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Abstract To inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children’s Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33% (n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14% (41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance of data sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice.

The mutualistic symbiotic relationship between insects and bacteria greatly influences the growth and development of host insects. Tessaratoma javanica (Thunberg) (Hemiptera: Tessaratomidae), also referred to as the litchi stink bug, has recently been established as an important insect pest of Litchi chinensis Sonn. and causes substantial yield loss in India. To design effective and environmentally safe management strategies, an understanding of the diversity and functions of microbiota harbored across the development stages is very important. The assessment of the diversity of development-associated bacteria in T. javanica and their predicted functions was conducted using 16S rRNA gene sequences obtained by the Illumina MiSeq technology. The result showed that taxonomic analysis of associated bacteria in different developmental stages includes a total of 46 phyla, encompassing 139 classes, 271 orders, 474 families, and 893 genera of bacteria. All developmental stages of T. javanica shared a total of 42.82 percent of operational taxonomic units (OTUs), with a 97 % similarity threshold. Alpha diversity indices showed maximum species richness in the egg and adult stages. The phyla Proteobacteria followed by Firmicutes, Bacteriodetes, and Actinobacteria, exhibited the highest levels of abundance across all the developmental stages of T. javanica. Microbiota were most different between the egg and the 4th nymphal stage (χ2 = 711.67) and least different between the 2nd and 4th nymphal instars (χ2 = 44.45). The predicted functions of the microbiota associated with T. javanica are mainly involved in amino acid metabolism, cell motility, cellular processes and signaling, glycan biosynthesis and metabolism, lipid metabolism, and membrane transport. The present study documentation and information on symbiotic bacteria across T. javanica life stages will prompt the development of novel biological management strategies.

Abstract Widespread, comprehensive sequencing of patient tumors has facilitated the usage of precision medicine (PM) drugs to target specific genomic alterations. Therapeutic clinical trials are necessary to test new PM drugs to advance precision medicine, however, the abundance of patient sequencing data coupled with complex clinical trial eligibility has made it challenging to match patients to PM trials. To facilitate enrollment onto PM trials, we developed MatchMiner, an open-source platform to computationally match genomically profiled cancer patients to PM trials. Here, we describe MatchMiner’s capabilities, outline its deployment at Dana-Farber Cancer Institute (DFCI), and characterize its impact on PM trial enrollment. MatchMiner’s primary goals are to facilitate PM trial options for all patients and accelerate trial enrollment onto PM trials. MatchMiner can help clinicians find trial options for an individual patient or provide trial teams with candidate patients matching their trial’s eligibility criteria. From March 2016 through March 2021, we curated 354 PM trials containing a broad range of genomic and clinical eligibility criteria and MatchMiner facilitated 166 trial consents (MatchMiner consents, MMC) for 159 patients. To quantify MatchMiner’s impact on trial consent, we measured time from genomic sequencing report date to trial consent date for the 166 MMC compared to trial consents not facilitated by MatchMiner (non-MMC). We found MMC consented to trials 55 days (22%) earlier than non-MMC. MatchMiner has enabled our clinicians to match patients to PM trials and accelerated the trial enrollment process.

Cloud computing has brought about a transformation in the delivery model of information technology from a product to a service. It has enabled the availability of various software, platforms and infrastructural resources as scalable services on demand over the internet. However, the performance of cloud computing services is hampered due to their inherent vulnerability to failures owing to the scale at which they operate. It is possible to utilize cloud computing services to their maximum potential only if the performance related issues of reliability, availability, and throughput are handled effectively by cloud service providers. Therefore, fault tolerance becomes a critical requirement for achieving high performance in cloud computing. This paper presents a comprehensive overview of fault tolerance-related issues in cloud computing; emphasizing upon the significant concepts, architectural details, and the state-of-art techniques and methods. The objective is to provide insights into the existing fault tolerance approaches as well as challenges yet required to be overcome. The survey enumerates a few promising techniques that may be used for efficient solutions and also, identifies important research directions in this area.

Meckel’s diverticulum is a true diverticulum of the alimentary tract occurring resulting from the persistence of remnants of the vitello-intestinal duct. They are often asymptomatic and incidentally diagnosed during surgery. Complications such as intestinal obstruction, diverticulitis, intestinal haemorrhage and perforation may occur with Meckel’s diverticulum, which renders them symptomatic. The clinical and imaging diagnosis of Meckel’s diverticulum is very challenging. As a result of the rare occurrence of complicated Meckel’s diverticulum and the difficult preoperative diagnosis, knowledge of its imaging features is limited. The presented case series describes a spectrum of complications caused by Meckel’s diverticulum and its CT imaging features. It highlights the importance of a high clinical suspicion by carefully searching for a Meckel’s diverticulum on CT in its characteristic location to avoid missing it preoperatively.

Abstract Background COVID-19 is the most recent zoonotic outbreak of coronaviruses. Mostly, it invades the cells of the respiratory system by binding to the receptor angiotensin-converting enzyme 2 (ACE2) which is also present in other organs like the kidney, testis, ovaries, breast, heart, and intestine, rendering them prone to be infected. The reproductive potential is a must for the sustenance of any species and it is our prime duty to safeguard the reproductive system of the present generation from such a deadly virus. The previously reported coronaviruses like severe acute respiratory syndrome coronavirus (SARS-CoV) had a detrimental impact on reproductive organs. There is a dearth of sufficient research to provide substantial evidence for the harmful effects of this novel virus on the reproductive system. Hence, our review compiles the knowledge available until now to boost research in this regard and to take the necessary steps in time. Main body of abstract Here we tried to compile all the data available on the effect of SARS-CoV-2 on the reproductive system as well as vertical transmission of the virus. All related articles published from February to August 2020 were reviewed and thoroughly analyzed. SARS-CoV-2 has been found to affect the sperm concentration and motility, thus degrading the fertility of males. In females, it is suspected that this virus affects the oocyte quality and ovarian function, resulting in infertility or miscarriage. Traces of SARS-CoV-2 virus have also been found in the breast milk of the infected mothers and the semen of infected males. Vertical transmission of SARS-CoV-2 has also been reported in some cases. Conclusion Based on the literature review, SARS-CoV-2 seems to have the potential of affecting both male and female reproductive tracts. This review brings together the findings and observations made in the area of reproductive health during the current pandemic. The reproductive system of the young population is preordained for subsequent disorders, infertility, reduced sperm count, and motility. Therefore, the research and medical practices should focus on possible vulnerability being posed by SARS-CoV-2 to the gametes and future generations. We, hereby, recommend close monitoring of young and pregnant COVID-19 patients concerning reproductive health with utmost priority.

Abstract Background The apicomplexan parasite Theileria parva causes a livestock disease called East coast fever (ECF), with millions of animals at risk in sub-Saharan East and Southern Africa, the geographic distribution of T. parva. Over a million bovines die each year of ECF, with a tremendous economic burden to pastoralists in endemic countries. Comprehensive, accurate parasite genome annotation can facilitate the discovery of novel chemotherapeutic targets for disease treatment, as well as elucidate the biology of the parasite. However, genome annotation remains a significant challenge because of limitations in the quality and quantity of the data being used to inform the location and function of protein-coding genes and, when RNA data are used, the underlying biological complexity of the processes involved in gene expression. Here, we apply our recently published RNAseq dataset derived from the schizont life-cycle stage of T. parva to update structural and functional gene annotations across the entire nuclear genome. Results The re-annotation effort lead to evidence-supported updates in over half of all protein-coding sequence (CDS) predictions, including exon changes, gene merges and gene splitting, an increase in average CDS length of approximately 50 base pairs, and the identification of 128 new genes. Among the new genes identified were those involved in N-glycosylation, a process previously thought not to exist in this organism and a potentially new chemotherapeutic target pathway for treating ECF. Alternatively-spliced genes were identified, and antisense and multi-gene family transcription were extensively characterized. Conclusions The process of re-annotation led to novel insights into the organization and expression profiles of protein-coding sequences in this parasite, and uncovered a minimal N-glycosylation pathway that changes our current understanding of the evolution of this post-translational modification in apicomplexan parasites.

Purpose. We aim to determine the predictive value of endometrial thickness by transvaginal ultrasonography (TVS) in diagnosing endometrial pathology and to evaluate whether Doppler complements its diagnostic efficacy in perimenopausal women with abnormal uterine bleeding. Methods. This cross-sectional observational study was conducted among 70 perimenopausal women with AUB who underwent TVS measurement of endometrial thickness (ET) and Doppler flow indices followed by endometrial sampling and histopathological examination (HPE). Results. In HPE, 51 (73%) women had normal diagnosis while 19 (27%) women had neoplastic histology either benign or malignant. They were categorised into group I and group II, respectively. There was a significant difference in age (P=0.001) and incidence of obesity (P=0.01) between the two groups. The ETs measured in group I and group II were 7.89 ± 2.62 mm and 14.07 ± 3.96 mm, respectively, with significant difference (P45 years) and obesity (BMI>30) significantly escalate the chances of developing endometrial pathology.

Please note, following publication of the original article [1], the authors have advised of two errors that are present in the published article.

Abstract Background Malaria is one of the deadliest infectious diseases caused by protozoan parasite of Plasmodium spp. Increasing resistance to anti-malarials has become global threat in control of the disease and demands for novel anti-malarial interventions. Naturally-occurring coumarins, which belong to a class of benzo-α-pyrones, found in higher plants and some essential oils, exhibit therapeutic potential against various diseases. However, their limited uptake and non-specificity has restricted their wide spread use as potential drug candidates. Methods Two series of carbohydrate fused pyrano[3,2-c]pyranone carbohybrids which were synthesized by combination of 2-C-formyl galactal and 2-C-formyl glucal, with various freshly prepared 4-hydroxycoumarins were screened against Plasmodium falciparum. The anti-malarial activity of these carbohybrids was determined by growth inhibition assay on P. falciparum 3D7 strain using SYBR green based fluorescence assay. Haemolytic activity of carbohybrid 12, which showed maximal anti-malarial activity, was determined by haemocompatibility assay. The uptake of the carbohybrid 12 by parasitized erythrocytes was determined using confocal microscopy. Growth progression assays were performed to determine the stage specific effect of carbohybrid 12 treatment on Pf3D7. In silico studies were conducted to explore the mechanism of action of carbohybrid 12 on parasite microtubule dynamics. These findings were further validated by immunofluorescence assay and drug combination assay. Results 2-C-formyl galactal fused pyrano[3,2-c]pyranone carbohybrid 12 exhibited maximum growth inhibitory potential against Plasmodium with IC50 value of 5.861 µM and no toxicity on HepG2 cells as well as no haemolysis of erythrocytes. An enhanced uptake of this carbohybrid compound was observed by parasitized erythrocytes as compared to uninfected erythrocytes. Further study revealed that carbohybrid 12 arrests the growth of parasite at trophozoite and schizonts stage during course of progression through asexual blood stages. Mechanistically, it was shown that the carbohybrid 12 binds to α,β-heterodimer of tubulin and affects microtubule dynamics. Conclusion These findings show carbohydrate group fusion to 4-hydroxycoumarin precursor resulted in pyrano-pyranones derivatives with better solubility, enhanced uptake and improved selectivity. This data confirms that, carbohydrate fused pyrano[3,2-c]pyranones carbohybrids are effective candidates for anti-malarial interventions against P. falciparum.

Background and objectives: Haemoglobin content is the well accepted indicator for anaemia assessment. The high prevalence of anaemia, maternal health care issues and adverse delivery outcome in Jharkhand, we investigated whether delivering women with anaemia would present a modifiable risk of preterm (PTB) and low birth weight (LBW). Methods: A facility-based cross-sectional study involving pregnant women, with screening for pregnancy endpoints and haemoglobin assay, were conducted. Anaemia was classified according to World Health Organization's definition of anaemia in pregnancy. Confounding variables were adjusted in a logistic model. The adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were used for analyzing the association among maternal anaemia, PTB and LBW. Results: We observed a high prevalence of anaemia (78.45%) in delivering women, whereas high prevalence of preterm birth (34.75%) and LBW (32.81%) in delivering women overall. In the adjusted analysis, overall anaemia in pregnancy was strongly associated with preterm birth (OR, 3.42; 95% CI, 1.98–5.88; P ≤ .0001) as compared to LBW (OR, 1.12; 95% CI, 0.65–1.61; P = .0003). The risk of PTB and LBW were dependent on the stratification of the anaemia group, as the strongest association was observed in severe (OR, 4.86) followed by mild (OR, 3.66) and moderate (OR, 3.18) anaemia in PTB; whereas risk of LBW was found in severe (OR, 2.5) followed by moderate (OR, 1.11) and mild (OR, 0.57) anaemia. The risk of PTB and LBW across six pregnancy haemoglobin groups were compared, haemoglobin of 10–10.9 g/dl (OR, 1.25) and ≤ 8 g/dl (OR, 1.03) have shown association with PTB and LBW, respectively. However, high haemoglobin concentration was not associated with either PTB or LBW. Conclusions: Anaemia in delivering women was associated with an elevated risk of PTB and LBW and the risk increased with the severity of anaemia in pregnant women. Keywords: Maternal anaemia, Preterm birth, Low birth weight, Pregnancy, Jharkhand

Background: Although conventional 60 mg of prasugrel allows for rapid and potent platelet inhibition within 30 min after loading dose, the efficacy and safety of lower doses of prasugrel in Indian patients has not yet been investigated. Objective: The study sought to compare the efficacy of a lower loading dose of prasugrel with conventional loading dose of prasugrel in Indian patients. Material and methods: Three hundred thirty-two Indian patients undergoing elective percutaneous coronary intervention (PCI) were enrolled in the study. Participants were randomly administered loading doses of prasugrel 60 mg (group A, n = 166) or 30 mg (group B, n = 166) before undergoing elective PCI in a 1:1 manner. Primary efficacy end point was composite of in-hospital death and stent thrombosis at 96 h, while safety end point was in-hospital bleeding. Results: The two groups did not differ in their baseline characteristics. The primary efficacy end point was 0.6% in both the conventional 60 mg loading dose (LD) and lower 30 mg LD groups (p = not significant). Minor bleeding was significantly less in group B [Bleeding Academic Research Consortium 1, A = 6.63% vs B = 1.81%, odds ratio (OR) = 3.86, 95% confidence interval (CI) = 1.06–14.08, P = 0.05]. Major bleeding was higher in group A (A = 3.61%, vs B = 1.81%, OR = 2.04, 95% CI = 0.50–8.29, P = 0.50). Conclusion: In Indian patients, 30 mg of prasugrel loading is as effective as 60 mg of prasugrel with significantly less minor bleeding. Keywords: Prasugrel, Loading dose, Percutaneous coronary intervention

Fungi of the order Mucorales can cause life-threatening infections. Here, Chibucos et al. present genomic and transcriptomic analyses of a diverse set of Mucorales fungi, shedding light on their evolution and identifying potential therapeutic targets in the pathogens and the host.

The two terms, pseudocyesis and delusion of pregnancy, were frequently used for pseudopregnancy. Delusion of pregnancy is a special form of hypochondriacal/somatic delusion reported in various psychiatric and organic disorders. The origin of the delusion of pregnancy in schizophrenia has often been explained by psycho-analytic interpretations attributing wish fulfilling, protective role to false beliefs, and mother establishes an undisturbed union with her fetus during pregnancy, which eliminate loneliness and helplessness. The current case is a 49-year-old married female with an illness of total duration of 10 years. Initial symptoms were delusion of infidelity and persecution and 2nd and 3rd person auditory hallucination; however, the patient started reporting around 2 years back that she was pregnant and there were three female children inside her abdominal cavity rather than in uterus. She was firm on this belief and was not convinced by family members even giving evidence contrary to her belief like showing ultrasonography report. She firmly believed that these are gift of God, and they are special children who would be delivered through special procedure. Blood investigation revealed raised prolactin level, blood sugar and ultra sonography suggestive of cholelithisis. Patient's psychiatric symptoms including delusion of pregnancy were significantly improved with treatment, and medical and surgical comorbidities were managed with appropriate consultations.

The erosion of plant biodiversity is a matter of global concern. Due to unawareness the building blocks of entire ecosystems are disappearing. Some medicinal plants like Taxus baccata Linn., Thymus serpyllum Linn., Coleus forskohli Will., Oroxylum indicum Linn., Valeriana hardwickii Wall., Malaxis acuminata D.Don, Habenaria edgeworthii Hook. f.ex.Collett., Costus speciosus (Koen.) Sm., Dioscorea deltodea Wall., Gloriosa superba Linn., Polygonatum cirrhifolium Wall. and Polygonatum verticillatum Linn., Thalictrum foliolosum DC., Berberis aristata DC., Baliospermum montanum Will., Bergenia ciliata (Haworth) Sternb., Clerodendrum serratum Linn., Valeriana jatamansii Jones, Celastrus paniculatus Will., Habenaria intermedeia D. Don, and Curculigo orchioides Gaerth are reached on the border of extinction. The 2008 IUCN Red List shows that the number of threatened plant species is increasing gradually (IUCN 2008). Therefore, there is an immediate need for conservation steps to be taken up along with promotion of conservation of medicinal plants.

Background: This study is aimed to find out the correlation between change in macular volume on optical coherence tomography (OCT) in patients with uncontrolled HbA1c levels . Methods: It is a observational study. Patients with diabetes mellitus for over 5 years were included in the study. Only one eye of each patient was selected for analysis. Eyes with proliferative diabetic retinopathy were not included in the study. Chronic HBA1c level was defined as mean HbA1c value in last one year duration. Central Subfield Volume (CSV) , Central Subfield Thickness (CST) and Total Macular Volume (TMV) were all measured by OCT. Results: 50 eyes from 50 patients (22 women and 28 men ; mean age 63.5 years ). Mean duration of Diabetes Mellitus (DM) being 10.5 years. 6 patients had Type 1 DM and 44 patients had Type 2 DM. Of these , 19 eyes (38 % ) had no diabetic retinopathy (DR) and 31 eyes (62 % ) had non proliferative diabetic retinopathy. In statistical analysis , CST ( mean 188.82 ± 27.62 µm , p = 0.03 ) , CSV ( mean 0.148 ± 0.022 mm3 , p = 0.03 ) and TMV ( mean 6.495 ± 0.717 mm3 , p = 0.003 ), all positively correlated with chronic HBA1c level (8.95 ± 1.40 % ). Conclusion: There is a positive correlation between chronic HbA1c and macular volume in patients with DM > 5 years duration without Macular oedema. Our studies suggest that there are changes in values of subclinical macular volume or thickness before onset of diabetic macular oedema (DMO) becomes clinically significant. Strict glycaemic control ( HbA1c levels below 6 ) is needed in case of diabetic patients to prevent development and further deterioration of macular function prior to development of DMO .

Background: This is a prospective study of ocular trauma profile related to road traffic accidents that presented to a tertiary care centre in Western Maharashtra. Aims & Objectives: To study the epidemiology and pattern of ocular trauma among the road traffic accident cases in western Maharashtra. Methodology: Hospital based study conducted from September 2013 to March 2015. 114 subjects (122 eyes) were enrolled in the study. 8 of these subjects had bilateral ocular trauma. The examination involved assessment of visual acuity and description of nature and extent of ocular injury. The visual outcome was taken to be the best corrected vision at 3 months post trauma. The chi-square test was used to statistically analyze the data. Results: It was observed that 32.79% of injuries were extra ocular, 59.02% were closed globe intraocular injuries and 8.19% were open globe intraocular injuries. 78.69 % of the injuries were mild, 9.84% were moderate and 11.84% were severe. The visual outcome was good (visual acuity of more than 6/18 at 3 months post-trauma) in 89.34%. Only 4.10% of the total cases studied had used safety measures viz., helmets or seat belts. A total of 12% of subjects were found to be under the influence of alcohol at the time of accident. Conclusions: Primary preventive approach such as promoting safe riding practices and strict implementation of traffic rules like riding at safe speed wearing helmet and avoiding alcohol before driving are needed to prevent road traffic accidents associated ocular morbidity.