Transfusion transmissible malaria: seroprevalence of malaria parasitemia in blood donors in Garhwal region of Uttarakhand, India.

Background and Objectives: Malaria was the first ever reported case of transfusion transmitted infection (TTI). Transfusion transmissible malaria (TTM) can result in febrile transfusion reaction in the recipient. TTM can be fatal if the blood transfusion recipient is from vulnerable population i.e. pregnant women or young children. Therefore, the present study was done to estimate the seroprevalence of malaria parasitemia among blood donors in Garhwal region. Materials and Methods: Study subjects were healthy blood donors who had passed the screening criteria for blood donation. Donors with a history of malaria were temporarily deferred for 3 months following full recovery. Screening of the donated blood units for malaria parasite was done using immunochromatography based rapid diagnostic test. Thin smear examination was performed for malaria parasite species identification. Results: A total of 1984 blood donations were screened for TTI. The seroprevalence of HBV, HCV HIV and syphilis was 0.3% (n=6), 0.25% (n=5), 0% (n=0) and 0% (n=0) respectively. The seroprevalence of malaria parasite was 0.05% (n=1). Plasmodium vivax was identified upon thin smear examination. The donor reactive for malaria parasite was a replacement donor and gave no recent history of fever or any past history of malaria. Conclusion: Meticulous donor screening combined with rapid diagnostic tests for malaria parasite is the most practical strategy to prevent TTM in Garhwal region of India.

Application of the Nadaraya-Watson estimator based attention mechanism to the field of predictive maintenance.

Attention mechanism has recently gained immense importance in the natural language processing (NLP) world. This technique highlights parts of the input text that the NLP task (such as translation) must pay "attention" to. Inspired by this, some researchers have recently applied the NLP domain, deep-learning based, attention mechanism techniques to predictive maintenance. In contrast to the deep-learning based solutions, Industry 4.0 predictive maintenance solutions that often rely on edge-computing, demand lighter predictive models. With this objective, we have investigated the adaptation of a simpler, incredibly fast and compute-resource friendly, "Nadaraya-Watson estimator based" attention method. We develop a method to predict tool-wear of a milling machine using this attention mechanism and demonstrate, with the help of heat-maps, how the attention mechanism highlights regions that assist in predicting onset of tool-wear. We validate the effectiveness of this adaptation on the benchmark IEEEDataPort PHM Society dataset, by comparing against other comparatively "lighter" machine learning techniques - Bayesian Ridge, Gradient Boosting Regressor, SGD Regressor and Support Vector Regressor. Our experiments indicate that the proposed Nadaraya-Watson attention mechanism performed best with an MAE of 0.069, RMSE of 0.099 and R2 of 83.40 %, when compared to the next best technique Gradient Boosting Regressor with figures of 0.100, 0.138, 66.51 % respectively. Additionally, it produced a lighter and faster model as well.•We propose a Nadaraya-Watson estimator based "attention mechanism", applied to a predictive maintenance problem.•Unlike the deep-learning based attention mechanisms from the NLP domain, our method creates fast, light and high-performance models, suitable for edge computing devices and therefore supports the Industry 4.0 initiative.•Method validated on real tool-wear data of a milling machine.

Characterization of an African swine fever virus outbreak in India and comparative analysis of immune genes in infected and surviving crossbreed vs. indigenous Doom pigs.

Since 2020, African swine fever (ASF) has affected all pig breeds in Northeast India except Doom pigs, a unique indigenous breed from Assam and the closest relatives of Indian wild pigs. ASF outbreaks result in significant economic losses for pig farmers in the region. Based on sequencing and phylogenetic analysis of the B646L (p72) gene, it has been determined that ASFV genotype II is responsible for outbreaks in this region. Recent studies have shown that MYD88, LDHB, and IFIT1, which are important genes of the immune system, are involved in the pathogenesis of ASFV. The differential expression patterns of these genes in surviving ASFV-infected and healthy Doom breed pigs were compared to healthy controls at different stages of infection. The ability of Doom pigs to withstand common pig diseases, along with their genetic resemblance to wild pigs, make them ideal candidates for studying tolerance to ASFV infection. In the present study, we investigated the natural resistance to ASF in Doom pigs from an endemic area in Northeast India. The results of this study provide important molecular insights into the regulation of ASFV tolerance genes.

Rupture of thin liquid trilayer films with soluble surfactants: fundamentals and applications to droplet coalescence.

Understanding the stability of thin liquid trilayer films is of direct relevance to applications such as multilayer coatings and polymer processing. The stability of trilayer films can also be used to provide insights into emulsion dynamics, such as the rupture of the thin film formed between two droplets during coalescence. Often, emulsions are laden with surfactants and other additives, which can be present in one or both phases as well as at the interfaces between the liquids. In experimental studies, complicating factors such as variations in droplet sizes, curvatures, and collision processes make it difficult to specifically isolate the influence of surfactant transport on droplet coalescence and film rupture. The present work addresses this issue by systematic consideration of a model problem involving a thin liquid trilayer film. Surfactant is soluble in either the outer layers or the inner layer, corresponding to surfactant soluble in the droplets or the continuous phase. Rupture of the inner layer is driven by van der Waals forces. Lubrication theory is applied to derive coupled nonlinear evolution equations describing the perturbations to the interface positions and the surfactant concentrations. Our findings reveal that surfactant better stabilizes the film when soluble in the inner layer, and the stabilizing effect is more pronounced when the outer layers are thicker. These findings are consistent with experimental observations involving emulsions, where emulsions tend to be more stable when surfactant is in the continuous phase rather than in the droplets, with the distinction being more pronounced when droplets are larger.

Role of Neurocellular Endoplasmic Reticulum Stress Response in Alzheimer's Disease and Related Dementias Risk.

Currently, more than 55 million people around the world suffer from dementia, and Alzheimer's Disease and Related Dementias (ADRD) accounts for nearly 60-70% of all those cases. The spread of Alzheimer's Disease (AD) pathology and progressive neurodegeneration in the hippocampus and cerebral cortex is strongly correlated with cognitive decline in AD patients; however, the molecular underpinning of ADRD's causality is still unclear. Studies of postmortem AD brains and animal models of AD suggest that elevated endoplasmic reticulum (ER) stress may have a role in ADRD pathology through altered neurocellular homeostasis in brain regions associated with learning and memory. To study the ER stress-associated neurocellular response and its effects on neurocellular homeostasis and neurogenesis, we modeled an ER stress challenge using thapsigargin (TG), a specific inhibitor of sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), in the induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) of two individuals from our Mexican American Family Study (MAFS). High-content screening and transcriptomic analysis of the control and ER stress-challenged NSCs showed that the NSCs' ER stress response resulted in a significant decline in NSC self-renewal and an increase in apoptosis and cellular oxidative stress. A total of 2300 genes were significantly (moderated t statistics FDR-corrected p-value ≤ 0.05 and fold change absolute ≥ 2.0) differentially expressed (DE). The pathway enrichment and gene network analysis of DE genes suggests that all three unfolded protein response (UPR) pathways, protein kinase RNA-like ER kinase (PERK), activating transcription factor-6 (ATF-6), and inositol-requiring enzyme-1 (IRE1), were significantly activated and cooperatively regulated the NSCs' transcriptional response to ER stress. Our results show that IRE1/X-box binding protein 1 (XBP1) mediated transcriptional regulation of the E2F transcription factor 1 (E2F1) gene, and its downstream targets have a dominant role in inducing G1/S-phase cell cycle arrest in ER stress-challenged NSCs. The ER stress-challenged NSCs also showed the activation of C/EBP homologous protein (CHOP)-mediated apoptosis and the dysregulation of synaptic plasticity and neurotransmitter homeostasis-associated genes. Overall, our results suggest that the ER stress-associated attenuation of NSC self-renewal, increased apoptosis, and dysregulated synaptic plasticity and neurotransmitter homeostasis plausibly play a role in the causation of ADRD.

Legal Frameworks Upholding Deceased Individuals' Rights and Enabling the Use of Cadavers in Anatomy Education and Research: A Systematic Review.

The study of human cadavers is essential for teaching, advanced training, and research in medical and anatomical sciences. Medical institutions around the globe presently face a scarcity of cadaver supplies. For the majority of countries, unclaimed bodies are still the primary source of cadavers despite guidelines issued by the International Federation of Associations of Anatomists, which discourage the use of unclaimed bodies. This self-funded study aims to conduct a review of the existing national and international laws safeguarding the several rights of a deceased person. The study also reviewed the existing anatomy acts (and related acts) across various countries that facilitate cadaver supply for anatomy education and research. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an online search for publications in four medical databases (PubMed, Scopus, Web of Sciences, and Google Scholar) was conducted from 1950 till 2022. A research review protocol was registered in PROSPERO prospectively (registration ID: CRD42023469534) using the Mesh terms like cadaver, anatomy education, dead person and rights, body donation program, unclaimed bodies, and anatomy acts. After the application of the eligibility criteria, 149 publications were shortlisted. After reviewing all the shortlisted articles, laws, and guidelines, using the data extraction checklist prepared by both authors, five international laws, three supreme court case decisions, two high court case decisions, four Indian penal Code Sections, and 22 anatomy acts were selected. Articles from other medical databases could not be reviewed, which was the limitation of this study. The anatomy/human tissue/tissue transplantation acts and advisories from regulatory bodies of individual African, Middle-Eastern, and European countries could not be retrieved. The review findings will emphasize the distinctions between India's anatomy acts and those of other developed nations, thereby broadening our perspective as we propose a model anatomy act for uniform implementation across the country to streamline the procurement of cadavers.

Heterogeneity-induced retraction in viscoelastic fluids following cessation of flow.

Complex fluids including colloidal suspensions, microgels, and entangled wormlike micelles (WLMs) can develop heterogeneous flow regions under imposed steady shear. In some of these systems, the evolution to this flow state from rest is accompanied by flow reversal - when a portion of the fluid moves opposite to the imposed flow direction. Flow reversal was proposed to occur in shear startup when (1) the fluid has significant elasticity, and (2) the flow becomes heterogeneous immediately following the stress overshoot [McCauley et al., J. Rheol., 2023, 67, 661-681]. To verify this hypothesis, a new method is developed for measuring flow heterogeneity. Upon cessation of the imposed flow, elasticity and flow heterogeneity cause retraction of the fluid, which is quantified with particle tracking velocimetry. Flow is stopped at key times during shear startup in two systems: a gel-like WLM that exhibits flow reversal before heterogeneous flow and a viscoelastic, fluid-like WLM that does not. The degree of flow heterogeneity is inferred from the shape and magnitude of velocity profiles measured during retraction. Flow heterogeneity develops earlier in gel-like WLMs - supporting the proposed flow reversal criteria. For comparison, heterogeneous Couette flows described with the upper-convected Maxwell or Germann-Cook-Beris models are analyzed. These theoretical flow problems confirm that stark differences in rheological properties across the flow geometry can cause significant fluid retraction and reproduce key features of the experimentally observed retraction. This new method can be used to extract quantitative information about spatially heterogeneous flows in viscoelastic complex fluids, whether or not flow reversal occurs.

Achieving a High Thermally Conductive One Micron AlN Deposition by High Power Impulse Magnetron Sputtering plus Kick.

High-power impulse magnetron sputtering (HiPIMS) plus kick is a physical vapor deposition method that employs bipolar microsecond-scale voltage pulsing to precisely control the ion energy during sputter deposition. HiPIMS plus kick for AlN deposition is difficult since nitride deposition is challenged by low surface diffusion and high susceptibility to ion damage. In this current study, a systematic examination of the process parameters of HiPIMS plus kick was conducted. Under optimized main negative pulsing conditions, this study documented that a 25 V positive kick biasing for AlN deposition is ideal for optimizing a high quality film, as shown by X-ray diffraction and transmission electron microscopy as well as optimal thermal conductivity while increasing high speed deposition (25 nm/min) and obtaining ultrasmooth surfaces (rms roughness = 0.5 nm). HiPIMS plus kick was employed to deposit a single-texture 1 µm AlN film with a 7.4° rocking curve, indicating well oriented grains, which correlated with high thermal conductivity (121 W/m·K). The data are consistent with the optimal kick voltage enabling enhanced surface diffusion due to ion-substrate collisions without damaging the AlN grains.

Evaluation of Osteogenic Potential of a Polysaccharide-Based Hydrogel Coating on Titanium.

INTRODUCTION: Reducing the healing period after surgical placement of dental implants can facilitate the loading of dental prostheses. AIM: The aim is to compare the osteogenic potential of unmodified titanium disks with titanium disks that were surface-modified or hydrogel-coated. MATERIALS AND METHODOLOGY: One hundred eight titanium disks (Ø6 × 2-mm) were divided into three groups: (1) unmodified titanium as control (Ti-C); (2) sandblasted and acid-etched (Ti-SLA), and (3) coated with tamarind kernel polysaccharide hydrogel grafted with acrylic acid (Ti-TKP-AA). The osteogenic potential and cytotoxic effect of various groups of titanium were compared using human osteoblasts Saos-2. The surface topography of the titanium disks and morphology of osteoblasts grown on disks were investigated by scanning electron microscopy (n = 3). Cell attachment to the disks and actin expression intensity were investigated by confocal imaging (n = 3). Cytotoxicity was quantified by cell viability assay (n = 9). Osteoblast maturation was determined by alkaline phosphatase assay (n = 9). Cell mineralization was quantified by Alizarin red staining (n = 9). One-way analysis of variance followed by Tukey's multiple comparisons test was used for intergroup comparisons (α= 0.05). RESULTS: The surface modifications on Ti-SLA and Ti-TKP-AA support better morphology and proliferation of osteoblasts than Ti-C (P< 0.001) and significantly higher levels of actin cytoskeleton accumulation (P< 0.0001). Ti-TKP-AA showed a significantly higher maturation rate than Ti-C (P< 0.001). Ti-TKP-AA showed > twofold increased mineralization than Ti-C and Ti-SLA (P< 0.001). CONCLUSIONS: TKP-AA hydrogel-coated titanium promotes faster osteoblast proliferation, maturation, and mineralization than SLA-treated or untreated titanium. These advantages can be explored for achieving early osseointegration and prosthetic loading of titanium dental implants.

Genome-wide association study identifies novel loci and candidate genes for rust resistance in wheat (Triticum aestivum L.).

BACKGROUND: Wheat rusts are important biotic stresses, development of rust resistant cultivars through molecular approaches is both economical and sustainable. Extensive phenotyping of large mapping populations under diverse production conditions and high-density genotyping would be the ideal strategy to identify major genomic regions for rust resistance in wheat. The genome-wide association study (GWAS) population of 280 genotypes was genotyped using a 35 K Axiom single nucleotide polymorphism (SNP) array and phenotyped at eight, 10, and, 10 environments, respectively for stem/black rust (SR), stripe/yellow rust (YR), and leaf/brown rust (LR). RESULTS: Forty-one Bonferroni corrected marker-trait associations (MTAs) were identified, including 17 for SR and 24 for YR. Ten stable MTAs and their best combinations were also identified. For YR, AX-94990952 on 1A + AX-95203560 on 4A + AX-94723806 on 3D + AX-95172478 on 1A showed the best combination with an average co-efficient of infection (ACI) score of 1.36. Similarly, for SR, AX-94883961 on 7B + AX-94843704 on 1B and AX-94883961 on 7B + AX-94580041 on 3D + AX-94843704 on 1B showed the best combination with an ACI score of around 9.0. The genotype PBW827 have the best MTA combinations for both YR and SR resistance. In silico study identifies key prospective candidate genes that are located within MTA regions. Further, the expression analysis revealed that 18 transcripts were upregulated to the tune of more than 1.5 folds including 19.36 folds (TraesCS3D02G519600) and 7.23 folds (TraesCS2D02G038900) under stress conditions compared to the control conditions. Furthermore, highly expressed genes in silico under stress conditions were analyzed to find out the potential links to the rust phenotype, and all four genes were found to be associated with the rust phenotype. CONCLUSION: The identified novel MTAs, particularly stable and highly expressed MTAs are valuable for further validation and subsequent application in wheat rust resistance breeding. The genotypes with favorable MTA combinations can be used as prospective donors to develop elite cultivars with YR and SR resistance.

Novel chitosan-based smart bio-nanocomposite films incorporating TiO2 nanoparticles for white bread preservation.

Chitosan (CS)-based bio-nanocomposite food packaging films were prepared via solvent-casting method by incorporating a unique combination of additives and fillers, including polyvinyl alcohol (PVA), glycerol, Tween 80, castor oil (CO), and nano titanium dioxide (TiO2) in various proportions to enhance film properties. For a comprehensive analysis of the synthesized films, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), tensile testing, field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), and UV-vis spectrophotometry were employed. Furthermore, the antimicrobial efficacy of the films against S. aureus, E. coli, and A. niger was examined to assess their potential to preserve food from foodborne pathogens. The results claimed that the inclusion of castor oil and TiO2 nanoparticles considerably improved antimicrobial properties, UV-vis light barrier properties, thermal stability, optical transparency, and mechanical strength of the films, while reducing their water solubility, moisture content, water vapor and oxygen permeability. Based on the overall analysis, CS/PVA/CO/TiO2-0.3 film can be selected as the optimal one for practical applications. Furthermore, the practical application of the optimum film was evaluated using white bread as a model food product. The modified film successfully extended the shelf life of bread to 10 days, surpassing the performance of commercial LDPE packaging (6 days), and showed promising attributes for applications in the food packaging sector. These films exhibit superior antimicrobial properties, improved mechanical strength, and extended shelf life for food products, marking a sustainable and efficient alternative to conventional plastic packaging in both scientific research and industrial applications.

Pinning-depinning transition of droplets on inclined substrates with a three-dimensional topographical defect.

Droplets on inclined substrates can depin and slide freely above a critical substrate inclination angle. Pinning can be caused by topographical defects on the substrate, and understanding the influence of defect geometry on the pinning-depinning transition is important for diverse applications such as fog harvesting, droplet-based microfluidic devices, self-cleaning surfaces, and inkjet printing. Here, we develop a lubrication-theory-based model to investigate the motion of droplets on inclined substrates with a single three-dimensional Gaussian-shaped defect that can be in the form of a bump or a dent. A precursor-film/disjoining-pressure approach is used to capture contact-line motion, and a nonlinear evolution equation is derived which describes droplet thickness as a function of the position along the substrate and time. The evolution equation is solved numerically using an alternating direction implicit finite-difference scheme to study how the defect geometry influences the critical inclination angle and the shape of a pinned droplet. It is found that the critical substrate inclination angle increases as the defect becomes taller/deeper or wider along the direction lateral to the droplet-sliding direction. However, the critical inclination angle decreases as the defect becomes wider along the sliding direction. Below the critical inclination angle, the advancing contact line of the droplet at the droplet centerline is pinned to the defect at the point having maximum negative slope. Simple scaling relations that reflect the influence of defect geometry on the droplet retention force arising from surface tension are able to account for many of the trends observed in the numerical simulations.

Reappraisal of the morphological and morphometric study of the psoas minor muscle with clinical and developmental insights: cadaveric study.

BACKGROUND: The Psoas Minor (PMi) is the most unstable muscle of the psoas group of the posterior abdominal muscle. This muscle has a fusiform shape and consists of a short fusiform belly continuing distally as a long tendon inserted on the pecten pubis and the iliopectineal arch. The present study was conducted to obtain more detailed information about the muscle and to expand knowledge about its morphology and morphometry. MATERIALS AND METHODS: The posterior abdominal wall of 30 adult cadavers was dissected. Anatomical variabilities in origin, insertion, length, width, and muscle-to-cone ratio were measured when PMi was found. The data collected was interpreted descriptively. RESULTS: PMi was found in 12 cases, ten bilateral and two unilateral. The origin was constant in all cases and, except for three cases, extended into the iliac fascia and the iliopubic eminence. Morphometric analysis revealed that the average length of the proximal muscle belly and distal tendons was 4.52 ± 1.35 cm and 13.05 ± 0.90 cm, respectively. The mean width of the muscle belly was 1.71 ± 0.17 cm, and that of the tendon was 0.47 ± 0.10 cm. On average, the muscle belly occupied the proximal 33.71 ± 6.15% of the total musculotendinous unit. CONCLUSIONS: Findings confirm the inconsistency of PMi in the study population. Morphological variations became more evident as the tendon approached the insertion level. The muscle's distal attachment to the iliac fascia may partially control the position, mechanical stability of the underlying iliopsoas and this circumstantial function may be clinically related to iliopsoas inflammation and pathology. However, further studies recommended to determine biomechanical validity and clinical applicability of this vestigial muscle in human.

Insights into the cumulative effect of Colletotrichum gloeosporioides and Fusarium acutatum causing anthracnose-twister disease complex of onion.

Colletotrichum is an important plant pathogenic fungi that causes anthracnose/-twister disease in onion. This disease was prevalent in the monsoon season from August to November months and the symptoms were observed in most of the fields. This study aimed to investigate the pathogenicity and cumulative effect, if any of Colletotrichum gloeosporioides and Fusarium acutatum. The pot experiment was laid out to identify the cause responsible for inciting anthracnose-twister disease, whether the Colletotrichum or Fusarium or both, or the interaction of pathogens and GA3. The results of the pathogenicity test confirmed that C. gloeosporioides and F. acutatum are both pathogenic. C. gloeosporioides caused twisting symptoms independently, while F.acutatum independently caused only neck elongation. The independent application of GA3 did not produce any symptoms, however, increased the plant height. The combined treatment of C. gloeosporioides and F. acutatum caused twisting, which enhanced upon interaction with GA3 application giving synergistic effect. The acervuli were found in lesions infected with C. gloeosporioides after 8 days of inoculation on the neck and leaf blades. Symptoms were not observed in untreated control plants. Koch's postulates were confirmed by reisolating the same pathogens from the infected plants.

Dietary polyphenols represent a phytotherapeutic alternative for gut dysbiosis associated neurodegeneration: A systematic review.

Globally, neurodegeneration and cerebrovascular disease are common and growing causes of morbidity and mortality. Pathophysiology of this group of diseases encompasses various factors from oxidative stress to gut microbial dysbiosis. The study of the etiology and mechanisms of oxidative stress as well as gut dysbiosis-induced neurodegeneration in Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, autism spectrum disorder, and Huntington's disease has recently received a lot of attention. Numerous studies lend credence to the notion that changes in the intestinal microbiota and enteric neuroimmune system have an impact on the initiation and severity of these diseases. The prebiotic role of polyphenols can influence the makeup of the gut microbiota in neurodegenerative disorders by modulating intracellular signalling pathways. Metabolites of polyphenols function directly as neurotransmitters by crossing the blood-brain barrier or indirectly via influencing the cerebrovascular system. This assessment aims to bring forth an interlink between the consumption of polyphenols biotransformed by gut microbiota which in turn modulate the gut microbial diversity and biochemical changes in the brain. This systematic review will further augment research towards the association of dietary polyphenols in the management of gut dysbiosis-associated neurodegenerative diseases.

TRPV4 Activator-Containing CMT-Hy Hydrogel Enhances Bone Tissue Regeneration In Vivo by Enhancing Mitochondrial Health.

Treating different types of bone defects is difficult, complicated, time-consuming, and expensive. Here, we demonstrate that transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechanosensitive, thermogated, and nonselective cation channel, is endogenously present in the mesenchymal stem cells (MSCs). TRPV4 regulates both cytosolic Ca2+ levels and mitochondrial health. Accordingly, the hydrogel made from a natural modified biopolymer carboxymethyl tamarind CMT-Hy and encapsulated with TRPV4-modulatory agents affects different parameters of MSCs, such as cell morphology, focal adhesion points, intracellular Ca2+, and reactive oxygen species- and NO-levels. TRPV4 also regulates cell differentiation and biomineralization in vitro. We demonstrate that 4α-10-CMT-Hy and 4α-50-CMT-Hy (the hydrogel encapsulated with 4αPDD, 10 and 50 nM, TRPV4 activator) surfaces upregulate mitochondrial health, i.e., an increase in ATP- and cardiolipin-levels, and improve the mitochondrial membrane potential. The same scaffold turned out to be nontoxic in vivo. 4α-50-CMT-Hy enhances the repair of the bone-drill hole in rat femur, both qualitatively and quantitatively in vivo. We conclude that 4α-50-CMT-Hy as a scaffold is suitable for treating large-scale bone defects at low cost and can be tested for clinical trials.

A three-arm randomised phase II study of the MEK inhibitor selumetinib alone or in combination with paclitaxel in metastatic uveal melanoma.

AIMS: The MAPK pathway is constitutively activated in uveal melanoma (UM). Selumetinib (AZD6244, ARRY-142886), a MEK inhibitor, has shown limited activity as monotherapy in metastatic UM. Pre-clinical studies support synergistic cytotoxic activity for MEK inhibitors combined with taxanes, and here we sought to assess the clinical efficacy of combining selumetinib and paclitaxel. PATIENTS AND METHODS: Seventy-seven patients with metastatic UM who had not received prior chemotherapy were randomised to selumetinib alone, or combined with paclitaxel with or without interruption in selumetinib two days before paclitaxel. The primary endpoint was progression free survival (PFS). After amendment, the combination arms were combined for analysis and the sample size adjusted to detect a hazard ratio (HR): 0.55, 80% power at 1-sided 5% significance level. RESULTS: The median PFS in the combination arms was 4.8 months (95% CI: 3.8 - 5.6) compared with 3.4 months (2.0 - 3.9) in the selumetinib arm (HR 0.62 [90% CI 0.41 - 0.92], 1-sided p-value = 0.022). ORR was 14% and 4% in the combination and monotherapy arms respectively. Median OS was 9 months for the combination and was not significantly different from selumetinib alone (10 months) with HR of 0.98 [90% CI 0.58 - 1.66], 1-sided p-value = 0.469. Toxicity was in keeping with the known profiles of the agents involved. CONCLUSIONS: SelPac met its primary endpoint, demonstrating an improvement in PFS for combination selumetinib and paclitaxel. No improvement in OS was observed, and the modest improvement in PFS is not practice changing.

Pre-Infection Innate Immunity Attenuates SARS-CoV-2 Infection and Viral Load in iPSC-Derived Alveolar Epithelial Type 2 Cells.

A large portion of the heterogeneity in coronavirus disease 2019 (COVID-19) susceptibility and severity of illness (SOI) remains poorly understood. Recent evidence suggests that SARS-CoV-2 infection-associated damage to alveolar epithelial type 2 cells (AT2s) in the distal lung may directly contribute to disease severity and poor prognosis in COVID-19 patients. Our in vitro modeling of SARS-CoV-2 infection in induced pluripotent stem cell (iPSC)-derived AT2s from 10 different individuals showed interindividual variability in infection susceptibility and the postinfection cellular viral load. To understand the underlying mechanism of the AT2's capacity to regulate SARS-CoV-2 infection and cellular viral load, a genome-wide differential gene expression analysis between the mock and SARS-CoV-2 infection-challenged AT2s was performed. The 1393 genes, which were significantly (one-way ANOVA FDR-corrected p ≤ 0.05; FC abs ≥ 2.0) differentially expressed (DE), suggest significant upregulation of viral infection-related cellular innate immune response pathways (p-value ≤ 0.05; activation z-score ≥ 3.5), and significant downregulation of the cholesterol- and xenobiotic-related metabolic pathways (p-value ≤ 0.05; activation z-score ≤ -3.5). Whilst the effect of post-SARS-CoV-2 infection response on the infection susceptibility and postinfection viral load in AT2s is not clear, interestingly, pre-infection (mock-challenged) expression of 238 DE genes showed a high correlation with the postinfection SARS-CoV-2 viral load (FDR-corrected p-value ≤ 0.05 and r2-absolute ≥ 0.57). The 85 genes whose expression was negatively correlated with the viral load showed significant enrichment in viral recognition and cytokine-mediated innate immune GO biological processes (p-value range: 4.65 × 10-10 to 2.24 × 10-6). The 153 genes whose expression was positively correlated with the viral load showed significant enrichment in cholesterol homeostasis, extracellular matrix, and MAPK/ERK pathway-related GO biological processes (p-value range: 5.06 × 10-5 to 6.53 × 10-4). Overall, our results strongly suggest that AT2s' pre-infection innate immunity and metabolic state affect their susceptibility to SARS-CoV-2 infection and viral load.

Functional insight into multi-omics-based interventions for climatic resilience in sorghum (Sorghum bicolor): a nutritionally rich cereal crop.

MAIN CONCLUSION: The article highlights omics-based interventions in sorghum to combat food and nutritional scarcity in the future. Sorghum with its unique ability to thrive in adverse conditions, has become a tremendous highly nutritive, and multipurpose cereal crop. It is resistant to various types of climatic stressors which will pave its way to a future food crop. Multi-omics refers to the comprehensive study of an organism at multiple molecular levels, including genomics, transcriptomics, proteomics, and metabolomics. Genomic studies have provided insights into the genetic diversity of sorghum and led to the development of genetically improved sorghum. Transcriptomics involves analysing the gene expression patterns in sorghum under various conditions. This knowledge is vital for developing crop varieties with enhanced stress tolerance. Proteomics enables the identification and quantification of the proteins present in sorghum. This approach helps in understanding the functional roles of specific proteins in response to stress and provides insights into metabolic pathways that contribute to resilience and grain production. Metabolomics studies the small molecules, or metabolites, produced by sorghum, provides information about the metabolic pathways that are activated or modified in response to environmental stress. This knowledge can be used to engineer sorghum varieties with improved metabolic efficiency, ultimately leading to better crop yields. In this review, we have focused on various multi-omics approaches, gene expression analysis, and different pathways for the improvement of Sorghum. Applying omics approaches to sorghum research allows for a holistic understanding of its genome function. This knowledge is invaluable for addressing challenges such as climate change, resource limitations, and the need for sustainable agriculture.

A portable EIS-based biosensor for the detection of microcystin-LR residues in environmental water bodies and simulated body fluids.

Due to the eutrophication of water bodies around the world, there is a drastic increase in harmful cyanobacterial blooms leading to contamination of water bodies with cyanotoxins. Chronic exposure to cyanotoxins such as microcystin leads to oxidative stress, inflammation, and liver damage, and potentially to liver cancer. We developed a novel and easy-to-use electrochemical impedance spectroscopy-based immunosensor by fabricating stencil-printed conductive carbon-based interdigitated microelectrodes and immobilising them with cysteamine-capped gold nanoparticles embedded in polyaniline. It has been also coupled with a custom handheld device enabling regular on-site assessment, especially in resource-constrained situations encountered in developing countries. The sensor is able to detect microcystin-LR up to 0.1 µg L-1, having a linear response between 0.1 and 100 µg L-1 in lake and river water and in serum and urine samples. In addition to being inexpensive, easy to fabricate, and sensitive, it also has very good selectivity.