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Introduction: Severe Acute Malnutrition (SAM) is a major public health concern that is linked to a high mortality rate in children under the age of five. Government of Gujarat has expanded treatment network from government facilities to private institutions and non-governmental organizations through various initiative in an effort to address the issue of SAM. Objective: To assess the treatment outcome among SAM children (0-5 years) admitted at Niramay Bal Poshan Kendra, Jam Khambhalia, Devbhumi Dwarka District of Gujarat. Method: A longitudinal study was conducted among SAM children admitted at The Niramay Bal Poshan Kendra (Public Private Partnership model under Bal Poshan Yojana) which is a day care center providing treatment to SAM children for 14 days according to the protocol of NRC (Nutrition Rehabilitation Centre). Under Bal Poshan Yojana, RBSK medical officers screened children for SAM and referred them for treatment at empanelled NGO/Private institution. Total 1557 under five children were screened by them between 6th September 2021 and 5th February 2022. Out of them 121 SAM children were identified, 95 children could be mobilized at the study site (Niramay Bal Poshan Kendra). Out of 95 children, 76 SAM children completed the treatment along with all three follow up at the study site. The data of these 76 Children was analyzed. Results: Among 76 children, average weight gain was 566 grams at the time of discharge and 1000 grams at the time of third follow-up. An average weight gain for the cohort is 5.2 gram/kg/day. At the end of treatment, 92% children moved out of the SAM category at the completion of three follow-up, 55% moved to Moderate Acute Malnutrition and 37% to normal weight category. Conclusion: An average weight gain among the study population was satisfactory. Day care treatment model provides advantage of improved treatment completion rate and higher follow-up completion. Similar models of SAM treatment can help in effectively tackling menace of malnutrition in Gujarat.

Introduction: Anaemia is the global public health crisis, so also in India. The most direct connection between Pandu Roga and nutritional deficiency anaemia can be found in Ayurveda. Ayurvedic remedy was put through a clinical study on anaemic adolescent girls because anaemia is commonly prevalent that affects the society and the side effects of oral allopathic iron preparations are highly common. The present study assesses the impact of ayurvedic medicines in improving the nutritional status among anemic adolescent girls and severely underweight children under five years of age in Devbhumi Dwarka district of Gujarat. Method: The pre-post study was registered with Clinical Trial Registry of India conducted at Devbhumi Dwarka district of Gujarat. A total of 450 anaemic adolescent girls and 179 severely underweight children were screened respectively. Adolescent girls were provided with Faltrikadhi Kavath, Purnanavardi Mandur, and Amalaki Rasayan. Under-five children was given Shishubhaishaj granules in powder form. The study was conducted in three phases (Baseline, Intervention and Endline Assessment). Results: A total of 219 adolescent girls and 120 under-five children was evaluated during endline assessment. The mean improvement in Hb was +0.36 gm/dL for 219 subjects, however subjects (n=99) with better compliance shows significant improvement (+1.07 gm/dL, P=0.005). Under five children shows improvement in their anthropometric measurements (WAZ). Conclusion: The present study revealed that Ayurvedic intervention can improve Hb status of adolescent girls only with better compliance. The study also reports the reason of non-compliance and ways to address it.

Background To estimate the determinants of anxiety and depression among university teachers in Lahore, Pakistan, during COVID-19. Methods A cross-sectional study was conducted by enrolling 668 teachers from the universities of Lahore, Pakistan. Data were collected using a questionnaire. Chi-square for significance and logistic regression for the association were used. Results Majorly, the university teachers, with an average age of 35.29 years, had regular jobs (72.8%), job experience of > 6 years (51.2%) and good self-reported health (55.4%). The majority of the teachers were working as lecturers (59.6%), lecturing in arts (33.5%) or general science (42.5%) departments, having MPhil (37.9%) or master (28.9%) degrees, and teaching via synchronous video (59.3%) mode. Anxiety and depression, severe and extremely severe, were higher among lecturers, MPhil or master degree holders, teachers lecturing arts and general science subjects, and in those on contract employment. Anxiety was significantly associated with academic departments; arts (OR;2.5, p = 0.001) and general science (OR;2.9, p = 0.001), poor health status (OR;4.4, p = 0.018), and contractual employment (OR;1.8, p = 0.003). Depression was associated with academic departments; arts (OR;2.7, p = 0.001) and general science (OR;2.5, p = 0.001), and health status (OR;2.3, p = 0.001). Conclusion Among university teachers, anxiety and depression, severe and extremely severe, were prevalent among lecturers having MPhil or master degrees, belonging to arts and general science departments, and among contract employees. Anxiety and depression were significantly associated with academic disciplines, lower cadre, and poor health status.

Prostate cancer is the most common cancer among men, with the most common metastatic sites in bone, regional lymph nodes, liver and thorax. It is most commonly diagnosed in the early stages with clinical findings of enlarged prostate on digital rectal exam and positive prostate specific antigen. Distant metastases associated with prostate cancer commonly occur to bone. It is imperative to be cautious in assuming primary breast, lung or head and neck malignancy in patients presenting with lymphadenopathy in the upper aerodigestive pathways. Cervical lymphadenopathy due to prostate cancer is becoming more prevalent since previously reported. Here we present a case of prostate cancer recurrence found through metastasis to supraclavicular lymph nodes and we also highlight homeobox protein CDX2 as a potential clinico-pathological marker in metastatic prostate cancer.

ImportanceApproximately 10% to 20% of large vessel occlusion (LVO) strokes involve tandem lesions (TLs), defined as concomitant intracranial LVO and stenosis or occlusion of the cervical internal carotid artery. Mechanical thrombectomy (MT) may benefit patients with TLs; however, optimal management and procedural strategy of the cervical lesion remain unclear.ObjectiveTo evaluate the association of carotid artery stenting (CAS) vs no stenting and medical management with functional and safety outcomes among patients with TL-LVOs.Design, Setting, and ParticipantsThis cross-sectional study included consecutive patients with acute anterior circulation TLs admitted across 17 stroke centers in the US and Spain between January 1, 2015, and December 31, 2020. Data analysis was performed from August 2021 to February 2022. Inclusion criteria were age of 18 years or older, endovascular therapy for intracranial occlusion, and presence of extracranial internal carotid artery stenosis (>50%) demonstrated on pre-MT computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography.ExposuresPatients with TLs were divided into CAS vs nonstenting groups.Main Outcomes and MeasuresPrimary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale (mRS) score of 0 to 2 and symptomatic intracranial hemorrhage (sICH), respectively. Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), discharge mRS score, ordinal mRS score, and mortality at 90 days.ResultsOf 685 patients, 623 (mean [SD] age, 67 [12.2] years; 406 [65.2%] male) were included in the analysis, of whom 363 (58.4%) were in the CAS group and 260 (41.6%) were in the nonstenting group. The CAS group had a lower proportion of patients with atrial fibrillation (38 [10.6%] vs 49 [19.2%], P = .002), a higher proportion of preprocedural degree of cervical stenosis on digital subtraction angiography (90%-99%: 107 [32.2%] vs 42 [20.5%], P P = .003), a lower median (IQR) National Institutes of Health Stroke Scale score (15 [10-19] vs 17 [13-21], P P = .007), favorable shift in mRS scores (aOR, 1.46; 95% CI, 1.02-2.10; P = .04), and successful reperfusion (aOR, 1.70; 95% CI, 1.02-3.60; P = .002) were significantly higher for the CAS group compared with the nonstenting group. Both groups had similar odds of sICH (aOR, 0.90; 95% CI, 0.46-2.40; P = .87) and 90-day mortality (aOR, 0.78; 95% CI, 0.50-1.20; P = .27). No heterogeneity was noted for 90-day functional outcome and sICH in prespecified subgroups.Conclusions and RelevanceIn this multicenter, international cross-sectional study, CAS of the cervical lesion during MT was associated with improvement in functional outcomes and reperfusion rates without an increased risk of sICH and mortality in patients with TLs.

Background and PurposeWe aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions (TLs) and whether using intraprocedural antiplatelet therapy (APT) influences MT’s safety with IVT treatment.MethodsThis is a sub-analysis of a pooled, international multicenter cohort of patients with acute anterior circulation TLs treated with MT. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2 (PH2). Additional outcomes included hemorrhagic transformation (HT), successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] 2b-3), complete reperfusion (mTICI 3), favorable functional outcome (90-day modified Rankin score [mRS] 0-2), excellent functional outcome (90-day mRS 0-1), in-hospital mortality, and 90-days mortality.ResultsOf 691 patients, 599 were included (255 underwent IVT+MT and 344 MT alone). There was no difference in the risk of sICH (aOR=1.43; 95%CI:0.72–2.87;p=0.308), PH2 (aOR=1.14; 95%CI:0.57– 2.28;p=0.705), and HT (aOR=0.92; 95%CI:0.54–1.57;p=0.751) between the IVT+MT and MT alone groups after adjusting for confounders. There was an IVT-by-intraprocedural APT interaction for sICH (pinteraction=0.031). Administration of IVT was associated with an increased risk of sICH in patients who received IV-APT (aOR=3.58; 95%CI:1.17–10.89;p=0.025). The IVT+MT group had higher odds of 90-days mRS 0-2 (aOR=1.76; 95%CI:1.05–2.94;p=0.030). The odds of successful reperfusion, complete reperfusion, 90-days mRS 0-1, in-hospital mortality, or 90-days mortality did not differ between the IVT+MT vs. MT alone groups.ConclusionOur study showed that the combination of IVT with MT for TL did not increase the overall risk of sICH, PH2, or overall HT independently of the cervical revascularization technique used. However, intraprocedural IV-ATP during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT prior to MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcome at 90 days.

Multiple primary cancers are defined as primary malignant tumors of different histological origins in one person. Desmoid-type fibromatosis (DF) is an extremely rare, locally aggressive, connective tissue malignancy that can be rooted anywhere in the body with the most common sites being thoracic wall and extremities. In contrast, granular cell tumors are rare neoplasms derived from Schwann cells commonly found in the oral cavity, skin and gastrointestinal tract. Moreover, diagnosing a patient with two primary cell tumors has become more common and the challenge of treatment becomes the focus in clinical situations. However, findings of a mass containing DF encapsulated by a granular cell tumor. Currently, there are no established guidelines for this rare condition. This case report serves to raise awareness of these two uncommon primary tumors emerging in an idiosyncratic nature.

Disorders of consciousness are complex conditions characterised by persistent loss of responsiveness due to brain injury. They present diagnostic challenges and limited options for treatment, and highlight the urgent need for a more thorough understanding of how human consciousness arises from coordinated neural activity. The increasing availability of multimodal neuroimaging data has given rise to a wide range of clinically- and scientifically-motivated modelling efforts, seeking to improve data-driven stratification of patients, to identify causal mechanisms for patient pathophysiology and loss of consciousness more broadly, and to develop simulations as a means of testing in silico potential treatment avenues to restore consciousness. As a dedicated Working Group of clinicians and neuroscientists of the international Curing Coma Campaign, here we provide our framework and vision to understand the diverse statistical and generative computational modelling approaches that are being employed in this fast-growing field. We identify the gaps that exist between the current state of the art in statistical and biophysical computational modelling in human neuroscience, and the aspirational goal of a mature field of modelling disorders of consciousness; which might drive improved treatments and outcomes in the clinic. Finally, we make several recommendations for how the field as a whole can work together to address these challenges.

Introduction Severe acute malnutrition (SAM) carries severe implications for a child's development. The survival of a child suffering from severely acute malnourishment is majorly dependent on the management of SAM, and scaling up the framework for addressing malnutrition is one of its main components. A severely malnourished child has a higher risk of mortality as compared to an ideally nourished child. Bal Poshan Yojana under the aegis of Project Tushti, a public-private partnership (PPP) model, aims at strengthening the framework of treatment for SAM children by working towards building a sustainable eco-system through engaging the government body, private practitioners and implementing bodies. Methods Bal Poshan Yojana is a novel approach implemented for the first time in the Devbhumi Dwarka district of Gujarat for the management of SAM under a PPP model. The private practitioners and centres were empanelled and trained on the treatment of SAM. SAM children with medical complications were screened through anthropometric measurements and appetite tests carried out by Rashtriya Bal Swasthya Karyakram (or RBSK, a program for child health) medical team. High-risk cases were referred to the nearest empanelled Bal Poshan Centre in the area. Children were treated for 14 days at the Bal Poshan Centre as per the protocol of the National Rehabilitation Centre and then discharged if the children fulfilled the criteria. The treatment included a 14-day treatment protocol and three follow-ups in an interval of 15 days each. The data was analyzed with appropriate statistical tests. Results Since its inception, a total of 102 severely malnourished children under five years of age have completed their treatment successfully, including three follow-ups. Around 60.79% of SAM children have been found to become normal in their nutritional status. The mean weight gain upon discharge was 0.57 kg and after three follow-ups, it was 1.051 kg. Conclusion Bal Poshan Yojana is a one of its kind initiative to tackle the growing burden of malnutrition among under-five age group children. The initiative has a focused approach. Strong referral and verification mechanisms ensure complete transparency and yielding of desired results.

Backgroundand Purpose: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There is limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors.Methods:This is a secondary analysis of the ACTION-CVT study which is a multi-center international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de-novo CVT. We compared characteristics between patients with vs. without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis.Results:947 patients were included with a mean age was 45.2 years, 63.9% were women, and 83.6% had at least 3-months of follow-up. During a median follow-up of 308 (IQR 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 de-novo CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted HR 2.13, 95% CI 1.14-3.98, p = 0.018), prior history of VTE (aHR 3.40, 95% CI 1.80-6.42, p < 0.001) and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p < 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings.Conclusion:Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT.

Background: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. Results: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140–720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51–1.73]; P =0.84), death (aHR, 0.78 [95% CI, 0.22–2.76]; P =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48–1.73]; P =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15–0.82]; P =0.02). Conclusions: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

Cancer is the second biggest killer worldwide. It has been estimated that specific lifestyle and dietary measures can prevent 30–40% of all cancers. Consumption of nutrient sparse foods, such as refined flour products and concentrated sugars, consumption of red meat, low fibre intake, and disproportion of omega 3 and omega 6 fatty acids, contributes to cancer risks. Microbiological and chemical food contaminants as well as conventional and industrial food processing methods may further increase the carcinogenicity of diets while protective agents in a cancer prevention diet include folic acid, selenium, vitamin D, vitamin B-12, chlorophyll, and antioxidants such as the carotenoids, kryptoxanthin, lycopene, and lutein. Diet can also influence the gut microbes that may have positive or adverse effects on cancer risk. The authors summarize cancer prevention by functional foods and discuss the role of different dietary factors such as promoter or inhibitor in pathogenesis of different subtypes of cancer worldwide.

A number of anti-retroviral drugs are being used for treating Human Immunodeficiency Virus (HIV) infection. Due to emergence of drug resistant strains, there is a constant quest to discover more effective anti-HIV compounds. In this endeavor, computational tools have proven useful in accelerating drug discovery. Although methods were published to design a class of compounds against a specific HIV protein, but an integrated web server for the same is lacking. Therefore, we have developed support vector machine based regression models using experimentally validated data from ChEMBL repository. Quantitative structure activity relationship based features were selected for predicting inhibition activity of a compound against HIV proteins namely protease (PR), reverse transcriptase (RT) and integrase (IN). The models presented a maximum Pearson correlation coefficient of 0.78, 0.76, 0.74 and 0.76, 0.68, 0.72 during tenfold cross-validation on IC50 and percent inhibition datasets of PR, RT, IN respectively. These models performed equally well on the independent datasets. Chemical space mapping, applicability domain analyses and other statistical tests further support robustness of the predictive models. Currently, we have identified a number of chemical descriptors that are imperative in predicting the compound inhibition potential. HIVprotI platform (http://bioinfo.imtech.res.in/manojk/hivproti) would be useful in virtual screening of inhibitors as well as designing of new molecules against the important HIV proteins for therapeutics development. Electronic supplementary material The online version of this article (10.1186/s13321-018-0266-y) contains supplementary material, which is available to authorized users.

Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic molecules owing to their selectivity to inhibit the mutant allele or associated single-nucleotide polymorphisms (SNPs) sparing the expression of the wild-type counterpart. Thus, a dedicated bioinformatics platform encompassing updated ASP-siRNAs and an algorithm for the prediction of their inhibitory efficacy will be helpful in tackling currently intractable genetic disorders. In the present study, we have developed the ASPsiRNA resource (http://crdd.osdd.net/servers/aspsirna/) covering three components viz (i) ASPsiDb, (ii) ASPsiPred, and (iii) analysis tools like ASP-siOffTar. ASPsiDb is a manually curated database harboring 4543 (including 422 chemically modified) ASP-siRNAs targeting 78 unique genes involved in 51 different diseases. It furnishes comprehensive information from experimental studies on ASP-siRNAs along with multidimensional genetic and clinical information for numerous mutations. ASPsiPred is a two-layered algorithm to predict efficacy of ASP-siRNAs for fully complementary mutant (Effmut) and wild-type allele (Effwild) with one mismatch by ASPsiPredSVM and ASPsiPredmatrix, respectively. In ASPsiPredSVM, 922 unique ASP-siRNAs with experimentally validated quantitative Effmut were used. During 10-fold cross-validation (10nCV) employing various sequence features on the training/testing dataset (T737), the best predictive model achieved a maximum Pearson’s correlation coefficient (PCC) of 0.71. Further, the accuracy of the classifier to predict Effmut against novel genes was assessed by leave one target out cross-validation approach (LOTOCV). ASPsiPredmatrix was constructed from rule-based studies describing the effect of single siRNA:mRNA mismatches on the efficacy at 19 different locations of siRNA. Thus, ASPsiRNA encompasses the first database, prediction algorithm, and off-target analysis tool that is expected to accelerate research in the field of RNAi-based therapeutics for human genetic diseases.

Hepatitis C virus plays a significant role in the development of hepatocellular carcinoma (HCC) globally. The pathogenic mechanisms of hepatocellular carcinoma with HCV infection are generally linked with inflammation, cytokines, fibrosis, cellular signaling pathways, and liver cell proliferation modulating pathways. HCV encoded proteins (Core, NS3, NS4, NS5A) interact with a broad range of hepatocytes derived factors to modulate an array of activities such as cell signaling, DNA repair, transcription and translational regulation, cell propagation, apoptosis, membrane topology. These four viral proteins are also implicated to show a strong conversion potential in tissue culture. Furthermore, Core and NS5A also trigger the accretion of the β-catenin pathway as a common target to contribute viral induced transformation. There is a strong association between HCV variants within Core, NS4, and NS5A and host single nucleotide polymorphisms (SNPs) with the HCC pathogenesis. Identification of such viral mutants and host SNPs is very critical to determine the risk of HCC and response to antiviral therapy. In this review, we highlight the association of key variants, mutated proteins, and host SNPs in development of HCV induced HCC. How such viral mutants may modulate the interaction with cellular host machinery is also discussed.

Peptide-based antiviral therapeutics has gradually paved their way into mainstream drug discovery research. Experimental determination of peptides' antiviral activity as expressed by their IC50 values involves a lot of effort. Therefore, we have developed "AVP-IC50 Pred," a regression-based algorithm to predict the antiviral activity in terms of IC50 values (μM). A total of 759 non-redundant peptides from AVPdb and HIPdb were divided into a training/test set having 683 peptides (T(683)) and a validation set with 76 independent peptides (V(76)) for evaluation. We utilized important peptide sequence features like amino-acid compositions, binary profile of N8-C8 residues, physicochemical properties and their hybrids. Four different machine learning techniques (MLTs) namely Support vector machine, Random Forest, Instance-based classifier, and K-Star were employed. During 10-fold cross validation, we achieved maximum Pearson correlation coefficients (PCCs) of 0.66, 0.64, 0.56, 0.55, respectively, for the above MLTs using the best combination of feature sets. All the predictive models also performed well on the independent validation dataset and achieved maximum PCCs of 0.74, 0.68, 0.59, 0.57, respectively, on the best combination of feature sets. The AVP-IC50 Pred web server is anticipated to assist the researchers working on antiviral therapeutics by enabling them to computationally screen many compounds and focus experimental validation on the most promising set of peptides, thus reducing cost and time efforts. The server is available at http://crdd.osdd.net/servers/ic50avp.

Knockdown of host genes using high-throughput genome-wide RNA interference screens has identified numerous host factors that affect viral infections, which would be helpful in understanding host-virus interactions. We have developed a vhfRNAi web resource based on genome-wide RNAi experiments for viruses. It contains experimental details of 12 249 entries (host factors + restriction factors) for 18 viruses. Simultaneously, this resource encompasses analysis of overlapping genes, genome wide association studies, gene ontology (GO), pathogen interacting proteins, interaction networks and pathway enrichment. Using overlap analysis, it was found that Influenza A virus shared overlapping host genes with the majority of viruses including Hepatitis C virus and Dengue virus 2. In the genome wide association studies analysis, 429 diseases/traits were mapped, of which obesity-related traits were the most common. GO analysis revealed that the major categories belonged to metabolic processes, molecule transport, signal transduction, proteolysis, etc. In the pathogen interacting protein analysis, protein interaction data from different resources can be explored for further understanding of host-virus biology. By pathway enrichment analysis, a total of 8955 genes were mapped on 303 pathways with most of the hits coming from metabolic pathways. We have found 491 genes that are not essential for the host but essential for the virus and can be targeted to inhibit the virus. These may be explored as potential candidates for drug targets. The resource is freely accessible at and will be useful in understanding host-virus biology as well as identification of targets for the development of antiviral therapeutics.

Antiviral peptides (AVPs) have exhibited huge potential in inhibiting viruses by targeting various stages of their life cycle. Therefore, we have developed AVPdb, available online at http://crdd.osdd.net/servers/avpdb, to provide a dedicated resource of experimentally verified AVPs targeting over 60 medically important viruses including Influenza, HCV, HSV, RSV, HBV, DENV, SARS, etc. However, we have separately provided HIV inhibiting peptides in 'HIPdb'. AVPdb contains detailed information of 2683 peptides, including 624 modified peptides experimentally tested for antiviral activity. In modified peptides a chemical moiety is attached for increasing their efficacy and stability. Detailed information include: peptide sequence, length, source, virus targeted, virus family, cell line used, efficacy (qualitative/quantitative), target step/protein, assay used in determining the efficacy and PubMed reference. The database also furnishes physicochemical properties and predicted structure for each peptide. We have provided user-friendly browsing and search facility along with other analysis tools to help the users. Entering of many synthetic peptide-based drugs in various stages of clinical trials reiterate the importance for the AVP resources. AVPdb is anticipated to cater to the needs of scientific community working for the development of antiviral therapeutics.

Current Zika virus (ZIKV) outbreaks that spread in several areas of Africa, Southeast Asia, and in pacific islands is declared as a global health emergency by World Health Organization (WHO). It causes Zika fever and illness ranging from severe autoimmune to neurological complications in humans. To facilitate research on this virus, we have developed an integrative multi-omics platform; ZikaVR (http://bioinfo.imtech.res.in/manojk/zikavr/), dedicated to the ZIKV genomic, proteomic and therapeutic knowledge. It comprises of whole genome sequences, their respective functional information regarding proteins, genes, and structural content. Additionally, it also delivers sophisticated analysis such as whole-genome alignments, conservation and variation, CpG islands, codon context, usage bias and phylogenetic inferences at whole genome and proteome level with user-friendly visual environment. Further, glycosylation sites and molecular diagnostic primers were also analyzed. Most importantly, we also proposed potential therapeutically imperative constituents namely vaccine epitopes, siRNAs, miRNAs, sgRNAs and repurposing drug candidates.

Small interfering RNA (siRNA) technology has vast potential for functional genomics and development of therapeutics. However, it faces many obstacles predominantly instability of siRNAs due to nuclease digestion and subsequently biologically short half-life. Chemical modifications in siRNAs provide means to overcome these shortcomings and improve their stability and potency. Despite enormous utility bioinformatics resource of these chemically modified siRNAs (cm-siRNAs) is lacking. Therefore, we have developed siRNAmod, a specialized databank for chemically modified siRNAs. Currently, our repository contains a total of 4894 chemically modified-siRNA sequences, comprising 128 unique chemical modifications on different positions with various permutations and combinations. It incorporates important information on siRNA sequence, chemical modification, their number and respective position, structure, simplified molecular input line entry system canonical (SMILES), efficacy of modified siRNA, target gene, cell line, experimental methods, reference etc. It is developed and hosted using Linux Apache MySQL PHP (LAMP) software bundle. Standard user-friendly browse, search facility and analysis tools are also integrated. It would assist in understanding the effect of chemical modifications and further development of stable and efficacious siRNAs for research as well as therapeutics. siRNAmod is freely available at: http://crdd.osdd.net/servers/sirnamod.

In the battle against viruses, antiviral peptides (AVPs) had demonstrated the immense potential. Presently, more than 15 peptide-based drugs are in various stages of clinical trials. Emerging and re-emerging viruses further emphasize the efforts to accelerate antiviral drug discovery efforts. Despite, huge importance of the field, no dedicated AVP resource is available. In the present study, we have collected 1245 peptides which were experimentally checked for antiviral activity targeting important human viruses like influenza, HIV, HCV and SARS, etc. After removing redundant peptides, 1056 peptides were divided into 951 training and 105 validation data sets. We have exploited various peptides sequence features, i.e. motifs and alignment followed by amino acid composition and physicochemical properties during 5-fold cross validation using Support Vector Machine. Physiochemical properties-based model achieved maximum 85% accuracy and 0.70 Matthew's Correlation Coefficient (MCC). Performance of this model on the experimental validation data set showed 86% accuracy and 0.71 MCC which is far better than the general antimicrobial peptides prediction methods. Therefore, AVPpred-the first web server for predicting the highly effective AVPs would certainly be helpful to researchers working on peptide-based antiviral development. The web server is freely available at http://crdd.osdd.net/servers/avppred.

RNAi technology has been emerging as a potential modality to inhibit viruses during past decade. In literature a few siRNA databases have been reported that focus on targeting human and mammalian genes but experimentally validated viral siRNA databases are lacking. We have developed VIRsiRNAdb, a manually curated database having comprehensive details of 1358 siRNA/shRNA targeting viral genome regions. Further, wherever available, information regarding alternative efficacies of above 300 siRNAs derived from different assays has also been incorporated. Important fields included in the database are siRNA sequence, virus subtype, target genome region, cell type, target object, experimental assay, efficacy, off-target and siRNA matching with reference viral sequences. Database also provides the users with facilities of advance search, browsing, data submission, linking to external databases and useful siRNA analysis tools especially siTarAlign which align the siRNA with reference viral genomes or user defined sequences. VIRsiRNAdb contains extensive details of siRNA/shRNA targeting 42 important human viruses including influenza virus, hepatitis B virus, HPV and SARS Corona virus. VIRsiRNAdb would prove useful for researchers in picking up the best viral siRNA for antiviral therapeutics development and also for developing better viral siRNA design tools. The database is freely available at http://crdd.osdd.net/servers/virsirnadb.

Peptide‐based antiviral therapeutics has gradually paved their way into mainstream drug discovery research. Experimental determination of peptides' antiviral activity as expressed by their IC50 values involves a lot of effort. Therefore, we have developed “AVP‐IC50Pred,” a regression‐based algorithm to predict the antiviral activity in terms of IC50 values (μM). A total of 759 non‐redundant peptides from AVPdb and HIPdb were divided into a training/test set having 683 peptides (T683) and a validation set with 76 independent peptides (V76) for evaluation. We utilized important peptide sequence features like amino‐acid compositions, binary profile of N8‐C8 residues, physicochemical properties and their hybrids. Four different machine learning techniques (MLTs) namely Support vector machine, Random Forest, Instance‐based classifier, and K‐Star were employed. During 10‐fold cross validation, we achieved maximum Pearson correlation coefficients (PCCs) of 0.66, 0.64, 0.56, 0.55, respectively, for the above MLTs using the best combination of feature sets. All the predictive models also performed well on the independent validation dataset and achieved maximum PCCs of 0.74, 0.68, 0.59, 0.57, respectively, on the best combination of feature sets. The AVP‐IC50Pred web server is anticipated to assist the researchers working on antiviral therapeutics by enabling them to computationally screen many compounds and focus experimental validation on the most promising set of peptides, thus reducing cost and time efforts. The server is available at http://crdd.osdd.net/servers/ic50avp. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 753–763, 2015.

MicroRNA (MIR) signatures are critical to pathobiology and prognosis of acute myeloid leukemia (AML). MIR223 is expressed at low levels in progenitor cells, whereas high expression is induced by granulocytic differentiation. Novel-targeted therapies through epigenetic manipulation of MIR223 regulators are being explored in AML but correlative data between established clinical prognostic markers and MIR223 expression in AML is lacking. MIR223 has inverse relationship with LMO2 protein expression and our group has recently reported a close association between LMO2 protein expression and chromosomal findings in AML patients. In this study, we examined the expression of MIR223 in a large cohort of AML patients and correlated it with LMO2 protein expression, cytogenetic data, degree of differentiation [French-American and British (FAB)/World Health Organization classifications], and overall survival. MIR223 expression was upregulated in only a subset of patients (37%). Suppression of MIR223 was more frequent among patients with aneuploid karyotype compared with diploid karyotype (P=0.005). In AML, not otherwise specified category, AML with maturation (FAB-M2) showed higher levels of MIR223 when compared with either AML without maturation (FAB M0/M1) (P=0.001); AML with monoblastic differentiation (FAB M4/M5) (P=0.004) or AML with myelodysplasia-related changes (P=0.011). Among cytogenetic risk groups, suppression of MIR223 was universal (>95%) in high-risk group when compared with intermediate-risk group (P=0.004). No correlation between MIR223 and LMO2 protein expression was identified. In conclusion, we have shown that suppression of MIR223 expression, as compared with controls, is associated with lack of differentiation and adverse cytogenetic profile, but unrelated with LMO2 protein expression or overall survival.

Background Young children who experience human rhinovirus (HRV)-associated wheezing illnesses are more likely to develop subsequent asthma [1]. This has led to the hypothesis that HRV infection may be involved in the pathogenesis of airway remodeling in asthma [2]. Increased airway smooth muscle (ASM) mass, in which ASM cells are in close proximity to the subepithelial region, is a characteristic feature of airway remodeling [3]. We have shown that HRV infection of human bronchial epithelial (HBE) cells, both in vitro and in vivo, results in the upregulation of airway remodeling mediators [4]. We now sought to determine whether HRV infection of HBE cells is associated with airway smooth muscle (ASM) chemotaxis.

International audience; Viral microRNAs (miRNAs) regulate gene expression of viral and/or host genes to benefit the virus. Hence, miRNAs play a key role in host-virus interactions and pathogenesis of viral diseases. Lately, miRNAs have also shown potential as important targets for the development of novel antiviral therapeutics. Although several miRNA and their target repositories are available for human and other organisms in literature, but a dedicated resource on viral miRNAs and their targets are lacking. Therefore, we have developed a comprehensive viral miRNA resource harboring information of 9133 entries in three subdatabases. This includes 1308 experimentally validated miRNA sequences with their isomiRs encoded by 44 viruses in viral miRNA ' VIRMIRNA: ' and 7283 of their target genes in ' VIRMIRTAR': . Additionally, there is information of 542 antiviral miRNAs encoded by the host against 24 viruses in antiviral miRNA ' AVIRMIR': . The web interface was developed using Linux-Apache-MySQL-PHP (LAMP) software bundle. User-friendly browse, search, advanced search and useful analysis tools are also provided on the web interface. VIRmiRNA is the first specialized resource of experimentally proven virus-encoded miRNAs and their associated targets. This database would enhance the understanding of viral/host gene regulation and may also prove beneficial in the development of antiviral therapeutics. Database URL: http://crdd.osdd.net/servers/virmirna.

Spondylolithesis is forward slipping of upper vertebra in relation to its lower one, which at times requires surgery. The objective of present study is to document the outcome of surgical treatment in spondylolisthesis of lumbosacral region.We reviewed outcome of surgery in 45 patients with spondylolisthesis. Improvement in pain intensity, neurological status and union achieved after surgery was studied. All patients requiring surgical treatment were included in the study. The patients were operated by single spine surgeon. A Performa was made for each patient and records were kept in a custom built Microsoft access database.Majority of our patient were in 4th and 51th decade with some male domination. Pain was main indication for surgery which was excruciating in 6. severe in 33, and moderate in 6 cases. The neurological status was normal in 34 cases while 11 patients had some deficit. L5-S1 was affected in 26, L4-L5 in 13 and multi or high level was found in rest of cases. Slip grade was measured with Meyerding grades, 18 had grade II, 15 had I, 9 had III and 3 had IV spondylolisthesis. Posterior lumbar inter body fusion (PLIF) was done in 24 patients, posterolateral, transforaminal lumbar inter body and anterior inter body fusion in others. Translaminar screw fixation, transpedicular transdiscal transcorporial and Delta fixation in some cases. Pedicle screw fixation was done in most cases, AO fixator internae and 4.5 mm screw in others. Average follow up was 2 years and 5 months, max 5 years and minimum 6 months. Pain relief was achieved in 82%, neurological improvement 60% and union in 91% cases. There was no deterioration of neurological status, two implant failure and one wound infection.Surgical procedure for Spondylolisthesis must be individualised. Young patients with spondylolysis can be treated with osteosynthesis and sparing of motion segment. PLIF provides satisfactory results in majority of low to moderate cases with some reduction. Transpedicular transdiscal transcorprial and delta fixation is good procedure for severe slips in adult.

Cushing's disease in children is not rare but in infants it is quite rare and an important medical condition needing proper line of investigations and management options. Craniopharyngioma as a cause of Cushing's disease is well reported and practical inference of the condition is of clinical importance. Craniopharyngioma generally affects children at 5 - 10 years of age and is rarely seen in infancy. It usually manifests as endocrinological deficits such as short stature, delayed puberty, and obesity. We report the case of a 7 months old infant who presented with obesity and Cushing's disease associated with craniopharyngioma.

8568 Background: DLBCL is a heterogeneous disease. Gene expression profile (GEP) based distinction into ABC and GCB sub-types, provides basis for risk stratification in DLBCL patients. GEP is an in...

7066 Background: AL is a heterogenous and aggressive disease with dismal prognosis. Chromosomal translocations constitute the basis of current WHO classification and are central to AL pathogenesis....

This Memorial seeks to present a framework of legal arguments with respect to the validity and and legal effects of an arms embargo emposed by United Nations Security Council Resolution 713 in September 1991 on the Socialist Federal Republic of Yugoslavia (Yugoslavia), before its dissolution, and since treated as being in force with respect to the new states that have succeeded Yugoslavia. More particularly, the Memorial addresses the legality of maintaining (or at least, having maintained during the crucial time period) the arms embargo in force, either de jure or de facto, against the Republic of Bosnia and Herzegovina (Bosnia) in light of evdience that the arm's embargo's maintenance vis-a-vis Bosnia has contributed to the inability of the Government of Bosnia to prevent the perpetration on Bosnia's territory of acts of genocide by Bosnian Serb forces as well as combined acts of genocide and aggression by the neighboring state of Serbia and Montenegro (Serbia). [Co-authored with Craig Scott, Abid Qureshi, Paul Michell, Peter Copeland and Francis Chang]

Selection of effective viral siRNA is an indispensable step in the development of siRNA based antiviral therapeutics. Despite immense potential, a viral siRNA efficacy prediction algorithm is still not available. Moreover, performances of the existing general mammalian siRNA efficacy predictors are not satisfactory for viral siRNAs. Therefore, we have developed “VIRsiRNApred” a support vector machine (SVM) based method for predicting the efficacy of viral siRNA. In the present study, we have employed a new dataset of 1725 viral siRNAs with experimentally verified quantitative efficacies tested under heterogeneous experimental conditions and targeting as many as 37 important human viruses including HIV, Influenza, HCV, HBV, SARS etc. These siRNAs were divided into training (T1380) and validation (V345) datasets. Important siRNA sequence features including mono to penta nucleotide frequencies, binary pattern, thermodynamic properties and secondary structure were employed for model development. During 10-fold cross validation on T1380 using hybrid approach, we achieved a maximum Pearson Correlation Coefficient (PCC) of 0.55 between predicted and actual efficacy of viral siRNAs. On V345 independent dataset, our best model achieved a maximum correlation of 0.50 while existing general siRNA prediction methods showed PCC from 0.05 to 0.18. However, using leave one out cross validation PCC was improved to 0.58 and 0.55 on training and validation datasets respectively. SVM performed better than other machine learning techniques used like ANN, KNN and REP Tree. VIRsiRNApred is the first algorithm for predicting inhibition efficacy of viral siRNAs which is developed using experimentally verified viral siRNAs. We hope this algorithm would be useful in predicting highly potent viral siRNA to aid siRNA based antiviral therapeutics development. The web server is freely available at http://crdd.osdd.net/servers/virsirnapred/ .