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5-Fluorouracil (5-FU) is the leading chemotherapeutic drug used to treat hepatocellular carcinoma, one of the major cancer diseases after atherosclerosis. Because of chemo-resistance, the success rate of treatment declines with time due to continuous drug exposure. Though autophagy induction is majorly responsible for acquired resistance, the exact role of this evolutionary conserved mechanism is unknown in cancer cell survival and suppression. The usual practice involves the combinatorial use of chemotherapeutic drugs with autophagy inhibitors like Chloroquine and Bafilomycin A, while neglecting the side effects caused by autophagy impairment in healthy cells. Starvation is a well-known physiological inducer of autophagy. In this study, by caloric modulation, we tried to circumvent the resistance imposed by prolonged drug exposure and investigated the effect of 5-FU in nutrient-sufficient and deficient conditions. Our findings show a substantial correlation between autophagy and increased cancer cell death in the presence of 5-FU, with negligible effects on normal cells. Experimental data revealed that nutritional deprivation augmented cell death in the presence of 5-FU through mitochondrial membrane damage and excessive reactive oxygen species (ROS) production, initiating apoptosis. Lipidation study also unveiled that under such combinatorial treatment cellular metabolism shifts from glucose to lipid biosynthesis. Overall, our experimental findings suggest that nutritional deprivation in combination with chemotherapeutic medication can be a new effective strategy to control hepatocellular carcinoma., (© 2024. The Author(s).)

Psoriasis is a chronic, non-contagious, immune-mediated skin disorder. Inflammation of the skin's surface is characterised by scaly white, red, or silvery spots that occur due to the hyper-proliferation of keratinocytes in the epidermal layer. Primarily, pharmaceutical drugs or immune therapy are used to treat psoriasis. We are all aware that, certain therapeutic strategies can have some adverse effects, and over time, that hidden inflammation may manifest. This article introduces a mathematical model for psoriasis, formulated by employing a set of nonlinear ordinary differential equations (ODEs) that describe the densities of T-cells, dendritic cells (DCs), keratinocytes, and mesenchymal stromal cells (MSCs) as basic cell populations. A tumor necrosis factor- α ( T N F - α ) inhibitor has been imposed from the initial stage of the treatment regime, using the optimal control theoretic approach, and the numerical results have been observed. After 80 days of monitoring using only biologic T N F - α inhibitors, if this approach did not provide the intended outcomes (when severity arises), stem cells are administered a few times in a pulsed manner as a cell replacement technique in addition to this anti T N F - α medicine. We have observed the combined therapeutic benefit of stem cell replacement with a T N F - α inhibitor from a mathematical point of view. The theoretical analysis and the numerical results revealed that stem cell transplantation, along with a T N F - α inhibitor, is a promising psoriasis treatment option moving forward., (© 2024. The Author(s).)

Replacement of water-intensive winter rice with strawberry (Fragaria × ananassa Duch.) may restrict groundwater extraction and improve water productivity and sustainability of agricultural production in the arsenic-contaminated Bengal basin. The potential of strawberry cultivation in terms of yield obtained and water use efficiency need to be evaluated under predominant soil types with mulch applications. Water-driven model AquaCrop was used to predict the canopy cover, soil water storage and above-ground biomass of strawberry in an arsenic-contaminated area in the Bengal basin. After successful calibration and validation over three seasons, AquaCrop was used over a range of management scenarios (nine drip-irrigation × three soil types × four mulch materials) to identify the best irrigation options for a drip-irrigated strawberry crop. The most appropriate irrigation of 176 mm for clay loam soil in lowland and 189 mm for sandy clay loam in medium land rice areas and the use of organic mulch from locally available jute agrotextile improved 1.4 times higher yield and 1.7 times higher water productivity than that of without mulch. Strawberry can be introduced as an alternative crop replacing rice in non-traditional upland and medium land areas of the arsenic-contaminated Bengal basin with 88% lower groundwater extraction load and better economic return to farmers., (© 2024. The Author(s).)

The first step in any dietary monitoring system is the automatic detection of eating episodes. To detect eating episodes, either sensor data or images can be used, and either method can result in false-positive detection. This study aims to reduce the number of false positives in the detection of eating episodes by a wearable sensor, Automatic Ingestion Monitor v2 (AIM-2). Thirty participants wore the AIM-2 for two days each (pseudo-free-living and free-living). The eating episodes were detected by three methods: (1) recognition of solid foods and beverages in images captured by AIM-2; (2) recognition of chewing from the AIM-2 accelerometer sensor; and (3) hierarchical classification to combine confidence scores from image and accelerometer classifiers. The integration of image- and sensor-based methods achieved 94.59% sensitivity, 70.47% precision, and 80.77% F1-score in the free-living environment, which is significantly better than either of the original methods (8% higher sensitivity). The proposed method successfully reduces the number of false positives in the detection of eating episodes., (© 2024. The Author(s).)

The Early Jurassic and Cretaceous deposits of India are known for their diverse sauropod fauna, while little is known from the Middle and Late Jurassic. Here we report the first ever remains of a dicraeosaurid sauropod from India, Tharosaurus indicus gen. et sp. nov., from the Middle Jurassic (early-middle Bathonian) strata of Jaisalmer Basin, western India. Known from elements of the axial skeleton, the new taxon is phylogenetically among the earlier-diverging dicraeosaurids, and its stratigraphic age makes it the earliest known diplodocoid globally. Palaeobiogeographic considerations of Tharosaurus, seen in conjunction with the other Indian Jurassic sauropods, suggest that the new Indian taxon is a relic of a lineage that originated in India and underwent rapid dispersal across the rest of Pangaea. Here we emphasize the importance of Gondwanan India in tracing the origin and early evolutionary history of neosauropod dinosaurs., (© 2023. Springer Nature Limited.)

Given an infected host, estimating the time that has elapsed since initial exposure to the pathogen is an important problem in public health. In this paper we use longitudinal gene expression data from human challenge studies of viral respiratory illnesses for building predictive models to estimate the time elapsed since onset of respiratory infection. We apply sparsity driven machine learning to this time-stamped gene expression data to model the time of exposure by a pathogen and subsequent infection accompanied by the onset of the host immune response. These predictive models exploit the fact that the host gene expression profile evolves in time and its characteristic temporal signature can be effectively modeled using a small number of features. Predicting the time of exposure to infection to be in first 48 h after exposure produces BSR in the range of 80-90% on sequestered test data. A variety of machine learning experiments provide evidence that models developed on one virus can be used to predict exposure time for other viruses, e.g., H1N1, H3N2, and HRV. The interferon [Formula: see text] signaling pathway appears to play a central role in keeping time from onset of infection. Successful prediction of the time of exposure to a pathogen has potential ramifications for patient treatment and contact tracing., (© 2023. The Author(s).)

This study evaluates the volumetric modulated arc therapy (VMAT) dosimetric comparison between Halcyon ring gantry and TrueBeam c-arm linear accelerators for craniospinal irradiation (CSI) of the neuro-axis. 25 patients, who received treatment for medulloblastoma and primitive neuro-ectodermal tumors between 2018 and 2021, were planned for VMAT in True Beam (TB), and Halcyon (HAL) linear accelerators using 6 MV unflattened (FFF) photon beams (HALFFF and TBFFF). Dose-volume statistics for the target and organs at risk (OARs) and the total number of monitoring units (MUs) in the treatment plans were compared which included dose received by 95% PTV volume (V95%), volume receiving ≥ 107% dose, homogeneity index (HI), conformity index (PI), MU and dose spillage (D10%, D30%, D50%, D70%, D90%). In all 26 OARs were considered of which five were serial and the remaining were parallel structures. For the former, the dose received by 0.2 cm 3 , volume = D0.2 cm 3 ) were evaluated and for the latter mean dose were evaluated. Both arms were statistically compared with paired sample t-test with a significant value of ≤ 0.05. 11 patients received treatment with the Halcyon and the rest 14 in the TrueBeam C-arm linear accelerator. Patients in the low- and intermediate-risk category (n = 13) received 23.4 Gy in 13 fractions. The remaining patients were in the high-risk category and received 35 Gy in 21 fractions or 36 Gy in 20 fractions. For HALFFF and TBFFF, PTVV95% were 97.5 ± 0.8% and 97.4 ± 0.9% respectively (p = 0.371) while the V107% were 0.6 ± 0.4% and 0.5 ± 0.5 respectively (p = 0.504). However, the number of monitoring units showed statistical significance (p < 0.001) with values of 1331.9 ± 243.4 MU and 1089 ± 206.7 MU respectively for the HAL and TB plans. The differences in spillage dose were also statistically significant, favouring HAL plans at D30% (p = 0.002), D50% (p < 0.001), D70% (p = 0.039), and D90% (p = 0.01) level except for D10% (p = 0.090). Conformity index also showed statistical significance with PI&#95;HAL = 0.9 ± 0.02 and PI&#95;TB = 0.89 ± 0.03 (p = 0.029). For 10 of the 21 parallel structures, the mean dose differences were statistically significant in favouring of HAL plans. Halcyon based VMAT CSI plans are dosimetrically superior in terms of organ dose, especially for the large organs, and offer lower spillage doses than the TrueBeam plans. Plans generated by both linear accelerators are suitable for the patients' treatments., (© 2023. The Author(s).)

Regulator-of-G-protein-signaling-5 (RGS5), a pro-apoptotic/anti-proliferative protein, is a signature molecule of tumor-associated pericytes, highly expressed in several cancers, and is associated with tumor growth and poor prognosis. Surprisingly, despite the negative influence of intrinsic RGS5 expression on pericyte survival, RGS5 high pericytes accumulate in progressively growing tumors. However, responsible factor(s) and altered-pathway(s) are yet to report. RGS5 binds with Gαi/q and promotes pericyte apoptosis in vitro, subsequently blocking GPCR-downstream PI3K-AKT signaling leading to Bcl2 downregulation and promotion of PUMA-p53-Bax-mediated mitochondrial damage. However, within tumor microenvironment (TME), TGFβ appeared to limit the cytocidal action of RGS5 in tumor-residing RGS5 high pericytes. We observed that in the presence of high RGS5 concentrations, TGFβ-TGFβR interactions in the tumor-associated pericytes lead to the promotion of pSmad2-RGS5 binding and nuclear trafficking of RGS5, which coordinately suppressed RGS5-Gαi/q and pSmad2/3-Smad4 pairing. The RGS5-TGFβ-pSmad2 axis thus mitigates both RGS5- and TGFβ-dependent cellular apoptosis, resulting in sustained pericyte survival/expansion within the TME by rescuing PI3K-AKT signaling and preventing mitochondrial damage and caspase activation. This study reports a novel mechanism by which TGFβ fortifies and promotes survival of tumor pericytes by switching pro- to anti-apoptotic RGS5 signaling in TME. Understanding this altered RGS5 signaling might prove beneficial in designing future cancer therapy., (© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

This paper addresses the development of predictive models for distinguishing pre-symptomatic infections from uninfected individuals. Our machine learning experiments are conducted on publicly available challenge studies that collected whole-blood transcriptomics data from individuals infected with HRV, RSV, H1N1, and H3N2. We address the problem of identifying discriminatory biomarkers between controls and eventual shedders in the first 32 h post-infection. Our exploratory analysis shows that the most discriminatory biomarkers exhibit a strong dependence on time over the course of the human response to infection. We visualize the feature sets to provide evidence of the rapid evolution of the gene expression profiles. To quantify this observation, we partition the data in the first 32 h into four equal time windows of 8 h each and identify all discriminatory biomarkers using sparsity-promoting classifiers and Iterated Feature Removal. We then perform a comparative machine learning classification analysis using linear support vector machines, artificial neural networks and Centroid-Encoder. We present a range of experiments on different groupings of the diseases to demonstrate the robustness of the resulting models., (© 2021. The Author(s).)

Globally, ~1 billion people, mostly residing in Africa and South Asia (e.g. India), still lack access to clean drinking water and sanitation. Resulting, unsafe disposal of fecal waste from open-defecation to nearby drinking water sources severely endanger public health. Until recently, India had a huge open-defecating population, leading declining public health from water-borne diseases like diarrhoea by ingesting polluted water, mostly sourced to groundwater. However, in recent past, sanitation development to achieve Sustainable Development Goals (SDGs) has been encouraged throughout India, but their effect to groundwater quality and human health conditions are yet-unquantified. Here, for the first time, using long term, high-spatial resolution measurements (>1.7 million) across India and analyses, we quantified that over the years, groundwater fecal coliform concentration (2002-2017, -2.56 ± 0.06%/year) and acute diarrheal cases (1990-2016, -3.05 ± 0.01%/year) have significantly reduced, potentially influenced by sanitation development (1990-2017, 2.63 ± 0.01%/year). Enhanced alleviation of groundwater quality and human health have been observed since 2014, with initiation of acceletated constructions of sanitation infrastructures through Clean India (Swachh Bharat) Mission. However, the goal of completely faecal-pollution free, clean drinking water is yet to be achieved. We also evaluated the suitability of using satellite-derived night-time light (NL an , 1992-2013, 4.26 ± 0.05%/year) as potential predictor for such economic development. We observed that in more than 80% of the study region, night-time light demonstrated to be a strong predictor for observed changes in groundwater quality, sanitation development and water-borne disease cases. While sanitation and economic development can improve public health, poor education level and improper human practices can strongly influence on water-borne diseases loads and thus health in parts of India.

Decoupling of different plasmon resonance modes (in-plane, and out-of-plane dipole and quadrupole resonances) by tuning nanoparticle's size and shape offers a new field of plasmonics as colorimetric assay-based optical-ruler for ultra-trace sensing. Driven by its low cost, easy to perform and efficient way to measure trace level (up to 30 ppt in presence of common mining elements in natural gold ore) abundance, this study develops a highly selective and ultrasensitive turn-on colorimetric sensor to detect gold-ion from environmental samples. Different level of gold-ion tracer makes size variable spherical- and disc-shaped silver nanoparticles when added to a 'growth solution' which results decoupling of in-plane dipole resonance from in-plane quadrupole and out-of-plane dipole resonances with a wide range of in-plane dipole plasmon tunability to generate different colors. This color-coded sensing of gold-ion shows high selectivity and ultrasensitivity over other metal ions in the ppt level with an impurity aberration limit of 1 ppm. A plausible explanation explains the possible role of catalytic gold-ion to initiate unfavorable silver ion (Ag + ) reduction by ascorbic acid to generate silver nanoparticles. Proposed technology has been applied in real mining sample (Bugunda Gold Deposit, Tajikistan) to detect gold concentration from ores to find potential application in mining technology.

The development of nano-enabled composite materials has led to a paradigm shift in the manufacture of high-performance nanocomposite membranes with enhanced permeation, thermo-mechanical, and antibacterial properties. The major challenges to the successful incorporation of nanoparticles (NPs) to polymer films are the severe aggregation of the NPs and the weak compatibility of NPs with polymers. These two phenomena lead to the formation of non-selective voids at the interface of the polymer and NPs, which adversely affect the separation performance of the membrane. To overcome these challenges, we have developed a new method for the fabrication of robust TFN reverse osmosis membranes. This approach relies on the simultaneous synthesis and surface functionalization of TiO 2 NPs in an organic solvent (heptane) via biphasic solvothermal reaction. The resulting stable suspension of the TiO 2 NPs in heptane was then utilized in the interfacial (in-situ) polymerization reaction where the NPs were entrapped within the matrix of the polyamide (PA) membrane. TiO 2 NPs of 10 nm were effectively incorporated into the thin PA layer and improved the thermal stability and anti-biofouling properties of the resulting TFN membranes. These features make our synthesized membranes potential candidates for applications where the treatment of high-temperature streams containing biomaterials is desirable.

Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify new factors controlling proliferation versus differentiation during tissue formation. Here, we generated a combinatorial, fluorescent reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations during brain development. Transcriptome sequencing revealed numerous novel long non-coding (lnc)RNAs and uncharacterized protein-coding transcripts identifying the signature of neurogenic commitment. Importantly, most lncRNAs overlapped neurogenic genes and shared with them a nearly identical expression pattern suggesting that lncRNAs control corticogenesis by tuning the expression of nearby cell fate determinants. We assessed the power of our approach by manipulating lncRNAs and protein-coding transcripts with no function in corticogenesis reported to date. This led to several evident phenotypes in neurogenic commitment and neuronal survival, indicating that our study provides a remarkably high number of uncharacterized transcripts with hitherto unsuspected roles in brain development. Finally, we focussed on one lncRNA, Miat, whose manipulation was found to trigger pleiotropic effects on brain development and aberrant splicing of Wnt7b. Hence, our study suggests that lncRNA-mediated alternative splicing of cell fate determinants controls stem-cell commitment during neurogenesis.