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Abstract The increasing global energy demand and environmental concerns have highlighted the need for sustainable and renewable energy sources. Lignocellulosic biomass (LCB), rich in cellulose, hemicellulose, and lignin, is a promising resource for biofuel production. However, the recalcitrant nature of lignin poses a significant challenge by obstructing effective LCB decomposition. This review provides a comprehensive analysis of recent advancements in genetic and metabolic engineering techniques, focusing on directed and random mutagenesis to enhance cellulase production in fungi. It explores how these techniques can overcome challenges in lignin degradation and improve LCB conversion efficiency. Lignin's high resistance to degradation, due to its complex association with cellulose and hemicelluloses, necessitates the development of advanced fungal strains through mutagenesis. Fungi, which are efficient lignin degraders, benefit from these practices to enhance enzyme production and address environmental pollution from burning LCB. The review emphasizes engineering cellulolytic fungi through mutagenesis, gene-editing, and synthetic biology, highlighting CRISPR-Cas innovations and nanoparticle-based delivery systems for precise CRISPR-Cas application. It also discusses the role of transcription factors in boosting enzyme production and the practical applications of these techniques for in-situ LCB biodegradation. Effective implementation of these advancements could foster a sustainable economy and mitigate the negative environmental impacts of current agricultural practices.

Abstract Human respiratory syncytial virus (RSV) is a major cause of acute respiratory infection. In 2020, RSV was eliminated from New Zealand due to non-pharmaceutical interventions (NPI) used to control the spread of SARS-CoV-2. However, in 2021, following a brief quarantine-free travel agreement with Australia, there was a large-scale nationwide outbreak of RSV that led to reported cases more than five-times higher than typical seasonal patterns. We generated 1470 viral genomes of both RSV-A and RSV-B sampled between 2015–2022 from across New Zealand. Using a phylodynamics approach, we used these data to better understand RSV transmission patterns in New Zealand prior to 2020, and how RSV became re-established in the community following the relaxation of COVID-19 restrictions. We found that in 2021, there was a large epidemic of RSV due to an increase in importations, leading to several large genomic clusters of both RSV-A ON1 and RSV-B BA9 genotypes. However, while a number of viral importations were detected, there was also a major reduction in RSV genetic diversity compared to pre-pandemic years. These data reveal the impact of NPI used during the COVID-19 pandemic on other respiratory infections and highlight the important insights that can be gained from viral genomes.

In this research, we analyzed narratives from the National Electronic Injury Surveillance System (NEISS) dataset to predict the top two injury codes using a comparative study of ensemble machine learning (ML) models. Four ensemble models were evaluated: Random Forest (RF) combined with Logistic Regression (LR), K-Nearest Neighbor (KNN) paired with RF, LR combined with KNN, and a model integrating LR, RF, and KNN, all utilizing a probabilistic likelihood-based approach to improve decision-making across different classifiers. The combined KNN + LR ensemble achieved an accuracy of 90.47% for the top one prediction, while the KNN + RF + LR model excelled in predicting the top two injury codes with a very high accuracy of 99.50%. These results demonstrate the significant potential of ensemble models to enhance unstructured narrative classification accuracy, particularly in addressing underrepresented cases, and the potential of the proposed probabilistic ensemble framework ML models in improving decision-making in public health and safety, providing a foundation for future research in automated clinical narrative classification and predictive modeling, especially in scenarios with imbalanced data.

Immunoassay interferences, including those from exogenous substances like biotin, can lead to misinterpretation of laboratory results and clinical decision-making challenges. A 28-year-old unmarried female presented to dermatologist with 4-year history of acne, hirsutism, and hair loss. Hormonal assays using chemiluminescence immunoassays (CLIA) and enzyme-linked immunosorbent assays (ELISA) revealed alarmingly high testosterone levels, suggesting neoplastic androgen excess and severe insulin resistance. This prompted referral to endocrinology for further evaluation. Patient's menarche occurred at age 11, with regular menstrual cycles. Family history indicated diabetes and hirsutism, but not infertility. Physical examination revealed body mass index (BMI) of 21.8 kg/m2 and Ferriman-Gallwey score of 11. Despite severe biochemical hyperandrogenism, her clinical presentation was mild. Differential diagnoses included polycystic ovary syndrome (PCOS) and late-onset congenital adrenal hyperplasia (CAH). Repeat hormonal testing, performed at multiple laboratories using liquid chromatography-mass spectrometry (LCMS), CLIA, and ELISA, showed normal testosterone, free testosterone, and insulin levels, suggesting that the initial results were falsely elevated. Review of her dermatology prescriptions revealed that she had taken a single 10 mg tablet of biotin 33 hours before first blood draw, leading to diagnosis of biotin interference in immunoassays. After the two-week biotin washout period, her subsequent endocrinology work-up had indicated “normalized” hormonal levels. Pelvic and abdominal ultrasound imaging revealed normal ovaries and adrenal areas. Thus, biotin associated testosterone (and insulin) immunoassay interference can confound clinical diagnosis and management. Any observed discordance between clinical symptoms, signs and hormonal levels should raise possibility of immunoassay interferences, reemphasizing need for heightened physician awareness.

Introduction: Maxillary constriction is a very common type of malocclusion found at any age. It is recommended to treat it as early as possible to avoid the worsening of the situation and to re-establish optimal function and aesthetics. Expansion of the maxillary arch is considered the best treatment procedure in a growing child. There are various appliances used for the expansion of the arch. The Nickel Titanium (NiTi) expander is considered the hallmark in orthodontics, but it has a few drawbacks. To overcome these drawbacks, the Sawangi Flexiforce Expander (SFE) has been introduced. The present study aims to evaluate and compare the effects of SFE against NiTi expander. Need for the study: The commercially available NiTi expander is very expensive. As most dental practices are located in rural areas, not every patient requiring arch expansion can afford it. Therefore, there is a need for an appliance that is as effective as the NiTi expander but affordable for everyone. Aim: To evaluate and compare the three-dimensional skeletal and dentoalveolar effects of SFE against the NiTi expander in class II (vertical) cases with maxillary constriction using the Finite Element Method (FEM). Materials and Methods: The present FEM study will be conducted in the Department of Orthodontics and Dentofacial Orthopaedics at Sharad Pawar Dental College in Wardha, Maharashtra, India. The study will take place from November 2023 to October 2024. A single patient with a vertically growing pattern will be selected for a Computed Tomography scan (CT scan) of the Nasomaxillary complex based on inclusion and exclusion criteria. The CT scan of the patient will then be converted into a 3D finite element model. The 3D models of the NiTi expander, SFE, and nasomaxillary complex will be studied to evaluate and compare the three-dimensional effects. Parameters such as stress distribution and displacement at skeletal, dental, and dentoalveolar landmarks of the nasomaxillary complex in three directions due to both expanders will be evaluated. An unpaired t-test will be used to determine significant differences between the two expanders and to compare the outcomes. The displacement at each landmark due to 1 mm of activation of both expanders will be correlated using the Pearson’s correlation test. A p-value

Abstract By early 2022, the highly transmissible Omicron variant of SARS-CoV-2 had spread across most of the world. For the first time since the pandemic began, New Zealand was experiencing high levels of community transmission of SARS-CoV-2. We enroled a cohort of households to better understand differences in transmission dynamics among subvariants of Omicron. We enroled 71 households, comprising 289 participants, and aimed to use viral genomes to gain a clearer understanding of variant-specific differences in epidemiological parameters affecting transmission dynamics. Approximately 80% of the households enroled experienced transmission of BA.2, while most of the remaining households had infections with BA.1 or BA.5. Using a logistic regression generalised linear mixed model, we found no difference in household secondary infection rate between Omicron subvariants BA.1, BA.2 and BA.5. Of the households recruited, the vast majority (92%) experienced a single chain of transmission with one inferred introduction. Further, we found that in 48% of the households studied, all household participants became infected following an index case. Most household participants tested positive within a week following an introduction, supporting the seven-day isolation requirement for household contacts that was in place in New Zealand at the time. By integrating genomic and epidemiological data, we show that viral transmission dynamics can be investigated with a higher level of granularity than with epidemiological data alone. Overall, households are a high risk setting for viral transmission in New Zealand.

The forensic literature has described unusual wounds of entry into fatal stab wounds that are rarely found in autopsies. Stab wounds are considered fatal injuries when they occur in vital organs. Many authors have suggested that the description of the wound track helps recreate the crime scene. Still, many say that the recreation of a crime scene is a static event, whereas the actual event is dynamic. We received the dead body of a 25-year-old male for postmortem examination. During autopsy, we found a wedge-shaped stab wound in the epigastric region. Interestingly, when we dissected the skin and subcutaneous tissue without disturbing the wound, we observed two separate wedge-shaped wounds over the rectus sheath. A knife can produce an atypical appearance after plunging into the body. With a single external primary stab wound, two different wound tracks can be made internally. Thus, examining only the wound track made it impossible to comment on the circumstances of violence.

Objective Older patients with cancer have traditionally been under-represented in global clinical trials. There are no data from India regarding this issue.Methods and analysis This was a retrospective analysis done at our institute on interventional studies conducted between 2003 and 2023 in adult patients with malignancies. We excluded studies done exclusively in the paediatric population and observational studies.Results We included 21 894 patients enrolled in 150 interventional trials from the departments of surgical, medical, and radiation oncology, anaesthesia, and clinical pharmacology; 110 (73.3%) were investigator initiated. There were 38 trials (25.3%) in breast cancer (6141 patients, 28%), and 33 (22%) in head and neck cancer (6975 patients, 31.9%). Studies were predominantly phase III (97 trials (64.7%)). Multicentric studies comprised approximately one-third (48, 32%). The median age of enrolled patients was 51 years (IQR 43–59). There were 5132 (23.4%) participants aged ≥60 years, 2678 (12.2%) ≥65 years and 1045 (4.8%) ≥70 years. Data from the hospital registry revealed that 30% of adult registrations were ≥60 years. There was a significant increase in the proportion of older patients enrolled in clinical trials from 2003 (8%) to 2019 (22%) compared with their proportion in the hospital registry (stable at 28%–29%); p

Background: For intraocular surgery, the optimal local anesthetic agent must have a rapid onset of action and a sufficient duration of effect so as to enable a painless, motionless procedure without prolonging akinesia. Aims and Objective: This prospective, comparative observational study compares ropivacaine and 0.5% bupivacaine for cataract surgery peribulbar block. Hyaluronidase is utilized in both groups because it promotes local anesthetic diffusion. Material and Methods: Present prospective, observational, comparative study performed at the Department of Anesthesia Tertiary Care Teaching Institute of India for the duration of 1 year. All eligible patients were allocated in two groups as GROUP B and GROUP R. GROUP B: 10 mL of 0.5% bupivacaine and 15 I.U./mL of hyaluronidase. GROUP R: 10 mL of 0.5% ropivacaine and 15 I.U./mL of hyaluronidase. Patients were assessed for sensory block, eyelid, and ocular movements at an interval of 2 min, and Visual Analog Scale score for pain assessment. Results: Age and gender did not differ significantly between the two study groups, according to the findings. Comparable and similar patient characteristics distinguished the two study groups. (P>0.05). The difference in onset of eyelid motor blockade between the two groups was not statistically significant. The difference in the onset of motor blockade [ocular movement] between the two groups was not statistically significant (P>0.05). (P>0.05) Analgesia duration differed significantly between the two groups in a statistical sense. Ropivacaine exhibits a significantly prolonged duration of analgesic effect than bupivacaine (P≤0.05). Conclusion: Peribulbar block utilizing 0.5% ropivacaine is a more favorable and secure option for a local anesthetic that effectively extends postoperative pain alleviation, in comparison to the use of 0.5% bupivacaine.

Abstract Red blood cells (RBCs) become sickle‐shaped and stiff under hypoxia as a consequence of hemoglobin (Hb) polymerization in sickle cell anemia. Distinguishing between sickle cell disease and trait is crucial during the diagnosis of sickle cell disease. While genetic analysis or high‐performance liquid chromatography (HPLC) can accurately differentiate between these two genotypes, these tests are unsuitable for field use. Here, we report a novel microscopy‐based diagnostic test called ShapeDx™ to distinguish between disease and trait blood in less than 1 h. This is achieved by mixing an unknown blood sample with low and high concentrations of a chemical oxygen scavenger and thereby subjecting the blood to slow and fast hypoxia, respectively. The different rates of Hb polymerization resulting from slow and fast hypoxia lead to two distinct RBC shape distributions in the same blood sample, which allows us to identify it as healthy, trait, or disease. The controlled hypoxic environment necessary for differential Hb polymerization is generated using an imaging microchamber, which also reduces the sickling time of trait blood from several hours to just 30 min. In a single‐blinded proof‐of‐concept study conducted on a small cohort of clinical samples, the results of the ShapeDx™ test were 100% concordant with HPLC results. Additionally, our field studies have demonstrated that ShapeDx™ is the first reported microscopy test capable of distinguishing between sickle cell disease and trait samples in resource‐limited settings with the same accuracy as a gold standard test.

Hypertriglyceridemia (HTG) is a common cardiovascular risk factor characterized by elevated triglyceride (TG) levels. Researchers have assessed the genetic factors that influence HTG in studies focused predominantly on individuals of European ancestry. However, relatively little is known about the contribution of genetic variation of HTG in people of African ancestry (AA), potentially constraining research and treatment opportunities. Our objective was to characterize genetic profiles among individuals of AA with mild-to-moderate HTG and severe HTG versus those with normal TGs by leveraging whole-genome sequencing data and longitudinal electronic health records available in the All of Us program. We compared the enrichment of functional variants within five canonical TG metabolism genes, an AA-specific polygenic risk score for TGs, and frequencies of 145 known potentially causal TG variants between HTG patients and normal TG among a cohort of AA patients (N = 15,373). Those with mild-to-moderate HTG (N = 342) and severe HTG (N ≤ 20) were more likely to carry APOA5 p.S19W (odds ratio = 1.94, 95% confidence interval = [1.48–2.54], P = 1.63 × 10−6 and OR = 3.65, 95% confidence interval: [1.22–10.93], P = 0.02, respectively) than those with normal TG. They were also more likely to have an elevated (top 10%) polygenic risk score, elevated carriage of potentially causal variant alleles, and carry any genetic risk factor. Alternative definitions of HTG yielded comparable results. In conclusion, individuals of AA with HTG were enriched for genetic risk factors compared to individuals with normal TGs.

Background: This was the first Phase III randomized study comparing an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib, to standard-of-care chemotherapy (pemetrexed + carboplatin followed by pemetrexed maintenance) in advanced EGFR-mutated lung cancer. The initial interim analysis showed the superiority of gefitinib over chemotherapy in terms of progression-free survival (PFS), objective response rate (ORR), and safety. Objectives: We aimed to evaluate the long-term outcomes. Our primary endpoint was to evaluate the overall survival (OS) and the secondary endpoints were progression-free survival 2 (PFS2) and duration of response (DOR). Materials and Methods: This was a Phase III open-label, randomized, parallel-group study conducted in the Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India, in patients with EGFR mutation-positive treatment-naïve Stage IIIB or IV lung adenocarcinoma. Patients were randomized to gefitinib (250 mg orally daily) or carboplatin (area under the curve 5) and pemetrexed (500 mg/m2) chemotherapy, followed by maintenance pemetrexed (500 mg/m2). Results: Between February 2012 and April 2016, 290 patients were randomized:145 to each arm. At a median follow-up of 104 months, all 290 (100%) patients had progressed, and 287 (99%) deaths had occurred. The median OS in the gefitinib arm was 19.5 months (95% confidence interval [CI], 16.7-24.8) compared to 22.6 months (95% CI, 19.2-25.2) in the chemotherapy arm; hazard ratio [HR], 1.11; 95% CI, 0.87-1.39; P, 0.423. The median PFS2 in the gefitinib arm was 15.5 months (95% CI, 13.5-18.1) compared to 12.5 months (95% CI, 11.1-14.5) in the chemotherapy arm; HR, 0.86 (95% CI, 0.66-1.13); P, 0.270. The median DOR was improved in the gefitinib arm (7.6 months; 95% CI, 5.45-9.88) compared to 3.9 months (95% CI, 3.49-6.35) in the chemotherapy arm; HR, 0.59; 95% CI, 0.42-0.82; P, 0.002. The 5-year survival was 4.1% in the gefitinib arm versus 6.8% in the chemotherapy arm. Conclusions: This study establishes the advantages of first-line EGFR TKI therapy over chemotherapy in terms of a durable response and numerically superior PFS2. Due to crossover post-progression, there was is no significant difference in OS (Clinical Trials Registry of India number: CTRI/2015/08/006113).

Introduction: Vitamin D is essential for bone mineral metabolism and for the growth and development of the skeleton. The American Academy of Paediatrics and the Indian Academy of Paediatrics recommend the administration of 400 IU per day of oral Vitamin D to all infants in the first year of life. The authors hypothesised that routine supplementation of 400 IU of Vitamin D to exclusively breastfed infants would result in better physical growth. Aim: To examine the effect of routine vitamin D supplementation (400 IU/day) on the weight, length, and head circumference of term, exclusively breastfed infants at six months of age. Materials and Methods: An observational study was conducted at Department of Paediatrics, Smt. Kashibai Navale Medical College, Pune, Maharashtra, India, from November 2018 to March 2020, comparing the weight, length, and head circumference at birth and at six months of age for 111 exclusively breastfed term, appropriate for gestational age, healthy infants who were not supplemented with oral Vitamin D (Group-I) with 111 infants who were supplemented with 400 IU of oral Vitamin D daily (Group-II). Infants who presented at the Paediatric Out-Patient Department of SKNMC, Pune at around six months of age were enrolled in the study. Birth data and anthropometry at birth were recorded from available medical records. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 23.0. Quantitative data were presented with the mean and standard deviation. Comparison among the study groups was done using an unpaired t-test as per the results of the normality test. Association among the study groups was assessed with the help of a Student's t-test. A p-value of

Objective: The aim of this research was to investigate the role of the cornified epithelium, the outermost layer of the oral mucosa, engineered to prevent water loss and microorganism invasion, in severe forms of periodontitis (stage III or IV, grade C). Methods: Porphyromonas gingivalis, a major periodontal disease pathogen, can affect cornified epithelial protein expression through chronic activation of signal transducer and activator of transcription 6 (Stat6). We used a mouse model, Stat6VT, that mimics this to determine the effects of barrier defect on P gingivalis–induced inflammation, bone loss, and cornified epithelial protein expression, and compared histologic and immunohistologic findings with tissues obtained from human controls and patients with stage III and IV, grade C disease. Alveolar bone loss in mice was assessed using micro-computerised tomography, and soft tissue morphology was qualitatively and semi-quantitatively assessed by histologic examination for several proteins, including loricrin, filaggrin, cytokeratin 1, cytokeratin 14, a proliferation marker, a pan-leukocyte marker, as well as morphologic signs of inflammation. Relative cytokine levels were measured in mouse plasma by cytokine array. Results: In the tissues from patients with periodontal disease, there were greater signs of inflammation (rete pegs, clear cells, inflammatory infiltrates) and a decrease and broadening of expression of loricrin and cytokeratin 1. Cytokeratin 14 expression was also broader and decreased in stage IV. P gingivalis–infected Stat6VT mice showed greater alveolar bone loss in 9 out of 16 examined sites, and similar patterns of disruption to human patients in expression of loricrin and cytokeratins 1 and 14. There were also increased numbers of leukocytes, decreased proliferation, and greater signs of inflammation compared with P gingivalis–infected control mice. Conclusions: Our study provides evidence that changes in epithelial organisation can exacerbate the effects of P gingivalis infection, with similarities to the most severe forms of human periodontitis.

Multi-analyte determination techniques are favored over those that can only determine a single analyte at a time because they enable resource savings (cost, time, and solvents) and reduce generated waste and the number of samples required for analysis. This research presents a novel method for the simultaneous determination of brinzolamide (BRZ) and timolol maleate (TML) in pharmaceutical ophthalmic preparations using first-order derivative UV–Visible spectroscopy. The proposed approach is environmentally friendly and yet to be previously reported in the literature. In this approach, the peak amplitude of BRZ was quantified at the zero-crossing point of TML, i.e., 248.80 nm, whereas TML was determined by measuring absorbance at 297.60 nm. The developed method was validated according to the International Council for Harmonisation guidelines Q2(R1). The developed method was linear with excellent correlation coefficient values (R2 > 0.9998) in the range of 4 – 24 µg/ml for BRZ and 5 – 25 µg/ml for TML. The accuracy and precision results were within limits for both the analytes (%Relative standard deviation, RSD

Background: Pregnancy is associated with a higher risk of adverse symptoms and outcomes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for both mother and neonate. Antibodies can provide protection against SARS-CoV-2 infection and are induced in pregnant women after vaccination or infection. Passive transfer of these antibodies from mother to fetus in utero may provide protection to the neonate against infection. However, it is unclear whether the magnitude or quality and kinetics of maternally derived fetal antibodies differs in the context of maternal infection or vaccination. Objective: We aimed to determine whether antibodies transferred from maternal to fetus differed in quality or quantity between infection- or vaccination-induced humoral immune responses. Methods: We evaluated 93 paired maternal and neonatal umbilical cord blood plasma samples collected between October 2020 and February 2022 from a birth cohort of pregnant women from New Orleans, Louisiana, with histories of SARS-CoV-2 infection and/or vaccination. Plasma was profiled for the levels of spike-specific antibodies and induction of antiviral humoral immune functions, including neutralization and Fc-mediated innate immune effector functions. Responses were compared between 4 groups according to maternal infection and vaccination. Results: We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies compared to naive subjects. Vaccinated mothers and cord samples had the highest anti-spike antibody levels and antiviral function independent of the time of vaccination during pregnancy. Conclusions: These results show that the most effective passive transfer of functional antibodies against SARS-CoV-2 in utero is achieved through vaccination, highlighting the importance of vaccination in pregnant women.

Introduction: The outcomes in advanced NSCLC have improved owing to the availability of more effective systemic and improved supportive care. This has increased the number of patients who seek treatment in the third line and beyond setting. We conducted this study to compare the quality of life (QoL), toxicity, and outcomes in patients receiving chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) in this setting. Methods: In this phase 3, randomized, open-label study, patients with stage III or IV NSCLC with disease progression on at least two prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior EGFR TKI exposure, and stable brain metastases (if any) were included. Patients were randomized to receive chemotherapy (gemcitabine or docetaxel or paclitaxel or vinorelbine) or an EGFR TKI (erlotinib or gefitinib). The primary end point was the change in QoL at 8 to 10 weeks; the secondary outcomes were safety and overall survival (OS). Patients underwent clinical evaluation at every visit, and toxicity was assessed as per Common Terminology Criteria for Adverse Events version 4.03. A radiological tumor response assessment was done every 8 to 12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C30 and LC13 questionnaires. The change in QoL scores was calculated as the difference between scores at baseline and scores at 8 to 10 weeks (Δ) for each QoL domain. The Mann-Whitney U test was used to compare the mean difference (Δ) for each domain. OS and progression-free survival (PFS) were determined using the Kaplan-Meier method and Cox proportional regression analysis. Results: A total of 246 patients were enrolled in the study, with 123 in each arm. There was a male predominance with 69.1% male patients in the chemotherapy arm and 70.7% in the EGFR TKI arm. The median age of patients in the chemotherapy arm was 54 years and 55 years in the chemotherapy and EGFR TKI arms, respectively. There was no significant difference in the change in QoL at baseline and the second visit (Δ) in both arms in all domains of EORTC QLQ C30 except cognitive function (p = 0.0045) and LC13 except alopecia (0.01249). The mean Δ Global Health Status was −28 in the chemotherapy arm and −26.8 in the EGFR TKI arm; this was not statistically significant (p = 0.973). The median follow-up was 88.1 months (95% confidence interval [CI]: 39.04–137.15). On the intention-to-treat analysis, the median PFS was 3.13 months (95% CI: 2.15–4.11) in the chemotherapy arm and 2.26 months (95% CI: 2.1–2.43) in the EGFR TKI arm, with hazard ratio at 1.074 (95% CI: 0.83–1.38) (p = 0.58). There were 120 deaths in each arm. The median OS was 7.63 months (95% CI: 5.96–9.30) in the chemotherapy arm and 7.5 months in the EGFR TKI arm (95% CI: 5.85–9.14); hazard ratio at 1.033 (95% CI: 0.80–1.33) (p = 0.805). The toxicity profile was similar in both arms except for a significantly higher incidence of fatigue (p = 0.043), peripheral neuropathy (0.000), alopecia, hypokalemia (0.037), and pedal edema (0.007) in the chemotherapy arm and dry skin (p = 0.000) and skin rash (p = 0.019) in the EGFR TKI arm. Conclusions: There was no significant difference in most QoL scales (except cognitive function and alopecia), OS, and PFS of patients with advanced NSCLC receiving an EGFR TKI as compared with chemotherapy TKI in the third-line setting. The toxicity profile is consistent with the known toxicities of the agents.

IntroductionThere was shortage of essential diagnostic and therapeutic supplies in public hospitals during the second wave of COVID-19 in India.Materials and methodsThe Local Heroes Project, a hyperlocal project initiated by the World Youth Heart Federation (WYHF). Pilot project was conducted in six cities, and a nationwide project was scaled up to 58 city groups with 438 volunteers. Three-step model of needs assessment, fundraising, and establishment of the supply chain was undertaken. A national team was formed consisting of representatives from multiple international organizations and stakeholders. Local Volunteers were recruited and empowered in each city to conduct donation drives. The Qualitative Comparative Analysis (QCA) model was used to assess the impact of the intervention.Results48.2% of the city groups completed needs assessment and 37.9% completed their donations. Factors such as team strength more than 4, local needs assessment, regular reporting during monthly meeting, receptive local administration, donation to more than 2 health centers and donation of supplies worth >= Rs 5,000 in each city (raw coverage 0.44, consistency 1) were more important contributors for success of the outcome. Supplies worth INR 2.45 million were donated.ConclusionHyperlocal projects can effectively address essential supply shortages. A three-step model of needs assessment, fundraising, and supply chain establishment can be an effective approach. Community involvement and donations are crucial for the success and sustainability of such projects.

Abstract Background Amino acid production features of Corynebacterium glutamicum were extensively studied in the last two decades. Many metabolic pathways, regulatory and transport principles are known, but purely rational approaches often provide only limited progress in production optimization. We recently generated stable synthetic co-cultures, termed Communities of Niche-optimized Strains (CoNoS), that rely on cross-feeding of amino acids for growth. This setup has the potential to evolve strains with improved production by selection of faster growing communities. Results Here we performed adaptive laboratory evolution (ALE) with a CoNoS to identify mutations that are relevant for amino acid production both in mono- and co-cultures. During ALE with the CoNoS composed of strains auxotrophic for either l-leucine or l-arginine, we obtained a 23% growth rate increase. Via whole-genome sequencing and reverse engineering, we identified several mutations involved in amino acid transport that are beneficial for CoNoS growth. The l-leucine auxotrophic strain carried an expression-promoting mutation in the promoter region of brnQ (cg2537), encoding a branched-chain amino acid transporter in combination with mutations in the genes for the Na+/H+-antiporter Mrp1 (cg0326-cg0321). This suggested an unexpected link of Mrp1 to l-leucine transport. The l-arginine auxotrophic partner evolved expression-promoting mutations near the transcriptional start site of the yet uncharacterized operon argTUV (cg1504-02). By mutation studies and ITC, we characterized ArgTUV as the only l-arginine uptake system of C. glutamicum with an affinity of KD = 30 nM. Finally, deletion of argTUV in an l-arginine producer strain resulted in a faster and 24% higher l-arginine production in comparison to the parental strain. Conclusion Our work demonstrates the power of the CoNoS-approach for evolution-guided identification of non-obvious production traits, which can also advance amino acid production in monocultures. Further rounds of evolution with import-optimized strains can potentially reveal beneficial mutations also in metabolic pathway enzymes. The approach can easily be extended to all kinds of metabolite cross-feeding pairings of different organisms or different strains of the same organism, thereby enabling the identification of relevant transport systems and other favorable mutations.

Autonomic imbalance is seen in hypertensive. This study was designed to compare heart rate variability in normotensive and hypertensive Indian adults. HRV records beat to beat variation in R-R intervals in milliseconds in electrocardiogram. Lead II ECG was recorded and a 5 minutes’ stationary, artifacts free recording was selected for data analysis. HRV measures like total power was significantly less in hypertensive (303.37 ± 438.1) as compared to normotensive (534.16 ± 818.41). Standard deviation of normal-to-normal RR intervals was significantly reduced in hypertensive. A significant reduction of HRV was seen in hypertensive as compared to normotensive.

In the nonsurgical therapy of periodontal disease, scaling and root planing (SRP) is the gold standard. Bacterial recolonization occurs from the residual subgingival plaque or from other oral contaminants. To avoid bacterial recolonization, regular periodontal care is essential, as well as the inclusion of coadjutants and active debridement, including such antibiotic therapy and photodynamic therapy. Therefore, the aim of this systematic review and meta-analysis is to evaluate periodontal tissue changes after photodynamic therapy in aggressive periodontitis. An electronic search was conducted on PubMed/ MEDLINE, GOOGLE SCHOLAR, and HAND SEARCH of a reference list of archived articles published from January 2015 to August 2018. After thorough scrutiny, five studies assessing clinical attachment level (CAL) and probing pocket depth (PPD) were considered for the meta-analysis. Using fixed and random effect models, the standardized mean differences (SMDs) were calculated. Results of the fixed and random-effect models had slightly distinct estimates of SMD of CAL, both models resulted in positive and significant treatment effects. The fixed effect was slightly different and positive for PPD (SMD = 0.843, 95 percent CI = 0.510 to 1.176, P = 0.001, significant), while random effects were somewhat different and positive for PPD (SMD = 1.227, 95 percent CI = -0.129 to 2.582, P = 0.076, not significant). Because of heterogeneity, one model indicated substantial treatment effects for PPD, whereas another model showed non-significant treatment effects. Hence, the results concluded the beneficial effects of photodynamic therapy in aggressive periodontitis.

Introduction: Full-coronal restoration is the choice of treatment for restoring pulpally treated tooth or tooth with multiple surface involvement. In paediatric dentistry, semi-permanent stainless steel crowns (SSCs) are considered gold standard, but with increasing need of aesthetics, zirconia crowns have started gaining importance. Hence, this study was conducted to evaluate the clinical performance of SSCs and zirconia crowns and to compare the child satisfaction and parental ratings of impact of treatment using these preformed crowns. Materials and Methodology: This study was a part of randomised controlled trial performed on 60 children of 4–8 years old. The primary molars were cemented with either SSCs or zirconia crowns and were evaluated clinically at baseline, 6-month and 12-month follow-up for crown retention, crown fracture, gingival and debris index, wear, marginal integrity and recurrent caries. The trials also evaluated parental satisfaction and child satisfaction based on five-point Likert scale at the end of 12-month follow-up. The data were analysed using Chi-square test for categorical data and independent sample t-test for quantitative data. Results: Both the crowns were 100% retentive at 12-month follow-up. Fair debris score and mild gingivitis were reported in 3% with SSC at 6–12 months. One zirconia crown fractured at 12 months. Fifty-four per cent of parents in zirconia and 57% in SSC stated that the crowns improved masticatory function. Children reported a mean Likert score of 3.0 for SSC and 4.89 for zirconia which was highly significant. Conclusion: Both the crowns increased the overall health of crowned tooth and were fully retentive for the studied duration. However, zirconia crowns were more gingival friendly and had an edge over SSC in terms of aesthetics.

Background: Dengue infections caused by the four antigenically distinct dengue virus serotypes (DENV1, DENV2, DENV3, DENV4) of the family Flaviviridae are the most major arboviral diseases in humans in terms of geographic spread, morbidity, and mortality. Objective: serum lactate as a predictor of severity in dengue infection Methodology: A prospective observational study was carried out among indoor patients admitted to the general medicine department of the tertiary care hospital SMIMER Surat. The study's duration was 15 to 18 months. Result: our study found out of a total of 154 cases, the majority of cases belonged to 83(53.90%) cases were from less than 30 years. the male contributed 96 (62.34%), the majority of cases had a duration of fever 39(25.32%), 66 (42.66%) cases had high LDH, comparison of serum lactate dehydrogenase with the severity of dengue mean lactate dehydrogenase of dengue without severity was mean was 148.45 and SD 11.81, while in severe dengue mean serum lactate dehydrogenase 388.23 and SD 99.47 with p value 0.001 which was statically significant. Conclusion: According to this study, it is preferable to monitor serial lactate levels as opposed to using a single lactate number.

Background: During minor dental surgical procedures, the greater palatine nerve block is commonly utilized to achieve anesthesia. The greater palatine nerve and arteries are transmitted through the greater palatine foramen (GPF). Furthermore, this region serves as a soft-tissue donor site. The goal of this research was to interpret the location of the GPF and its diameter in an Indian population by utilizing cone-beam computed tomography (CBCT). Materials and Methods: The position of GPF relative to the maxillary molars was estimated by utilizing 120 CBCT scans. Furthermore, the GPF's diameter and distance between the mid-palatine suture and the alveolar ridge were also determined. Results: Of the 120 GPFs examined, 102 were found to be in the third molar region. The GPF's distance from the mid-palatine suture and alveolar ridge was 14.01 ± 1.12 mm and 6.74 ± 1.95 mm, respectively. The mean anteroposterior diameter was 3.43 ± 0.3 mm. On considering the age group ≤45 years, the GPF's average distance from the mid-palatine suture (14.35 ± 1.10 mm) and alveolar ridge (7.87 ± 2.09 mm) was significantly higher than >45 years (P = 0.0329 and P < 0.0001, respectively). All the measurements were significantly higher in males. Conclusion: The location of GPF is variable but more closely related to the third molar. Sound knowledge of the GPF anatomy is crucial for an effective nerve block and also for preventing complications.

Summary: Huntington’s disease (HD) is caused by expanded CAG repeats in the huntingtin gene (HTT) resulting in expression of mutant HTT proteins (mHTT) with extended polyglutamine tracts, including in striatal neurons and astrocytes. It is unknown whether pathophysiology in vivo can be attenuated by lowering mHTT in either cell type throughout the brain, and the relative contributions of neurons and astrocytes to HD remain undefined. We use zinc finger protein (ZFP) transcriptional repressors to cell-selectively lower mHTT in vivo. Astrocytes display loss of essential functions such as cholesterol metabolism that are partly driven by greater neuronal dysfunctions, which encompass neuromodulation, synaptic, and intracellular signaling pathways. Using transcriptomics, proteomics, electrophysiology, and behavior, we dissect neuronal and astrocytic contributions to HD pathophysiology. Remarkably, brain-wide delivery of neuronal ZFPs results in strong mHTT lowering, rescue of HD-associated behavioral and molecular phenotypes, and significant extension of lifespan, findings that support translational development.

ABSTRACT In Corynebacterium glutamicum the protein kinase PknG phosphorylates OdhI and thereby abolishes the inhibition of 2-oxoglutarate dehydrogenase activity by unphosphorylated OdhI. Our previous studies suggested that PknG activity is controlled by the periplasmic binding protein GlnH and the transmembrane protein GlnX, because ΔglnH and ΔglnX mutants showed a growth defect on glutamine similar to that of a ΔpknG mutant. We have now confirmed the involvement of GlnH and GlnX in the control of OdhI phosphorylation by analyzing the OdhI phosphorylation status and glutamate secretion in ΔglnH and ΔglnX mutants and by characterizing ΔglnX suppressor mutants. We provide evidence for GlnH being a lipoprotein and show by isothermal titration calorimetry that it binds l-aspartate and l-glutamate with moderate to low affinity, but not l-glutamine, l-asparagine, or 2-oxoglutarate. Based on a structural comparison with GlnH of Mycobacterium tuberculosis, two residues critical for the binding affinity were identified and verified. The predicted GlnX topology with four transmembrane segments and two periplasmic domains was confirmed by PhoA and LacZ fusions. A structural model of GlnX suggested that, with the exception of a poorly ordered N-terminal region, the entire protein is composed of α-helices and small loops or linkers, and it revealed similarities to other bacterial transmembrane receptors. Our results suggest that the GlnH-GlnX-PknG-OdhI-OdhA signal transduction cascade serves to adapt the flux of 2-oxoglutarate between ammonium assimilation via glutamate dehydrogenase and energy generation via the tricarboxylic acid (TCA) cycle to the availability of the amino group donors l-glutamate and l-aspartate in the environment. IMPORTANCE Actinobacteria comprise a large number of species playing important roles in biotechnology and medicine, such as Corynebacterium glutamicum, the major industrial amino acid producer, and Mycobacterium tuberculosis, the pathogen causing tuberculosis. Many actinobacteria use a signal transduction process in which the phosphorylation status of OdhI (corynebacteria) or GarA (mycobacteria) regulates the carbon flux at the 2-oxoglutarate node. Inhibition of 2-oxoglutarate dehydrogenase by unphosphorylated OdhI shifts the flux of 2-oxoglutarate from the TCA cycle toward glutamate formation and, thus, ammonium assimilation. Phosphorylation of OdhI/GarA is catalyzed by the protein kinase PknG, whose activity was proposed to be controlled by the periplasmic binding protein GlnH and the transmembrane protein GlnX. In this study, we combined genetic, biochemical, and structural modeling approaches to characterize GlnH and GlnX of C. glutamicum and confirm their roles in the GlnH-GlnX-PknG-OdhI-OdhA signal transduction cascade. These findings are relevant also to other Actinobacteria employing a similar control process.

Four species of the genus Hedychium can be found in Brazil. Hedychium coronarium is a species endemic to India and Brazil. In this paper, we collected six specimens of H. coronarium for evaluation of their volatile chemical profiles. For this, the essential oils of these specimens were extracted using hydrodistillation from plant samples collected in the state of Pará, Brazil, belonging to the Amazon region in the north of the country. Substance compounds were identified with GC/MS. The most abundant constituent identified in the rhizome and root oils was 1,8-cineole (rhizome: 35.0–66.1%; root: 19.6–20.8%). Leaf blade oil was rich in β-pinene (31.6%) and (E)-caryophyllene (31.6%). The results from this paper allow for greater knowledge about the volatile chemical profile of H. coronarium specimens, in addition to disseminating knowledge about the volatile compounds present in plant species in the Amazon region.

Abstract Background Checkpoint inhibitors (Nivolumab and Pembrolizumab) are approved for multiple indications in solid tumors. However access to these therapies is limited in low and middle income countries. Hence we performed an audit to identify accessibility, adverse event rates, compliance, progression free survival and overall survival in solid tumors. Methods This was a single center retrospective analysis of prospective data base of patients with non‐melanoma solid tumors who were treated with immunotherapy from August 2015 to November 2018. Adverse events during immunotherapy were documented and graded using CTCAE (Common terminology criteria for adverse events), v. 4.02. The response rates to immunotherapy, toxicities and the time to onset and resolution of toxicities were also evaluated as secondary endpoints. Results Out of 9610 patients, only 155 patients (1.61%) could receive immunotherapy. The most common malignancies included metastatic non‐small cell lung cancer, metastatic renal cell carcinoma, metastatic urothelial carcinoma and relapsed/recurrent head and neck squamous cell carcinoma. Median overall survival in patients who received immunotherapy in non‐melanoma solid malignancies was 5.37 months (95% CI, 3.73–9.73). Poor performance status at baseline was the only adverse prognostic factor. The median progression free survival was 2.57 months (95% CI, 1.73–3.83). Immunotherapy was well tolerated with most common side effects being fatigue 14.8% and anorexia 5.8%. The cumulative incidence of immune related adverse events like hepatitis, pneumonitis, colitis and nephritis was less than 10%. Conclusion Real‐world data in Indian setting confirms the benefit of immunotherapy in patients with advanced non‐melanoma solid tumors.

The aim of this study was to employ and understand the feasibility of an infrared (IR)/red-diode laser with a wavelength of 808 nm for the selective laser sintering (SLS)-mediated sintering of 3D printlets, altering the dye composition and temperature variations. Kollicoat® IR (KIR) and an infrared (IR) laser-absorbing dye were physically mixed at various concentrations and subjected to SLS-mediated sintering to achieve 3D printlets by varying printing temperature (feed and print beds) at a fixed laser power ratio. Initially, the desired concentration of dye (1.25% w/w) was selected based on its sintering performance, and the same concentration was used to sinter the physical mixtures (PMs) at different feed bed temperatures (between 100 °C and 130 °C) and print bed temperature (120 °C to 150 °C), keeping the laser power ratio constant (1.0). It was found that good sintering performance was associated with a feed bed temperature of 130 °C and a print bed temperature of 150 °C. Printlets obtained from the aforementioned conditions showed highest dimensional accuracy (9.31 ± 0.30 mm diameter and 3.56 ± 0.04 mm thickness) in respect to feeded CAD dimensions (10 mm diameter and 3.60 mm thickness) with an average weight of 77.45 ± 4.56 mg. In addition, no physical/thermal or chemical degradation of the sintered 3D printlets was observed during the thermal and functional group analysis, respectively. Depending on the conditions given, we can conclude that an IR/red diode laser with a wavelength of 808 nm and a laser power ratio of 1.0 is feasible for sintering 3D printlets.

Abstract Background In recent times, Plasmodium vivax (P. vivax) has become a serious threat to public health due to its ability to cause severe infection with fatal outcomes. Its unique biology makes it resilient to control measures that are otherwise effective against P. falciparum. A deeper understanding of P. vivax biology and pathogenesis is, therefore, essential for developing the right control strategies. Proteomics of P. falciparum has been helpful in studying disease biology and elucidating molecular mechanisms involved in the development of disease. However, unlike P. falciparum, proteomics data for P. vivax infection is minimal due to the absence of a continuous culture system. The dependence on clinical samples and animal models has drastically limited P. vivax research, creating critical knowledge gaps in our understanding of the disease. This study describes an in-depth proteomics analysis of P. vivax-infected human plasma and parasite isolates, to understand parasite biology, pathogenesis, and to identify new diagnostic targets for P. vivax malaria. Methods A mass-spectrometry- (MS) based proteomics approach (Q Exactive) was applied to analyze human plasma and parasite isolates from vivax malaria patients visiting a primary health centre in India. Additionally, a targeted proteomics assay was standardized for validating unique peptides of most recurring parasite proteins. Results Thirty-eight P. vivax proteins were detected in human plasma with high confidence. Several glycolytic enzymes were found along with hypothetical, cytoskeletal, ribosomal, and nuclear proteins. Additionally, 103 highly abundant P. vivax proteins were detected in parasite isolates. This represents the highest number of parasite proteins to be reported from clinical samples so far. Interestingly, five of these; three Plasmodium exported proteins (PVX_003545, PVX_003555 and PVX_121935), a hypothetical protein (PVX_083555) and Pvstp1 (subtelomeric transmembrane protein 1, PVX_094303) were found in both plasma and parasite isolates. Conclusions A parasite proteomics investigation is essential to understand disease pathobiology and design novel interventions. Control strategies against P. vivax also depend on early diagnosis. This work provides deeper insights into the biology of P. vivax by identifying proteins expressed by the parasite during its complex life-cycle within the human host. The study also reports antigens that may be explored as diagnostic candidates.

Calendula officinalis Linn. (CO) is a popular medicinal plant from the plant kingdom’s Asteraceae family that has been used for millennia. This plant contains flavonoids, triterpenoids, glycosides, saponins, carotenoids, volatile oil, amino acids, steroids, sterols, and quinines. These chemical constituents confer multifaceted biological effects such as anti-inflammatory, anti-cancer, antihelminthic, antidiabetes, wound healing, hepatoprotective, and antioxidant activities. Additionally, it is employed in cases of certain burns and gastrointestinal, gynecological, ocular, and skin conditions. In this review, we have discussed recent research from the last five years on the therapeutic applications of CO and emphasized its myriad capabilities as a traditional medicine. We have also elucidated CO’s molecular mechanisms and recent clinical studies. Overall, this review intends to summarize, fill in the gaps in the existing research, and provide a wealth of possibilities for researchers working to validate traditional claims and advance the safe and effective use of CO in treating various ailments.

Nanoparticle synthesis has seen exponential development recently as its characteristics of high surface area, high rate of adsorption, and easy, cost-effective synthesis have been exploited for the purpose of ground water purification via the removal of organic and inorganic compounds, along with the removal of heavy metals and microbes. The synthesis of Zero-Valent Iron Nanoparticles (ZVI NPs) by green methods has proved to be environmentally friendly in many ways as it employs the use of naturally occurring plant extracts. These nanoparticles have large surface areas and efficiently remove heavy metals. The reducing potential of these ZVI NPs is mostly −0.44 V, thus allowing them to reduce heavy metal compounds such as cadmium, lead, zinc, copper, and arsenic present in wastewater. Irradiated nanoparticles have also exhibited antimicrobial resistance and adsorption. It is also observed that nanoparticles show a higher rate of efficacy at a lower pH. The adsorbent, which is ZVI NPs in this case, when present in large doses reduces heavy metal compounds rapidly and effectively.

Background: The interest in the use of Eucalyptus genus members, in parallel with preclinical studies has been steadily growing over the last few decades in the field of pharmaceuticals, agriculture, cosmetics, food, etc. Eucalyptol (1,8-cineole or cineole), the main terpenoid constituent in Eucalyptus species, has been studied in both preclinical and clinical settings for its various pharmacologic activities. Investigations into the pharmacological activities of the genus Eucalyptus revealed that it manifests astounding potential in the treatment and management of respiratory disorders, COVID-19, pain, oral health, infectious diseases, cancer, etc. Purpose: This review congregates and discusses the hitherto scattered data on Eucalyptus species morphology, chemical composition, some of its profusely investigated multifaceted therapeutic applications with insights into their molecular mechanisms, and clinical studies. The current understanding of the molecular mechanisms arising from cell lines, animal models, and clinical trials are emphasized. Lattermost, this review sheds light on various reported Eucalyptus-based formulations and relevant patents. Overall, this review aims to summarize and bridge the lacunae in the current research and offer a plethora of opportunities for the researchers engaged in the validation of the traditional claims and development in Eucalyptus utilization for safe and effective treatment of various diseases Method: The systematic and comprehensive review was carried out by adhering to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements. PubMed, Scopus, ScienceDirect, Google Scholar, and Google patents databases were used to explore literature published till April 2021 by using relevant keywords. Results: The systematic search retrieved 306 papers that were potentially relevant and after the selection procedure, 103 studies were included in this review and discussed. The evidence reviewed herein suggested that several Eucalyptus species possess anti-inflammatory, anti-microbial, anti-viral, anti-oxidant, anti-nociceptive, anti-cancer, anti-diabetic, etc., activities. Conclusion: Preclinical and clinical studies have shown that the Eucalyptus plant and its chemical constituents have enormous potential for disease prevention and treatment. Eucalyptus, an ancient and underutilized ally with its diverse therapeutic applications can give rise to a paradigm shift in the treatment regime of several diseases in this era of modern science.

Cultural heritage (CH) values are important for understanding the significance of heritage assets. For that reason, the presentation of CH should go beyond providing factual information. It should reflect relevant values that are held by the curators, the heritage experts and the communities of non-expert citizen stakeholders. Associating values with the information content in a CH communication product is a challenging task. Digital technologies require special attention to communicate values along with heritage information to achieve meaningful and impactful communication. In this paper, we focus on a socio-technological framework for the integration of values into the information content provided to visitors. We have designed, applied and evaluated an eight-stage process for the inclusion of CH values in the information content and their communication to museum visitors. It has been applied at the Hecht Museum, located at the University of Haifa, Israel, where museum artefacts are currently presented to the visitors with informational panels that have been designed without any attention to values. Two digital applications, built by applying the eight-stage process, were developed. One was designed to cover the information and heritage values already available within the museum descriptions. The other was developed by following the suggested process, which accounts for values that were collected through a review of the literature, interviews with experts and interactions with non-experts. The two applications were tested, iterated and evaluated to assess the impact of value inclusion. Results show that both visitors and experts appreciated the value-enhanced communication. The evaluation of user feedback has further substantiated the creation of content that is inclusive of CH values, for the communication of museum artefacts.

One of the common indications of ascitic fluid examination in gynecological oncopathology is the detection and classification of malignant cells, especially in cases of clinically suspicious tubo-ovarian masses. The present study was undertaken to assess and validate the diagnostic utility of cell blocks (CBs) and compare its results with the corresponding conventional smears, prepared from effusion samples. CBs were prepared by thromboplastin technique in 220 cases. In 208 cases, diagnostic concordance between results obtained from smears and corresponding CBs was evaluated. Various antibody markers were tested, as per individual case. The average age of patients was 52.2 years. Positive immunohistochemical (IHC) staining for various markers was observed in 182 cases (82.7%) The most frequently positive antibody marker was PAX8 (101/134), followed by p53 (85/92) [mutation type (either diffusely positive or completely negative)], WT1 (tumor cells) (80/112), calretinin (2/87) (diffuse), BerEP4 (21/49), CA125 (21/24), CK7 (31/39) and CK20 and CDX2, together (5/16). Various other IHC markers utilized, including their positive expression, were TTF1 (1/10), p40 (3/3), p63 (2/4), ER (21/29), HBME1 (1/7), GATA3 (1/4), and MIC2 (1/1). Complete diagnostic concordance between CBs and smears was observed in 170/208 cases (81.7%). There were 20 major discordances, 10 minor and 8 cases with sampling errors. IHC was useful in classifying 158/182 (86.8%) cases, including serous or Müllerian adenocarcinoma (n = 123), mostly high-grade (121); metastatic squamous carcinoma (3); gastrointestinal-type adenocarcinoma (8); pulmonary adenocarcinoma (1); breast adenocarcinoma (1); Ewing sarcoma (1); and mesothelioma (2). CBs are complementary to smears in the detection of gynecological malignancies, mostly high-grade serous adenocarcinomas. These provide an opportunity for testing several IHC markers, for a precise diagnosis, including in various uncommon case scenarios, associated with significant therapeutic implications.

Introduction: The phenomenon of reversal of incipient or early enamel caries forms an important part of prevention leading to apparent repair of the lesion. Recently, novel biomaterials such as the bioactive glass (BAGs) and nano-hydroxyapatite (n-HAP) crystal have been introduced as remineralising agents. Aim: This study aimed to evaluate and compare the remineralising efficacy of BAG agent and nano-hydroxyapatite (NHA) dentifrices on artificial carious lesion in primary teeth. Methodology: Thirty human extracted primary teeth were selected for the study, and the specimens were randomly divided into Group A: BAGs agent toothpaste group and Group B: n-HAP toothpaste group. The surface microhardness of the teeth was measured using a Vickers microhardness tester at the baseline and after demineralisation and remineralisation. The statistical analysis was done using independent t-test for intergroup comparison and paired t-test for intragroup comparison. Results: On intergroup comparison, microhardness differences of baseline to exposure to dentifrice between the two groups showed that microhardness differences of baseline to exposure to dentifrice were higher in Group B with a t value of −2.158 and was statistically significant (P < 0.001). On intragroup comparison of the mean values of baseline microhardness and microhardness after exposure to dentifrices, the mean values of baseline microhardness were higher in both the groups with a difference of 14.3 and 20.45 in Group A and Group B, respectively. Conclusion: Both BAG and NHA toothpastes were considered to be effective for the remineralisation of caries-like lesions of primary teeth. The remineralising efficacy of n-HAP toothpastes was found to be slightly higher than that of BAGs toothpastes, which was statistically significant.

Amorphous solid dispersions (ASDs) are among the most popular and widely studied solubility enhancement techniques. Since their inception in the early 1960s, the formulation development of ASDs has undergone tremendous progress. For instance, the method of preparing ASDs evolved from solvent-based approaches to solvent-free methods such as hot melt extrusion and Kinetisol®. The formulation approaches have advanced from employing a single polymeric carrier to multiple carriers with plasticizers to improve the stability and performance of ASDs. Major excipient manufacturers recognized the potential of ASDs and began introducing specialty excipients ideal for formulating ASDs. In addition to traditional techniques such as differential scanning calorimeter (DSC) and X-ray crystallography, recent innovations such as nano-tomography, transmission electron microscopy (TEM), atomic force microscopy (AFM), and X-ray microscopy support a better understanding of the microstructure of ASDs. The purpose of this review is to highlight the recent advancements in the field of ASDs with respect to formulation approaches, methods of preparation, and advanced characterization techniques

Introduction: Helicobacter pylori (H.pylori) is associated with many gastro-duodenal diseases like peptic ulcers and gastric adenocarcinoma. Hence, it is important to identify H.Pylori in the endoscopic gastric biopsies. Though Immunohistochemistry (IHC) is time-consuming and expensive, it has shown excellent results and is considered as gold standard method for detecting H.Pylori. Aim: To study the morphological patterns of gastric lesions, different histo-pathological gastric lesions with clinical presentation and the association of H.Pylori using Haematoxylin and Eosin (H&E), Giemsa and IHC staining techniques and their efficacy. Materials and Methods: The present study was an observational study conducted at a tertiary care hospital Kalaburagi for a period of 5 years (1 July 2014 to 30 June 2019). All patients were referred to endoscopic section for the biopsy. History was documented and clinical examination was performed. For the retrospective cases, clinical details were obtained from medical records section, blocks were retrieved, stained with H&E, Giemsa and IHC, studied, tabulated and results were analysed. Results: A total of 95 samples (mean age 49.74 years) were studied. Male: female ratio was 2.8:1. Most common histological benign lesions were Chronic Active Gastritis (CAG) 23 (24.21%) and Chronic Superficial Gastritis (CSG) 14 (14.73%). Malignant tumours were seen in 23 cases, among which moderately (39.13%) and poorly differentiated (39.13%) adenocarcinoma was the commonest. H pylori was identified by IHC in benign and malignant lesions in 20 (23.53%) and 01 (4.35%), respectively. Sensitivity and specificity of H&E and Giemsa was 57.14%, 66.67% and 100%, 100%, respectively. Positive Predictive Value (PPV) was 100% for both stains and Negative Predictive Value (NPV) was 89.16% and 91.36% for H&E and Giemsa. Conclusion: The present study highlights the utility of IHC in detecting H.Pylori in gastric lesions as inflammation and other factors are known to affect the detection rate by H&E and Giemsa staining methods. Hence, IHC can be considered as the best method in detecting H.pylori.

Chronic non-specific contamination of the reproductive tract in animals is a major issue during early postpartum, natural coitus, or artificial insemination. Uterine infection is one of the major concerns reducing fertility, production loss, and early culling of the animals. Therefore, the aim of this study was to identify any novel bacterium if present in the uterine environment of Bubalus bubalis causing infections. A strictly anaerobic bacterial strain designated as Paraclostridium bifermentans GBRC was isolated and characterized. Bacterium was found to be Gram positive moderate rod with motility. The optimum growth was observed at 40 ± 2 °C. The pathogenic characteristics of the GBRC strain, such as hemolysis, gelatin hydrolysis, and the production of volatile sulfur compounds, were similar to those seen in the epithelial layer invading pathogenic strains. Assembled genome size was 3.6 MB, with 78 contigs, and a G + C content of 28.10%. Furthermore, the whole genome sequence analysis confirmed the presence of genes encoding virulence factors and provided genomic insights on adaptation of the strain in the uterine environment. Based on the phenotypic and genetic differences with phylogenetic relatives, strain GBRC is proposed to represent a first reported species of the genus Paraclostridium with potential pathogenic character, from the buffalo uterine environment. This study analysis of the GBRC strain serves as a key reference point for the investigation of potential pathogenic strains that may cause endometritis and metritis in bovine.

Introduction: Restoring Class II lesions in deciduous molars has always been a nightmare for the dentist. This survey was designed to understand the perception of dentists regarding the treatment choice. Aim: The aim of this study is to determine the choice of material and influencing factors for the treatment of proximal lesions in primary molars. Materials and Methods: The cross-sectional web-based survey enclosing nine closed-ended questions was conducted among 180 paediatric dentists and post-graduates of Gujarat. Data were obtained and evaluated at the statistical significance level ofP < 0.05. Results: For 65% of respondents' stainless steel crowns (SSCs) was preferred material for the treatment of cavitated Class II lesions followed by composite and for non-cavitated incipient proximal lesions silver diamine fluoride was preferred by 71% of respondents. Childs age and child's behaviour were the most influencing factors affecting the choice of material (P < 0.001). Conclusion: Different clinical situation requires a different choice of material. The present study enlightens current perception and preference regarding the material of choice in a different situation while restoring Class II lesions in primary molars. We concluded that SSC was the most suitable material of choice amongst a wide range of materials by paediatric. The older concept 'excavation for prevention' is still applied as compared to newer minimal invasive strategies. Many factors contribute to the treatment and material choice for restoring Class II lesions; thus, one ultimate material cannot be selected for all kinds of situations. Thus, it highlights the current trends followed among paediatric dentist.

Abstract Background More than 350 K described species, Coleoptera (beetles) represent the most diverse order from Class Insecta in the entire animal kingdom. However, their phylogeny is highly controversial due to their morphological crypticness and multiple markers used previously for sequence homology. Although many studies suggest that their diversity currently relies majorly on morphological analysis, nevertheless DNA barcodes may provide a functional, standardized tool for their unique identification. In the present report, a fragment of the mitochondrial cytochrome c oxidase I (COI) gene has been proposed as standard DNA barcoding marker for the identification of organisms. Result To evaluate this hypothesis, a random sampling was conducted in and around Vadodara, Gujarat, where 2690 individual of 65 species belonging to 16 families were reported from different sites, and diversity indices were employed to unravel the species composition of that habitat. Further, 12 beetles from dominant families were selected for sequence analysis using various bioinformatics tools and were compared with the rest of the beetles to obtain a more robust phylogeny which is not reported earlier in previous studies. Conclusion Hence, the present study suggests that Scarabaeidae tends to be more diverse in and nearby of Vadodara compared to all other families of Coleoptera and while in contrast Chrysomelidae showed maximum diversity of pest species. DNA barcoding and nucleotide analysis resolves the phylogeny of controversial taxa; (Adephaga(Gyrinidae+ (Dytiscidae++ Carabidae)) (Polyphaga(Histeridae+Buprestidae+Lampyridae+Elateridae+(Scarabaeidae+(Coccinelidae+ Apionidae+Curculionidae+ (Meloidae+Tenebrionidae+(Cerambycidae+Chrysomelidae)))))).