Search

ImportanceThe hepatitis C virus (HCV) causes liver disease, affecting millions. Even though we have effective antivirals that cure HCV, they cannot stop terminal liver disease. We used an adult stem cell-derived liver organoid system to understand how HCV infection leads to the progression of terminal liver disease. Here, we show that HCV maintains low-grade infections in liver organoids for the first time. HCV infection in liver organoids leads to transcriptional reprogramming causing cancer cell development and altered immune response. Our finding shows how HCV infection in liver organoids mimics HCV infection and patient pathogenesis. These results reveal that HCV infection in liver organoids contributes to liver disease progression.

Solid tumors such as prostate cancer (PCa) commonly develop an acidic microenvironment with pH 6.5-7.2, owing to heterogeneous perfusion, high metabolic activity, and rapid cell proliferation. In preclinical prostate cancer models, disease progression is associated with a decrease in tumor extracellular pH, suggesting that pH imaging may reflect an imaging biomarker to detect aggressive and high-risk disease. Therefore, we developed a hyperpolarized carbon-13 MRI method to image the tumor extracellular pH (pHe) and prepared it for clinical translation for detection and risk stratification of PCa. This method relies on the rapid breakdown of hyperpolarized (HP) 1,2-glycerol carbonate (carbonyl-13C) via base-catalyzed hydrolysis to produce HP 13CO32-, which is neutralized and converted to HP H13CO3-. After injection, HP H13CO3- equilibrates with HP 13CO2 in vivo and enables the imaging of pHe. Using insights gleaned from mechanistic studies performed in the hyperpolarized state, we solved issues of polarization loss during preparation in a clinical polarizer system. We successfully customized a reaction apparatus suitable for clinical application, developed clinical standard operating procedures, and validated the radiofrequency pulse sequence and imaging data acquisition with a wide range of animal models. The results demonstrated that we can routinely produce a highly polarized and safe HP H13CO3- contrast agent suitable for human injection. Preclinical imaging studies validated the reliability and accuracy of measuring acidification in healthy kidney and prostate tumor tissue. These methods were used to support an Investigational New Drug application to the U.S. Food and Drug Administration. This methodology is now ready to be implemented in human trials, with the ultimate goal of improving the management of PCa.

Abstract: Over recent decades, our understanding of climate change has accelerated greatly, but unfortunately, observable impacts have increased in tandem. Both mitigation and adaptation have not progressed at the level or scale warranted by our collective knowledge on climate change. More effective approaches to engage people on current and future anthropogenic climate change effects are urgently needed. Here, we show how species whose distributions are shifting in response to climate change, that is, ‘species‐on‐the‐move’, present an opportunity to engage people with climate change by linking to human values, and our deep connections with the places in which we live, in a locally relevant yet globally coherent narrative. Species‐on‐the‐move can impact ecosystem structure and function, food security, human health, livelihoods, culture and even the climate itself through feedback to the climate system, presenting a wide variety of potential pathways for people to understand that climate change affects them personally as individuals. Citizen science focussed on documenting changes in biodiversity is one approach to foster a deeper engagement on climate change. However, other possible avenues, which may offer potential to engage people currently unconnected with nature, include arts, games or collaborations with rural agriculture (e.g. new occurrences of pest species) or fisheries organisations (e.g. shifting stocks) or healthcare providers (e.g. changing distributions of disease vectors). Through the importance we place on the aspects of life impacted by the redistribution of species around us, species‐on‐the‐move offer emotional pathways to connect with people on the complex issue of climate change in profound ways that have the potential to engender interest and action on climate change. Read the free Plain Language Summary for this article on the Journal blog.

Introduction: According to the literature, an existing correlation is said to be present between craniocervical and craniofacial morphology. Recent studies have revealed that there are certain variations among the different forms of craniofacial patterns with respect to the morphology of the vertebrae. Since there are very few studies comparing the curvature of the cervical column in relation to the cranial base in Cleft, Class-I and Class-III individuals, this study was carried out. Aim: To provide a comprehensive comparative analysis of the curvature of the cervical vertebral column and its relationship with the cranial base in Class-I, cleft, and Class-III individuals within the Central Indian population. Materials and Methods: In this cross-sectional study conducted at the Department of Orthodontics and Dentofacial Orthopaedics at Sharad Pawar Dental College and Hospital, Sawangi (M).Wardha, Maharashtra, India, patients with skeletal Class-I, Class-III, and Unilateral Cleft Lip and Palate (UCLP) or Bilateral Cleft Lip and Palate (BCLP) in the Central India region were included. The study duration was eight months, from April 2022 to January 2023. The research involves a meticulous examination of 90 individuals, divided into three groups: Class-I individuals (n=30), cleft individuals (n=30), and Class-III individuals (n=30). A comprehensive set of radiographic and cephalometric measurements will be employed to assess cervical vertebral curvature. One-way Analysis of Variance (ANOVA) test was used for analysis. Results: With the exception of Sella-Nasion to Gonion Gnathion (SA-Go-Gn), where the p-value was 0.13, a statistically significant difference between Class-I and Class-III was seen for all angles. For Class-III cases with clefts, every angle revealed a statistically significant difference. Except for SN-Go-Gn (p=0.65), all of the angles revealed a statistically significant difference when compared to Class-I with Cleft, with a p-value

Background: Neoadjuvant chemotherapy (NACT) affects the tumor protein marker’s expression and status. Changes in the expression of biomarkers during NACT may influence the clinical decision of adjuvant molecular and hormonal therapy. Hence, re-evaluation of receptor status has to be done after NACT to give a specific adjuvant therapy for patient benefit. Aims and Objectives: The aim of this study was to study the status of hormone receptors (HRs) – estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (Her-2/Neu), and Ki-67 in patients with locally advanced breast cancer (LABC) in both core needle biopsies and post-mastectomy specimens after administering neoadjuvant chemotherapy. Materials and Methods: The present study was conducted in the Department of Pathology in collaboration with the Department of Surgery, Pt B D Sharma PGIMS, Rohtak, for a period of 1 year. The study comprised 52 patients with LABC who received neoadjuvant chemotherapy and 20 control cases who did not receive neoadjuvant chemotherapy. Each case comprised two specimens: Trucut biopsy and a mastectomy specimen. Results: ER changed from positive to negative in 15.4% of the cases and from negative to positive in 1.9% of the cases. The overall change in ER was statistically significant (P=0.020). For PR, 9.6% of the cases changed from positive to negative while none of the cases showed change from negative to positive. The overall change in PR was statistically significant (P=0.025). For HER2/Neu, 19.2% of the cases changed from positive to negative, and 11.5% of the cases changed from negative to positive. The overall change in HER2/Neu was not statistically significant (P=0.317). For Ki-67, 30% of patients changed from positive to negative while 11.5% of patients changed from negative to positive. The overall change in Ki-67 was statistically significant (P=0.024). Conclusion: There was discordance in the HR status and proliferation marker after NACT in patients with breast cancer. The administration of NACT might be the main reason for the change in receptor status thus understanding the chemotherapy-induced biological conversion in the tumor cell behavior is strategically important in planning adjuvant endocrine therapy and for disease follow-up.

Background: In India, breast cancer forms the most common malignancy, accounting for 28.2% of all female cancers. Breast cancer consists of phenotypically diverse group of diseases. Due to different relapse abilities, doubling times, and different infiltrative capacities, it is important to identify potential biomarkers that could be used to screen high-risk patient and predict breast cancer prognosis in conjunction with classical pathological parameters. Aims and Objectives: The present study was conducted to evaluate immunohistochemical expression of CD44 in breast carcinoma and to correlate CD44 expression with other clinicopathological parameters and molecular classification of carcinoma breast. Materials and Methods: The present study was a prospective descriptive study conducted on 100 cases of carcinoma breast diagnosed on modified radical mastectomy specimens that were submitted to the Department of Pathology, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana, over the period of 2 years. Results: Out of 100, 64 cases (64%) were CD44 positive. Out of these 64 cases, 9 (9%) cases were 1+, 34 (34%) cases were 2+, and 21 (21%) cases showed 3+ positive expression of CD44 in tumor cells. Loss of CD44 expression was seen in 36 (36%) cases. A statistically significant association of CD44 was seen with multifocality of the tumor, negative estrogen receptor/progesterone receptor (ER/PR) expression, and molecular subtypes. No statistically significant association of CD44 was seen with age, side of tumor, lymph node metastasis, lymphovascular invasion, ductal carcinoma in situ and Ki67, and HER2neu expression. Conclusion: A high CD44 expression in breast carcinoma correlates with aggressive tumor characteristics such as multifocality, negative ER/PR expression, and belonging to the basal subtype which is associated with poor prognosis. Conversely, low CD44 expression is linked to Luminal A and Luminal B subtypes which have good prognosis. These indicate the role of CD44 as a prognostic biomarker in the carcinoma breast.

Introduction: Students-centered teaching and learning methods are the trends in medical education. Many innovative techniques are introduced and implemented to promote active learning by students, like crossword puzzles, a fun educational tool to generate interest, motivate, and enhance the critical thinking of medical students. Hence, this study was conducted to assess the perception of medical students toward crossword puzzles. Materials and Methods: This is an interventional study done on II MBBS students in the department of pathology. The crossword puzzles are created, and students are allowed to solve them for 15 min after a didactic lecture. Then, students are provided with a questionnaire to assess their perceptions toward this technique. The knowledge gained and retained was evaluated by short answer questions in comparison with topics dealt with only by traditional lectures. Descriptive and analytical statistical analysis of mean, standard deviation, and paired t-test for analysis of scores of both methods are done. Results: The majority of the students in this study perceived that crossword puzzles helped in better understanding of concepts, were fun education tools, challenging and problem-solving, emphasized the core topic, helped reinforcement of lectures, encouraged active learning, and improved overall thinking. The P value between the scores by only lecture method and that reinforced by crossword puzzles was extremely statistically significant. Thus crossword puzzles can be used to enhance retention and help in reinforcement learning. Conclusions: Crossword puzzles are an innovative learning method which promotes active learning and overall thinking of the students. This can be implemented in medical schools as a simple, creative, and effective means of holistic learning.

Abstract Anxiety disorders are found to be the most prevalent psychological problems among children and adolescents. Cognitive behaviour therapy (CBT) was found to be effective at reducing anxiety. The purpose of this study was to assess the effectiveness of a universal school-based intervention for reducing anxiety among Grade 9 schoolchildren. A randomized controlled cluster trial was conducted by randomly assigning 36 schools in the Colombo district in Sri Lanka into study and control arms, each comprising 18 schools with 360 students. The levels of anxiety, self-esteem and depression status were assessed using the validated Screen for Child Anxiety Related Disorders (SCARED) tool and the Rosenberg self-esteem scale, respectively, and the Depression, Anxiety and Stress Scale 21 (DASS-21) at baseline, after intervention, and after 3 months. A CBT-based universal intervention package was administered weekly by a trained teacher for eight weeks with a one-month self-practice period to a randomly selected Grade 9 class in each school in the study arm. The control arm received routine care. Anxiety and self-esteem scores and depression status were compared between the two arms after the intervention and at 3 months of follow-up using the generalized estimation equation (GEE), controlling for confounding and clustering. The nonresponse and loss to follow-up rates were

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important public health problem owing to its high prevalence and associated morbidity and mortality secondary to progressive liver disease and cardiovascular events. Resmetirom, a selective thyroid hormone receptor-β agonist has been developed as a therapeutic modality for MASLD. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of resmetirom compared to a placebo in the treatment of MASLD. Eligible studies were systematically identified by screening PubMed, Scopus, Web of Science, Cochrane library, Embase, and ClinicalTrials.gov from 2014 to 2024. Only randomized controlled trials comparing the efficacy and safety of resmetirom in the treatment of MASLD against placebo were included in the analysis. Meta-analysis was performed using RevMan 5.4 software. Four studies with low risk of bias and involving a total of 2359 participants were identified. The metanalysis included only three clinical trials with 2234 participants. A significant reduction in MRI-proton density fat fraction (MRI-PDFF) with 80 mg Resmetirom compared to that with placebo [SMD − 27.74 (95% CI − 32.05 to − 32.42), p

Introduction: Acute Coronary Syndrome (ACS) describes a range of myocardial ischaemic states that includes Unstable Angina (UA), Non ST Elevation Myocardial Infarction (NSTEMI), or ST-Elevation Myocardial Infarction (STEMI). Vaspin is an emerging adipokine, and low vaspin concentrations are found to be correlated with the severity of cardiovascular events. The Global Registry of Acute Coronary Events (GRACE) score is widely used to assess early risk stratification among ACS patients. Aim: To evaluate the severity of cardiovascular risk in patients with ACS using GRACE risk score and to study the correlation of serum vaspin levels with the risk score. Materials and Methods: This analytical cross-sectional study was conducted at the Intensive Care Unit (ICU) of the Cardiology Department at SRM Medical College, Tamil Nadu, India, from June 2023 to October 2023. A total of 89 patients diagnosed with ACS were included and stratified into three groups based on the GRACE score. Lipid profiles were assessed using a Beckman Coulter autoanalyser, while serum vaspin levels were measured using Enzyme Linked Immuno Sorbent Assay (ELISA). Statistical analyses including Kruskal-Wallis test, Spearman’s correlation, and Receiver Operating Characteristic (ROC) curve analysis were performed. Results: Among the study participants, 65.2% were males, and 34.8% were females, with mean ages of 56±8.8 years and 56±11.8 years, respectively. Out of the 89 participants, 32 (36%) were categorised as high-risk, 31 (34.8%) as intermediate risk, and 26 (29.2%) as low risk. Serum vaspin levels were observed to be lower in the high-risk group compared to the low and intermediate risk groups. A cut-off value for serum vaspin level was determined as ≤0.610 pg/mL in ACS, indicating an increased risk for complications. Conclusion: The levels of serum vaspin are decreased in ACS patients presenting with a greater degree of cardiovascular complications. These findings enhance the comprehension of vaspin’s role in the pathophysiology of ACS and its relevance in risk assessment.

Abstract Fungus-growing termites, like Odontotermes obesus, cultivate Termitomyces as their sole food source on fungus combs which are continuously maintained with foraged plant materials. This necessary augmentation also increases the threat of introducing non-specific fungi capable of displacing Termitomyces. The magnitude of this threat and how termites prevent the invasion of such fungi remain largely unknown. This study identifies these non-specific fungi by establishing the pan-mycobiota of O. obesus from the fungus comb and termite castes. Furthermore, to maximize the identification of such fungi, the mycobiota of the decaying stages of the unattended fungus comb were also assessed. The simultaneous assessment of the microbiota and the mycobiota of these stages identified possible interactions between the fungal and bacterial members of this community. Based on these findings, we propose possible interactions among the crop fungus Termitomyces, the weedy fungus Pseudoxylaria and some bacterial symbiotes. These possibilities were then tested with in vitro interaction assays which suggest that Termitomyces, Pseudoxylaria and certain potential bacterial symbiotes possess anti-fungal capabilities. We propose a multifactorial interaction model of these microbes, under the care of the termites, to explain how their interactions can maintain a predominantly Termitomyces monoculture.

Introduction: Bloodstream infection is a major cause of mortality and morbidity worldwide. Timely reporting of blood culture results is of utmost importance for better patient outcomes. The recently introduced Rapid Antimicrobial Susceptibility Testing (RAST) method is poised to profoundly influence clinical outcomes. Aim: To compare the results of RAST with Standard Antimicrobial Susceptibility Testing (SAST) and evaluate the impact of RAST reporting on the clinical management of septicaemia patients. Materials and Methods: This prospective, observational study was conducted in the Department of Microbiology, Government Medical College, Kurnool, Andhra Pradesh, India from May 2021 to September 2022. All positive blood culture bottles with only a single morphotype in gram staining were further processed using the RAST method, followed by conventional identification and SAST. Categorical agreement and disagreement between the RAST and SAST results were compared, along with the difference in the time at which results were available. Results: Out of a total of 1,146 blood cultures received, 228 were flagged as positive. A total of 514 isolate and antimicrobial agent combinations were evaluated, of which 496 (96.5%) showed categorical agreement. Only 18 (3.5%) showed categorical disagreement, with the majority being Major Errors (ME) (1.56%), followed by Very Major Errors (VME) (0.97%) and minor Errors (mE) (0.97%). Conclusion: RAST results demonstrated strong concurrence with SAST results. RAST is affordable, fast, and flexible and can potentially lead to a considerably shortened time for AST results to reach the bedside of the patient. This enables rapid modifications and adjustments in antibiotic therapy, including both escalation and de-escalation.

Research has shown that students' science achievement has declined because of outdated pedagogies and a lack of innovation in teaching and learning. The penetration of digital technologies into teaching could help improve this situation. This study aimed to see the effect of Google Sites on Year 5 students' science achievement. A quasi-experimental research design was used. The experimental group consisted of 35 students exposed to Google Sites, leading to more flexible and interactive learning. The students were exposed to various teaching materials such as videos and online notes and were more actively interacting with peers and teacher. In the control group, 31 students were exposed to the conventional teaching method. The pre/post-test encompassed higher-order thinking questions on the science topic -- States of Matter was the main data source. The data were analysed using Analysis of Covariance (ANCOVA) with pre-test as covariate. The findings revealed a statistical difference in the mean score of students' achievements between the control and experimental group: F (1,65) = 31.37, p < 0.001. The experimental group achieved better scores and gave better quality answers. The study implies that teachers could use free and user-friendly technological tools to improve the quality of their teaching. However, support and space for teachers to engage and get familiarised with these tools must be made available.

Chemoenzymatic techniques have been applied extensively to pharmaceutical development, most effectively when routine synthetic methods fail. The regioselective and stereoselective construction of structurally complex glycans is an elegant application of this approach that is seldom applied to positron emission tomography (PET) tracers. We sought a method to dimerize 2-deoxy-[18F]-fluoro-d-glucose ([18F]FDG), the most common tracer used in clinical imaging, to form [18F]-labeled disaccharides for detecting microorganisms in vivo based on their bacteria-specific glycan incorporation. When [18F]FDG was reacted with β-d-glucose-1-phosphate in the presence of maltose phosphorylase, the α-1,4- and α-1,3-linked products 2-deoxy-[18F]-fluoro-maltose ([18F]FDM) and 2-deoxy-2-[18F]-fluoro-sakebiose ([18F]FSK) were obtained. This method was further extended with the use of trehalose (α,α-1,1), laminaribiose (β-1,3), and cellobiose (β-1,4) phosphorylases to synthesize 2-deoxy-2-[18F]fluoro-trehalose ([18F]FDT), 2-deoxy-2-[18F]fluoro-laminaribiose ([18F]FDL), and 2-deoxy-2-[18F]fluoro-cellobiose ([18F]FDC). We subsequently tested [18F]FDM and [18F]FSK in vitro, showing accumulation by several clinically relevant pathogens including Staphylococcus aureus and Acinetobacter baumannii, and demonstrated their specific uptake in vivo. Both [18F]FDM and [18F]FSK were stable in human serum with high accumulation in preclinical infection models. The synthetic ease and high sensitivity of [18F]FDM and [18F]FSK to S. aureus including methicillin-resistant (MRSA) strains strongly justify clinical translation of these tracers to infected patients. Furthermore, this work suggests that chemoenzymatic radiosyntheses of complex [18F]FDG-derived oligomers will afford a wide array of PET radiotracers for infectious and oncologic applications.

Abstract A reply to the correspondence by Deora et al.- Critical insights on “Association of the C allele of rs479200 in the EGLN1 gene with COVID‑19 severity in Indian population: a novel finding”. The reply contains point-wise rebuttal to the concerns, particularly addressing the epidemiological, statistical, and mathematical issues raised by Deora et al.