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Abstract The 4D-5D connection allows us to view the same near horizon geometry as part of a 4D black hole or a 5D black hole. A much studied example of this phenomenon is the BMPV black hole uplifted to 6D with flat base space versus Taub-NUT base space. These black holes have identical near horizon AdS3 × S 3 geometry. In this paper, we study modes in AdS3 × S 3 and identify those that correspond to supersymmetric hair modes in the full black hole spacetimes. We show that these modes satisfy non-normalisable boundary conditions in AdS3. The non-normalisable boundary conditions are different for different hair modes and for different asymptotic completion. We also discuss how the supersymmetric hair modes on BMPV black holes fit into the classification of supersymmetric solutions of 6D supergravity.

Paraneoplastic neurologic syndromes are cancer-associated, immune-mediated neurologic manifestations that may involve any part of the nervous system. They usually present with characteristic neurologic features and should be considered in high-risk phenotypes such as limbic encephalitis, encephalomyelitis, rapidly progressive cerebellar syndrome, opsoclonus–myoclonus, sensory neuronopathy, enteric neuropathy, and Lambert–Eaton myasthenic syndrome. The diagnosis is made by antibody positivity in the serum or cerebrospinal fluid, in the presence of an appropriate clinical phenotype. Findings on antibody testing by immunoblot should always be verified by immunofluorescence. We report a rare case of sensory neuronopathy with triple paraneoplastic antibody positivity (anti-Hu, anti-collapsing response-mediator protein 5, and anti-amphiphysin) on immunoblot but only anti-Hu positivity on immunofluorescence. The presence of lower facial dyskinesias should raise the possibility of an immune-mediated neurologic syndrome in the appropriate clinical context.

Abstract Existing risk prediction models for hospitalized heart failure patients are limited. We identified patients hospitalized with a diagnosis of heart failure between 7 May 2013 and 26 April 2022 from a large academic, quaternary care medical centre (training cohort). Demographics, medical comorbidities, vitals, and labs were collected and were used to construct random forest machine learning models to predict in‐hospital mortality. Models were compared with logistic regression, and to commonly used heart failure risk scores. The models were subsequently validated in patients hospitalized with a diagnosis of heart failure from a second academic, community medical centre (validation cohort). The entire cohort comprised 21 802 patients, of which 14 539 were in the training cohort and 7263 were in the validation cohort. The median age (25th–75th percentile) was 70 (58–82) for the entire cohort, 43.2% were female, and 6.7% experienced inpatient mortality. In the overall cohort, 7621 (35.0%) patients had heart failure with reduced ejection fraction (EF ≤ 40%), 1271 (5.8%) had heart failure with mildly reduced EF (EF 41–49%), and 12 910 (59.2%) had heart failure with preserved EF (EF ≥ 50%). Random forest models in the validation cohort demonstrated a c‐statistic (95% confidence interval) of 0.96 (0.95–0.97), sensitivity (SN) of 87.3%, and specificity (SP) of 90.6% for the prediction of in‐hospital mortality. Models for those with HFrEF demonstrated a c‐statistic of 0.96 (0.94–0.98), SN 88.2%, and SP 91.0%, and those for patients with HFpEF showed a c‐statistic of 0.95 (0.93–0.97), SN 87.4%, and SP 89.5% for predicting in‐hospital mortality. The random forest model significantly outperformed logistic regression (c‐statistic 0.87, SN 75.9%, and SP 86.9%), and current existing risk scores including the Acute Decompensated Heart Failure National Registry risk score (c‐statistic of 0.70, SN 69%, and SP 62%), and the Get With the Guidelines‐Heart Failure risk score (c‐statistic 0.69, SN 67%, and SP 63%); P

Background and Aims: Precise airway management is vital in thoracic surgeries to ensure patient safety and optimal outcomes. Choosing the correct double-lumen tube (DLT) size is challenging, as it typically relies on height, gender and subjective experience. This study investigates using ultrasonography (USG) and computed tomography (CT) to measure cricoid cartilage diameter for objective DLT sizing. Methods: In a randomised study, 120 adult patients undergoing elective thoracic surgery were randomised to three groups: Group A (DLT size determined by USG), Group B (DLT size determined by CT) and Group C (DLT size determined by conventional methods based on height and gender). The primary outcome variable was the appropriateness of DLT size. Secondary outcome variables were the degree of lung collapse and sore throat. Student’s t-test and ꭓ2 test were used to analyse continuous and dichotomous variables, respectively. Results: DLT sizing based on cricoid cartilage diameter improved the accuracy, with inappropriate sizes found in 25% in the conventional group, 5% in the USG group and 2.5% in the CT group (P < 0.05). Lung collapse was better in the USG (excellent in 92.5%) and CT (95%) groups compared to the conventional group (70%) (P < 0.05). Moderate sore throat was higher in the conventional group (37.5%) compared to the USG (5%) and CT groups (7.5%). Conclusion: The study demonstrates that USG- and CT-guided measurements of cricoid cartilage diameter are reliable and effective methods for determining DLT size in thoracic surgery compared to conventional methods.

The 2004 tsunami affected the South Andaman coast, causing it to experience dynamic changes in the coastal geomorphology and making the region vulnerable. We focus on pre-and post-tsunami shoreline and land use–land cover changes from 2004, 2005, and 2022 to analyze the dynamic change in hazard. We used General Bathymetric Chart of the Ocean (GEBCO) data to calculate run-up [m], arrival times [min], and inundation [m] at a few locations using three tsunamigenic earthquake source parameters, namely the 2004 Sumatra, 1941 North Andaman, and 1881 Car Nicobar earthquakes. The Digital Shoreline Analysis System is used for the shoreline change estimates. Landsat data are used to calculate shoreline and land use–land cover (LULC) change in five classes, namely built-up areas, forests, inundation areas, croplands, and water bodies during the above period. We examine the correlation between the LULC changes and the dynamic change in shoreline due to population flux, infrastructural growth, and gross state domestic product growth. The Indian industry estimates the Andaman and Nicobar Islands losses exceeded INR 10 billion during 2004, which would today see a 5-fold increase in economic loss due to a doubling of built-up area, a 3-fold increase in tourist inflow, and population density growth. The unsustainable decline in the forest cover, mangroves, and cropland would affect sustainability during a disaster despite coastal safety measures.

Background: Thyroid Disorders are often underdiagnosed. This is probably due to the fact that most of the clinicians are unaware of that fact that clinical entities like Subclinical Hypothyroidism & Subclinical Hyperthyroidism do exist. Overt Hypothyroidism & Hyperthyroidism form only the tip of the iceberg of Thyroid Disorders. It has been shown in previous studies that unchecked subclinical hypothyroidism (SCH) in young individuals poses a risk for cardiovascular events in the future. This study attempts to assess the extent of Subclinical Hypothyroidism & Autoimmune Sub Clinical Hypothyroidism in the male members of the Indian Armed Forces. Through this study, the authors endeavour to bring to the notice that Subclinical Thyroid Disorders are an emerging health problem among the young individuals. It is also evident that clinical parameters alone are insufficient in establishing a diagnosis of hypothyroidism and are often misleading, thus biochemical confirmation is a must. Aims & Objectives: 1) To assess the thyroid function among asymptomatic male members of the Indian Armed Forces. 2) To study the distribution of non neoplastic thyroid disorders, if any, among the asymptomatic male members of the Armed Forces. 3) To detect the levels of Anti TPO antibodies among the members of the Armed Forces. 4) To correlate the variation in the T3, T4, TSH levels with the presence of Anti TPO antibodies. 5) To ascertain correlation, if any, between age of the subjects & presence of Anti thyroid antibodies. Materials & Methods: This is an Observation Crossectional Study performed at a Tertiary Care Naval Hospital over a period of 15 months.100 Male volunteers meeting the Inclusion & Exclusion criteria were enrolled using simple random sampling. The samples were tested for Serum T3, T4, TSH & Anti TPO Antibody levels using the STRATEC SR 300 Analyser on the day of collection. The data was analysed using the SPSS software & depicted in figures. Results: The prevalent non neoplastic Thyroid Disorders in the study population were Subclincal Hypothyroidism, Autoimmune Subclinical Hypothyroidism, Overt Hypothyroidism & High Anti TPO Antibody levels with normal Thyroid Function.The Mean Age of Presentation of Subclinical Hypothyroidism, Positive Anti TPO Antibodies & Autoimmune Subclinical Hypothyroidism were 27 ± 8.36 years (p>0.05), 26.12 ± 9.0 years (p>0.05) & 26.5 ± 7.0 years (p>0.05) respectively .The prevalence of Autoimmune Subclinical Hypothyroidism (p=0.0004), Overt Hypothyroidism (p value 0.042) & Anti TPO Antibody positivity (p=0.017) in the study population was significantly lower compared to the results of the prevalence of these disorders in General Population Based Studies. The Serum T4 levels and Age in the study population were found to have a statistically significant inverse correlation (p=0.041) Conclusion: Subclinical Autoimmune Hypothyroidism & Overt Hypothyroidism are the most prevalent non neoplastic thyroid disorders in the Male members of the Indian Armed with their prevalence in the study population being significantly less than the General population. Anti TPO antibody positivity precedes thyroid symptoms & deranged Thyroid Profile. Serum T4 has a significant inverse correlation with age & serum TSH levels. However, the correlation serum Anti TPO Antibody levels & age of the individuals is insignificant.

Background: The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate the bacterial and viral etiological diagnosis of ME in children less than 5 years of age. Materials and Methods: The present study was conducted in Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, King George’s Medical University, Lucknow, from July 2020 to June 2022. Serum, cerebrospinal fluid (CSF), and nose/throat swabs were collected from all the enrolled cases of meningoencephalitis in children below 5 years of age and tested for various etiological agents by ELISA and/or real-time PCR. Results: Of 130 enrolled cases, 50 (38.5%) cases tested positive for one or more etiological agents. Etiological agents of ME detected were Japanese encephalitis virus (JEV) (8.46%), adenovirus (6.92%), influenza virus (5.38%), dengue virus (3.85%), Parvo B-19 virus (3.08%), Orientia tsutsugamushi (3.08%), Herpes Simplex Virus-1 (HSV-1) (1.54%), measles virus (1.54%), and Varicella-Zoster Virus (VZV) (1.54%). Rubella virus, Chikungunya virus (CHKV), Mumps virus, Enteroviruses, Parecho virus, John Cunningham virus (JC), BK virus, Nipah virus, Kyasanur Forest Disease virus (KFD), Chandipura virus, Herpes Simplex Virus (HSV-2), SARS CoV-2, N. Meningitides, and H. Influenzae were tested but not detected in any of the cases. Conclusion: We identified the etiological agents in 50/130 (38.5%) suspected ME cases in children less than 5 years of age, using molecular and ELISA-based diagnostic methods. The four most common pathogens detected were JEV, adenovirus, influenza virus, and dengue virus.

Abstract Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD) that leads to progressive and irreversible vision loss. Identifying patients with greatest risk of GA progression is important for targeted utilization of emerging therapies. This study aimed to comprehensively evaluate the role of shape-based fractal dimension features ( $${F}_{fd}$$ F fd ) of sub-retinal pigment epithelium (sub-RPE) compartment and texture-based radiomics features ( $${F}_{t}$$ F t ) of Ellipsoid Zone (EZ)-RPE and sub-RPE compartments for risk stratification for subfoveal GA (sfGA) progression. This was a retrospective study of 137 dry AMD subjects with a 5-year follow-up. Based on sfGA status at year 5, eyes were categorized as Progressors and Non-progressors. A total of 15 shape-based $${F}_{fd}$$ F fd of sub-RPE surface and 494 $${F}_{t}$$ F t from each of sub-RPE and EZ-RPE compartments were extracted from baseline spectral domain-optical coherence tomography scans. The top nine features were identified from $${F}_{fd}$$ F fd and $${F}_{t}$$ F t feature pool separately using minimum Redundancy maximum Relevance feature selection and used to train a Random Forest (RF) classifier independently using three-fold cross validation on the training set ( $${S}_{t}$$ S t , N = 90) to distinguish between sfGA Progressors and Non-progressors. Combined $${F}_{fd}$$ F fd and $${F}_{t}$$ F t was also evaluated in predicting risk of sfGA progression. The RF classifier yielded AUC of 0.85, 0.79 and 0.89 on independent test set ( $${S}_{v}$$ S v , N = 47) using $${F}_{fd}$$ F fd , $${F}_{t}$$ F t , and their combination, respectively. Using combined $${F}_{fd}$$ F fd and $${F}_{t}$$ F t , the improvement in AUC was statistically significant on $${S}_{v}$$ S v with p-values of 0.032 and 0.04 compared to using only $${F}_{fd}$$ F fd and only $${F}_{t}$$ F t , respectively. Combined $${F}_{fd}$$ F fd and $${F}_{t}$$ F t appears to identify high-risk patients. Our results show that FD and texture features could be potentially used for predicting risk of sfGA progression and future therapeutic response.

Abstract Background/Aims Anti-tumor necrosis factor (Anti-TNF) agents have proven beneficial for the treatment of chronic non-infectious uveitis, yet rare neurological complications and demyelinating disease can occur with their use. Management of uveitis and neurological disease after developing these rare complications is not well understood. We sought to identify these specific cases and their outcomes through a retrospective observational case series. Methods Electronic Medical Record (EMR) chart review of 394 non-infectious uveitis patients on anti-TNF therapy focused on identifying patients seen by uveitis specialists at a single institution who were on anti-TNF therapy and had developed neurological symptoms. Cases were reviewed for subsequent management and outcomes of both their neurologic and ocular inflammatory disease. Results Five (5) patients were included following complaints of neurological symptoms while on anti-TNF therapy. Subsequent demyelinating diagnosis, acute treatment, and long-term course were described. All five patients continue to be inactive at around three years of anti-TNF discontinuation. Conclusion Unidentified rare neurological symptoms and demyelinating disease associated with the use of anti-TNF agents can be detrimental to patient treatment outcomes. Emphasis is given on possible avoidance and early identification of exacerbating underlying disease through a detailed neurologic history and use of imaging when suspicion is high. Patients may have no evidence of higher neurological risk prior to starting an anti-TNF treatment. Discontinuation of an anti-TNF agent and subsequent control of disease is possible with alternative immunosuppressive treatments.

Abstract This study aimed to assess retinal alterations following membrane peeling procedures using novel ILM Forceps with laser ablated surface with the help of intraoperative optical coherence tomography (iOCT). A post-hoc analysis was performed to evaluate iOCT findings in eyes that underwent membrane peeling procedures with the novel ILM Forceps. Pre-peel and post-peel iOCT videos and images were evaluated for each eye to assess for post-peel anatomic alterations. Surgical video/iOCT scan correlation was conducted to evaluate the etiology of anatomic alterations. Thirty-two eyes were included in the analysis. Three eyes (9%) had focal full thickness retinal elevations identified on iOCT following tissue-instrument interaction with the ILM Forceps. Two eyes (6%) had focal inner retinal elevations and one eye (3%) had a full-thickness retinal elevation that were not related to direct tissue-instrument interaction but rather indirect peeling forces. iOCT-identified architectural alterations related to direct-tissue instrument interaction were relatively infrequent (

Abstract Dysbindin-1, a protein encoded by the schizophrenia susceptibility gene DTNBP1, is reduced in the hippocampus of schizophrenia patients. It is expressed in various cellular populations of the brain and implicated in dopaminergic and glutamatergic transmission. To investigate the impact of reduced dysbindin-1 in excitatory cells on hippocampal-associated behaviors and synaptic transmission, we developed a conditional knockout mouse model with deletion of dysbindin-1 gene in CaMKIIα expressing cells. We found that dysbindin-1 reduction in CaMKII expressing cells resulted in impaired spatial and social memories, and attenuation of the effects of glutamate N-methyl-d-asparate receptor (NMDAR) antagonist MK801 on locomotor activity and prepulse inhibition of startle (PPI). Dysbindin-1 deficiency in CaMKII expressing cells also resulted in reduced protein levels of NMDAR subunit GluN1 and GluN2B. These changes were associated with increased expression of immature dendritic spines in basiliar dendrites and abnormalities in excitatory synaptic transmission in the ventral hippocampus. These results highlight the functional relevance of dysbindin-1 in excitatory cells and its implication in schizophrenia-related pathologies.

Background: Several observational studies have reported the prevalence of cerebral microbleeds (CMBs) and their risk factors in an elderly population. Any information in this regard is currently lacking from India. Aim of this study was to estimate the prevalence, risk factors of CMBs, and association with cognition in an Indian urban population aged 50 years and above. Methods: Household surveys were conducted as part of ongoing Longitudinal Cognition and Aging Research on Population of the National Capital Region (LoCARPoN) study in areas of urban Delhi. Magnetic resonance imaging of the brain was performed in 2599 participants. Using standard neuropsychological battery, mean Z-scores for each domain (memory, executive, information) were derived. Binary and stepwise logistic regression models were used to determine associated risk factors for the presence of CMB and its association with cognitive domains. Results: The prevalence of CMBs was 14.42% (95% confidence interval [CI]: 13.06–15.73). Of these, 203 (7.81%) participants had single CMBs and 172 (6.61%) had multiple microbleeds (≥2). Higher prevalence was observed in older age (60–70 years: odds ratio [OR]: 1.25 [95% CI: 0.93–1.67]; 70–80 years: OR: 2.05 [95% CI: 1.48–2.84]; ≥80 years: OR: 3.27 [95% CI: 1.97–5.44]) compared to individuals in the age group 50–60 years. History of stroke (OR: 2.97 [95% CI: 1.56–5.66]), hypertension (OR: 1.36 [95% CI: 1.05–1.75]), and smoking (OR: 1.43 [95% CI: 1.11–1.85]) was associated with at least one CMB. Multiple CMBs were associated with worse scores in memory and executive domains. Conclusion: Older age, hypertension, history of stroke, and history of smoking emerged as important risk factors for the presence of multiple CMBs. Follow-up study is required to determine implications of CMBs.

Abstract Giardia duodenalis, a major cause of waterborne infection, infects a wide range of mammalian hosts and is subdivided into eight genetically well-defined assemblages named A through H. However, fragmented genomes and a lack of comparative analysis within and between the assemblages render unclear the molecular mechanisms controlling host specificity and differential disease outcomes. To address this, we generated a near-complete de novo genome of AI assemblage using the Oxford Nanopore platform by sequencing the Be-2 genome. We generated 148,144 long-reads with quality scores of > 7. The final genome assembly consists of only nine contigs with an N50 of 3,045,186 bp. This assembly agrees closely with the assembly of another strain in the AI assemblage (WB-C6). However, a critical difference is that a region previously placed in the five-prime region of Chr5 belongs to Chr4 of Be-2. We find a high degree of conservation in the ploidy, homozygosity, and the presence of cysteine-rich variant-specific surface proteins (VSPs) within the AI assemblage. Our assembly provides a nearly complete genome of a member of the AI assemblage of G. duodenalis, aiding population genomic studies capable of elucidating Giardia transmission, host range, and pathogenicity.

Abstract Tandem nucleotide repeat (TNR) expansions, particularly the CNG nucleotide configuration, are associated with a variety of neurodegenerative disorders. In this study, we aimed to identify novel unstable CNG repeat loci associated with the neurogenetic disorder spinocerebellar ataxia (SCA). Using a computational approach, 15,069 CNG repeat loci in the coding and noncoding regions of the human genome were identified. Based on the feature selection criteria (repeat length >10 and functional location of repeats), we selected 52 repeats for further analysis and evaluated the repeat length variability in 100 control subjects. A subset of 19 CNG loci observed to be highly variable in control subjects was selected for subsequent analysis in 100 individuals with SCA. The genes with these highly variable repeats also exhibited higher gene expression levels in the brain according to the tissue expression dataset (GTEx). No pathogenic expansion events were identified in patient samples, which is a limitation given the size of the patient group examined; however, these loci contain potential risk alleles for expandability. Recent studies have implicated GLS, RAI1, GIPC1, MED15, EP400, MEF2A, and CNKSR2 in neurological diseases, with GLS, GIPC1, MED15, RAI1, and MEF2A sharing the same repeat loci reported in this study. This finding validates the approach of evaluating repeat loci in different populations and their possible implications for human pathologies.

In this study, we examine a model of inventory for things that are deteriorating along with the price dependent demand. The deterioration rate is constant and Salvage value is related to goods that are deteriorating, and holding cost is time-dependent. The suggested approach allows for some backlog in the shortage. Based on the length of time it will be before the next replenishment, the backlog rate is determined. This framework is solved to reduce the overall cost of given inventory to showing some numerical examples with sensitivity analysis to find the optimal solution for various parameters.

This study introduces a novel SI2HR model, where “I2” denotes two infectious classes representing asymptomatic and symptomatic infections, aiming to investigate and analyze the cost-effective optimal control measures for managing COVID-19. The model incorporates a novel concept of infectious density-induced additional screening (IDIAS) and accounts for treatment saturation. Furthermore, the model considers the possibility of reinfection and the loss of immunity in individuals who have previously recovered. To validate and calibrate the proposed model, real data from November–December 2022 in Hong Kong are utilized. The estimated parameters obtained from this calibration process are valuable for prediction purposes and facilitate further numerical simulations. An analysis of the model reveals that delays in screening, treatment, and quarantine contribute to an increase in the basic reproduction number R0, indicating a tendency towards endemicity. In particular, from the elasticity of R0, we deduce that normalized sensitivity indices of baseline screening rate (θ), quarantine rates (γ, αs), and treatment rate (α) are negative, which shows that delaying any of these may cause huge surge in R0, ultimately increases the disease burden. Further, by the contour plots, we note the two-parameter behavior of the infectives (both symptomatic and asymptomatic). Expanding upon the model analysis, an optimal control problem (OCP) is formulated, incorporating three control measures: precautionary interventions, boosted IDIAS, and boosted treatment. The Pontryagin's maximum principle and the forward-backward sweep method are employed to solve the OCP. The numerical simulations highlight that enhanced screening and treatment, coupled with preventive interventions, can effectively contribute to sustainable disease control. However, the cost-effectiveness analysis (CEA) conducted in this study suggests that boosting IDIAS alone is the most economically efficient and cost-effective approach compared to other strategies. The CEA results provide valuable insights into identifying specific strategies based on their cost-efficacy ranking, which can be implemented to maximize impact while minimizing costs. Overall, this research offers significant insights for policymakers and healthcare professionals, providing a framework to optimize control efforts for COVID-19 or similar epidemics in the future.

Precise spatial mapping of individual species using hyperspectral data is crucial for effective forest management and policy-making. This study focuses on Rhododendron arboreum, known for its medicinal properties attributed to the flavonoid Quercitrin. Sample data and spectroradiometer data were collected from the complex terrain of the Kumaon region in the Himalayas. Hyperspectral data, which includes signal variations based on biophysical and biochemical properties along with noise, were preprocessed using filtering techniques to enhance signal clarity by removing noise. Smoothing techniques were applied to remove noisy bands from the spectra, such as the Savitzky-Golay filter for reduced least square fit complexity and the Average Mean filter for taking mean spectral values. Subsequently, Spectral Analysis (SA) techniques, including first derivative, second derivative, and continuum removal, were employed. These mathematical transformations highlighted absorption troughs and determined the effect of Quercitrin on spectral wavelengths. Principal Component Analysis (PCA) was used to identify the most relevant bands related to Quercitrin. Additionally, regression analysis was applied on resampled spectral data, selected significant wavelengths based on variable importance values, pinpointing the most prominent wavelengths: 1196, 1229, 1328, 1383, 1425, 1636, 1661, 1699, 1785, and 1715 nm. Over 50 two-band combination indices were tested, and those with p-values less than 0.05 were deemed significant. For the development of prediction model, Machine Learning (ML) algorithms, including Support Vector Machine (SVM), Relevance Vector Machine (RVM), Random Forest (RF), and Artificial Neural Network (ANN), were applied. The Random Forest model, which splits input data into trees to simulate the best model based on observed values, demonstrated high effectiveness in predicting Quercitrin levels, achieving a training correlation of 0.864 and a testing correlation of 0.570. Hence RF proved to be a best technique of band selection as well as robust for Quercitrin prediction. This methodological approach highlights the importance of advanced data processing and analysis techniques in remote sensing applications for forest phytochemical prediction.

Handling hot oil spillage, particularly from oil refineries, petrochemical industry and automobiles is challenging and there have been limited solutions to address the issue. Polyetherimide (PEI) electrospun fibrous membranes were developed in this study by leveraging PEI's high-temperature stability to serve as promising materials for hot oil sorption. The morphology of the membrane forming fibers varied from circular to dumbbell shaped, by judicious choice of solvents of varying boiling points, to study the effect of fiber morphology on oil sorption capacity. Crosslinking of PEI membranes was carried out using ethylenediamine (EDA) to impart structural integrity and resiliency to the membranes. The PEI membrane composed of dumbbell-shaped fibers demonstrated an oil-sorption capacity of 25.4 ±1.5 g/g for engine oil at 150°C within one hour, outperforming a commercial polypropylene (PP) nonwoven absorbent, which failed and collapsed under the same high-temperature conditions. Enhanced oil sorption in the dumbbell-shaped fibrous membrane was achieved due to its lower tortuosity, aligned inter-fiber channels, and higher capillary pressure. Usefulness and sorption capacity of PEI based electrospun membranes may further be explored for controlling the oil spillage through introduction of specific surface features and functionalization.

Despite a record number of clinical studies investigating various anti-myeloma treatments, the 5-year survival rate for multiple myeloma (MM) patients in the US is only 55%, and almost all patients relapse. Poor patient outcomes demonstrate that myeloma cells are “born to survive” which means they can adapt and evolve following treatment. Thus, new therapeutic approaches to combat survival mechanisms and target treatment resistance are required. Importantly, Mcl-1, anti-apoptotic protein, is required for the development of MM and treatment resistance. This study looks at the possibility of KS18, a selective Mcl-1 inhibitor, to treat MM and overcome resistance. Our investigation demonstrates that KS18 effectively induces cell death in MM by dual regulatory mechanisms targeting the Mcl-1 protein at both transcriptional and post-translational levels. Specifically, KS18 suppresses Mcl-1 activation via STAT-3 pathway and promotes Mcl-1 phosphorylation/ubiquitination/proteasome-dependent protein degradation (UPS). Significantly, KS18 triggered caspase-dependent apoptosis in MM patient samples and bortezomib-resistant cells, synergizing with venetoclax to boost apoptosis. KS18 promises to overcome bortezomib and venetoclax resistance and re-sensitize myeloma cells to chemotherapy. Furthermore, the study shows the tremendous impact of KS18 in inhibiting colony formation in bortezomib-resistant cells and demonstrates significant tumor shrinkage in KS18-treated NSG mice without notable toxicity signs after 4 weeks of therapy with a single acceptable dose each week, indicating its powerful anti-neoplastic and anti-resistance characteristics. This study strongly implies that KS18 may treat MM and provide new hope to patients who are experiencing recurrence or resistance.

Study objective: The association of prior to admission guideline-directed medical therapy (GDMT) use in patients hospitalized with Heart Failure with Reduced Ejection Fraction (HFrEF, ejection fraction ≤40 %) and Coronavirus Disease 2019 (COVID-19) with in-hospital outcomes has not been well studied. Design/setting/participants/interventions/outcome measures: Using the American Heart Association's Get With The Guidelines Heart Failure Registry, we identified HFrEF patients presenting with acute decompensated heart failure (ADHF) and compared rates of GDMT prescription between those presenting prior to and during the pandemic. In a subgroup of patients with a concomitant COVID-19 diagnosis, we evaluated the association of prior to admission GDMT use with in-hospital mortality and severe COVID-19. Results: 23,899 patients were admitted with HFrEF during the pandemic (2/16/20–3/24/21) and 26,459 patients were admitted in the year prior (2/16/19–2/15/20). In this overall cohort, prior to admission ACEI/ARB/ARNI (45.6 % vs 48.1 %, p

Solitary fibrous tumor (SFT) of the pleura is a rare mesenchymal tumor with

Abstract Overexpression of Glycine max disease resistant 1 (GmDR1) exhibits broad-spectrum resistance against Fusarium virguliforme, Heterodera glycines (soybean cyst nematode), Tetranychus urticae (Koch) (spider mites), and Aphis glycines Matsumura (soybean aphids) in soybean. To understand the mechanisms of broad-spectrum immunity mediated by GmDR1, the transcriptomes of a strong and a weak GmDR1-overexpressor following treatment with chitin, a pathogen- and pest-associated molecular pattern (PAMP) common to these organisms, were investigated. The strong and weak GmDR1-overexpressors exhibited altered expression of 6098 and 992 genes, respectively, as compared to the nontransgenic control following chitin treatment. However, only 192 chitin- and 115 buffer-responsive genes exhibited over two-fold changes in expression levels in both strong and weak GmDR1-overexpressors as compared to the control. MapMan analysis of the 192 chitin-responsive genes revealed 64 biotic stress-related genes, of which 53 were induced and 11 repressed as compared to the control. The 53 chitin-induced genes include nine genes that encode receptor kinases, 13 encode nucleotide-binding leucine-rich repeat (NLR) receptor proteins, seven encode WRKY transcription factors, four ethylene response factors, and three MYB-like transcription factors. Investigation of a subset of these genes revealed three receptor protein kinases, seven NLR proteins, and one WRKY transcription factor genes that are induced following F. virguliforme and H. glycines infection. The integral plasma membrane GmDR1 protein most likely recognizes PAMPs including chitin and activates transcription of genes encoding receptor kinases, NLR proteins and defense-related genes. GmDR1 could be a pattern recognition receptor that regulates the expression of several NLRs for expression of PAMP-triggered immunity and/or priming the effector triggered immunity.

Abstract The interaction between nuclear receptor coactivator 4 (NCOA4) and the iron storage protein ferritin is a crucial component of cellular iron homeostasis. The binding of NCOA4 to the FTH1 subunits of ferritin initiates ferritinophagy—a ferritin-specific autophagic pathway leading to the release of the iron stored inside ferritin. The dysregulation of NCOA4 is associated with several diseases, including neurodegenerative disorders and cancer, highlighting the NCOA4-ferritin interface as a prime target for drug development. Here, we present the cryo-EM structure of the NCOA4-FTH1 interface, resolving 16 amino acids of NCOA4 that are crucial for the interaction. The characterization of mutants, designed to modulate the NCOA4–FTH1 interaction, is used to validate the significance of the different features of the binding site. Our results explain the role of the large solvent-exposed hydrophobic patch found on the surface of FTH1 and pave the way for the rational development of ferritinophagy modulators.

Hydrological Ecosystem Services (HES) are crucial components of environmental sustainability and provide indispensable benefits. The present study identifies critical hot and cold spots areas of HES in the Aglar watershed of the Indian Himalayan Region using six HES descriptors, namely water yield (WYLD), crop yield factor (CYF), sediment yield (SYLD), base flow (LATQ), surface runoff (SURFQ), and total water retention (TWR). The analysis was conducted using weightage-based approaches under two methods: (1) evaluating six HES descriptors individually and (2) grouping them into broad ecosystem service categories. Furthermore, the study assessed pixel-level uncertainties that arose because of the distinctive methods used in the identification of hot and cold spots. The associated synergies and trade-offs among HES descriptors were examined too. From method 1, 0.26% area of the watershed was classified as cold spots and 3.18% as hot spots, whereas method 2 classified 2.42% area as cold spots and 2.36% as hot spots. Pixel-level uncertainties showed that 0.57 km2 and 6.86 km2 of the watershed were consistently under cold and hot spots, respectively, using method 1, whereas method 2 identified 2.30 km2 and 6.97 km2 as cold spots and hot spots, respectively. The spatial analysis of hot spots showed consistent patterns in certain parts of the watershed, primarily in the south to southwest region, while cold spots were mainly found on the eastern side. Upon analyzing HES descriptors within broad ecosystem service categories, hot spots were mainly in the southern part, and cold spots were scattered throughout the watershed, especially in agricultural and scrubland areas. The significant synergistic relation between LATQ and WYLD, and sediment retention and WYLD and trade-offs between SURFQ and HES descriptors like WYLD, LATQ, sediment retention, and TWR was attributed to varying factors such as land use and topography impacting the water balance components in the watershed. The findings underscore the critical need for targeted conservation efforts to maintain the ecologically sensitive regions at watershed scale.

Emerging insights in osteoimmunology have enabled researchers to explore in depth the role of immune modulation in regulating bone health. Bone is one of the common sites of metastasis notably in case of breast cancer, prostate cancer and several other cancer types. High calcium ion concentration and presence of several factors within the mineralized bone matrix including TGF-β, BMP etc., aid in tumor growth and proliferation. Accumulating evidence has substantiated the role of the gut-microbiota (GM) in tumorigenesis, further providing a strong impetus for the growing “immune-cancer-gut microbiota” relationship. Recent advancements in research further highlight the importance of the intra-tumor microbiota in conjunction with GM in cancer metastasis. Intratumoral microbiota owing to their ability to cause genetic instability, mutations, and epigenetic modifications within the tumor microenvironment, has been recognized to affect cancer cell physiology. The host microbiota and immune system crosstalk shapes the innate and adaptive arms of the immune system, which is the key player in cancer progression. In this review, we aim to decipher the role of microorganisms mediating bone metastasis by shedding light on the immuno-onco-microbiome (IOM) axis. We discussed the feasible cancer therapeutic interventions based on the modulation of the microbiome-immune cell axis which includes prebiotics, probiotics, and postbiotics. Here, we leverage the conceptual framework based on the published articles on microbiota-based therapies to target bone metastases. Understanding this complicated nexus will provide insights into fundamental factors governing bone metastases which will subsequently help in managing this malignancy with better efficacy.

Algal blooms are a serious menace to freshwater bodies all over the world. These blooms typically comprise cyanobacterial outgrowths that produce a heptapeptide toxin, Microcystin-LR (MC-LR). Chronic MC-LR exposure impairs mitochondrial-nuclear crosstalk, ROS generation, activation of DNA damage repair pathways, apoptosis, and calcium homeostasis by interfering with PC/MAPK/RTK/PI3K signaling. The discovery of the toxin's biosynthesis pathways paved the way for the development of molecular techniques for the early detection of microcystin. Phosphatase inhibition-based bioassays, high-performance liquid chromatography, and enzyme-linked immunosorbent tests have recently been employed to identify MC-LR in aquatic ecosystems. Biosensors are an exciting alternative for effective on-site analysis and field-based characterization. Here, we present a synthesis of evidence supporting MC-LR as a mitotoxicant, examine various detection methods, and propose a novel theory for the relevance of MC-LR-induced breakdown of mitochondrial machinery and its myriad biological ramifications in human health and disease.

Abstract In the field of coastal geomorphology, advancements in space technology have revolutionized coastal mapping and understanding. Satellite‐derived bathymetry (SDB) research has progressed, focusing on various estimation methods using high‐resolution satellite imagery and in‐situ data. Challenges arise when applying these methods to the Indian coastline due to its turbid waters and intricate features such as creeks and deltas, laden with sediment and submerged rocks. A study aims to assess multivariate machine learning (ML) regression techniques for estimating bathymetric data. The study employs ground‐truth data and imagery from Aster, Landsat‐8, and Sentinel‐2 at distinct sites known for complex underwater landscapes. Several algorithms including Multiple Linear Regression, Support Vector Regressor, Gaussian Process Regression (GPR), Decision Tree Regression, K‐Neighbors Regressor, k‐fold cross‐validation with Decision Tree Regression, and Random Forest (RF) are evaluated for SDB. Results from the Vengurla Site show that using the Landsat‐8 data set with the GPR algorithm achieves R2 0.94, root mean squared error (RMSE) 1.53 m, and MAE 1.14 m, utilizing visible spectrum bands. At Mormugao, the Sentinel‐2 data set with GPR and RF algorithms attains R2 0.97 and RMSE 1.23 m, with GPR outperforming RF, having an MAE of 1.05 m compared to RF's 1.22 m. This study underscores the potential of ML regression techniques in overcoming challenges with using SDB for mapping coastal geomorphology, particularly in intricate underwater terrains and turbid waters by assimilating sophisticated algorithms and their refined cartographic representation.

Background and objective: Intravitreal injection of anti-VEGF agents is the first-line treatment for patients with neovascular-age related macular degeneration (nAMD). One unique serious adverse event that may be associated with these agents is intraocular inflammation (IOI). The main purpose of this analysis was to evaluate the potential presence of texture-based radiomics features characterizing heterogeneity within the vitreous compartment of spectral domain optical coherence tomography (SD-OCT) images that may precede or develop in association with IOI and might serve as OCT biomarkers for IOI. Methods: This is a post-hoc analysis of a subset of cases (N = 67) involving IOI, endophthalmitis, and/or retinal vascular occlusion in the phase 3 HAWK trial. These were investigator determined diagnoses that were also confirmed by the safety review committee. Intraocular inflammation was any signs of inflammation within the eye, endophthalmitis was inflammation associated with presumed infection, and retinal vascular occlusions consisted of intraocular inflammation with concurrent vascular occlusions/vasculitis. Out of 67 eyes, 34 belonged to the Safety group with an IOI event and 33 were propensity-matched Controls. A total of 481 texture-based radiomics features were extracted from the vitreous compartment of the SD-OCT scans at pre-IOI time point (i.e., much earlier than the actual event). Most discriminating five features, selected by the Wilcoxon Rank Sum feature selection were evaluated using Random Forest (RF) classifier on the training set (Str, N = 47) to differentiate between the two patient groups. Classifier performance was subsequently validated on the independent test set (St, N = 20). Additionally, the classifier performance in discriminating the Control and Safety group was also validated on St at the IOI event timepoint. Results: The RF classifier yielded area under the Receiver Operating Characteristics curve (AUC) of 0.76 and 0.81 on St using texture-based radiomics features at pre-IOI and event time-point, respectively. Conclusions: In this analysis, the presence of a pre-IOI safety signal was detected in the form of textural heterogeneity within the vitreous compartment even prior to the actual event being identified by the investigator. This finding may help the clinicians to assess for underlying posterior inflammation.

The previous decades have seen a massive increase in the research towards reproducible and optimized surface-enhanced Raman spectroscopy (SERS) substrates. While traditional colloidal synthesis methods have commonly been used for SERS substrate fabrication, they lack reproducibility hindering their usage for many applications. The need for reproducible nanostructures showing high orders of enhancement factors has brought about a shift in the methods one can use to fabricate SERS nanostructures. Lithographic techniques have thus piqued the interest of researchers as a viable option for SERS substrate fabrication. Not only do they offer high enhancement factors and reproducible nanostructures, they also provide the ability to fabricate nanostructures with many different geometries, shapes, sizes and periodicities. Some of the most established lithographic techniques include electron beam lithography, nanosphere lithography, laser interference lithography and many more. This review discusses established lithographic techniques, such as mentioned above, along with other upcoming lithographic techniques to understand the principles and the methodology behind them. A deep understanding of how various parameters can influence the nanostructure fabrication and thereby influence the SERS enhancement is developed. A detailed description of how these nanostructures can be fabricated is also provided for better insight. In addition, strengths and limitations of each method are discussed in detail. Lastly, we also discuss the applicability of SERS substrates for commercial applications comparing the performance of chemical synthesis routes and lithography for SERS substrate fabrication. This review serves as a base to understand the concept and application of SERS from a microfabrication perspective.

Pramipexole, a dopaminergic agonist, has rarely been implicated as a cause of hyponatremia in patients with Parkinson’s disease (PD). Pramipexole-induced stimulation of anti-diuretic hormone results in euvolemic hyponatremia. This is often neglected, and hyponatremia may lead to worsening of the motor symptoms with PD and an unnecessary increase in dopaminergic medications, causing disabling dyskinesias. This case report describes a patient with young-onset PD who developed newonset hyponatremia due to pramipexole-induced syndrome of inappropriate anti-diuretic hormone within 3 months of starting the drug.

Abstract Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

The power system network is moving towards a smarter grid with increasing deployment of distributed generators, and prosumers, embedded with distributed control. An evolving active distribution network will require a distribution system operator (DSO) which will utilize information and communication technology to perform optimization and control of distributed energy resources (DERs). There are two major challenges in performing simulation and analysis of a distribution system. The first one is the detailed modelling and integration of a large number of distributed generators and the second one is the integration of communication and power layers in real-time simulation. In this paper, a co-simulation framework is proposed, which facilitates the performance monitoring of both layers simultaneously. A CIGRE benchmark system is used to investigate the performance of the communication layer along with the detailed modelling of distributed generators. A network topology with different network scenarios is used to analyze the impact of the network performance. This analysis helps in determining network scenarios for the optimal operation of the distribution system. The simulation study has utilized Real-Time Digital Simulator (RTDS), Typhoon, and OpalRT real-time simulators for the power layer, and NetSim for designing a communication layer between all the simulators and emulating the actual communication.

The power grid is evolving with the increased integration of Distributed Energy Resources (DERs) and the growing need for bidirectional communication to manage DERs. As this evolution unfolds, the communication system supporting the power grid operation demands thorough analysis. Traditionally sparse wired mediums cannot support increasing number of DERs connection. The continuous advancement of alternative wireless technologies provides possibility of efficient and economical communication methods. This paper explores the multifaceted area of alternative communication mediums tailored for DER-centric power distribution networks (PDN). A meticulous examination of the performance of diverse alternative mediums supported by experimental analysis and measured against a set of performance metrics, are presented. A comprehensive comparative analysis and guidelines considering existing protocols, to ensure a resilient power distribution system with DERs are also provided, highlighting the role of communication systems for a distributed energy landscape.

Patients with head and neck cancer (HNC) have ongoing pain but Stellate ganglion block which is a sympatholytic block may be a viable therapy for treating it. The data were retrospectively collected from five histopathologically confirmed HNC patients who had completed chemotherapy and radiation doses. Stellate ganglion block was given to these patients and was subsequently monitored for 3 months to assess pain alleviation and overall satisfaction. Over a 3-month period, there was a decrease in the pain levels with a better quality of life so the stellate ganglion block can be a promising modality for reducing the pain of HNC.

Bidirectional wireless communication is employed in various smart grid components such as smart meters and control and monitoring applications where security is vital. The Trusted Third Party (TTP) and wireless connectivity between the smart meter and the third party in the key management-based encryption techniques for the smart grid are expected to be totally trustworthy and dependable. In a wired/wireless medium, however, a man-in-the-middle may seek to disrupt, monitor and manipulate the network, or simply execute a replay attack, revealing its vulnerability. Recognizing this, this study presents a novel authentication management (model) comprised of two layer security schema. The first layer implements an efficient novel encryption method for secure data exchange between meters and control center with the help of two partially trusted simple servers (constitutes the TTP). In this setting, one server handles the data encryption between the meter and control center/central database, and the other server administers the random sequence of data transmission. The second layer monitors and verifies exchanged data packets among smart meters. It detects abnormal packets from suspicious sources. To implement this node-to-node authentication, One class support vector machine algorithm is proposed which takes advantages of the location information as well as the data transmission history (node identification, packet size, and data transmission frequency). This schema secures data communication, and imposes a comprehensive privacy throughout the system without considerably extending the complexity of the conventional key management scheme.

Abstract Background Pigeon pea is affected by the cyst nematode Heterodera cajani limiting the production. H. cajani can be managed by biological agents such as Trichoderma harzianum. Thus, the determination of this experiment was to estimate native strains of T. harzianum isolated from pigeon pea fields in India on population of cyst, eggs and juveniles of H. cajani. Pots experiment was conducted at the playhouse of Sam Higginbottom University of Science and Technology, Prayagraj (UP), India, during the year of 2018–2020. Earthen pots were filled with sterilized soil @ 10 kg/pot for each replicate of the treatments. Ten days before sowing of the pigeon pea seed, about 5000 spores of T. harzianum were amended in to the soil for proper colonization. Fifteen days after seed germination, 200 cysts/pot were inoculated near the root zone of pigeon pea plant. The pots were irrigated when required. Observations were recorded of cyst population, eggs and second juveniles of H. cajani/500gm of pigeon pea rhizospheric soil at 90 days after sowing. Results Among all the isolates of T. harzianum, the treatment (T 7) reduced of cyst population (12), eggs population (234) and juveniles’ population (153) as compared with all other treatments including control at 90 days after sowing of pigeon pea seeds in the year 2018–2019. Similarly, in 2019–2020 reduction in cyst population (11), eggs population (189) and juveniles population (160) was observed at 90 days after sowing in Trichoderma isolates (T 7) as compared to control. Conclusions The findings of this study are very relevant since seven isolates of native T. harzianum were promising to suppress the number of cysts in 79.31 and 83.07%, eggs in 22.00 and 38.83% and juveniles’ population in 17.74 and 20.39% of the nematode H. cajani, besides promoting the pigeon pea plant growth.

Advancements in digital automation for smart grids have led to the installation of measurement devices like phasor measurement units (PMUs), micro-PMUs ( $\mu $ -PMUs), and smart meters. However, large amount of data collected by these devices bring several challenges as control room operators need to use this data with models to make confident decisions for reliable and resilient operation of the cyber-power systems. Machine-learning (ML) based tools can provide a reliable interpretation of the deluge of data obtained from the field. For the decision-makers to ensure reliable network operation under all operating conditions, these tools need to identify solutions that are feasible and satisfy the system constraints, while being efficient, trustworthy and interpretable. This resulted in the increasing popularity of physics-informed machine learning (PIML) approaches, as these methods overcome challenges that model-based or data-driven ML methods face in silos. This work aims at the following: a) review existing strategies and techniques for incorporating underlying physical principles of the power grid into different types of ML approaches (supervised/semi-supervised learning, unsupervised learning, and reinforcement learning (RL)); b) explore the existing works on PIML methods for anomaly detection, classification, localization, and mitigation in power transmission and distribution systems, c) discuss improvements in existing methods through consideration of potential challenges while also addressing the limitations to make them suitable for real-world applications.

Abstract Eimeria tenella is a major cause of caecal coccidiosis in commercial poultry chickens worldwide. Here, we report chromosomal scale assembly of Eimeria tenella strain APU2, a strain isolated from commercial broiler chickens in the U.S. We obtained 100× sequencing Oxford Nanopore Technology (ONT) and more than 800× Coverage of Illumina Next-Seq. We created the assembly using the hybrid approach implemented in MaSuRCA, achieving a contiguous 51.34 Mb chromosomal-scale scaffolding enabling identification of structural variations. The AUGUSTUS pipeline predicted 8060 genes, and BUSCO deemed the genomes 99% complete; 6278 (78%) genes were annotated with Pfam domains, and 1395 genes were assigned GO-terms. Comparing E. tenella strains (APU2, US isolate and Houghton, UK isolate) derived Houghton strain of E. tenella revealed 62,905 high stringency differences, of which 45,322 are single nucleotide polymorphisms (SNPs) (0.088%). The rate of transitions/transversions among the SNPs are 1.63 ts/tv. The strains possess conserved gene order but have profound sequence heterogeneity in a several chromosomal segments (chr 2, 11 and 15). Genic and intergenic variation in defined gene families was evaluated between the two strains to possibly identify sequences under selection. The average genic nucleotide diversity of 2.8 with average 2 kb gene length (0.145%) at genic level. We examined population structure using available E. tenella sequences in NCBI, revealing that the two E. tenella isolates from the U.S. (E. tenella APU2 and Wisconsin, “ERR296879”) share a common maternal inheritance with the E. tenella Houghton. Our chromosomal level assembly promotes insight into Eimeria biology and evolution, hastening drug discovery and vaccine development.

Mitigation of greenhouse gases (GHGs), improving nutrient-use efficiency (NUE), and maximizing yield in rainfed lowland rice cultivation poses significant challenges. To address this, a two-year field experiment (2020 and 2021) was conducted in Assam, India, to examine the impact of different fertilizer-management practices on grain yield, NUE, and GHGs in wet direct-seeded rice (Wet-DSR) during the kharif season. The experiment included eight treatments: control; farmer’s practice (30-18.4-36 kg N-P2O5-K2O ha−1); state recommended dose of fertilizer (RDF) @ 60-20-40 kg N-P2O5-K2O ha−1 with N applied in three splits @ 30-15-15 kg ha−1 as basal, at active tillering (AT), and panicle initiation (PI); best fertilizer management practices (BMPs): 60-20-40 kg N-P2O5-K2O ha−1 with N applied in three equal splits as basal, at AT, and PI; and fertilizer deep placement (FDP) of 120%, 100%, 80%, and 60% N combined with 100% PK of RDF. The experiment was arranged out in a randomized complete block design with three replications for each treatment. The highest grain yield (4933 kg ha−1) and straw yield (6520 kg ha−1) were achieved with the deep placement of 120% N + 100% PK of RDF. FDP with 80% N + 100% PK reduced 38% N2O emissions compared to AAU’s RDF and BMPs, where fertilizer was broadcasted. This is mainly due to the lower dose of nitrogen fertilizer and the application of fertilizer in a reduced zone of soil. When considering both productivity and environmental impact, applying 80% N with 100% PK through FDP was identified as the most effective practice.

Summary: Spinocerebellar Ataxia type-12 (SCA12) is a neurodegenerative disease caused by tandem CAG repeat expansion in the 5′-UTR/non-coding region of PPP2R2B. Molecular pathology of SCA12 has not been studied in the context of CAG repeats, and no appropriate models exist. We found in human SCA12-iPSC-derived neuronal lineage that expanded CAG in PPP2R2B transcript forms nuclear RNA foci and were found to sequester variety of proteins. Further, the ectopic expression of transcript containing varying length of CAG repeats exhibits non-canonical repeat-associated non-AUG (RAN) translation in multiple frames in HEK293T cells, which was further validated in patient-derived neural stem cells using specific antibodies. mRNA sequencing of the SCA12 and control neurons have shown a network of crucial transcription factors affecting neural fate, in addition to alteration of various signaling pathways involved in neurodevelopment. Altogether, this study identifies the molecular signatures of SCA12 disorder using patient-derived neuronal cell lines.

RNA editing, a common and potentially highly functional form of RNA modification, encompasses two different RNA modifications, namely adenosine to inosine (A-to-I) and cytidine to uridine (C-to-U) editing. As inosines are interpreted as guanosines by the cellular machinery, both A-to-I and C-to-U editing change the nucleotide sequence of the RNA. Editing events in coding sequences have the potential to change the amino acid sequence of proteins, whereas editing events in noncoding RNAs can, for example, affect microRNA target binding. With advancing RNA sequencing technology, more RNA editing events are being discovered, studied, and reported. However, RNA editing events are still often overlooked or discarded as sequence read quality defects. With this position paper, we aim to provide guidelines and recommendations for the detection, validation, and follow-up experiments to study RNA editing, taking examples from the fields of cardiovascular and brain disease. We discuss all steps, from sample collection, storage, and preparation, to different strategies for RNA sequencing and editing-sensitive data analysis strategies, to validation and follow-up experiments, as well as potential pitfalls and gaps in the available technologies. This paper may be used as an experimental guideline for RNA editing studies in any disease context.