SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure.

SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID-19 patients. However, there is limited understanding of SARS-CoV-2 in ocular transmission, tropism, and associated pathologies. The presence of viral RNA in corneal/conjunctival tissue and tears, along with the evidence of viral entry receptors on the ocular surface, has led to speculation that the eye may serve as a potential route of SARS-CoV-2 transmission. Here, we investigated the interaction of SARS-CoV-2 with cells lining the blood-retinal barrier (BRB) and the role of the eye in its transmission and tropism. The results from our study suggest that SARS-CoV-2 ocular exposure does not cause lung infection and moribund illness in K18-hACE2 mice despite the extended presence of viral remnants in various ocular tissues. In contrast, intranasal exposure not only resulted in SARS-CoV-2 spike (S) protein presence in different ocular tissues but also induces a hyperinflammatory immune response in the retina. Additionally, the long-term exposure to viral S-protein caused microaneurysm, retinal pigmented epithelium (RPE) mottling, retinal atrophy, and vein occlusion in mouse eyes. Notably, cells lining the BRB, the outer barrier, RPE, and the inner barrier, retinal vascular endothelium, were highly permissive to SARS-CoV-2 replication. Unexpectedly, primary human corneal epithelial cells were comparatively resistant to SARS-CoV-2 infection. The cells lining the BRB showed induced expression of viral entry receptors and increased susceptibility towards SARS-CoV-2-induced cell death. Furthermore, hyperglycemic conditions enhanced the viral entry receptor expression, infectivity, and susceptibility of SARS-CoV-2-induced cell death in the BRB cells, confirming the reported heightened pathological manifestations in comorbid populations. Collectively, our study provides the first evidence of SARS-CoV-2 ocular tropism via cells lining the BRB and that the virus can infect the retina via systemic permeation and induce retinal inflammation.

Genomic surveillance uncovers a pandemic clonal lineage of the wheat blast fungus.

Wheat, one of the most important food crops, is threatened by a blast disease pandemic. Here, we show that a clonal lineage of the wheat blast fungus recently spread to Asia and Africa following two independent introductions from South America. Through a combination of genome analyses and laboratory experiments, we show that the decade-old blast pandemic lineage can be controlled by the Rmg8 disease resistance gene and is sensitive to strobilurin fungicides. However, we also highlight the potential of the pandemic clone to evolve fungicide-insensitive variants and sexually recombine with African lineages. This underscores the urgent need for genomic surveillance to track and mitigate the spread of wheat blast outside of South America and to guide preemptive wheat breeding for blast resistance.

Viral infections and pathogenesis of glaucoma: a comprehensive review.

Glaucoma is a leading cause of irreversible blindness worldwide, caused by the gradual degeneration of retinal ganglion cells and their axons. While glaucoma is primarily considered a genetic and age-related disease, some inflammatory conditions, such as uveitis and viral-induced anterior segment inflammation, cause secondary or uveitic glaucoma. Viruses are predominant ocular pathogens and can impose both acute and chronic pathological insults to the human eye. Many viruses, including herpes simplex virus, varicella-zoster virus, cytomegalovirus, rubella virus, dengue virus, chikungunya virus, Ebola virus, and, more recently, Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been associated with sequela of either primary or secondary glaucoma. Epidemiological and clinical studies suggest the association between these viruses and subsequent glaucoma development. Despite this, the ocular manifestation and sequela of viral infections are not well understood. In fact, the association of viruses with glaucoma is considered relatively uncommon in part due to underreporting and/or lack of long-term follow-up studies. In recent years, literature on the pathological spectrum of emerging viral infections, such as ZIKV and SARS-CoV-2, has strengthened this proposition and renewed research activity in this area. Clinical studies from endemic regions as well as laboratory and preclinical investigations demonstrate a strong link between an infectious trigger and development of glaucomatous pathology. In this article, we review the current understanding of the field with a particular focus on viruses and their association with the pathogenesis of glaucoma.

Rapid mini-chromosome divergence among fungal isolates causing wheat blast outbreaks in Bangladesh and Zambia.

The fungal pathogen, Magnaporthe oryzae Triticum pathotype, causing wheat blast disease was first identified in South America and recently spread across continents to South Asia and Africa. Here, we studied the genetic relationship among isolates found on the three continents. Magnaporthe oryzae strains closely related to a South American field isolate B71 were found to have caused the wheat blast outbreaks in South Asia and Africa. Genomic variation among isolates from the three continents was examined using an improved B71 reference genome and whole-genome sequences. We found strong evidence to support that the outbreaks in Bangladesh and Zambia were caused by the introductions of genetically separated isolates, although they were all close to B71 and, therefore, collectively referred to as the B71 branch. In addition, B71 branch strains carried at least one supernumerary mini-chromosome. Genome assembly of a Zambian strain revealed that its mini-chromosome was similar to the B71 mini-chromosome but with a high level of structural variation. Our findings show that while core genomes of the multiple introductions are highly similar, the mini-chromosomes have undergone marked diversification. The maintenance of the mini-chromosome and rapid genomic changes suggest the mini-chromosomes may serve important virulence or niche adaptation roles under diverse environmental conditions.

Rmg10, a novel wheat blast resistance gene derived from Aegilops tauschii.

Wheat blast, caused by Pyricularia oryzae (syn. Magnaporthe oryzae) pathotype Triticum (MoT), is a devastating disease that can result in up to 100% yield loss in affected fields. To find new resistance genes against wheat blast, we screened 199 accessions of Aegilops tauschii Coss., the D genome progenitor of common wheat (Triticum aestivum L.) by seedling inoculation assays with Brazilian MoT isolate Br48, and found 14 resistant accessions. A synthetic hexaploid wheat line (Ldn/KU-2097) derived from a cross between the T. turgidum cultivar 'Langdon' (Ldn) and resistant Ae. tauschii accession KU-2097 exhibited resistance in seedlings and spikes against Br48. In an F2 population derived from 'Chinese Spring' (CS) × Ldn/KU-2097, resistant and susceptible individuals segregated in a 3:1 ratio, suggesting that the resistance from KU-2097 is controlled by a single dominant gene. We designated this gene Rmg10. Genetic mapping using an F2:3 population from the same cross mapped the RMG10 locus to the short arm of chromosome 2D. Rmg10 was ineffective against Bangladesh isolates but effective against Brazilian isolates. Field tests in Bolivia showed increased spike resistance in a synthetic octaploid wheat line produced from a cross between common wheat cultivar 'Gladius' and KU-2097. These results suggest that Rmg10 would be beneficial in farmers' fields in South America.

Novel technique for laparoscopic common bile duct exploration using flexible videobronchoscope to study on clinical outcomes of single-stage (laparoscopic cholecystectomy and laparoscopic common bile duct exploration) versus dual-stage (endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy) for cholelithiasis with choledocholithiasis - Prospective study in a tertiary care centre (BRACE study - BRonchoscope Assisted Common bile duct Exploration Study).

INTRODUCTION: This study aimed to study on clinical outcomes of single-stage (laparoscopic cholecystectomy [LC] and laparoscopic common bile duct [CBD] exploration using flexible videobronchoscope) versus dual-stage (endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy) for cholelithiasis with choledocholithiasis-prospective study in a tertiary care centre (BRACE STUDY-Bronchoscope-Assisted CBD Exploration [CBDE] Study). PATIENTS AND METHODS: Between April 2022 and April 2023, patients who underwent LC with laparoscopic CBDE and endoscopic retrograde cholangiopancreatography (ERCP) followed by LC participated in this single-centre prospective research. The Institute Ethics Committee granted its approval after receiving an ethical review. The primary endpoint of the proposed research was the removal of the gall bladder and CBD stones. The secondary outcomes studied were complications using the Clavien-Dindo score, cost-effectiveness, patient satisfaction score and post-procedure duration of hospital stay. RESULTS: A total of 168 patients were included in the study. The success rate of LC with laparoscopic CBD exploration using a flexible videobronchoscope (Group 1) was significantly higher as compared to ERCP f/b LC (Group 2) (96.4% vs. 84.5%, P value = 0.02). Out of the 84 patients in Group 1, direct choledochotomies were performed on 83 of them. Group 1 had a considerably shorter hospital stay (4.6 ± 2.4 vs. 5.3 ± 6.2 days; P = 0.03). Both the cost (P = 0.002) and the number of procedures per patient (P < 0.001) were considerably higher in Group 2. Major complications (Clavien-Dindo grade 3 and above) were significantly higher in Group 2 (P = 0.04). Patient satisfaction in Group 1 scored more favourably than those in Group 2 (2.26 ± 0.3 vs. 1.92 ± 0.7; P = 0.006). CONCLUSION: For concurrent gall bladder and CBD stones, single-stage management by LCBDE using a flexible videobronchoscope has a significantly better primary outcome and lower major complications than dual-stage management. The single-stage strategy also has advantages in terms of a shorter hospital stay, the need for fewer procedures, cost efficiency and patient satisfaction.

Butyrate Ameliorates Intraocular Bacterial Infection by Promoting Autophagy and Attenuating the Inflammatory Response.

Despite an important link between the gut and ocular health, the role of the gut-eye axis remains elusive in ocular infections. In this study, we investigated the role of butyrate, a gut microbial metabolite, in the pathobiology of intraocular bacterial (Staphylococcus aureus) infection, endophthalmitis. We found that intravitreal administration of butyrate derivatives, sodium butyrate (NaB), or phenylbutyrate (PBA) reduced intraocular bacterial growth and retinal inflammatory response. The ocular tissue architecture and retinal function were preserved in butyrate-treated eyes. In cultured mouse bone marrow-derived macrophages (BMDMs) and human retinal Müller glia, NaB or PBA treatment reduced S. aureus-induced inflammatory response by inhibiting NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. However, in vivo data showed NLRP3-independent effects of butyrate. The butyrate-treated mouse retina and cells exhibited induced expression of antimicrobial molecules CRAMP (LL37) and S100A7/A8, resulting in increased bacterial phagocytosis and killing. Moreover, butyrate treatment enhanced AMP-activated protein kinase (AMPK)-dependent autophagy and promoted the co-localization of CRAMP in autophagosomes, indicating autophagy-mediated bacterial killing. Furthermore, pharmacological inhibition of autophagy in mice revealed its role in butyrate-mediated protection. Finally, butyrate exhibited synergy with antibiotic in promoting endophthalmitis resolution. Collectively, our study demonstrated the protective mechanisms of butyrate in ameliorating bacterial endophthalmitis. Therefore, butyrate derivatives could be explored as immunomodulatory and anti-bacterial therapeutics to improve visual outcomes in ocular bacterial infections.

Dynamic assessment of oropharynx with ultrasonography as a screening tool for obstructive sleep apnea.

Ultrasonography is an easily available and portable tool to assess the dynamic changes in the upper airway and surrounding soft tissue. This study aimed to evaluate the utility of oropharynx ultrasonography as a screening tool for obstructive sleep apnea (OSA). The study sequentially enrolled overweight individuals (body mass index >25 kg/m2 ) and subjected them to OSA screening tools (Berlin questionnaire, Epworth Sleepiness Scale and STOP-Bang scores), ultrasonography of the oropharynx followed by overnight polysomnography. A total of 30 healthy individuals were also recruited as controls. Detailed dynamic and static ultrasonography measurements of the oropharynx and surrounding tissue were done. The diagnostic ability of various ultrasonography parameters to detect OSA was determined using receiver operating characteristic curve analysis. A total of 63 subjects were enrolled, with 33 in the OSA group and 30 in non-OSA overweight group. All baseline characteristics were similar in the two groups. Except for the dynamic measurements of oropharynx (Retropalatal% change-inspiration, retropalatal% change-Muller manoeuvre, retroglossal% change-inspiration, and retroglossal% change-Muller manoeuvre) all other parameters were similar in the OSA and non-OSA overweight subjects. The area under the receiver operating characteristic curve was highest for retropalatal% change-inspiration: 0.989, followed by retropalatal% change-Muller manoeuvre: 0.988. Both were also significant predictors of OSA with odds ratios of 0.338 (p = 0.003; 95% confidence interval [CI] 0.164-0.696) and 0.346 (p = 0.018; 95% CI 0.143-0.837), respectively. Ultrasonography provides a near complete picture of the dynamic changes and collapsibility of the oropharynx and can be an effective tool in screening for OSA.

Heterologous expression and characterization of ToxA1 haplotype from India and its interaction with Tsn1 for spot blotch susceptibility in spring wheat.

BACKGROUND: ToxA, a necrotrophic effector protein, is present in the genome of fungal species like Parastagnospora nodorum, Pyrenophora tritici-repentis and Bipolaris sorokiniana. Tsn1 is the sensitivity gene in the host whose presence indicates more susceptibility to ToxA carrying pathogen, and ToxA-Tsn1 interaction follows an inverse gene-for-gene relationship. METHODS AND RESULTS: The present study involved cloning and expressing the ToxA1 haplotype from B. sorokiniana. It was found that the amplicon exhibited an expected product size of 471 bp. Sequence analysis of the ToxA1 nucleotide sequence revealed the highest identity, 99.79%, with P. tritici-repentis. The protein expression analysis showed peak expression at 16.5 kDa. Phylogenetic analysis of the ToxA1 sequence from all the Bipolaris isolates formed an independent clade along with P. tritici-repentis and diverged from P. nodorum. ToxA-Tsn1 interaction was studied in 18 wheat genotypes (11 Tsn1 and 7 tsn1) at both seedling and adult stages, validating the inverse gene-for-gene relationship, as the toxin activity was highest in the K68 genotype (Tsn1) and lowest in WAMI280 (tsn1). CONCLUSION: The study indicates that the haplotype ToxA1 is prevailing in the Indian population of B. sorokiniana. It would be desirable for wheat breeders to select genotypes with tsn1 locus for making wheat resistant to spot blotch.

Genomic Prediction of Resistance to Tan Spot, Spot Blotch and Septoria Nodorum Blotch in Synthetic Hexaploid Wheat.

Genomic prediction combines molecular and phenotypic data in a training population to predict the breeding values of individuals that have only been genotyped. The use of genomic information in breeding programs helps to increase the frequency of favorable alleles in the populations of interest. This study evaluated the performance of BLUP (Best Linear Unbiased Prediction) in predicting resistance to tan spot, spot blotch and Septoria nodorum blotch in synthetic hexaploid wheat. BLUP was implemented in single-trait and multi-trait models with three variations: (1) the pedigree relationship matrix (A-BLUP), (2) the genomic relationship matrix (G-BLUP), and (3) a combination of the two matrices (A+G BLUP). In all three diseases, the A-BLUP model had a lower performance, and the G-BLUP and A+G BLUP were statistically similar (p ≥ 0.05). The prediction accuracy with the single trait was statistically similar (p ≥ 0.05) to the multi-trait accuracy, possibly due to the low correlation of severity between the diseases.

Utility and timing of the respiratory rate-oxygenation index in the prediction of high-flow oxygen therapy failure in acute hypoxemic respiratory failure of infective etiology: a prospective observational study.

During and following the COVID-19 pandemic, the world has witnessed a surge in high-flow oxygen therapy (HFOT) use. The ability to provide high oxygenation levels with remarkable comfort levels has been the grounds for the same. Despite the advantages, delays in intubation leading to poor overall outcomes have been noticed in subgroups of patients on HFOT. The respiratory rate-oxygenation (ROX) index has been proposed to be a useful indicator to predict HFOT success. In this study, we have examined the utility of the ROX index prospectively in cases of acute hypoxemic respiratory failure (AHRF) due to infective etiologies. A total of 70 participants were screened, and 55 were recruited for the study. The majority of participants were males (56.4%), with diabetes mellitus being the most common comorbidity (29.1%). The mean age of the study subjects was 46.27±15.6 years. COVID-19 (70.9%) was the most common etiology for AHRF, followed by scrub typhus (21.8%). 19 (34.5%) experienced HFOT failure, and 9 (16.4%) subjects died during the study period. Demographic characteristics did not differ between either of the two groups (HFOT success versus failure and survived group versus expired group). The ROX index was significantly different between the HFOT success versus failure group at baseline, 2, 4, 6, 12, and 24 hours. The best cut-offs of the ROX index at baseline and 2 hours were 4.4 (sensitivity 91.7%, specificity 86.7%) and 4.3 (sensitivity 94.4% and specificity 86.7%), respectively. The ROX index was found to be an efficient tool in predicting HFOT failure in cases of AHRF with infective etiology.

Essential Role of NLRP3 Inflammasome in Mediating IL-1ß Production and the Pathobiology of Staphylococcus aureus Endophthalmitis.

Staphylococcal endophthalmitis is one of the leading causes of blindness following ocular surgery and trauma. Dysregulated inflammation during bacterial endophthalmitis causes host-induced inflammatory damage and vision loss if it remains unchecked. Emerging evidence indicates that inflammasome plays a critical role in regulating innate immunity in various infectious and inflammatory diseases. However, the role of the inflammasome in endophthalmitis remains elusive. Here, using a mouse model of Staphylococcus (S) aureus endophthalmitis, we show that NLRP3/ASC/Caspase-1 signaling regulates IL-1ß production in endophthalmitis. We also show that S. aureus and its cell wall components and toxins induce the activation of the NLRP3 inflammasome complex in mouse eyes. Moreover, we found that both infiltrating neutrophils and retinal microglia contribute toward NLRP3 activation and IL-1ß production in S. aureus-infected eyes. Furthermore, our data using NLRP3-/- and IL-1ß-/- mice revealed that NLRP3 and IL-1ß deficiency leads to increased intraocular bacterial burden and retinal tissue damage. Altogether, our study demonstrated an essential role of NLRP3 inflammasome activation in regulating innate immune responses in bacterial endophthalmitis.

AMP-Activated Protein Kinase Restricts Zika Virus Replication in Endothelial Cells by Potentiating Innate Antiviral Responses and Inhibiting Glycolysis.

Viruses are known to perturb host cellular metabolism to enable their replication and spread. However, little is known about the interactions between Zika virus (ZIKV) infection and host metabolism. Using primary human retinal vascular endothelial cells and an established human endothelial cell line, we investigated the role of AMP-activated protein kinase (AMPK), a master regulator of energy metabolism, in response to ZIKV challenge. ZIKV infection caused a time-dependent reduction in the active phosphorylated state of AMPK and of its downstream target acetyl-CoA carboxylase. Pharmacological activation of AMPK using 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), metformin, and a specific AMPKα activator (GSK621) attenuated ZIKV replication. This activity was reversed by an AMPK inhibitor (compound C). Lentivirus-mediated knockdown of AMPK and the use of AMPKα-/- mouse embryonic fibroblasts provided further evidence that AMPK has an antiviral effect on ZIKV replication. Consistent with its antiviral effect, AMPK activation potentiated the expression of genes with antiviral properties (e.g., IFNs, OAS2, ISG15, and MX1) and inhibited inflammatory mediators (e.g., TNF-α and CCL5). Bioenergetic analysis showed that ZIKV infection evokes a glycolytic response, as evidenced by elevated extracellular acidification rate and increased expression of key glycolytic genes (GLUT1, HK2, TPI, and MCT4); activation of AMPK by AICAR treatment reduced this response. Consistent with this, 2-deoxyglucose, an inhibitor of glycolysis, augmented AMPK activity and attenuated ZIKV replication. Thus, our study demonstrates that the anti-ZIKV effect of AMPK signaling in endothelial cells is mediated by reduction of viral-induced glycolysis and enhanced innate antiviral responses.

Identification of QTLs for zinc deficiency tolerance in a recombinant inbred population of rice (Oryza sativa L.).

BACKGROUND: Deficiency of Zn is a major soil constraint in rice plant growth and yield. Edaphic factors such as Zn deficiency in soil in relation to plant performance are still poorly understood. Here, we report promising quantitative trait loci (QTL) conferring tolerance to Zn deficiency, which were identified through biparental mapping. The experiment was conducted using the 236 F7 recombinant inbred line mapping population derived from the cross of Kinandang Patong (Zn deficiency sensitive) and A69-1 (Zn deficiency tolerant). RESULTS: A total of six QTLs (qLB-2B, qLB-4B, qPM-4B, qPM-6B, qRZC-4B, qSZC-4B) on chromosomes 2, 4 and 6 were identified for environment 1, whereas five QTLs (qLB-2 N, qLB-4 N, qPM-4 N, qRZC-4 N, qSZC-4 N) on chromosomes 2 and 4 were detected for environment 2. Among these, five major (51.30, 48.70, 28.60, 56.00, 52.00 > 10 R2 ) and one minor (5.40 < 10 R2 ) QTLs for environment 1 and four major (51.48, 50.20, 53.00, 48.00 > 10 R2 ) and one minor (4.44 < 10) QTLs for environment 2 for Zn deficiency tolerance with a logarithm of odd threshold value higher than 3 were identified. The QTLs (qLB-4B, qPM-4B, qRZC-4B, qSZC-4B, qLB-4 N, qPM-4 N, qRZC-4 N, qSZC-4 N) for leaf bronzing, plant mortality root zinc concentration and shoot zinc concentration identified on chromosome 4 were found to be the most promising and highly reproducible across the locations that explained phenotypic variation from 48.00% to 56.00% with the same marker interval RM6748-RM303. CONCLUSION: The new QTLs and its linked markers identified in the present study can be utilized for Zn deficiency tolerance in elite cultivars using marker-assisted backcrossing. © 2022 Society of Chemical Industry.

COFE-Net: An ensemble strategy for Computer-Aided Detection for COVID-19.

Biomedical images contain a large volume of sensor measurements, which can reveal the descriptors of the disease under investigation. Computer-based analysis of such measurements helps detect the disease, and thereby swiftly aid medical professionals to choose adequate therapy. In this paper, we propose a robust deep learning ensemble framework known as COVID Fuzzy Ensemble Network, or COFE-Net. This strategy is proposed for the task of COVID-19 screening from chest X-rays (CXR) and CT Scans, as a part of Computer-Aided Detection (CADe) for medical practitioners. We leverage the strategy of Transfer Learning for Convolutional Neural Networks (CNNs) widely adopted in recent literature, and further propose an efficient ensemble network for their combination. The principles of fuzzy logic have been leveraged to combine the measured decision scores generated by three state-of-the-art CNNs - Inception V3, Inception ResNet V2 and DenseNet 201 - through the Choquet fuzzy integral. Experimental results support the efficacy of our approach over empirical ensembling, as the fuzzy ensembling strategy for biomedical measurement consists of dynamic refactoring of the classifier ensemble weights on the fly, based upon the confidence scores for coalitions of inputs. This is the chief advantage of our biomedical measurement strategy over others as other methods do not adjust to the multiple generated measurements dynamically unlike ours.Impressive results on multiple datasets demonstrate the effectiveness of the proposed method. The source code of our proposed method is made available at: https://github.com/theavicaster/covid-cade-ensemble.

Incidence, Risk Factors, and Outcomes of Transition of Acute Kidney Injury to Chronic Kidney Disease in Cirrhosis: A Prospective Cohort Study.

Transition to chronic kidney disease (CKD) after an episode of acute kidney injury (AKI) is known in patients without cirrhosis. We studied the incidence and risk factors for development of CKD in patients with cirrhosis. Competing risk analysis was performed to identify risk factors for CKD development. Of 818 patients with cirrhosis (age, 50.4 ± 11.8 years; 84% males; Model for End-Stage Liver Disease [MELD], 19.9 ± 9.9), 36% had AKI at enrollment, 27% had previous AKI, and 61% developed new episodes of AKI during the follow-up period. CKD developed in 269 (33%) patients. Serum cystatin C (CysC; subdistribution hazard ratio [SHR], 1.58; 1.07-2.33), episodes of previous AKI (SHR, 1.26; 1.02-1.56), and AKI stage at enrollment (no AKI [SHR, 1] vs. stage 1 [SHR, 3.28; 1.30-8.25] vs. stage 2 [SHR, 4.33; 1.76-10.66] vs. stage 3 [SHR, 4.5; 1.59-12.73]) were identified as baseline risk factors for CKD development. On time-varying competing risk analysis, MELD (SHR, 1.01; 1.00-1.03), number of AKI episodes (SHR, 1.25; 1.15-1.37), and CysC (SHR, 1.38; 1.01-1.89) predicted CKD development. Development of CKD was associated with higher risk of death. Reduction in glomerular filtration rate (GFR) not meeting CKD criteria was observed in 66% of patients with cirrhosis, more so in those with previous AKI episodes and a high CysC level and MELD score. Renal histology, available in 55 patients, showed tubulointerstitial injury in 86%, cholemic nephrosis in 29%, and glomerular changes in 38%. Conclusion: Almost two-thirds of patients with cirrhosis develop episodes of AKI and reduction in GFR; one-third progress to CKD, resulting in adverse outcomes. Higher MELD and CysC levels and number of AKI episodes predict development of CKD in patients with cirrhosis.

Toll-like receptor 2 (TLR2) engages endoplasmic reticulum stress sensor IRE1α to regulate retinal innate responses in Staphylococcus aureus endophthalmitis.

Endoplasmic reticulum (ER) stress response has been implicated in a variety of pathophysiological conditions, including infectious and inflammatory diseases. However, its contribution in ocular bacterial infections, such as endophthalmitis, which often cause blindness is not known. Here, using a mouse model of Staphylococcus (S.) aureus endophthalmitis, our study demonstrates the induction of inositol-requiring enzyme 1α (IRE1α) and splicing of X-box binding protein-1 (Xbp1) branch of the ER-stress pathway, but not the other classical ER stress sensors. Interestingly, S aureus-induced ER stress response was found to be dependent on Toll-like receptor 2 (TLR2), as evident by reduced expression of IRE1α and Xbp1 mRNA splicing in TLR2 knockout mouse retina. Pharmacological inhibition of IRE1α using 4µ8C or experiments utilizing IRE1α-/- macrophages revealed that IRE1α positively regulates S aureus-induced inflammatory responses. Moreover, IRE1α inhibition attenuated S aureus-triggered NF-κB, p38, and ERK pathways activation and cells treated with these pathway-specific inhibitors reduced Xbp1 splicing, suggesting a positive feedback inhibition. In vivo, inhibition of IRE1α diminished the intraocular inflammation and reduced PMN infiltration in mouse eyes, but, increased the bacterial burden and caused more retinal tissue damage. These results revealed a critical role of the IRE1α/XBP1 pathway as a regulator of TLR2-mediated protective innate immune responses in S aureus-induced endophthalmitis.

A Tri-Stage Wrapper-Filter Feature Selection Framework for Disease Classification.

In machine learning and data science, feature selection is considered as a crucial step of data preprocessing. When we directly apply the raw data for classification or clustering purposes, sometimes we observe that the learning algorithms do not perform well. One possible reason for this is the presence of redundant, noisy, and non-informative features or attributes in the datasets. Hence, feature selection methods are used to identify the subset of relevant features that can maximize the model performance. Moreover, due to reduction in feature dimension, both training time and storage required by the model can be reduced as well. In this paper, we present a tri-stage wrapper-filter-based feature selection framework for the purpose of medical report-based disease detection. In the first stage, an ensemble was formed by four filter methods-Mutual Information, ReliefF, Chi Square, and Xvariance-and then each feature from the union set was assessed by three classification algorithms-support vector machine, naïve Bayes, and k-nearest neighbors-and an average accuracy was calculated. The features with higher accuracy were selected to obtain a preliminary subset of optimal features. In the second stage, Pearson correlation was used to discard highly correlated features. In these two stages, XGBoost classification algorithm was applied to obtain the most contributing features that, in turn, provide the best optimal subset. Then, in the final stage, we fed the obtained feature subset to a meta-heuristic algorithm, called whale optimization algorithm, in order to further reduce the feature set and to achieve higher accuracy. We evaluated the proposed feature selection framework on four publicly available disease datasets taken from the UCI machine learning repository, namely, arrhythmia, leukemia, DLBCL, and prostate cancer. Our obtained results confirm that the proposed method can perform better than many state-of-the-art methods and can detect important features as well. Less features ensure less medical tests for correct diagnosis, thus saving both time and cost.

Hough Transform-Based Angular Features for Learning-Free Handwritten Keyword Spotting.

Handwritten keyword spotting (KWS) is of great interest to the document image research community. In this work, we propose a learning-free keyword spotting method following query by example (QBE) setting for handwritten documents. It consists of four key processes: pre-processing, vertical zone division, feature extraction, and feature matching. The pre-processing step deals with the noise found in the word images, and the skewness of the handwritings caused by the varied writing styles of the individuals. Next, the vertical zone division splits the word image into several zones. The number of vertical zones is guided by the number of letters in the query word image. To obtain this information (i.e., number of letters in a query word image) during experimentation, we use the text encoding of the query word image. The user provides the information to the system. The feature extraction process involves the use of the Hough transform. The last step is feature matching, which first compares the features extracted from the word images and then generates a similarity score. The performance of this algorithm has been tested on three publicly available datasets: IAM, QUWI, and ICDAR KWS 2015. It is noticed that the proposed method outperforms state-of-the-art learning-free KWS methods considered here for comparison while evaluated on the present datasets. We also evaluate the performance of the present KWS model using state-of-the-art deep features and it is found that the features used in the present work perform better than the deep features extracted using InceptionV3, VGG19, and DenseNet121 models.

Glycolytic inhibitor 2-deoxyglucose suppresses inflammatory response in innate immune cells and experimental staphylococcal endophthalmitis.

Previously, we have shown that Staphylococcus (S) aureus induces a glycolytic response in retinal residential (microglia) and infiltrated cells (neutrophils and macrophages) during endophthalmitis. In this study, we sought to investigate the physiological role of glycolysis in bacterial endophthalmitis using a glycolytic inhibitor, 2-deoxyglucose (2DG). Our data showed that 2DG treatment attenuated the inflammatory responses of mouse bone marrow-derived macrophages (BMDM) and neutrophils (BMDN) when challenged with either live or heat-killed S. aureus (HKSA). Among the inflammatory mediators, 2DG caused a significant reduction in levels of cytokines (TNF-α, IL-1ß, IL-6) and chemokines (CXCL1 and CXCL2). Western blot analysis of 2DG treated cells showed downregulation of bacterial-induced MEK/ERK pathways. In vivo, intravitreal administration of 2DG both pre- and post-bacterial infection resulted in a significant reduction in intraocular inflammation in C57BL/6 mouse eyes and downregulation of ERK phosphorylation in retinal tissue. Collectively, our study demonstrates that 2DG attenuates inflammatory response in bacterial endophthalmitis and cultured innate immune cells via inhibition of ERK signaling. Thus glycolytic inhibitors in combination with antibiotics could mitigate inflammation-mediated tissue damage in ocular infections.