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Abstract SUMOylation regulates numerous cellular stress responses, yet targets in the apoptotic machinery remain elusive. We show that a single, DNA damage-induced monoSUMOylation event controls PIDDosome (PIDD1/RAIDD/caspase-2) formation and apoptotic death in response to unresolved DNA interstrand crosslinks (ICLs). SUMO-1 conjugation occurs on conserved K879 in the PIDD1 death domain (DD); is catalyzed by PIAS1 and countered by SENP3; and is triggered by ATR phosphorylation of neighboring T788 in the PIDD1 DD, which enables PIAS1 docking. Phospho/SUMO-PIDD1 proteins are captured by nucleolar RAIDD monomers via a SUMO-interacting motif (SIM) in the RAIDD DD, thus compartmentalizing nascent PIDDosomes for caspase-2 recruitment. Denying SUMOylation or the SUMO-SIM interaction spares the onset of PIDDosome assembly but blocks its completion, thus eliminating the apoptotic response to ICL repair failure. Conversely, removal of SENP3 forces apoptosis, even in cells with tolerable ICL levels. SUMO-mediated PIDDosome control is also seen in response to DNA breaks but not supernumerary centrosomes. These results illuminate PIDDosome formation in space and time and identify a direct role for SUMOylation in the assembly of a major pro-apoptotic device.

Abstract This work focuses on the prediction and comparison of the fatigue life of topologically optimized pads in an externally adjustable fluid film (EAFF) bearing. It integrates one-way/two-way fluid–structure interaction analysis, topological optimization (TO), and design modifications of the pad of an externally adjustable fluid film bearing. The major goal is to create an optimum pad design that minimizes weight and maintains structural integrity, and then to predict and compare the fatigue life of these alternative designs. The outcomes of the present study are as follows: (i) Two-way FSI results show a decrease of 65.64% in hydrodynamic fluid film pressure when compared to one-way FSI results because they take into account modifications in the fluid region's geometry caused by pad deformation; (ii) even though the maximum pad deformation in optimized pad geometry (Type-4) resulting from oil film pressure is relatively small (0.0036551 mm), the influence of pad deformation on the fluid domain due to hydrodynamic fluid film pressure cannot be understated; and (iii) when comparing the TO technique's results with fatigue life results, four elongated holes in the radial direction (Type-4) are most appropriate.

Background A holistic architectural education is the culmination of learning knowledge, skills, attitudes, and values, which eventually reflects in the quality of graduates. Even though different schools of thought have made various kinds of qualitative contributions towards the evolution of architectural education in India, it has largely been dominated by the quantitative and technical aspects of its regulating framework. Architects engage with the demanding contradictions between responsibilities of an ethical nature, the dynamic challenges of practice, and the intricacies of architectural imagination. The aesthetical and imaginative foundations of the field make it incumbent upon the architects to possess a balance of ecumenical proficiencies for accountability and personalization. The purpose of the study is to identify relevant attributes of Competency Based Education (CBE) that can be adopted for architectural education in India. Methods This research follows a narrative review approach and a descriptive-analytic method to broadly understand the attributes of CBE and its potential relevance to architectural education in India. 323 articles were searched on various search strings based on their relevance to the inquiry. 76 documents written in English language were included and appraised through the Scale of the Assessment for Narrative Review Articles (SANRA) tool to avoid any risk of bias. The PRISMA 2020 checklist and flow diagram has been used to report the findings of this narrative review. Result The study identifies eight critical parameters of CBE with respect to its definitions, origins, transitions, regulatory environment, characteristics, approaches and implications on teaching-learning, frameworks and models of assessment; and challenges, which makes a case for the relevance of CBE for architectural education in India, which hasn’t been explored yet. Conclusion The broader expectations of ‘being competent’ can be addressed through a conscious adoption of strategies of relevant attributes of CBE which can encourage building attitudes and temperament for life-long learning.

Abstract Decaprenylphosphoryl-β-D-ribose-2′-epimerase (DprE1), a crucial enzyme in the process of arabinogalactan and lipoarabinomannan biosynthesis, has become the target of choice for anti-TB drug discovery in the recent past. The current study aims to find the potential DprE1 inhibitors through in-silico approaches. Here, we built the pharmacophore and 3D-QSAR model using the reported 40 azaindole derivatives of DprE1 inhibitors. The best pharmacophore hypothesis (ADRRR_1) was employed for the virtual screening of the chEMBL database. To identify prospective hits, molecules with good phase scores (> 2.000) were further evaluated by molecular docking studies for their ability to bind to the DprE1 enzyme (PDB: 4KW5). Based on their binding affinities (

Abstract Plants get exposed to diseases, insects and fungus. This causes heavy damages to crop resulting in various leaves diseases. Leaf diseases can be diagnosed at an early stage with the aid of a smart computer vision system and timely disease prevention can be targeted. Black pepper is a medicinal plant that is extensively used in Ayurvedic medicine because of its therapeutic properties. The proposed work represents an intelligent transfer learning technique through state-of-the-art deep learning implementation using convolutional neural network to predict the presence of prominent diseases in black pepper leaves. The ImageNet dataset available online is used for training deep neural network. Later, this trained network is utilized for the prediction of the newly developed black pepper leaf image dataset. The developed data set consist of real time leaf images, which are candidly taken from the fields and annotated under supervision of an expert. The leaf diseases considered are anthracnose, slow wilt, early stage phytophthora, phytophthora and yellowing. The hyperparameters chosen for tuning in to deep learning models are initial learning rates, optimization algorithm, image batches, epochs, validation and training data, etc. The accuracy obtained with 0.001 learning rate ranges from 99.1 to 99.7% for the Inception V3, GoogleNet, SqueezeNet and Resnet18 models. Proposed Resnet18 model outperforms all model with 99.67% accuracy. The resulting validation accuracy obtained using these models is high and the validation loss is low. This work represents improvement in agriculture and a cutting edge deep neural network method for early stage leaf disease identification and prediction. This is an approach using a deep learning network to predict early stage black pepper leaf diseases.

Abstract Fiber Metal Laminates (FMLs) have garnered considerable attention and are increasingly being utilized in the development of protective armors for explosion and ballistic scenarios. While most research has focused on assessing the response of FMLs to single impacts, real battlefield situations often require shielding structures to endure multiple impacts. Thus, this study revolves around the creation of hybrid FMLs designed for shock shielding purposes. The primary focus is on how these laminates withstand repetitive impacts from high-intensity shock waves, aiming to pinpoint the optimal sequence that offers the highest resistance against multiple shock impacts. To establish effective shielding, a multi-layered FML configuration is employed. This configuration incorporates AA6061-T6 facing plates, ballistic-grade synthetic materials like aramid/epoxy ply, and ultra-high molecular weight polyethylene (UHMWPE)/epoxy ply. Additionally, a paperboard/epoxy lamina is introduced to induce functional grading based on layerwise shock impedance mismatches. Shock impact experiments are conducted using a shock tube equipped with helium as the driver gas. Critical shock parameters, including Mach Number, positive impulse, and peak overpressure, are meticulously evaluated. For validation purposes, a numerical model is employed to project the damage profile as a function of radial distance across different laminate sequences. The study unveils that ply deformations are strongly influenced by the arrangement of core layers, particularly the positions of the paperboard and UHMWPE layers within the core structure. To contextualize the findings, the shock impact results obtained from this study are compared with those from prior experiments that employed nitrogen-driven shocks.

Abstract Atrial natriuretic peptide (ANP) is a peptide hormone that regulates blood pressure and volume. ANP interacts with natriuretic peptide receptor-A (NPR-A) to lower the blood pressure through vasodilation, diuresis and natriuresis. Previously, we designed two human ANP analogues, one with exclusively diuretic function (DGD-ANP) and the other with exclusively vasodilatory function (DRD-ANP). Although both ANP analogues interact with NPR-A, their ability to produce cGMP was different. Three alternatively spliced isoforms of NPR-A were previously identified in rodents. Here, we evaluated the putative human isoforms for their cGMP production independently and in combination with WT NPR-A in various percentages. All three NPR-A isoforms failed to produce cGMP in the presence of ANP, DGD-ANP, or DRD-ANP. Co-expression of isoforms with WT NPR-A were found to significantly impair cGMP production. Considering the differential tissue expression levels of all three spliced isoforms in rodents have previously been demonstrated, the existence of these non-functional receptor isoforms may act as negative regulator for ANP/NPR-A activation and fine-tune cGMP production by WT NPR-A to different degree in different tissues. Thus, NPR-A isoforms potentially contribute to tissue-specific functions of ANP.

Abstract Novel materials such as fiber-metal laminates (FMLs) have demonstrated significant potential in a variety of applications. They must contend with problems such fatigue, creep, high-speed projectile impact, and deformation at high strain rates while in use. When employed as structural materials in aircraft, especially when exposed to shock wave impact and high velocity impact, fiber-metal laminates’ high strain rate characteristics become crucial. Shock impedance matching is a revolutionary approach used for shock-tuning the separate layers. The novelty of the current work is in developing custom shielding laminates, with in-depth analysis on the response of the shock impedance tuning of individual layers on the laminate behaviour at high strain rates. In the current study, five stackups of FMLs comprising metallic (AA 6061-T6) and fiber-reinforced polymer (FRP) plies, were formulated, incorporating shock impedance matching. The fiber-polymer plies used in the FMLs include ultra-high molecular weight polyethylene (UHMWPE), p-aramid for supplementing the impact resistance. Transmission loss functions (TL) estimated from the impedance tube experiments were used to indicate the shock tuning of the various laminates. The laminates underwent testing using a Split Hopkinson Pressure Bar (SHPB) apparatus to determine their properties at high strain rates ( $$350\, \textrm{s}^{-1}$$ 350 s - 1 to $$460\, \textrm{s}^{-1}$$ 460 s - 1 ). The variation in the Shock Energy (SE) absorbed by the laminates at various strain rates was analyzed as a function of the corresponding Transmission Loss employing regression. The dynamic stress-strain curves showed an increase in shock energy absorption at higher strain rates. The sequence SSP-IV and SSP-II showed the highest values of energy absorption as well as Transmission Loss.

Abstract Dengue (DENV) and chikungunya (CHIKV) viruses are among the most preponderant arboviruses. Although primarily transmitted through the bite of Aedes aegypti mosquitoes, Aedes albopictus and Aedes malayensis are competent vectors and have an impact on arbovirus epidemiology. Here, to fill the gap in our understanding of the molecular interactions between secondary vectors and arboviruses, we used transcriptomics to profile the whole-genome responses of A. albopictus to CHIKV and of A. malayensis to CHIKV and DENV at 1 and 4 days post-infection (dpi) in midguts. In A. albopictus, 1793 and 339 genes were significantly regulated by CHIKV at 1 and 4 dpi, respectively. In A. malayensis, 943 and 222 genes upon CHIKV infection, and 74 and 69 genes upon DENV infection were significantly regulated at 1 and 4 dpi, respectively. We reported 81 genes that were consistently differentially regulated in all the CHIKV-infected conditions, identifying a CHIKV-induced signature. We identified expressed immune genes in both mosquito species, using a de novo assembled midgut transcriptome for A. malayensis, and described the immune architectures. We found the JNK pathway activated in all conditions, generalizing its antiviral function to Aedines. Our comprehensive study provides insight into arbovirus transmission by multiple Aedes vectors.

Abstract Trends of kidney cancer cases worldwide are expected to increase persistently and this inspires the modification of the traditional diagnosis system to respond to future challenges. Renal Cell Carcinoma (RCC) is the most common kidney cancer and responsible for 80–85% of all renal tumors. This study proposed a robust and computationally efficient fully automated Renal Cell Carcinoma Grading Network (RCCGNet) from kidney histopathology images. The proposed RCCGNet contains a shared channel residual (SCR) block which allows the network to learn feature maps associated with different versions of the input with two parallel paths. The SCR block shares the information between two different layers and operates the shared data separately by providing beneficial supplements to each other. As a part of this study, we also introduced a new dataset for the grading of RCC with five different grades. We obtained 722 Hematoxylin & Eosin (H &E) stained slides of different patients and associated grades from the Department of Pathology, Kasturba Medical College (KMC), Mangalore, India. We performed comparable experiments which include deep learning models trained from scratch as well as transfer learning techniques using pre-trained weights of the ImageNet. To show the proposed model is generalized and independent of the dataset, we experimented with one additional well-established data called BreakHis dataset for eight class-classification. The experimental result shows that proposed RCCGNet is superior in comparison with the eight most recent classification methods on the proposed dataset as well as BreakHis dataset in terms of prediction accuracy and computational complexity.

PREGCARE is a new strategy for families who had a child with a pathogenic de novo mutation, that efficiently identifies couples at higher recurrence risk due to parental mosaicism, while reassuring many others that their recurrence risk is negligible.

Abstract Sub-Optimal deployment of Self expanding interwoven stents (Supera) has been shown to increase the rate of Clinically Driven Target Lesion Revascularization (CD-TLR). Meanwhile, drug coated balloons (DCB) have been shown to reduce CD-TLR in the femoral-popliteal segment in de- novo and restenotic lesions. However, the clinical effects of vessel preparation with DCB in nominal, compressed, and elongated Supera has not been widely studied. The purpose of this study is to assess the outcomes of clinically driven re-intervention, major amputations, and mortality in relation to the use of DCB as vessel preparation in different deployment conditions (nominal, compressed, elongated) of the Supera stent. Patient chart data was collected at a single center hospital between March 2015 and May 2020. All patients were adults (≥ 18 years old) and were treated with at least one (≥ 1) Supera stent. Deployment status was extrapolated from anonymized angiograms. The primary endpoint of this study was CD-TLR. Secondary endpoints included amputation and mortality rates associated with each deployment condition. A total of 670 limbs were treated and patients were followed for 36 months. Nominal stent deployment was observed in 337 limbs, followed by elongated condition (n = 176), then by compressed conditions (n = 159). CD-TLR was observed most frequently with elongated deployment. Drug coated balloons were used as vessel prep prior to stenting and showed a protective effect regardless of deployment status; O.R = 0.44 (CI 0.30–0.66, p

The research on natural fiber-reinforced composites has seen a rapid increase in recent years. The present study aims to further enhance the knowledge of composites by analyzing the mechanical properties of natural fiber-reinforced composites with flax and jute fibers. The properties of a composite are compared with those of a synthetic reinforcement like ultrahigh molecular weight polyethylene (UHMWPE). Melamine formaldefghyde (MF) is employed as a matrix for the preparation of composites. Fabrication is performed with eight layers of each fabric type to produce composite panels of 4 mm thickness. Composites are fabricated using a combination of hand lay-up and temperature-induced compression molding techniques. Mechanical characteristics, particularly, flexural, interlaminar shear, and impact strength, are investigated. Flax-reinforced composites with a flexural strength of 36 MPa, an interlaminar shear strength of 3.5 MPa, and an impact strength of 11.57 kJ/m2 fared better than jute and ultrahigh molecular weight polyethylene composites, signifying the superiority of flax fiber composites. The application of a nondestructive technique like cone-beam computed tomography provided further insight into the failure mechanisms of the composites. Scanning electron microscopy images of the impact specimens revealed failure mechanisms like fiber breakage, fibers shearing and splitting, matrix cracks, voids, and delamination.

In this paper, a review of natural fibers composites used in protective armors for ballistic applications like bulletproof vests is presented. It seeks to compile the results and establish natural fiber composites as an alternative to absolute synthetic composites used for the same application. The review assesses the latest articles under two categories viz. only natural fibers and hybrid composites with natural and synthetic fibers. It covers a range of fibers from flax, basalt, curaua, kenaf, aramid, jute, coir, and hemp. The study systematically classifies the composites based on the ballistic limit they exhibit and the back face signature measured during standardized ballistic testing. In accordance with the results, the findings are compared against standard materials such as Kevlar used in ballistic armors. The hybrid composites are seen to present superior properties in comparison to plain natural fiber composites. Natural fibers provide an ecological and economical alternative to existing composites. The review shows promising results and immense future scope for natural fibers in the area of ballistic applications and they must be actively considered for replacing synthetic fibers in armor.

Abstract Physicians who participate in medical-aid-in-dying (MAID) cannot be easily identified and studied due to cost and anonymity barriers. We developed and empirically tested a novel methodology to identify and survey physicians highly likely to participate in MAID activities. We used a state-level comprehensive administrative claims database to identify a cohort of patients with diagnoses and hospice enrollment similar to those known to have filled a prescription for MAID from 2017–2018. We then identified physicians who provided routine outpatient care to these patients using National Provider Identifier numbers. We surveyed these physicians in 3 waves (n = 583 total surveys), ranking physicians in order of their likelihood of being asked about MAID for each wave based on characteristics including specialty and the number of unique patients they had provided care to. We re-ranked physicians in waves 2 and 3 based on responses from prior waves. Physicians were surveyed only once and there was no follow-up to preserve anonymity. Surveys assessed the proportion of respondents who participated in MAID activities (discussions, referrals, and/or prescriptions). We identified 6369 physicians that provided care to 2960 patients. In survey waves one, two, and three respectively, response rates (55%, 52%, and 55%; p = 0.98) and the proportion of respondents that participated in MAID activities (58%, 56%, and 42%; p = 0.05) were similar. Small adjustments made to physician ranking criteria in waves two and three did not increase the proportion of physicians that participated in MAID activities. We used a novel methodology using administrative data to identify and survey physicians at high likelihood of participating in MAID activities. We achieved good overall response rates (52%), and a high proportion of respondents that participated in MAID activities (52%), demonstrating that it is possible to overcome cost and anonymity barriers to conducting quantitative research on MAID. This methodology could be used in larger scale studies of MAID or other bioethical issues with “hidden” physician populations.

Abstract Arboviruses such as dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses infect close to half a billion people per year, and are primarily transmitted through Aedes aegypti bites. Infection-induced changes in mosquito salivary glands (SG) influence transmission by inducing antiviral immunity, which restricts virus replication in the vector, and by altering saliva composition, which influences skin infection. Here, we profiled SG proteome responses to DENV serotype 2 (DENV2), ZIKV and CHIKV infections by using high-resolution isobaric-tagged quantitative proteomics. We identified 218 proteins with putative functions in immunity, blood-feeding or related to the cellular machinery. We observed that 58, 27 and 29 proteins were regulated by DENV2, ZIKV and CHIKV infections, respectively. While the regulation patterns were mostly virus-specific, we separately depleted four uncharacterized proteins that were upregulated by all three viral infections to determine their effects on these viral infections. Our study suggests that gamma-interferon responsive lysosomal thiol-like (GILT-like) has an anti-ZIKV effect, adenosine deaminase (ADA) has an anti-CHIKV effect, salivary gland surface protein 1 (SGS1) has a pro-ZIKV effect and salivary gland broad-spectrum antiviral protein (SGBAP) has an antiviral effect against all three viruses. The comprehensive description of SG responses to three global pathogenic viruses and the identification of new restriction factors improves our understanding of the molecular mechanisms influencing transmission.

Bleeding complications limits the use of effective antithrombotics therapeutics. Here, the authors developed next-generation direct thrombin inhibitors with low bleeding risks as safe peri-percutaneous coronary intervention anticoagulants when used in combination with antiplatelets.

In vitro protein folding can often result in aggregation and low yields. Here the authors use nanoscale exoshells to improve soluble yield, functional yield and specific activity of folded proteins.

Vaccine hesitancy and refusal remain a major concern for healthcare professionals and policymakers. Hence, it is necessary to ascertain the underlying factors that promote or hinder the uptake of vaccines. Authorities and policy makers are experimenting with vaccine promotion messages to communities using loss and gain-framed messages. However, the effectiveness of message framing in influencing the intention to be vaccinated is unclear. Based on the Theory of Planned Behaviour (TPB), this study analysed the impact of individual attitude towards COVID-19 vaccination, direct and indirect social norms, perceived behavioural control and perceived threat towards South Indian millennials' intention to get vaccinated. The study also assessed the effect of framing vaccine communication messages with gain and loss framing. Data was collected from 228 Millennials from South India during the COVID-19 pandemic from September to October 2021 and analysed using PLS path modelling and Necessary Condition Analysis (NCA). The findings reveal that attitudes towards vaccination, perceived threat and indirect social norms positively impact millennials' intention to take up vaccines in both message frames. Further, independent sample t-test between the framing groups indicate that negative (loss framed message) leads to higher vaccination intention compared to positive (gain framed message). A loss-framed message is thus recommended for message framing to promote vaccine uptake among millennials. These findings provide useful information in understanding the impact of message framing on behavioural intentions, especially in the context of vaccine uptake intentions of Millennials in South India.

ObjectiveMindfulness-based cognitive therapy (MBCT) includes a combination of focused attention (FA) and open monitoring (OM) meditation practices. The aim of this study was to assess both short- and long-term between- and within-group differences in affective disturbance among FA, OM and their combination (MBCT) in the context of a randomized controlled trial.MethodOne hundred and four participants with mild to severe depression and anxiety were randomized into one of three 8-week interventions: MBCT (n = 32), FA (n = 36) and OM (n = 36). Outcome measures included the Inventory of Depressive Symptomatology (IDS), and the Depression Anxiety Stress Scales (DASS). Mixed effects regression models were used to assess differential treatment effects during treatment, post-treatment (8 weeks) and long-term (20 weeks). The Reliable Change Index (RCI) was used to translate statistical findings into clinically meaningful improvements or deteriorations.ResultsAll treatments demonstrated medium to large improvements (ds = 0.42-1.65) for almost all outcomes. While all treatments were largely comparable in their effects at post-treatment (week 8), the treatments showed meaningful differences in rapidity of response and pattern of deteriorations. FA showed the fastest rate of improvement and the fewest deteriorations on stress, anxiety and depression during treatment, but a loss of treatment-related gains and lasting deteriorations in depression at week 20. OM showed the slowest rate of improvement and lost treatment-related gains for anxiety, resulting in higher anxiety in OM at week 20 than MBCT (d = 0.40) and FA (d = 0.36), though these differences did not reach statistical significance after correcting for multiple comparisons (p's = .06). MBCT and OM showed deteriorations in stress, anxiety and depression at multiple timepoints during treatment, with lasting deteriorations in stress and depression. MBCT showed the most favorable pattern for long-term treatment of depression.ConclusionsFA, OM and MBCT show different patterns of response for different dimensions of affective disturbance.Trial registrationThis trial is registered at (v NCT01831362); www.clinicaltrials.gov.

At least three species of Pantoea are responsible for bacterial blight disease and grain discoloration of rice in Sub-Saharan Africa. Thus, measures need to be taken to limit the pathogens' dispersion and robust diagnostic tools are required for rapid and cheap diagnosis in the field as well as for routine seed certification or control. Therefore, several diagnostic tools such as simplex and multiplex PCR schemes and a semi-selective medium have been developed and are being used. However, the use of these tools is time-consuming, expensive and therefore limited to laboratories that can afford the chemicals. We have therefore developed two isothermal loop amplification (LAMP) protocols, one of which detects all Pantoea species in the genus and another one that is specific for P. ananatis. • The novel LAMP assays allow rapid and sensitive detection of these bacteria. • They will help plant protection services in routine field and laboratory tests especially for monitoring the phytosanitary status of rice seeds.

Crop diseases are responsible for considerable yield losses worldwide and particularly in sub-Saharan Africa. To implement efficient disease control measures, detection of the pathogens and understanding pathogen spatio-temporal dynamics is crucial and requires the use of molecular detection tools, especially to distinguish different pathogens causing more or less similar symptoms. We report here the design a new molecular diagnostic tool able to simultaneously detect five bacterial taxa causing important diseases on rice in Africa: (1) Pseudomonas fuscovaginae, (2) Xanthomonas oryzae, (3) Burkholderia glumae and Burkholderia gladioli, (4) Sphingomonas and (5) Pantoea species. This new detection tool consists of a multiplex PCR, which is cost effective and easily applicable. Validation of the method is presented through its application on a global collection of bacterial strains. Moreover, sensitivity assessment for the detection of all five bacteria is reported to be at 0.5 ng DNA by μl. As a proof of concept, we applied the new molecular detection method to a set of 256 rice leaves collected from 16 fields in two irrigated areas in western Burkina Faso. Our results show high levels of Sphingomonas spp. (up to 100% of tested samples in one field), with significant variation in the incidence between the two sampled sites. Xanthomonas oryzae incidence levels were mostly congruent with bacterial leaf streak (BLS) and bacterial leaf blight (BLB) symptom observations in the field. Low levels of Pantoea spp. were found while none of the 256 analysed samples was positive for Burkholderia or Pseudomonas fuscovaginae. Finally, many samples (up to 37.5% in one studied field) were positive for more than one bacterium (co-infection). Documenting co-infection levels are important because of their drastic consequences on epidemiology, evolution of pathogen populations and yield losses. The newly designed multiplex PCR for multiple bacterial pathogens of rice is a significant improvement for disease monitoring in the field, thus contributing to efficient disease control and food safety.

IntroductionDelivering integrated sexual and reproductive health services (SRHS) in emergencies is important in order to save lives of the most vulnerable as well as to combat poverty, reduce inequities and social injustice. More than 60% of preventable maternal deaths occur in conflict areas and especially among the internally displaced persons (IDP). Between 2016 and 2018, unprecedented violence erupted in the Kasaï's region, in the Democratic Republic of Congo (DRC), called the Kamuina Nsapu Insurgency. During that period, an estimated three million of adolescent girls and women were forced to flee; and have faced growing threat to their health, safety, security, and well-being including significant sexual and reproductive health challenges. Between August 2016 and May 2017, the "Sous-Cluster sur les violences basées sur le genre (SC-VBG)" in DRC (2017) reported 1,429 Gender Based Violence (GBV) incidents in the 49 service delivery points in the provinces of Kasaï, Kasaï Central and Kasaï Oriental. Rape cases represented 79% of reported incidents whereas sexual assault and forced marriage accounted for respectively 11% and 4% of Gender Based Violence (GBV) among women and adolescent girls. This study aims to assess the availability of SRHS in the displaced camps in Kasaï; to evaluate the SRHS needs of young girls and women in the reproductive age (12-49). Studies of sexual and reproductive health (SRH) in the Democratic Republic of Congo (DRC) have often included adolescent girls under the age of 15 because of high prevalence of child marriage and early onset of childbearing, especially in the humanitarian context. According to the 2013 Demographic and Health Survey (DHS), about 16% of surveyed women got married by age 14 while the prevalence of early child marriage (marriage by 15) was estimated at 30%; to assess the use of SRHS services and identify barriers as well as challenges for SRH service delivery and use. Findings from this study will help provide evidence to inform towards more needs-based and responsive SRH service delivery. This is hoped for ultimately improve the quality and effectiveness of services, when considering service delivery and response in humanitarian settings.Data and methodsWe will conduct a mixed-methods study design, which will combine quantitative and qualitative approaches. Based on the estimation of the sample size, quantitative data will be drawn from the community-based survey (500 women of reproductive age per site) and health facility assessments will include assessments of 45 health facilities and 135 health providers' interviews. Qualitative data will comprise materials from 30 Key Informant Interviews (KII) and 24 Focus Group Discussions (FGDs), which are believed to achieve the needed saturation levels. Data analysis will include thematic and content analysis for the KIIs and FGDs using ATLAS.ti software for the qualitative arm. For the quantitative arm, data analysis will combine frequency and bivariate chi-square analysis, coupled with multi-level regression models, using Stata 15 software. Statistic differences will be established at the significance level of 0.05. We submitted this protocol to the national ethical committee of the ministry of health in September 2019 and it was approved in January 2020. It needs further approval from the Scientific Oversee Committee (SOC) and the Provincial Ministry of Health. Prior to data collection, informed consents will be obtained from all respondents.

High-risk coronary plaques have been considered predictive of adverse cardiac events. Both wall shear stress (WSS) in patients with hemodynamically significant lesions and optical coherence tomography (OCT) -verified thin-cap fibroatheroma (TCFA) are associated with plaque rupture, the most common underlying mechanism of acute coronary syndrome. The aim of the study was to test the hypothesis that invasive coronary angiography-based high WSS is associated with the presence of TCFA detected by OCT in obstructive lesions. From a prospective study of patients who underwent OCT examination for angiographically obstructive lesions (Yellow II), we selected patients who had two angiographic projections to create a 3-dimensional reconstruction model to allow assessment of WSS. The patients were divided into 2 groups according to the presence and absence of TCFA. Mean WSS was assessed in the whole lesion and in the proximal, middle and distal segments. Of 70 patients, TCFA was observed in 13 (19%) patients. WSS in the proximal segment (WSSproximal) (10.20 [5.01, 16.93Pa]) and the whole lesion (WSSlesion) (12.37 [6.36, 14.55Pa]) were significantly higher in lesions with TCFA compared to WSSproximal (5.84 [3.74, 8.29Pa], p = 0.02) and WSSlesion (6.95 [4.41, 11.60], p = 0.04) in lesions without TCFA. After multivariate analysis, WSSproximal was independently associated with the presence of TCFA (Odds ratio 1.105; 95%CI 1.007-1.213, p = 0.04). The optimal cutoff value of WSSproximal to predict TCFA was 6.79 Pa (AUC: 0.71; sensitivity: 0.77; specificity: 0.63 p = 0.02). Our results demonstrate that high WSS in the proximal segments of obstructive lesions is an independent predictor of OCT-verified TCFA.

In this study borassus and tamarind fruit fibers were extracted and their physical and mechanical properties such as diameter, density, tensile strength and interfacial adhesion strength (IAS) were experimentally determined. To study the effect of alkali treatment, both the fruit fibers were treated with 5% vol. sodium hydroxide solution for 0.5 h, 1 h, 2 h, and 4 h durations. Morphological studies of untreated and alkali treated fibers by using scanning electron microscope (SEM) revealed the presence of the surface impurities on the untreated fiber whereas the same were absent on the treated fibers. Fourier transform infrared spectrometry (FTIR) and X-ray diffraction (XRD) analysis also confirmed the elimination of amorphous hemicellulose of the fibers on treatment. Borassus fruit fine fibers and tamarind fruit fibers treated for 2 h exhibited better mechanical properties and improved IAS with Cashew Nut Shell Liquid (CNSL) -Epoxy matrix.

Natural fiber-reinforced polyester composites were prepared using bast fibers as the reinforcement which were extracted from Grewia serrulata trees. Chemical treatments such as alkali pretreatment followed by permanganate treatment, acetylation and silane treatment were exclusively applied to modify the fiber surface. Hand lay-up technique with compression molding was adapted for the fabrication of axially oriented fiber reinforced composites. Tensile, flexural and impact strength properties of the specimens prepared were evaluated following the standard procedures. The SEM images of the fractured surfaces shows improvement in compatibility between the chemically treated fibers and the matrix. It was found that the tensile and flexural strengths of chemically treated fiber-reinforced polyester composites have significantly improved when compared to untreated fiber-reinforced polyester specimens. The properties of 1200 hrs water aged specimens were found deteriorated considerably due to diffusion of water into the composite material system. The chemical treatment of fibers prior to fabrication of composites improves the resistance to water absorption tendencies.

Abstract Residual atherothrombotic risk remains higher in patients with versus without diabetes mellitus (DM) despite statin therapy. The underlying mechanisms are unclear. This is a retrospective post-hoc analysis of the YELLOW II trial, comparing patients with and without DM (non-DM) who received rosuvastatin 40 mg for 8–12 weeks and underwent intracoronary multimodality imaging of an obstructive nonculprit lesion, before and after therapy. In addition, blood samples were drawn to assess cholesterol efflux capacity (CEC) and changes in gene expression in peripheral blood mononuclear cells (PBMC). There was a significant reduction in low density lipoprotein-cholesterol (LDL-C), an increase in CEC and beneficial changes in plaque morphology including increase in fibrous cap thickness and decrease in the prevalence of thin cap fibro-atheroma by optical coherence tomography in DM and non-DM patients. While differential gene expression analysis did not demonstrate differences in PBMC transcriptome between the two groups on the single-gene level, weighted gene coexpression network analysis revealed two modules of coexpressed genes associated with DM, Collagen Module and Platelet Module, related to collagen catabolism and platelet function respectively. Bayesian network analysis revealed key driver genes within these modules. These transcriptomic findings might provide potential mechanisms responsible for the higher cardiovascular risk in DM patients.

Augmenter of Liver Regeneration (ALR) is a sulfhydryl oxidase carrying out fundamental functions facilitating protein disulfide bond formation. In mammals, it also functions as a hepatotrophic growth factor that specifically stimulates hepatocyte proliferation and promotes liver regeneration after liver damage or partial hepatectomy. Whether ALR also plays a role during vertebrate hepatogenesis is unknown. In this work, we investigated the function of alr in liver organogenesis in zebrafish model. We showed that alr is expressed in liver throughout hepatogenesis. Knockdown of alr through morpholino antisense oligonucleotide (MO) leads to suppression of liver outgrowth while overexpression of alr promotes liver growth. The small-liver phenotype in alr morphants results from a reduction of hepatocyte proliferation without affecting apoptosis. When expressed in cultured cells, zebrafish Alr exists as dimer and is localized in mitochondria as well as cytosol but not in nucleus or secreted outside of the cell. Similar to mammalian ALR, zebrafish Alr is a flavin-linked sulfhydryl oxidase and mutation of the conserved cysteine in the CxxC motif abolishes its enzymatic activity. Interestingly, overexpression of either wild type Alr or enzyme-inactive Alr(C131S) mutant promoted liver growth and rescued the liver growth defect of alr morphants. Nevertheless, alr(C131S) is less efficacious in both functions. Meantime, high doses of alr MOs lead to widespread developmental defects and early embryonic death in an alr sequence-dependent manner. These results suggest that alr promotes zebrafish liver outgrowth using mechanisms that are dependent as well as independent of its sulfhydryl oxidase activity. This is the first demonstration of a developmental role of alr in vertebrate. It exemplifies that a low-level sulfhydryl oxidase activity of Alr is essential for embryonic development and cellular survival. The dose-dependent and partial suppression of alr expression through MO-mediated knockdown allows the identification of its late developmental role in vertebrate liver organogenesis.

Snake venoms are rich sources of biologically active proteins and polypeptides. Three-finger toxins are non-enzymatic proteins present in elapid (cobras, kraits, mambas and sea snakes) and colubrid venoms. These proteins contain four conserved disulfide bonds in the core to maintain the three-finger folds. Although all three-finger toxins have similar fold, their biological activities are different. A new three-finger toxin (hemachatoxin) was isolated from Hemachatus haemachatus (Ringhals cobra) venom. Its amino acid sequence was elucidated, and crystal structure was determined at 2.43 Å resolution. The overall fold is similar to other three-finger toxins. The structure and sequence analysis revealed that the fold is maintained by four highly conserved disulfide bonds. It exhibited highest similarity to particularly P-type cardiotoxins that are known to associate and perturb the membrane surface with their lipid binding sites. Also, the increased B value of hemachotoxin loop II suggests that loop II is flexible and may remain flexible until its interaction with membrane phospholipids. Based on the analysis, we predict hemachatoxin to be cardiotoxic/cytotoxic and our future experiments will be directed to characterize the activity of hemachatoxin.

The inhibition of thrombin is one of the important treatments of pathological blood clot formation. Variegin, isolated from the tropical bont tick, is a novel molecule exhibiting a unique 'two-modes' inhibitory property on thrombin active site (competitive before cleavage, noncompetitive after cleavage). For the better understanding of its function, we have determined the crystal structure of the human α-thrombin:synthetic-variegin complex at 2.4 Å resolution. The structure reveals a new mechanism of thrombin inhibition by disrupting the charge relay system. Based on the structure, we have designed 17 variegin variants, differing in potency, kinetics and mechanism of inhibition. The most active variant is about 70 times more potent than the FDA-approved peptidic thrombin inhibitor, hirulog-1/bivalirudin. In vivo antithrombotic effects of the variegin variants correlate well with their in vitro affinities for thrombin. Our results encourage that variegin and the variants show strong potential for the development of tunable anticoagulants.

Background: Lymphatic filariasis (LF) is a debilitating neglected tropical disease that remains a major public challenge in endemic countries. In addition to providing mass drugs administration (ivermectin, albendazole and diethylcarbamazine) to reduce parasite burden in endemic communities, there is also a need to mitigate the challenges associated with lymphedema progression. Filarial lymphedema is known to be complicated by secondary bacterial infections; however, this is yet to receive considerable attention in LF-endemic communities in rural Ghana. Thus, the focus of this study was to understand the skin microbiome of individuals presenting with filarial lymphedema over a period. Methods: This longitudinal study employed culture and Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) to characterize the microbiota of filarial lymphedema lesions over 24 months follow-ups and considered how different it is from the skin bacterial composition of non-filarial individuals described previously in literature. Results: The result reveals that filarial lymphedema lesions had four main phyla: Firmicutes (69.7%), Proteobacteria (16.6%), Actinobacteria (13.3%), and Bacteroidetes (0.3%). Firmicutes presented the highest abundance. There were observable differences in the distribution of Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria, with the Firmicutes and Proteobacteria phyla enriched while the Bacteroidetes and Actinobacteria were markedly diminished in the filarial lymphedema lesions, relative to healthy skin. Propionibacterium and Corynebacterium, which are usually resident and abundant in healthy skin, were underrepresented in the skin from lymphedema lesions. Most of the taxa found in the skin from lymphedema lesions are not the typical organisms in human skin instead they were potentially pathogenic, with the Streptococcus, Acinetobacter, Klebsiella, Pseudomonas, Bacillus, Corynebacterium, Micrococcus, Enterococcus, Proteus and Staphylococcus genera being topmost isolates. Conclusion: Our data revealed a significant shift of the bacterial population with the introduction of potentially pathogenic bacteria to compete with the healthy skin resident microbiota during LF infection.

Background: The extensive adoption and usage of emerging technologies furthered by the global coronavirus disease 2019 (COVID-19) pandemic, has reduced direct face to face communications. New FinTech (financial technology) apps and technologies are flooding the Indian digital payments market and competitors are striving hard to attract and retain their customers. Especially when customer engagement behaviours (CEBs) are digital in nature, it is essential to gauge the intrinsically driven customer motivations which drive a positive CEB. The objective of this paper was to empirically test the influence of customer-based antecedents such as emotions, moral identity, self-concept, communal focus, perceived cost and perceived benefits on non-transactional experiential customer engagement behaviours (CEBs) and CEB’s effect on customer advocacy in the FinTech industry. Methods: Data from 380 financial app users in south India were gathered by administering a survey that captured customer predispositions, CEBs, and customer advocacy. Structural equation modelling (SEM) using smart PLS (partial least squares) 3.0 was applied to test the theoretical model. Results: Results indicate that CEB fully mediates the relationship between self-concept and customer advocacy. The positive CEBs get formed through customer predispositions leading to referral/advocacy behaviours. Conclusions: This paper provides directions for FinTech practitioners, marketers, technologists, and academicians to devise marketing strategies customized to customer needs and factors. This is one of the first research studies to demonstrate and empirically validate the CEB model for the FinTech industry during the COVID-19 pandemic.

Background: Kikuchi-Fujimoto disease (KFD) is a rare, benign condition of unknown etiology, presenting as cervical lymphadenitis. Lymphadenopathy is usually tender and maybe associated with systemic symptoms. Despite the extensive literature on this disease, it continues to be misdiagnosed owing to its misleading clinical presentation. Methods: A retrospective hospital-based descriptive cross-sectional study was conducted in tertiary care hospitals from 2011 to 2019. All patients with confirmed KFD diagnosis were included and after ethics committee approval the clinical details and histopathological data was retrieved from the medical records department and analyzed. Results: A total of 67 cases were included. The mean age was 26.9±11.3 years with a female: male ratio of 1.9:1. There were 50 patients with tender cervical lymphadenopathy which was the most common clinical presentation. The mean length and width of palpable lymph nodes were 2.3±1.0 cm and 2.2±0.7 cm respectively. Histology revealed proliferative stage in majority of patients (n=40, 59.7%). Lymphadenopathy resolved in 83.6% within 2 months. There were 42 patients who had complete recovery with symptomatic treatment within a period of 9 months. Conclusions: KFD is prevalent in young, female patients of Asian descent and often presents as tender cervical lymphadenopathy. Early diagnosis with excisional lymph node biopsy is crucial to avoid unnecessary investigations and treatment. Treatment is symptomatic unless complicated, where steroid therapy is considered. KFD has an excellent prognosis with almost no risk of fatality.

Summary: Dengue symptoms include alteration of blood coagulation and fibrinolysis, causing severe hemorrhage and death. Here, we demonstrate that higher concentration of plasmin, the human fibrinolytic factor, in blood meal enhances dengue virus (DENV) infection in mosquito midgut and dissemination in mosquitoes. We also show that mosquitoes express a plasmin-selective Kazal-type inhibitor (AaTI) in the midgut to inhibit plasmin proteolysis and revert the enhanced infection. Using bio-layer interferometry, we show that DENV, plasmin, and AaTI interact to form a tripartite complex. Eventually, plasmin increases midgut internalization of dextran molecules and this is reverted by AaTI. Our study demonstrates that (1) DENV recruits plasmin to increase local proteolytic activity in the midgut, thus degrading the glycocalyx and enhancing DENV internalization and (2) AaTI can act as a transmission-blocking agent by inhibiting plasmin proteolysis. Our results indicate that dengue pathogenesis enhances DENV fitness by increasing its infectivity to mosquitoes. : Virology; Entomology Subject Areas: Virology, Entomology

INTRODUCTION:According to Joint National Committee-7 (JNC-7) guidelines, a systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic blood pressure (DBP) of 80 to 89 mm Hg is considered as pre-hypertension. Existing evidence suggest that the cardiovascular morbidities are increasing among pre-hypertensive individuals compared to normal. OBJECTIVE:To assess the magnitude and factors associated with pre-hypertension among young adults (20-30 years) in coastal villages of Udupi Taluk (an area of land with a city or town that serves as its administrative centre and usually a number of villages), Udupi District, Karnataka state, India. DESIGN:Community based cross sectional study. SETTING:6 (out of total 14) coastal villages of Udupi Taluk, Karnataka state, India. SAMPLE:1,152 young adults (age group: 20-30 years) selected by stratified random sampling in 6 coastal villages of Udupi Taluk, Karnataka state, India. METHOD:A semi structured pre-tested questionnaire was used to elicit the details on socio-demographic variables, dietary habits, tobacco use, alcohol consumption, physical activity, family history of hypertension and stress levels. Anthropometric measurements and blood pressure were recorded according to standard protocols. Serum cholesterol was measured in a sub sample of the study population. Multivariate logistic regression was applied to identify the independent correlates of pre-hypertension among young adults (20-30 years). MAIN OUTCOME MEASURES:Prevalence, Odds ratio (OR) and adjusted (adj) OR for pre-hypertension among young adults (20-30 years). RESULTS:The prevalence of pre-hypertension in the study population was 45.2% (95%CI: 42.4-48). Multivariate logistic regression analysis revealed that age group of 25-30 years (adj OR: 4.25, 95% CI: 2.99-6.05), white collared (adj OR: 2.29, 95% CI: 1.08-4.85) and skilled occupation (adj OR: 3.24, 95% CI: 1.64-6.42), students (adj OR: 2.46, 95% CI: 1.22-4.95), using refined cooking oil (adj OR: 0.53, 95% CI: 0.29-0.95), extra salt in meals (adj OR: 2.46, 95% CI: 1.52-3.99), salty food items (adj OR: 6.99, 95% CI: 3.63-13.48), pre-obese (adj OR: 1.66, 95% CI: 1.03-2.67) and obese (adj OR: 9.16, 95% CI: 2.54, 36.4) were the significant correlates of pre-hypertension. CONCLUSION:In the study population, prevalence of pre-hypertension among young adults (20-30 years) was high (45.2%). Biological (age 25-30 years, pre-obesity and obesity) and behavioral (sedentary occupation, intake of extra salt in meals/salty food and not using refined cooking oil) factors were associated with pre-hypertension. Study emphasizes the need of community based screening of pre-hypertension under National Rural Health Mission. It also provides apt information for the evidence based designing of interventions for lifestyle modifications among high risk young adults in the study area.

The complete sequence characterization of snake venom proteins by mass spectrometry is rather challenging due to the presence of multiple isoforms from different protein families. In the present study, we investigated the tryptic digest of the venom of the viperid snake Sistrurus catenatus edwardsii by a combined approach of liquid chromatography coupled to either electrospray (online) or MALDI (offline) mass spectrometry. These different ionization techniques proved to be complementary allowing the identification a great variety of isoforms of diverse snake venom protein families, as evidenced by the detection of the corresponding unique peptides. For example, ten out of eleven predicted isoforms of serine proteinases of the venom of S. c. edwardsii were distinguished using this approach. Moreover, snake venom protein families not encountered in a previous transcriptome study of the venom gland of this snake were identified. In essence, our results support the notion that complementary ionization techniques of mass spectrometry allow for the detection of even subtle sequence differences of snake venom proteins, which is fundamental for future structure-function relationship and possible drug design studies.