Most of the human genome, except for a small region that transcribes protein-coding RNAs, was considered junk. With the advent of RNA sequencing technology, we know that much of the genome codes for ...RNAs with no protein-coding potential. Long non-coding RNAs (lncRNAs) that form a significant proportion are dynamically expressed and play diverse roles in physiological and pathological processes. Precise spatiotemporal control of their expression is essential to carry out various biochemical reactions inside the cell. Intracellular organelles with membrane-bound compartments are known for creating an independent internal environment for carrying out specific functions. The formation of membrane-free ribonucleoprotein condensates resulting in intracellular compartments is documented in recent times to execute specialized tasks such as DNA replication and repair, chromatin remodeling, transcription, and mRNA splicing. These liquid compartments, called membrane-less organelles (MLOs), are formed by liquid–liquid phase separation (LLPS), selectively partitioning a specific set of macromolecules from others. While RNA binding proteins (RBPs) with low complexity regions (LCRs) appear to play an essential role in this process, the role of RNAs is not well-understood. It appears that short nonspecific RNAs keep the RBPs in a soluble state, while longer RNAs with unique secondary structures promote LLPS formation by specifically binding to RBPs. This review will update the current understanding of phase separation, physio-chemical nature and composition of condensates, regulation of phase separation, the role of lncRNA in the phase separation process, and the relevance to cancer development and progression.
Cross-reactive epitopes (CREs) are similar epitopes on viruses that are recognized or neutralized by same antibodies. The S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as ...HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated. Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses. In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined. These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize. As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2. Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2 pseudoviruses. Collectively, our observations suggest that human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile.
Unlocking Telecom Domain Knowledge Using LLMs Roychowdhury, Sujoy; Jain, Nishkarsh; Soman, Sumit
2024 16th International Conference on COMmunication Systems & NETworkS (COMSNETS),
2024-Jan.-3
Conference Proceeding
Conversational assistants have become increasingly popular as they use Large Language Models (LLMs) and Retrieval Augmented Generation (RAG) for domain context. In this work, we present an end-to-end ...solution that leverages RAG for telecom domain Question Answering (QA) on standards documents. We highlight that retrieval quality is important, along with an efficient indexing mechanism for the document embeddings. We also index images and tables for QA on standards documents. Our Telecom Knowledge Assistant is useful for handling specific queries from telecom domain experts, as well as for novice learners. The developed approach and solution are amenable to adapt for other domains as well.
Ivermectin is an antiparasitic drug which has in-vitro efficacy in reducing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load. Hence, Ivermectin is under investigation as a ...repurposed agent for treating COVID-19.
In this pilot, double blind, randomized controlled trial, hospitalized patients with mild-to-moderate COVID-19 were assigned to a single oral administration of an elixir formulation of Ivermectin at either 24 mg or 12 mg dose, or placebo in a 1:1:1 ratio. The co-primary outcomes were conversion of RT-PCR to negative result and the decline of viral load at day 5 of enrolment. Safety outcomes included total and serious adverse events. The primary outcomes were assessed in patients who had positive RT-PCR at enrolment (modified intention-to-treat population). Safety outcomes were assessed in all patients who received the intervention (intention-to-treat population).
Among the 157 patients randomized, 125 were included in modified intention-to-treat analysis. 40 patients each were assigned to Ivermectin 24 mg and 12 mg, and 45 patients to placebo. The RT-PCR negativity at day 5 was higher in the two Ivermectin arms but failed to attain statistical significance (Ivermectin 24 mg, 47.5%; 12 mg arm, 35.0%; and placebo arm, 31.1%; p-value = 0.30). The decline of viral load at day 5 was similar in each arm. No serious adverse events occurred.
In patients with mild and moderate COVID-19, a single oral administration of Ivermectin did not significantly increase either the negativity of RT-PCR or decline in viral load at day 5 of enrolment compared with placebo.
Airway management forms the foundation of any anaesthetic management. However, unanticipated difficult airway (DA) and its sequelae continue to dread any anaesthesiologist. In spite of development of ...various clinical parameters to judge DA, no single parameter has proved to be accurate in predicting it. Radiological evaluation may help assess the aspects of patient's airway not visualised through the naked eye. Starting from traditional roentgenogram to ultramodern three-dimensional printing, imaging may assist the anaesthesiologists in predicting DA and formulate plan for its management. Right from predicting DA, it has been used for estimating endotracheal tube sizes, assessing airway pathologies in paediatric patients and planning extubation strategies. This article attempts to provide exhaustive overview on radiological parameters which can be utilised by anaesthesiologists for prediction of DA.
Ultrasonographic assessment of airway Jain, Kinshuki; Yadav, Mukesh; Gupta, Nishkarsh ...
Journal of Anaesthesiology-Clinical Pharmacology/Journal of anaesthesiology clinical pharmacology,
01/2020, Volume:
36, Issue:
1
Journal Article
Peer reviewed
Open access
Ultrasound is gaining increasing popularity among anesthesiologists as it is readily available and provides real-time imaging for various procedures. It is considered as a "visual stethoscope" of the ...anesthesiologist. After establishing its use in regional blocks and central venous catheter insertion, it is now finding increasing use in anticipation of difficult airway and securing and maintaining it. It has challenged the classical approach of clinical assessment of airway and allows more dynamic bedside assessment. This article attempts to briefly outline the role of ultrasound and its applications for airway management in patients.
Background: Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by deposition of lipoproteinaceous material within alveoli, with a variable clinical course. Here, we report an ...experience of management of PAP at our center. A systematic review of previously reported cases from India is also included in the article. Materials and Methods: This study included patients with primary PAP managed at our center from 2009 to 2015. Diagnosis of primary PAP was based on histopathologic diagnosis on bronchoalveolar lavage or transbronchial lung biopsy and absence of causes of secondary PAP. For systematic review of Indian publications, the literature search was performed using PubMed and EMBASE databases using the terms "pulmonary alveolar proteinosis'" or "alveolar proteinosis" and "India" or "Indian." Results: During the above-specified period, five patients with diagnosis of PAP were admitted at our center. Median age of patients was 32 years (interquartile range IQR 30.5-59); 80% were female. Mean duration (± standard deviation) of symptoms was 6.2 (±1.79) months. Anti-granulocyte-macrophage colony stimulating factor (GM-CSF) antibodies were elevated in 4 out of 5 patients (80%). For management, whole lung lavage (WLL) was done for four patients with median volume of 32.5 (IQR 18-74) L per patient. All the patients showed significant symptomatic as well as improvement in physiological parameters. Subcutaneous GM-CSF and ambroxol were given to 3 patients and 1 patient, respectively. The median follow-up of all patients was 18 (IQR 5-44) months. A systematic review of all Indian studies of PAP revealed thirty publications. Conclusions: WLL is the most common, effective, and safe therapy in patients with PAP. GM-CSF administration is an efficacious treatment for patients with incomplete response after WLL.
The "second wave" of the COVID-19 pandemic hit India from early April 2021 to June 2021. We describe the clinical features, treatment trends, and baseline laboratory parameters of a cohort of ...patients with SARS-CoV-2 infection and their association with the outcome.
This was a retrospective cohort study. Multivariate logistic regression models were fitted to identify clinical and biochemical predictors of developing hypoxia, deterioration during the hospital stay, and death.
A total of 2080 patients were included. The case fatality rate was 19.5%. Among the survivors, the median duration of hospital stay was 8 (5-11) days. Out of 853 (42.3%%) of patients who had COVID-19 acute respiratory distress syndrome at presentation, 340 (39.9%) died. Patients aged >45 years had higher odds of death as compared to the 18-44 years age group. Vaccination reduced the odds of death by 40% (odds ratio OR 95% confidence interval CI: 0.6 0.4-0.9, P = 0.032). Patients with hyper inflammation at baseline as suggested by leukocytosis (OR 95% CI: 2.1 1.5-3.1, P < 0.001), raised d-dimer >500 mg/dL (OR 95% CI: 3.2 2.2-4.7, P < 0.001), and raised C-reactive peptide >0.5 mg/L (OR 95% CI: 3.7 2.2-13, P = 0.037) had higher odds of death. Patients who were admitted in the 2
week had lower odds and those admitted in the 3
week had higher odds of death.
This study shows that vaccination status and early admission during the inflammatory phase can change the course of illness of these patients. Improving vaccination rates and early admission of patients with moderate and severe COVID-19 can improve the outcomes.
Over the past decade, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an indispensable tool in the diagnostic armamentarium of the pulmonologist. As the ...expertise with EBUS-TBNA has evolved and several innovations have occurred, the indications for its use have expanded. However, several aspects of EBUS-TBNA are still not standardized. Hence, evidence-based guidelines are needed to optimize the diagnostic yield and safety of EBUS-TBNA. For this purpose, a working group of experts from India was constituted. A detailed and systematic search was performed to extract relevant literature pertaining to various aspects of EBUS-TBNA. The modified GRADE system was used for evaluating the level of evidence and assigning the strength of recommendations. The final recommendations were framed with the consensus of the working group after several rounds of online discussions and a two-day in-person meeting. These guidelines provide evidence-based recommendations encompassing indications of EBUS-TBNA, pre-procedure evaluation, sedation and anesthesia, technical and procedural aspects, sample processing, EBUS-TBNA in special situations, and training for EBUS-TBNA.
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