Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet+ subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c+CD80+ cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.

Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation.

Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.

Study of secondary organic aerosol formation and aging using ambient air in an oxidation flow reactor during high pollution events over Delhi.

Secondary aerosols constitute a significant fraction of atmospheric aerosols, yet our understanding of their formation mechanism and fate is very limited. In this work, the secondary organic aerosol (SOA) formation and aging of ambient air of Delhi are studied using a potential aerosol mass (PAM) reactor, an oxidation flow reactor (OFR), coupled with aerosol chemical speciation monitor (ACSM), proton transfer reaction time of flight mass spectrometer (PTR-ToF-MS), and scanning mobility particle sizer with counter (SMPS + C). The setup mimics atmospheric aging of up to several days with the generation of OH radicals. Variations in primary volatile organic compounds (VOCs) and oxygenated volatile organic compounds (OVOCs) as a function of photochemical age were investigated. Primary VOCs such as benzene, toluene, xylene, trimethyl benzene, etc. decrease and OVOCs like formic acid, formaldehyde, acetone, ethanol, etc. increase substantially upon oxidation in OFR. The highest organic aerosol (OA) enhancement was observed for the 4.2 equivalent photochemical days of aging i.e., 1.84 times the ambient concentration, and net OA loss was observed at very high OH exposure, typically after 8.4 days of photochemical aging due to heterogeneous oxidation followed by fragmentation/evaporation. In ambient air, OA enhancement is highest during nighttime due to the high concentrations of precursor VOCs in the atmosphere. SMPS + C results demonstrated substantial new particle formation upon aging and decrement in preexisting aerosol mass. This is the first experimental study conducting an in-situ evaluation of potential SOA mass generated from the ambient aerosols in India.

Carbon conundrums: Geopolitical clashes and market mayhem in the race for sustainability.

This research presents an in-depth investigation into the dynamic correlation between geopolitical conflicts and carbon markets utilizing the Time-Varying Parameter Vector Autoregression (TVP-VAR) technique. The analysis focuses on the interconnectedness between the Geopolitical Risk Index Daily (GPRD) and vital carbon pricing instruments, specifically the Intercontinental Exchange Endex European Union Allowance (ECEFDC), KraneShares California Carbon Allowance Strat ETF (KCCAK), Shanghai Environment and Energy Exchange China Emission Allowances Online Transactions (SAXCEA), and S&P Global Ex-Japan LargeMidCap Carbon Efficient Index (SPGJ). The daily fluctuations were traced from May 2021 to July 2023. The analysis is divided into short- and long-term connectedness, with particular emphasis on the impact of the Russia-Ukraine conflict on the GPRD's spillover on carbon markets. The short-term connectedness (1-5 days) between GPRD and ECEFDC shows variability, fluctuating between 10% and 40%. Conversely, long-term connectedness exhibited a significant increase during the conflict, peaking at approximately 34% by mid-2022. The analysis of the Total Dynamic Connectedness (TCI) between the GPRD and the KCCAK indicates comparable magnitudes, although with minor initial discrepancies. The short-term connectedness of GPRD and KCCAK decreases from its peak of approximately 10% to approximately 1%. Conversely, long-term connectedness varies between approximately 32% and 2% from May 2022 onwards. The long-term connectedness between GPRD and SAXCEA revealed variable patterns, peaking at around 18% at the beginning of the sample period and rapidly reducing to around 1% within two months. The analysis of the connectedness between GPRD and the SPG) identifies intense fluctuations in both TCI and long-term connectedness. After an initial increase and decrease, these patterns rebound and experience another increase. This research provides significant insights into the complex dynamics of geopolitical conflicts and carbon markets, particularly the impact of the Russia-Ukraine conflict on carbon market behavior.

Effect of glucocorticoids on the development of COVID-19-associated pulmonary aspergillosis: A meta-analysis of 21 studies and 5174 patients.

COVID-19-associated pulmonary aspergillosis (CAPA) remains a high mortality mycotic infection throughout the pandemic, and glucocorticoids (GC) may be its root cause. Our aim was to evaluate the effect of systemic GC treatment on the development of CAPA. We systematically searched the PubMed, Google Scholar, Scopus and Embase databases to collect eligible studies published until 31 December 2022. The pooled outcome of CAPA development was calculated as the log odds ratio (LOR) with 95% confidence intervals (CI) using a random effect model. A total of 21 studies with 5174 patients were included. Of these, 20 studies with 4675 patients consisting of 2565 treated with GC but without other immunomodulators (GC group) and 2110 treated without GC or other immunomodulators (controls) were analysed. The pooled LOR of CAPA development was higher for the GC group than for the controls (0.54; 95% CI: 0.22, 0.86; p < .01). In the subgroups, the pooled LOR was higher for high-dose GC (0.90; 95% CI: 0.17, 1.62: p = .01) and dexamethasone (0.71; 95% CI: 0.35, 1.07; p < .01) but had no significant difference for low-dose GC (0.41; 95% CI: -0.07, 0.89; p = .09), and non-dexamethasone GC (0.21; 95% CI: -0.36, 0.79; p = .47), treated patients versus controls. GC treatment increases the risk of CAPA development, and this risk is particularly associated with the use of high-dose GC or dexamethasone treatment.

Clinical profile and outcome of COVID-19 in haematological malignancies: experience from tertiary care centre in India.

There is limited evidence on various clinical aspects of SARS-CoV-2 infection in patients with haematological cancers. The risk factors, prognosis, and outcome of patients with haematological cancers with coexistent COVID-19 need to be explored in different subsets of population. A single-institutional prospective observational study was conducted at a tertiary level medical institute in North India. The clinical details of the recruited patients having haematological malignancies and diagnosed with COVID-19 between 15 March 2020 and 31 May 2021 were prospectively collected through the electronic patient database system. The outcomes with respect to 28-day and 56-day mortality and the associated risk factors for prognostication were analysed. Of the 5750 hospital admissions (inpatient and day-care) during the study period, two hundred and forty-two patients (4.2%) were diagnosed with COVID-19. Acute leukaemia was the most common haematological malignancy, seen in 117 (48.3%) patients. Eighty-nine (36.8%) patients had moderate-to-severe COVID-19 while 153 (63.2%) patients presented with mild infection. The 28-day and 56-day mortality rates in our cohort were 13.3% and 19.8% respectively. Amongst the risk factors associated with poor outcome, the severity of COVID-19 (HR = 1.8, 95% CI 1.16-10.35; p = 0.04), presence of secondary infection (HR = 2.1, 95% CI 2.45-21.3; p = 0.023), and need for invasive mechanical ventilation (HR = 2.3, 95% CI 1.8-18.43; p = 0.01) were prognostically significant on multivariate log rank analysis. The risk of SARS-CoV-2 infection does not increase with haematological malignancies; however, the outcome remains poor in patients with severe COVID-19, requirement of invasive mechanical ventilation, and pre-existing bacterial/fungal infection at presentation.

New insights into development and mortality of COVID-19-associated pulmonary aspergillosis in a homogenous cohort of 1161 intensive care patients.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real-world insights about the disease. METHODS: We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non-CAPA and deceased/survived CAPA patients using univariable and multivariable models. RESULTS: The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non-CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1-2.8]). Diabetes (odds ratio [OR] 1.92 [1.15-3.21]); persistent fever (2.54 [1.17-5.53]); hemoptysis (7.91 [4.45-14.06]); and lung lesions of cavitation (8.78 [2.27-34.03]), consolidation (9.06 [2.03-40.39]), and nodules (8.26 [2.39-28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09-6.55]), a high computed tomography score index (OR 1.18 [1.08-1.29]; p < .001), and pulse glucocorticoid treatment (HR 4.0 [1.3-9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03-1.15] and mortality: 1.17 [1.08-1.28]) and lymphopenia (development: 0.68 [0.51-0.91] and mortality: 0.40 [0.20-0.83]) were associated with the development as well as mortality of CAPA. CONCLUSION: We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality.

Heparan sulfate proteoglycan expression in the regenerating zebrafish fin.

BACKGROUND: Heparan sulfate proteoglycan (HSPG) expression is found in many animal tissues and regulates growth factor signaling such as of Fibroblast growth factors (Fgf), Wingless/Int (Wnt) and Hedgehog (HH). Glypicans, which are GPI (glycosylphosphatidylinositol)-anchored proteins, and transmembrane-anchored syndecans represent two major HSPG protein families whose involvement in development and disease has been demonstrated. Their participation in regenerative processes both of the central nervous system and of regenerating limbs is well documented. However, whether HSPG are expressed in regenerating zebrafish fins, is currently unknown. RESULTS: Here, we carried out a systematic screen of glypican and syndecan mRNA expression in regenerating zebrafish fins during the outgrowth phase. We find that 8 of the 10 zebrafish glypicans and the three known zebrafish syndecans show specific expression at 3 days post amputation. Expression is found in different domains of the regenerate, including the distal and lateral basal layers of the wound epidermis, the distal most blastema and more proximal blastema regions. CONCLUSIONS: HSPG expression is prevalent in regenerating zebrafish fins. Further research is needed to delineate the function of glypican and syndecan action during zebrafish fin regeneration.

Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development.

Extracellular signals play essential roles during embryonic patterning by providing positional information in a concentration-dependent manner, and many such signals, like Wnt, fibroblast growth factor (FGF), Hedgehog (Hh), and retinoic acid, act by being secreted into the extracellular space, thereby triggering receptor-mediated responses in other cells. Isthmin1 (ism1) is a secreted protein whose gene expression pattern coincides with that of early dorsal determinants, nodal ligand genes like sqt and cyc, and with fgf8 during various phases of zebrafish development. Ism1 functions in early embryonic patterning and development are poorly understood; however, it has recently been shown to interact with nodal pathway genes to control organ asymmetry in chicken. Here, we show that misexpression of ism1 deletion constructs disrupts embryonic patterning in zebrafish and exhibits genetic interactions with both Fgf and nodal signaling. Unlike Fgf and nodal pathway mutants, CRISPR/Cas9-engineered ism1 mutants did not show obvious developmental defects. Further, in vivo single molecule fluorescence correlation spectroscopy (FCCS) showed that Ism1 diffuses freely in the extra-cellular space, with a diffusion coefficient similar to that of Fgf8a; however, our measurements do not support direct molecular interactions between Ism1 and either nodal ligands or Fgf8a in the developing zebrafish embryo. Together, data from gain- and loss-of-function experiments suggest that zebrafish Ism1 plays a complex role in regulating extracellular signals during early embryonic development.

Diagnostic accuracy and feasibility of portable sleep monitoring in patients with obstructive sleep apnea: Re-exploring the utility in the current COVID-19 pandemic.

Portable sleep monitoring (PSM) is a promising alternative diagnostic tool for Obstructive Sleep Apnea (OSA) especially in high burden resource limited settings. We aimed to determine the diagnostic accuracy and feasibility of PSM device-based studies in patients presenting for evaluation of OSA at a tertiary care hospital in North-India. PSM studies (using a Type-III PSM device) were compared for technical reliability and diagnostic accuracy with the standard laboratory-based Type-I polysomnography (PSG). Patients were also interviewed about their experience on undergoing an unsupervised PSM studies. Fifty patients (68% males) were enrolled in the study, of which only 30% patients expressed their concerns about undergoing unsupervised PSM studies which included safety issues, ease of use, diagnostic accuracy, etc. Technical acceptability criteria were easily met by the PSM studies with signal loss in 12% studies (complete data loss and inaccessible data in 6% studies), warranting repetition sleep studies in four patients. The overall sensitivity of PSM device (AHI ≥5) was 93.5% (area under curve; AUC: 0.87). The diagnostic accuracy was 68.5%, 80%, and 91.4% for mild, moderate, and severe cases of OSA, respectively. An overall strong correlation was observed between PSM-AHI (apnoea-hypopnoea index) and PSG (r>0.85, p≤0.001), especially in severe OSA. The observed sensitivity was >90% for AHI>20 (clinically significant OSA), with high specificity of 91% for severe OSA (AUC: 0.94, 0.97 for AHI>20, AHI>30 respectively). The overall Bland-Altman concordance analysis also demonstrated only a small dispersion for PSM studies with a Cronbach's coefficient of 0.95. Therefore, there is good diagnostic accuracy as well as feasibility of home-based portable sleep studies in Indian patients. It can be promoted for widespread use in high burden countries like India for diagnosing and managing appropriately selected stable patients with high clinical probability of OSA, especially during the ongoing crises of COVID-19 pandemic.

VASCULAR PLANT ONE-ZINC FINGER1 (VOZ1) and VOZ2 Interact with CONSTANS and Promote Photoperiodic Flowering Transition.

In plants, endogenous and environmental signals such as light control the timing of the transition to flowering. Two phytochrome B-interacting transcription factors, VASCULAR PLANT ONE-ZINC FINGER1 (VOZ1) and VOZ2, redundantly promote flowering in Arabidopsis (Arabidopsis thaliana). In the voz1 voz2 mutant, the expression of FLOWERING LOCUS C (FLC) was up-regulated and that of FLOWERING LOCUS T (FT) was down-regulated, which was proposed to be the cause of late flowering in voz1 voz2 However, the detailed mechanism by which the VOZ genes promote flowering is not well understood. Here, we show that neither the reduced FT expression nor the late-flowering phenotype of voz1 voz2 is suppressed in the voz1 voz2 flc triple mutant. Genetic interaction experiments between voz1 voz2 and constans-2 (co-2) mutants reveal that the VOZs and CO work in the same genetic pathway. Using in vitro pull-down, electrophoretic mobility shift, and bimolecular fluorescence complementation assays, we show that VOZ1 and VOZ2 interact with CO. The voz1 voz2 35S::CO:YFP plants show suppression of the early-flowering phenotype induced by CO overexpression, suggesting that CO requires VOZ for the induction of flowering. Determination of the VOZ consensus-binding site followed by genome-wide sequence analysis failed to identify any VOZ-binding sites near known flowering time genes. Together, these results indicate that the VOZ genes regulate flowering primarily through the photoperiod pathway, independent of FLC, and suggest that VOZs modulate CO function to promote flowering.

Pharmacokinetic profiling of anticancer phytocompounds using computational approach.

INTRODUCTION: Natural products exhibit diverse scaffolds and are considered as suitable candidates for development of leads. However, poor pharmacokinetics often acts as a hindrance during the drug discovery process. OBJECTIVE: With a view of exploring the absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of plant-based anticancer compounds, open-access databases (NPACT, CancerHSP and TaxKB) were analysed to identify molecules having properties favourable for drug ability. METHODOLOGY: Our workflow involved identification of molecules capable of passing each of the ADMET barriers based on physicochemical properties of molecules, and physiological barriers and factors. RESULTS: The results revealed that out of 5086 phytomolecules, 63% were orally absorbable and 52% distributable. Also, an appreciable proportion of these compounds (45%) could be metabolised and excreted. Furthermore, 28% were found to be non-toxic for cardio toxicity and central nervous system (CNS) activity. Additionally, comparison against known anticancer drugs (reference dataset) revealed that the three libraries exhibit similar trends, thus providing additional confidence to the predictions. Overall, 28% of the molecular dataset was found to have suitable pharmacokinetic properties. We have also discussed a few natural products which exhibit favourable ADMET as well as low nano-micromolar in vitro anticancer activity. CONCLUSION: We have created an interactive database (ADMETCan), which provides access to predicted ADMET of these anticancer phytomolecules. The ease of availability of this dataset is expected to minimise failure rate of these compounds and thus is expected to be beneficial to the scientific community involved in anticancer identification and development.

Generation of a conditional lima1a allele in zebrafish using the FLEx switch technology.

Gene trapping has emerged as a valuable tool to create conditional alleles in various model organisms. Here we report the FLEx-based gene trap vector SAGFLEx that allows the generation of conditional mutations in zebrafish by gene-trap mutagenesis. The SAGFLEx gene-trap cassette comprises the rabbit ß-globin splice acceptor and the coding sequence of GFP, flanked by pairs of inversely oriented heterotypic target sites for the site-specific recombinases Cre and Flp. Insertion of the gene-trap cassette into endogenous genes can result in conditional mutations that are stably inverted by Cre and Flp, respectively. To test the functionality of this system we performed a pilot screen and analyzed the insertion of the gene-trap cassette into the lima1a gene locus. In this lima1a allele, GFP expression faithfully recapitulated the endogenous lima1a expression and resulted in a complete knockout of the gene in homozygosity. Application of either Cre or Flp was able to mediate the stable inversion of the gene trap cassette and showed the ability to conditionally rescue or reintroduce the gene inactivation. Combined with pharmacologically inducible site specific recombinases the SAGFLEx vector insertions will enable precise conditional knockout studies in a spatial- and temporal-controlled manner.

Cardiac Sympathetic Dominance and Systemic Inflammation in COPD.

Cardiac autonomic dysfunction is an independent determinant of adverse outcomes in many diseases. The available literature on the relative changes in sympathetic and parasympathetic components in chronic obstructive pulmonary disease (COPD) is equivocal, the clinical and physiological correlates are poorly defined and association with markers of systemic inflammation has not been explored. As both autonomic dysfunction and systemic inflammation may contribute to cardiovascular morbidity in COPD, we hypothesized that these may be associated. Sixty three stable patients of COPD and 36 controls underwent spirometry, estimation of diffusion capacity, six-minute walk test and measurements of serum interleukin-6 (IL-6) and high-sensitivity C-Reactive protein. Cardiac autonomic activity was evaluated by standard five-minute heart rate variability (HRV) recordings to obtain time- and frequency-domain indices and the averaged heart rate. We observed that HRV indices of overall autonomic modulation, the standard deviation of time intervals between consecutive normal beats (SDNN) and total power, were greater in patients with higher levels of indices of both parasympathetic and sympathetic activity. The heart rate was significantly higher in patients indicating an overall sympathetic dominance and was inversely correlated with diffusion capacity. Serum IL-6 was inversely correlated with pNN50, an index of parasympathetic activity, and positively with LF/HF ratio, a measure of sympathetic: parasympathetic balance. None of the HRV indices was significantly correlated with physiological measures of severity. It was concluded that patients with COPD have increased cardiac autonomic modulation with sympathetic dominance. This is associated with decreased lung diffusion capacity and systemic inflammation.

Comparing Transvaginal Ultrasound Measurements of Cervical Length to Bishop Score in Predicting Cesarean Section Following Induction of Labor: A Prospective Observational Study.

INTRODUCTION:  Bishop score (BS) has been used to see the favorability of the cervix for induction of labor (IOL), but it has limitations in today's diverse patient population. We aimed to assess the predictive value of transvaginal ultrasound (TVUS) measurements of cervical length (CL) compared to BS in determining the likelihood of cesarean section (CS) following IOL. METHODOLOGY: A prospective observational study was conducted on 120 women requiring IOL in a tertiary care hospital in central India. The inclusion criteria of the study were antenatal women more than 18 years of age, in need of IOL, having a singleton pregnancy with a gestational age of > 37 weeks as determined from the date of the last menstrual period and confirmed by sonographic measurements in the first trimester, presenting with a cephalic presentation, and having intact fetal membranes. Women with prior uterine scars and those unwilling to IOL were excluded from the study. TVUS was done just before induction. Statistical analyses were done to compare the predictive abilities of CL and BS for CS. RESULTS: The mean age and gestation period were 25.96 years and 39 weeks 3 days, respectively. The majority of the study population comprised multigravida (69, 57.5%), followed by primigravida (47, 39.2%), and grand multigravida (≥ G5) (4, 3.3%). Post-maturity (34, 28.3%), preeclampsia (21, 17.5%), and intrahepatic cholestasis of pregnancy (17, 14.2%) were common indications for induction. The overall CS rate was 35.8% (43/120). Women with CS had lower BS (3.60 vs. 4.70, P = 0.010) and higher CL (31.5 mm vs. 23.4 mm, P < 0.001). CL exhibited an area under the curve (AUC) of 0.857, outperforming BS (AUC = 0.643) in predicting CS. Using a CL cutoff of 26.5 mm yielded sensitivity (79.1%), specificity (81.8%), and overall accuracy (80.8%). CONCLUSIONS: TVUS measurement of CL (>26.5 mm) demonstrated superior predictive ability for CS following labor induction compared to BS (≤5). This study highlights the potential of CL measurement as an objective and reliable tool for optimizing decision-making in labor induction.

Biophysical modeling and diffusion kurtosis imaging reveal microstructural alterations in normal-appearing white-matter regions of the brain in obstructive sleep apnea.

Study Objectives: Studies have indicated that sleep abnormalities are a strong risk factor for developing cognitive impairment, cardiomyopathies, and neurodegenerative disorders. However, neuroimaging modalities are unable to show any consistent markers in obstructive sleep apnea (OSA) patients. We hypothesized that, compared with those of the control cohort, advanced diffusion MRI metrics could show subtle microstructural alterations in the brains of patients with OSA. Methods: Sixteen newly diagnosed patients with moderate to severe OSA and 15 healthy volunteers of the same age and sex were considered healthy controls. Multishell diffusion MRI data of the brain, along with anatomical data (T1 and T2 images), were obtained on a 3T MRI system (Siemens, Germany) after a polysomnography (PSG) test for sleep abnormalities and a behavioral test battery to evaluate cognitive and executive brain functions. Diffusion MRI data were used to compute diffusion tensor imaging and diffusion kurtosis imaging (DKI) parameters along with white-matter tract integrity (WMTI) metrics for only parallel white-matter fibers. Results: OSA was diagnosed when the patient's apnea-hypopnea index was ≥ 15. No significant changes in cognitive or executive functions were observed in the OSA cohort. DKI parameters can show significant microstructural alterations in the white-matter region, while the WMTI metric, the axonal-water-fraction (fp), reveals a significant decrease in OSA patients concerning the control cohort. Conclusions: Advanced diffusion MRI-based microstructural alterations in the white-matter region of the brain suggest that white-matter tracts are more sensitive to OSA-induced intermittent hypoxia.

NCCP-ICS joint consensus-based clinical practice guidelines on medical thoracoscopy.

ABSTRACT: Medical Thoracoscopy (MT) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. The aim of the study was to provide evidence-based information regarding all aspects of MT, both as a diagnostic tool and therapeutic aid for pulmonologists across India. The consensus-based guidelines were formulated based on a multistep process using a set of 31 questions. A systematic search of published randomized controlled clinical trials, open labelled studies, case reports and guidelines from electronic databases, like PubMed, EmBase and Cochrane, was performed. The modified grade system was used (1, 2, 3 or usual practice point) to classify the quality of available evidence. Then, a multitude of factors were taken into account, such as volume of evidence, applicability and practicality for implementation to the target population and then strength of recommendation was finalized. MT helps to improve diagnosis and patient management, with reduced risk of post procedure complications. Trainees should perform at least 20 medical thoracoscopy procedures. The diagnostic yield of both rigid and semirigid techniques is comparable. Sterile-graded talc is the ideal agent for chemical pleurodesis. The consensus statement will help pulmonologists to adopt best evidence-based practices during MT for diagnostic and therapeutic purposes.

Abnormal heart rate recovery and chronotropic incompetence on exercise in chronic obstructive pulmonary disease.

Chronotropic incompetence (CI; failure to reach the targeted heart rate (HR) on exercise) and a delayed HR recovery (HRR; ≤12 beats decline within the first minute after cessation) reflect autonomic dysfunction (AD) and predict adverse cardiac prognosis. As chronic obstructive pulmonary disease (COPD) is known to be associated with AD, we hypothesized that these patients may manifest these responses on exercise. The prevalence and predictors of these responses in COPD and their association with its severity have not been evaluated. Normoxemic, stable male patients with COPD (n = 39) and 11 healthy controls underwent lung function testing and incremental leg ergometry. HR responses were monitored during exercise and recovery to compute the HRR and CI. Of all the patients, 33 (84.6%) had at least one of the two exercise responses as abnormal, with the majority (23, 58.9%) having both an abnormal HRR and CI. The frequency of abnormal responses increased with increasing Global Initiative for Chronic Obstructive Lung Disease stage and body mass index, airflow obstruction, dyspnoea and exercise capacity index. After adjusting for smoking history and post-bronchodilator forced expiratory volume in 1 second, only a reduced diffusion capacity for carbon monoxide predicted abnormal HRR, though weakly. We concluded that abnormal HRR and CI are common in patients with COPD. These responses are observed with increasing frequency as the severity of disease increases.

The Design, Development, and Implementation of a Web-Enabled Informatics Platform to Enhance the Well-being of Individuals Aged 18-24 Years: Protocol for an Experimental Study.

BACKGROUND: Well-being is multidimensional, complex, and dynamic in nature. It is an amalgam of physical and mental health, essential for disease prevention and the promotion of a healthy life. OBJECTIVE: This study aims to explore the features that impact the well-being of individuals between 18 and 24 years of age in an Indian setting. It further aims to design, develop, and evaluate the usefulness and effectiveness of a web-based informatics platform or stand-alone intervention to enhance the well-being of individuals aged 18-24 years in an Indian setting. METHODS: This study follows a mixed method approach to identify factors influencing the well-being of individuals in the age group of 18-24 years in an Indian setting. The college-going students in this age group from the states of Uttarakhand (urban settings of Dehradun) and Uttar Pradesh (urban settings of Meerut) will be enrolled. They will be randomly allocated to the control and intervention groups. The participants in the intervention group will have access to the web-based well-being platform. RESULTS: This study will examine the factors that influence the well-being of individuals aged 18-24 years. It will also facilitate the design and development of the web-based platform or stand-alone intervention, which will enhance the well-being of individuals in the age group of 18-24 years in an Indian setting. Furthermore, the results of this study will help generate a well-being index for individuals to plan tailored interventions. The 60 in-depth interviews have been conducted as of September 30, 2022. CONCLUSIONS: The study will help understand the factors that influence the well-being of individuals. The findings of this study will help in the design and development of the web-based platform or stand-alone intervention to enhance the well-being of individuals in the age group of 18-24 years in an Indian setting. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/38632.

Development of an Artificial Intelligence-Guided Citizen-Centric Predictive Model for the Uptake of Maternal Health Services Among Pregnant Women Living in Urban Slum Settings in India: Protocol for a Cross-sectional Study With a Mixed Methods Design.

BACKGROUND: Pregnant women are considered a "high-risk" group with limited access to health facilities in urban slums in India. Barriers to using health services appropriately may lead to maternal and child mortality, morbidity, low birth weight, and children with stunted growth. With the increase in the use of artificial intelligence (AI) and machine learning in the health sector, we plan to develop a predictive model that can enable substantial uptake of maternal health services and improvements in adverse pregnancy health care outcomes from early diagnostics to treatment in urban slum settings. OBJECTIVE: The objective of our study is to develop and evaluate the AI-guided citizen-centric platform that will support the uptake of maternal health services among pregnant women seeking antenatal care living in urban slum settings. METHODS: We will conduct a cross-sectional study using a mixed methods approach to enroll 225 pregnant women aged 18-44 years, living in the urban slums of Delhi for more than 6 months, seeking antenatal care, and who have smartphones. Quantitative and qualitative data will be collected using an Open Data Kit Android-based tool. Variables gathered will include sociodemographics, clinical history, pregnancy history, dietary history, COVID-19 history, health care facility data, socioeconomic status, and pregnancy outcomes. All data gathered will be aggregated into a common database. We will use AI to predict the early at-risk pregnancy outcomes (in terms of the type of delivery method, term, and related complications) depending on the needs of the beneficiaries translating into effective service-delivery improvements in enhancing the use of maternal health services among pregnant women seeking antenatal care. The proposed research will help policy makers to prioritize resource planning, resource allocation, and the development of programs and policies to enhance maternal health outcomes. The academic research study has received ethical approval from the University Research Ethics Committee of Dehradun Institute of Technology (DIT) University, Dehradun, India. RESULTS: The study was approved by the University Research Ethics Committee of DIT University, Dehradun, on July 4, 2021. Enrollment of the eligible participants will begin by April 2022 followed by the development of the predictive model by October 2022 till January 2023. The proposed AI-guided citizen-centric tool will be designed, developed, implemented, and evaluated using principles of human-centered design that will help to predict early at-risk pregnancy outcomes. CONCLUSIONS: The proposed internet-enabled AI-guided prediction model will help identify the potential risk associated with pregnancies and enhance the uptake of maternal health services among those seeking antenatal care for safer deliveries. We will explore the scalability of the proposed platform up to different geographic locations for adoption for similar and other health conditions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/35452.