The combined utility of many one and two dimensional NMR methodologies and DFT-based theoretical calculations have been exploited to detect the intramolecular hydrogen bond (HB) in number of ...different organic fluorine-containing derivatives of molecules, viz. benzanilides, hydrazides, imides, benzamides, and diphenyloxamides. The existence of two and three centered hydrogen bonds has been convincingly established in the investigated molecules. The NMR spectral parameters, viz., coupling mediated through hydrogen bond, one-bond NH scalar couplings, physical parameter dependent variation of chemical shifts of NH protons have paved the way for understanding the presence of hydrogen bond involving organic fluorine in all the investigated molecules. The experimental NMR findings are further corroborated by DFT-based theoretical calculations including NCI, QTAIM, MD simulations and NBO analysis. The monitoring of H/D exchange with NMR spectroscopy established the effect of intramolecular HB and the influence of electronegativity of various substituents on the chemical kinetics in the number of organic building blocks. The utility of DQ-SQ technique in determining the information about HB in various fluorine substituted molecules has been convincingly established.
Technology and the rapid growth in the area of brain imaging technologies have forever made for a pivotal role in analyzing and focusing the new views of brain anatomy and functions. The mechanism of ...image processing has widespread usage in the area of medical science for improving the early detection and treatment phases. Deep neural networks (DNN), till date, have demonstrated wonderful performance in classification and segmentation task. Carrying this idea into consideration, in this paper, a technique for image compression using a deep wavelet autoencoder (DWA), which blends the basic feature reduction property of autoencoder along with the image decomposition property of wavelet transform is proposed. The combination of both has a tremendous effect on sinking the size of the feature set for enduring further classification task by using DNN. A brain image dataset was taken and the proposed DWA-DNN image classifier was considered. The performance criterion for the DWA-DNN classifier was compared with other existing classifiers such as autoencoder-DNN or DNN, and it was noted that the proposed method outshines the existing methods.
► Sensitive Taqman based qRT-PCR, nested RT-PCR and MAC ELISA were developed for rapid and accurate diagnosis of suspected Kyasanur Forest Disease (KFD) cases in India. ► Clinical samples and ...different KFD virus strains were screened using real-time RT-PCR and nRT-PCR and were found that real-time RT-PCR could detect a very low copy number of KFD viral RNA. ► IgM ELISA was also very sensitive for detection of IgM specific to KFDV for human clinical samples.
Kyasanur forest disease (KFD) is a zoonotic viral disease caused by infection by a Flavivirus, a member of the family Flaviviridae. KFD is a public health concern in the Karnataka State in southern India. Available conventional diagnostic tests such as virus isolation and serological tests, such as haemagglutination inhibition and complement fixation tests are time consuming. This study reports the development of a nested RT-PCR nRT-PCR and a TaqMan-based real-time RT-PCR and IgM antibodies capture ELISA MAC-ELISA for rapid and accurate diagnosis of suspected KFD cases. The nRT-PCR and the TaqMan-based real-time RT-PCR assays were developed using gene sequences of the NS-5/non-coding region. Both the assays detected KFD viral RNA in acute phase human serum samples and can provide early diagnosis of infection. Real-time RT-PCR was found to be more sensitive than nRT-PCR, which could detect 38 copies of KFDV RNA. MAC-ELISA was developed for the detection of recent infections. Although real-time RT-PCR and nRT-PCR require expensive reagents, expensive equipment and trained personnel, the developed MAC-ELISA can be used easily in the affected areas. These tests add to the existing diagnosis arsenal against haemorrhagic viruses that are prevalent in India. These assays will also help to extend our knowledge of the pathology of KFD virus and its associated clinical features, by measuring the viral titre during infection and at the time of seroconversion. Information, which is not available currently because of the lack of appropriate diagnostic methods. In addition, early laboratory diagnosis of KFDV infection will help in the application of appropriate control measures and management of KFD cases.
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•Ashwagandha root extract was safe and tolerable for the participants.•Participants' vital signs and hematological parameters were stable.•Ashwagandha did not interfere with the ...normal liver function.•Thyroid hormone levels were stable.
Ashwagandha (Withania somnifera) is a well-established and reputed herb in Ayurvedic medicine. It has been used as a “Rasayana” (rejuvenator), nootropic, and as a powerful natural adaptogen. The herb extract is extensively used for general wellbeing and in specific ailments. However, only a few studies have investigated the safety and tolerability of Ashwagandha in humans. This study evaluated the safety of Ashwagandha root extract consumption in healthy adults.
: In this randomized, double-blind, placebo-controlled, and parallel-group study, 80 healthy participants (40 males, 40 females) were randomized in a 1:1 ratio to receive either Ashwagandha 300 mg or a placebo of the same dosage, twice daily, orally for 8 weeks. The study was conducted at MV Hospital, and King George Medical University, Lucknow, India. The primary safety outcomes considered were laboratory assessment of hematological parameters, serum biochemistry analysis including hepatotoxicity evaluation, and thyroid function parameters. The secondary outcomes of this study were the clinical adverse events and the vital parameters. The within and between the groups' datasets were compared using the Wilcoxon signed-rank test and the Mann Whitney U test, respectively.
A detailed evaluation of the vital signs such as body weight, body temperature, pulse rate, respiratory rate, systolic and diastolic blood pressure, and Body Mass Index (BMI) were conducted for each participant at the baseline and the end of the study for treatment and placebo groups. Similarly, hematological and biochemical parameters were evaluated at the baseline and at the end of study. The outcome did not indicate any untoward effects in any of the treated volunteers. No statistically significant change or abnormality was observed in the considered parameters including thyroid hormonal profile in both the groups. No adverse events were reported by any of the participants in this study.
Ashwagandha is being consumed since time immemorial following the Ayurvedic medicine practices. Modern science requires evidence of the safety and efficacy of the Ashwagandha extract before mass consumption for various health issues and as a supplement. The present study revealed that the consumption of Ashwagandha root extract for 8 weeks was safe in both males and females volunteers. However, long term study and varying dosage ranges should be investigated in the future.
Herein, we report a highly efficient and unprecedented approach for heteroarylation of congested α-bromoamides via electrophilic aromatic substitution of imidazo-heteroarenes and indolizines under ...mild reaction conditions (room temperature, metal, and oxidant free). The participation of an in situ generated aza-oxyallyl cation as an alkylating agent is the hallmark of this transformation. The method was readily adapted to synthesize novel imidazo-heteroarene-fused dibenzoazepinone architectures of potential medicinal value.
The number of casualties and fatalities brought on by road accidents is one of the most significant concerns in the modern world. Instead of dispatching ambulances only at the time of demand, ...pre-positioning them can reduce the response time and provide prompt medical attention. Deep learning techniques hold great potential and have proven to be essential for problem-solving and decision-making in the field of healthcare services. This study introduces a deep-embedded clustering-based approach to predict optimal locations for ambulance positing. Various factors and patterns in a geographical region greatly influence the occurrence of road crashes, hence understanding such relationships while model building is crucial. The present study also emphasizes the need of preserving such patterns during model building to ensure real-time results and implements them with the help of another deep-learning-based model, Cat2Vec. The proposed framework is also compared with traditional clustering algorithms like K-means, GMM, and Agglomerative clustering. Moreover, to calculate response time and distance in real time, a novel scoring function has also been introduced for the performance evaluation of various algorithms. The proposed ambulance-positing system exhibits remarkable performance, achieving an accuracy of 95% with k-fold cross-validation and a novel distance score of 7.581 proving the use of the proposed approach is better than all the other traditional algorithms used.
Aspect-based sentiment analysis (ABSA) includes aspect extraction and sentiment analysis on those extracted aspects. This paper is mainly focused on the explicit aspect extraction from product based ...online customer reviews. Many research studies on explicit aspect extractions have adopted dependency rule-based techniques but limited their focus to only nouns and noun phrases as potential aspects. Moreover, extraction of multiple-aspects and multi-word aspects from online reviews are also not addressed by previous research studies. In this paper, we have proposed a Dependency structure-based rules using ROOT Node (DS-RN) technique using spaCy dependency parser to extract nouns, noun phrases, verbs, verb phrases in addition to single word, multiple aspects and multi word aspect extractions from customer review datasets. In our proposed methodology, 30 new dependency-based rules are formulated and implemented on 5 different product-based datasets. This study is based on the pattern analysis of dependency structures of review sentences to develop dependency-based rules for explicit aspect extraction. The proposed approach also incorporated lexicon-based pruning techniques to remove irrelevant aspects and retain correct aspects. The performance results on 5 different product-based customer review datasets demonstrate that our proposed DS-RN approach outperforms all other state-of-the-art baseline works with averaged value of precision as 87%, recall with 97% and 91% as F1-score.
The outcome of the disease visceral leishmaniasis (VL), caused by Leishmania donovani (LD), largely relies on the relative dominance of host-protective type-1 T helper (Th1) cell response versus ...disease-promoting type-2 T helper (Th2) cell response. The Th1 and Th2 responses, in turn, are believed to be elicited by type-1 conventional dendritic cells (cDC1) and type-2 conventional DCs (cDC2), respectively. However, it is still unknown which DC subtype (cDC1 or cDC2) predominates during chronic LD infection and the molecular mechanism governing such occurrence. Here we report that in chronically infected mice, the splenic cDC1-cDC2 balance shifted toward the cDC2 subtype and that the receptor T cell immunoglobulin and mucin protein-3 (TIM-3) expressed by DCs played a key role in mediating this effect. Transfer of TIM-3-silenced DCs in fact prevented the predominance of the cDC2 subtype in mice with chronic LD infection. We also found that LD actually upregulated TIM-3 expression on DCs by triggering a TIM-3-mediated signaling pathway STAT3 (signal transducer and activator of transcription 3)→interleukin (IL)-10→c-Src→transcription factors Ets1, Ets2, USF1, and USF2. Notably, TIM-3 promoted STAT3 activation via a non-receptor tyrosine kinase Btk. Adoptive transfer experiments further demonstrated a critical role for STAT3-driven TIM-3 upregulation on DCs in increasing cDC2 abundance in chronically infected mice, which ultimately aided disease pathogenesis by augmenting Th2 responses. These findings document a new immunoregulatory mechanism contributing to disease pathology during LD infection and define TIM-3 as a key mediator of this process.
Kyasanur Forest disease virus (KFDV) is enzootic to India and maintained in ticks, mammals, and birds. It causes severe febrile illness in humans and was first recognized in 1957 associated with a ...high number of deaths among monkeys in Kyasanur Forest. Genetic analysis of 48 viruses isolated in India during 1957-2006 showed low diversity (1.2%). Bayesian coalescence analysis of these sequences and those of KFDVs from Saudi Arabia and the People's Republic of China estimated that KFDVs have evolved at a mean rate of approximately 6.4 x 10(-4) substitutions/site/year, which is similar to rates estimated for mosquito-borne flaviviruses. KFDVs were estimated to have shared a common ancestor in approximately 1942, fifteen years before identification of the disease in India. These data are consistent with the view that KFD represented a newly emerged disease when first recognized. Recent common ancestry of KFDVs from India and Saudi Arabia, despite their large geographic separation, indicates long-range movement of virus, possibly by birds.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway that leading to progressive motor and nonmotor symptoms. The formation of newborn ...neurons in the adult hippocampus is affected by many factors such as anxiety, depression and impairment in learning and memory that are commonly observed nonmotor symptoms in PD, indicating the role of adult neurogenesis in PD pathophysiology. Acetyl-l-carnitine (ALCAR), regulate mitochondrial metabolism and has been reported to improve cognitive functions in different neurodegenerative disorders through an unknown mechanism. For the first time, we investigated the effect of ALCAR on adult neurogenesis in the 6-hydroxydopamine (6-OHDA) induced rat model of PD-like phenotypes and also explored the possible underlying mechanism of action. A single unilateral administration of 6-OHDA into the medial forebrain bundle reduced neural progenitor cell (NPC) proliferation, long-term survival and neuronal differentiation in the hippocampus. Interestingly, chronic treatment with ALCAR (100 mg/kg/day, i.p) potentially enhanced proliferation, long term survival and neuronal differentiation of NPCs in rat model of PD-like phenotypes. ALCAR treatment stimulates cell survival related signals (AKT and BCL-2) by inhibiting cell death related cues (GSK-3β and BAX) which might be responsible for a neuroprotective effect of ALCAR in rat model of PD-like phenotypes. We conclude that ALCAR exerts neuroprotective effects against 6-OHDA-induced impairment in hippocampal neurogenesis by regulating cell survival and cell death-related signals.
•6-OHDA reduces the NSC proliferation, long-term survival and hippocampal neurogenesis in adult rats.•ALCAR treatment potentially enhanced NSC proliferation and adult hippocampal neurogenesis.•ALCAR-induced hippocampal neurogenesis by regulating proneural genes and cell survival related signals.
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