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Magnetic Hyperthermia in Cancer Treatment: The Role of Particle Size

Anusha Belakod

and 2 more

March 06, 2023
Anusha Belakod2 Vanuja Hosamani1, and Nivedita Awati11S. B. Arts and K. C. P. Science CollegeSmt.Bangaramma Sajjan Campus, Solapur Road Vijayapur-Karnataka-India2B.L.D.E.A’s V.P. Dr.P.G.Halakatti College of Engineering and TechnologyDepartment of Electronics and Communication EngineeringAshram Rd, Adarsh Nagar, Vijayapura, Karnataka 586103, India
Magnetic Contrast Agents in Magnetic Resonance Imaging: Current Applications and Futu...
Vanuja Hosamani

Vanuja Hosamani

and 2 more

March 06, 2023
Vanuja Hosamani1, Nivedita Awati1 and Anusha Belakod21S. B. Arts and K. C. P. Science CollegeSmt.Bangaramma Sajjan Campus, Solapur Road Vijayapur-Karnataka-India2B.L.D.E.A’s V.P. Dr.P.G.Halakatti College of Engineering and TechnologyDepartment of Electronics and Communication EngineeringAshram Rd, Adarsh Nagar, Vijayapura, Karnataka 586103, India
PUBLIC-PRIVATE PARTNERSHIPS (PPPS) IN UGANDA: IMPLICATIONS FOR PRACTICE AND POLICYMAK...
Thekiso  Molokwane
Alex  Nduhura

Thekiso Molokwane

and 4 more

February 11, 2023
While literature on PPPs globally can be found in abundance, in Africa, there is still limited literature on the contextualization, application, trends, inventory and account of existing and upcoming PPPs in Uganda. Based on a review of literature, this study reveals that there is heightened momentum for the adoption of PPPs compared to a decade ago. Notwithstanding, a deficiency exists in studies providing a countrywide review of PPP adoption over the last several decades in Uganda. To this end, this article investigates the origins of PPPs in Uganda, its legal and regulatory framework, and surveys existing and upcoming PPPs in the country. The study also provides a synthesis of how PPPs have performed so far---including their benefits and challenges. Finally, this study discusses the implications for practice and policy and outlines a research agenda for PPPs in Uganda.
Abstracts from the 28th Annual International Atrial Fibrillation Symposium, February...
E. Heist

E. Heist

February 11, 2023
A document by E. Heist. Click on the document to view its contents.
Roflumilast Ameliorates Diabetic Nephropathy in Rats Through Down-Regulation of JAK/S...
Sandip Patel
Priyal Patel

Sandip Patel

and 4 more

February 11, 2023
Diabetes nephropathy (DN) is one of the most prevalent microvascular complications of Diabetes Mellitus (DM). The present study was carried out to explore the role of roflumilast, a PDE4 inhibitor, as a potential treatment option for DN. The model was developed by feeding a high-fat diet for four weeks and following streptozotocin (30 mg/kg) injection intraperitoneally. The rats with >13.8 mmol/L blood glucose were included in the study. The diabetic rats were treated with roflumilast (0.25, 0.5, 1 mg/kg) and standard metformin (100 mg/kg) orally once a day for eight weeks. Roflumilast (1 mg/kg) remarkably improved renal damage, which was indicated by an increase in 16% albumin, a decrease in 5% serum creatinine, 12% BUN, 19% HbA1c, and 34% blood glucose. It also significantly improves the oxidative stress levels, which was indicated by a decrease in 18% MDA level and an increase in GSH, SOD, and catalase by 6%, 4%, and 5%, respectively. Roflumilast (1 mg/kg) decreased the HOMA-IR index by 28% and increased the pancreatic β-cells functioning by 30%. Moreover, significant improvement in histopathological abnormalities was observed in roflumilast treatment groups. Roflumilast treatment was shown to down-regulate the gene expression of TNF-α, NF-kB, MCP-1, fibronectin, and collagen IV, and upregulated the expression of the Nrf2 gene. The gene expression was significantly reduced by 2.1-fold, 2.3-fold, 2.5-fold, 2.7-fold, and 1.52-fold individually. The Nrf2 gene was upregulated by 1.43-fold. These results manifested that roflumilast alleviated renal injuries in DN rats, which might be associated with suppressing the JAK/STAT signaling pathway.
An Overview of Biomagnetic Separation Techniques: Advancements and Applications
Vanuja Hosamani

Vanuja Hosamani

and 2 more

March 06, 2023
Vanuja Hosamani1, Nivedita Awati1 and Anusha Belakod21S. B. Arts and K. C. P. Science CollegeSmt.Bangaramma Sajjan Campus, Solapur Road Vijayapur-Karnataka-India2B.L.D.E.A’s V.P. Dr.P.G.Halakatti College of Engineering and TechnologyDepartment of Electronics and Communication EngineeringAshram Rd, Adarsh Nagar, Vijayapura, Karnataka 586103, India
Real or fake? Verifying protein domain gain and loss events by an automated fact-chec...
Julie D. Thompson
Arnaud Kress

Julie D. Thompson

and 3 more

February 11, 2023
The comparison of protein domain architectures provides insight into the evolution and function of proteins. By comparing the domains of different proteins, scientists can identify common domains, classify proteins based on their domain architecture, and highlight proteins that have evolved differently in one or more species or clades. Such proteins are often thought to represent genetic novelty underlying unique adaptations. However, genome-wide identification of different protein domain architectures involves a complex error-prone pipeline that includes genome sequencing, prediction of gene exon/intron structures, and inference of protein sequences and domain annotations. Here we developed an automated fact-checking approach to distinguish true domain loss/gain events from false events caused by errors that occur during the annotation process. Using genome-wide ortholog sets and taking advantage of the high-quality human and Saccharomyces cerevisiae genome annotations, we analyzed the domain gain and loss events in the predicted proteomes of 9 non-human primates (NHP) and 20 non- S. cerevisiae fungi (NSF) as annotated in the Uniprot and Interpro databases. Our approach allowed us to quantify the impact of errors on estimates of protein domain gains and losses, and we show that domain losses are over-estimated ten-fold and three-fold in the NHP and NSF proteins respectively. This is in line with previous studies of gene-level losses, where sequencing issues or incorrect gene prediction led to genes being falsely inferred as absent. For the first time, to our knowledge, we show that domain gains are also over-estimated by three-fold and two-fold respectively in NHP and NSF proteins. Based on our more accurate estimates, we infer that true domain losses and gains in NHP with respect to humans are observed at similar rates, while domains gains in the more divergent NSF are observed twice as frequently as domain losses with respect to S. cerevisiae. This study highlights the need to critically examine the scientific validity of protein annotations, and represents a significant step toward scalable computational fact-checking methods that may one day mitigate the propagation of wrong information in protein databases.
Clinical characteristics and risk factors for tigecycline-induced pancreatitis in a t...
Wenjuan Fan
Qinghai Tan

Wenjuan Fan

and 6 more

January 20, 2023
Aims: To analyze the clinical characteristics and risk factors for tigecycline-induced pancreatitis (TIP) and evaluate the safety and efficiency of tigecycline use in non-TIP. Methods: A retrospective case-control study was conducted on adult and juvenile patients administered tigecycline for >3 days. The adults were classified as TIP, non-TIP (pancreatitis with other causes), and non-pancreatitis. Univariate analyses were performed to compare TIP and non-pancreatitis, and multivariate analysis was used to identify risk factors for TIP. The clinical characteristics of TIP and the safety and efficiency of tigecycline use in non-TIP were evaluated. Results: A total of 3910 patients (3823 adults and 87 juveniles) were enrolled. The adult patients comprised 21 TIP, 82 non-TIP, and 3720 non-pancreatitis. The TIP prevalences were 0.56% in adults and 1.15% in juveniles. The mean time from tigecycline use to symptom onset was 7.2 days, and all cases were mild pancreatitis. The mean time from tigecycline withdrawal to symptom relief was 3.6 days. The multivariate analysis identified comorbid renal insufficiency as an independent risk factor for TIP (odds ratio = 3.032). Among the 82 non-TIP patients, 81.7% had severe pancreatitis and 47.6% had necrotizing pancreatitis. The modified computed tomography severity score after tigecycline use was similar to that before tigecycline use, but the pancreatic enzymes and infection indices were significantly decreased. Conclusion: The prevalence of TIP was low. Comorbid renal insufficiency was as an independent risk factor for TIP. Tigecycline is safe and efficient for treatment of pancreatitis, especially necrotizing pancreatitis, with intra-abdominal infection
Identification of tyrphostin AG879 and A9 inhibiting replication of Chikungunya virus...
Hailin Tang
Yanhua He

Hailin Tang

and 8 more

February 11, 2023
Chikungunya virus (CHIKV) is a globally public health threat. There are currently no medications available to treat CHIKV infection. High-throughput screening of 419 kinase inhibitors was performed based on the cytopathic effect method, and six kinase inhibitors with reduced cytopathic effects, including tyrphostin AG879 (AG879), tyrphostin 9 (A9), sorafenib, sorafenib tosylate, regorafenib, and TAK-632, were identified. The anti-CHIKV activities of two receptor tyrosine kinase inhibitors, AG879 and A9, that have not been previously reported, were selected for further evaluation. The results indicated that 50% cytotoxic concentration (CC 50) of AG879 and A9 in Vero cells were greater that than 30 μM and 6.50 μM, respectively and 50% effective concentration (EC 50) were 0.84 μM and 0.36 μM, respectively. The time-of-addition and time-of-removal assays illustrated that both AG879 and A9 function in the middle stage of CHIKV life cycle. Further, AG879 and A9 do not affect viral attachment; however, they inhibit viral RNA replication, and exhibit antiviral activity against CHIKV Eastern/Central/South African and Asian strains, Ross River virus and Sindbis virus in vitro.
COVID-19 and Retinal Layer Thickness: A bidirectional Mendelian Randomization Study
lili Lang
Kun Zhao

lili Lang

and 12 more

February 11, 2023
Observational studies have reported that COVID-19 is associated with alterations in retinal layer thickness, including changes in the ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL). However, observational studies are susceptible to confounding factors and reverse causality. Therefore, we assessed the direction and strength of the causal relationship between COVID-19 patient phenotypes (susceptibility, hospitalization, and severity) and GCIPL and RNFL thicknesses using a bidirectional two-sample Mendelian randomization (MR) design. The inverse-variance weighted (IVW) method is the primary approach used to estimate causal effects. MR Egger, weighted median, weighted mode, MR Egger (bootstrap), and penalized weighted median methods were applied. In addition, we performed sensitivity analyses using RadialMR, MRPRESSO, MR Egger regression, Cochran’s Q statistic, and Leave-one-out analysis. Forward MR analysis revealed that genetically identified COVID-19 susceptibility significantly increased the risk of GCIPL thickness (OR: 2.428, 95% confidence interval[CI]:1.493-3.947, PIVW=3.579 ×10 -4) and RNFL thickness (OR: 1.735,95%CI:1.198-2.513, PIVW=3.580×10 -3). The results after excluding MRPRESSO and RadialMR to identify outliers and SNPs associated with confounding factors showed RNFL thickness(OR:1.800,95%CI: 1.192-2.717, PIVW=5.147×10 -3).Reverse MR analysis did not indicate a significant causal association between GCIPL and RNFL thicknesses and COVID-19 phenotypes. In conclusion, the host genetic liability to COVID-19 susceptibility was causally associated with increased GCIPL and RNFL thicknesses. Documenting this association increases our understanding of the pathophysiological mechanisms underlying COVID-19 susceptibility in retinopathy.
Evaluating stony coral tissue loss disease intervention success through whole-transcr...
Michael Studivan
Ryan Eckert

Michael Studivan

and 5 more

February 11, 2023
Stony coral tissue loss disease (SCTLD) remains an unprecedented disease outbreak due to its high mortality rate and rapid spread throughout Florida’s Coral Reef and wider Caribbean. A collaborative effort is underway to evaluate disease intervention strategies that mitigate the spread of SCTLD across coral colonies and reefs. We conducted an in-situ experiment in Southeast Florida to assess molecular responses among SCTLD-affected Montastraea cavernosa pre- and post-application of the most widely-used intervention method, CoreRx Base 2B with amoxicillin. Through Tag-Seq gene expression profiling of apparently healthy, diseased, and treated corals, we identified modulation of metabolomic and immune pathways following antibiotic treatment. In a complementary ex-situ disease challenge experiment, we exposed nursery-cultured M. cavernosa and Orbicella faveolata fragments to SCTLD-affected donor corals to compare transcriptomic profiles among clonal individuals from unexposed controls, those exposed and displaying disease signs, and corals exposed and not displaying disease signs. Suppression of metabolic functional groups and activation of stress gene pathways as a result of SCTLD exposure were apparent in both species. Amoxicillin treatment led to a ‘reversal’ of the majority of gene pathways implicated in disease response, suggesting potential recovery of corals following antibiotic application. In addition to increasing our understanding of molecular responses to SCTLD, we provide resource managers with transcriptomic evidence that disease interventions with antibiotics appear to be successful and may help to modulate coral immune responses to SCTLD. These results contribute to feasibility assessments of intervention efforts following disease outbreaks and improved predictions of coral reef health in Southeast Florida.
Seasonal Dietary Shifts Alter the Gut Microbiota of a Frugivorous Lizard Teratoscincu...
Lei Shi
Weizhen Gao

Lei Shi

and 2 more

February 11, 2023
Seasonal dietary shifts of animals are important ecological adaptation strategies. An increasing number of studies have shown that seasonal dietary shifts can influence or even determine the composition of gut microbiota. The turpan wonder gecko Teratoscincus roborowskii lives in extreme desert environments, which have flexible dietary shift to fruit-eating in warm seasons. But the impact of such shifts on gut microbiota is poorly understood. Here, 16SrRNA sequencing and LC-MS metabolomics we used to examine the changes of gut microbiota composition and metabolic pattern of T. roborowskii. The results demonstrated that the gut microbes of T. roborowskii had significant seasonal changes, the diversity and abundance of gut microbiota in autumn were higher than those of in spring. Firmicutes, Bacteroidetes and Proteobacteria were the core gut microbes of T. roborowskii. Verrucomicrobia and Proteobacteria exhibit dynamic pattern of ebb and flow between spring and autumn.The composition and structure of gut microbes in different seasons perform specific metabolic functions, and this change may be an important adaptation for T. roborowskii to cope with dietary shifts and improve energy acquisition. Our study will provide a theoretical basis for exploring the adaptive evolution to special frugivorous behavior of the T. roborowskii, which is an important supplement to the study of the gut microbiology of desert lizards.
Robust Guidance and Control with Collision Avoidance for Fully Actuated Multirotor Ae...
Jorge A. Ricardo Jr
D.A. Santos

Jorge A. Ricardo

and 1 more

February 11, 2023
This paper is concerned with the robust guidance and control of fully actuated multirotor aerial vehicles in the presence of moving obstacles, linear velocity constraints, and matched model uncertainties and disturbances. We address this problem by adopting a standard hierarchical flight control architecture consisting of a supervisory outer-loop guidance module and an inner-loop stabilizing control one. The position and attitude control laws are designed using a proportional-derivative approach combined with a sliding mode disturbance observer. On the other hand, to design the guidance, we propose a robust version of the continuous-control-obstacles method, which derives from the velocity obstacles one, to drive the vehicle to a target pose while avoiding collision with moving obstacles and violation of linear velocity constraints. The overall method have been numerically evaluated and shown to be effective in providing satisfactory tracking performance, collision-free guidance, and satisfaction of linear velocity constraints.
A pile of pipelines: an overview of the bioinformatics software for metabarcoding dat...
Ali Hakimzadeh
Alejandro Abdala Asbun

Ali Hakimzadeh

and 25 more

February 11, 2023
Environmental DNA (eDNA) metabarcoding has gained growing attention as a strategy for monitoring biodiversity in ecology. However, taxa identifications produced through metabarcoding require sophisticated processing of high-throughput sequencing data from taxonomically informative DNA barcodes. Various sets of universal and taxon-specific primers have been developed, extending the usability of metabarcoding across archaea, bacteria, and eukaryotes. Accordingly, a multitude of metabarcoding data analysis tools and pipelines have also been developed. Often, several developed workflows are designed to process the same amplicon sequencing data, making it somewhat puzzling to choose one amongst the plethora of existing pipelines. However, each pipeline has its own specific philosophy, strengths, and limitations, which should be considered depending on the aims of any specific study, as well as the bioinformatics expertise of the user. In this review, we outline the input data requirements, supported operating systems, and particular attributes of thirty-one amplicon processing pipelines with the goal of helping users to select a pipeline for their metabarcoding projects.
Tensile and Fatigue Behaviors of Additively Manufactured AlSi10Mg: Effect of Solution...
Nima Shamsaei
Shaharyar Baig

Nima Shamsaei

and 3 more

February 11, 2023
The effects of various heat treatments on the microstructure and mechanical properties of laser beam powder bed fused AlSi10Mg were investigated. Specimens were solutionized at three different temperatures of 425, 475 and 525 °C followed by natural aging (T4) prior to microstructural and mechanical characterization. In addition, the effect of aging was studied by artificially aging (i.e., T7) some of the solutionized specimens at 165 °C. Solutionizing at all temperatures was observed to fully dissolve the additive manufacturing (AM) induced dendritic microstructure, leaving bulky Si and needle-shaped β-AlFeSi precipitates in the grain interiors and boundaries. Tensile results revealed that T4 specimens exhibited more ductility, while T7 specimens showed substantially higher strengths with slightly reduced ductility. Interestingly, no significant effect of heat treatment on strain-life fatigue behavior was observed. Fractography found the Si-particles to be responsible for tensile fracture, while AM volumetric defects were the main initiators of fatigue cracks.
ASSESSMENT OF MATERNAL ABDOMINAL SUBCUTANEOUS FAT THICKNESS (SFT) AS AN INDEPENDENT P...
NILA SURENDRAN
PRATIKSHA GUPTA

NILA SURENDRAN

and 3 more

February 11, 2023
Introduction: Obese pregnant women are at increased risk for a variety of maternal and perinatal complications. The maternal risks related to obesity include Gestational Diabetes mellitus, Preeclampsia, increased caesarian sections. The fetus is at risk of stillbirth, preterm birth and congenital anomalies.This study focuses on the use of Maternal abdominal subcutaneous fat thickness (SFT) as a surrogate measure for central obesity as measured by ultrasound, and determining its efficacy compared to BMI in predicting obesity related pregnancy complications. Objective: To measure mid-trimester SFT in antenatal women and establish SFT as an independent predictor of obesity related adverse pregnancy outcomes Methods: This was a prospective cohort study. 150 pregnant women between 20-40 years of age were recruited. Demographic data of each participant was collected from the OPD. USG for abdominal subcutaneous fat thickness (SFT) was done at 18-22 wks period of gestation.The participants were followed up to labour. Adverse pregnancy outcomes and their correlation with the SFT measured was studied. Results: There was significant positive correlation between BMI and SFT (r=0.591, p<0.001) .A positive correlation was noticed between BMI and adverse pregnancy outcomes such as PIH, GDM , preterm birth , postdatism and NICU admissions.SFT independently showed a positive correlation with the above parameters. The mean SFT among women without PIH was 11.45 mm, and with PIH was 16.48 mm[p <0.001].Mean SFT were 11.68mm and 16.24 mm among the ladies without and with GDM respectively[p<0.001]. The mean SFT for term pregnancies was 12.06 mm whereas the mean SFT for preterm births was 14.21 showing positive correlation between SFT and preterm birth. SFT also showed positive correlation with need for NICU admission for neonates [ SFT avg being 11.72mm and 14.94 mm in the 2 groups]. A comparative analysis was done between BMI and SFT regarding their correlation to the various outcomes. SFT showed higher correlation coefficients for these variables than BMI, with lower p values suggesting more statistical significance. Conclusion: BMI showed a positive correlation with adverse pregnancy outcomes in mother as well as fetus, SFT showed greater and more statistically significant correlation for adverse outcomes. Thus it was concluded that SFT is a better independent predictor of obesity related adverse pregnancy outcomes.
MicroRNA-21 promotes hypopharyngeal cancer induced transition of bone marrow mesenchy...
shi fang he
hao wang

shi fang he

and 5 more

February 11, 2023
Abstract Objective: At present, human bone marrow mesenchymal stem cells (hBMSCs) used as target vectors for hypopharyngeal cancer is a new therapeutic direction of great potential. However, hBMSCs would be transmitted into cancer-associated fibroblasts(CAFs) under the induction of hypopharyngeal cancer. Here, we aimed to determine whether microRNA-21(miR-21) in exosomes from FaDu cells would play a role in hypopharyngeal cancer induced transition of hBMSCs to CAFs. Methods: qRT-PCR and western blot were employed to investigate expression level of miR-21 in hypopharyngeal cancer patient samples and FaDu cells. The exosomes were collected from FaDu cells then isolated and identified. Cell morphological changes were observed by inverted phase contrast microscope. Expression level of CAF-related proteins, includingα-SMA and FAP, were assessed by qRT-PCR and western blot. Cell cycle of hBMSCs were determined by flow cytometry. Results: MiR-21 expression level was up-regulated in hypopharyngeal cancer tissue and FaDu cells. Exosomes from FaDu cells promoted CAFs-like features of hBMSCs, including up-regulation of α-SMA and FAP and cell morphological changes. Proportions of hMBSCs in G1 phase significantly decreased, while proportions of hMBSCs in G2 phase significantly decreased at the presence of exosomes from FaDu cells. What’s more, miR-21 knock-out in FaDu cells suppressed transition of bone marrow mesenchymal stem cells to cancer-associated fibroblasts and reversed the cell cycle change. Conclusions: Our data showed that miR-21 promotes hypopharyngeal cancer induced transition of bone marrow mesenchymal stem cells to cancer-associated fibroblasts. Keywords: Hypopharyngeal cancer, Bone marrow mesenchymal stem cells, Cancer-associated fibroblasts, MicroRNA-21, Exosomes
Hospital-Acquired Venous Thromboembolism in Children with Sickle Cell Disease
Shreya Agarwal
Kayla L. Foster

Shreya Agarwal

and 7 more

February 11, 2023
Objectives: Sickle cell disease (SCD) is well recognized as a hypercoagulable state, however venous thromboembolism (VTE) risk factors in children remain largely unknown. In this study, we aim to describe the clinical characteristics, outcomes and recurrence of hospital acquired VTE in patients younger than 21 years of age. Study Design/Methods: Data were extracted from electronic medical records over a 10-year period (2011-2021). Data regarding sickle cell genotype, demographics, reason for admission, location of thrombus, presence of central venous catheter (CVC), intensive care unit (ICU) admission, presence of thrombophilia risk factors, resolution of VTE, mortality, and bleeding outcomes on anticoagulation were collected. Recurrence of VTE at 1 and 5 years was assessed. Descriptive statistics were used as indicated. Results: We identified a total of 21 VTE events over the ten-year study period. Six of these events occurred in those younger than 12 years of age. Fifteen (71%) VTE events occurred in the HbSS or HbSβThal 0 genotypes compared to 8 (29%) in HbSC. Eleven (52%) patients were admitted with acute chest syndrome (ACS). Most VTE events were associated with ICU admissions (n=13, 62%) and presence of central venous catheter (n=12, 57%). Major bleeding on anticoagulation occurred in 10%.All patients had resolution of index VTE at 12 weeks. Recurrence rate for VTE at 5 years was 13%. One patient died from the VTE event. Conclusions: Our study highlights that VTE can complicate SCD in children and young adults. Hospital acquired VTE were most associated with ICU admission, CVC, and ACS, but larger studies are indicated to validate our findings.
Immunogenicity and in vivo protective effects of recombinant nucleocapsid-based SARS-...
Sevastyan O. Rabdano
Ellina Ruzanova

Sevastyan O. Rabdano

and 20 more

February 11, 2023
Background The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, S and RBD from SARS-CoV-2 variants of concerns show considerable sequence variations and repeated injections for boosting specific immunity are necessary. Aim of this study was to develop and characterize a SARS-CoV-2 vaccine targeting the highly conserved nucleocapsid (N) protein. Methods Recombinant N protein was expressed in Escherichia coli, purified to homogeneity by chromatography and characterized by SDS-PAGE, immunoblotting, mass spectrometry, dynamic light scattering and differential scanning calorimetry. The N protein vaccine was obtained by formulation of recombinant N as squalane-based emulsion and used to immunize Balb/c mice, NOD scid gamma (NSG) mice engrafted with human PBMC, rabbits and marmoset monkeys to study safety as well as antibody and cellular immunity using ELISA for antibodies, measurement of N-specific Th1 and Th2 cytokine secretion and carboxyfluorescein succinimidyl ester (CFSE) dilution assays for CD4 + and CD8 + T cell responses. The protective effect of the vaccine was studied in SARS-CoV-2-infected Syrian hamsters. Results Immunization of mice, rabbits and Syrian hamsters with the recombinant N protein-based vaccine formulated as squalane-based emulsion (Convacell®) induced sustainable N-specific IgG responses and a N-specific mixed Th1/Th2 cytokine response. In marmoset monkeys a N-specific CD4 + as well as CD8 + T cell response was observed. Vaccinated and then infected Syrian hamsters showed reduced lung histopathology, reduced virus was detected in lung tissue, lung weight relative to the body was not increased after challenge and body weight was regained faster than in non-vaccinated animals. Repeated dose toxicity studies in mice and rabbits showed that Convacell® was well tolerated and safe. Conclusions Convacell® induced a SARS-CoV-2-specific protective immune response in Syrian hamsters. It is a new vaccine targeting the nucleocapsid protein of SARS-CoV-2 and thus may augment the armamentarium of vaccines for COVID-19.
Does allergen immunotherapy impact the susceptibility and severity of COVID-19?
Ya-dong Gao
Wang Yin

Ya-dong Gao

and 8 more

February 11, 2023
Does allergen immunotherapy impact the susceptibility and severity of COVID-19?To the editor,Allergic asthma (AA) and allergic rhinitis (AR) might be protective against SRAS-CoV-2 infection and progress to severe disease of coronavirus disease 2019 (COVID-19)1. COVID-19 vaccination was safe and well tolerated in patients receiving allergen immunotherapy (AIT)2,3, and the adherence to subcutaneous immunotherapy (SCIT) was not affected during COVID-19 pandemic4. Whether AIT impacts the susceptibility and severity of COVID-19 is still unknown. In December 2022, China ended its “Zero-COVID” policy and more than 70% of the population got infected with SARS-CoV-2 within one month. We conducted an online WeChat questionnaire between 3rd Jan and 10th Jan 2023 to investigate the infection and hospitalization rates and symptom duration of COVID-19 in AR and/or AA patients receiving SCIT with house-dust mite (HDM) extract in China. The relatives of these SCIT patients, who did not receive SCIT, were also surveyed and divided into two groups: allergy group and non-allergy group. The study was approved by the Medical Ethic Committee of Tongji Hospital of Huazhong University of Science and Technology (Approval Number: TJ-IRB20230204). The informed consent was waived since the voluntary nature of responding to the questionnaire.A total of 1246 SCIT patients and 1078 of their relatives (370 allergic and 708 non-allergic) responded to the questionnaire. SCIT patients were generally younger than allergy and non-allergy group. The proportion of male were higher in SCIT patients compared to allergy and nonallergy group. 82.4% of the SCIT patients were diagnosed with AR, only 5.3% were asthmatics, and the rest were AR with asthma (12.3%). The average duration of AIT was 1.4 ± 1.3 years. SCIT patients had a lower proportion of both at least one dose and completed three doses of COVID-19 vaccines when compared to allergy and non-allergy group (P = 0.000) (Table S1).Most respondents had been infected with SARS-CoV-2. SCIT was associated with a lower infection rate (78.6%) compared to allergy (81.4%) and non-allergy group (81.5%) (P < 0.0001) (Table S2). The duration of COVID-19 symptoms was shorter in SCIT group (5.7 ± 4.0 days) compared to allergy group (7.0 ± 4.5 days, P = 0.000) and non-allergy group (7.7 ± 4.4 days, P = 0.000) (Table S2). The hospitalization rate was 0.4% in SCIT group, which was significantly lower than that in non-allergy group (1.73%) (P = 0.008).We then performed a two-to-one matching of SCIT group with allergy and non-allergy group to adjust age and sex difference between the three groups. The infection rate was still slightly lower in SCIT group compared to allergy and non-allergy group (78.3% vs. 81.9%, 81.4%). The duration of symptoms and hospitalization rate did not show much difference among three groups after adjusting (Table 1).Moreover, we found that patients receiving 6-12 months SCIT had a shorter duration of symptoms caused by SARS-CoV-2 infection compared to those in SCIT course < 6 months and those receiving SCIT > 12 months, even though only one fourth of them completed three doses of COVID-19 vaccines (Table 2). shorter duration of symptoms. The duration of SCIT has no impacts on both infection and hospitalization rate (Table 2).A lower expression of angiotensin converting enzyme 2 (ACE2) in airway epithelia5 may contribute to the protecting effect of type 2 inflammation against SARS-CoV-2 infection and severe COVID-196. This study revealed an almost same infection rates in allergic and non-allergic individuals after adjusting age and sex, suggesting ACE2 expression level had no effect on Omicron infection. More importantly, SCIT patients has a slightly lower infection rate compared to allergy and non-allergy groups, suggesting that repeated allergen stimulation during SCIT in HDM-sensitized individuals may elicit a strong T cell response with ability to cross-react with SARS-CoV-2, as demonstrated in silico analysis7, which may protect SCIT individuals from infection. The proportion with three doses COVID-19 vaccines were significantly lower in SCIT patients, albeit SCIT was reported to dampen immune responses to SASR-CoV-2 vaccines8, the infection rate of SARS-CoV-2 was still lower in SCIT patients. We also observed a shorter duration of symptoms due to SARS-CoV-2 infection in those receiving 6-12 months HDM-SCIT compared to those receiving < 6 months and > 12 months HDM-SCIT, consistent with previous studies showing the immune responses to SCIT reach a peak during 6-12 months9. EAACI stated recently in a position paper that AIT and COVID-19 immune responses do not seem to interfere negatively, and AIT patients might even benefit from AIT10. Thus, our results for the first time demonstrated that SCIT may have a protective effect against SARS-CoV-2 infection, especially immediately after completing the dose-escalation phase.KEYWORDS: Allergic rhinitis; Allergen immunotherapy; SARS-CoV-2; Coronavirus disease 2019; InfectionCONFLICT OF INTEREST: The authors declare that they have no conflicts of interest.Author Contributions: YDG, RFZ and YDC conceived the study, YW and HuC designed the questionnaire and collected data. XD, HaC, YQY and HLL dispensed the questionnaire and monitored the survey. RFZ analyzed the data and YDG wrote the manuscript. All authors contributed to the final review.Acknowledgment : We thank all members of Hubei Provincial Doctors Association Allergic Physicians Branch for their help in the recruitment of patients and relatives into this study.Funding information: none.Yin Wang1Huan Chen2Xiang Dong3Hao Chen1Hui-ling Liang3Ya-qi Yang1Yan-dan Chen2Rong-fei Zhu1Ya-dong Gao3Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Otolaryngology-Head and Neck Surgery and Allergy, Central Hospital of Huangshi City, Huangshi, ChinaDepartment of Allergology, Zhongnan Hospital of Wuhan University, Wuhan China
Phenology of tropical lower montane forests in southern highlands of Vietnam: leafing...
Ai Nagahama
Shuichiro Tagane

Ai Nagahama

and 12 more

February 11, 2023
The premise of the study Though phenological studies in montane forests are important, particularly in tropical Asia where primitive angiosperms are found, the phenology in these forests is still poorly understood. To characterize the phenological patterns and reveal the relationships between meteorological factors and phenology, we observed the leafing, flowering, and fruiting phenology in the tropical montane forests of Vietnam. Methods We observed the leafing, flowering, and fruiting phenology of 91 species every three months in five plots (elev. 1460–1920 m) in Bidoup-Nui Ba National Park, Vietnam, and analyzed how the number of species that were leafing, flowering, or fruiting varied in relation to precipitation, temperature, or daylength. Key results The leafing phenology showed a peak at the beginning of the wet season (April) and was significantly influenced by all of day length, precipitation, and temperature. The flowering phenology did not show any distinct peaks and was influenced by day length and precipitation. The fruiting phenology showed a low peak from the wet season (July) to the beginning of the dry season (December) and was not significantly influenced by any of the meteorological factors. Main conclusion The community-wide phenological patterns of leafing, flowering, and fruiting in the tropical montane forest of Bidoup-Nui Ba are unique among the tropical forests of East and Southeast Asia. In particular, our observation suggests that masting in tropical montane forests may be an ancestral state of both general flowering in tropical rainforests and masting found in temperate forests in East and Southeast Asia.
Salivary cortisol concentration and perceived stress measure in response to acute com...
Noa Rofe
Yuval Shay Brosh

Noa Rofe

and 5 more

February 10, 2023
Chronotype determines morningness-eveningness preference over a 24-h period. Significant data indicates meaningful differences between evening types (ET) and morning types (MT) in behavior, personality traits, health and well-being. The aim of this study was to investigate cortisol response and subjective perceived stress of MT and ET individuals in response to an acute natural stressor. Twenty six definite MT and twenty six definite ET college students were recruited for this study. Participants were instructed to evaluate their perceived subjective stress and to provide saliva samples for cortisol levels at four different time points: Morning of regular school day, morning immediately before a final exam, afternoon of a regular school day and afternoon immediately before a final exam. For general mood assessment, the participants were also asked to fill out the Positive and Negative Affect Schedule (PANAS) questionnaire. The most outstanding finding of this study was the blunting of cortisol increase in response to acute stress in the morning in the ET group: Salivary cortisol was higher before a final exam only in MT but not in ET. However, no differences between the groups were found in the subjective stress measure. In the PANAS scale, ET showed lower positive affect, and a trend towards a higher negative affect. Overall, our results suggest dysregulation of the HPA axis in ET individuals, possibly due to their daily struggle to function in a morning-oriented society. These results further highlight the challenges faced by ET individuals and raise the question of possible interventions to assist them.
Association between Elevated TNF-α Levels and Severe Malaria
Khalid Abdelsamea Mohamedahmed

Khalid Abdelsamea Mohamedahmed

February 13, 2023
Khalid Abdelsamea Mohamedahmed1,2*1Department of Hematology and Immunohematology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan.2Department of Hematology and Immunology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan.*Corresponding author: Khalid Abdelsamea Mohamedahmed, Department of Hematology and Department of Immunology, Faculty of Medical Laboratory Science, University of Gezira, Wad Medani, Sudan. ORCID No: 0000-0001-7084-6106, Tel: +249114660424, Email: khalid.gu89@gmail.comTNF-α is predominantly produced by γδ T cells and CD14+ monocytes during immune responses to malaria and helps in the control of parasitemia. TNF-α and IFN-γ act synergistically to optimize nitric oxide production which in turn leads to parasite killing. Also, TNF-α enhances human neutrophil killing of the plasmodium parasite (1).TNF-α is play important role in the pathogenesis of multiple inflammatory disorders, autoimmune diseases, and infectious diseases including malaria (2-3). At low levels, TNF-α is believed to augment parasite killing by macrophage activation and subsequent release of cytokines, whereas high TNF-α level has been associated with severe manifestations. Individual variation in TNF-α production mainly by macrophages and NK cells is likely to influence severe disease manifestation (2). Severe malarial infection is associated with the rupture of parasitized red blood cells releasing malaria pigment and other soluble antigens and toxins that stimulate the overproduction of TNF-α in human monocytes and may also stimulate intense T helper type 1-like response locally, in tissues of vital organs which result in upregulation of expression of endothelial adhesion molecules such as ICAM-1 or other adhesion molecules. This in turn leads to increased and enhanced parasite adherence and sequestration of parasitized red cells that leads to subsequent microvascular obstruction, decreasing oxygen delivery, and/or possibly the release of NO from the endothelium which may ultimately contribute to the pathogenesis (4). Also, elevated TNF-α levels stimulated phagocytosis and thereby enhanced clearance of parasitized erythrocytes but the prolonged response was associated with severe disease syndromes. TNF-α has been shown to increase the severity of inflammation by inducing cyclooxygenase (COX)-2 and subsequently generating effector molecules, such as prostaglandins. Many of the signs and symptoms and complications associated with malaria be linked to TNF-α (4-5). TNF-α is considered to be important for parasite destruction and elimination, as well as in the development of fever and other clinical symptoms, and it also contributes to the development of severe malaria disease (6).TNF-α could affect the outcome of malaria in several ways. TNF-α promotes fever, which may suppress parasite growth, and it also induces the expression of adhesion molecules and proinflammatory molecules (7). Lethal CM has been associated with a high level of TNF-α in serum (7). The TNF-α overproduction in malaria can contribute to reduced red cell production and anemia through suppression of bone marrow erythropoiesis and dyserythropoiesis (1, 8). The overproduction of TNF-α could be associated with more rapid resolution of fever and parasite clearance but predisposes to severe pathology of disease (9).Severe malaria is associated with several genes; including TNF-α gene polymorphisms. TNF-α is thought to be a critical factor in malaria pathogenesis, the control of parasitemia, and increased susceptibility to severe malaria (2, 10). High TNF-α plasma levels have been associated with increased susceptibility to severe malaria (2, 10). The variation in the TNF-α gene phenotypes related to malaria infection and severe disease (10).In conclusion, Tumor necrosis factor (TNF-α) is a common proinflammatory cytokine. It plays a central role in malaria pathogenicity either in the cure or complication of malaria. Their high level is associated with the severe outcome of malaria.
Executive Functioning and Acute Stress Responses: The Role of Cognitive Appraisals, R...
Elise Grimm
Stefan Agrigoroaei

Elise Grimm

and 1 more

February 10, 2023
Exposure to stress can have significant, negative consequences on long-term health. Among potentially modifiable targets for promoting more adaptive stress responses, executive functioning has emerged as a promising candidate. These functions may be involved in limiting excessive stress reactivity when exposed to an acute stressor, while also promoting faster recovery (i.e., return to baseline). Fewer studies have been conducted to date on the role of executive functioning in acute stress – especially with a focus on its distinct facets (e.g., inhibition, flexibility, working memory, and updating). Moreover, there is a need for research focused on potential cognitive and behavioral mediators explaining the relationship between executive functioning and stress responses. Thus, the current study sought to examine the extent to which executive functioning facets may play a beneficial role in acute stress reactivity and recovery. Furthermore, we will examine the mediational role of cognitive appraisals, repetitive negative thinking, and emotion regulation. The findings may shed light on existing cognition-stress pathways that promote more adaptive acute stress responses.
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