bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology and Phenotypic Characteristics of Dual Molecular Diagnosis Cases in Skeletal Abnormality
Authors: Liu Lian , Sun Liying , Chen Yujun , Yu Chenxi , Huang Yingzhao , Zhao Sen , Du Huakang , Chen Shaoke , Fan Xin , Tian Wen , Wu Zhihong , Qiu Guixing , Zhang Terry Jianguo , Wu Nan
Published: July 2021

Background Skeletal abnormality is a heterogeneous group of disorders that affects the composition and structure of bone and cartilage. In our previous studies, we have revealed that a substantial proportion of cases with early-onset scoliosis could be explained by monogenic disorders such as Marfan syndrome and Ehlers-Danlos syndrome. More recently complex phenotypes caused by more than one genetic defect (i.e., dual molecular diagnosis) have also been reported in skeletal abnormalities. To explore the molecular epidemiology and phenotypic characteristics of dual diagnosis in skeletal abnormalities, we described cases with dual molecular diagnosis from the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study.Results In total, 1108 patients with skeletal abnormality from the DISCO study underwent Exome Sequencing. We identified eight probands with dual molecular diagnosis, including three (0.7%) from individuals with early-onset scoliosis (EOS), three (0.5%) from individuals with short stature, and two (2%) from individuals with congenital hand/foot deformity (CHFA). Other skeletal abnormalities observed in these individuals included bone fracture and interphalangeal joint contracture. All the eight probands have dual diagnosis of two autosomal dominant (AD) diseases. A total of 16 variants in 12 genes were identified. A substantial rate (5 of 10) of the identified causal variants were of de novo origin. The frequently observed molecular diagnoses (observed in more than one patient) include Osteogenesis Imperfecta Type I (COL1A1, MIM:166200), Neurofibromatosis, Type I (NF1, MIM:162200) and Marfan Syndrome (FBN1, MIM:154700). These patients with dual molecular diagnosis often present blended phenotypes of two diseases, which significantly complicate their diagnostic process. Conclusions This study revealed the molecular epidemiology and complex diagnostic odyssey of dual molecular diagnosis through analyzing the clinical traits of skeletal abnormalities in eight patients.
Transcriptomics Analysis of Daheng Broilers Reveals that PLIN2 Regulates Chicken Preadipocyte Proliferation, Differentiation and Apoptosis
Authors: Li Jingjing , Yang Chaowu , Ren Peng , Lin Zhongzhen , Zhang Donghao , Jiang Xiaosong , Wang Li , Liu Yiping
Published: July 2021

Intramuscular fat content, an important meat quality trait, strongly affects flavor, juiciness, and tenderness. Sex hormones regulate lipid metabolism, and female hormones stimulate fat deposition, thereby making the female chickens always fatter than males. In this study, the effect of sex on IMF deposition was screened following transcriptomics in chickens. Results confirmed significantly higher IMF content of 150-day female chickens as compared to the male chickens. The female chickens manifested higher serum TG, LDL-C, and VLDL, and significantly lower HDL-C contents than male chickens. Moreover, differential expression of genes involved in lipid metabolism were obtained in the muscle and liver between female and male chicken, which could partly interpret the possible reasons for the sex-mediated differences of IMF content. Cellular results revealed that inhibition of PLIN2 significantly inhibited chicken preadipocyte proliferation and induces apoptosis of preadipocytes, as well as promoted adipocyte differentiation.
Polycystic Ovary Syndrome Phenotype Does Not Have Impact on Oocyte Morphology
Authors: Uk Audrey , Decanter Christine , Grysole Camille , Keller Laura , Béhal Hélène , Silva Mauro , Dewailly Didier , Robin Geoffroy , barbotin anne-laure
Published: July 2021

Purpose The primary objective of the present study of women participating in an ICSI program was to determine whether the morphologic quality of oocytes was related to the polycystic ovary syndrome (PCOS) phenotype.Methods We performed a retrospective cohort study in the IVF unit at the Lille University Medical Center (Lille, France) between 2006 and 2015. Oocyte morphology (fragmented first polar body, abnormal zona pellucida, large perivitelline space, material in perivitelline space, abnormal shape of oocyte, granular cytoplasm and intracytoplasmic vacuoles) was evaluated in PCOS women and according to different subgroup (depending on the presence or absence of the cardinal features polycystic ovarian morphology (PCOM), hyperandrogenism (HA), and oligo-anovulation (OA)).Results A total of 1496 metaphase II oocytes (n=602 for phenotype A combining PCOM + HA + OA, n=462 oocytes for phenotype C: PCOM + HA, and n=432 for phenotype D: PCOM + OA) were assessed. The phenotypes A, C and D did not differ significantly with regard to the proportion of normal oocytes (adjusted percentages (95%CI): 35.2% (31.5% to 39.1%), 25.8% (21.9% to 29.9%) and 34.0% (29.7% to 38.6%), respectively: adjusted p=0.13). Likewise, there were no significant intergroup differences in oocyte morphology. The ICSI outcome was not significantly associated with the PCOS phenotype.Conclusion The present study is the first to show that the PCOS phenotype (notably the presence vs. absence of OA and/or HA) is not significantly associated with the morphological quality of oocytes.
Molecular Genotypic Diversity of Populations of Brinjal Shoot and Fruit Borer, Leucinodes Orbonalis and Development of SCAR Marker for Pesticide Resistance
Authors: Murali Palraju , Hilda Karuppiah , Ramakrishnan Muthusamy , Ganesh Arumugam , Bhuvaragavan Sreeramulu , Janarthanan Sundaram
Published: July 2021

The brinjal shoot and fruit borer, Leucinodes orbonalis is a destructive pest of Solanum melongena. The control of L. orbonalis with extensive application of synthetic chemical insecticides resulted in the development of resistance with known genetic heterogeneity among populations. Understanding the genetic diversity of their populations is important in developing strategies for their management. The present investigation was performed to characterize populations of L. orbonalis for their genetic diversity in the entire region of Tamil Nadu, South India using random amplified polymorphic DNA (RAPD) primers as a tool of the molecular marker. Among sixty random 10-mer primers, only ten primers generated reproducible and scorable banding profile. Among the ten different random primers, the primers namely OPG 7, OPG 8, OPS 2 and OPS 7 generated the highest genetic variation with over 80% genetic polymorphism. Phylogram analysis produced 18 clusters with 8 major and 10 minor clusters. Cluster analysis, statistical fitness, population structure and analysis of molecular variance confirmed the significant genetic variation among different populations. A trait specific marker obtained through RAPD was cloned, sequenced and used to develop a stable diagnostic SCAR marker for DNA fingerprinting to distinguish the populations. Amplification of this locus in the samples of 20 different populations indicated recognition of the trait for pesticide resistance in 12 populations. The results suggest that the biochemical nature of host plant varieties of this insect pest and variation in the application of different insecticides are essential contributing factors for the genotypic variations observed among populations of L. orbonalis.
A New Method for Measuring Stress Inside Movable Element in Contact
Authors: Yu Gonggui , He Jun , Hoang Van Cuong , Huang Ping
Published: July 2021

The subsurface stress plays an important role in the damage of the movable contact element, but most subsurface stresses are obtained with numerical calculations according to the contact mechanics. In the present paper, a new method to measure the subsurface stress of the movable element is proposed with using photoelastic technology. Although the technology has been widely used in measuring the stress of the static elements, it is seldom used in the moving body because the observed point is moving. After the experimental tester is introduced in detail, the principles of the photoelastic technology are presented. The tester is designed to be able to working in the three conditions, the static, the rolling and the sliding in the line or surface contacts. The experimental results, that is the interference fringes, of the three states are then presented in the different loads and the rotational speeds. Because the fringe figures indicate the maximum shear stress distribution in the body of the moving element, we can find what the real stress distribution in the rolling or sliding element is alike.
Prognostic and Therapeutic Potential of The OIP5 Network in Papillary Renal Cell Carcinoma
Authors: Chow Mathilda , Gu Yan , He Lizhi , Lin Xiaozeng , Dong Ying , Mei Wenjuan , Kapoor Anil , Tang Damu
Published: July 2021

Background: Papillary renal cell carcinoma (pRCC) is an aggressive but minor type of RCC compared to the main RCC type, clear cell RCC. The current understanding and management of pRCC remain poor. OIP5 possesses oncogenic functions; its contributions to pRCC remain unknown.Methods: OIP5 expression in pRCC at both the protein and mRNA levels was determined using tissue microarray and TCGA dataset. OIP5 was ectopically expressed in metastatic ACHN pRCC cells; xenografts were performed with gene expression profiled by RNA-seq. Differentially expressed genes (DEGs) were analyzed for prognostic potential and impact on pRCC. The effect of PLK1, an OIP5-related DEG, on pRCC tumor growth in vivo was examined.Results: OIP5 expression is upregulated in pRCC. The upregulation associates with pRCC adverse features (T1P<T2P<CIMP, Stage1+2<Stage 3<Stage 4, and N0<N1) and effectively stratifies the fatality risk. OIP5 promotes ACHN pRCC cell proliferation and xenograft formation. RNA-seq reveals network alterations related to immune regulation, metabolism, and hypoxia in ACHN OIP5 tumors compared to empty vector tumors. A set of DEGs was derived from ACHN OIP5 xenografts and primary pRCCs (n=282) contingent to OIP5 upregulation; both DEG sets share 66 overlap genes. Overlap66 effectively predicts overall survival (p<2e-16) and relapse (p<2e-16) possibilities. The prediction is associated with a good out-of-sample performance, supporting its clinical applications. High-risk tumors stratified by Overlap66 risk score possess an immune suppressive environment, evident by elevations in Treg cells and PD1 expression in CD8 T cells. Upregulation of PLK1 occurs in both xenografts and primary pRCC tumors with OIP5 elevations. PLK1 displays a synthetic lethality relationship with OIP5; PLK1 inhibitor BI2356 causes G2/M arrest in ACHN OIP5 cells in vitro and significantly inhibits the growth of xenografts formed by ACHN OIP5 cells in vivo. Conclusions: Our research reveals that OIP5 and its network possess robust prognostic and therapeutic potentials; the prognostic value of Overlap66 and the therapeutic potential of PLK1 inhibitors may pave the way for developing personalized medicine for pRCC management.
Title: Efficacy of Psychosocial Group Treatment for Post-traumatic Stress Disorder among Genocide Survivors in Rwanda, 25 Years After 1994 Genocide Against Tutsi.
Authors: SIMBI Clarisse Marie Claudine , Zhang Yuhong , Wang Zhizhong
Published: July 2021

Background: Prior studies indicated that post-traumatic stress disorder is becoming a global health concern even though still poorly known and treated. In the aftermath of 1994 Genocide against Tutsi, studies found high rates of depressive and anxious symptoms along with PTSD among genocide survivors. Due to the highest cruelty in which the Genocide was committed, genocide survivors still need high special humanitarian services, of those including specialized health care services. The aim of this study was to assess the efficacy of psychosocial group therapies created by AVEGA Agahozo in reducing PTSD symptoms among Genocide survivors in Rwanda, 25 years after 1994 Genocide against Tutsi.Methods: We conducted a comparative cross-sectional study design with a sample of 98 genocide survivors who received group therapy by AVEGA Agahozo. We used a multi-stage random sampling method to select participants and 7 trained psychologists interviewed genocide survivors about their PTSD status before and after treatment using Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. The analysis was performed using SPSS version 17.1.Results: The results showed that women were 97.96% and men presented 2.04% of all participants because AVEGA Agahozo mainly focuses on helping women survivors who lost their husbands in Genocide and previous findings also concluded that women are very prone to suffer from PTSD than men. Paired t-test results showed significant differences between symptoms, before and after treatment (P<0.001 in all pairs). Cohen's d results also showed high effect sizes (d>0.5), only in pair 8 where the difference appears to be less significant (d=0.28). The descriptive statistics showed that the severity of PTSD symptoms dramatically reduced after treatment. But this difference of severity is only statistically significant among five (5) PTSD symptoms.: (Marked physiological reactivity after exposure to trauma-related stimuli [P=0.045, x2=38.111]; inability to recall key features of the traumatic event [P<001, x2=56.309]; persistent negative trauma-related emotions [P=0.013, x2=43.184]; self-destructive or reckless behavior [P=0.041, x2=38.535]; hypervigilance [P=0.020, x2=41.596]. Conclusion: Psychosocial group therapies created by AVEGA Agahozo effectively alleviate post-traumatic stress disorder symptoms and severity among genocide survivors.
Team-Based Learning in a Physiology Course To Prepare for The International Inter-Medical School Physiology Written Quiz in Kunming Medical University
Authors: Bian Hui , Bian Yan
Published: July 2021

Background

International Inter-medical School Physiology Quiz (IMSPQ) is a global event that purportedly engages students in team work, critical thinking and active learning of physiology. Team-based learning (TBL) is an interactive analytic teaching approach and has been used extensively in medical education. However, there is little evidence of its use in preparing for IMSPQ. The purpose of the present study was to investigate whether a TBL approach is effective to prepare for the written section of IMSPQ.
Methods

Five students from Grade 2014 majoring in Clinical Medicine, were selected, based on academic performance in physiology and English, to be taught in a TBL physiology course to prepare for the written section of 14th IMSPQ.
Results

In 2016, this TBL teaching method worked well and for the first time the team from Kunming Medical University entered the top forty teams at the written competition of 14th IMSPQ in Yogyakarta.
Conclusion

TBL method was effective to prepare for the IMSPQ in Kunming Medical University and provided an improved team performance in the written section of 14th IMSPQ.
Contribution In Determining The Fatigue Endurance of Slide Diamond Burnishing AISI52100 Steel Components
Authors: Taamallah Ouahiba , Hamadache Hamid , Amirat Abdelaziz , Boussaid Ouzine
Published: July 2021

The present paper is an investigation on the effect of slide diamond burnishing on the fatigue endurance of a component made of AISI52100 steel. Burnishing operation has been performed on cylindrical specimens using optimal parameters statistically selected such as burnishing force, burnishing feed and number of tool passes. Bending fatigue tests in air at R= -1 and S-N curves have been plotted by incrementing the applied stress from a maximum stress level of about 66% of the ultimate tensile stress to a stress value below which fatigue does not occur. Results show that slide diamond burnishing has increased the fatigue resistance comparing to unburnished specimens. The fatigue endurance is respectively 222 MPa and 190 MPa. At high stress levels, the fatigue resistance improvement is clearly observed and the fatigue trends are in good agreement with those reported in literature. However, the present results are slightly lower and that is attributed to the shoulder fillet value of the specimen. For small fillet radius, fatigue resistance is lowered.
Exosomal Long Noncoding RNA HOXD-AS1 Promotes Prostate Cancer Metastasis via miR-361-5p/FOXM1 Axis
Authors: Jiang Yongming , Zhao Hui , Chen Yuxiao , Li Kangjian , Chen Jianheng , Li Tianjie , Zhang Baiyu , Guo Caifen , Qing Liangliang , Shen Jihong , Liu Xiaodong , Gu Peng
Published: July 2021

Background: Development of distant metastasis is the main cause of deaths in prostate cancer (PCa) patients. Understanding the mechanism of PCa metastasis is of utmost importance to improve its prognosis. The role of exosomal long noncoding RNA (lncRNA) has been reported yet fully understood in the metastasis of PCa. Methods: Co-culture assay, in-situ hybridization and quantitative PCR (qPCR) were applied to identify the presence of HOXD-AS1 overexpressing exosomes secreted by of castration resistant prostate cancer (CRPC) cells. Migration and wound healing assays were carried out to evaluate the biological function of exosomal HOXD-AS1. Then a mouse model was used to elucidate the effect of exosomal HOXD-AS1 on distant metastasis of PCa in vivo. Further RNA immunoprecipitation and luciferase assay were applied to identify the interaction between HOXD-AS1 and miR-361-5p. Moreover, rescue experiment was conducted to prove the binding of exosomal HOXD-AS1 and miR-361-5p. Last but not least, the application of serum exosomal HOXD-AS1 as a diagnostic and prognostic biomarker for PCa was evaluated. Results: We discovered the exosomal lncRNA HOXD-AS1 is upregulated in CRPC cell line derived exosomes and serum exosomes from metastatic PCa patients, which correlated with its tissue expression. Further investigation confirmed exosomal HOXD-AS1 promotes prostate cancer cell metastasis in vitro and in vivo by inducing metastasis associated phenotype. Mechanistically exosomal HOXD-AS1 was internalized directly by PCa cells, acting as competing endogenous RNA (ceRNA) to modulate the miR-361-5p/FOXM1 axis, therefore promoting PCa metastasis. In addition, we found that serum exosomal HOXD-AS1 was upregulated in metastatic PCa patients, especially those with high volume disease. And it is correlated closely with Gleason Score, distant and nodal metastasis, Prostatic specific antigen (PSA) recurrence free survival and progression free survival (PFS). Conclusions: Our study sheds a new insight into the regulation of PCa distant metastasis by exosomal HOXD-AS1 mediated miR-361-5p/FOXM1 axis, and provided a promising liquid biopsy biomarker as well as therapeutic target to the detection and treatment of metastatic PCa.
Tracking Microbial Communities Across Aedes Albopictus Life Stages and Larval Habitat Types
Authors: Tokash-Peters Amanda G. , Woodhams Douglas C.
Published: July 2021

Aedes albopictus, the Tiger Mosquito, has been hailed as one of the most invasive arbovirus-transmitting mosquitoes globally. With the growing potential of microbial methods for mosquito control, it has become increasingly imperative to understand the factors that contribute to naturally-occurring microbiome communities. Here, we analyzed the impact of larval water type and life stage on the microbial community of Aedes albopictus. The field-collected water samples from tree holes and tires that were used to rear larval mosquitoes in the laboratory were significantly different from each other in terms of sOTU (bacterial species) richness, with tree holes having a far greater number of sOTUs. For beta diversity measures (Bray-Curtis dissimilarity) Aedes albopictus were not significantly different from adult Aedes aegypti, but mosquito sex, life stage, and overall treatment group were significantly different when analyzed by ANOSIM. Based on our findings, the environment surrounding larval mosquitoes (and subsequent adult mosquitoes from those habitats) and the life stage of mosquitoes (regardless of species) shapes mosquito microbiome assemblages. This work further supports the idea that mosquito adults maintain a microbiome specific to larval habitat, despite major reductions to their microbiome prior to eclosion, which could shape the success of implemented microbial engineering or control methods.
Efficient Gene Editing Through an Intronic Selection Marker in Cells
Authors: Wang Shang , Li Yuqing , Zhong Li , Wu Kai , Zhang Ruhua , Kang Tiebang , Wu Song , Wu Yuanzhong
Published: July 2021

Background Gene editing technology has provided researchers with the ability to modify genome sequences in almost all eukaryotes. Gene-edited cell lines are being used with increasing frequency in both bench research and targeted therapy. Despite the great importance and universality of gene editing, however, precision and efficiency are hard to achieve with the prevailing editing strategies, such as homology-directed DNA repair (HDR) and the use of base editors (BEs). Results & Discussion Our group has developed a novel gene editing technology to indicate DNA variation with an independent selection marker using an HDR strategy, which we named Gene Editing through an Intronic Selection marker (GEIS). GEIS uses a simple process to avoid nonhomologous end joining (NHEJ)-mediated false-positive effects and achieves editing efficiency as high as 91% without disturbing endogenous gene splicing and expression. We re-examined the correlation of the conversion tract and editing efficiency, and our data suggest that GEIS has the potential to edit approximately 99% of gene editing targets in human and mouse cells. The results of further comprehensive analysis suggest that the strategy may be useful for introducing multiple DNA variations in cells.
Enhanced Surveillance in a Digital Health Landscape: The Role of the Near-Real Time Right to Care Knowledge Centre within South Africa’s APACE HIV Program
Authors: Pedro Pisa , Melinda Potgieter , Marcus Rennick , Onaga Chuka , Molefi Seithati , Muzvidziwa Tafadzwa , Chirowodza Admire , Majuba Pappie , Sanne Ian , Brahmbhatt Heena , Mdl David , Mdl Bheki , Mtungwa Ishmael , Mogane Pharais
Published: July 2021

Introduction: Right to Care (RTC), through support from the United States Agency for International Development (USAID) implements innovations that improve data accessibility and utilization for improved program performance and patient outcomes for large scale HIV care and treatment programs. Frequent and accessible data, coupled with changes to business practices to use that data, allow for targeted and timely HIV program interventions that impact patient outcomes in Ehlanzeni district, Mpumalanga, South Africa.Methods: In South Africa, within the USAID Accelerating Program Achievements to Control the Epidemic (APACE) program, the Knowledge Centre (KC) – an interoperable automated data warehouse and visualization near real-time solution - allow for rapid daily assessment of over- and under-performance cross-sectionally. The authors established the impact of the KC intervention for 29 USAID-selected Siyenza facilities, before the KC intervention (Dec 2018 to Feb 2019) compared to HIV outcomes during the KC intervention (March 2019 to May 2019), stratified by facility classification as included or not included in the Siyenza program using both non-parametric and parametric methodologies.Results: Average facility ART initiations increased by 16% from a monthly average of 54 new initiations pre-Siyenza to 62 new ART initiations during Siyenza; retention increased to a net retention in care ratio of 1.15 indicating that patients labelled as lost to care were brought back. An independent-samples t-test indicated that the net retention in care scores were significantly higher for Siyenza facilities (M =.379, SD =.808) compared to non-Siyenza facilities (M=-.061, SD =1.016), t(208) = 2.224, p < 0.027, d = .445 during the Siyenza period. A significant difference was noted between the means with a 62.3% chance that the Siyenza facilities have a higher observed mean than the non-Siyenza facilities during the intervention period. Results indicate that Siyenza facilities maintain cohort growth, while non-Siyenza facilities continued to lose patients. Conclusion: The accessibility and utilization of near to real-time interoperable data within HIV programs allowed for rapid responses to program performance, needs and improved patient outcomes. Daily data review meetings facilitated precision programming and contributed to the behavior change necessary to institute routine data use for decision making and evaluations within programs.
Attenuation and Dispersion on Terahertz Wireless Channels in Falling Rain
Authors: Ma Jianjun , Li Peian , Zhao Liangbin , Wang Jianchen , Liu Wenbo , Mei Yu , Bu Xiangyuan , An Jianping
Published: July 2021

Investigations on wireless channel performance in adverse weathers could be helpful and important for the future applications of terahertz communication technique in outdoor scenarios. However, in most cases only amplitude performance has been studied by using a broadband-pulsed terahertz source or an amplitude modulated data stream, not including phase degradation (temporal dispersion). This limitation may mask important aspects of channel performance with phase modulation schemes, especially for wide bandwidth signals. In this work, we report the amplitude and phase characterizations of a terahertz channel in falling rain by a time-domain spectrometer system. We also demonstrate error rate performance by a 16 quadrature amplitude modulated (16-QAM) terahertz signal at a data rate of 5 gigabits per second. We observe that, besides strong water vapor absorption, the weak water absorption line could also lead to obvious dispersion effects. Our work highlights the importance of new frequency band boundaries for minimum temporal dispersion and optimized digital communications in the terahertz frequency range.
Chemical Sedimentation as a Driver of Habitat Diversity in Dryland Wetlands
Authors: Humphries Marc , McCarthy Terence
Published: July 2021

Freshwater wetlands located in dryland environments are characterised by high evapotranspiration rates and frequent periods of desiccation, which strongly influence the water chemistry and solute budgets of these systems. The transpiration of groundwater, especially by trees, is an important mechanism through which dryland wetlands can lose water. This process can lead to groundwater salinization and the precipitation of substantial quantities of mineral phases within the soil, the accumulation of which can have profound consequences for wetland structure and function. This paper aims to bring together current knowledge on the processes that result in solute accumulation and chemical sedimentation which assist in maintaining freshwater conditions in many seasonal dryland wetlands. Examples from central and southern Africa, Australia and South America are presented to illustrate the geomorphically diverse settings under which chemical sedimentation can occur, and the importance of these processes for the resilience and longevity of dryland wetlands. We show that the localised development of saline groundwater and subsurface precipitation of minerals within soils can play a key role in creating and maintaining the habitat diversity of dryland wetlands. Wetland vegetation focuses the accumulation of deleterious constituents, thereby preventing widespread salinization and playa-lake formation, and thus ensuring that the bulk of the surface water remains fresh. Although such processes remain widely understudied, we suggest that chemical sedimentation could be a common phenomenon in many dryland wetlands and have important implications for the future management of these ecosystems.
The Effect of Glutamine Supplementation on Serum Levels of Some Inflammatory Factors, Oxidative Stress, and Appetite in COVID-19 Patients: A Case-Control Study
Authors: mohajeri mahsa , horriatkhah ehsan
Published: July 2021

Background: Malnutrition is seen in COVID-19 patients, and reducing malnutrition with appropriate therapies may improve these patients' health. this case-control study aimed to assess and compare serum levels of some inflammatory factors and oxidative stress and appetite in COVID-19 patients with respiratory infections that receive glutamine treatment with a control group. Method: In this study, patients who consented to use glutamine were considered as the case group and other patients who did not use glutamine were considered as a control group. Twenty-seven Covid-19 patients (10 female, 48.5 ± 9.1) using L-Glutamine and 27 Covid-19 patients (12 female, 48.8 ± 4.6) with similar age, gender, and clinical status were included in the study. For five days, the case group was given 10g/day of glutamine supplement. At the end of the fifth day, blood samples were taken again to test for serum levels of IL1β, tumor necrosis factor-alpha, malondialdehyde, and total antioxidant capacity, then all data were analyzed. Results: Serum levels of beta-1 interleukin, tumor necrosis factor-alpha, and hs-CRP were significantly reduced with five days of glutamine supplementation (p <0.05), and patients' appetite during five days of glutamine supplementation compared with the control group had a significant increase (p <0.05. Conclusion: Glutamine supplementation in COVID-19 patients with respiratory infection significantly reduces serum levels of interleukin-1 beta, hs-CRP, and tumor necrosis factor-alpha and significantly increases appetite, so glutamine supplementation may be useful for COVID-19 patients in the hospital.
[18F]FDG PET-CT in Patients With DLBCL Treated With CAR-T Cell Therapy: A Practical Approach of Reporting Pre- and Post-treatment Studies
Authors: Cohen Dan , Luttwak Efrat , Beyar-Katz Ofrat , Krauthammer Shir Hazut , Bar-On Yael , Amit Odelia , Gold Ronit , Perry Chava , Avivi Irit , Ram Ron , Even-Sapir Einat
Published: July 2021

Purpose: The introduction of CD19-specific chimeric antigen receptor T-cell therapy (CAR-T) for treatment of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) gives hope to patients with otherwise dismal prognosis. Therapy outcomes depend, however, on selection of patients and on accurate early identification of non-responders. Patients treated with CAR-T usually undergo [18F]FDG PET-CT at time of decision (TD), time of CAR-T transfusion (TT), one month (M1) and three months (M3) post therapy. The purpose of the current study was to identify the specific parameters that should be addressed when reporting PET-CT studies in the clinical setting of CAR-T therapy.Methods: A total of 138 PET-CT scans (30 TD, 42 TT, 44 M1, 22 M3) of 48 patients treated with CAR-T were included. SUVmax, TMTV, TLG were calculated in all scans. Response was assessed using Deauville scale and ΔSUVmax method. Overall survival (OS) was the primary endpoint. Median follow-up was 12.8 (IQR 6.4-16.0) months from CAR-T infusion.Results: In a univariate analysis, TD-SUVmax > 17.1 and TT-SUVmax > 12.1 were associated with shorter OS (Pv<0.05). In a multivariate analysis, three factors were significantly associated with shorter OS: TD-SUVmax > 17.1 (HR 10.3; Pv<0.01), LDH > 450 U/l (HR 7.7; Pv<0.01) and ECOG score > 1 (HR 5.5; Pv=0.04). Data from TD and TT PET-CT scans were not predictive of toxicity. On M1-PET-CT, patients with Deauville score > 3 had significantly shorter OS (median 7.9 months, versus not reached, Pv<0.01). ΔSUVmax ≤ 66% on M1-PET-CT predicted shorter OS when comparison of M1-SUVmax was made to TD-SUVmax (Pv=0.02) and not to TT-SUVmax (Pv=0.38).Conclusion: Pre-treatment SUVmax may guide patient selection for CAR-T therapy. On M1-PET-CT, Deauville score and ΔSUVmax from TD may identify early therapy failure. These parameters are easy to obtain and should be included in the PET-CT report.
Intra-articular Administrated Hydrogels of Hyaluronic Acid Hybridized with Triptolide/Gold Nanoparticles for Targeted Delivery to Rheumatoid Arthritis Combined with Photothermal-chemo Therapy
Authors: Li Chenxi , Liu Rui , Song Yurong , Zhu Dongjie , Yu Liuchunyang , Huang Qingcai , Zhang Zhengjia , Xue Zeyu , Hua Zhenglai , Lu Cheng , Liu Yuanyan
Published: July 2021

Triptolide (TP) as a disease-modifying anti-rheumatic drug (DMARD) is effective on the treatment of rheumatoid arthritis (RA). To alleviate the toxicity and elevate therapeutic specificity, hyaluronic acid (HA) hydrogels load RGD-attached gold nanoshell containing TP are synthesized, which can be used for targeted photothermal-chemo therapy, and imaging of RA in vivo. The hydrogels system composed of thiol and tyramine modified HA conjugates has been applied artificial tissue models of cartilage for studying drug delivery and release properties. After the degradation of HA chains, heat together with drugs can be delivered to the inflammatory joints simultaneously due to the near-infrared resonance (NIR) irradiation of Au nanoshell. RA is a chronic inflamed disease, which is characterized by synovial inflammation of multiple joints, and can be penetrated with NIR light. These intra-articular administrated hybrid hydrogels combined with NIR irradiation can improve clinical arthritic conditions and inflamed joints in collagen-induced arthritis (CIA) mice, which just need a smaller dosage of TP with non-toxicity. Additionally, the TP-Au/HA hybrid hydrogels treatment reduced the invasion and migration of RA fibroblast-like synoviocytes (RA-FLSs) in vitro significantly, through reducing the phosphorylation of mTOR and p70S6K, its substrates, and confirmed that the mTOR pathway was inhibited.
Detection of Inherited Mutations in Brazilian Breast Cancer Patients Using Multi-Gene panel Testing
Authors: Guindalini Rodrigo Santa Cruz , Viana Danilo Vilela , Kitajima João Paulo Fumio Whitaker , Rocha Vinícius Marques , López Rossana Verónica Mendoza , Zheng Yonglan , Freitas Érika , Monteiro Fabiola Paoli Mendes , Valim André , Schlesinger David , Kok Fernando , Olopade Olufunmilayo I. , Folgueira Maria Aparecida Azevedo Koike
Published: July 2021

Genetic diversity of germline variants in breast cancer (BC) predisposition genes, is unexplored in miscegenated people, such as Latin American populations. We evaluated 1,662 Brazilian BC patients, who underwent hereditary multi-gene panel testing (20–38 cancer susceptibility genes), to determine the spectrum and prevalence of (likely) pathogenic variants (P/LP) and variants of uncertain significance (VUS). In total, 161 (9.7%) participants carried germline P/LP variants in BRCA1/2 and 162 (9.7%) in other cancer predisposition genes. Overall, 341 distinctive P/LP variants were identified in 22 genes, including BRCA1(28%), BRCA2(19%), TP53(11%), MUTYH heterozygous (10%), ATM(9%), CHEK2(6%), and PALB2(5%). The Brazilian variant TP53 R337H (c.1010G > A, p.Arg337His), detected in 1.6% of BC patients and 0.09% of reference controls (RC), was strongly associated with odds of disease (OR = 17.67; 95%CI:9.21–34.76; p < 0.001). Heterozygous MUTYH c.1187G > A and MUTYH c.536A > G, detected in 0.78% (0.90% RC) and 0.48% (0.40% RC) of the patients, respectively, were not associated with the odds of BC, the former with OR = 0.87 (95%CI:0.49–1.53; p = 0.63) and the latter with OR = 1.20 (95%CI:0.58–2.49; p = 0.63). Besides, 766 individuals (46.1%) had 1 or more VUS. Concluding, the use of multi-gene panel testing doubled the identification of mutation carriers in Brazilian BC patients. Special attention should be given to TP53 mutations.
Time slows down on a crowded train
Authors: Sadeghi Saeedeh , Daziano Ricardo , Yoon So-Yeon , Anderson Adam
Published: July 2021

Numerosity, complexity and affect are among factors known to dilate perceived time. While such objective and subjective factors are usually tested in isolation with simple stimuli in the lab, here we examined the perceived passage of time in the ecology of daily social life: crowded public transit. Higher crowding level denotes a higher numerosity along with increased negative affect. Accordingly, we hypothesized that crowding lengthens subjective trip duration. Participants (N=41) experienced short (between 1 to 2 minutes) immersive subway trips using Virtual Reality (VR). Each individual experienced multiple virtual trips with different crowding levels. After each trip, they were asked to estimate the trip duration and rate its affective pleasantness. Presence of one additional person per square meter of the train significantly increased perceived travel time by an average of 1.8 seconds. Rather than objective factors, this effect was mediated by subjective negative feelings induced by crowding. Analysis of cardiac data also revealed the slope of change in heart rate during a trip as a physiological source of perceived travel time, independent of the crowding level. This study is an example of bringing basic psychological and physiological findings into an ecologically valid setting using VR technology. Findings have broader implications for the effects of disliking social crowding on our daily perceptions, which is likely more pronounced during or even after the COVID-19 pandemic.
Identification of Candidate Genes that Specifically Regulate Subcutaneous and Intramuscular Fat Deposition Using Transcriptomic and Proteomic Profiles in Dingyuan Pigs
Authors: Zhang Pan , Li Qinggang , Wu Yijing , Zhang Yawen , Zhang Hao , Zhang Bo
Published: July 2021

Background: Subcutaneous fat and intramuscular fat (IMF) deposition are closely related to meat production and pork quality. The Dingyuan pig is a local pig breed in Anhui Province, China, that has great potential for fat deposition. Individuals with extreme subcutaneous fat and intramuscular fat content can be found in this breed, which provides a good study system for investigating the molecular mechanisms regulating these two types of fat deposit.Results: In this study, we used RNA-Seq and tandem mass tags-based proteomics to analyze the key pathways and genes that specifically regulate subcutaneous fat and intramuscular fat deposition in Dingyuan pigs. We identified 191 differentially expressed genes (DEGs) and 61 differentially abundant proteins (DAPs) in the high backfat thickness (HBF) and low backfat thickness (LBF) groups. In the high intramuscular fat and low intramuscular fat groups, we found 85 DEGs and 12 DAPs. The gene ontology and KEGG pathway enrichment analysis showed that the DEGs and DAPs in the backfat groups were mainly involved in various metabolic pathways, such as those related to carbohydrates, amino acids, esters, and fatty acids, whereas the DEGs and DAPs of the IMF groups were involved in a wide range of signaling pathways, including metabolic pathways, the insulin pathway, ketone body synthesis and degradation, longevity, and some disease-related pathways. Among the genes related to the metabolic pathways of carbohydrates, amino acids, esters, and fatty acids, we found 26 candidate genes that specifically regulate subcutaneous fat deposition and 7 genes that specifically regulate IMF deposition in Dingyuan pigs.Conclusion: Our data show that subcutaneous fat deposition and IMF deposition are regulated by the same genes, but there are also genes that specifically regulate these two fat depositions. Our data provide insights into the mechanisms of pig fat deposition.
Evaluating Machine Learning Classifiers for Glaucoma Referral Decision Support in Primary Care Settings
Authors: Kaskar Omkar G. , Wells-Gray Elaine , Fleischman David , Grace Landon
Published: July 2021

Several artificial intelligence algorithms have been proposed to help diagnose glaucoma by analyzing the functional and/or structural changes in the eye. These algorithms require carefully curated datasets with access to ocular images. In the current study, we have modeled and evaluated classifiers to predict self-reported glaucoma using a single, easily obtained ocular feature (intraocular pressure (IOP)) and non-ocular features (age, gender, race, body mass index, systolic and diastolic blood pressure, and comorbidities). The classifiers were trained on publicly available data of 3,015 subjects without a glaucoma diagnosis at the time of enrollment. 337 subjects subsequently self-reported a glaucoma diagnosis in a span of 1-12 years after enrollment. The classifiers were evaluated on the ability to identify these subjects by only using their features recorded at the time of enrollment. Support vector machine, logistic regression, and adaptive boosting performed similarly on the dataset with F1 scores of 0.31, 0.30, and 0.28, respectively. Logistic regression had the highest sensitivity at 60% with a specificity of 69%. Predictive classifiers using primarily non-ocular features have the potential to be used for identifying suspected glaucoma in non-eye care settings, including primary care. Further research into finding additional features that improve the performance of predictive classifiers is warranted.
WITHDRAWN: Inclined, Expanded and Curved Interference Pattern of Double Slit Experiment---Mathematical Description (1)
Authors: Peng Hui
Published: July 2021

Young’s double slit experiments express the mystery of quantum mechanics. To explore the mystery, varieties of the double slit experiments were performed. It has been shown that the following three phenomena emerged simultaneously in one double slit experiment: (1) the interference patterns incline towards the axis that perpendicular to the axis the diaphragm rotating around; (2) the interference patterns curved; (3) the distances between the fringes of the interference patterns expanded. To determine the direction the interference pattern curved towards, we proposed the right-hand rule for the clockwise rotating diaphragm and the left-hand rule for the counterclockwise rotating diaphragms. In this article we derived the mathematical formulars for the first phenomenon that interference patterns incline. We show that the inclination of the interference pattern is determined by two angles, one is the original orientation of the double slit, other one is the rotating angle of the diaphragm, either clockwise or counterclockwise.
Covid-19 vaccine-induced antibodies are attenuated and decay rapidly in infliximab treated patients
Authors: Lin Simeng , Kennedy Nicholas A , Saifuddin Aamir , Sandoval Diana Muñoz , Reynolds Catherine , Seoane Rocio Castro , Kottoor Sherine , Pieper Franziska , Lin Kai-Min , Butler David K , Chanchlani Neil , Nice Rachel , Chee Desmond , Bewshea Claire , Janjua Malik , McDonald Timothy J , Sebastian Shaji , Alexander James L , Constable Laura , Lee James C , Murray Charles D , Hart Ailsa L , Irving Peter M , Jones Gareth-Rhys , Kok Klaartje B , Lamb Christopher A , Lees Charlie W , Altmann Daniel M , Boyton Rosemary J , Goodhand James R , Powell Nick , Ahmad Tariq
Published: July 2021

To inform healthcare policy for immunosuppressed patients there is a need to define SARS-CoV-2 vaccine responses. Here we report SARS-CoV-2 vaccine-induced antibody and T cell responses in patients treated with anti-tumour necrosis factor (anti-TNF), a commonly used biologic in inflammatory diseases, compared to patients treated with vedolizumab, a gut-specific antibody targeting integrin a4b7 that does not impair systemic immunity. In anti-TNF recipients, the magnitude of anti-SARS-CoV2 antibodies was reduced five-fold, and rapidly decayed towards the seroconversion threshold by 14 weeks after second dose of vaccine. In contrast, anti-SARS-CoV-2 antibodies were sustained up to 16 weeks in vedolizumab-treated patients. Anti-SARS-CoV2 antibody decay was not observed in vaccinated patients previously infected with SARS-CoV-2. T cell responses were absent in one-fifth of anti-TNF and vedolizumab-treated patients after a second dose of either vaccine. Our data have important implications for anti-TNF recipients, including the need for vaccine prioritization, booster doses, and social distancing strategies.
Experimental analysis on the optimal excitation wavelength for fine-grained identification of refined oil pollutants on water surface based on laser-induced fluorescence
Authors: Xie Ming , Jia Yunpeng , Li Ying , Cai Xiaohua , Cao Kai
Published: July 2021

Laser-induced fluorescence (LIF) is an effective, all-weather oil spill identification method that has been widely applied for oil spill monitoring. However, the distinguishability on oil types is seldom considered while selecting excitation wavelength. This study is intended to find the optimal excitation wavelength for fine-grained classification of refined oil pollutants using LIF by comparing the distinguishability of fluorometric spectra under various excitation wavelengths on some typical types of refined-oil samples. The results show that the fluorometric spectra of oil samples significantly vary under different excitation wavelengths, and the four types of oil applied in this study are most likely to be distinguished under the excitation wavelengths of 395 nm and 420 nm. This study is expected to improve the ability of oil types identification using LIF method without increasing time or other cost, and also provides theoretical basis for the development of portable LIF devices for oil spill identification.
Hepatobiliary disease in XLMTM. A common comorbidity with potential impact on treatment strategies
Authors: D'Amico Adele , Longo Antonella , Fattori Fabiana , Tosi Michele , Bosco Luca , Testa Maria Beatrice Chiarini , Paglietti Giovanna , Cherchi Claudio , Carlesi Adelina , Mizzoni Irene , Bertini Enrico
Published: July 2021

BACKGROUND: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from pathogenic variants in the MTM1 gene. Affected male subjects typically present with severe hypotonia and respiratory distress at birth and they often require intensive supportive care. Long-term survivors are often non-ambulant, ventilator and feeding tube–dependent and they generally show additional organ manifestations, indicating that myotubularin does play a vital role in tissues other than muscle. For XLMTM several therapeutic strategies are under investigation.A recent clinical trial delivering the MTM1 gene using a recombinant AAV8 vector to XLMTM patients showed encouraging results in term of efficacy, but some concerns about safety arised due to three fatal events related to hepatotoxicity in boys that were exposed to the higher dose.RESULTS: We report prospective and retrospective clinical data of 12 XLMTM patients collected over a period of up to 10 years. In particular, we carried out a thorough review of the data about incidence and the course of hepatobiliary disease in our case series.CONCLUSIONS: We demonstrate that hepatobiliary disease represents a common comorbidity of XLMTM that seems irrespective to age and diseases severity. We recommend to carefully explore and monitor the hepatobiliary function in XLMTM patients. We believe that a better understanding of the pathogenic mechanisms that induce hepatobiliary damage is essential to understand the fatal events that may occur in the gene therapy program.