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Chitin is converted into chitosan by the gladius of the Uroteuthis sibogae(U. sibogae). Chitosan (CH) is then converted into carboxymethyl chitosan (CMC). The structural and functional groups of CH and CMC, respectively, are ascertained using FT-IR and NMR spectroscopy. The molecular weight of the isolated CMC is 731.87 Da. The degree of deacetylation (DDA) is confirmed at about 83%, and the CMC degree of substitution (DS) of 0.8 is determined. Moreover, using the crosslinker sodium tripolyphosphate (TPP), nano-CMC (N-CMC) is synthesized from the obtained CMC. The N-CMC particle size is 146 nm, and 68% of N-CMC is soluble in distilled water. N-CMC is thermostable up to 194.25°C as determined by thermogravimetric analysis (TGA). Zebrafish embryos (ZFE) exposed to N-CMC at a concentration of 4 μg/mL revealed teratogenic effects. The locomotor activity of the N-CMC (1 to 4 mg/L) treated zebrafish was significantly (P<0.05) decreased during the third week of the experiment by using ToxTrac software.

Isopropanol is a versatile biofuel and industrial chemical used as a solvent, intermediary material, and fuel. Traditional petroleum-based production methods are energy-intensive and environmentally harmful, driving interest in sustainable microbial synthesis. To optimize microbial production systems, it is essential to understand the molecular interactions governing substrate and enzyme dynamics in isopropanol biosynthesis. This study aims to uncover these interactions using advanced computational tools and systems biology through an in-silico analysis of chain-specific substrate interactions in two wild-type NADP-dependent bacterial secondary alcohol dehydrogenase (sADH) proteins. The methodology involved selecting 11 available FASTA amino acid sequences of sADH from representative microbes known for isopropanol synthesis. Multiple sequence alignments were performed to identify conserved domains and evolutionary relationships. Two best-available crystal structures, 1PED and 7XPM, were validated using evaluation techniques such as 2Struc, PROCHECK, and ERRAT. Subsequently, 8 representative substrates were docked with these protein model to analyze the enzyme-substrate molecular interactions through molecular docking and dynamic analysis. Results from the phylogenetic analysis indicated that all selected proteins share conserved regions in the substrate-binding domain, crucial for isopropanol production. The study demonstrated that out of the eight substrates, cellobiose exhibited the highest affinity for the wild-type NADP-dependent bacterial sADH from Clostridium beijerinckii(1PED) and Escherichia coli(7XPM). This research marks the first molecular-level investigation of enzyme-substrate interactions using in-silico methods. Additionally, the study suggests a novel approach to enhance the production of desired products by designing proteins with a single interacting chain, potentially suitable for in vivo validation. This work provides insights that could guide future genetic and metabolic engineering efforts aimed at improving isopropanol production through microbial synthesis.

To understand the role of T cells in the pathogenesis of ulcerative colitis (UC), we analyzed colonic T cells isolated from patients with UC and controls. Here we identified colonic CD4+and CD8+T lymphocyte subsets with gene expression profiles resembling stem-like progenitors, previously reported in several mouse models of autoimmune disease. Stem-like T cells were increased in inflamed areas compared to non-inflamed regions from the same patients. Furthermore, TCR sequence analysis indicated stem-like T cells were clonally related to proinflammatory T cells, suggesting their involvement in sustaining effectors that drive inflammation. Using an adoptive transfer colitis model in mice, we demonstrated that CD4+T cells deficient in either BCL-6 or TCF1, transcription factors that promote T cell stemness, had decreased colon T cells and diminished pathogenicity. Our results establish a strong association between stem-like T cell populations and UC pathogenesis, highlighting the potential of targeting this population to improve clinical outcomes.

AbstractObjective:To identify urinary catheter (UC)–associated urinary tract infection (CAUTI) incidence and risk factors.Design:A prospective cohort study.Setting:The study was conducted across 623 ICUs of 224 hospitals in 114 cities in 37 African, Asian, Eastern European, Latin American, and Middle Eastern countries.Participants:The study included 169,036 patients, hospitalized for 1,166,593 patient days.Methods:Data collection took place from January 1, 2014, to February 12, 2022. We identified CAUTI rates per 1,000 UC days and UC device utilization (DU) ratios stratified by country, by ICU type, by facility ownership type, by World Bank country classification by income level, and by UC type. To estimate CAUTI risk factors, we analyzed 11 variables using multiple logistic regression.Results:Participant patients acquired 2,010 CAUTIs. The pooled CAUTI rate was 2.83 per 1,000 UC days. The highest CAUTI rate was associated with the use of suprapubic catheters (3.93 CAUTIs per 1,000 UC days); with patients hospitalized in Eastern Europe (14.03) and in Asia (6.28); with patients hospitalized in trauma (7.97), neurologic (6.28), and neurosurgical ICUs (4.95); with patients hospitalized in lower–middle-income countries (3.05); and with patients in public hospitals (5.89).The following variables were independently associated with CAUTI: Age (adjusted odds ratio [aOR], 1.01; P< .0001), female sex (aOR, 1.39; P< .0001), length of stay (LOS) before CAUTI-acquisition (aOR, 1.05; P< .0001), UC DU ratio (aOR, 1.09; P< .0001), public facilities (aOR, 2.24; P< .0001), and neurologic ICUs (aOR, 11.49; P< .0001).Conclusions:CAUTI rates are higher in patients with suprapubic catheters, in middle-income countries, in public hospitals, in trauma and neurologic ICUs, and in Eastern European and Asian facilities.Based on findings regarding risk factors for CAUTI, focus on reducing LOS and UC utilization is warranted, as well as implementing evidence-based CAUTI-prevention recommendations.

This study has addressed the issue of enhanced biobutanol production through Consolidated Bioprocessing, with the use of clostridial co-cultures combining C. acetobutylicum(Cac) and C. pasteurianum(Cpa). To begin with, the total Acetone-Butanol-Ethanol (ABE) solvent production and butanol selectivity of individual clostridial cultures grown on different carbon sources present in lignocellulosic hydrolysates. Thereafter, statistical optimization of ABE fermentation with co-culture system was carried out using Box-Behnken design. The optimization variables were Cacto Cpainoculum ratio (X1in mL mL−1), sodium concentration in the medium (X2g L−1), and xylose/glucose ratio (X3g g−1L L−1), whereas response variables were butanol titre (Y1in g L−1), biomass growth (Y2OD600), total ABE titre (Y3in g L−1). Maximum values of the response variables with the corresponding set of optimization parameters were as follows: Y1, max= 12.1 ± 0.45 (for X1= 0.30, X2= 5.90, X3= 0), Y2, max= 4.15 ± 0.03 (for X1= 0.3, X2= 2.42, X3= 0.14), Y3, max= 23.1 ± 0.55 (for X1= 0.46, X2= 6.36, X3= 0). The study demonstrated a substantial ≈ 22% and 61% increment in butanol titre in co-culture system compared to individual fermentations with Cacand Cpagrown on pure glucose, respectively.

The influence of grain size, in the range of 10 to 180 μm, on creep properties of 304HCu stainless steel (SS) was evaluated at 180 MPa and 923 K. A 30 μm grain size showed a peak in creep life and minimum in steady-state creep rate with low damage potential. Detailed microstructural investigations revealed an increase in the tendency to intergranular fracture at grain sizes above 30 μm, whereas ‘transgranular fracture coupled with isolated intergranular cracks/cavities’ have been observed with decreasing grain size from 30 to 10 μm.

The present study evaluated the influence of food-to-food fortification of wheat flour (WF) with two varieties of Musaceaeflours (MF) (nendran(NMF) and pachhebale(PMF)) on the rheological characteristics of WF, quality and nutritional profiles of layered flat-bread (LFB). The increase in water absorption capacity of wheat flour was 56.8–73.6% for NMF and 56.8–71.7% for PMF with the addition of MF at 0% (control)10%, 20%, and 30% levels. The dough development time increased while dough stability was reduced with the addition of either NMF or PMF. In addition, there was an increased resistance to extension with less extensibility, reflecting in the smaller spread of the LFB with increasing amounts of MF. All the starch viscosity parameters decreased in the presence of NMF or PMF. The diameter of LFB decreased, and thickness increased with MF. Satisfactory sensory attributes were observed at 20% level of fortification in both NMF and PMF. The highest amount of resistant starch was detected in N20 (6.13%) followed by P20 (5.78%) and control (4.32%). The content of dietary fiber, Mg, Fe, Zn and Mn were also higher in N20 than in P20. Thus, although the nutritional analysis indicated MF as a potential functional ingredient to improve the nutritional properties of LFB, beyond 20% level, the rheological and sensory characteristics are adversely affected.

The low-lying isomers of SiC4H2are investigated to understand the kinetics of isomerization pathways using density functional theory. In our earlier work, we studied the various possible isomers (J. Phys. Chem. A, 2020, 124, 987–1002) and the chemical bonding of low-lying isomers of SiC4H2(J. Phys. Chem. A, 2022, 126, 9366–9374). Among them, four isomers, 1-ethynyl-3-silacycloprop-1-en-3-ylidene (1), 3-silapent-1,4-diyn-3-ylidene (2), 1-silapent-1,2,3,4-tetraen-1-ylidene (4), and 1-silapent-2,4-diyn-1-ylidene (5) have already been identified in the laboratory. The previously known theoretical isomer 2-methylene-1-silabicyclo[1.1.0]but-1(3)-en-4-ylidene (3) and the newly identified unknown isomer through the present kinetic studies 5-silabicyclo[2.1.0]pent-1(4),2-dien-5-ylidene (N6) remain elusive in the laboratory to date. The isomerization pathways of the low-lying isomers of SiC4H2are predicted through the transition state structures. Intrinsic reaction coordinate analysis identifies the minimum energy reaction pathways connecting the transition state from one isomer to another of the investigated system. The present kinetic data reveal the isomerization of global minimum energy isomer 1to thermodynamically stable low-lying isomers, 2and 5. Interestingly, isomer 3interconverts to the experimentally known low-energy isomer 4, the second most thermodynamically stable isomer among them. The thermodynamic and kinetic parameters of the low-lying isomers of SiC4H2are also documented in this work. The rate coefficient and equilibrium constant for isomerization reactions are calculated using the Rice–Ramsperger–Kassel–Marcus theory. The equilibrium constant delineates the difficulties in forming N6and 3through the isomerization pathways. Furthermore, ab initio molecular dynamics studies dictate the stability of low-lying isomers of SiC4H2within the time scale of the simulation.

Introduction:Autism spectrum disorders (ASDs) are complex neurodevelopmental disorders characterized by restrictive repetitive behavior and impairment in social and communication skills. They are extremely heterogeneous with a strong genetic preponderance. They are clinically highly convoluted, presenting with multiple comorbid conditions and syndromic features. More than 100 genes have been identified to date. Method:Whole exome sequencing (WES) has emerged as a valuable tool in evaluating the genetic underpinnings of ASDs, be it the syndromic or the idiopathic variants. In the current study, we performed WES on a multiplex family of Indian origin to investigate the disease etiology in the siblings (S1 [Female] and S2 [Male]) exhibiting ASD syndromic features, at both clinical and genetic aspects. Results:Exome sequencing identified a missense variant (NM_030665.4:c.5320C>T; p.Arg1774Trp) in S1 resulting in RAI1haploinsufficiency. Validation by Sanger sequencing confirmed that the variant was true positive and maternally transmitted in the subject. Likewise, we report an inherited missense variant at the same locus (17p11.2) corresponding to the FLII gene(NM_002018.4:c.2030A>C; p.Glu677Ala) in the other sibling, S2. Both the variants were reported in the Smith Magenis syndrome (SMS) critical region justifying their contribution to the presentation of the syndromic SMS features. These WES findings were consistent with the clinical findings that imply SMS features in both siblings. Conclusion:The current study employed WES to provide insights into the genetic complexity associated with syndromic ASD and how that contributes to the disease heterogeneity. Moving forward, combinatorial approaches and findings from syndromic ASDs can potentially act as indicators to understand the genetic and phenotypic variations seen in idiopathic ASD.

Aims: To evaluate the safety profile of robotic cholecystectomy performed within the United Kingdom (UK) Robotic Hepatopancreatobiliary (HPB) training programme. Methods: A retrospective evaluation of prospectively collected data from eleven centres participating in the UK Robotic HPB training programme was conducted. All adult patients undergoing robotic cholecystectomy for symptomatic gallstone disease or gallbladder polyp were considered. Bile duct injury, conversion to open procedure, conversion to subtotal cholecystectomy, length of hospital stay, 30-day re-admission, and post-operative complications were the evaluated outcome parameters. Results: A total of 600 patients were included. The median age was 53 (IQR 65–41) years and the majority (72.7%; 436/600) were female. The main indications for robotic cholecystectomy were biliary colic (55.5%, 333/600), cholecystitis (18.8%, 113/600), gallbladder polyps (7.7%, 46/600), and pancreatitis (6.2%, 37/600). The median length of stay was 0 (IQR 0–1) days. Of the included patients, 88.5% (531/600) were discharged on the day of procedure with 30-day re-admission rate of 5.5% (33/600). There were no bile duct injuries and the rate of conversion to open was 0.8% (5/600) with subtotal cholecystectomy rate of 0.8% (5/600). Conclusion: The current study confirms that robotic cholecystectomy can be safely implemented to routine practice with a low risk of bile duct injury, low bile leak rate, low conversion to open surgery, and low need for subtotal cholecystectomy.

The reliable connectivity over wireless network is of key importance in the connected car ecosystem to provide critical services for both drivers and the passengers. To address the connectivity challenge, a novel framework for the connected car has been proposed in this paper called CDCS (Car Data Connectivity and Security System), an intelligent, secure and efficient run-time middle-ware framework that analyzes wireless network behavior, network traffic monitoring, to seamless switch-over between Cellular and WiFi networks for the car to have always-on network connectivity. The proposed CDCS framework was successfully tested on a concept car–Hyundai Santro model in real time and the results based on ANOVA technique with deeper insights demonstrates the promising potential to actual deployment in the newly car models.

Study design: Retrospective cohort study. Objectives: The purpose was to analyze the effect of care bundle protocol on SSI in our institution. Summary of background data: Postoperative surgical site infections (SSI) pose significant health burden. In spite of the use of prophylactic antibiotics, surgical advances and postoperative care, wound infection continues to affect patient outcomes after spine surgery. Methods: Retrospective analysis of 9607 consecutive patients who underwent spine procedures from 2014 to 2018 was performed. Preventive care bundle was implemented from January 2017 consisting of (a) preoperative bundle-glycemic control, chlorhexidine gluconate (CHG) bath, (b) intra-operative bundle-time specified antibiotic prophylaxis, CHG+ alcohol-based skin preparation (c) postoperative bundle-five moments of hand hygiene, early mobilization and bundle auditing. Patients operated from January 2017 were included in the post-implementation cohort and prior to that the pre-implementation cohort was formed. Data were drawn from weekly and yearly spine audits from the hospital infection committee software. Infection data were collected based on CDC criteria, further sub classification was done based on procedure, spinal disorders and spine level. Variables were analyzed and level of significance was set as &lt; 0.05. Results: A total of 7333 patients met the criteria. The overall SSI rate decreased from 3.42% (131/3829) in pre-implementation cohort to 1.22% (43/3504, p= 0.0001) in post-implementation cohort (RR = 2.73, OR = 2.79). Statistically significant reduction was seen in all the groups (a) superficial and deep, (b) early and late and (c) instrumented and uninstrumented groups but was more pronounced in early (p= 0.0001), superficial (p= 0.0001) and instrumented groups (p= 0.0001). On subgroup analysis based on spine level and spinal disorders, significant reduction was seen in lumbar (p= 0.0001) and degenerative group (p= 0.0001). Conclusions: Our study revealed significant reduction of SSI secondary to strict bundle adherence and monitored compliance compared to patients who did not receive these interventions. Level of evidence: III.

Background: Approximately 20% of women develop an ovarian cyst or pelvic mass at some point in their lives. Due to high false positivity of CA-125, women with various benign ovarian tumors simulating malignant masses undergo extensive debulking surgery resulting in increased morbidity. Serum HE4 is a useful test for better discrimination of benign or malignant nature of pelvic masses in preoperative period. Our study gives an update on the biological markers specifically CA-125 and a novel tumor marker HE4 and aims to reduce the debulking surgeries done for benign pathology. Materials and Methods: The total study population (n= 302) included women who were operated with suspicious ovarian malignant mass (n= 238) with benign (n= 98), borderline (n= 6), and malignant (n= 134) ovarian tumors. Cutoff of CA-125 was 35 U/mL, and for HE4 140 pM for postmenopausal and 70 pM for premenopausal women were calculated at 86% and 81% accuracy, respectively. Statistical analysis was done using SPSS version 20. Results: The cutoff values of CA-125 were able to differentiate between benign, borderline, and malignant tumors with statistical significance (p&lt; 0.05), whereas the cutoff values of HE4 significantly (p&lt; 0.05) differentiated benign tumors from the malignant tumors, but not from the borderline tumors. Serum CA-125 has significantly higher sensitivity and NPV (95%, 72%, respectively) compared to HE4 (81%, 52%) and combined HE4 plus CA-125 (84%, 59%), whereas specificity, PPV, and AUC were higher for combined CA-125 plus HE4 (93%, 98%, 90%, respectively) compared to HE4 (83%, 95%, 88%) and CA-125 (48%, 88%, 87%). Conclusion: Measuring serum HE4 along with CA-125 in preoperative diagnosis helps in excluding benign ovarian tumors in which CA-125 was falsely raised, especially in center where frozen section is not available, thus potentially decreasing morbid debulking surgeries done for benign ovarian tumors.

We recognize that a variety of tools and groupware used by distributed teams can strongly influence the manner in which team members can obtain awareness of the project. Considering that is often a necessity and even advantageous to use a variety of applications as well as the fact that project awareness is most essential, we propose an "Awareness Framework" that seeks to bind heterogeneous tools and groupware. This research discusses the architecture of the framework as well as a process that is necessary to manage it and project awareness.

Graphical Abstract:

Structural deformation of reinforced cement concrete (RCC) structures often initiated by the corrosion of reinforcement bars has been a major issue in the construction industry. The inadvertent presence of chloride ion is perceived to be the primary cause of corrosion in seashore areas, where the rate of corrosion enhanced under hot, humid and salty environment. Most of the analytical instrumentation installed for concrete corrosion studies have contact sensors which face many challenges in producing accurate and reliable results from long-term continuous monitoring. The aim of the present study is to develop a novel embeddable potential sensor using titanium dioxide (TiO2) nanoparticles with provisions for flexible spatial installation for corrosion detection in RCC structures. The sensors are developed by indigenously fabricating the electrodes and emplacing them inside concrete environment in sequence while casting. The corrosion rate is monitored in terms of potential measurements by exposing the electrodes to interact with the hydrochemistry of concrete. The results indicate that intrinsic anticorrosive resistance of the nano-based sensor is favourable for detecting early signals of chloride corrosion with good sensitivity ( ≤ ± 5 mV). The potentiodynamic results confirm the stability of the sensor under different aggressive environmental conditions. The interpretations of the ionic corrosion potential results suggest reliability of the peak signals which helps in estimating the spatial extent of corrosion migration for initiating necessary preventive measures. The proposed sensors can be effectively employed for sustainable rehabilitation operations by easy detection of environmental stresses such as moisture ingress and saline intrusion on the exposed surfaces.

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n= 1391), Burkina Faso (n= 353) and South Africa (n= 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.

Background Somatosensory impairments in the upper limb are a common occurrence in >50% of post-stroke individuals. The effects of a combined sensorimotor therapy program on improving functional outcomes have not been studied extensively especially in the acute and subacute phase post-stroke.Methods Through a randomized controlled trial of PROBE design, participants, selected on a pre-set selection criteria will either receive the a structured regime of sensorimotor therapy in addition to routine care or only routine care for over 14 days or until discharge. Outcomes will be analyzed on the “Action Research Arm test” and “Erasmus modified Nottingham Sensory Assessment” scale at discharge and then at the third and sixth months.Results and Conclusion The proposed study will allow development and implementation of sensory rehabilitation components to the existing stroke rehabilitation protocols. Initiating intervention within the acute and subacute phase post-stroke in suitable patients will allow early intervention for sensorimotor impairments subsequently leading to improved upper limb outcomes.

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Although mucosal-associated invariant T (MAIT) cells provide rapid, innate-like responses, they are not pre-set, and memory-like responses have been described for MAIT cells following infections. The importance of metabolism for controlling these responses, however, is unknown. Here, following pulmonary immunization with a Salmonellavaccine strain, mouse MAIT cells expanded as separate CD127−Klrg1+and CD127+Klrg1−antigen-adapted populations that differed in terms of their transcriptome, function and localization in lung tissue. These populations remained altered from steady state for months as stable, separate MAIT cell lineages with enhanced effector programmes and divergent metabolism. CD127+MAIT cells engaged in an energetic, mitochondrial metabolic programme, which was critical for their maintenance and IL-17A synthesis. This programme was supported by high fatty acid uptake and mitochondrial oxidation and relied on highly polarized mitochondria and autophagy. After vaccination, CD127+MAIT cells protected mice against Streptococcus pneumoniaeinfection. In contrast, Klrg1+MAIT cells had dormant but ready-to-respond mitochondria and depended instead on Hif1a-driven glycolysis to survive and produce IFN-γ. They responded antigen independently and participated in protection from influenza virus. These metabolic dependencies may enable tuning of memory-like MAIT cell responses for vaccination and immunotherapies.

The construction of photoactive units in the proximity of a stable framework support is one of the promising strategies for uplifting photocatalysis. In this work, the ultrasmall Pd NPs implanted onto core–shell (CS) metal organic frameworks (MOFs), i.e., CS@Pd nanoarchitectures with tailored electronic and structural properties are reported. The all-in-one heterogeneous catalyst CS@Pd3 improves the surface functionalities and exhibits an outstanding hydrogen evolution reaction (HER) activity rate of 12.7 mmol g–1h–1, which is 10-folds higher than the pristine frameworks with an apparent quantum efficiency (AQE) of 9.02%. The bifunctional CS@Pd shows intriguing results when subjected to photocatalytic CO2reduction with an impressive rate of 71 μmol g–1h–1of MeOH under visible-light irradiation at ambient conditions. Spectroscopic data reveal efficient charge migrations and an extended lifetime of 2.4 ns, favoring efficient photocatalysis. The microscopic study affirms the formation of well-ordered CS morphology with precise decoration of Pd NPs over the CS networks. The significance of active Pd and Co sites is addressed by congruent charge-transfer kinetics and computational density functional theory calculations of CS@Pd, which validate the experimental findings with their synergistic involvement in improved photocatalytic activity. This present work provides a facile and competent avenue for the systematic construction of MOF-based CS heterostructures with active Pd NPs.

Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation.

In the electroless nickel-boron coating process, surfactant helps to minimize the surface tension between the substrate and the electrolyte in the bath. Despite, its high cost and the formation of micelles from monomeric surfactant molecules at its critical micelle concentration (CMC), it is essential to optimize the concentration while using in the bath. In this study, to solve this problem, mathematical models are developed using regression and artificial neural network (ANN) techniques to relate the concentration of amphoteric surfactant (0-0.162 g/L) as an independent variable and microhardness as a dependent variable. Then, the developed model was used to optimize microhardness at CMC using a genetic algorithm (GA). The goodness of fit of the models was evaluated using the coefficient of determination (R2). The ANN model was found to be the best fit with R2 = 0.99. The maximum microhardness of 852 HV was achieved at the CMC of 0.064 g/L, from the GA using the validated model as a fitness function.

A subset of endometrial endometrioid carcinomas (EECs) with low-grade histology recur with poor outcomes. Published evidence suggests that poor outcomes may be associated with loss of expression of ER-alpha (ER-α) as well as with β-Catenin-1 (CTNNB1) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. This study reports on institutional experience with the incidence of recurrence in low-grade EEC and their association with CTNNB1and KRASmutations as well as estrogen/progesterone receptor (ER/PR) expression. Forty-eight (8.5%) out of 568 cases of low-grade EEC with biopsy-proven recurrence were identified; and were analyzed by immunohistochemistry for ER, PR, p53, MMR protein, and mutation analysis for exon 3 of the CTNNB1and exon 2 of KRASin relation to recurrence type, local or distant metastasis/recurrence. Twenty-three patients (4%) developed local, and 25 patients (4.4%) developed distant metastases/recurrence. Decreased expression or loss of ER/PR was found in 17/44 (38.6%) patients with recurrence. Eighty-four percent of patients with low-grade EEC and local recurrence had CTNNB1mutations. Seventy-three percent of patients with distant metastasis/recurrence had KRASmutations. The association of these mutations with the type of recurrence was statistically significant for both. Five cases with the morphology of low-grade EEC were reclassified as mesonephric-like carcinoma and were universally characterized by distant metastasis/recurrence, loss of ER/PR expression, large tumor size, absence of CTNNB1mutations, and the presence of KRASmutations. In low-grade EEC, CTNNB1and KRASmutations are associated with local recurrence and distant metastasis/recurrence, respectively, suggesting that these 2 different progression types may be conditioned by tumor genotype. ER/PR immunohistochemistry may be helpful in identifying poor performers in low-grade EEC. Furthermore, identification of the decreased expression or loss of ER/PR in tumors with low-grade histology should prompt consideration of mesonephric-like carcinoma, which is a more aggressive tumor than the low-grade EEC. KRASmutations were associated with distant metastasis/recurrence in tumors with and without mesonephric-like phenotype.

Background/aimTo evaluate the safety and efficacy of ruthenium-106 (Ru-106) plaque brachytherapy in managing invasive ocular surface squamous neoplasia (OSSN).MethodsThis is a retrospective, non-comparative, interventional case series of 42 eyes with OSSN with histopathologically-proven corneal stromal and/or scleral invasion that underwent Ru-106 plaque brachytherapy. Main outcome measures were tumour regression, eye salvage, final visual acuity, treatment complications and metastasis.ResultsAt presentation, the mean tumour basal diameter was 9.3 mm (range 5–26 mm) and thickness 3.1 mm (range 1.5–11 mm). Prior treatment included excision biopsy in two patients (5%), incision biopsy and topical interferon in one each (2%). Following excision with 4 mm clinically clear margins, corneal stromal and/or scleral invasion of OSSN was confirmed in all 42 cases, with the excised base showing invasive squamous cell carcinoma. A total dose of 5000 cGy over a mean duration of 19.7 hours (range 7–41 hours) was provided to an axial depth of 2 mm using Ru-106 surface plaque. Over a mean follow-up of 36.9 months (range 22.3–72 months), complete tumour regression was achieved in all eyes (100%). Two eyes (5%) showed conjunctival tumour growth remote from the site of prior treatment. Visual acuity was maintained at ≥20/200 in 35 eyes (83%), with a loss of >2 Snellen lines in 1 eye (2%). There was no evidence of regional lymph node or systemic metastasis.ConclusionHistopathology-guided use of Ru-106 surface plaque brachytherapy is a safe and an effective adjuvant therapy in the management of corneal stromal and/or scleral invasion of OSSN.

Sono-enzymatic biodiesel synthesis from different feedstocks has been significantly investigated in recent years, which reports the impact of ultrasound (US) on the structure of lipases. However, the links between alteration in the structure of lipases due to US and its activity enhancement have yet to be established. This study reveals the molecular mechanism of US-induced enhancement of lipase-catalyzed reactions in biodiesel synthesis. Using molecular simulations, we first analyzed the 3D structures and amino acid (aa) composition of the binding pockets of two lipases, viz. CALB and TLL. Next, docking analysis of different ligands (substrates and products of the reactions) with lipases was performed to reveal the interacting residues. We identified the US-induced alteration in the secondary structure of lipase from previous reports. Our analysis revealed that most binding pockets are located in the α-helix and random coil motifs, and binding interactions are mainly hydrogen bonding and hydrophobic interactions. We observed a rise in α-helix and random coils of lipase with sonication. The net effect of sonication is the widening of the catalytic cavity, thus easy substrate accessibility to the active site. Thus, enhanced enzymatic activity is manifested as faster kinetics of the reactions with higher yields.

Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection can result in severe immune dysfunction, hospitalization, and death. Many patients also develop long‐COVID‐19, experiencing symptoms months after infection. Although significant progress has been made in understanding the immune response to acute SARS‐CoV‐2 infection, gaps remain in our knowledge of how innate immunity influences disease kinetics and severity. We hypothesized that cytometry by time‐of‐flight analysis of PBMCs from healthy and infected subjects would identify novel cell surface markers and innate immune cell subsets associated with COVID‐19 severity. In this pursuit, we identified monocyte and dendritic cell subsets that changed in frequency during acute SARS‐CoV‐2 infection and correlated with clinical parameters of disease severity. Subsets of nonclassical monocytes decreased in frequency in hospitalized subjects, yet increased in the most severe patients and positively correlated with clinical values associated with worse disease severity. CD9, CD163, PDL1, and PDL2 expression significantly increased in hospitalized subjects, and CD9 and 6‐Sulfo LacNac emerged as the markers that best distinguished monocyte subsets amongst all subjects. CD9+monocytes remained elevated, whereas nonclassical monocytes remained decreased, in the blood of hospitalized subjects at 3–4 months postinfection. Finally, we found that CD9+monocytes functionally released more IL‐8 and MCP‐1 after LPS stimulation. This study identifies new monocyte subsets present in the blood of COVID‐19 patients that correlate with disease severity, and links CD9+monocytes to COVID‐19 progression. SARS‐CoV‐2 infection induces long‐lasting changes in the myeloid cell compartment, and novel monocyte subsets, distinguished by expression of CD9 and Slan, correlate with COVID‐19 severity.