Search

Multi-parametric MRI (mpMRI) is widely used for prostate cancer (PCa) diagnosis. Deep learning models show good performance in detecting PCa on mpMRI, but domain-specific PCa-related anatomical information is sometimes overlooked and not fully explored even by state-of-the-art deep learning models, causing potential suboptimal performances in PCa detection. Symmetric-related anatomical information is commonly used when distinguishing PCa lesions from other visually similar but benign prostate tissue. In addition, different combinations of mpMRI findings are used for evaluating the aggressiveness of PCa for abnormal findings allocated in different prostate zones. In this study, we investigate these domain-specific anatomical properties in PCa diagnosis and how we can adopt them into the deep learning framework to improve the models detection performance. We propose an anatomical-aware PCa detection Network (AtPCa-Net) for PCa detection on mpMRI. Experiments show that the AtPCa-Net can better utilize the anatomical-related information, and the proposed anatomical-aware designs help improve the overall model performance on both PCa detection and patient-level classification.

Abstract The goal of this research is to create an ensemble deep learning model for Internet of Things (IoT) applications that specifically target remote patient monitoring (RPM) by integrating long short-term memory (LSTM) networks and convolutional neural networks (CNN). The work tackles important RPM concerns such early health issue diagnosis and accurate real-time physiological data collection and analysis using wearable IoT devices. By assessing important health factors like heart rate, blood pressure, pulse, temperature, activity level, weight management, respiration rate, medication adherence, sleep patterns, and oxygen levels, the suggested Remote Patient Monitor Model (RPMM) attains a noteworthy accuracy of 97.23%. The model's capacity to identify spatial and temporal relationships in health data is improved by novel techniques such as the use of CNN for spatial analysis and feature extraction and LSTM for temporal sequence modeling. Early intervention is made easier by this synergistic approach, which enhances trend identification and anomaly detection in vital signs. A variety of datasets are used to validate the model's robustness, highlighting its efficacy in remote patient care. This study shows how using ensemble models' advantages might improve health monitoring's precision and promptness, which would eventually benefit patients and ease the burden on healthcare systems.

Abstract Reproductive tract infections (RTIs) are a persistent public health threat worldwide, particularly among women in low-income countries of Africa, including Ethiopia, where drug resistance is also a growing problem. It is crucial to address this problem to ensure women's health and well-being. A cross-sectional study was carried out among a cohort of 398 women of reproductive age who sought medical attention at the Gynecology Department of the Arba Minch General Hospital, southern Ethiopia, from January to June 2020. They were chosen through systematic random sampling, and a pre-tested structured questionnaire was used to collect the data. The collection of vaginal and/or cervical swabs were done to diagnose bacterial vaginosis (BV) and aerobic vaginitis (AV) using Nugent and AV score analyses, respectively. The swabs were subjected to standard microbiological culture techniques to detect the isolates causing AV and vaginal candidiasis (VC). The susceptibility profiles of the causative agents of AV were checked by the Kirby-Bauer disc diffusion technique. Descriptive and inferential statistical analyses were also done. Aerobic vaginitis was the predominantly diagnosed RTI (n = 122, 30.7%), followed by BV (n = 117, 29.4%) and VC (n = 111, 27.9%). The prominent bacteria of AV were Escherichia coli (n = 36, 34.2%) and Klebsiella pneumoniae (n = 30, 28.5%). The overall rate of multidrug-resistant (MDR) bacteria was 65.71% (n = 69). History of abortion (p = 0.01; AOR = 4.0, 95% CI = 2.1, 7.7) and the habit of using vaginal pH-altering contraceptives (p = 0.01; AOR = 4.7, 95% CI = 2.5, 8.8) have the greatest odds of RTI. The high prevalence of RTIs in our study warrants an urgent intervention to minimize the associated morbidities and complications. The overall rate of MDR bacterial isolates necessitates the implementation of an effective surveillance program in the study setting.

Abstract Fins are widely used in many industrial applications, including heat exchangers. They benefit from a relatively economical design cost, are lightweight, and are quite miniature. Thus, this study investigates the influence of a wavy fin structure subjected to convective effects with internal heat generation. The thermal distribution, considered a steady condition in one dimension, is described by a unique implementation of a physics-informed neural network (PINN) as part of machine-learning intelligent strategies for analyzing heat transfer in a convective wavy fin. This novel research explores the use of PINNs to examine the effect of the nonlinearity of temperature equation and boundary conditions by altering the hyperparameters of the architecture. The non-linear ordinary differential equation (ODE) involved with heat transfer is reduced into a dimensionless form utilizing the non-dimensional variables to simplify the problem. Furthermore, Runge–Kutta Fehlberg’s fourth–fifth order (RKF-45) approach is implemented to evaluate the simplified equations numerically. To predict the wavy fin's heat transfer properties, an advanced neural network model is created without using a traditional data-driven approach, the ability to solve ODEs explicitly by incorporating a mean squared error-based loss function. The obtained results divulge that an increase in the thermal conductivity variable upsurges the thermal distribution. In contrast, a decrease in temperature profile is caused due to the augmentation in the convective-conductive variable values.

Abstract This investigation reported a one-step green synthesis of nickel oxide nanoparticles (NiO NPs) using aloe vera leaves extract solution for their application in a supercapacitor. This method used aloe vera leaves as a reducing agent, which is very simple and cost-effective. The synthesized NPs were thoroughly characterized using various techniques. The X-ray diffraction analysis unequivocally confirmed the crystalline nature; field emission scanning electron microscopy and transmission electron microscopy images showed different shapes and forms of an agglomerated cluster of synthesized NPs. The absorption spectra were recorded from UV visible spectroscopy, while Fourier transform infrared spectroscopy provided insights into the functional groups present. Electrochemical assessments were carried out via cyclic voltammetry, galvanostatic charging-discharging and electrochemical impedance spectroscopy. These experiments were performed using a 2 M KOH electrolyte within a 1.0 V potential window. Impressively, the single electrode displayed a remarkable specific capacitance of 462 F g−1 at a scan rate of 1 mV s−1 and 336 F g−1 at a current density of 0.76 A g−1. Further, a symmetric two-electrode device (NiO||NiO) has been successfully fabricated by employing a separator between the electrodes. The device exhibited an exceptional specific capacitance of approximately 239 F g−1, along with an energy density of 47.8 Wh kg−1 and a power density of 545 W kg−1 at 1 A g−1 current density within a 1.2 V potential window. The fabricated device also shows a retention capacity of 89% at 10 A g−1 after 2000 cycles with 114% of columbic efficiency. The present study underscores the effectiveness of the green synthesis approach in producing NiO NPs and establishes their potential as highly promising candidates for supercapacitor applications, showcasing both excellent electrochemical performance in a three-electrode system and remarkable stability in a practical two-electrode device. The results collectively highlight the efficacy of the green approach in producing NiO NPs, establishing its potential as a highly promising candidate for supercapacitor application.

Abstract Multi-parametric MRI (mpMRI) is widely used for prostate cancer (PCa) diagnosis. Deep learning models show good performance in detecting PCa on mpMRI, but domain-specific PCa-related anatomical information is sometimes overlooked and not fully explored even by state-of-the-art deep learning models, causing potential suboptimal performances in PCa detection. Symmetric-related anatomical information is commonly used when distinguishing PCa lesions from other visually similar but benign prostate tissue. In addition, different combinations of mpMRI findings are used for evaluating the aggressiveness of PCa for abnormal findings allocated in different prostate zones. In this study, we investigate these domain-specific anatomical properties in PCa diagnosis and how we can adopt them into the deep learning framework to improve the model’s detection performance. We propose an anatomical-aware PCa detection Network (AtPCa-Net) for PCa detection on mpMRI. Experiments show that the AtPCa-Net can better utilize the anatomical-related information, and the proposed anatomical-aware designs help improve the overall model performance on both PCa detection and patient-level classification.

Abstract Stroke remains a global health concern, necessitating early prediction for effective management. Atherosclerosis-induced internal carotid and intra cranial stenosis contributes significantly to stroke risk. This study explores the relationship between blood pressure and stroke prediction, focusing on internal carotid artery (ICA) branches: middle cerebral artery (MCA), anterior cerebral artery (ACA), and their role in hemodynamics. Computational fluid dynamics (CFD) informed by the Windkessel model were employed to simulate patient-specific ICA models with introduced stenosis. Central to our investigation is the impact of stenosis on blood pressure, flow velocity, and flow rate across these branches, incorporating Fractional Flow Reserve (FFR) analysis. Results highlight differential sensitivities to blood pressure variations, with M1 branch showing high sensitivity, ACA moderate, and M2 minimal. Comparing blood pressure fluctuations between ICA and MCA revealed heightened sensitivity to potential reverse flow compared to ICA and ACA comparisons, emphasizing MCA's role. Blood flow adjustments due to stenosis demonstrated intricate compensatory mechanisms. FFR emerged as a robust predictor of stenosis severity, particularly in the M2 branch. In conclusion, this study provides comprehensive insights into hemodynamic complexities within major intracranial arteries, elucidating the significance of blood pressure variations, flow attributes, and FFR in stenosis contexts. Subject-specific data integration enhances model reliability, aiding stroke risk assessment and advancing cerebrovascular disease understanding.

Abstract With the advent of long-term human habitation in space and on the moon, understanding how the built environment microbiome of space habitats differs from Earth habitats, and how microbes survive, proliferate and spread in space conditions, is becoming more important. The microbial tracking mission series has been monitoring the microbiome of the International Space Station (ISS) for almost a decade. During this mission series, six unique strains of Gram-stain-positive bacteria, including two spore-forming and three non-spore-forming species, were isolated from the environmental surfaces of the ISS. The analysis of their 16S rRNA gene sequences revealed > 99% similarities with previously described bacterial species. To further explore their phylogenetic affiliation, whole genome sequencing was undertaken. For all strains, the gyrB gene exhibited

Abstract This work reports experimental investigation and numerical validation of millimeter-sized Spherical Bragg Resonators (SBRs) fabricated using 3D printing technology. The frequency dependencies of the reflection and transmission coefficients were analyzed, and eigenfrequency values were calculated to examine the density of photonic states in air/PLA-polylactide SBRs, showing the appearance of an eigenmode and an increase in the local density of states in the core of a defect cavity. A decay rate enhancement of $${\sim 10}^{2}$$ ∼ 10 2 was obtained for a dipole placed in the core of the defect SBR. The study also investigated the influence of the source position on the resonator's electromagnetic wave energy. Scattering efficiencies up to order twelve of the multipole electric and magnetic contribution in a 10-layer SBR were calculated to validate the presence of the resonant modes observed in the scattering measurements performed for parallel and perpendicular polarizations. The results demonstrate that SBRs can act as omnidirectional cavities to enhance or inhibit spontaneous emission processes by modifying the density of electromagnetic states compared to free space. This finding highlights the potential of SBRs engineering spontaneous electromagnetic emission processes in various applications, including dielectric nanoantennas, optoelectronics devices, and quantum information across the entire electromagnetic spectrum.

Abstract We have prepared novel potent breast cancer drug molecules from non-toxic and inexpensive method. Column chromatography is not necessary for purification of target molecules. The value of overall atom economy, environmental factor, environmental catalyst and product mass intensity gives additional merits for this synthetic method. Synthesized flexible dimeric imidazolium bromides showed less toxicity and gives excellent anticancer response against normal mammary epithelial cells. Novel dimeric pyridinium bromides showed excellent anticancer response against tested cancer cell lines. In cell cycle, novel flexible dimeric pyridinium bromides showed significant arrest in the G2/M phase by nearly three folds, when compared with control drug. We have studied the targeting epidermal growth factor receptor for all the synthesized flexible amino substituted and methyl substituted dimeric pyridinium bromides.

Abstract Previous studies have shown that human platelets and megakaryocytes carry microRNAs suggesting their role in platelet function and megakaryocyte development, respectively. However, a comprehensive study on the microRNAs and their targets has not been undertaken. Zebrafish thrombocytes could be used as a model to study their role in megakaryocyte maturation and platelet function because thrombocytes have both megakaryocyte features and platelet properties. In our laboratory, we identified 15 microRNAs in thrombocytes using single-cell RNA sequencing. We knocked down each of these 15 microRNAs by the piggyback method and found knockdown of three microRNAs, mir-7148, let-7b, and mir-223 in adult zebrafish led to an increase in the percentage of thrombocytes. Functional thrombocyte analysis using plate tilt assay showed no modulatory effect of the three microRNAs on thrombocyte aggregation/agglutination. We also found enhanced thrombosis using arterial laser thrombosis assay in a group of zebrafish larvae after mir-7148, let-7b, and mir-223 knockdowns. These results suggested mir-7148, let-7b, and mir-223 are repressors for thrombocyte production. We then explored miRWalk database for let-7b downstream targets and then selected those that are expressed in thrombocytes, and from this list based on their role in differentiation selected 14 genes, rorca, tgif1, rfx1a, deaf1, zbtb18, mafba, cebpa, spi1a, spi1b, fhl3b, ikzf1, irf5, irf8, and lbx1b that encode transcriptional regulators. The qRT-PCR analysis of expression levels of the above genes following let-7b knockdown showed changes in the expression of 13 targets. We then studied the effect of the 13 targets on thrombocyte production and identified 5 genes, irf5, tgif1, irf8, cebpa, and rorca that showed thrombocytosis and one gene, ikzf1 that showed thrombocytopenia. Furthermore, we tested whether mir-223 regulates any of the above 13 transcription factors after mir-223 knockdown using qRT-PCR. Six of the 13 genes showed similar gene expression as observed with let-7b knockdown and 7 genes showed opposing results. Thus, our results suggested a possible regulatory network in common with both let-7b and mir-223. We also identified that tgif1, cebpa, ikzf1, irf5, irf8, and ikzf1 play a role in thrombopoiesis. Since the ikzf1 gene showed a differential expression profile in let-7b and mir-223 knockdowns but resulted in thrombocytopenia in ikzf1 knockdown in both adults and larvae we also studied an ikzf1 mutant and showed the mutant had thrombocytopenia. Taken together, these studies showed that thrombopoiesis is controlled by a network of transcription regulators that are regulated by multiple microRNAs in both positive and negative manner resulting in overall inhibition of thrombopoiesis.

Abstract Quantitative real-time polymerase chain reaction (RT-qPCR) using a stable reference gene is widely used for gene expression research. Barnyard millet (Echinochloa spp.) is an ancient crop in Asia and Africa that is widely cultivated for food and fodder. It thrives well under drought, salinity, cold, and heat environmental conditions, besides adapting to any soil type. To date, there are no gene expression studies performed to identify the potential candidate gene responsible for stress response in barnyard millet, due to lack of reference gene. Here, 10 candidate reference genes, Actin (ACT), α-tubulin (α-TUB), β-tubulin (β-TUB), RNA pol II (RP II), elongation factor-1 alpha (EF-1α), adenine phosphoribosyltransferase (APRT), TATA-binding protein-like factor (TLF), ubiquitin-conjugating enzyme 2 (UBC2), ubiquitin-conjugating enzyme E2L5 (UBC5) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were selected from mRNA sequences of E. crus-galli and E. colona var frumentacea. Five statistical algorithms (geNorm, NormFinder, BestKeeper, ΔCt, and RefFinder) were applied to determine the expression stabilities of these genes in barnyard millet grown under four different abiotic stress (drought, salinity, cold and heat) exposed at different time points. The UBC5 and ɑ-TUB in drought, GAPDH in salinity, GAPDH and APRT in cold, and EF-1α and RP II in heat were the most stable reference genes, whereas ß-TUB was the least stable irrespective of stress conditions applied. Further Vn/Vn + 1 analysis revealed two reference genes were sufficient to normalize gene expression across all sample sets. The suitability of identified reference genes was validated with Cu-ZnSOD (SOD1) in the plants exposed to different abiotic stress conditions. The results revealed that the relative quantification of the SOD1 gene varied according to reference genes and the number of reference genes used, thus highlighting the importance of the choice of a reference gene in such experiments. This study provides a foundational framework for standardizing RT-qPCR analyses, enabling accurate gene expression profiling in barnyard millet.

Abstract In this work we demonstrate the integration of a spectrometer directly into smartphone screen by femtosecond laser inscription of a weak Raman–Nath volume grating either into the Corning Gorilla glass screen layer or in the tempered aluminosilicate glass protector screen placed in front of the phone camera. Outside the thermal accumulation regime, a new writing regime yielding positive refractive index change was found for both glasses which is fluence dependent. The upper-bound threshold for this thermal-accumulation-less writing regime was found for both glasses and were, respectively at a repetition rate less than 150 kHz and 101 kHz for fluence of 8.7 × 106 J/m2 and 1.4 × 107 J/m2. A weak volume Raman–Nath grating of dimension 0.5 by 3 mm and 3 μm pitch was placed in front of a Samsung Galaxy S21 FE cellphone to record the spectrum using the 2nd diffraction order. This spectrometer covers the visible band from 401 to 700 nm with a 0.4 nm/pixel detector resolution and 3 nm optical resolution. It was used to determine the concentration detection limit of Rhodamine 6G in water which was found to be 0.5 mg/L. This proof of concept paves the way to in-the-field absorption spectroscopy for quick information gathering.

Intranasal insulin (INI) has shown promise as a treatment for Alzheimer's disease (AD) in pilot clinical trials. In a recent phase 2 trial, participants with mild cognitive impairment (MCI) or AD who were treated with INI with one of two delivery devices showed improved cerebral spinal fluid (CSF) biomarker profiles and slower symptom progression compared with placebo. In the cohort which showed benefit, we measured changes in CSF markers of inflammation, immune function and vascular integrity and assessed their relationship with changes in cognition, brain volume, and CSF amyloid and tau concentrations. The insulin-treated group had increased CSF interferon-γ (p = 0.032) and eotaxin (p = 0.049), and reduced interleukin-6 (p = 0.048) over the 12 month trial compared to placebo. Trends were observed for increased CSF macrophage-derived chemokine for the placebo group (p = 0.083), and increased interleukin-2 in the insulin-treated group (p = 0.093). Insulin-treated and placebo groups showed strikingly different patterns of associations between changes in CSF immune/inflammatory/vascular markers and changes in cognition, brain volume, and amyloid and tau concentrations. In summary, INI treatment altered the typical progression of markers of inflammation and immune function seen in AD, suggesting that INI may promote a compensatory immune response associated with therapeutic benefit.

Abstract In the current article, we use a random supercontinuum based on a random Raman distributed feedback laser to investigate the generation of random numbers by spectrally demultiplexing the broad supercontinuum spectrum in parallel channels. By tuning the spectral separation between two independent channels, we test the most typically used statistical tests’ abilities to identify the required minimum spectral separation between channels, especially after the use of post-processing steps. Out of all the tests that were investigated, the cross-correlation across channels using the raw data appears to be the most robust. We also demonstrate that the use of post-processing steps, either least significant bits extraction or exclusive-OR operations, hinders the ability of these tests to detect the existing correlations. As such, performing these tests on post-processed data, often reported in literature, is insufficient to properly establish the independence of two parallel channels. We therefore present a methodology, which may be used to confirm the true randomness of parallel random number generation schemes. Finally, we demonstrate that, while tuning a single channel’s bandwidth can modify its potential randomness output, it also affects the number of available channels, such that the total random number generation bitrate is conserved.

Abstract We demonstrate laser induced cooling in ytterbium doped silica (SiO2) glass with alumina, yttria co-doping (GAYY-Aluminum: Yttrium: Ytterbium Glass) fabricated using the modified chemical vapour deposition (MCVD) technique. A maximum temperature reduction by − 0.9 K from room temperature (296 K) at atmospheric pressure was achieved using only 6.5 W of 1029 nm laser radiation. The developed fabrication process allows us to incorporate ytterbium at concentration of 4 × 1026 ions/m3 which is the highest value reported for laser cooling without clustering or lifetime shortening, as well as to reach a very low background absorptive loss of 10 dB/km. The numerical simulation of temperature change versus pump power well agrees with the observation and predicts, for the same conditions, a temperature reduction of 4 K from room temperature in a vacuum. This novel silica glass has a high potential for a vast number of applications in laser cooling such as radiation-balanced amplifiers and high-power lasers including fiber lasers.

Abstract Early Infant Diagnosis of HIV infection services are crucial for managing the perinatally acquired HIV infection. Assessing the performance of the EID services and its underlying determinants is important for the National AIDS Control Program, India. The objectives of this study were to find out access to HIV testing, the timeliness of the testing cascade, and the proportion of HIV exposed infants who are followed up to 18 months for a definitive diagnosis of HIV. The study design was a mixed method. A total of 11 states accounting for 80% of HIV-positive pregnant women were selected. Program records from a total of 62 Integrated counselling and testing centres (ICTCs) served as the source of information. The qualitative component included interviews of program managers at the state and district level, service providers at the ICTC level, and caregivers of HIV exposed infants. In the sampled 62 ICTCs, 78% of the HIV exposed infants had at least one HIV test. Of the infants who had HIV tests, 50% had at first sample collected by 8 weeks of age. The median turnaround time from sample collection to DNA PCR testing was 36 (IQR 19–70) days and that to next sample collection in case of detection of virus in the first sample was 66 (IQR 55–116) days. At 18 months of age, 544 (62%) HIV exposed infants were retained in the EID testing cascade. A total of 30 infants were diagnosed with HIV at a median age of 421 (IQR 149–650) days. More than three fourth of the HIV exposed infants had access to early infant diagnosis (EID) services. Both demand and supply-side factors contribute to access, timeliness and retention and there is a need to address these factors.

Abstract Decreased estrogens during menopause are associated with increased risk of anxiety, depression, type 2 diabetes and obesity. Similarly, depleting estrogens in rodents by ovariectomy, combined with a high-fat diet (HFD), increases anxiety and adiposity. How estrogens and diet interact to affect anxiety and metabolism is poorly understood. Mounting evidence indicates that gut microbiota influence anxiety and metabolism. Here, we investigated the effects of estradiol (E) and HFD on anxiety, metabolism, and their correlation with changes in gut microbiota in female mice. Adult C57BL/6J mice were ovariectomized, implanted with E or vehicle-containing capsules and fed a standard diet or HFD. Anxiety-like behavior was assessed and neuronal activation was measured by c-fos immunoreactivity throughout the brain using iDISCO. HFD increased anxiety-like behavior, while E reduced this HFD-dependent anxiogenic effect. Interestingly, E decreased neuronal activation in brain regions involved in anxiety and metabolism. E treatment also altered gut microbes, a subset of which were associated with anxiety-like behavior. These findings provide insight into gut microbiota-based therapies for anxiety and metabolic disorders associated with declining estrogens in menopausal women.

Abstract Isolated active sites have great potential to be highly efficient and stable in heterogeneous catalysis, while enabling low costs due to the low transition metal content. Herein, we present results on the synthesis, first catalytic trials, and characterization of the Ga9Rh2 phase and the hitherto not-studied Ga3Rh phase. We used XRD and TEM for structural characterization, and with XPS, EDX we accessed the chemical composition and electronic structure of the intermetallic compounds. In combination with catalytic tests of these phases in the challenging propane dehydrogenation and by DFT calculations, we obtain a comprehensive picture of these novel catalyst materials. Their specific crystallographic structure leads to isolated Rhodium sites, which is proposed to be the decisive factor for the catalytic properties of the systems.

Abstract Viscum album L. (Santalaceae) is an important medicinal plant traditionally used to treat several diseases, including cancer therapy. This paper provides detailed morpho-anatomical characteristics of the leaves, stems and berries of Viscum album subsp. album growing as hemi-parasite on the branches of Malus domestica (Suckow) Borkh. (Rosaceae) to aid species identification and botanical characterization. Additionally, for the first time, microchemical analyses of all tissues and Energy Dispersive X-Ray Spectroscopy analyses of the calcium oxalate crystals are provided for the first time. The plant features leathery presents green leaves with parallel veins, small yellow unisexual flowers in 3-flowered cymes, and the dioecious inflorescences usually consist of three flowers, with female flowers generating white fleshy berries, in which a seed is embedded in the mucilaginous mesocarp, normally containing two embryos. Anatomically, the analyzed leaves were isobilateral and amphistomatic, and showed straight anticlinal epidermal cell walls, thick cuticles with epicuticular wax crystalloids, and paracytic stomata. The midrib is flat on both sides and has a single vascular bundle, whereas the strongly shortened petiole is concave-convex in shape and contains five bundles. The stems show a primary structure with a ring of nine vascular bundles enclosing the pith. Calcium oxalate druses and cubic and quadrangular prisms were observed in different plant parts. The results of this study provide new microscopy information that can help in the authentication of mistletoe raw materials.

Abstract Increasing the inertia is widely considered to be the solution to resolving unstable interactions between coupled oscillators. In power grids, Virtual Synchronous Generators (VSGs) are proposed to compensate for reducing inertia as rotating fossil-fuel-based generators are being phased out. Yet, modeling how VSGs and rotating generators simultaneously contribute energy and inertia, we surprisingly find that instabilities of a small-signal nature could arise despite fairly high system inertia if the generators’ controls are not coordinated at the system level. Importantly, we show there exist both an optimal and a maximum number of such VSGs that can be safely supported, a previously unknown result directly useful for power utilities in long-term planning and prosumer contracting. Meanwhile, to resolve instabilities in the short term until system-level coordination can be achieved, we argue that the new market should include another commodity that we call stability storage, whereby—analogous to energy storage buffering energy imbalances—VSGs act as decentralized stability buffers. While demonstrating the effectiveness of this concept for a wide range of energy futures, we provide policymakers and utilities with a roadmap towards achieving a 100% renewable grid.

Abstract Diabetic retinopathy (DR) at risk of vision loss (referable DR) needs to be identified by retinal screening and referred to an ophthalmologist. Existing automated algorithms have mostly been developed from images acquired with high cost mydriatic retinal cameras and cannot be applied in the settings used in most low- and middle-income countries. In this prospective multicentre study, we developed a deep learning system (DLS) that detects referable DR from retinal images acquired using handheld non-mydriatic fundus camera by non-technical field workers in 20 sites across India. Macula-centred and optic-disc-centred images from 16,247 eyes (9778 participants) were used to train and cross-validate the DLS and risk factor based logistic regression models. The DLS achieved an AUROC of 0.99 (1000 times bootstrapped 95% CI 0.98–0.99) using two-field retinal images, with 93.86 (91.34–96.08) sensitivity and 96.00 (94.68–98.09) specificity at the Youden’s index operational point. With single field inputs, the DLS reached AUROC of 0.98 (0.98–0.98) for the macula field and 0.96 (0.95–0.98) for the optic-disc field. Intergrader performance was 90.01 (88.95–91.01) sensitivity and 96.09 (95.72–96.42) specificity. The image based DLS outperformed all risk factor-based models. This DLS demonstrated a clinically acceptable performance for the identification of referable DR despite challenging image capture conditions.

Abstract A novel antibacterial immunostimulant using Platinum nanoparticles (PtNPs) and lectin from Metapenaeus dobsoni (Md-Lec) was developed. The Md-Lec and PtNPs (Pt-lec) hybrid formed through non-covalent interaction exhibits antimicrobial activity against fish specific pathogens by affecting membrane integrity and producing excess reactive oxygen species. The therapeutic efficacy of Pt-lec was demonstrated through rescuing Aeromonas hydrophila infected Nile Tilapia. Pt-lec prevents the infection spreading and reduces the bacterial bioburden in less than 12 h, and as a result of this the fish were restored to normalcy. To assess immunostimulation, we studied the expression of three different immune related genes, namely LEC, Myd88 and COX-2 in the gills, liver, spleen and kidney of fish under various experimental conditions. Our results showed that Pt-lec treatment appeared to be better when compared to lectin alone in enhancing the expression of Myd88 and COX-2, but LEC was not as expected. These results suggest that Pt-lec has the ability to protect Nile Tilapia against bacterial infection by restricting bacterial bioburden through their direct effects on the bacterial membrane and indirectly through their effects on host immune-related gene expression. This hybrid could have potential “green” application in fish farming in rescuing infected animals when compared to widely and unregulated antibiotics.

Abstract The COVID-19 pandemic outbreak led to a global ventilator shortage. Hence, various strategies for using a single ventilator to support multiple patients have been considered. A device called Ventil previously validated for independent lung ventilation was used in this study to evaluate its usability for shared ventilation. We performed experiments with a total number of 16 animals. Eight pairs of pigs were ventilated by a ventilator or anesthetic machine and by Ventil for up to 27 h. In one experiment, 200 ml of saline was introduced to one subject’s lungs to reduce their compliance. The experiments were analyzed in terms of arterial blood gases and respiratory parameters. In addition to the animal study, we performed a series of laboratory experiments with artificial lungs (ALs). The resistance and compliance of one AL (affected) were altered, while the tidal volume (TV) and peak pressure (Ppeak) in the second (unaffected) AL were analyzed. In addition, to assess the risk of transmission of pathogens between AL respiratory tracts, laboratory tests were performed using phantoms of virus particles. The physiological level of analyzed parameters in ventilated animals was maintained, except for CO2 tension, for which a permissive hypercapnia was indicated. Experiments did not lead to injuries in the animal’s lungs except for one subject, as indicated by CT scan analysis. In laboratory experiments, changes in TV and Ppeak in the unaffected AL were less than 11%, except for 2 cases where the TV change was 20%. No cross-contamination was found in simulations of pathogen transmission. We conclude that ventilation using Ventil can be considered safe in patients undergoing deep sedation without spontaneous breathing efforts.

Abstract Despite having a high risk of soil-transmitted helminths (STHs) infection, no national level study has been conducted to assess incidence and correlates of STHs in Nepal. Thus, we hypothesized that micronutrients and social status are linked with incidence of STHs infection among 6–59 months children and 15–49 years non-pregnant women in Nepal and Kato-Katz technique was adopted to measure the type and intensity of STHs infections using fresh stool specimens and venous blood was used to examine micronutrients biomarkers. Anthropometric measurements such as height and weight, sociodemographic and health status were determined using structured questionnaire. Logistic regression was used to assess unadjusted and adjusted odds ratio (AOR) and the 95% CIs of ORs. The bivariate association of STHs was assessed with the covariates variables. Overall, 12% children and 19% non-pregnant women had STHs infection; A. lumbricoides was the predominant helminth in both study participants. In multivariate model; age, ethnicity, anaemia and zinc deficiency were associated with STHs infections in children. Similarly, higher odds of STHs occurrence was observed among non-pregnant women with vitamin A deficiency. Findings from this study suggest that high-risk population, with a focus on those of lower socioeconomic status should be on priority of deworming program, nutrition intervention, and mass administration of preventive chemotherapy and sanitation champions supplement to reduce the STHs infections in Nepal.

Abstract Extracorporeal membrane oxygenation (ECMO) may be a viable salvage therapy in selected patients with septic shock. As ECMO use increases, we studied left ventricular (LV) performance during sepsis with and without ECMO using a pressure–volume (PV) loop in a murine model and aimed to understand LV hemodynamics in septic shock with ECMO. The rats were divided into Group 1 (ECMO applied to healthy rats), Group 2 (ECMO for septic rats), Group 3 (Controls, n = 20) and Group 4 (Sepsis induction only, n = 20). The cardiac parameters include end-diastolic volume (EDV), end-systolic volume (ESV), end-diastolic pressure (EDP), and end-systolic pressure (ESP), ejection fraction (EF), end-systolic elastance (Ees), diastolic time constant (Tau) index, arterial elastance (Ea), pressure–volume area (PVA), stroke work (SW), and potential energy (PE). We compared the changes of parameters in all groups. A total of 74 rats were included in the analyses. After 2 h on ECMO, Group 2 was associated with significant increases in ESP, EDV, ESV, PVA, PE, and SW. The difference ratio of PE and PVA was significantly higher in Group 2 compared to Group 1 (P

Abstract Sub-Optimal deployment of Self expanding interwoven stents (Supera) has been shown to increase the rate of Clinically Driven Target Lesion Revascularization (CD-TLR). Meanwhile, drug coated balloons (DCB) have been shown to reduce CD-TLR in the femoral-popliteal segment in de- novo and restenotic lesions. However, the clinical effects of vessel preparation with DCB in nominal, compressed, and elongated Supera has not been widely studied. The purpose of this study is to assess the outcomes of clinically driven re-intervention, major amputations, and mortality in relation to the use of DCB as vessel preparation in different deployment conditions (nominal, compressed, elongated) of the Supera stent. Patient chart data was collected at a single center hospital between March 2015 and May 2020. All patients were adults (≥ 18 years old) and were treated with at least one (≥ 1) Supera stent. Deployment status was extrapolated from anonymized angiograms. The primary endpoint of this study was CD-TLR. Secondary endpoints included amputation and mortality rates associated with each deployment condition. A total of 670 limbs were treated and patients were followed for 36 months. Nominal stent deployment was observed in 337 limbs, followed by elongated condition (n = 176), then by compressed conditions (n = 159). CD-TLR was observed most frequently with elongated deployment. Drug coated balloons were used as vessel prep prior to stenting and showed a protective effect regardless of deployment status; O.R = 0.44 (CI 0.30–0.66, p

Abstract The house mouse species complex (Mus musculus) is comprised of three primary subspecies. A large number of secondary subspecies have also been suggested on the basis of divergent morphology and molecular variation at limited numbers of markers. While the phylogenetic relationships among the primary M. musculus subspecies are well-defined, relationships among secondary subspecies and between secondary and primary subspecies remain less clear. Here, we integrate de novo genome sequencing of museum-stored specimens of house mice from one secondary subspecies (M. m. bactrianus) and publicly available genome sequences of house mice previously characterized as M. m. helgolandicus, with whole genome sequences from diverse representatives of the three primary house mouse subspecies. We show that mice assigned to the secondary M. m. bactrianus and M. m. helgolandicus subspecies are not genetically differentiated from M. m. castaneus and M. m. domesticus, respectively. Overall, our work suggests that the M. m. bactrianus and M. m. helgolandicus subspecies are not well-justified taxonomic entities, emphasizing the importance of leveraging whole-genome sequence data to inform subspecies designations. Additionally, our investigation provides tailored experimental procedures for generating whole genome sequences from air-dried mouse skins, along with key genomic resources to inform future genomic studies of wild mouse diversity.

Abstract P-glycoprotein (Pgp) is the most studied ATP-binding cassette (ABC) efflux transporter and contributes to chemoresistance. A few tracers have been developed to detect the in-vivo status of chemoresistance using positron emission tomography (PET) imaging. In our study, we have synthesized labeled AVT-011 with fluorine-18 (18F) followed by in-vitro and in-vivo analysis. Tosylate AVT-011 precursor was synthesized and characterized by 1H-NMR and 13C-NMR. AVT-011 was labeled with 18F using the nucleophilic substitution method, and a standard set of quality control was performed. The specificity for Pgp was tested in U87MG cells with and without an inhibitor (tariquidar). The biodistribution and in-vivo stability were tested in the small animals (mice). The biodistribution data of [18F]-AVT-011 was extracted from the PET-CT imaging of breast cancer patients (n = 6). The precursor was synthesized with 36 ± 4% yield and 97 ± 2% purity. The labeling was more than 95% with a 42 ± 2% yield, as evaluated by Radio-HPLC. The cell-binding assay showed a specificity of the tracer for Pgp as the uptake increased by twice after blocking the Pgp receptors. The radiotracer showed a hepatorenal excretion pathway for clearance in an animal study. The uptake was higher in the liver, lungs, spleen, and heart at 15 min and decreased at 60 min. The patients' distribution showed similar uptake patterns as observed in the small animals. [18F]AVT-011 was characterized successfully with high radiochemical purity and yield. The in-vitro and in-vivo studies proved its specificity for Pgp and safe for patient use.