Circadian transcriptome of pancreatic adenocarcinoma unravels chronotherapeutic targets.

Pancreatic ductal adenocarcinoma (PDA) is a lethal cancer characterized by a poor outcome and an increasing incidence. A significant majority (>80%) of newly diagnosed cases are deemed unresectable, leaving chemotherapy as the sole viable option, though with only moderate success. This necessitates the identification of improved therapeutic options for PDA. We hypothesized that there are temporal variations in cancer-relevant processes within PDA tumors, offering insights into the optimal timing of drug administration - a concept termed chronotherapy. In this study, we explored the presence of the circadian transcriptome in PDA using patient-derived organoids and validated these findings by comparing PDA data from The Cancer Genome Atlas with noncancerous healthy pancreas data from GTEx. Several PDA-associated pathways (cell cycle, stress response, Rho GTPase signaling) and cancer driver hub genes (EGFR and JUN) exhibited a cancer-specific rhythmic pattern intricately linked to the circadian clock. Through the integration of multiple functional measurements for rhythmic cancer driver genes, we identified top chronotherapy targets and validated key findings in molecularly divergent pancreatic cancer cell lines. Testing the chemotherapeutic efficacy of clinically relevant drugs further revealed temporal variations that correlated with drug-target cycling. Collectively, our study unravels the PDA circadian transcriptome and highlights a potential approach for optimizing chrono-chemotherapeutic efficacy.

Putative rhamnogalacturonan-II glycosyltransferase identified through callus gene editing bypasses embryo lethality.

Rhamnogalacturonan II (RG-II) is a structurally complex and conserved domain of the pectin present in the primary cell walls of vascular plants. Borate crosslinking of RG-II is required for plants to grow and develop normally. Mutations that alter RG-II structure also affect crosslinking and are lethal or severely impair growth. Thus, few genes involved in RG-II synthesis have been identified. Here we developed a method to generate viable loss-of-function Arabidopsis (Arabidopsis thaliana) mutants in callus tissue via CRISPR/Cas9-mediated gene editing. We combined this with a candidate gene approach to characterize the male gametophyte defective 2 (MPG2) gene that encodes a putative family GT29 glycosyltransferase. Plants homozygous for this mutation do not survive. We showed that in the callus mutant cell walls, RG-II does not crosslink normally because it lacks 3-deoxy-D-manno-octulosonic acid (Kdo) and thus cannot form the α-L-Rhap-(1→5)-α-D-kdop-(1→ sidechain. We suggest that MGP2 encodes an inverting RG-II CMP-ß-Kdo transferase (RCKT1). Our discovery provides further insight into the role of sidechains in RG-II dimerization. Our method also provides a viable strategy for further identifying proteins involved in the biosynthesis of RG-II.

Emerging trends in biomedical trait-based human identification: A bibliometric analysis.

Personal human identification is a crucial aspect of modern society with applications spanning from law enforcement to healthcare and digital security. This bibliometric paper presents a comprehensive analysis of recent advances in personal human identification methodologies focusing on biomedical traits. The paper examines a diverse range of research articles, reviews, and patents published over the last decade to provide insights into the evolving landscape of biometric identification techniques. The study categorizes the identified literature into distinct biomedical trait categories, including but not limited to, fingerprint and palmprint recognition, iris and retinal scanning, facial recognition, voice and speech analysis, gait recognition, and DNA-based identification. Through systematic analysis, the paper highlights key trends, emerging technologies, and interdisciplinary collaborations in each category, revealing the interdisciplinary nature of research in this field. Furthermore, the bibliometric analysis examines the geographical distribution of research efforts, identifying prominent countries and institutions contributing to advancements in personal human identification. Collaboration networks among researchers and institutions are visualized to depict the knowledge flow and collaborative dynamics within the field. Overall, this study serves as a valuable reference for researchers, practitioners, and policymakers, shedding light on the current status and potential future directions of personal human identification leveraging biomedical traits.

Venous pathology targeted surgical management in Hirayama disease: A comprehensive case series of nine cases exploring this potential etiology.

Objective: Hirayama disease is a rare cause of cervical myelopathy predominantly affecting young individuals. The disease is classically characterized by muscle atrophy in the distal upper limbs. While various etiopathogenesis such as dural sac dysplasia, nerve root dysplasia, structural abnormalities of the spinal ligament, and venous dysplasia have been proposed, this study explores the potential role of venous pathology and surgical management on the basis of it. Methodology: This is a prospective descriptive case series of nine cases. The diagnosis was made based on the Huashan diagnostic criteria which includes clinical manifestation, imaging, and electrophysiology. In cases where magnetic resonance imaging (MRI) failed to demonstrate engorged veins, a computed tomography (CT) venogram of the cervical spine was used as an imaging tool. All patients underwent cervical laminectomy and coagulation of the posterior epidural venous plexus with or without laminoplasty. All the patients were followed up regularly; clinical improvement and neck disability index were assessed. Results: All nine patients were male and exhibited classical clinical features, electrophysiological abnormalities, and MRI findings except, in one patient where a CT venogram helped in establishing the diagnosis as the MRI was inconclusive. Postoperatively, all patients had neurological improvement and stabilization of the disease. All patients who underwent CT venogram and cervical spine X-ray in neutral and dynamic position demonstrated no recurrence of engorged venous plexus or significant instability except one patient developing kyphosis. One patient experiencing symptoms in the other limb underwent a second surgery. Conclusion: This comprehensive case series strongly supports venous pathology as a potential etiology of Hirayama disease. Surgical management with laminectomy and venous coagulation with or without expansile laminoplasty has delivered consistent improvement in neurological outcomes and long-term disease stabilization without the restriction of movements and lesser complications. However, further research is warranted to elucidate the mechanism underlying cervical venous dilatation.

A Comprehensive Review on Exploring the Impact of Telemedicine on Healthcare Accessibility.

Telemedicine has emerged as a transformative force in healthcare delivery, particularly in improving healthcare accessibility. This comprehensive review examines the impact of telemedicine on healthcare accessibility, exploring its ability to overcome geographical, financial, sociocultural, and infrastructural barriers to healthcare access. Through remote consultations, monitoring, and diagnosis facilitated by technology, telemedicine extends healthcare reach to remote and underserved areas while enhancing temporal accessibility with round-the-clock availability. By streamlining healthcare delivery systems, telemedicine reduces costs and promotes efficiency, ultimately fostering health equity and improving health outcomes. However, technological barriers, regulatory hurdles, and patient acceptance remain. To realize telemedicine's full potential, collaboration among stakeholders in the healthcare and technology sectors is imperative. Policymakers must enact supportive regulations, healthcare providers must integrate telemedicine into their practices, and technology companies must innovate to develop user-friendly platforms. Through concerted efforts, telemedicine can catalyze advancing healthcare accessibility and enhance the health and well-being of individuals worldwide.

Protobothrops jerdonii (Jerdon's pit viper) and Protobothrops himalayanus (Himalayan lance-headed pit viper) bites: Clinical report on envenomings from North-East India, managed through remote consultation by a national-level Poison control center.

Members of the genus Protobothrops are amongst the more than twenty-eight range-restricted Indian pit viper species. Their bites and envenomings are rarely documented from India. Pit viper envenomings can be challenging to treat in the Indian setting, since available antivenoms do not satisfactorily neutralize their venoms. Herein, we present the first Indian reports on bites and envenoming by Protobothrops jerdonii and Protobothrops himalayanus resulting in local effects, coagulopathy and acute kidney injury in the case of the former and possible mild, isolated coagulopathy in the case of the latter; and discuss management-related challenges in the context of absent specific antivenoms.

Effects of Vitamin D and E Supplementation on Prevention of Bronchopulmonary Dysplasia (BPD) in Premature Neonates: A Systematic Review and Meta-Analysis.

BACKGROUND: Bronchopulmonary Dysplasia (BPD) has a multifactorial etiology. Vitamin E and vitamin D play an important role in lung development and can potentially be beneficial in the prevention of BPD. OBJECTIVE: The study aimed to compare the risk of BPD occurrence in preterm neonates supplemented with vitamin D or E versus those who did not get supplementation. METHODS: The literature search was conducted for this systematic review by searching the PubMed, Scopus, and Web of Science databases up to December 2022. Randomized controlled trials involved administering vitamin D or E to preterm neonates and examining the occurrence of BPD. We excluded non-English articles, and articles with non-relevant and insufficient data. We used the Critical Appraisal Skills Programme (CASP) checklist to assess the quality of the included studies. We used Egger's test to evaluate the risk of bias among the included studies. Heterogeneity was also assessed through Q-test and I2. We applied the random effect model for analysis. A P-value less than 0.05 was considered as significant. All the statistical analysis in the current study was performed using STATA 14. The Relative Risk (RR) was calculated as the effect size with 95% Confidence Interval (CI). RESULTS: Three eligible studies seeking the role of vitamin D in the prevention of BPD were analysed. Meta-analysis revealed that receiving vitamin D supplementation can significantly reduce the risk of BPD in preterm infants (RR = 0.357, 95% CI: 0.189-0.675, I2 = 0.0%; p = 0.002). Similarly, for assessing the role of Vitamin E in the prevention of BPD, three eligible studies were analysed. Vitamin E supplementation was not found to play a significant role in the reduction of BPD (RR = 0.659, 95%CI = 0.243-1.786, I2 = 38.7%; p = 0.412). CONCLUSION: Vitamin D supplementation could be beneficial in preventing BPD in preterm infants. However, evidence is not enough regarding vitamin E's role in reducing the incidence of BPD in preterm infants.

Connecting Health and Technology: A Comprehensive Review of Social Media and Online Communities in Healthcare.

This review provides an in-depth analysis of the intersection between health and technology, focusing specifically on social media's and online communities' role in healthcare. It explores the significance of these digital platforms in patient education, empowerment, and support, highlighting their potential to improve healthcare delivery and patient outcomes. Key findings are synthesized by examining existing literature, including the wide-reaching impact of social media on health information dissemination and the value of online communities in facilitating peer support. However, privacy concerns and misinformation are also addressed, emphasizing the need for careful consideration and strategic implementation of these technologies. The implications for healthcare practice and research are discussed, with recommendations for future actions and priorities outlined. Overall, this review underscores the transformative potential of social media and online communities in reshaping the healthcare landscape. It also highlights the importance of ethical and responsible use to maximize benefits.

Antioxidant Defense and Ionic Homeostasis Govern Stage-Specific Response of Salinity Stress in Contrasting Rice Varieties.

Salt stress is one of the most severe environmental stresses limiting the productivity of crops, including rice. However, there is a lack of information on how salt-stress sensitivity varies across different developmental stages in rice. In view of this, a comparative evaluation of contrasting rice varieties CSR36 (salt tolerant) and Jaya (salt sensitive) was conducted, wherein NaCl stress (50 mM) was independently given either at seedling (S-stage), tillering (T-stage), flowering (F-stage), seed-setting (SS-stage) or throughout plant growth, from seedling till maturity. Except for S-stage, CSR36 exhibited improved NaCl stress tolerance than Jaya, at all other tested stages. Principal component analysis (PCA) revealed that the improved NaCl stress tolerance in CSR36 coincided with enhanced activities/levels of enzymatic/non-enzymatic antioxidants (root ascorbate peroxidase for T- (2.74-fold) and S+T- (2.12-fold) stages and root catalase for F- (5.22-fold), S+T- (2.10-fold) and S+T+F- (2.61-fold) stages) and higher accumulation of osmolytes (shoot proline for F-stage (5.82-fold) and S+T+F- (2.31-fold) stage), indicating better antioxidant capacitance and osmotic adjustment, respectively. In contrast, higher shoot accumulation of Na+ (14.25-fold) and consequent increase in Na+/K+ (14.56-fold), Na+/Mg+2 (13.09-fold) and Na+/Ca+2 (8.38-fold) ratio in shoot, were identified as major variables associated with S-stage salinity in Jaya. Higher root Na+ and their associated ratio were major deriving force for other stage specific and combined stage salinity in Jaya. In addition, CSR36 exhibited higher levels of Fe3+, Mn2+ and Co3+ and lower Cl- and SO42-, suggesting its potential to discriminate essential and non-essential nutrients, which might contribute to NaCl stress tolerance. Taken together, the findings provided the framework for stage-specific salinity responses in rice, which will facilitate crop-improvement programs for specific ecological niches, including coastal regions.

Lesions Misdiagnosed as Endodontic Pathosis: A Narrative Review.

In daily practice, clinicians come across certain radiographic abnormalities which may or may not be asymptomatic. This abstract discusses radiographic abnormalities encountered by clinicians in daily practice, some of which resemble endodontic lesions. Prompt attention is crucial as these lesions can be benign or malignant. The article emphasizes the importance of differential diagnosis for accurate identification of periapical pathosis.

Immunomodulation by juglone alleviates acute graft-versus-host disease without compromising the graft-versus-leukaemia activity in mice.

BACKGROUND AND PURPOSE: Acute graft-versus-host disease (GVHD) remains a major barrier to successful transplantation outcomes. Recent studies have shown that pharmacotherapy for GVHD should target both the innate and adaptive inflammatory immune responses. Juglone, a redox-active phytochemical found in walnuts, has shown potent anti-inflammatory effects in models of colitis and inflammatory bowel disease. However, its effects on T-cell-mediated immune responses remain largely unknown. Considering the overlapping mediators of inflammation in GVHD and the aforementioned conditions, we investigated the use of juglone as a prophylactic agent for GVHD. EXPERIMENTAL APPROACH: Immunomodulatory activity and mechanism of action of juglone were studied using murine splenic leukocytes in vitro. The GVHD prophylactic efficacy of orally administered juglone was evaluated using a murine model of allogeneic haematopoietic stem cell transplantation based on an MHC mismatch. KEY RESULTS: Juglone exhibited immunomodulatory activity by (i) inhibiting the activation of dendritic cells and CD4+ T-cells, (ii) inhibiting cytokine secretion and lymphocyte proliferation, and (iii) inducing exhaustion of CD4+ T-cells, as shown by increased expression of CTLA-4 (CD152) and Fas (CD95). Oral administration of juglone significantly reduced mortality and morbidity associated with GVHD while maintaining graft-versus-leukaemia activity. This was accompanied by a decrease in the number of naïve CD4+ cells, and an increase in the number of CD4+ and CD8+ central memory T-cells. CONCLUSION AND IMPLICATIONS: Juglone is a potent immunomodulator for GVHD prophylaxis. Our study is the first to provide a dosage framework for the oral administration of juglone that can be used for clinical development.

Txnrd1 as a prognosticator for recurrence, metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patients.

Thioredoxin reductase 1 (Txnrd1) is known to have prognostic significance in a subset of breast cancer patients. Despite the pivotal role of Txnrd1 in regulating several cellular and physiological processes in cancer progression and metastasis, its clinical significance is largely unrecognized. Here, we undertook a retrospective comprehensive meta-analysis of 13,322 breast cancer patients from 43 independent cohorts to assess prognostic and predictive roles of Txnrd1. We observed that Txnrd1 has a positive correlation with tumor grade and size and it is over-expressed in higher-grade and larger tumors. Further, hormone receptor-negative and HER2-positive tumors exhibit elevated Txnrd1 gene expression. Patients with elevated Txnrd1 expression exhibit significant hazards for shorter disease-specific and overall survival. While Txnrd1 has a positive correlation with tumor recurrence and metastasis, it has a negative correlation with time to recurrence and metastasis. Txnrd1High patients exhibit 2.5 years early recurrence and 1.3 years early metastasis as compared to Txnrd1Low cohort. Interestingly, patients with high Txnrd1 gene expression exhibit a pathologic complete response (pCR) to neoadjuvant chemotherapy, but they experience early recurrence after radiotherapy. Txnrd1High MDA-MB-231 cells exhibit significant ROS generation and reduced viability after doxorubicin treatment compared to Txnrd1Low MCF7 cells. Corroborating with findings from meta-analysis, Txnrd1 depletion leads to decreased survival, enhanced sensitivity to radiation induced killing, poor scratch-wound healing, and reduced invasion potential in MDA-MB-231 cells. Thus, Txnrd1 appears to be a potential predictor of recurrence, metastasis and therapy response in breast cancer patients.

Antibiotic resistance and virulence genes profile of Non typhodial Salmonella species isolated from poultry enteritis in India.

Salmonella species (spp) is the most important gastrointestinal pathogen present ubiquitously. Non typhoidal Salmonella (NTS) is commonly associated with gastroenteritis in humans. Layer birds once get infection with NTS, can become persistently infected with Salmonella Typhimurium and intermittently shed the bacteria. It results in a high risk of potential exposure of eggs to the bacteria. The current study was conducted to determine the serotype diversity, presence of virulence genes, antibiotic resistance pattern, and genes of NTS from poultry enteritis. Out of 151 intestinal swabs from poultry total 118 NTS were isolated, which were characterized serologically as S. Typhimurium (51 strains), S. Weltevreden (57 strains) and untypable (10 strains). Most effective antibiotics were amikacin, gentamycin and ceftriaxone (33.05%) followed by ampicillin, azithromycin and ciprofloxacin (16.69%), co-trimoxazole (13.55%), and tetracycline (6.78%). Multidrug resistance recorded in 17.70% (N = 21/118) strains. Antimicrobial-resistant genes i.e. blaTEM, blaSHV, blaCTX-M, tet(A), tet(B), tet(C), sul1, sul2, sul3. blaTEM and tet(A) were present in 95% (20/21). Eleven virulence genes i.e. invA, hilA, sivH, tolC, agfA, lpfA, spaN, pagC, spiA, iroN and fliC 2 were present in all the 30 isolates. While, sopE was present in only 2 isolates, NTS strains with characteristics of pathogenicity and multidrug resistance from poultry enteritis were detected. Multidrug resistance showed the necessity of prudent use of antibiotics in the poultry industry.

Variability in Intraoperative Opioid and Nonopioid Utilization During Intracranial Surgery: A Multicenter, Retrospective Cohort Study.

BACKGROUND: Key goals during intracranial surgery are to facilitate rapid emergence and extubation for early neurologic evaluation. Longer-acting opioids are often avoided or administered at subtherapeutic doses due to their perceived risk of sedation and delayed emergence. However, inadequate analgesia and increased postoperative pain are common after intracranial surgery. In this multicenter study, we describe variability in opioid and nonopioid administration patterns in patients undergoing intracranial surgery. METHODS: This was a multicenter, retrospective observational cohort study using the Multicenter Perioperative Outcomes Group database. Opioid and nonopioid practice patterns in 31,217 cases undergoing intracranial surgery across 11 institutions in the United States are described. RESULTS: Across all 11 institutions, total median [interquartile range] oral morphine equivalents, normalized to weight and anesthesia duration was 0.17 (0.08 to 0.3) mg.kg.min-1. There was a 7-fold difference in oral morphine equivalents between the lowest (0.05 [0.02 to 0.13] mg.kg.min-1) and highest (0.36 [0.18 to 0.54] mg.kg.min-1) prescribing institutions. Patients undergoing supratentorial surgery had higher normalized oral morphine equivalents compared with those having infratentorial surgery [0.17 [0.08-0.31] vs. 0.15 [0.07-0.27] mg/kg/min-1; P<0.001); however, this difference is clinically small. Nonopioid analgesics were not administered in 20% to 96.8% of cases across institutions. CONCLUSION: This study found wide variability for both opioid and nonopioid utilization at an institutional level. Future work on practitioner-level opioid and nonopioid use and its impact on outcomes after intracranial surgery should be conducted.

Identification of miR-29a as a novel biomarker for lumpy skin disease virus exposure in cattle.

Micro RNAs (miRNAs) have been implicated in the regulation of maturation, proliferation, differentiation, and activation of immune cells. In this study, we demonstrated that miR-29a antagonizes IFN-γ production at early times post-LSDV infection in cattle. miR-29a was predicted to target upstream IFN-γ regulators, and its inhibition resulted in enhanced IFN-γ production in sensitized peripheral blood mononuclear cells (PBMCs). Further, stimulation of PBMCs with LSDV antigen exhibited lower levels of miR-29a, concomitant with a potent cell-mediated immune response (CMI), characterized by an increase in LSDV-specific CD8+ T cell counts and enhanced levels of IFN-γ, which eventually facilitated virus clearance. In addition, a few immunocompromised cattle (developed secondary LSDV infection at ~ 6 months) that failed to mount a potent cell-mediated immune response, were shown to maintain higher miR-29a levels. Furthermore, as compared to the sensitized crossbred cattle, PBMCs from sensitized Rathi (a native Indian breed) animals exhibited lower levels of miR-29a along with an increase in CD8+ T cell counts and enhanced levels of IFN-γ. Finally, we analysed that a ≥ 60% decrease in miR-29a expression levels in the PBMCs of sensitized cattle correlated with a potent CMI response. In conclusion, miR-29a expression is involved in antagonizing the IFN-γ response in LSDV-infected cattle and may serve as a novel biomarker for the acute phase of LSDV infection, as well as predicting the functionality of T cells in sensitized cattle. In addition, Rathi cattle mount a more potent CMI response against LSDV than crossbred cattle.

Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice.

Introduction: Aging studies in humans and mice have played a key role in understanding the intestinal microbiome and an increased abundance of "inflammaging" Gram-negative (Gn) bacteria. The mechanisms underlying this inflammatory profile in the aging microbiome are unknown. We tested the hypothesis that an aging-related decrease in colonic crypt epithelial cell anti-microbial peptide (AMP) gene expression could promote colonic microbiome inflammatory Gn dysbiosis and inflammaging. Methods: As a model of aging, C57BL/6J mice fecal (colonic) microbiota (16S) and isolated colonic crypt epithelial cell gene expression (RNA-seq) were assessed at 2 months (mth) (human: 18 years old; yo), 15 mth (human: 50 yo), and 25 mth (human: 84 yo). Informatics examined aging-related microbial compositions, differential colonic crypt epithelial cell gene expressions, and correlations between colonic bacteria and colonic crypt epithelial cell gene expressions. Results: Fecal microbiota exhibited significantly increased relative abundances of pro-inflammatory Gn bacteria with aging. Colonic crypt epithelial cell gene expression analysis showed significant age-related downregulation of key AMP genes that repress the growth of Gn bacteria. The aging-related decrease in AMP gene expressions is significantly correlated with an increased abundance in Gn bacteria (dysbiosis), loss of colonic barrier gene expression, and senescence- and inflammation-related gene expression. Conclusion: This study supports the proposed model that aging-related loss of colonic crypt epithelial cell AMP gene expression promotes increased relative abundances of Gn inflammaging-associated bacteria and gene expression markers of colonic inflammaging. These data may support new targets for aging-related therapies based on intestinal genes and microbiomes.

The Influence of Nickel-Titanium (Ni-Ti) Rotary Instrument Systems on Debris and Smear Layer Formation in Endodontic Procedures: An In Vitro Scanning Electron Microscopy Study.

Background Successful endodontic treatment relies on the effective removal of debris and the prevention of smear layer formation within the root canals. The choice of nickel-titanium (Ni-Ti) rotary instrument systems can significantly impact these outcomes. Aim This study aims to evaluate and compare the debris and smear layer formation in root canals of extracted mandibular second premolar teeth following instrumentation with the ProTaper Universal (Dentsply Sirona, Charlotte, NC) (Group II), Twisted File (Kerr Endodontics, Gilbert, AZ) (Group III), and XP Endo (FKG Dentaire, La Chaux-de-Fonds, Switzerland) (Group IV) Ni-Ti rotary instrument systems. Methods In this in vitro study, 60 extracted mandibular second premolar teeth were randomly divided into four groups, each containing 15 teeth. Group I served as the control with no instrumentation. Groups II, III, and IV were instrumented with the ProTaper Universal rotary file, the Twisted File, and the XP Endo file systems, respectively. Debris and smear layer formation were evaluated through scanning electron microscopy (SEM), and photomicrographs were scored using a standardized index. Results Group II (ProTaper) exhibited the highest mean debris and smear layer scores, with values of 3.50 and 2.70, respectively. Group IV (XP Endo) demonstrated the least debris and smear layer formation, with mean scores of 2.65 and 2.08, respectively. Statistical analysis confirmed significant differences among the groups for both debris and smear layer formation. Conclusion The results highlight the practical importance of selecting appropriate Ni-Ti rotary instrument systems to minimize debris and smear layer formation during endodontic procedures. The XP Endo file system showed promise as a favorable choice in this regard, but further clinical research is needed to validate these findings.

Assessing the effectiveness and safety of transbronchial lung cryobiopsy utilizing a flexible bronchoscope with an endobronchial blocker in diffuse parenchymal lung lesions.

Transbronchial lung cryobiopsy (TBLC) with flexible bronchoscope represents an encouraging modality to obtain a larger size specimen without crush artifact, and a higher diagnostic yield in patients with diffuse parenchymal lung lesions/diseases as compared to conventional transbronchial lung biopsy, and fewer complications as opposed to surgical lung biopsy. Artificial airway is preferred as it provides better airway protection in cases of severe bleeding. Although various researchers have published data on different modalities, the data is not sufficient to standardize a single technique. This study describes the procedural technique, safety, and yield of TBLC using a flexible bronchoscope with an endobronchial blocker. We performed a retrospective analysis of 100 consecutive patients who underwent TBLC using flexible bronchoscopy from May 2018 to June 2022. TBLC samples were obtained under moderate sedation without the use of artificial airway or fluoroscopy. Among the 100 patients, the majority were male (63%). The mean age of the enrolled patients was 44.43±15.92 years. The predominant diagnoses in our study were hypersensitivity pneumonitis (27%), followed by sarcoidosis (12%) and tuberculosis (10%). We obtained alveolated lung tissue in 90 out of 100 cases with a median biopsy size of 5 mm (in greatest dimension, interquartile range 5-4 mm), resulting in a specific histopathological diagnosis in 82 cases. The most frequent complications were bleeding and pneumothorax (13%). Mild bleeding occurred in 58% of the patients, and moderate bleeding occurred in 20% of the patients. There was no episode of severe/life-threatening bleeding. None of the patients required intensive care unit admission or endotracheal intubation. In conclusion, the use of TBLC through flexible bronchoscopy with an endobronchial blocker emerges as a minimally invasive, secure, time-efficient, and readily reproducible technique. Significantly, this procedure can be seamlessly executed in the bronchoscopy suite, eliminating the requirement for an artificial airway or general anesthesia.