Search

Since the COVID-19 pandemic, considerable advances have been made to improve epidemic preparedness by accelerating diagnostics, therapeutics, and vaccine development. However, we argue that it is crucial to make equivalent efforts in the field of outbreak analytics to help ensure reliable, evidence-based decision making. To explore the challenges and key priorities in the field of outbreak analytics, the Epiverse-TRACE initiative brought together a multidisciplinary group of experts, including field epidemiologists, data scientists, academics, and software engineers from public health institutions across multiple countries. During a 3-day workshop, 40 participants discussed what the first 100 lines of code written during an outbreak should look like. The main findings from this workshop are summarised in this Viewpoint. We provide an overview of the current outbreak analytic landscape by highlighting current key challenges that should be addressed to improve the response to future public health crises. Furthermore, we propose actionable solutions to these challenges that are achievable in the short term, and longer-term strategic recommendations. This Viewpoint constitutes a call to action for experts involved in epidemic response to develop modern and robust data analytic approaches at the heart of epidemic preparedness and response., Competing Interests: Declaration of interests This Viewpoint was written by the attendees of a workshop held in December, 2022, hosted by Epiverse-TRACE at the Wellcome Trust (London, UK). Epiverse-TRACE is funded by Data.org, which is supported by The Rockefeller Foundation and Mastercard Center for Inclusive Growth. Data.org is also supported by the Wellcome Trust and the International Development Research Centre (IDRC). The authors of this study have not been paid to write this article by a pharmaceutical company or other agency. CTC received funding from Data.org. AC received funding from the UK National Institute of Health Research, UK Medical Research Council, Pfizer, and the Academy of Medical Sciences. ZMC received funding from the Ministry of Science and Technology of Colombia via the AGORA Research Grant and the IDRC via the TRACE-LAC Research Grant; a research grant for enhancing tools for response, analytics, and control of epidemics in Latin America and the Caribbean (Project ID 109848); a mathematical modelling and development of epidemiological analysis, estimates, and projections for priority public health diseases in the Americas region grant; and support for attending meetings and travel from WHO, Pan American Health Organization, and The Lancet Commission. AYB received funding from Medecins Sans Frontières. CC is supported by ETH Zurich and the Centers for Disease Control and Prevention. JAL received funding from Pfizer. JT received funding from the Yeotown Scholarship, awarded by New College, Oxford. DSQ received funding from the Pontificia Universidad Javeriana. AFS received funding from Epiverse-TRACE to attend meetings and travel. AJK received funding from the Wellcome Trust and Data.org. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Enhancing the production of economically and medically important plant metabolites by genetic and metabolic manipulation is a lucrative approach for enhancing crop quality. Nevertheless, the task of identifying suitable biosynthetic pathways related to certain bioactivities has proven to be challenging due to the intricate interconnections of the major metabolic and biochemical processes in commercially important plants. The commercial significance of plants belonging to the genus Aloe stems from their extensive utilization across several industries, such as cosmetics, pharmaceuticals, and wellness items, due to their medicinal properties. In the present study, we have utilized a reverse association approach to identify potential target metabolic pathways for enhancing the production of commercially important metabolites of Aloe spp., based on their metabolic pathway enrichment profile. The leaves of five highly utilized Aloe sp. were subjected to untargeted gas chromatography-mass spectrometry analysis followed by testing of free-radical scavenging effects against components of the Fenton and Haber-Weiss reaction. Through the application of appropriate bioinformatics tools, we identified distinct phytochemical classes and determined the enrichment of their corresponding biosynthetic pathways, associated the pathways with bioactivities, and also identified the inter-relation between the commonly enriched pathways. The strong association between metabolic pathways and antioxidant potentials suggested the necessity to enhance distinct but closely related metabolic pathways in order to enhance the quality of Aloe spp. and maximize their antioxidant effects for commercial exploitation in cosmetic industries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 Published by Elsevier Ltd.)

Excitons, Coulomb-driven bound states of electrons and holes, are typically composed of integer charges 1,2 . However, in bilayer systems influenced by charge fractionalization 3,4 , a more interesting form of interlayer exciton can emerge, in which pairing occurs between constituents that carry fractional charges. Despite numerous theoretical predictions for these fractional excitons 5-16 , their experimental observation has remained unexplored. Here we report transport signatures of excitonic pairing in fractional quantum Hall effect states. By probing the composition of these excitons and their impact on the underlying wavefunction, we discover two new types of quantum phases of matter. One of these can be viewed as the fractional counterpart of the exciton condensate at a total filling of 1, whereas the other involves a more unusual type of exciton that obeys non-bosonic quantum statistics, challenging the standard model of bosonic excitons., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Reintroduction of tumor-suppressive microRNA-7-5p (miR-7) that is depleted in non-small cell lung cancer (NSCLC) represents a new therapeutic approach, whereas previous studies mainly used miR-7 mimics chemoengineered in vitro. Here we aim to establish the pharmacological actions and therapeutic potential of novel bioengineered RNA bearing a payload miR-7 (BioRNA/miR-7) molecule produced in vivo. First, through confocal imaging and immunoblot studies, we revealed that BioRNA/miR-7 altered NSCLC cell mitochondrial morphology accompanied by the downregulation of known target genes, epidermal growth factor receptor (EGFR), mitochondrial solute carrier family 25A37 (SLC25A37), and import inner membrane translocase subunit (TIM50). Second, through luciferase reporter and immunoblot studies, we validated mitochondrial acylglycerol kinase (AGK) as a new direct target for miR-7. Third, through real-time live-cell analyses, we revealed BioRNA/miR-7 to modulate mitochondrial respiration and glycolytic capacity. Fourth, live-cell and endpoint viability studies demonstrated that the combination of BioRNA/miR-7 with pemetrexed (PEM) elicited a strong synergistic effect to inhibit NSCLC cell growth, associated with an increased intracellular PEM accumulation, as quantified by a liquid chromatography tandem mass spectrometry method. Finally, through in vivo therapy study using NSCLC patient-derived xenograft mouse model, we demonstrated the efficacy and tolerability of BioRNA/miR-7 monotherapy and combination therapy with PEM to control tumor progression. Our collective works establish a role for miR-7 in NSCLC metabolism and PEM disposition and support our novel, in vivo produced BioRNA/miR-7-5p for molecular pharmacological research. Our findings further illustrate the potential of BioRNA/miR-7 plus PEM combination as a potential treatment to combat NSCLC tumor progression. SIGNIFICANCE STATEMENT: MiR-7 is a tumor-suppressive microRNA depleted in non-small cell lung cancer (NSCLC), and in vitro chemoengineered miR-7 mimics were shown to inhibit tumor growth in NSCLC cell-derived xenograft mice. Here, a novel in vivo bioengineered miR-7 molecule, namely BioRNA/miR-7, was used to effectively control target gene expression and NSCLC cell metabolism. Furthermore, BioRNA/miR-7 was demonstrated to remarkably improve pemetrexed antitumor activity in NSCLC patient-derived tumor mice, supporting the role of miR-7 in NSCLC metabolism and potential for BioRNA/miR-7 to improve NSCLC therapy., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Gene therapy has made substantial progress in the treatment of the genetic diseases, focussing on the reduction of characteristics of recessive/dominant disorders, as well as various cancers. Extensive research has been conducted in the past few decades to investigate the application of nanotechnology and CRISPR/Cas technology in gene therapy. Nanotechnology due to attributes such has targeted drug delivery, controlled release, scalability and low toxicity has gained attention of the medical world. CRISPR/Cas9 system is considered as an impactful genome editing tool in the area of next-generation therapeutics and molecular diagnostics. CRISPR technology emphasises on gene editing, gene regulation modulation, and formulation of defined genetic changes. Its applications in treatment of the genetic disorders are extended beyond traditional therapies. These techniques are being explored as treatment of several genetic disorders including Duchenne muscular dystrophy, cystic fibrosis, Alzheimer's disease, Parkinson's disease, and Huntington disease. Despite considerable therapeutic potential of gene therapy, several obstacles must be addressed before it can be widely adopted in clinical practice, particularly in terms of ensuring safety and effectiveness. As research advances in this captivating field, these therapies will become the primary treatments and will have significant beneficial effects on the lives of patients with genetic disorders., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Eosinophilic gastrointestinal disorders (EGIDs) are representative of eosinophilic invasion of various sections of the gastrointestinal tract and do not pertain to any secondary causes. To affirm the diagnosis of eosinophilic infiltration of the gastrointestinal tract, tissue biopsy evidence must be demonstrated. Both iron deficiency anemia and gastritis symptoms may be brought on by mucosal eosinophilic infiltration. One of the most common dietary deficiencies globally is iron deficiency anemia which affects most developing populations. Reduced dietary iron and poor iron absorption are significant reasons for iron deficiency anemia (IDA), although the most common causes are menstruation and GI bleeding in women. Here, we describe a case of an 18-year-old female, with iron deficiency anemia, who was diagnosed with eosinophilic duodenitis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bal et al.)

Laccase is a multicopper oxidase enzyme that target different types of phenols and aromatic amines. The enzyme can be isolated and characterized from microbes, plants and insects. Its ubiquitous nature and delignification ability makes it a valuable tool for research and development. Sustainable production methods are being employed to develop low cost biomanufacturing of the enzyme while achieving high titers. Laccase have significant industrial application ranging from food industry where it can be used for wine stabilization, texture improvement and detection of phenolic compounds in food products, to cosmetics offering benefits such as skin brightening and hair colouring. Dye decolourization/degradation, removal of pharmaceutical products/emerging pollutants and hydrocarbons from wastewater, biobleaching of textile fabrics, biofuel production and delignification of biomass making laccase a promising green biocatalyst. Innovative methods such as using inducers, microbial co-culturing, recombinant DNA technology, protein engineering have pivotal role in developing laccase with tailored properties. Enzyme immobilization using new age compounds including nanoparticles, carbonaceous components, agro-industrial residues enhance activity, stability and reusability. Commercial formulations of laccase have been prepared and readily available for a variety of applications. Certain challenges including production cost, metabolic stress in response to heterologous expression, difficulty in purification needs to be addressed., Competing Interests: Declaration of competing interest On behalf of all authors, it is stated that there is no conflict of interest related to the present manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Total hip replacement (THR) is a common surgical procedure aimed at alleviating pain and improving function in patients with hip joint pathology. Effective postoperative pain management is crucial for patient recovery, satisfaction, and overall outcomes. This narrative review examines the comparative efficacy, safety, and implications of using opioids versus non-opioid analgesics in managing postoperative pain following THR. Opioids, while effective for severe pain, pose significant risks such as addiction, tolerance, and adverse effects. Non-opioid analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and regional anesthesia techniques, offer alternatives with potentially fewer side effects. This review synthesizes current evidence from clinical trials, observational studies, and expert guidelines to provide a comprehensive understanding of the benefits and drawbacks of each analgesic approach. The goal is to inform clinical decision-making and optimize pain management strategies for THR patients, balancing efficacy and safety., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Singh et al.)

This narrative review analyzes muscle strength recovery following total hip replacement (THR) and looks at various factors affecting postoperative muscle function restoration. The review synthesizes evidence from various studies regarding the timing and degree of muscular strength recovery, different rehabilitation protocols, and patient-specific variables such as age, preoperative physical condition, and comorbidities, among others. Overall, it appears that THR is associated with improved hip function and quality of life, but this usually takes a long time due to individualized physical therapy interventions. In addition, postoperative rehabilitation has been found not to exist without any personal factors involved such as age or gender whereby for instance senior citizens have no alternative but to go for THR surgery, making their lower limbs weaker than those who are younger. Based on the findings in this review on muscle recovery after THR surgeries, one may conclude that this endeavor should begin as early as possible and include regular resistance training programs with performance-focused functional training after surgery. In addition, more longitudinal studies should be conducted regarding post-surgical outcomes comparing other traditional medical practices., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Singh et al.)

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among individuals with type 1 diabetes (T1D), necessitating effective prevention strategies. This comprehensive review consolidates current knowledge and evidence on preventing CVD in T1D patients. It begins by exploring the pathophysiological mechanisms that link T1D to an increased risk of CVD, highlighting factors such as chronic hyperglycemia, hypertension, dyslipidemia, and inflammation. The review also examines the epidemiology and specific risk factors for CVD in this population, emphasizing the need for rigorous risk assessment and screening. Lifestyle modifications, including dietary interventions, regular physical activity, and smoking cessation, are evaluated for their effectiveness in reducing CVD risk. Additionally, the review discusses pharmacological interventions, such as insulin therapy for glycemic control, antihypertensive medications, lipid-lowering agents, and antiplatelet therapy, underscoring their critical role in CVD prevention. Emerging therapies and future research directions are explored, focusing on novel pharmacological agents, advances in insulin delivery systems, and personalized medicine approaches. The importance of integrated care models involving multidisciplinary teams and the use of technology is highlighted as essential for comprehensive management. Challenges and barriers to implementing these strategies, including healthcare system limitations, patient adherence, and socioeconomic factors, are also addressed. This review provides a detailed synthesis of current strategies and future directions for preventing CVD in individuals with T1D, serving as a valuable resource for clinicians, researchers, and policymakers dedicated to improving cardiovascular outcomes in this high-risk population., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ahuja et al.)

In prostate cancer (PCa), androgens upregulate tumorigenesis, whereas in benign tissue, the revival of androgen receptor (AR) signaling suppresses aggressive behaviors, suggesting therapeutic potential. Dogs, natural PCa models, often lack AR in PCa. We restored AR in dog PCa to investigate resultant characteristics. Three AR-null canine PCa lines (1508, Leo, 1258) were transfected with canine wild-type AR and treated with dihydrotestosterone (DHT). In 1508, AR restoration decreased clonogenicity ( p = 0.03), viability ( p = 0.004), migration ( p = 0.03), invasion ( p = 0.01), and increased expression of the tumor suppressor NKX3.1 , an AR transcriptional target ( p = 0.001). In Leo, AR decreased clonogenicity ( p = 0.04) and the expression of another AR transcriptional target FOLH1 ( p < 0.001) and increased the expression of NKX3.1 ( p = 0.01). In 1258, AR increased migration ( p = 0.006) and invasion ( p = 0.03). Epithelial-mesenchymal transition (EMT) marker ( Vimentin , N-cadherin , SNAIL1 ) expression increased with AR restoration in Leo and 1258 but not 1508; siRNA vimentin knockdown abrogated AR-induced 1258 migration only. Overall, 1508 showed AR-mediated tumor suppression; AR affected proliferation in Leo but not migration or invasion; and EMT and AR regulated migration and invasion in 1258 but not proliferation. This study highlights the heterogeneous nature of PCa in dogs and cell line-specific effects of AR abrogation on aggressive behaviors.

Background: Fumarate hydratase (FH)-deficient (FH-d) leiomyomas are included in the recent World Health Organization fascicle of the female genital tumors. These are known to be associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. The tumors can be diagnosed based on certain histopathological features, along with loss of immunohistochemical expression of FH immunostain in most tumors. Currently, there is no documentation on these tumors from our subcontinent., Aims: We analyzed eight FH-d leiomyomas diagnosed at our institute., Results: The most common presentation was vaginal bleeding (menorrhagia). Pelvic ultrasonogram revealed multiple fibroids in most patients except in two, who harbored a single fibroid. The size of these fibroids ranged from 3 to 19 cm. Five patients underwent myomectomies, while three underwent a total abdominal hysterectomy and bilateral salphino-ophorectomy. The most consistently observed histopathological features were hemangiopericytomatous vascular patterns, cytoplasmic globules, increased cellularity, distinct eosinophilic nucleoli, and cytological atypia (8/8, 100% tumors), followed by multinucleate giant cells and perivascular edema, seen in 62% and 50% tumors, respectively. Immunohistochemically, all tumors were positive for desmin, smooth muscle actin, and h-caldesmon and showed loss of FH immunostain, along with low Ki-67/MIB1. None of those patients had any renal or cutaneous manifestations., Conclusions: This constitutes the first such study from the Indian subcontinent and reinforces that although uterine leiomyomas constitute an integral component of the diagnosis of HLRCC syndrome, these occur in the absence of renal or cutaneous manifestations. FH-d uterine leiomyomas are more likely sporadic and could be a false alarm to raise the possibility of HLRCC with their exclusive presence., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Introduction Iron deficiency anemia and beta-thalassemia trait are two common and important differentials of microcytic hypochromic anemia. Various discrimination indices using two or more common complete blood cell count (CBC) parameters have been used to distinguish between the two since 1973. Recently, a new discriminant index, the CRUISE index, was proposed in the year 2019. The efficacy of various older indices along with the CRUISE index was evaluated for patients in our geographical area. Materials and method Ours was a laboratory-based, cross-sectional study where 100 patients, based on inclusion and exclusion criteria, with microcytic hypochromic anemia were evaluated for CBC parameters along with serum ferritin and hemoglobin-high performance liquid chromatography (Hb HPLC). A total of eight discrimination indices namely, Mentzer, Srivastava, Shine & Lal, Green & King, RDWI, England & Fraser, Kerman I and CRUISE index were used and evaluated for their diagnostic efficacy using different statistical parameters. ROC curves were obtained and a new cut-off value was proposed for our population. Data was analysed using Microsoft Excel (Microsoft ® Corp., Redmond, WA, USA) and SPSS v29.0.2.0 (20) (IBM Corp., Armonk, NY, USA). Results Out of the total 100 cases, 39 were beta-thalassemia trait and 61 were iron deficiency anemia cases. The average age was 36.7 (±12.7 SD) years. Among the 73 females, 43 were diagnosed as iron deficiency anemia (IDA) and 30 as beta-thalassemia trait (BTT) cases. Among the 27 males, 18 were diagnosed as IDA and nine as BTT cases. The mean values were significantly lower in IDA patients for mean corpuscular volume (MCV) (p=.008), mean corpuscular haemoglobin (MCH) (p=.003), and mean corpuscular haemoglobin concentration (MCHC) (p=.003) and significantly higher for red cell distribution width (RDW) (p=.020). The mean ferritin levels in cases of IDA were 7.61 (±3.75) mcg/L and in BTT were 87.09 (±66.77 SD) mcg/L. The mean HbA2 levels in IDA cases were 2.75% (±0.41% SD) and BTT cases were 5.57% (±0.73% SD). CRUISE index revealed the highest AUC (0.934), YI (76.21) and accuracy (90%) followed by the Mentzer index with a diagnostic accuracy of 81%. Shine & Lal index revealed the lowest AUC (0.710), YI (3.28) and accuracy (41%). Conclusion CRUISE index, which was recently proposed, was ranked 1 st in terms of AUC, YI, and accuracy and was considered 2 nd best in terms of sensitivity for differentially diagnosing the two conditions. Mentzer index, a commonly used index, also revealed a high diagnostic accuracy in our study for differentiating BTT from IDA. CRUISE index being a novel index, more research work needs to be carried out in various other geographical setups to evaluate the efficacy of this index., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. MMIMSR Ethical Committee issued approval 2528. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hans et al.)

Labial fusion, though rare, can present during puberty, or even adolescence leading to challenges in diagnosis and management. This case report offers a detailed examination of the clinical manifestation, diagnostic process, and therapeutic approach in an adolescent girl with labial fusion. This report emphasizes the importance of early intervention to improve patient outcomes for this complex medical condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gupta et al.)

The vertebrobasilar system is made up of the two vertebral arteries that unite to form the basilar artery near the base of the skull. Aneurysms in the vertebrobasilar system are distinct from other cerebral aneurysms due to their unique morphologic characteristics. They can be large and bulging (massive), pressing on the brainstem. Alternatively, they might be weak and splitting apart (dissecting) or have an elongated shape (fusiform). On the other end of the spectrum, Vertebral artery aneurysms (VAAs) can also be small and rounded (saccular). These aneurysms can occur at the vertebral artery itself or where it joins the posterior inferior cerebellar artery (PICA). Anatomically, they are situated near the brainstem and cranial nerves, deep within the posterior fossa. The cerebrospinal fluid is kept in transit and flux by the ventricular system's chambers circulating the fluid within themselves. An intraventricular hemorrhage (IVH) can occasionally result from vertebral artery aneurysmal ruptures that result in bleeding into the subarachnoid space and then extravasate into the ventricles. Persistent and poorly controlled hypertension affects about 50% of individuals with IVH. In this case report, we study a 74-year-old woman who complained of a sudden onset headache that had been bothering her for three days at the medical emergency room. She had been diagnosed with systemic hypertension eight years prior and had not taken her medicines as prescribed. She was discovered to have rigidity in her neck and a blood pressure reading of 170/100 mmHg, which had been followed by an episode of vomiting. Radiological investigations revealed a VAA that had a high risk of rupturing and causing an IVH., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Chavhan et al.)

Synthetic biology constitutes a scientific domain focused on intentional redesign of organisms to confer novel functionalities or create new products through strategic engineering of their genetic makeup. Leveraging the inherent capabilities of nature, one may address challenges across diverse sectors including medicine. Inspired by this concept, we have developed an innovative bioengineering platform, enabling high-yield and large-scale production of biological small interfering RNA (BioRNA/siRNA) agents via bacterial fermentation. Herein, we show that with the use of a new tRNA fused pre-miRNA carrier, we can produce various forms of BioRNA/siRNA agents within living host cells. We report a high-level overexpression of nine target BioRNA/siRNA molecules at 100% success rate, yielding 3-10 mg of BioRNA/siRNA per 0.25 L of bacterial culture with high purity (>98%) and low endotoxin (<5 EU/μg RNA). Furthermore, we demonstrate that three representative BioRNA/siRNAs against GFP, BCL2, and PD-L1 are biologically active and can specifically and efficiently silence their respective targets with the potential to effectively produce downstream antiproliferation effects by PD-L1-siRNA. With these promising results, we aim to advance the field of synthetic biology by offering a novel platform to bioengineer functional siRNA agents for research and drug development.

Complications of acute-on-chronic liver failure (ACLF) include increased short-term mortality. Extrahepatic organ failures result from chronic liver disease and acute hepatic injury. This combination characterizes end-stage liver disease. Its rapid progression makes it challenging for hepatologists and intensivists to treat. The varied definitions of this condition lead to varied clinical presentations. Hepatic or extrahepatic failures are more prevalent in chronic hepatitis B or cirrhosis patients who receive an additional injury. Numerous intensity parameters and prognosis ratings, including those for hepatitis B virus (HBV), have been developed and verified for various patients and causes of the disease. Liver regeneration, liver transplantation (LT), or antiviral therapy for HBV-related ACLF are the main treatment aims for various organ failures. LT is the best treatment for HBV-ACLF. In some HBV-related ACLF patients, nucleos(t)ide analogs and artificial liver assistance may enhance survival. Combining epidemiological and clinical studies, this review updates our understanding of HBV-ACLF's definition, diagnosis, epidemiology, etiology, therapy, and prognosis., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Batra et al.)

Introduction: Primary pulmonary salivary gland-type tumours (PPSGT) are rare lung neoplasms arising from submucosal seromucinous glands in the central airway., Methods and Results: We retrospectively analysed the clinicopathological features of 111 PPSGTs diagnosed at our institute between 2003 and 2021. The mean age at diagnosis was 43.8 years(range 6-78 years) and a male-to-female ratio of 2:1. On imaging, 92 % of cases had centrally located tumours and 37.3 % were early stage. The histopathological types included 70 cases (63 %) of mucoepidermoid carcinoma (MEC), 31 cases (27.7 %) of adenoid cystic carcinoma (ADCC), two cases of myoepithelial carcinoma, one case each of acinic cell carcinoma (ACC), clear cell carcinoma (CCC), epithelial myoepithelial carcinoma (EMC) and 5 others [including adenocarcinoma of minor salivary gland origin(n = 3), carcinoma with sebaceous differentiation(n = 1) and poorly differentiated carcinoma of salivary gland type(n = 1)]. The size of the tumours found in the resection specimens ranged from 1 cm to 13 cm, with an average size of 4.9 cm. High-risk attributes such as lymphovascular invasion (LVI), perineural invasion (PNI), pleural involvement, positive resection margins, and nodal metastasis were identified in 15.3 %, 15.3 %, 13.6 %,15.2 % and 6.7 % of cases, respectively. These attributes were found to be more frequent in ADCC than in MEC. Surgery was the main treatment modality [68/84 (80 %) cases]. ADCC cases had more recurrence and distant metastasis than MEC cases. The 3- year overall-survival (OS) and recurrence-free survival(RFS) were better in patients with age lesser than 60 years(p-value <0.0001), low pT stage (p-value 0.00038) and lower grade of MEC(p-value-0.0067)., Conclusion: It is crucial to have an acquaintance with the morphologic spectrum and immunophenotypic characteristics of PPSGT to recognize them in this unusual location. In tandem, it is crucial to differentiate them from conventional primary non-small cell lung carcinoma, as the management protocols and prognostic implications differ significantly., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fractional charges of anyons can be extracted from shot noise in two ways. One can use either the autocorrelation noise of the current in one drain or the cross-correlation noise between two drains on the two sides of the device. The former approach typically overestimates the charge. This may happen due to upstream edge modes. We propose a mechanism for the excess autocorrelation noise without upstream modes. It applies to systems with multiple copropagating edge modes and assumes that the noise is measured at a low but nonzero frequency.

Genome-derived microRNAs (miRNAs or miRs) govern posttranscriptional gene regulation and play important roles in various cellular processes and disease progression. While chemo-engineered miRNA mimics or biosimilars made in vitro are widely available and used, miRNA agents produced in vivo are emerging to closely recapitulate natural miRNA species for research. Our recent work has demonstrated the success of high-yield, in vivo production of recombinant miRNAs by using human tRNA (htRNA) fused precursor miRNA (pre-miR) carriers. In this study, we aim to compare the production of bioengineered RNA (BioRNA) molecules with glycyl versus leucyl htRNA fused hsa-pre-miR-34a carriers, namely, BioRNA Gly and BioRNA Leu , respectively, and perform the initial functional assessment. We designed, cloned, overexpressed, and purified a total of 48 new BioRNA/miRNAs, and overall expression levels, final yields, and purities were revealed to be comparable between BioRNA Gly and BioRNA Leu molecules. Meanwhile, the two versions of BioRNA/miRNAs showed similar activities to inhibit non-small cell lung cancer cell viability. Interestingly, functional analyses using model BioRNA/miR-7-5p demonstrated that BioRNA Gly /miR-7-5p exhibited greater efficiency to regulate a known target gene expression ( EGFR ) than BioRNA Leu /miR-7-5p, consistent with miR-7-5p levels released in cells. Moreover, BioRNA Gly /miR-7-5p showed comparable or slightly greater activities to modulate MRP1 and VDAC1 expression, compared with miRCURY LNA miR-7-5p mimic. Computational modeling illustrated overall comparable 3D structures for exemplary BioRNA/miRNAs with noticeable differences in htRNA species and payload miRNAs. These findings support the utility of hybrid htRNA/hsa-pre-miR-34a as reliable carriers for RNA molecular bioengineering, and the resultant BioRNAs serve as functional biologic RNAs for research and development., (© 2024 Traber et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Hepatitis B viral infection poses a significant challenge during pregnancy, as the risk of vertical transmission carries serious consequences for both maternal and neonatal well-being. This comprehensive review delves into the intricacies surrounding hepatitis B infection during the perinatal period, shedding light on its impact on pregnancy outcomes and stressing the necessity of addressing it within the broader framework of perinatal care. By scrutinizing current evidence, diagnostic methodologies, management techniques, and preventive measures, this review emphasizes the urgent need for enhanced screening protocols, timely interventions, and augmented public health initiatives. Notably, key findings underscore the elevated likelihood of chronic hepatitis B virus (HBV) infection in infants and its enduring implications for the health of both mothers and newborns. The imperative call to action advocates for a multifaceted approach, engaging healthcare professionals, policymakers, and public health agencies to optimize strategies for management and prevention, thereby striving for improved outcomes for pregnant women and their infants affected by hepatitis B viral infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Singh Thakur et al.)

Background: Chemotherapy-induced cardiac dysfunction (CIC) is a significant and concerning complication observed among cancer patients. Despite the demonstrated cardioprotective benefits of statins in various cardiovascular diseases, their effectiveness in mitigating CIC remains uncertain. Objective: This meta-analysis aims to comprehensively evaluate the potential cardioprotective role of statins in patients with CIC. Methods: A systematic literature search was conducted using PubMed, Embase, and Scopus databases to identify relevant articles published from inception until 10th May 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CIs). Results: This meta-analysis comprised nine studies involving a total of 5532 patients, with 1904 in the statin group and 3628 in the non-statin group. The pooled analysis of primary outcome shows that patients who did not receive statin suffer a greater decline in the LVEF after chemotherapy compared to those who receive statin (MD, 3.55 (95% CI: 1.04-6.05), p = 0.01). Likewise, we observed a significantly higher final mean LVEF among chemotherapy patients with statin compared to the non-statin group of patients (MD, 2.08 (95% CI: 0.86-3.30), p > 0.001). Additionally, there was a lower risk of incident heart failure in the statin group compared to the non-statin group of patients (OR, 0.41 (95% CI: 0.27-0.62), p < 0.001). Lastly, the change in the mean difference for LVEDV was not statistically significant between the statin and non-statin groups (MD, 1.55 (95% CI: -5.22-8.33), p = 0.65). Conclusion: Among patients of CIC, statin use has shown cardioprotective benefits by improving left ventricular function and reducing the risk of heart failure.

This review explores recent advancements in wearable digital health technology specifically designed to manage epilepsy. Epilepsy presents unique challenges in monitoring and management due to the unpredictable nature of seizures. Wearable devices offer continuous monitoring and real-time data collection, providing insights into seizure patterns and trends. Wearable technology is important in epilepsy management because it enables early detection, prediction, and personalized intervention, empowering patients and healthcare providers. Key findings highlight the potential of wearable devices to improve seizure detection accuracy, enhance patient empowerment through real-time monitoring, and facilitate data-driven decision-making in clinical practice. However, further research is needed to validate the accuracy and reliability of these devices across diverse patient populations and clinical settings. Collaborative efforts between researchers, clinicians, technology developers, and patients are essential to drive innovation and advancements in wearable digital health technology for epilepsy management, ultimately improving outcomes and quality of life for individuals with this neurological condition., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ahuja et al.)

This comprehensive review delves into the multifaceted landscape of postpartum depression (PPD), exploring its prevalence, impact on maternal and infant well-being, and the efficacy of existing screening and intervention practices. PPD emerges as a critical concern, with implications extending beyond individual mental health to encompass the dynamics of mother-infant relationships and societal well-being. The analysis underscores the complexity of addressing PPD, emphasizing the challenges associated with screening tools and the importance of evidence-based interventions. A call to action resonates throughout, urging healthcare providers, policymakers, and stakeholders to prioritize mental health support for new mothers through enhanced screening protocols and improved accessibility to interventions. Furthermore, the review highlights the need for destigmatization and awareness campaigns to foster a supportive environment. Future research directions are outlined, emphasizing the refinement of screening tools, developing innovative interventions, and exploring cultural and socioeconomic influences on PPD outcomes. The review envisions a collaborative effort to dispel the shadows of PPD, striving for a future where mothers receive comprehensive support, ensuring optimal mental health and overall well-being., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Gupta et al.)

After total abdominal hysterectomy (TAH), intestinal prolapse is uncommon. We report an instance of a 48-year-old woman who had TAH and then intestinal prolapse. Two weeks after the operation, symptoms started to show up, and the vaginal vault developed a bulging bulge. The problem was satisfactorily treated with an urgent laparotomy. The significance of being vigilant for unusual complications following TAH is shown by this example., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Singh Thakur et al.)

This case report is about a middle-aged female who presented with complaints of pain in the abdomen with intractable vomiting for three months, pain and weakness in bilateral lower limbs for two months, and irritability for three days. She was previously treated for lumbar disc bulge and severe narrowing of the spinal cord whose treatment also included vitamin D supplements. After taking high doses of a vitamin D supplement daily for approximately four months, it resulted in vitamin D toxicity. The sodium level of the patient was in the normal range throughout the treatment. Her magnetic resonance imaging brain revealed features of central pontine myelinolysis. The development of central pontine myelinolysis due to vitamin D toxicity, with normal sodium levels, makes this a rare case for discussion., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ahuja et al.)

Background: Open bite is a common orthodontic malocclusion that can have functional and aesthetic implications. Traditional orthodontic treatments have been used to correct open bites, but the effectiveness of Invisalign, a clear aligner therapy, in open bite correction remains a topic of interest., Materials and Methods: A retrospective analysis was conducted on a cohort of 50 patients with open bites who underwent Invisalign treatment. Pre-treatment and post-treatment records, including cephalometric radiographs, dental models, and clinical photographs, were assessed. The open bite was defined as a negative overbite greater than 2 mm. Treatment duration, number of aligners used, and patient compliance were also recorded. Statistical analysis, including paired t-tests and subjective patient feedback, was employed to evaluate the treatment outcomes., Results: The mean pre-treatment open bite was -3.5 mm (SD = 1.2), and the mean treatment duration was 18 months (SD = 2.5). On average, patients received 24 sets of aligners (SD = 4.1) during the treatment. Post-treatment evaluation showed that the mean overbite improved to + 1.5 mm (SD = 0.8), indicating successful open bite correction. The paired t -test revealed a statistically significant difference between pre-treatment and post-treatment open bite measurements ( P < 0.001). Patient satisfaction was high, with 90% of participants reporting improved aesthetics and comfort., Conclusion: Invisalign treatment demonstrates effectiveness in correcting open bites, with statistically significant improvements in overbite measurements., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

This comprehensive review explores the complex dynamics of nosocomial infections in individuals with sickle cell anemia (SCA) and advocates for a collaborative strategy to enhance prevention. SCA patients, marked by compromised immunity and susceptibility to infections, face unique challenges that necessitate tailored preventive measures. The review underscores the importance of vaccination, antibiotic prophylaxis, education, and environmental hygiene in mitigating the risk of nosocomial infections. Addressing socioeconomic factors, healthcare system limitations, patient-related issues, and cultural considerations is imperative for effective prevention. The call to action emphasizes the pivotal roles of healthcare professionals, policymakers, researchers, and community engagement in implementing targeted interventions. By fostering a collective effort, this review envisions an improved landscape for infection prevention in SCA patients, enhancing their overall health outcomes and quality of life., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Batra et al.)

This review provides a comprehensive exploration of the roles of placenta growth factor (PlGF) and pregnancy-associated plasma protein A (PAPP-A) in the context of pre-eclampsia, a pregnancy-related hypertensive disorder with significant implications for maternal and fetal health. The background elucidates the clinical significance of pre-eclampsia, highlighting its prevalence and impact. The review delves into the biological importance of PlGF and PAPP-A, emphasizing their critical roles in normal placental development and their dysregulation in pre-eclampsia. Notably, altered levels of these biomarkers emerge as potential diagnostic indicators, offering insights into the pathophysiology of the disorder. The exploration of pathophysiological mechanisms, including angiogenic imbalance and placental dysfunction, provides a nuanced understanding of pre-eclampsia's molecular landscape. The therapeutic implications of targeting PlGF and PAPP-A open avenues for future research, aiming at effective intervention strategies. The conclusion summarizes key findings, outlines implications for future research, and underscores the crucial role of PlGF and PAPP-A in understanding and managing pre-eclampsia, with the ultimate goal of improving outcomes for both mothers and infants., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Singh Thakur et al.)

Objective: The location of infraorbital foramen varies between geographic locations. Thus, population-specific information is required to facilitate the prediction of its exact location., Methods:  A cross-sectional study was conducted on 100 cone beam computed tomography (CBCT) sections to evaluate the distance between the infraorbital foramen and incisal edge of the maxillary central incisor, the occlusal plane of the maxillary second premolar, and the alveolar crest over the maxillary second premolar using CBCT in Central Gujarat, Indian population. Descriptive statistical analysis was performed to calculate means and standard deviations for each measured parameter. The statistical significance level was defined at p<0.05., Results: The distance between the infraorbital foramen and incisal surface of the maxillary central incisor was (mean ± standard deviation) R=49.39 ± 3.12 mm and L=49.49 ± 3.29 mm, the occlusal plane of the maxillary second premolar was R=39.02 ± 2.65 mm and L=39.49 ± 2.53 mm, and the alveolar crest over the maxillary second premolar was R=32.64 ± 2.67 mm and L=31.64 ± 2.33 mm. There was no significant difference in the mean values of all variables between genders and age groups (p>0.05). The distance between the infraorbital foramen and the alveolar crest over the maxillary second premolar was greater on the right side (p<0.05)., Conclusion: The results of this study were analogous to those observed in a cohort of the Turkish population but varied from those observed in a cohort of the Sri Lankan population. Hence, more population-specific studies are required., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Desai et al.)

The multifaceted chemo-immune resistance is the principal barrier to achieving cure in cancer patients. Identifying a target that is critically involved in chemo-immune-resistance represents an attractive strategy to improve cancer treatment. iRhom1 plays a role in cancer cell proliferation and its expression is negatively correlated with immune cell infiltration. Here we show that iRhom1 decreases chemotherapy sensitivity by regulating the MAPK14-HSP27 axis. In addition, iRhom1 inhibits the cytotoxic T-cell response by reducing the stability of ERAP1 protein and the ERAP1-mediated antigen processing and presentation. To facilitate the therapeutic translation of these findings, we develop a biodegradable nanocarrier that is effective in codelivery of iRhom pre-siRNA (pre-siiRhom) and chemotherapeutic drugs. This nanocarrier is effective in tumor targeting and penetration through both enhanced permeability and retention effect and CD44-mediated transcytosis in tumor endothelial cells as well as tumor cells. Inhibition of iRhom1 further facilitates tumor targeting and uptake through inhibition of CD44 cleavage. Co-delivery of pre-siiRhom and a chemotherapy agent leads to enhanced antitumor efficacy and activated tumor immune microenvironment in multiple cancer models in female mice. Targeting iRhom1 together with chemotherapy could represent a strategy to overcome chemo-immune resistance in cancer treatment., (© 2024. The Author(s).)

To address the under reporting of sexual offences against children, the Protection of Children from Sexual Offences (POCSO) Act, 2012, makes reporting of such offences mandatory. The duty to report such offences has been extended to healthcare professionals. The inclusion of healthcare professionals within mandatory reporting, however, strikes at the very foundation of the doctor- patient relationship based on trust and confidentiality and conflicts with the patient confidentiality safeguards of the Mental Healthcare Act, 2017. It also has unintended public health consequences, such as denial of medical termination of pregnancy due to fear of prosecution under POCSO. An urgent reassessment of these mandatory reporting norms for healthcare professionals, and a solution-based approach that harmonises societal interest in the reporting of sexual crimes with the child's right to health is essential.

Pectinases are a collection of multiple enzymes that have a common substrate, that is, pectin. They can act on different parts of pectin due to the structural heterogeneity of pectin. Therefore, they have been placed in different groups, such as protopectinases, polygalacturonases, polymethylesterases, pectin lyases, and pectate lyases. They are naturally present both in multicellular organisms such as higher plants and in unicellular organisms such as microbes. In past decade, it has been witnessed that chemical and mechanical methods employed in industrial processes have led to environmental hazards and serious health disorders, thus increasing the search for eco-friendly approaches with minimal health risks. Hence, microbial enzymes have been extensively used as safer alternative for these environmentally unsafe methods. Among these microbial enzymes, pectinases hold great significance and is one of the principal enzymes that have been used commercially. It is predominantly used as a green biocatalyst for fruit, fiber, oil, textile, beverage, pulp, and paper industry. Thus, this review focuses on the structure of pectin, microbial sources of pectin, and principle industrial applications of pectinases., (© 2023 International Union of Biochemistry and Molecular Biology, Inc.)

During the development of therapeutic microRNAs (miRNAs or miRs), it is essential to define their pharmacological actions. Rather, miRNA research and therapy mainly use miRNA mimics synthesized in vitro . After experimental screening of unique recombinant miRNAs produced in vivo , three lead antiproliferative miRNAs against human NSCLC cells, miR-22-3p, miR-9-5p, and miR-218-5p, were revealed to target folate metabolism by bioinformatic analyses. Recombinant miR-22-3p, miR-9-5p, and miR-218-5p were shown to regulate key folate metabolic enzymes to inhibit folate metabolism and subsequently alter amino acid metabolome in NSCLC A549 and H1975 cells. Isotope tracing studies further confirmed the disruption of one-carbon transfer from serine to folate metabolites by all three miRNAs, inhibition of glucose uptake by miR-22-3p, and reduction of serine biosynthesis from glucose by miR-9-5p and -218-5p in NSCLC cells. With greater activities to interrupt NSCLC cell respiration, glycolysis, and colony formation than miR-9-5p and -218-5p, recombinant miR-22-3p was effective to reduce tumor growth in two NSCLC patient-derived xenograft mouse models without causing any toxicity. These results establish a common antifolate mechanism and differential actions on glucose uptake and metabolism for three lead anticancer miRNAs as well as antitumor efficacy for miR-22-3p nanomedicine, which shall provide insight into developing antimetabolite RNA therapies., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Catamenial epistaxis is a rare form of epistaxis (nosebleed) that occurs in women during menstruation due to hormonal changes. There are numerous hypotheses on the cellular mechanisms and pathophysiology of endometriosis. Endometriosis may present a wide range of symptoms depending on where endometrial tissue was implanted. This entity's diagnosis is neither simple nor difficult. There are numerous clinical and laboratory diagnostic techniques in use, but none of them is considered to be the best. Every woman who experiences recurrent symptoms (such as epistaxis and hemoptysis) of extrapelvic organs should be clinically suspicious of endometriosis because of its multipotent location and the variety of clinical manifestations of the condition. This case report demonstrates that periodic epistaxis may infrequently be the root cause of the extra pelvic endometrium in the nasal septum in a woman who has had treatment for recurrent pelvic discomfort and dysmenorrhea., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Batra et al.)

Mucoepidermoid carcinoma is a locally invasive tumor of the major and minor salivary glands. A 29-year-old male patient reported a complaint of slow-growing, painless, non-ulcerated palatal swelling. On clinical evaluation, the swelling appeared benign; hence, the complete excision of the lesion was carried out under general anesthesia, with closure by reconstruction with a partial-thickness flap. Healing was uneventful. The histopathological evaluation revealed low-grade mucoepidermoid carcinoma. This case report aims to highlight the importance of proper clinical and histopathological evaluation to rule out malignancy, as mucoepidermoid carcinoma can have variable presentations and mimic various benign salivary gland lesions, similar to the occurrence in the present case., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mishra et al.)

Patients present to the orthopedic outpatient department with complaints of shoulder pain on movement or restriction of movement in the shoulder joint and are referred for magnetic resonance imaging (MRI) of the shoulder joint. Almost all the patients have similar complaints but may have a wide range of pathology affecting the joint and causing pain. Rotator cuff tears or tendinopathy are the most common causes of shoulder pain. Ultrasound (USG) and MRI are the most commonly used imaging modalities for assessing rotator cuff pathologies. There is a wide range of pathologies affecting the shoulder joint, other than rotator cuff tendinopathies or tears, for which USG is less sensitive and specific in detecting accurate pathology. MRI is the choice of imaging for shoulder joint pathologies. We present a pictorial review discussing and depicting MRI features of a wide list of pathologies of the shoulder joint complex that should be kept in mind when the patient presents with shoulder pain., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sood et al.)

Degeneration of the lumbar intervertebral disc is the most common cause of lower back pain. It is directly related to daily activities, mechanical stress, and other biological factors. We use imaging modalities to assess the degree of disc degeneration, out of which magnetic resonance imaging (MRI) is the most popular non-invasive modality. It is believed that early changes in disc degeneration are due to the biochemical events in the disc and can be evaluated by sequences in MRI involving the diffusion of water molecules. The apparent diffusion coefficient (ADC) is one such sequence that captures the signals based on the diffusion of water molecules. Ten articles were chosen from PubMed and Google Scholar using the MeSH terms 'lumbar spine degeneration' and 'apparent diffusion coefficient'. This review article has summarized various studies intending to gain a better understanding of the biochemical events leading to the development of disc degeneration. This study has also gathered the role of various sequences in MRI that can quantitatively assess disc degeneration., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sood et al.)

Prostate cancer is initially regulated by the androgen receptor (AR), a ligand-activated, transcription factor, and is in a hormone-dependent state (hormone-sensitive prostate cancer (HSPC)), but eventually becomes androgen-refractory (castration-resistant prostate cancer (CRPC)) because of mechanisms that bypass the AR, including by activation of ErbB3, a member of the epidermal growth factor receptor family. ErbB3 is synthesized in the cytoplasm and transported to the plasma membrane for ligand binding and dimerization, where it regulates downstream signaling, but nuclear forms are reported. Here, we demonstrate in prostatectomy samples that ErbB3 nuclear localization is observed in malignant, but not benign prostate, and that cytoplasmic (but not nuclear) ErbB3 correlated positively with AR expression but negatively with AR transcriptional activity. In support of the latter, androgen depletion upregulated cytoplasmic, but not nuclear ErbB3, while in vivo studies showed that castration suppressed ErbB3 nuclear localization in HSPC, but not CRPC tumors. In vitro treatment with the ErbB3 ligand heregulin-1β (HRG) induced ErbB3 nuclear localization, which was androgen-regulated in HSPC but not in CRPC. In turn, HRG upregulated AR transcriptional activity in CRPC but not in HSPC cells. Positive correlation between ErbB3 and AR expression was demonstrated in AR-null PC-3 cells where stable transfection of AR restored HRG-induced ErbB3 nuclear transport, while AR knockdown in LNCaP reduced cytoplasmic ErbB3. Mutations of ErbB3's kinase domain did not affect its localization but was responsible for cell viability in CRPC cells. Taken together, we conclude that AR expression regulated ErbB3 expression, its transcriptional activity suppressed ErbB3 nuclear translocation, and HRG binding to ErbB3 promoted it., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Published by Elsevier Inc.)

Endo 1,4-β-d-xylanases (EC3.2.1.8) are one of the key lignocellulose hydrolyzing enzymes. Xylan, which is present in copious amounts on earth, forms the primary substrate of endo-xylanases, which can unchain the constituent monosaccharides linked via β-1,4-glycosidic bonds from the xylan backbone. Researchers have shown keen interest in the xylanases belonging to glycoside hydrolase families 10 and 11, whereas those placed in other glycoside hydrolase families are yet to be investigated. Various microbes such as bacteria and fungi harbor these enzymes for the metabolism of their lignocellulose fibers. These microbes can be used as miniature biofactories of xylanase enzymes for a plethora of environmentally benign applications in pulp and paper industry, biofuel production, and for improving the quality of food in bread baking and fruit juice industry. This review highlights the potential of microbes in production of xylanase for industrial biotechnology., (© 2023 International Union of Biochemistry and Molecular Biology, Inc.)

The association between nonalcoholic fatty liver disease (NAFLD) with cardiovascular and cerebrovascular outcomes, as well as their clinical impact, has yet to be established in the literature. This meta-analysis aims to evaluate the association between the NAFLD patients and the risk of atrial fibrillation (AF), heart failure (HF), stroke, cardiovascular mortality (CVM), and revascularization incidence. We performed a systematic literature search using PubMed, Embase, Scopus, and Cochrane libraries for relevant articles from inception until August 2022. A total of 12 cohort studies with 18,055,072 patients (2,938,753 NAFLD vs 15,116,319 non-NAFLD) were included in our analysis. The mean age of the NAFLD patients group and the non-NAFLD group was comparable (55.68 vs 55.87). The most common comorbidities among the NAFLD patients group included hypertension (38% vs 24%) and diabetes mellitus (14% vs 8%). The mean follow-up duration was 6.26 years. The likelihood of AF (risk ratio (RR), 1.42 (95% CI 1.19, 1.68), p < 0.001), HF (RR, 1.43(95% CI 1.03, 2.00), p < 0.001), stroke (RR, 1.26(95% CI 1.16, 1.36), p < 0.001), revascularization (RR, 4.06(95% CI 1.44, 11.46), p = 0.01), and CVM (RR, 3.10(95% CI 1.43, 6.73), p < 0.001) was significantly higher in the NAFLD patients group compared to that of the non-NAFLD group. However, all-cause mortality was comparable between both the groups of patients (RR, 1.30 (95% CI 0.63, 2.67), p = 0.48). In conclusion, the patients with NAFLD are at increased risk of AF, HF, and CVM.

Background: National Institute for Health and Clinical Effectiveness (NICE), UK, guideline published in 2019 recommends the use of volume-targeted ventilation (VTV). It recommends synchronised intermittent mandatory ventilation (SIMV) over the modes that support-all-breaths, for example, assist control ventilation (ACV). We conducted a systematic review and meta-analysis of the studies comparing SIMV mode with triggered modes supporting all breaths., Methods: Patients: Neonates receiving mechanical ventilation., Intervention: SIMV ventilation.Comparison: Modes that support-all-breaths: ACV, pressure support ventilation and neurally adjusted ventilation., Outcomes: Death before discharge and bronchopulmonary dysplasia (BPD) at 36 weeks' corrected gestation, weaning duration, incidence of air leaks, extubation failure, postnatal steroid use, patent ductus arteriosus requiring treatment, severe (grade 3/4) intraventricular haemorrhage, periventricular leukomalacia and neurodevelopmental outcome at 2 years.Randomised or quasi-randomised clinical trials comparing SIMV with triggered ventilation modes supporting all breaths in neonates, reporting on at least one outcome of interest were eligible for inclusion in the review., Results: Seven publications describing eight studies fulfilled the eligibility criteria. No significant difference in mortality (OR 0.74, 95% CI 0.32 to 1.74) or BPD at 36 weeks (OR 0.63, 95% CI 0.33 to 1.24), but the weaning duration was significantly shorter in support-all-breaths group with a mean difference of -22.67 hours (95% CI -44.33 to -1.01). No difference in any other outcomes., Conclusion: Compared with SIMV, synchronised modes supporting all breaths are associated with a shorter weaning duration with no statistically significant difference in mortality, BPD at 36 weeks or other outcomes. Larger studies with explicit ventilator and weaning protocols are needed to compare these modes in the current neonatal population., Prospero Registration Number: The review was prospectively registered with PROSPERO: CRD42020207601., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Globally, since 1 January 2020 and as of 24 January 2023, there have been over 664 million cases of COVID-19 and over 6.7 million deaths reported to WHO. WHO developed an evidence-based alert system, assessing public health risk on a weekly basis in 237 countries, territories and areas from May 2021 to June 2022. This aimed to facilitate the early identification of situations where healthcare capacity may become overstretched., Methods: The process involved a three-stage mixed methods approach. In the first stage, future deaths were predicted from the time series of reported cases and deaths to produce an initial alert level. In the second stage, this alert level was adjusted by incorporating a range of contextual indicators and accounting for the quality of information available using a Bayes classifier. In the third stage, countries with an alert level of 'High' or above were added to an operational watchlist and assistance was deployed as needed., Results: Since June 2021, the system has supported the release of more than US$27 million from WHO emergency funding, over 450 000 rapid antigen diagnostic testing kits and over 6000 oxygen concentrators. Retrospective evaluation indicated that the first two stages were needed to maximise sensitivity, where 44% (IQR 29%-67%) of weekly watchlist alerts would not have been identified using only reported cases and deaths. The alerts were timely and valid in most cases; however, this could only be assessed on a non-representative sample of countries with hospitalisation data available., Conclusions: The system provided a standardised approach to monitor the pandemic at the country level by incorporating all available data on epidemiological analytics and contextual assessments. While this system was developed for COVID-19, a similar system could be used for future outbreaks and emergencies, with necessary adjustments to parameters and indicators., Competing Interests: Competing interests: None declared., (© World Health Organization 2023. Licensee BMJ.)

Background: Current methods of burn estimation can lead to incorrect estimates of the total body surface area (TBSA) burned, especially among injured children. Inaccurate estimation of burn size can impact initial management, including unnecessary transfer to burn centres and fluid overload during resuscitation. To address these challenges, we developed a smartphone application (EasyTBSA) that calculates the TBSA of a burn using a body-part by body-part approach. The aims of this study were to assess the accuracy of the EasyTBSA application and compare its performance to three established methods of burn size estimation (Lund-Browder Chart, Rule of Nines and Rule of Palms)., Methods: Twenty-four healthcare providers used each method to estimate burn sizes on moulaged manikins. The manikins represented different ages (infant, child and adult) with different TBSA burns (small <20%, medium 20%-49% and large >49%). We calculated the accuracy of each method as the difference between the user-estimated and actual TBSA. The true value of the complete body surface area of the manikins was obtained by three-dimensional scans. We used multivariable modelling to control for manikin size and method., Results: Among all age groups and burn sizes, the EasyTBSA application had the greatest accuracy for burn size estimation (-0.01%, SD 3.59%) followed by the Rule of Palms (3.92%, SD 10.71%), the Lund-Browder Chart (4.42%, SD 5.52%) and the Rule of Nines (5.05%, SD 6.87%)., Conclusions: The EasyTBSA application may improve the estimation of TBSA compared with existing methods., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Keratoconjunctivitis sicca or dry eye disease (DED) is a multifactorial disorder underpinned by a complex inflammatory cycle. Introduction of topical cyclosporine has been a significant advance in the management of DED. In recent years advancements in formulation technology have led to development of micellar nano-particulate (MNP) cyclosporine formulations that promise better penetration into ocular target tissues and potential for reduced ocular surface irritation., Methods: We compared two dosing regimes of a proprietary MNP cyclosporine emulsion with the widely marketed topical cyclosporine formulation Restasis™ in a multicenter parallel-group randomised trial in patients with DED. Patients were randomised to one of 3 treatment groups with 90 patients eligible for the per protocol analysis: 30 in the higher dose test arm A; 32 in the lower dose test arm B; and 28 in the Restasis™ control arm C. All scored efficacy endpoints were tested for significance by comparing the mean change in scores from baseline in the test groups with that in the control group at 12 weeks, using the Student's t test. Wilcoxon's rank sum test was used to test individual symptom scores and clinician's global evaluation of treatment grades., Results: Corneal fluorescein staining score, the primary efficacy endpoint, decreased by 6.8 ± 4.0, 5.7 ± 3.9, and 4.6 ± 3.6 points in the 3 groups respectively, indicating superior efficacy in test arm A in comparison to control arm C (p = 0.0026). Schirmer's tear test, conjunctival lissamine staining score, ocular surface disease index, and individual dry eye symptom scores also favoured higher dose MNP cyclosporine over Restasis™. The study failed to differentiate the treatment arms in terms of clinician's global evaluation of treatment, use of tear substitutes, best corrected visual acuity or safety and toleration., Conclusion: The results indicate that the dose of 1 drop of a 0.05% w/v ophthalmic emulsion of MNP cyclosporine administered topically twice daily yields better outcomes at 12 weeks than the lower dose tested in the study, and is more efficacious than an equivalent dose of Restasis™, the active control used in the study., Trial Registration: This trial was registered in the Clinical Trials Registry of India on 29/03/2019, and was assigned registration number CTRI/2019/03/018319., (© 2023. The Author(s).)

Parents are at increased risk for psychological sequelae following their child's burn injury which has demonstrated negative impacts on the child. The current study sought to address gaps in the literature on risk factors for parental distress by examining the relationships among demographic variables, burn characteristics, and child functioning after burn injury, with parent post-traumatic stress symptoms (PTSS). Participants included parents of 660 pediatric burn patients from a regional burn clinic. Parents completed measures during their initial visit to the burn clinic. Additional demographic and burn data were retrospectively collected by medical chart review. Fifteen percent of parents reported at-risk levels of parent PTSS. Parent PTSS was independently associated with child burn characteristics of total body surface area (TBSA) affected by the burn, required hospitalization, number of nights hospitalized, and number of ambulatory burn appointments attended. Minority race was associated with higher parent PTSS than non-minority race status, with Asian parents endorsing the highest scores. Furthermore, when considered simultaneously, impaired child quality of life (QOL), a higher number of ambulatory burn appointments attended, and racial minority status were associated with higher parent PTSS. These findings highlight the need for routine parent trauma screening in pediatric burn clinics, while additionally identifying a feasible screening measure., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is limited and conflicting data available regarding the cardiovascular disease outcomes associated with inflammatory bowel disease (IBD)., Objective: We aim to perform a systematic review to evaluate the cardiovascular outcomes and mortality associated with IBD patients., Methods: A systematic literature search has been performed on PubMed, Embase, Cochrane, and Scopus from inception till May 2022 without any language restrictions., Results: A total of 2,029,941 patients were included in the analysis from 16 studies. The mean age of the patients was 45.6 years. More females were found compared with males (57% vs 43%). The most common risk factors for cardiovascular disease (CVD) included smoking (24.19%) and alcohol (4.60%). The most common comorbidities includes hypertension (30%), diabetes mellitus (14.41%), dyslipidemia (18.42%), previous CVD (22%), and renal disease (10%). Among outcomes, all-cause mortality among IBD patients was 1.66%; ulcerative colitis (UC): 15.92%; and Crohn disease (CD): 0.30%. Myocardial Infarction (MI) among IBD patients were 1.47%, UC: 30.96%; and CD: 34.14%. CVD events among IBD patients were 1.95%. Heart failure events among IBD patients were 5.49%, stroke events among IBD patients were 0.95%, UC: 2.63%, and CD: 2.41%, respectively., Conclusion: IBD patients are at higher risk for adverse cardiovascular outcomes, especially in women. Although there remains a lack of concrete treatment algorithms and assessment parameters that better characterize IBD risk factors, nutritional modifications and physical activity should be at the forefront of CVD prevention in IBD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Simultaneous bilateral spontaneous pneumothorax is a situation that rarely occurs. The patient can have various presentations, from dyspnoea and chest pain to significant respiratory failure. Although it causes lung collapse in nearly two thirds of cases, early diagnosis and treatment are of the utmost importance. Here, we present the case of an 18-year-old boy who presented with complaints of sudden onset respiratory distress. He was immediately put on mechanical ventilation. He was diagnosed with simultaneous bilateral spontaneous pneumothorax on chest X-ray. He needed bilateral intra-thoracic drainage, following which a video-assisted thoracoscopy was done on the left side., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Gaidhane et al.)