lin Dong-Qiang , Yao Shan-Jing
Published: December 2021

The cellulase cocktail of marine Aspergillus niger exhibited halo-tolerant and thermostable properties, which is of great potential in industrial application. In order to excavate the single tolerant cellulase components from complex cellulase cocktail, constitutive homologous expression was employed for direct obtainment of the endoglucanase (AnEGL). Enzymatic property study revealed that AnEGL exhibited a property of halo-tolerance and an outstanding thermostability in high salinity environment. Significantly, its activity increased by 29% and the half-life at 65 °C increased by 26.7-fold with the presence of 4.5 M NaCl. Molecular dynamics simulation revealed that Na+ and Cl－ could form salt bridges with charged residues, and then influenced the activity of loops and the stability of substrate binding pocket, which accounted for the halo-tolerance and thermostability. Further, site-specific mutagenesis study proved that the residues Asp95 and Asp99 in the pocket were of great concern for the tolerant properties. The halo-tolerant and thermostable AnEGL was of great value in lignocellulosic utilization and the conjectural mechanisms were of referential significance for other tolerant enzymes.
Relationships Between Soil Microbial Communities and Plant Communities on Different Slope Aspects in a Subalpine Coniferous Forest
Authors: He Luoshu , Ma Suhui , Zhu Jiangling , Xiong Xinyu , Li Yangang , Zhu Biao , Ji Chengjun
Published: December 2021

Purpose The local microclimate of different slope aspects in the same area can not only impact soil environment and plant community but also affect soil microbial community. However, the relationship between aboveground plant communities and belowground soil microbial communities on various slope aspects has not been well understood.Methods We investigated the above- and belowground relationship on different slope aspects and explored how soil properties influence this relationship. Plant community attributes were evaluated by plant species richness and plant total basal area. Soil microbial community was assessed based on both 16S rRNA and ITS rRNA, using High-throughput Illumina sequencing. Results There was no significant correlation between plant richness and soil bacterial community composition on the north slope, but there was a positive correlation on the south slope and a significantly negative correlation on the flat site. There was a significantly negative correlation between soil fungal community composition and plant total basal area, which did not change with the slope aspect. In addition, there was no significant correlation between plant community species richness and soil microbial species richness.Conclusions In subalpine coniferous forests, the relationship between plant-soil bacteria varies with slope aspect, but the plant-soil fungi relationship is relatively consistent across different slope aspects. These results can improve our understanding of the relationship between plant and soil microorganisms in forest ecosystems under microtopographic changes and have important implications for the conservation of biodiversity and forest management in subalpine coniferous forests.
Efficacy of Three Antimalarial Regimens for Uncomplicated Plasmodium Falciparum Malaria in Cambodia, 2009 – 2011: A Randomized Control Trial
Authors: Lek Dysoley , Rachmat Agus , Harrison Dustin , Chin Geoffrey , Chaoratanakawee Suwanna , Saunders David , Menard Didier , Rogers William O.
Published: December 2021

Background: Antimalarial resistance remains an important public health challenge in Cambodia. The effectiveness of three therapies for uncomplicated Falciparum malaria were evaluated in Oddar Meanchey province in Northern Cambodia from 2009 – 2011.Methods: In this randomized, open-label, parallel group controlled trial, 211 subjects at least 5 years old with uncomplicated Falciparum malaria were treated with directly observed therapy. Over 3 days, 63 received artesunate-mefloquine (AS/MQ), 77 received dihydroartemisinin-piperaquine (DHA/PPQ), and 71 received atovaquone-proguanil (ATQ/PG). Subjects were followed for 42 days or until recurrent parasitemia. Genotyping of msp1, msp2, and glurp among individual parasite isolates distinguished recrudescence from reinfection. Pfmdr1 copy number was measured by real-time PCR and half-maximal parasite inhibitory concentrations (IC50) was measured in vitro by 48-hour isotopic hypoxanthine incorporation assay.Results: The primary outcome of per-protocol PCR-adjusted efficacy at 42 days was analyzed for 190 (90.0%) of the enrolled subjects. PCR-adjusted efficacy (95% confidence interval) at 42 days was 80.6% (70.8 – 90.5%) for AS/MQ, 97.2% (93.3 – 100%) for DHA/PPQ, and 92.9% (86.1 – 99.6%) for ATQ/PG. On day 3, 59.3% remained parasitemic. At baseline, 46.9% had microscopic P. falciparum gametocytemia. Both recurrences in the DHA/PPQ arm lost Pfmdr1 copy number amplification at recrudescence. All four recurrences in the ATQ/PG arm were wild-type for cytochrome bc1. One subject withdrew from the ATQ/PG arm due to drug allergy.Conclusions: This previously unpublished study was conducted at the epicenter of substantial multi-drug resistance that emerged soon thereafter. Occurring early in the national transition from AS/MQ to DHA/PPQ, both DHA/PPQ and ATQ/PG had acceptable efficacy against uncomplicated falciparum malaria. However, efficacy of AS/MQ was only 80% with apparent mefloquine resistance based on elevated Pfmdr1 copy number and IC50. By 2009, there was already significant evidence of artemisinin resistance not previously reported at the Northern Cambodia-Thai border. This study suggests the basis for early development of significant DHA/PPQ failures within 3 years of introduction. Artemisinin resistance likely occurred on the Northern border concurrently with that reported along the Western border in Pailin.Trial Registration: This legacy trial was conducted prior to International Committee of Medical Journal Editors’ requirements for preregistration on ClinicalTrials.gov. The full protocol has been provided.
An Approach For The Reconstruction of a Traditional Masonry-Wooden Building Located In An Archeological Area. Part I: Methodology
Authors: Akçay Cemil , Korkmaz Nail Mahir , Sayin Baris
Published: December 2021

This study, presented in a pair of articles, defines a comprehensive methodological approach to the reconstruction of a traditional masonry-timber mansion building constructed in the 1880s of the Turkish house typology on Istanbul’s historical peninsula area that was intentionally demolished in 1948. A historical process research was carried out in the first stage of the study, after which ground penetration radar measurements and an archeological excavation were carried out to determine any possible remains or ruins of the structure, and the original architectural features of the demolished building were ascertained from the obtained data. The proposed stages in the current paper can be considered a comprehensive approach to the determination of the authentic properties of demolished or destroyed buildings in historical areas, given that the methodology allows for the integration of construction features obtained separately and independently through different activities, such as excavations, georadar measurements and historical surveys. The result is a versatile approach to the complete and realistic reconstruction of historical buildings.
Microstructural and Mechanical Aspects of AlSi7Mg0.6 Alloy Related to Scanning Strategies in L-PBF
Authors: Yadav Pinku , Rigo Olivier , Arvieu Corinne , Lacoste Eric
Published: December 2021

AlSi7Mg0.6 alloy is the most widely used cast alloy for aerospace and automotive applications. Therefore, it is essential to explore the effect of scanning strategies parameters on the final part properties in the L-PBF process. The effect of stripes and chessboard strategies parameters such as stripes length, rotation angle, and chessboard island size on mechanical and microstructural properties of L-PBF processed AlSi7Mg0.6 alloy is studied. The evolution of the residual stresses is also investigated in the longitudinal and transverse directions. Cooling rates are also estimated using the cell size within the melt pool. Three distinct regions (i.e., fine, coarse, and heat affected zone) within the melt pool corresponding to different cooling rates could be identified based on Si morphology. The texture of the final material can be tailored by changing the scanning strategies. This study comprehensively presents the results concerning porosity, mechanical properties, crystallographic texture, cooling rates, grain morphology, and residual stresses for additively manufactured AlSi7Mg0.6 alloy.
Mosquito Species Composition And Insecticide Resistance Status of Anopheles Arabiensis In Itang Special Woreda, Gambella, Southwestern Ethiopia
Authors: Chanyalew Tebiban , Natea Gadisa , Amenu Desalegn , Yewhalaw Delenasaw , Simma Eba Alemayehu
Published: December 2021

Introduction: Anopheles arabiensis, member species of the Anopheles gambiae complex, is the primary vector of malaria widely distributed in Ethiopia. Anopheles funestus, An. pharoensis and An. nili are secondary vectors occurring with limited distribution in the country. Indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) are pillars for the interventions against malaria control and elimination efforts in Ethiopia. However, the emergence and widespread of insecticide resistance in the major malaria vector, An. arabiensis, might compromise the efforts of the country. The aim of this study was to investigate composition of mosquito species and insecticide resistance status of An. arabiensis in Itang special woreda (district), Gambella, southwestern Ethiopia.Materials and methods: Adult mosquitoes were sampled from September 2020 to Feburary 2021 using Centers for Disease Control and Prevention (CDC) light trap and Pyrethrum Spray Catch (PSC). Moreover, mosquito larvae were also collected from different breeding sites and reared to adults to assess susceptibility status of populations of An. gambiae s.l. in the study area. Susceptibility tests were conducted on two to three days old non blood fed female An. gambiae s.l using insecticide impregnated papers with deltamethrin (0.05%), alpha-cypermethrin (0.05%), propoxur (0.1%), pirimiphos-methyl (0.25%) and bendiocarb (0.1%) following World Health Organization (WHO) standard susceptibility test procedure. Molecular diagnostics were done for the identification of member species of An. gambiae s.l and detection of knockdown resistance (kdr) allele using species specific polymerase chain reaction (PCR) and allele specific PCR. Results: In total, 468 adult mosquitoes were collected from different houses. Culex mosquitoes were the most dominant (80.4%) followed by Anopheles mosquitoes. Three species of Anopheles mosquitoes (An. coustani, An. pharoensis, and An. gambiae (s.l.)) were identified, of which An. coustani was the dominant (8.1%) species. WHO bioassay tests revealed that the populations of An. gambiae s.l in the study area are resistant against alpha-cypermethrin and deltamethrin whereas, susceptible to bendiocarb, pirimiphos-methyl and propoxur. Out of the total 86 An. gambiae s.l specimens assayed, 79 (92%) successfully amplified and identified as An. arabiensis. West African Kdr (L1014F) mutation was detected with high Kdr allele frequency ranging from 67-88%.Conclusion: The detection of target site mutation, kdr L1014F allele, coupled with the phenotypic resistance against alpha-cypermethrin and deltamethrin call for continuous resistance monitoring.
First Detection of Rotavirus C in Asymptomatic Pigs from India with Unexpected Dominance and Characterization of the Structural and Nonstructural Genes
Authors: Joshi Madhuri S , Arya Shalu A. , Shinde Manohar S. , Gopalkrishna Varanasi
Published: December 2021

Epidemiological and molecular investigation was conducted on Rotavirus C (RVC), the viral agent documented with rising prevalence rate, disease severity and cross species transmission and large outbreak potential. Fecal specimens of pigs collected from two cities of Maharashtra state, India tested for RVC showed 20.1% detection rate with majority below 3 months of age. No significant difference in detection rates was observed in the specimens collected in 2009 from Northern and in 2013 from Western parts of Maharashtra. The phylogenetic analyses showed presence of the I7 and I10 genotypes of the VP6 gene and representative strains with G1 and E5 genotypes of the VP7 and NSP4 gene respectively. Full genome characterization of a single strain showed presence of G1, P1, I7, R1, C1, M3, A1, N5, T5, E5, H1 genotypes of the VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5 genes respectively. This is the first evidence of detection of porcine RVC in asymptomatic pigs in India as well as with highest detection rate reported in asymptomatic pigs till date globally. Identification of porcine RVC at two time intervals and two different parts of Maharashtra state indicates the possibility of continuous circulation of RVC in pig population through asymptomatic infections.
A Tumor-Infiltrating Lymphocyte-Based Risk Model Predicts Prognosis of Colon Cancer
Authors: Sui Ziqi , Zhu Yanli , Wu Kejia , Wang Shuxiang , Yuan Xixian , Wang Shuqiu
Published: December 2021

Tumor-infiltrating lymphocytes are relevant to the tumor prognosis and response to immunotherapy in colon cancer. The gene expression data of colon cancer was obtained from the cancer genome atlas (TCGA) database and the components of immune cell types were analyzed by CIBERSORT. Selection operator (LASSO) and multivariate Cox regression filtered immune cells and selected the most significant cell types to construct an immune risk model including memory B cells, plasma cells, T follicular helper (Tfh) cells, M0 macrophages and resting dendritic cells. Receiver operating characteristic (ROC) curves were used to verify the sensitivity and specificity of the model, which was validated in Gene Expression Omnibus (GEO) dataset. Combined with the clinical traits, a nomogram was established to predict the prognosis of colon cancer. According to function analyses through weighted correlation network analysis (WGCNA) and gene set enrichment analysis (GSEA), tumor-infiltrating immune cells showed significant importance in tumor immune-associated regulation, especially the adhesion, migration and invasion in colon cancer.
Expression of Thrombin-Cleaved Osteopontin and Integrin α9 and β1 Signaling Pathway Molecules in Chronic Subdural Hematomas
Authors: Osuka Koji , Ohmichi Yusuke , Ohmichi Mika , Suzuki Chiharu , Aoyama Masahiro , Iwami Kenichiro , Watanabe Yasuo , Miyachi Shigeru
Published: December 2021

Chronic subdural hematoma (CSDH) is considered to be an inflammatory and angiogenic disease. Osteopontin is an extracellular matrix protein. Osteopontin is cleaved by thrombin, resulting in N-half osteopontin, which is more prominent in integrin signal transduction. We examined the expression of N-half osteopontin in the CSDH fluid and the expression of integrin α9 and β1 and the downstream components of the angiogenic signaling pathways in the outer membrane of CSDHs. Twenty samples of CSDH fluid and 8 samples of CSDH outer membrane were included. The concentrations of N-half osteopontin in the CSDH fluid were measured using ELISA kits. The expression of integrin α9 and β1, vinculin, talin-1, focal adhesion kinase (FAK), paxillin, α-actin, Src and β-actin was examined by western blot analysis. The expression of integrin α9 and β1, FAK and paxillin was also examined by immunohistochemistry. We investigated whether CSDH fluid could activate FAK in cultured endothelial cells in vitro. The concentration of N-half osteopontin in CSDH fluid was significantly higher than that in the serum. Western blot analysis revealed above-mentioned molecules. In addition, integrin α9 and β1, FAK and paxillin were localized in the endothelial cells of vessels within the CSDH outer membrane. FAK was significantly phosphorylated immediately after treatment with CSDH fluid. Our data suggest that N-half osteopontin in CSDH fluid promotes neovascularization in endothelial cells through integrins α9 and β1. The N-half osteopontin and integrin signaling pathway might be a useful therapeutic target for treating the growth of refractory CSDH.
Nonequilibrium Band Occupation and Optical Response of Gold After Ultrafast XUV Excitation
Authors: Ndione Pascal D. , Weber Sebastian T. , Gericke Dirk O. , Rethfeld Baerbel
Published: December 2021

Free electron lasers offer unique properties to study matter in states far from equilibrium as they combine short pulses with a large range of photon energies. In particular, the possibility to excite core states drives new relaxation pathways that, in turn, also change the properties of the optically and chemically active electrons. Here, we present a theoretical model for the dynamics of the nonequilibrium occupation of the different energy bands in solid gold driven by exciting deep core states. The resulting optical response is in excellent agreement with recent measurements and, combined with our model, provides a quantitative benchmark for the description of electron-phonon coupling in strongly driven gold. Focusing on sub-picosecond time scales, we find essential differences between the dynamics induced by XUV and visible light.
A Novel NIR-II Theranostic Agent: A Win–win Strategy of Tracing and Blocking Tumor-associated Vessels for Oral Squamous Cell Carcinoma
Authors: Wei Zheng , Zhang Hongbo , Zou Huihui , Song Chuanhui , Zhao Sufeng , Zhao Zichen , Zhang Xinyu , Zhang Guorong , Cai Yu , Han Wei
Published: December 2021

Tumor vessel co-option is a crucial predictor for tumor invasiveness but is easy to ignore in tumor vascular targeting therapy. A high density of tumor vessel co-option located alongside the tumor frontier predicted a high tendency of tumor invasion and regional metastasis. Herein, a novel NIR-II nanoagent (CS NPs) was constructed with an organic COi8DFIC dye and sorafenib, which demonstrated high tissue penetration and low tissue autofluorescence, enabling imaging of vessel co-option and tumor micrometastasis. This nanotherapeutic agent displayed considerably improved quantum yield of fluorescence (0.89%), high ROS generation and fairly good biosafety in vivo. Compared with indocyanine green (ICG), CS NPs exhibited better photostability and photothermal conversion efficiency. By tracking tumor-associated vessels and real-time tumor imaging, CS NPs could open/stop vascular targeting therapy by laser on/off. The combination of vessel disruption and imaging-guided photothermal therapy/photodynamic therapy provided a win–win strategy for oral squamous cell carcinoma (OSCC).
Viral Haemorrhagic Fevers and Malaria Co-Infections Among Febrile Patients Seeking Health Care in Tanzania
Authors: Rugarabamu Sima , Rumisha Susan F. , Mwanyika Gaspary O. , Sindato Calvin , Lim Hee-Young , Misinzo Gerald , Mboera Leonard E.G.
Published: December 2021

Background: In recent years there have been reports of viral haemorrhagic fever (VHF) epidemics in Sub-Saharan Africa where malaria is endemic. VHF and malaria have overlapping clinical presentations making differential diagnosis a challenge. The objective of this study was to determine the prevalence of selected zoonotic VHFs and malaria co-infections among febrile patients seeking health care in Tanzania. Methods: This facility-based cross-section study was carried out in Buhigwe, Kalambo, Kyela, Kilindi, Kinondoni, Kondoa, Mvomero, and Ukerewe districts in Tanzania. The study involved febrile patients seeking health care from primary healthcare facilities. Blood samples were collected and tested for infections due to malaria, Crimean-Congo haemorrhagic fever (CCHF), Ebola virus disease (EVD), Marburg virus disease (MVD), Rift Valley fever (RVF) and yellow fever (YF). Malaria infections were tested using rapid diagnostics tests while exposure to VHFs was determined by screening for immunoglobulin M antibodies using commercial enzyme-linked immunosorbent assays. Results: A total of 308 participants (mean age=35±18.9 years) were involved in the study. Of these, 54 (17.5%) had malaria infection and 15 (4.8%) were positive for IgM antibodies against VHFs (RVF=8; CCHF=2; EBV=3; MBV=1; YF=1). Six (1.9%) individuals had both VHF (RVF=2; CCHF=1; EVD=2; MVD=1) and malaria infections. The highest co-infection prevalence (0.6%), was observed among individuals aged 46-60 years (p<0.05). District was significantly associated with co-infection (p<0.05) with the highest prevalence recorded in Buhigwe (1.2%) followed by Kinondoni (0.9%) districts. Headache (100%) and muscle, bone, back and joint pains (83.3%) were the most significant complaints among those infected with both VHFs and malaria (p=0.001). Conclusions: Co-infections of VHF and malaria are prevalent in Tanzania and affect more the older than the younger population. Since the overlapping symptoms in co-infected individuals may challenge accurate diagnosis, adequate laboratory diagnosis should be emphasized in the management of febrile illnesses.
Prognostic Impact of lncRNA MCM3AP-AS1 Expression in Malignant Solid Tumors: A Systematic Review and Meta-analysis
Authors: le qi , chen wei , Jiang Lei , Hu Wenwen , Yao Nan
Published: December 2021

Objectives: MCM3AP-AS1 is a newly discovered long non-coding RNA that functions as a biomarker in many different cancer types. However, the pooled role of lncRNA MCM3AP-AS1 in the prognosis of human cancers remains unclear. We performed a systematic review and meta-analysis to explore its potential prognosis for malignant tumors. Materials and methods: A literature survey was conducted by searching in the PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang databases for studies published as of September 1, 2021. The pooled hazard ratio (HR) and 95% confidence interval (95% CI) were calculated to evaluate the relationship between MCM3AP-AS1 expression and overall survival (OS). The endpoints also included various clinical parameters. Results: A total of 14 studies containing 921 cancer patients were finally included into this meta-analysis. The results comprehensively showed that increased MCM3AP-AS1 expression was significantly correlated with poor overall survival (HR = 1.83, 95% CI: 1.56-2.14, P<0.00001). A subgroup meta-analysis for overall survival was conducted. Additionally, high level of lncRNA MCM3AP-AS1 was significantly associated with worse differentiation (OR = 1.76, 95 % CI: 1.12–2.75, P = 0.01), larger tumor size (OR = 2.70, 95 % CI: 1.13–6.46, P = 0.03), advanced clinical stage (OR = 2.52, 95 % CI: 1.32–4.81, P = 0.005) and lymph node metastasis (OR = 2.85, 95 % CI: 1.16–7.00, P = 0.02), respectively. Conclusions: LncRNA MCM3AP-AS1 might be a potential and unfavorable prognostic biomarker of cancer.
Explaining the Challenges of Coping with Coronavirus Crisis in the Workplaces: A Qualitative Study
Authors: Tajvar Abdolhamid , Hosseini Zahra , Farahbakhsh Mohammadreza , Fakherpour Anahita , homayuni atefeh
Published: December 2021

Background: Workplaces play a highly important role in controlling or spreading the prevalence of COVID-19. Therefore, the lack of proper implementation of hygienic protocols in theses environments might increase the risk of getting infected with the COVID-19 among the employees, following the increase of the COVID-19 in the family and community levels. This qualitative study was aimed to explain the challenges of coping with coronavirus crisis in the workplaces.Methods: The present qualitative study was conducted with a conventional content analysis approach. We used the purposeful sampling with maximum diversity in terms of working processes. Data were collected through semi-structured interviews. Interviews were performed to the point of information saturation. MAXQDA software version 10 was used for data management.Results: Through the content analysis of the interviews with the participants, we identified 2 main classes and 9 sub-classes. The main classes included problems and limitations related to the intra-organizational factors (job nature, budget allocation problems, individual factors, disorganization, manpower and equipment, and Lack of commitment and insufficient support of managers) and extra-organizational factors (lack of accessibility to valid information, black market, and inter-sectorial coordination problems). Conclusion: The study findings indicated that organizations and industries face numerous internal and external challenges in coping with the COVID-19 pandemic. Paying attention to the mentioned limitations and attempting to eliminate them; especially, by the governmental organizations, employers, and managers could help in effective confronting the COVID-19 pandemic.
Atmospheric Modes Excited by the 2021 August Eruption of the Fukutoku-okanoba Volcano, Izu-bonin Arc, Observed as Harmonic Oscillations of QZSS Total Electron Conte
Authors: Heki Kosuke , Fujimoto Tatsuya
Published: December 2021

Continuous Plinian eruptions of volcanoes often excite atmospheric resonant oscillations with several distinct periods of a few minutes. We detected such harmonic oscillations excited by the 2021 August eruption of the Fukutoku-Okanoba volcano, a submarine volcano in the Izu-Bonin arc, in ionospheric total electron content (TEC) observed from global navigation satellite system (GNSS) stations deployed on three nearby islands, Chichijima, Hahajima, and Iwojima. Continuous records with the geostationary satellite of Quasi-Zenith Satellite System (QZSS) presented four frequency peaks of such atmospheric modes. The harmonic TEC oscillations, started at ~5:16 UT, exhibited an unprecedented large amplitude but decayed in a few hours.
Increased Expression of Integrin Subunit α3 is Correlated with Worse Recurrence-Free Survival in Thyroid Cancer
Authors: Ma Jun-jie , Xiang Cheng , Zhu Heng-qing , Bai Bing-long , Wang Ping
Published: December 2021

Objective: To investigate the potential effect of integrin subunit α3 (ITGA3) on thyroid cancer (THCA). Materials and Methods: Based on bioinformatics databases, the expression levels of ITGA3 were firstly analyzed, followed by evaluating the prognostic significance of ITGA3 in THCA patients. Cox regression analysis predicted the independent prognostic factors for THCA. Then, cBioportal and GSCA databases were applied to evaluate genetic alterations of ITGA3. Functional enrichment analysis was conducted using the R package. Finally, the upstream microRNAs of ITGA3 were determined. Results: ITGA3 gene and protein levels were higher in the THCA group than normal group (all P <0.05). And ITGA3 mRNA expression was significantly related to cancer stage and histological subtype (all P <0.01). Moreover, high expression of ITGA3 was associated with poor recurrence-free survival (RFS) of THCA patients in all subgroups (all P <0.01). Cox regression analysis presented that ITGA3 overexpression was an independent prognostic factor for worse RFS in THCA patients. Besides, significant relations were observed between ITGA3 and genetic alterations (FDR <0.01). Functional enrichment analysis indicated ECM-receptor interaction, and cell adhesion molecules were the shared regulatory pathways. We also found that ITGA3 might be the target gene of hsa-miR-3129, hsa-miR-181d, hsa-miR-181b, hsa-miR-199a, and hsa-miR-199b, which were all correlated with THCA patient prognosis. Conclusions: ITGA3 could be a reliable biomarker and promising therapeutic target for improving the diagnosis and clinical outcomes of THCA patients.
Mismatch Repair Deficiency, Chemotherapy and Survival for Resectable Gastric Cancer: an Observational Study from the German staR Cohort and a Meta-Analysis
Authors: Stolze Thilo , Franke Sabine , Haybaeck Johannes , Moehler Markus , Grimminger Peter P. , Lang Hauke , Roth Wilfried , Gockel Ines , Kreuser Nicole , Bläker Hendrik , Wittekind Christian , Lordick Florian , Vieth Michael , Veits Lothar , Waidmann Oliver , Lingohr Philipp , Peitz Ulrich , Schildberg Claus , Kruschewski Martin , Vassos Nikolaos , Goni Elisabetta , Bruns Christiane J. , Ridwelski Karsten , Wolff Stefanie , Lippert Hans , Schumacher Johannes , Malfertheiner Peter , Venerito Marino
Published: December 2021

Purpose. In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings.Methods. Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. Results. MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI: 0.13-3.37, P=0.63) and 1.44 (95% CI: 0.66-3.13, P=0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI: 0.14-0.91, P=0.03), whereas those with MMRp had a HR of 1.18 (95% CI: 0.89-1.58, P=0.26).Conclusion. Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.
Structural, Optical, Magnetic and Photon Attenuation of Novel Potassium Lead Borate Glasses Doped with MnO
Authors: Abouhaswa A. S. , Rammah Y. S.
Published: December 2021

Potassium lead borate glasses doped with MnO (40B2O3+40PbO+(20-x)K2O+xMnO: x= 0-5 mol%) have been prepared via standard melting quenching process. The impact of MnO on the structure, optical, magnetic and gamma-ray protection properties of pottisium lead borate glasses have been examined. The density was increased from 4.83±0.01 to 5.23±0.01 g/cm3 as MnO content increased. The obtained direct optical gap (Eg) values were 2.84, 2.59, 2.41, 2.19, 1.95, and 1.84 eV for the Mn-x (x=0, 1, 2, 3, 4, and 5) glass samples, respectively. FTIR spectra demonstrated that as the MnO concentration increases in the glass network the intensity and width of the IR bands were increased. The magnetic measurement revealed that the magnetic situation (Ms) was decreased while the magnetic coercivity (Hc) was increased with increasing MnO substitution ratio. The linear attenuation coefficient of the follows the order: µMn-0 < µMn-1 < µMn-2 < µMn-3 < µMn-4 < µMn-5. Half value layer (HVL) rises as µ decreases and vice versa. The range of the HVL is 0.002 – 3.378, 0.002 – 3.334, 0.002 – 3.291, 0.002 – 3.248, 0.002 – 3.176, and 0.002 – 3.106 cm for Mn-x (x=0, 1, 2, 3, 4, and5). The trend of Zeff variation is related to that of both linear and mass attenuation coefficients (µ and µm). The produced Mn-glasses can be employed in a variety of optical, magnetic and radiation protective applications.
Intranasal inhibitor blocks omicron and other variants of SARS-CoV-2
Authors: Mäkelä Anna R. , Uğurlu Hasan , Hannula Liina , Salminen Petja , Kant Ravi , Fagerlund Riku , Haveri Anu , Strandin Tomas , Kareinen Lauri , Hepojoki Jussi , Levanov Lev , Pasternack Arja , Naves Rauno A. , Ritvos Olli , Österlund Pamela , Sironen Tarja , Vapalahti Olli , Kipar Anja , Huiskonen Juha T. , Rissanen Ilona , Saksela Kalle
Published: December 2021

The emergence of the SARS-CoV-2 Omicron variant capable of escaping neutralizing antibodies emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Nasal epithelium is rich in the ACE2 receptor and important for SARS-CoV-2 transmission by supporting early viral replication before seeding to the lung1. Intranasal administration of SARS-CoV-2 neutralizing antibodies or antibody fragments has shown encouraging potential as a protective measure in animal models2-5. However, there remains a need for SARS-CoV-2 blocking agents that are more economical to produce in large scale, while less vulnerable to mutational variation in the neutralization epitopes of the viral Spike glycoprotein. Here we describe TriSb92, a highly manufacturable trimeric human nephrocystin SH3 domain-derived antibody mimetic targeted against a conserved region in the receptor-binding domain of the Spike. TriSb92 potently neutralizes SARS-CoV-2 and its variants of concern, including Delta and Omicron. Intranasal administration of a modest dose of TriSb92 (5 or 50 micrograms) as early as eight hours before the challenge with SARS-CoV-2 B.1.351 efficiently protected mice from infection. The target epitope of TriSb92 was defined by cryo-EM, which revealed triggering of a conformational shift in the Spike trimer rather than competition for ACE2 binding as the molecular basis of its strong inhibitory action. Our results highlight the potential of intranasal inhibitors in protecting susceptible individuals from SARS-CoV-2 infection, and describe a novel type of inhibitor that could be of use in addressing the challenge posed by the Omicron variant.