bluuebunny/crossref_metadata_2025 huggingface dataset:
EMBED: Essential Microbiome Dynamics, a dimensionality reduction approach for longitudinal microbiome studies
Authors: Shahin Mayar , Ji Brian , Dixit Purushottam
Published: March 2022

Dimensionality reduction can offer unique insights into high dimensional microbiome dynamics by leveraging collective abundance fluctuations of multiple bacteria driven by similar ecological perturbations. However, methods providing lower-dimensional representations of microbiome dynamics both at the community and individual taxa level are not currently available. To that end, we present EMBED: Essential MicroBiomE Dynamics, a probabilistic non-linear tensor factorization approach. Similar to normal mode analysis in structural biophysics, EMBED infers ecological normal modes (ECNs), which represent the unique orthogonal modes capturing the collective behavior of microbial communities. A very small number of ECNs can accurately approximate microbiome dynamics across multiple data sets. Inferred ECNs reflect specific ecological behaviors, providing natural templates along which the dynamics of individual bacteria may be partitioned. Moreover, the multi-subject treatment in EMBED systematically identifies subject-specific and universal abundance dynamics that are not detected by traditional approaches. Collectively, these results highlight the utility of EMBED as a versatile dimensionality reduction tool for studies of microbiome dynamics.
Elevated Serum Triglyceride Levels May be a Key Independent Predicting Factor for Gallbladder Cancer Risk in Gallbladder Stone Disease Patients: a Case-control Study
Authors: Wan Yong , Zhang Jianqin , Chen Min , Ma Mao , Sheng Binwu
Published: March 2022

Background Gallbladder stone diseases (GSD) is a main risk factor of gallbladder cancer (GBC). This study aimed to reveal their bridge relating to metabolic syndrome.Material/Method We summarized the clinical and experimental data of 2210 GBC patients, from 3524 Chinese patients, in our hospital from Jan. 2009 to Dec. 2020. The metabolic syndrome indexes, influencing factors for both GBC and GSD, were analyzed by unconditional logistic regression in this case-control study. Result There were significant higher morbidity of GBC in the overall, GSD and non-GSD with hypertriglyceridemia patients versus non-hypertriglyceridemia ones (P<0.001, all). In GSD patients, univariate regression showed significantly positive correlation between serum triglyceride, low density lipoprotein cholesterol (LDL-c), fasting insulin (FINS) levels, Homeostasis model assessment-insulin resistance (HOMA-IR), female being, body mass index, hypertriglyceridemia and hazard of GBC with GSD (P<0.001, all), while significantly negative correlation to systolic pressure (SBP), diastolic pressure (DBP), hypertension and high-density lipoprotein cholesterol (HDL-c), fasting blood glucose (FBG) (P<0.05, all); multivariate regression showed that serum triglyceride, was the most significantly positive associated to GBC (P<0.001, all) among the hazard factors including serum triglyceride, LDL-c levels, HOMA-IR, female being. In non-GSD ones, multivariate regression showed that HOMA-IR was the most significantly positive associated to GBC among the hazard factors including serum TG, LDL-c levels, HOMA-IR, female being, hypertriglyceridemia, while DM had a significantly inversion negative association (P<0.001). Conclusion We found initially that elevated serum TG levels could be the most remarkable independent predicting factor of GBC risk with GSD, while insulin resistance might act as the first one in non-GSD. More importantly, we advocated initially the sharp rise of serum TG levels as the potential of a candidate diagnostic or prognostic biomarker of GBC with GSD.
Entropy generation and heat transport in Carreau nanofluids flow within a converging/diverging enclosure
Authors: Hashim Hashim , Rehman Sohail
Published: March 2022

The entropy production by magnetohydrodynamic (MHD) flow and heat transport of non-Newtonian Carreau nanofluids through an irregular (converging/diverging) channel is addressed in this theoretical study. The second law of thermodynamics is employed to examine fluid flow, heat, and mass transport characteristics along with entropy generation arising within the system by incorporating the Buongiorno model for nanofluids. The Carreau nanofluids flowing across narrow and extending channels are modeled using the basic transport equations of continuity, momentum, energy, concentration, and entropy generation. Here, individual terms from the entropy transport equation are employed to study entropy accumulation and dissipation together within a flow. The transmuted equations are resolved via the Runge-Kutta Fehlberg technique and shooting quadrature in MATLAB software. The flow velocity, temperature, concentration, entropy generation rate, and Bejan profiles are evaluated and sketched graphically at various flow parameters. It's worth mentioning that the system's entropy generation grows along the diverse channel walls. Moreover, another important outcome of this analysis is that the rate of entropy formation increases as the Brinkmann number is estimated higher. This research could have substantial implications in high-temperature electronic devices, mechanical structures, heat exchangers, medical treatment, to mention a few.
Immunochromatography Versus Microscopy For Diagnosis Of Amoebiasis In Sohag, Egypt
Authors: El-Mawgood  , Ahmed Amal Mostafa Ahmed , Hashem Khoulood Zakaria Hashem , Ellah Asmaa kamal Abd
Published: March 2022

Amoebiasis; a parasitic infection caused by E histolytica protozoon, is still a major public health in developing countries. Delay in diagnosis and treatment may lead to fatality. So, rapid and accurate diagnosis plays a critical role in patient’s management. Therefore, this study aimed to evaluate the efficacy of immunochromatographic test (ICT) using RIDA®QUICK Entamoeba test compared with traditional microscopic examination as gold standard for the diagnosis of E histolytica /dispar infection. A Cross-sectional study was conducted on 100 patients complaining of dysentery or diarrhea with an age range of 3-62 years, attending Sohag University Hospitals and Endemic Diseases Hospital. All stool samples were examined by direct wet smears, formalin ethyl acetate concentration techniques, staining of the smears using Wiegert’s iron hematoxylin and Modified Ziehl-Neelsen method. Copro-antigen detection in stool sample was by using RIDA®QUICK Entamoeba test. Microscopic examination revealed 43 out of 100 patients (43%) were positives for E histolytica/dispar. The infection was significantly associated with residence (P value < 0.036) and family size (P value < 0.03) but not associated with gender (P value < 0.471) and age (P value < 0.344). The sensitivity, specificity, PPV and NPV of Rida®Quick Entamoeba tests were 97.67%, 96.49%, 95.45% and 98.21% respectively with an accuracy of 97%. There was no cross-reactivity with other intestinal parasites.Conclusion: Rida® Quick Entamoeba test is a simple, rapid, convenient, sensitive and specific assay for the diagnosis amebiasis and is therefore very suitable for large-scale field applications.
Construction of Drought Stress Regulation Networks in Potato Based on SMRT and RNA Sequencing Data
Authors: Jian Hongju , Sun Haonan , Liu Rongrong , Zhang Wenzhe , Shang Lina , Wang Jichun , Khassanov Vadim , Lyu Dianqiu
Published: March 2022

Background: Potato (Solanum tuberosum) is the fourth most important food crop in the world and plays an important role in food security. However, drought stress has a significantly negative impact on potato growth and production. Little information about the coordinated response in potato to drought stress has been obtained. The purpose of our research is to fully analyze the potato's response to drought stress.Results: In this study, next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing technology were used to study the transcription profiles in potato in response to drought stress. The leaves of the variety “Desiree” at the seedling stage after drought stress at six time points from 0 to 48 hours were used to perform NGS and SMRT sequencing. According to the sequencing data, a total of 12,798 differentially expressed genes (DEGs) were identified in six time points. The real-time (RT)-PCR results are significantly correlated with the sequencing data, confirming the accuracy of the sequencing data. Gene ontology and KEGG analysis show that these DEGs participate in response to drought stress through galactose metabolism, fatty acid metabolism, plant-pathogen interaction, glutathione metabolism and other pathways. Through the analysis of alternative splicing of 66,888 transcripts, the functional pathways of these transcripts were enriched, and 51,098 transcripts were newly discovered from alternative splicing events and 47,994 transcripts were functionally annotated. Moreover, 3,445 lncRNAs were predicted and enrichment analysis of corresponding target genes was also performed. Additionally, Alternative polyadenylation was analyzed by TADIS, and 26,153 poly (A) sites from 13,010 genes were detected in the Iso-Seq data. Conclusion: Our research greatly enhanced potato drought-induced gene annotations and provides transcriptome-wide insights into the molecular basis of potato drought resistance.
CSRP2 is involved in immune regulation and drug sensitivity in glioma cells by the LEF1- AS1/miR-128-3p/CSRP2 axis
Authors: Zuo Wei , Jia Liyan , Chen Lin , Chen Xinlu , Yin Chonggao , Liu Wei , Li Hongli
Published: March 2022

Background: Glioma is one of the most common intracranial malignancies. As competing for endogenous RNA (ceRNA), long chain non-coding RNA (lncRNA) can affect the binding of microRNA (miRNA) to mRNA and thus affect the occurrence and development of glioma, which has been suggested as a key role in the development of human cancers. This study was to investigate the effects of TCGA on the development of glioma.Results: Here, we screened the differential genes by differential analyses on the matrix data for glioma in TCGA and GEO databases and selected the potential prognostic markers among them. Surprisingly, LEF1-AS1 was identified capable of influencing the survival of glioma patients. The results derived from the proportional risk (Cox) regression model showed a significant association between LEF1-AS1 overexpression and poorer prognosis (HR = 1.518, P < 0.001). The ROC model validated the feasibility of LEF1-AS1 (AUC = 0.702). MiR-128-3p, the target gene for LEF1-AS1, was screened using the Bioinformatics Online website and found down-regulated with increasing glioma grade in glioma tissues. Then the target gene for miR-128-3p, CSRP2, was obtained through miRTarBase, TargetScan, and miRDB. The survival curve of CSRP2 showed that CSRP2 with low expression corresponded to a better prognosis in glioma patients. The level of CSRP2 was positively correlated with the infiltration ones of CD4+ T and CD8+ T cells in glioma tissues. In addition, the CellMiner database predicted three drugs (Elesclomol, Entinostat, and Staurosporine) with high sensitivity to CSRP2 expression, and their molecular structures were retrieved using the PubChem22 database.Conclusions: In summary, the LEF1-AS1/miR-128-3p/CSRP2 axis may play a vital role in the development of glioma and provide guiding significance for the early diagnosis and treatment for it.
In silico and in vitro analysis of salt stress tolerance by Selenium application in proso millet
Authors: Mushtaq Naveed Ul , Saleem Seerat , Tahir Inayatullah , Rehman Reiaz Ul
Published: March 2022

Background and aimIn order to withstand abiotic stress conditions, plants accumulate a wide range of metabolic products such as proline and there exists a co-relation between proline accumulation and salt stress alleviation in plants, suggesting its role in stress mitigation and osmotic adjustments. MethodsIn this study we assessed the effect of Selenium (Se) under salt (NaCl) stress on Pyrroline-5-carboxylate synthase (P5CS), Proline dehydrogenase (ProDH) and Ornithine aminotransferase (OAT) proteins using in silico and in vitro studies. ResultsBased on in silico analysis it was found that these enzymes demonstrated a better interaction with Se in comparison to NaCl. The predicted results implied the merit of using Se as a NaCl mitigant. The morphological results revealed a decline in the growth parameters of plants under NaCl stress in a dose dependent manner. However, the application of Se relieved the NaCl induced symptoms. It was found that 1µM Se mitigated the NaCl stress effectively and there was an increase in proline content. The transcriptomic studies also showed that Se up-regulated the expression of P5CS, ProDH and OAT. Based on above results Se fulfills the criteria as an excellent mitigant for exogenous application in proso millet during NaCl stress.ConclusionUnder salt stress, Se at lower concentration (1µM) functions as a mitigant to alleviate NaCl stress by regulating the synthesis of proline. Se has high binding affinities with proline biosynthesis enzymes, increasing their activities and expression, enhancing proline content and growth in proso millet.
Carbon quantum dots from pomelo peel as fluorescence probes for “turn-off–on” high-sensitivity detection of Fe 3+ and L-cysteine
Authors: Zhang Dianwei , Zhang Furui , Liao Yonghong , Wang Fenghuan , Liu Huilin
Published: March 2022

This study designed a “turn-off–on” fluorescence analysis method based on carbon quantum dots (CQDs) to detect metal ions and amino acids in real sample systems. CQDs were derived from green pomelo peel via a one-step hydrothermal process. The co-doped CQDs with N, S atoms imparted excellent optical properties (quantum yield = 17.31%). The prepared CQDs could be used as fluorescent “turn-off” probes to detect Fe3+ with a limit of detection of 0.086 µM, a linear detection range of 0.1-160 µM, and recovery of 92.09%–104.87% in water samples. The quenched CQDs fluorescence could be turned on after adding L-cysteine (L-Cys), which allowed detection of L-Cys with a detection limit of 0.34 µM and linear range of 0.4–85 µM. Recovery of L-Cys in amino acid beverage was 92.58%–106.76%. Visual paper-based testing strips and cellulose/CQDs composite hydrogels could be also used to detect Fe3+ and L-Cys.
Identification and Validation of Real Hub Genes in Hepatocellular Carcinoma Based on Weighted Gene Co-expression Network Analysis
Authors: Zhao Zhigang , Qiao Yu , Wang Xin , Hu Jun , Mao Yurong , Yuan Fahu
Published: March 2022

Background: Hepatocellular Carcinoma (HCC) is one of the most common liver malignancies in the world. With highly invasive biological characteristics and lack of obvious clinical manifestations, hepatocellular Carcinoma usually has a poor prognosis and ranks fourth in cancer mortality. The aetiology and exact molecular mechanism of primary hepatocellular carcinoma are still unclear. This work aims to help identify biomarkers of early HCC diagnosis or prognosis. Results: In this study, Expression data and clinical information of HTSEQ-Counts were downloaded from The Cancer Genome Atlas (TCGA) database, and Gene Expression map GSE121248 was downloaded from Gene Expression Omnibus (GEO). By differentially expressed genes (DEGs) and Weighted Gene co-expression Network Analysis（WGCNA）searched for modules in the two databases that had the same effect on the biological characteristics of HCC, and extracted the module genes with the highest positive correlation with HCC from two databases, and finally obtained overlapping genes. Then, we performed functional enrichment analysis on the overlapping genes to understand their potential biological functions. The top ten hub genes were screened according to MCC through the String database and Cytoscape software. By survival analysis, high expression of CDK1, CCNA2, CDC20, KIF11, DLGAP5, KIF20A, ASPM, CEP55, TPX2 was associated with poorer overall survival (OS) of HCC patients. The DFS curve was plotted using the online website GEPIA2. Finally, based on the enrichment of these genes in the KEGG pathway, real hub genes were screened out, which were CDK1, CCNA2 and CDC20 respectively. Conclusions: High expression of these three genes was negatively correlated with survival time in HCC, and the expression of CDK1, CCNA2 and CDC20 were significantly higher in tumour tissues of HCC patients than in normal liver tissues as verified again by the HPA database. All in all, this provides a new feasible target for early and accurate diagnosis of HCC, clinical diagnosis, treatment and prognosis.
OAHEGA: From Research to Production of Mobile Expression Detection Application
Authors: Kovenko Volodymyr , Shevchuk Vitalii
Published: March 2022

Nowadays machine learning algorithms allow us to solve various difficult problems and optimize things a lot. One of such problems is detection of facial expressions. Detection of facial expressions can be used for market analysis, self-driving cars and in the entertainment industry. However, many challenges arise when trying to build a classifier for custom emotion, such as covariate shift and imbalanced number of instances per class. In this paper we present a new image dataset OAHEGA, that consists of six emotions, and conduct experiments on it. We also provide a comprehensive study of building a successful application on top of a model trained using the highlighted dataset.
High and Low-Level Classification based Features for Content-based Image Retrieval in Privacy-Preserving
Authors: selvapattu sheeba , Nair Suchitra R
Published: March 2022

The authors have requested that this preprint be removed from Research Square.
Evaluating risk factors for cumulative life course impairment in psoriasis using Patient- Acceptable Symptom State and EQ-5D Running head: Risk factors for CLCI in psoriasis
Authors: Chularojanamontri Leena , Wongpraparut Chanisada , Silpa-archa Narumol , Chaiyabutr Chayada , Wongdama Supisara , Chiowchanwisawakit Praveena
Published: March 2022

The term “cumulative life course impairment” (CLCI) has been proposed to capture the overall effects of psoriasis that result in altered or impaired life potential during the life course of a patient. Severity and comorbidities were the most frequently studied risk factors for CLCI in psoriasis. This study evaluated the health-utility values and risk factors for CLCI using Patient Acceptable Symptom State (PASS) and EQ-5D. This cross-sectional investigation enrolled patients with psoriasis attending the Psoriasis Clinic, Siriraj Hospital, Bangkok. Patients were asked PASS questions about their overall self-perceived health state, adaptation, and expectations for current, future, and lifelong conditions. The patients also completed EQ-5D. The mean age of 139 enrolled patients was 45.8 ± 14.4 years, and 57.6% were women. There were 121 (87.1%) cases of chronic plaque psoriasis, 9 (6.5%) of guttate psoriasis, 4 (2.9%) of erythrodermic psoriasis, 3 (2.2%) of pustular psoriasis, and 2 (1.4%) of acrodermatitis continua of Hallopeau. For current PASS, satisfaction was significantly associated with older age, being married, and lower disease severity. The mean health-utility value and EQ-VAS score of the 139 patients were 0.89 ± 0.12 and 77.0 ± 17.4, respectively. Patients would not accept their disease if they had moderate to extreme problems in usual activities and depression/anxiety for the future and lifelong. Univariate analysis revealed that depression and usual activities were significantly associated with satisfaction for current PASS, future PASS, and lifelong PASS. In conclusion, disease severity, age, marital status, problems with usual activities, and depression/anxiety were significantly related to CLCI. These findings may allow physicians to identify psychosocial and psychological aspects of psoriatic patients at high risk for developing CLCI. Early and adequate treatment, good coping strategies, and good social support can prevent a negative impact on CLCI and major life-changing decisions.
Phase I trial of hypofractionated chemoradiotherapy in the palliative management of esophageal and gastro-esophageal cancer
Authors: Sridha Swetha , Day Fiona , Loh Jasmin , Lynam James , Smart Joanne , Holt Brandan , Mandaliya Hiren , Bonaventura Anthony , Kumar Mahesh , Martin Jarad
Published: March 2022

Background: Many patients with incurable esophageal cancer (ECa) present with dysphagia as their predominant symptom. Currently there is no consensus on how best to initially manage this scenario with multiple therapeutic options available. We aimed to assess the safety and efficacy of using hypofractionated radiotherapy given over a progressively shorter timeframe with concurrent carboplatin and paclitaxel in the management of patients with ECa and dysphagia. Methods: In this phase I trial we enrolled patients with histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus or the gastro-esophageal junction with symptomatic dysphagia from local disease and not for curative treatment. Patients needed to be 18 years or older, have an ECOG performance status of 0-2 and be suitable to receive carboplatin and paclitaxel chemotherapy. Patients were placed in four progressively shorter radiation schedules culminating in 30Gy in 10 fractions in a step wise manner, all with concurrent carboplatin AUC 2 and paclitaxel 50mg/m2 chemotherapy delivered weekly with the radiation therapy. The primary endpoint was the development of the dose limiting toxicities (DLTs) esophageal perforation or febrile neutropenia. Secondary endpoints were relief of dysphagia, time to improvement of dysphagia, dysphagia progression free survival and overall survival. Results: Eighteen patients were enrolled in the study between October 2014 and March 2019. There were no DLTs experienced during the trial. The most common grade 3+ acute toxicity experienced by patients were nausea and vomiting (both in 4/18 patients). The most common radiation specific acute toxicity experienced was esophagitis with 67% of patients experiencing grade 1-2 symptoms. All patients experienced improvement in dysphagia. The median time to dysphagia improvement was three weeks from the start of chemoradiotherapy (CTRT) (range 2-10 weeks). The median dysphagia free survival was 5.8 months with a median overall survival of 8.9 months. Conclusion: Hypofractionated palliative CTRT with 30Gy/10# of radiation therapy with concurrent weekly carboplatin and paclitaxel chemotherapy is well tolerated and provides a good response in improvement of dysphagia. Further studies need to be undertaken which provide both symptomatic improvement in the primary tumor but also control of the metastatic burden in these patients.Clinical Trial Registration: This trial was prospectively registered with www.anzctr.org.au Identifier: ACTRN12614000821695
Helical versus static approaches to delivering tomotherapy to the junctional target for patients taller than 135 cm undergoing total body irradiation
Authors: Köksal Mümtaz , Baumert Jonathan , Schoroth Felix , Müdder Thomas , Scafa Davide , Koch David , Leitzen Christina , Sarria Gustavo , Schmeel Leonard , Giordano Frank
Published: March 2022

Background: Helical TomoTherapy® is widely used for total body irradiation as a component of conditioning regimens before allogeneic bone marrow transplantation. However, this technique limits the maximum length of a planning target volume to 135 cm. Therefore, patients taller than 135 cm require two planning computed tomography scans and treatment plans. The junctional target between these two treatment plans is thus a critical region for treatment planning and delivery. Here, we compare radiation coverage of the junctional target between helical and static approaches to treatment planning and delivery to determine which approach allows high quality irradiation planning and provides more robustness against patient movement.Methods: We retrospectively analyzed 10 patients who underwent total body irradiation using a static four-field box planning approach and nine patients who underwent total body irradiation using a helical planning approach. All patients were taller than 135 cm. The junctional target volume was divided into 10 slices of 1-cm thickness (JT1-JT10) for analysis. Dosimetric parameters and dose-volume histograms were compared to assess the quality of coverage of the junctional target between the helical and static planning approaches.Results: The D50 for the total junctional target was slightly higher than the prescribed dose for both helical and static approaches, with a mean of 108.12% for the helical group and 107.81% for the static group. The mean D95 was 98.44% ± 4.19% for the helical group and 96.20% ± 4.59% for the static group. The mean homogeneity index covering the entire junctional target volume was 1.20 ± 0.04 for the helical group and 1.21 ± 0.05 for the static group. The mean homogeneity index ranged from 1.08 ± 0.01 in JT1 to 1.22 ± 0.06 in JT6 for the helical group and from 1.06 ± 0.02 in JT1 to 1.19 ± 0.05 in JT6 for the static group. There were no significant differences in parameters between helical and static groups. However, the static approach provided robustness against up to 30 mm of lateral movement of the patient.Conclusions: As long as TBI using helical TomoTherapy® is limited to a maximum length of 135 cm, the junctional target must be addressed during treatment planning. Our analysis shows that the static four-field box approach is viable and offers higher robustness against lateral movement of the patient than the helical approach.
Studies on structural and electrical properties of NaI doped PEO/CMC blend solid polymer electrolyte
Authors: N NAGAIAH , Samartharama B N , Ambika M R , Demappa T
Published: March 2022

Solid polymer blend electrolyte films of PEO/Na-CMC doped with NaI, were prepared by solution cast method and their structural, optical and electrical properties were investigated using X-Ray diffraction, Fourier transform infrared spectroscopy, UV-Vis spectrophotometer and Electrical impedance analyser respectively. X-Ray diffraction spectra indicate that, the deformation occurred in the structure of the blend followed by doping with NaI salt. The variation in intensity and shifting of characteristic bands in FTIR spectra provides the evidence for formation of complex due to the interaction occurred in the blend with the dopant. Optical energy band gap decreases in the blend samples upon doping and is confirmed by UV-Vis spectrophotometer analysis. Increase of Dielectric constant and loss upon doping, exhibits usual behaviour of the polymer electrolytes. The nature of increase in AC conductivity by doping and maximum conductivity obtained for 10/90 sample doped with 0.03% NaI indicates, the prepared sample can be used as polymer electrolytes in the manufacturing of energy storage devices.
Improved the methanol electrooxidation and carbon monoxide tolerance for direct methanol fuel cells using strontium molybdate
Authors: Chiang Tzu Hsuan , Hsu Jia-Wei
Published: March 2022

Electrocatalysts possess high methanol electrooxidation (MOR) and carbon monoxide (CO) tolerance abilities to meet application requirements for enhanced performance of direct methanol fuel cells (DMFCs). Higher MOR and CO tolerance activities measured via cyclic voltammetry (CV) are achieved based on a strontium molybdate (SrMoO4) mixed with Vulcan XC-72 carbon and loaded with 20% Pt. The synergistic effect of the bifunctional mechanism inducing the strontium molybdate is beneficial for removing CO-like intermediate products on the Pt surface, which leads to more Pt active sites released during MOR. The simultaneous unique structural formation of HxMoO3/HyMoO3 and SrMoO3 in uncalcined Sr0.5Mo0.5O4−δ provides key synergistic effects for the 20%-Pt/uncalcined Sr0.5Mo0.5O4−δ-C electrocatalysts, improving DMFCs performance. Results show that the 20%-Pt/uncalcined Sr0.5Mo0.5O4−δ-C electrocatalysts exhibit excellent electrocatalytic activity for MOR (with a forward peak current density of 12.56 mA/cm2 and large electrochemically active surface area (ECSAH) of 116.53 m2/g, the best CO tolerance for electrooxidation of carbon monoxide (largest ECSACO of 116.53 m2/g), and the highest electric conductivity (Rct of 940 Ω∙cm2). Furthermore, the fabricated DMFC shows excellent long-term electrochemical stability after 1000 cycles and a maximum power density (1.42 mW/cm2) higher than that with commercial 20%-Pt/C (1.27 mW/cm2).
YY1 Promotes Pancreatic Cancer Cell proliferation by Enhancing Mitochondrial Respiration
Authors: Jiang Minghua , Li Bin , Wang Junyi , Liao Jing , Wu Minghui , Yuan Xiangshu , Fang Hezhi , Shen Lijun
Published: March 2022

KRAS-driven metabolic reprogramming is one of the key features of pancreatic ductal adenocarcinoma (PDAC) cells; however, the metabolic roles of other oncogenic genes, such as YY1, in PDAC development are still unclear. In this study, we observed that YY1 expression was significantly elevated in human PDAC tissues and was positively correlated with a poor disease progression. Further, in vitro studies confirmed that YY1 deletion inhibited PDAC cell proliferation and tumorigenicity. Moreover, YY1 deletion also led to impaired mitochondrial RNA expression, which further induced mitochondrial oxidative phosphorylation (OXPHOS) complex assembly deficiency and altered cellular nucleotide homeostasis. Mechanistically, the impairment of mitochondrial OXPHOS function lowered the generation of aspartate, an output of the tricarboxylic acid cycle (TCA) and resulted in the inhibition of cell proliferation, owing to the absence of aspartate-associated nucleotide availability. Conversely, exogenous supplementation with aspartate fully restored PDAC cell proliferation. Altogether, our findings suggested that YY1 promotes PDAC cell proliferation by enhancing mitochondrial respiration and the TCA, which favors aspartate-associated nucleotide synthesis. These findings indicate that targeting nucleotide biosynthesis is a promising strategy for PDAC treatment.
Matrix Stiffness and Architecture Drive Fibro-adipogenic Progenitors’ Activation into Myofibroblasts
Authors: Loomis Taryn , Hu Lin-Ya , Wohlgemuth Ross P. , Chellakudam Rosemary R. , Smith Lucas R.
Published: March 2022

BackgroundFibro-adipogenic progenitors (FAPs) are essential in supporting regeneration in skeletal muscle but pathologically become the main source of excess extracellular matrix (ECM) deposition in fibrosis. Fibrosis can create a progressively degenerative feedback loop with fibrotic tissue leading to an increase in the fibrotic FAP phenotype. Fibrotic ECM has altered mechanical and architectural properties, but the interactions between FAPs and the ECM are not well understood.MethodsIn this study, we aimed to examine FAPs’ sensitivity to their environment and its effect on cell fate. Polyacrylamide and collagen hydrogels were utilized to investigate substrate stiffness and ECM architecture. Collagen hydrogels were manipulated to mimic aspects of healthy and fibrotic ECM including density, crosslinking, fibril size, and alignment. Collagen-coated polyacrylamide gels were utilized to analyze substrate stiffnesses that are physiologically relevant. YAP nuclear localization, proliferation, and myofibroblast activation were measured using immunofluorescence and custom FIJI: ImageJ scripts. Results Substrates of fibrotic stiffnesses had increased myofibroblast activation compared to substrates mimicking healthy muscle. The increase in myofibroblast activation correlated strongly with in Yes-associated protein (YAP) nuclear localization. Collagen crosslinking and increased fibril size inhibited myofibroblast activation, independent of YAP localization. Alignment of collagen did not affect FAP behavior.ConclusionsThis study shows that FAPs possess the ability to sense their ECM environment and that influences cell fate. Therefore, ECM mechanics and architecture are key targets to reduce the progression of fibrosis.
The 3a protein of SARS-CoV-2 is a potential calcium binding protein
Authors: Minakshi Rinki , Malik Zubbair , Rahman Safikur
Published: March 2022

The 3a protein is an accessory protein of SARS-CoV-2. We present here the result of bioinformatics analysis based on cryo-EM structure of 3a protein that has predicted calcium binding, majorly in cytoplasmic domain of 3a protein, thereby providing crucial information for further understanding of viral pathogenesis in context to its effect on cellular calcium signaling. The prediction analysis has also shown binding of antiviral drug amantadine with 3a protein of SARS-CoV-2.
Management and control of schistosomiasis in Agusan del Sur, Philippines: A modeling study
Authors: Riñon Jayrah Bena E. , Mendoza Renier , V Aurelio A. de los Reyes , Belizario Vicente Y. , Mendoza Victoria May P.
Published: March 2022

Schistosomiasis is a neglected tropical disease endemic in the Philippines, affecting 28 provinces in 12 regions. This parasitic disease is caused by Schistosoma japonicum, a zoonotic parasite that infects other mammalian hosts aside from humans. In this study, a mathematical model is developed to describe the transmission of schistosomiasis in Agusan del Sur, Philippines and investigate control strategies that could lead to possible elimination of the disease. The model considers humans as definitive hosts, carabaos as reservoir hosts, and snails as intermediate hosts. Available schistosomiasis data from the Philippine Department of Health are utilized to estimate the transmission probability, contact rate between snails and humans, and infectivity from humans and carabaos to snails. Various intervention measures in mitigating the disease are explored under the framework of optimal control theory. The strategies include efforts to increase treatment coverage and compliance of mass drug administration; efforts to reduce humans and snails contacts by providing access to latrines and clean water, improving hygiene practices, targeted mollusciciding, etc.; and efforts to reduce carabaos and snails contact by using mechanized tractors. Results highlight the significance of an integrated approach and prioritizing control strategies considering resource constraints.
A phase I study of C-CAR088, a novel humanized anti-BCMA CAR T cell therapy in relapsed/refractory multiple myeloma
Authors: Qu Xiaoyan , An Gang , Sui Weiwei , Wang Tingyu , Zhang Xian , Yang Junfang , Zhang Yan , Zhang Lu , Zhu Dan , Huang Jiaqi , Zhu Shigui , Yao Xin , Li Jing , Zheng Chengxiao , Zhu Kevin , Wei Yutiang , Lv Xiaoteng , Lan Liping , Yao Yihong , Zhou Daobin , Lu Peihua , Qiu Lugui , Li Jianyong
Published: March 2022

BackgroundAnti-B-cell maturation antigen (BCMA) chimeric antigen receptor-T cell (CAR T) therapy shows remarkable efficacy in patients with relapsed or refractory multiple myeloma (RRMM). C-CAR088, a novel second-generation humanized anti-BCMA CAR T cell therapy, was developed. MethodsThis phase I dose-escalation and expansion study assessed the safety and efficacy of three dosages of C-CAR088 in patients with RRMM. As of July 2, 2021, 31 patients had been infused with C-CAR088. ResultsAny grade cytokine release syndrome (CRS) developed in 29 patients (93.5%), and grade 3 CRS occurred in three patients (9.7%). One patient from the high-dose group (4.5-6.0 × 106 CAR T cells/kg) developed grade 1 neurotoxicity. No dose-limiting toxicities were observed in any dose group, and all adverse events were reversible after proper management. The overall response, stringent complete response, complete response (CR), and very good partial response rates were 96.4%, 46.4%, 10.7%, and 32.1%, respectively. The CR rate in the medium-dose (3.0 × 106 CAR T cells/kg) and high-dose (4.5-6.0 × 106 CAR T cells/kg) groups was 54.5% and 71.4%, respectively. In the CR group, 15 (93.7%) patients achieved minimal residual disease (MRD) negativity (test sensitivity >1/10-5). All seven patients with double-hit or triple-hit multiple myeloma achieved MRD-negative CR. ConclusionsOur findings demonstrate the manageable safety profile and potential efficacy of C-CAR088.Trial registrationNCT03815383 was registered in December 2018.NCT03751293 was retrospectively registered in May 2019.NCT04295018 was registered in October 2019. NCT04322292 was registered in March 2020.
TCERG1L Hypermethylation Is A Risk Factor Of Diabetic Retinopathy In Chinese Children With Type 1 Diabetes
Authors: Qian Yu , Xiao Ying , Lin Qiurong , Xiang Zhaoyu , Cui Lipu , Sun Jiaqi , Li Sicong , Qin Xinran , Jin Peiyao , Yang Chenhao , Zou Haidong
Published: March 2022

Background: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children.Methods/Results: This study consists of two surveys. 40 T1DM children with no DR participated in the first survey. Their DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay. Comparison of the methylation patterns was made between participants with macular retinal thinning (cases) and the others (controls). The second survey included 27 T1DM children, among which 4 had DR. Pyrosequencing was used to validate the results of the 850K array, and the methylation patterns of four DMS was compared between participants with and without DR.In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δβ|> 0.1 and Adj.P-value <0.05), while 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypometh­ylated in the case group relative to the controls. Four of the identified DMS with a potential role in diabetes were chosen to be validated in the second survey. Pyrosequencing revealed that the TCERG1L (cg07684215) gene was hypermethylated in the four T1DM children with DR (p=0.018), which was consistent with the result from the first survey. The methylation status of PDXK, PARK2 and PPARG showed no difference (all p>0.05) between participants with and without DR.Conclusions: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.
Severe burn injury caused by carbon monoxide poisoning: two case reports
Authors: Hu Delin , Jiang Wei , Liu Chun , Song Junhui , Meng Chengying , Lu Shiping , Hu Jiayan , Zhou Yan , Zhou Shunying , Yu Youxin , Sun Yexiang
Published: March 2022

CO poisoning is the most common cause of injuries and deaths after poisoning worldwide. Exposed charcoals and furnaces are often used for heating in parts of world. When CO poisoning occurs in a coma, people may faint on burning charcoal and furnace, and suffer severe burns. This article reports two cases of severe burns caused by CO poisoning, and the first patient even required amputation of his left leg. Besides, the long and painful treatments and irreversible changes in appearance and function have brought huge economic pressure and serious psychological barriers to patients. Therefore, education and prevention of CO poisoning are indeed worthy of attention.
The outcome of linezolid induced optic and peripheral neuropathy in a Pakistani patient treated for multidrug-resistant pulmonary tuberculosis: A case report
Authors: Nawaz Ahmad
Published: March 2022

Linezolid is a core second-line drug used for the treatment of extensively and multidrug-resistant tuberculosis. Linezolid showed the promised efficacy in the treatment of drugs resistant tuberculosis. However, the associated adverse effects such as optic and peripheral neuropathy are the major obstacles for its long-term therapy. We recently encountered a case of progressive deterioration of vision and numbness in the feet in a 32-years-old male undergoing linezolid therapy for 12 months for multidrug-resistant tuberculosis. Nerve conduction studies were highly suggestive of sensory polyneuropathy while the fundoscopic image was highly favorable of optic neuropathy. A slight improvement was seen in vision with no improvement or worsening of peripheral neuropathy on follow-up visits after the discontinuation of linezolid. In a developing country like Pakistan, whereas the management of developing resistance to tuberculosis is a major problem, awareness among physicians for close follow-up of a patient using long-term linezolid therapy should be created to avoid such serious optic and peripheral neuropathy.
Lncrna HOXD-AS1 Functions As A Cerna To Promote Hepatocellular Carcinoma Metastasis In Zebrafish Xenograft Models
Authors: Zhang Ying , Wang Xiao-Lu , Qin Feng , Jia Shao-Chang
Published: March 2022

Recent studies have suggested that long noncoding RNA (lncRNA) HOXD cluster antisense RNA 1 (HOXD-AS1) plays an important role in hepatocellular carcinoma (HCC) metastasis as a competing endogenous RNA (ceRNA). However, there is no in vivo evidence supporting this. Employing zebrafish HCC xenograft as an in vivo metastasis model, we aim to verify the role of ceRNA network of HOXD-AS1 in HCC metastasis. The quantitative reverse transcription PCR (qRT-PCR) assay was used to assess the expression level of HOXD-AS1 in HCC cell lines. Knockdown of HOXD-AS1 or miR-130a-3p was performed by transfecting small interfering RNA (siRNA) or microRNA (miRNA) inhibitor, respectively. The proliferation and migration of HCC cells in vitro were analyzed by CCK-8 and transwell assays. The growth and metastasis of HCC cells in vivo were assessed by zebrafish xenograft models. We verified that HOXD-AS1 was overexpressed in all tested HCC cell lines compared to the normal hepatic cells. Silence of HOXD-AS1 suppressed cell proliferation and migration in Hep3B and Huh7 HCC cell lines, respectively. In zebrafish xenograft models, knockdown of HOXD-AS1 also reduced the growth and metastasis of the two HCC cells. Downregulation of miR-130a-3p rescued the metastasis which inhibited by silence of HOXD-AS1 in vitro and in vivo. Moreover, HOXD-AS1 knockdown enhanced the inhibition effect of oxaliplatin for HCC progression in vitro and in vivo. Our study demonstrates the pro-metastastic role of the HOXD-AS1/miR-130a-3p ceRNA network in HCC cells, and provides evidence that HOXD-AS1 may serve as a biomarker and potential therapeutic target for HCC metastasis.
Does selection occur at the intermediate zone of two insufficiently isolated populations? A whole-genome analysis along an altitudinal gradient
Authors: Yoshida Naofumi , Morinaga Shin-Ichi , Wakamiya Takeshi , Ishii Yuu , Kubota Shosei , Hikosaka Kouki
Published: March 2022

Adaptive divergence would occur even between the insufficiently isolated populations when there is a great difference in the environments between their habitats. The individuals present in the intermediate zone of the two divergent populations are expected to have an admixed genetic structure due to gene flow. A selective pressure that acts on the genetically admixed individuals may limit the gene flow and promote the adaptive divergence. Here, we addressed a question whether the selection occurs in the genetically admixed individuals between the divergent populations and assessed its effects on the population divergence. We obtained the whole-genome sequences of a perennial montane plant, Arabidopsis halleri, which has clear phenotypic dimorphisms between altitudes, along an altitudinal gradient of 359–1,317 m with a high spatial resolution (mean altitudinal interval of 20 m). We found the zone where the highland and lowland genes were mixing (intermediate subpopulation). We sought genetic variants that had been selected in the intermediate subpopulation. In the intermediate subpopulation, we identified 9 and 22 genetic regions, which included 7 and 19 genes, had a high frequency of alleles that are accumulated in highland and lowland subpopulations, respectively, suggesting that these genes have been selected in the admixed zone. This selection might limit the gene flow and contribute to the adaptive divergence along the altitudes. We also identified a genetic region that contains different alleles from those in both highland and lowland subpopulations, though the variants were not included in encoded genes. We also identified 7 genetic regions had low heterozygote frequencies in the intermediate subpopulation. We could not find any genetic regions whose heterozygote frequency was higher than theoretical expectation. We conclude that different types of selection in addition to gene flow occur at the intermediate altitude and shape the genetic structure across altitudes.
Spatio-Temporal Control of THz Emission
Authors: Huang Hsin-hui , Juodkazis Saulius , Gamaly Eugene , Nagashima Takeshi , Yonezawa Tetsu , Hatanaka Koji
Published: March 2022

Polarization fine control of THz emission is demonstrated with a tilted micro-thin water flow by the irradiation of two cross-linearly-polarized femtosecond laser pulses (800 nm, 35 fs, transform-limited) with spatio-temporal offsets. With an optimized horizontal offset at ∼ 11 𝜇m between the ∼ 8 𝜇m focal spots and time delay at 4.7 ns, circularly-polarized THz emission was obtained with its intensity enhancement more than 1,500-times if compared with the single pulse irradiation. It is shown that the photon-number-based efficiency from the laser to THz at 7.1x10^−3 is achieved with the optimisation of the double pulse irradiation. Polarization-resolved THz time-domain spectroscopy and time-resolved shadowgraphy imaging revealed that the circularly-polarized THz emission originates from the focal volume in front of the water flow. Coupling between a shockwave due to air-breakdown and water ablation-mediated mass transport by the first pulse with a laser wake-field along the optical path of the main pulse is responsible for the point-like single-cycle THz source.
HIP Fracture REhabilitation Program for older adults with hip fracture (HIP-REP) based on Activity of Daily Living: a feasibility study
Authors: Røpke Alice , Morville Anne-Le , Møller Trine Elleby , Delkus Emma Cæcilie Guttzeit , Juhl Carsten Bogh
Published: March 2022

Background: A Rehabilitation Program for older adults with hip fracture (HIP-REP) based on Activity of Daily Living has been developed.Objectives: Assessing the feasibility and safety of the HIP-REP program to inform a future randomized controlled trial (RCT).Design: Feasibility study inspired by the Complex-intervention development (Medical Research Council framework phase II)Setting: Cross sectoral including Copenhagen University Hospital, Herlev and Gentofte and rehabilitation centers in Herlev, Gentofte and Lyngby-Taarbæk municipalities.Participants: Eighteen older adults (above 65 years) with hip fracture were recruited from the orthopedic wards.Intervention: A cross-sectoral rehabilitation intervention was tailored to the needs of older adults with hip fracture highlighting systematic goal setting and strategies focused on activities of daily living.Measurements: Pre-defined feasibility criteria: participants recruitment and retention, duration of measuring the outcome, adherence to intervention, and adverse events, along with self-reported outcomes and an objective measurement of performance in activity of daily living.Results: Recruitment rate was 4.5/month. Outcome measures were performed but length and number of questionnaires were a burden. Thirteen out of eighteen participants completed the study three dropped out and two died. Adherence among the 13 was 100%. Focus group revealed issues regarding coordinating the intervention, ensuring procedural processes across sectors regarding recruitment of participants, and documentation in the database. Participants expressed satisfaction with the intervention and felt safe during intervention. Assessment of Motor and Process Skills showed better increase between (range 0.4 to 1.6) in ADL motor ability measures and better increase between (range 0.4 to 0.7) for process ability. No clear association between outcome improvements and intervention adherence.Conclusions:The cross-sectoral intervention based on daily activities was feasible and safe for older adults with hip fracture. A future RCT, with an improved recruitment strategy and reduced number of outcome measures will evaluate the effectiveness in improving independence and safety performance of activity of daily living.Trial registration: ClinicalTrials.gov ID: NCT03828240