Long term analysis of air quality parameters for Ludhiana, India: sources, trends and health impact.

Ludhiana, a pollution hot spot in North India, has seen a rapid deterioration in air quality over the years due to urbanization and industrialization. This study interprets the variations of particulate matter (PM) and gaseous pollutants (Nitrogen oxide, Nitrogen dioxide, NOX, Sulphur dioxide, Carbon monoxide, Benzene, Toluene, Ozone, and Ammonia) for the data observed from 2017 to 2023 in Ludhiana. This also covers the analysis focused on capturing the changes that occurred at the times of lockdown imposed during the Coronavirus Disease (COVID-19). The maximum 24-h averaged mass concentration values exceeded the National Ambient Air Quality Standards (NAAQS) of 100 µg/m3 for PM10 concentration and 60 µg/m3 for PM2.5 concentration in 2018 by the factor of 5 and 8. With the onset of the COVID-19 lockdown in 2020 year, PM10 and PM2.5 reached the minimum level while CO, T, O3, and NO2 increased by the factor of 3.9, 1.9, 1.4, and 1.3 from their previous year. This NO2 is a precursor of ozone formation, a higher NO2 to NO ratio observed during the lockdown, confirms the role of nitrogen compounds in the higher ozone formation rate. Based on the NO2/NO ratio, the probability rate of ozone formation determined using survival analysis is observed to be 94% from 2017 to 2023. The local sources' contribution to these air pollutants during Pre-Lockdown, Lockdown, and Post-Lockdown are analyzed using principal component analysis. The impact of the lockdown on ozone concentration sources has been observed. During the Pre- and Post-Lockdown phases, three sources (PC1, PC2, and PC3) were positively identified. Ozone levels are linked to PC3 in these phases, but during the lockdown, a negative loading in PC3 and positive loadings in PC1 and PC2 indicate a decrease in ozone from reduced emissions and an increase from secondary reactions involving nitrogen compounds. Moreover, the Toluene to Benzene concentration ratio is > 2, indicating the source of their origin from industrial emission or other non-traffic sources. Health assessment for the years 2017-2019 reveals a significant decrease in the number of cases of all-cause mortality, ischemic heart disease, stroke, and chronic obstructive pulmonary disease associated with reducing PM2.5 concentrations to national and international standards.

An electroporation cytometry system for long-term, live cell cycle analysis.

Electric fields are used in biology to address a broad range of questions and through a variety of techniques, including electroporation, gene electrotransfer (GET), electrostimulation (ES), and electrochemotherapy. Each of these modalities requires specific conditions and has drastically different target outcomes on the cell. ES has demonstrated that non-pore forming electric fields alter cell cycle progression. However, pore forming electric fields such as with GET have not been as widely explored despite major clinical advancements. Additionally, the real-time visual analysis of electrical field effects on mammalian cell culture is currently lacking among most commercial systems. To facilitate investigations into these research areas, an electroporation cytometry system was developed including a custom chamber compatible with live cell imaging and exponential decay pulse generator for live cell analysis. The functionality of the system was demonstrated using a recombinant cell line using U-2 OS cells and FUCCI(CA)5 cell cycle reporter. The exposure of the cells to a 180 V pulse in both unsynchronized and synchronized populations revealed an effect on the cell cycle.

Long term measurements of aerosol mass concentration with optical particle counters: Discrepancies with plausible reasons.

Gravimetry-based direct measurements of mass concentration require offline analysis which is not suited for field campaigns. Hence such campaigns rely on the estimation of mass concentration by indirect methods mostly calibrated in controlled laboratory conditions. Optical particle counter (OPC) employs algorithms converting the measured number concentration to mass concentration using appropriate conversion factors. The accuracy of such conversion has not been validated for widely varying atmospheric conditions. This study compares the mass concentration estimated by OPC with those directly obtained from gravimetry-based instruments for outdoor samples collected in Bathinda City, Punjab, India from January 2022 to November 2023. The difference in the gravimetrically measured and OPC predicted values quantified in terms of ratios (gravimetric to optically estimated mass concentration), came out to be 1.42 ± 0.77, 0.99 ± 0.51, and 1.17 ± 0.58 for PM10, PM2.5 and PM1, respectively. This difference when estimated with the back-up filter of OPC itself (C Factor), was 1.37 ± 0.66. More than half of the samples showed ratios outside the 0.8-1.2 range thus indicating under or over-estimation in the OPC predicted values. The probable role of variation in density, shape, and refractive index of atmospheric aerosol particles towards the observed inaccuracy of estimated mass concentration has been highlighted. In the absence of clear guidelines and protocols, the study suggests ways to improve the accuracy via periodic measurement of the C Factor and/or incorporating calibration factors in such measurements.

Unveiling potential inhibitors targeting the nucleocapsid protein of SARS-CoV-2: Structural insights into their binding sites.

The Nucleocapsid (N) protein of SARS-CoV-2 plays a crucial role in viral replication and pathogenesis, making it an attractive target for developing antiviral therapeutics. In this study, we used differential scanning fluorimetry to establish a high-throughput screening method for identifying high-affinity ligands of N-terminal domain of the N protein (N-NTD). We screened an FDA-approved drug library of 1813 compounds and identified 102 compounds interacting with N-NTD. The screened compounds were further investigated for their ability to inhibit the nucleic-acid binding activity of the N protein using electrophoretic mobility-shift assays. We have identified three inhibitors, Ceftazidime, Sennoside A, and Tannic acid, that disrupt the N protein's interaction with RNA probe. Ceftazidime and Sennoside A exhibited nano-molar range binding affinities with N protein, determined through surface plasmon resonance. The binding sites of Ceftazidime and Sennoside A were investigated using [1H, 15N]-heteronuclear single quantum coherence (HSQC) NMR spectroscopy. Ceftazidime and Sennoside A bind to the putative RNA binding site of the N protein, thus providing insights into the inhibitory mechanism of these compounds. These findings will contribute to the development of novel antiviral agents targeting the N protein of SARS-CoV-2.

Health facility assessment of small and sick newborn care in low- and middle-income countries: systematic tool development and operationalisation with NEST360 and UNICEF.

BACKGROUND: Each year an estimated 2.3 million newborns die in the first 28 days of life. Most of these deaths are preventable, and high-quality neonatal care is fundamental for surviving and thriving. Service readiness is used to assess the capacity of hospitals to provide care, but current health facility assessment (HFA) tools do not fully evaluate inpatient small and sick newborn care (SSNC). METHODS: Health systems ingredients for SSNC were identified from international guidelines, notably World Health Organization (WHO), and other standards for SSNC. Existing global and national service readiness tools were identified and mapped against this ingredients list. A novel HFA tool was co-designed according to a priori considerations determined by policymakers from four African governments, including that the HFA be completed in one day and assess readiness across the health system. The tool was reviewed by > 150 global experts, and refined and operationalised in 64 hospitals in Kenya, Malawi, Nigeria, and Tanzania between September 2019 and March 2021. RESULTS: Eight hundred and sixty-six key health systems ingredients for service readiness for inpatient SSNC were identified and mapped against four global and eight national tools measuring SSNC service readiness. Tools revealed major content gaps particularly for devices and consumables, care guidelines, and facility infrastructure, with a mean of 13.2% (n = 866, range 2.2-34.4%) of ingredients included. Two tools covered 32.7% and 34.4% (n = 866) of ingredients and were used as inputs for the new HFA tool, which included ten modules organised by adapted WHO health system building blocks, including: infrastructure, pharmacy and laboratory, medical devices and supplies, biomedical technician workshop, human resources, information systems, leadership and governance, family-centred care, and infection prevention and control. This HFA tool can be conducted at a hospital by seven assessors in one day and has been used in 64 hospitals in Kenya, Malawi, Nigeria, and Tanzania. CONCLUSION: This HFA tool is available open-access to adapt for use to comprehensively measure service readiness for level-2 SSNC, including respiratory support. The resulting facility-level data enable comparable tracking for Every Newborn Action Plan coverage target four within and between countries, identifying facility and national-level health systems gaps for action.

Quantifying health facility service readiness for small and sick newborn care: comparing standards-based and WHO level-2 + scoring for 64 hospitals implementing with NEST360 in Kenya, Malawi, Nigeria, and Tanzania.

BACKGROUND: Service readiness tools are important for assessing hospital capacity to provide quality small and sick newborn care (SSNC). Lack of summary scoring approaches for SSNC service readiness means we are unable to track national targets such as the Every Newborn Action Plan targets. METHODS: A health facility assessment (HFA) tool was co-designed by Newborn Essential Solutions and Technologies (NEST360) and UNICEF with four African governments. Data were collected in 68 NEST360-implementing neonatal units in Kenya, Malawi, Nigeria, and Tanzania (September 2019-March 2021). Two summary scoring approaches were developed: a) standards-based, including items for SSNC service readiness by health system building block (HSBB), and scored on availability and functionality, and b) level-2 + , scoring items on readiness to provide WHO level-2 + clinical interventions. For each scoring approach, scores were aggregated and summarised as a percentage and equally weighted to obtain an overall score by hospital, HSBB, and clinical intervention. RESULTS: Of 1508 HFA items, 1043 (69%) were included in standards-based and 309 (20%) in level-2 + scoring. Sixty-eight neonatal units across four countries had median standards-based scores of 51% [IQR 48-57%] at baseline, with variation by country: 62% [IQR 59-66%] in Kenya, 49% [IQR 46-51%] in Malawi, 50% [IQR 42-58%] in Nigeria, and 55% [IQR 53-62%] in Tanzania. The lowest scoring was family-centred care [27%, IQR 18-40%] with governance highest scoring [76%, IQR 71-82%]. For level-2 + scores, the overall median score was 41% [IQR 35-51%] with variation by country: 50% [IQR 44-53%] in Kenya, 41% [IQR 35-50%] in Malawi, 33% [IQR 27-37%] in Nigeria, and 41% [IQR 32-52%] in Tanzania. Readiness to provide antibiotics by culture report was the highest-scoring intervention [58%, IQR 50-75%] and neonatal encephalopathy management was the lowest-scoring [21%, IQR 8-42%]. In both methods, overall scores were low (< 50%) for 27 neonatal units in standards-based scoring and 48 neonatal units in level-2 + scoring. No neonatal unit achieved high scores of > 75%. DISCUSSION: Two scoring approaches reveal gaps in SSNC readiness with no neonatal units achieving high scores (> 75%). Government-led quality improvement teams can use these summary scores to identify areas for health systems change. Future analyses could determine which items are most directly linked with quality SSNC and newborn outcomes.

Synthesis and Evaluation of Ivacaftor Derivatives with Reduced Lipophilicity.

Mutations in the unique ATP-binding cassette anion channel, the cystic fibrosis conductance regulator (CFTR), lead to the inherited fatal disease known as cystic fibrosis (CF). Ivacaftor enhances channel gating of CFTR by stabilizing its open state and has been approved as monotherapy for CF patients with CFTR gating mutations (e.g., G551D) and as part of combination therapy with lumacaftor for CFTR folding mutations (e.g., ΔF508). However, in the latter context, ivacaftor may destabilize folding-rescued ΔF508-CFTR and membrane-associated proteins and attenuate lumacaftor pharmacotherapy. Here, we tested the hypothesis that the high lipophilicity of ivacaftor may contribute to this effect. We describe the synthesis of three glutamic acid ivacaftor derivatives with reduced lipophilicity that bear different charges at neutral pH (compounds 2, 3, 4). In a cellular ion flux assay, all three restored G551D-CFTR channel activity at comparable or better levels than ivacaftor. Furthermore, unlike ivacaftor, compound 3 did not attenuate levels of folding-rescued ΔF508 at the cell surface. Molecular modeling predicts that the increased polarity of compound 3 allows engagement with polar amino acids present in the binding pocket with hydrogen bonding and ionic interactions, which are collectively higher in strength as compared to hydrophobic interactions that stabilize ivacaftor. Overall, the data suggests that reduced lipophilicity may improve the efficacy of this class of CFTR potentiators when used for folding-rescued ΔF508-CFTR.

Structural characterization of transcription-coupled repair protein UVSSA and its interaction with TFIIH protein.

UV-stimulated scaffold protein A (UVSSA) is a key protein in the Transcription-Coupled Nucleotide Excision Repair (TC-NER) pathway. UVSSA, an intrinsically disordered protein, interacts with multiple members of the pathway, tethering them into the complex. Several studies have reported that UVSSA recruits Transcription Factor IIH (TFIIH) via direct interaction, following which CSB is degraded and the lesion recognition TC-NER complex dissociates from the damage site to facilitate the DNA repair. Structural insights into these events remain largely unknown. Herein, we have investigated the interaction of human UVSSA with the Pleckstrin-Homology-domain of p62 subunit of TFIIH (p62-PHD) using biophysical techniques. We observed that UVSSA forms a stable complex with the p62-PHD in vitro. Small-angle scattering measurements using X-rays and neutrons revealed a significant change in pair-distance distribution function for UVSSA662/p62-PHD complex compared to UVSSA alone. Additionally, a significant decrease was observed in the radius of gyration of the complex. Our findings suggest that TFIIH binding to UVSSA causes significant conformational changes in UVSSA. We hypothesize that these conformational changes play an important role in the dissociation of the lesion recognition TC-NER complex.

A Proteomic Survey of the Cystic Fibrosis Transmembrane Conductance Regulator Surfaceome.

The aim of this review article is to collate recent contributions of proteomic studies to cystic fibrosis transmembrane conductance regulator (CFTR) biology. We summarize advances from these studies and create an accessible resource for future CFTR proteomic efforts. We focus our attention on the CFTR interaction network at the cell surface, thus generating a CFTR 'surfaceome'. We review the main findings about CFTR interactions and highlight several functional categories amongst these that could lead to the discovery of potential biomarkers and drug targets for CF.

Crystal structure of Synechococcus phycocyanin: implications of light-harvesting and antioxidant properties.

Phycobiliproteins is a family of chromophore-containing proteins having light-harvesting and antioxidant capacity. The phycocyanin (PC) is a brilliant blue coloured phycobiliprotein, found in rod structure of phycobilisome and has been widely studied for their therapeutic and fluorescent properties. In the present study, the hexameric assembly structure of phycocyanin (Syn-PC) from Synechococcus Sp. R42DM is characterized by X-ray crystallography to understand its light-harvesting and antioxidant properties. The crystal structure of Syn-PC is solved with 2.15 Å resolution and crystallographic R-factors, Rwork/Rfree, 0.16/0.21. The hexamer of Syn-PC is formed by heterodimer of two polypeptide chains, namely, α- and ß-subunits. The structure is analysed at atomic level to reveal the chromophore microenvironment and possible light energy transfer mechanism in Syn-PC. The chromophore arrangement in hexamer, deviation angle and distance between the chromophore contribute to the energy transfer efficiency of protein. The structural attributes responsible for the antioxidant potential of Syn-PC are recognized and annotated on its 3-dimensional structure. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03665-1.

Transcription coupled DNA repair protein UVSSA binds to DNA and RNA: Mapping of nucleic acid interaction sites on human UVSSA.

Transcription-coupled repair (TCR) is a dedicated pathway for the preferential repair of bulky transcription-blocking DNA lesions. These lesions stall the elongating RNA-polymerase II (RNAPII) triggering the recruitment of TCR proteins at the damaged site. UV-stimulated scaffold protein A (UVSSA) is a recently identified cofactor which is involved in stabilization of the TCR complex, recruitment of DNA-repair machinery and removal/restoration of RNAPII from the lesion site. Mutations in UVSSA render the cells TCR-deficient and have been linked to UV-sensitive syndrome. Human UVSSA is a 709-residue long protein with two short conserved domains; an N-terminal (residues 1-150) and a C-terminal (residues 495-605) domain, while the rest of the protein is predicted to be intrinsically disordered. The protein is well conserved in eukaryotes, however; none of its homologs have been characterized yet. Here, we have purified the recombinant human UVSSA and have characterized it using bioinformatics, biophysical and biochemical techniques. Using EMSA, SPR and fluorescence-based methods, we have shown that human UVSSA interacts with DNA and RNA. Furthermore, we have mapped the nucleic acid binding regions using several recombinant protein fragments containing either the N-terminal or the C-terminal domains. Our data indicate that UVSSA possesses at least two nucleic acid binding regions; the N-terminal domain and a C-terminal tail region (residues 606-662). These regions, far apart in sequence space, are predicted to be in close proximity in structure-space suggesting a coherent interaction with target DNA/RNA. The study may provide functional clues about the novel family of UVSSA proteins.

Hospital frailty risk score predicts worse outcomes in patients with chronic pancreatitis.

Background: Chronic pancreatitis (CP) is a pathological fibroinflammatory response to persistent inflammation or stress to the pancreas. The effect of frailty on outcomes in patients with CP has not been previously examined. In this study, we examined the effect of frailty on outcomes in hospitalized patients with CP. Methods: Records of patients with a primary or secondary discharge diagnosis of CP (ICD10-CM codes K86.0, K86.1) between January 2016 and December 2019 were obtained from the National Inpatient Sample database. Data were collected on patient demographics, hospital characteristics, comorbidities, and etiology of CP. The relationship between frailty and outcomes, including mortality, intensive care unit (ICU) admission, sepsis, shock, length of stay (LOS), and total hospitalization charges (THC), were analyzed using multivariate analysis. Results: 722,160 patients were included in the analysis. Patients with a high hospital frailty risk score had a higher mortality risk (adjusted odds ratio [aOR] 12.57, 95% confidence interval [CI] 10.42-15.16; P<0.001) compared to patients with low frailty scores. Patients with high frailty scores also had a higher risk of sepsis (aOR 5.75, 95%CI 4.97-6.66; P<0.001), shock (aOR- 26.25, 95%CI-22.83-30.19; P<0.001), ICU admission (aOR 25.86, 95% CI-22.58-29.62; P<0.001), and acute kidney injury (aOR 24.4, 95%CI 22.39-26.66; P<0.001). They also had a longer LOS (7.04 days, 95%CI 6.57-7.52; P<0.001) and higher THC ($72,200, 95%CI 65,904.52-78,496.66; P<0.001). Conclusions: Frail patients, as determined by their hospital frailty risk score, are at high risk of worse outcomes. This data suggests opportunities for physicians to risk-stratify patients and predict outcomes.

Implementation of distance learning IMCI training in rural districts of Tanzania.

BACKGROUND: The standard face-to-face training for the integrated management of childhood illness (IMCI) continues to be plagued by concerns of low coverage of trainees, the prolonged absence of trainees from the health facility to attend training and the high cost of training. Consequently, the distance learning IMCI training model is increasingly being promoted to address some of these challenges in resource-limited settings. This paper examines participants' accounts of the paper-based IMCI distance learning training programme in three district councils in Mbeya region, Tanzania. METHODS: A cross-sectional qualitative descriptive design was employed as part of an endline evaluation study of the management of possible serious bacterial infection in Busokelo, Kyela and Mbarali district councils of Mbeya Region in Tanzania. Key informant interviews were conducted with purposefully selected policymakers, partners, programme managers and healthcare workers, including beneficiaries and training facilitators. RESULTS: About 60 key informant interviews were conducted, of which 53% of participants were healthcare workers, including nurses, clinicians and pharmacists, and 22% were healthcare administrators, including district medical officers, reproductive and child health coordinators and programme officers. The findings indicate that the distance learning IMCI training model (DIMCI) was designed to address concerns about the standard IMCI model by enhancing efficiency, increasing outputs and reducing training costs. DIMCI included a mix of brief face-to-face orientation sessions, several weeks of self-directed learning, group discussions and brief face-to-face review sessions with facilitators. The DIMCI course covered topics related to management of sick newborns, referral decisions and reporting with nurses and clinicians as the main beneficiaries of the training. The problems with DIMCI included technological challenges related to limited access to proper learning technology (e.g., computers) and unfriendly learning materials. Personal challenges included work-study-family demands, and design and coordination challenges, including low financial incentives, which contributed to participants defaulting, and limited mentorship and follow-up due to limited funding and transport. CONCLUSION: DIMCI was implemented successfully in rural Tanzania. It facilitated the training of many healthcare workers at low cost and resulted in improved knowledge, competence and confidence among healthcare workers in managing sick newborns. However, technological, personal, and design and coordination challenges continue to face learners in rural areas; these will need to be addressed to maximize the success of DIMCI.

Crystal structure analysis of phycoerythrin from marine cyanobacterium Halomicronema.

Phycoerythrin (PE) is green light-absorbing pigment-protein that assists in efficient light harvesting in cyanobacteria and red-algae. PE in cyanobacteria stays less studied so far as compared to that in red algae. In this study, PE from marine cyanobacteria Halomicronema sp. R31DM is purified and subjected for its structural characterisation by X-ray crystallography in order to understand its light-harvesting characteristics. The crystal structure is solved to a resolution-limit of 2.21 Å with reasonable R-factors values, 0.16/0.21 (Rwork/ Rfree). PE forms hexamer of hetero-dimers made up of two peptide chains, α- and ß-subunits containing 2 and 3 phycoerythrobilin (PEB) chromophores covalently attached to them, respectively. Geometry of five chromophores is analysed along with their relative position within the PE hexamer. Also, their interactions with the surrounding microenvironment are analysed. The plausible energy transfer pathways in hexamer structure have been predicted based on relative position and geometry of chromophores. This structure enriches the structural information of cyanobacterial PE in order to understand its light-harvesting capacity.Communicated by Ramaswamy H. Sarma.

Predictors of leaving against medical advice in patients with alcohol-related hepatitis.

Background: Alcohol-related hepatitis is one of the most severe manifestations of alcohol-related liver disease and has been associated with significant morbidity, mortality and financial burden. Patients with alcohol use disorders are at risk of leaving against medical advice (LAMA); however, there is currently a lack of data in the literature to show which patients are at higher risk. In this study, we investigated the specific demographic factors and comorbidities associated with LAMA. Methods: Patients with a primary or secondary discharge diagnosis of alcohol-related hepatitis (ICD10-CM codes K70.4 and K70.1) between January 2016 and December 2019 were included in this study. Demographics, comorbidities, complications and interventions were studied in for patients who LAMA. Multivariate analysis was conducted to elucidate factors contributing to the increased risk of alcohol-related hepatitis. Results: A total of 538,750 patients were admitted with a diagnosis of alcohol-related hepatitis. Of these, 31,500 (5.84%) patients LAMA. Older age, Hispanic race, private insurance, and higher income status were associated with a lower risk of LAMA, while younger age, African American race, lack of insurance and being in the lowest income quartile were associated with the highest risk. Conclusions: Our findings demonstrated that significant differences exist between patients with alcohol-related hepatitis who LAMA and those who remain hospitalized until discharge. We believe that this study will help healthcare providers identify patients at risk of LAMA, and help promote the targeted education of specific subgroups to improve their understanding of their disease state and decrease adverse events.

Gender differences in esophageal variceal bleeding in the United States.

BACKGROUND AND AIMS: Esophageal variceal bleeding is a common reason for hospitalization in patients with cirrhosis. The main objective of this study was to analyze the effects of gender differences on outcomes in hospitalizations related to Esophageal variceal bleeding in the United States. METHODS: A retrospective observational cohort study was performed using the National Inpatient Sample (NIS) database for all hospitalizations with a discharge diagnosis of esophageal varices with hemorrhage from 2016 to 2019. The primary outcome was in-hospital mortality, while secondary outcomes included rate of early endoscopy (defined as less than 1 day), AKI, blood transfusion, sepsis, ICU admission and TIPS (Transjugular Intrahepatic Portosystemic Shunt). We also compared the length of stay and total hospitalization charges. RESULTS: We identified a total of 166,760 patients with variceal bleeding of which 32.7% were females. In-hospital mortality was higher in males, 9.91%, compared to females, 8.31% (adjusted odds ratio (aOR): 0.88, p-value=.008, when adjusted for confounding factors). The odds of undergoing an EGD, length of stay, or total hospitalization charges did not differ between the two groups. Compared to men, women had lower odds of receiving TIPS (aOR = 0.83, p-value=.002). CONCLUSION: Women hospitalised with esophageal variceal bleeding are at a lower risk of death compared to males. Further research is needed to elucidate the factors associated with this lower risk.

Seasonal Variations of Hospital Admissions for Alcohol-Related Hepatitis in the United States.

Background: Clinical experience suggests an increased hospitalization rate for alcohol-related hepatitis (AH) in the winter months; however, seasonal variations in the prevalence of hospitalizations for AH have not been described previously. We hypothesized that AH hospitalizations would be higher in the winter months due to the holiday season and increased alcohol sales. Methods: Patients with primary or secondary discharge diagnosis of AH were included in the study (International Classification of Diseases, Clinical Modification-10th Revision codes K70.4 and K70.1) between January 2016 and December 2019. The primary outcome measure for this study was daily hospitalizations by each month of the year. Secondary outcome measures included the rate of in-hospital mortality associated with AH, for each month. Results: The highest number of AH-related admissions was reported in July (n = 56,800; 9%), followed by August (n = 55,700; 8.8%) and May (n = 54,865; 8.7%). February had the lowest number of admissions (n = 46,550; 7.37%). The adjusted mortality was highest in December (overall mortality: 9.6%; adjusted odds ratio: 1.29; 95% confidence interval: 1.142 - 1.461; P < 0.0001) and lowest in May (overall mortality rate: 7.7%). No difference was noted between length of stay and total hospitalization cost between months. Conclusion: Our findings demonstrate that seasonal variations in hospitalizations related to AH do exist across the United States. Regional differences also exist and follow unique patterns. The increase in admissions for AH is in line with other studies suggesting that heavy drinking happens during the warm season. Hospital administrators and other stewards of healthcare resources can use seasonal patterns to guide allocation of resources.

Clusters of COVID-19 Indicators in India: Characterization, Correspondence and Change Analysis.

We conduct a long-term epidemiology study of COVID-19 in India from Mar 2020 to May 2021 using a number of indicators such as active cases, daily new cases, and deaths, on a micro (district level, per capita) and macro level (state level). Our automated shape-based cluster discovery of the per capita daily new cases (case rate) during the first wave in India (between Mar 2020 and Jan 2021) revealed four distinct shape patterns: sharp-rise and decline, steady-rise and decline, plateau and multiple relatively high peaks. These clusters exhibit a strong geographical correlation. To determine the correspondence between clusters obtained by different indicators, we design a novel metric for determining edge-weights in their intersection graph. This is used for comparative analysis and to develop informative hierarchical cartographic visualizations. We then perform dynamic cluster analysis for different time windows to answer some pertinent questions. Is the second wave similar to or different from the first wave? How has the relative ranking (on micro- and macro-level indicators) of the states varied over the last one year? How much medical resources have been stressed during the peak? We demonstrate that using multiple indicators, we can assess the impact of the epidemic holistically in a particular geography. Our analysis techniques and insights obtained can help the local and state governments in monitoring and managing COVID-19 situation and fine-tuning the ongoing vaccination drive in India.

Proximity Profiling of the CFTR Interaction Landscape in Response to Orkambi.

Deletion of phenylalanine 508 (∆F508) of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) anion channel protein is the leading cause of Cystic Fibrosis (CF). Here, we report the analysis of CFTR and ∆F508-CFTR interactomes using BioID (proximity-dependent biotin identification), a technique that can also detect transient associations. We identified 474 high-confidence CFTR proximity-interactors, 57 of which have been previously validated, with the remainder representing novel interaction space. The ∆F508 interactome, comprising 626 proximity-interactors was markedly different from its wild type counterpart, with numerous alterations in protein associations categorized in membrane trafficking and cellular stress functions. Furthermore, analysis of the ∆F508 interactome in cells treated with Orkambi identified several interactions that were altered as a result of this drug therapy. We examined two candidate CFTR proximity interactors, VAPB and NOS1AP, in functional assays designed to assess surface delivery and overall chloride efflux. VAPB depletion impacted both CFTR surface delivery and chloride efflux, whereas NOS1AP depletion only affected the latter. The wild type and ∆F508-CFTR interactomes represent rich datasets that could be further mined to reveal additional candidates for the functional rescue of ∆F508-CFTR.