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Background: Non-cardiac chest pain, a term that serves as a broad canvas, has a multitude of potential causes in which panic disorder emerges as a prevailing cause. The recognition and accurate diagnosis of panic disorder among patients with non-cardiac chest pain is important. Hence a study was conducted to understand the prevalence of panic disorder among patients with non-cardiac chest pain in a tertiary care center in Kerala. Methods: A hospital-based, cross-sectional study was done among 118 patients who were diagnosed with non-cardiac chest pain by a cardiologist. The study was conducted in the cardiology OPD in a tertiary care center in Kerala. Mini-International Neuropsychiatric Interview Panic disorder – Version 6.0.0 (M.I.N.I.) was used to diagnose panic disorder among these patients. Results: It was found that panic disorder was present in 39.8% (95% Confidence Interval - 30.9-49.3%). Conclusion: The prevalence of panic disorder in patients diagnosed with non-cardiac chest pain was 39.8%. Consultation liaison treatment using pharmacotherapy and/or psychotherapy with the help of a psychiatrist may benefit such patients.

Slow cortical oscillations play a crucial role in processing the speech amplitude envelope, which is perceived atypically by children with developmental dyslexia. Here we use electroencephalography (EEG) recorded during natural speech listening to identify neural processing patterns involving slow oscillations that may characterize children with dyslexia. In a story listening paradigm, we find that atypical power dynamics and phase-amplitude coupling between delta and theta oscillations characterize dyslexic versus other child control groups (typically-developing controls, other language disorder controls). We further isolate EEG common spatial patterns (CSP) during speech listening across delta and theta oscillations that identify dyslexic children. A linear classifier using four delta-band CSP variables predicted dyslexia status (0.77 AUC). Crucially, these spatial patterns also identified children with dyslexia when applied to EEG measured during a rhythmic syllable processing task. This transfer effect (i.e., the ability to use neural features derived from a story listening task as input features to a classifier based on a rhythmic syllable task) is consistent with a core developmental deficit in neural processing of speech rhythm. The findings are suggestive of distinct atypical neurocognitive speech encoding mechanisms underlying dyslexia, which could be targeted by novel interventions.

Background: Spiritual and religious ways of coping are adaptive for individuals battling schizophrenia in the face of various illness-related factors. Related research is mainly focused on those with acute symptoms. Schizophrenia and a qualitative analysis of the connotation of spirituality-religiosity (SR) in processing illness-related difficulties in Indian context is sparse. This study analyzed how the SR helps people with schizophrenia to handle various day-to-day challenges in life. Methods: A qualitative approach was adopted, and consenting patients were asked open-ended questions. Data collected from these in-depth interviews with 15 individuals with schizophrenia and currently in remission were analyzed according to a predetermined model. Data were collected and analyzed based on grounded theory principles. Results: Twelve out of 15 of the individuals regarded SR as an inherent part of their well-being. At a personal level, the descriptions reflected a tendency toward achieving inner peace, meaning, and purpose in life; whereas at social/interpersonal levels, it was more about acceptance and seeking other’s support. These individuals regarded SR as a way of sharing love, care, and support, which would further help them in handling difficulties and accepting responsibilities. Conclusion: A well-formed SR belief system helps the patients with schizophrenia to navigate better through the day-to-day life stressors by changing the ways of coping.

Background: Transesophageal echocardiography (TEE) probe insertion may be associated with many complications. Demographic factors and airway conditions such as high Mallampati scores (MMC) and Cormack-Lehane grades (MCLG) are likely to have an impact on its ease of insertion. The primary aim of this study was to identify the predictive factors for difficult real-time-three-dimensional TEE probe insertion. Methods: A total of 153 adult patients undergoing cardiac surgery were prospectively evaluated. The upper airway manipulations required for TEE probe placement were jaw thrust, reverse Sellick's maneuver, and laryngoscopy. All the patients who required airway manipulations were grouped under difficult TEE probe placement group. We evaluated the patients' predictive factors such as demographic characteristics and factors related to difficult intubation. Results: Out of 153 patients, 123 were males and 30 were females. Overall, 27.5% (n = 42) patients had difficulty in probe placement. About 31.7% (n = 39) males had difficulty in TEE probe placement against 13% (n = 4) females (P-value 0.045). Difficulty in TEE probe placement was found in 72.7% (n = 16) of obese patients (body mass index [BMI] > 30), compared to 18.6% (n = 17) in the patients with BMI less than 25 (P-value < 0.001). Probe insertion was significantly more difficult in the presence of MMC III and IV (50%, n = 18) compared to class I (19.2%, n = 10) (P-value 0.001) and MCLG III (73.3%, n = 22) compared to grade I (11.1%, n = 7) (P-value 0.001). Conclusion: Male gender, obesity, higher grades of MMC and MCLG were found to be the risk factors for difficult TEE probe placement in anesthetized patients.

Abstract In the last decade, Chimeric Antigen Receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach to fight cancers. This approach consists of genetically engineered immune cells expressing a surface receptor, called CAR, that specifically targets antigens expressed on the surface of tumor cells. In hematological malignancies like leukemias, myeloma, and non-Hodgkin B-cell lymphomas, adoptive CAR-T cell therapy has shown efficacy in treating chemotherapy refractory patients. However, the value of this therapy remains inconclusive in the context of solid tumors and is restrained by several obstacles including limited tumor trafficking and infiltration, the presence of an immunosuppressive tumor microenvironment, as well as adverse events associated with such therapy. Recently, CAR-Natural Killer (CAR-NK) and CAR-macrophages (CAR-M) were introduced as a complement/alternative to CAR-T cell therapy for solid tumors. CAR-NK cells could be a favorable substitute for CAR-T cells since they do not require HLA compatibility and have limited toxicity. Additionally, CAR-NK cells might be generated in large scale from several sources which would suggest them as promising off-the-shelf product. CAR-M immunotherapy with its capabilities of phagocytosis, tumor-antigen presentation, and broad tumor infiltration, is currently being investigated. Here, we discuss the emerging role of CAR-T, CAR-NK, and CAR-M cells in solid tumors. We also highlight the advantages and drawbacks of CAR-NK and CAR-M cells compared to CAR-T cells. Finally, we suggest prospective solutions such as potential combination therapies to enhance the efficacy of CAR-cells immunotherapy.

The emergence of novel and evolving variants of SARS-CoV-2 has fostered the need for change in the form of newer and more adaptive diagnostic methods for the detection of SARS-CoV-2 infections. On the other hand, developing rapid and sensitive diagnostic technologies is now more challenging due to emerging variants and varying symptoms exhibited among the infected individuals. In addition to this, vaccines remain the major mainstay of prevention and protection against infection. Novel vaccines and drugs are constantly being developed to unleash an immune response for the robust targeting of SARS-CoV-2 and its associated variants. In this review, we provide an updated perspective on the current challenges posed by the emergence of novel SARS-CoV-2 mutants/variants and the evolution of diagnostic techniques to enable their detection. In addition, we also discuss the development, formulation, working mechanisms, advantages, and drawbacks of some of the most used vaccines/therapeutic drugs and their subsequent immunological impact.Key message The emergence of novel variants of the SARS-CoV-2 in the past couple of months, highlights one of the primary challenges in the diagnostics, treatment, as well as vaccine development against the virus. Advancements in SARS-CoV-2 detection include nucleic acid based, antigen and immuno- assay-based and antibody-based detection methodologies for efficient, robust, and quick testing; while advancements in COVID-19 preventive and therapeutic strategies include novel antiviral and immunomodulatory drugs and SARS-CoV-2 targeted vaccines. The varied COVID-19 vaccine platforms and the immune responses induced by each one of them as well as their ability to battle post-vaccination infections have all been discussed in this review.

As a major shift in education technologies, Adaptive Learning Systems (ALS) use artificial intelligence and similar technologies, adapting the lessons to the needs of individual students. Emphasizing transformative pedagogy and teaching strategies that transform the learners' cognitive and interactive patterns, this study presents a comprehensive bibliometric analysis of ASL. Contrary to conventional teaching methods, ALS alters dramatically the way students think and interact with their environment. This research has utilized an all-inclusive bibliometric analysis to analyze the evolution, trends, and themes in ALS by using an extensive set of data from the Web of Science (WoS) and Scopus. The primary objective of Bibliometric analysis is to map the development of ALS in teaching and learning while marking the important trends, models, and thematic priorities. The relevance of this research lies in its comprehensive analysis of the Adaptive Learning Systems (ALS) field through bibliometric methods, offering critical insights into the trends, key contributors, and thematic developments over time. The systematic evaluation enables the appraisal of the impact created by major contributors like authors, organizations, journals, etc. The study also examines, using the advanced data collection technique, influential articles, and publications that enormously contributed to shaping ALS. Similarly, it does the rating effectively upon evaluating the mutual relationships among important terms, concepts, and factors through co-references and co-occurrences. It highlights the increasing scholarly output and identifies key contributors and influential works, underscoring the growing recognition of ALS's importance due to technological advancements. The study's findings on global research contributions, thematic analyses, and collaboration networks offer new insights into the field's dynamics, setting a foundation for future research directions. To visually represent bibliometric data, web analytic tools are used, explaining intricate relationships and thematic clusters. Identifying the unexplored areas and discussing the practical implications of ASL development, research, and analysis of combined data taken from WoS and Scopus provides a unique perspective. Consequently, researchers, educators, policymakers, etc., get valuable insights that enable advancing and understanding the area. This bibliometric analysis will undoubtedly guide future research in the area of transformative pedagogy as it is the most sought-after method in understanding the scholarly landscape of ALS.

Abstract Recent research shows that adults’ neural oscillations track the rhythm of the speech signal. However, the extent to which this tracking is driven by the acoustics of the signal, or by language-specific processing remains unknown. Here adult native listeners of three rhythmically different languages (English, French, Japanese) were compared on their cortical tracking of speech envelopes synthesized in their three native languages, which allowed for coding at each of the three language’s dominant rhythmic unit, respectively the foot (2.5 Hz), syllable (5 Hz), or mora (10 Hz) level. The three language groups were also tested with a sequence in a non-native language, Polish, and a non-speech vocoded equivalent, to investigate possible differential speech/nonspeech processing. The results first showed that cortical tracking was most prominent at 5 Hz (syllable rate) for all three groups, but the French listeners showed enhanced tracking at 5 Hz compared to the English and the Japanese groups. Second, across groups, there were no differences in responses for speech versus non-speech at 5 Hz (syllable rate), but there was better tracking for speech than for non-speech at 10 Hz (not the syllable rate). Together these results provide evidence for both language-general and language-specific influences on cortical tracking.

Introduction: The Duration of Untreated Psychosis (DUP) is the time interval between the manifestation of the first psychotic symptom in a patient and the starting of proper treatment. Though, considered as a modifiable factor in the outcome of mental illness, many confounding variables such as sociodemographic factors and illness related factors can affect the DUP. Aim: To identify the association between sociodemographic factors and the severity of psychiatric symptoms with the DUP in patients with the first episode of psychosis. Materials and Methods: A descriptive cross-sectional study conducted in the Department of Psychiatry, Government Medical College, Kottayam, Kerala, India, from March 2018 to February 2019. The first 50 consecutive patients reporting for treatment for the first time, who were diagnosed with psychotic disorders were recruited into the study. Details of the onset of psychosis were collected from the relative based on a clear, unequivocal description of symptoms by the relative. A specially designed proforma was used to gather the sociodemographic details and Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of psychotic symptoms. Statistical analysis was done using independent Student’s t-test, one-way Analysis of Variance (ANOVA) and Pearson’s correlation and p-value

BackgroundNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes with better overall survival, but only 15-40% of the patients respond to ICIs therapy. The search for predictive biomarkers of responses is warranted for better clinical outcomes. We aim here to identify pre-treatment soluble immune molecules as surrogate biomarkers for tissue PD-L1 (TPD-L1) status and as predictors of response to anti-PD-1/PD-L1 therapy in NSCLC patients. Sera from 31 metastatic NSCLC patients, eligible for anti-PD-1/PD-L1 or combined chemoimmunotherapy, were collected prior to treatment. Analysis of soluble biomarkers with TPD-L1 status showed significant up/down regulation of the immune inhibitory checkpoint markers (sSiglec7, sSiglec9, sULBP4 and sPD-L2) in patients with higher TPD-L1 (TPD-L1 >50%) expression. Moreover, correlation analysis showed significant positive linear correlation of soluble PD-L1 (sPD-L1) with higher TPD-L1 expression. Interestingly, only responders in the TPD-L1 >50% group showed significant down regulation of the immune inhibitory markers (sPD-L2, sTIMD4, sNectin2 and CEA). When responders vs. non-responders were compared, significant down regulation of other immune inhibitory biomarkers (sCD80, sTIMD4 and CEA) was recorded only in responding patients. In this, the optimal cut-off values of CD80

With the rapid growth of data sources, Big data security in Cloud is a big challenge. Different issues have ascended in the area of Big data security such as infrastructure security, data privacy, data management and data integrity. Currently, Big data processing, analytics and storage is secured using cryptography algorithms, which are not appropriate for Big data protection over Cloud. In this paper, we present a solution for addressing the main issues in Big data security over Cloud. We propose a novel system architecture called the Secure Authentication and Data Sharing in Cloud (SADS-Cloud). There are three processes involved in this paper including (i). Big Data Outsourcing, (ii). Big Data Sharing and (iii). Big Data Management. In Big data outsourcing, the data owners are registered to a Trust Center using SHA-3 hashing algorithm. The MapReduce model is used to split the input file into fixed-size of blocks of data and SALSA20 encryption algorithm is applied over each block. In Big data sharing, data users participate in a secure file retrieval. For this purpose, user's credentials (ID, password, secure ID, and current timestamp, email id) are hashed and compared with that stored in a database. In Big data management, there are three important processes implemented to organize data. They are as follows: Compression using Lemperl Ziv Markow Algorithm (LZMA), Clustering using Density-based Clustering of Applications with Noise (DBSCAN), and Indexing using Fractal Index Tree. The proposed scheme for these processes are implemented using Java Programming and performance tested for the following metrics: Information Loss, Compression Ratio, Throughput, Encryption Time and Decryption Time.

Abstract In this study, we experimentally manipulated the phonology of the cross-script prime-target dyads in an ERP-coupled masked priming paradigm to explore the role phonology plays in visual word processing. The written characters of certain bilingual dyads seldom show any visual/orthographic similarity, yet have the same phonological representation. While the Bilingual Interactive Activation (BIA) model relies on the orthographic similarity between the languages in a bilingual dyad, its revised version (BIA + model) additionally banks on the phonological (and semantic) similarity between the words in such dyads. Thus, there exists the need to investigate the role of phonological (and semantic) similarity between the words of a bilingual dyad, especially in the absence of orthographic similarity. Borrowed words from one language to another provide a suitable avenue to explore this question. Cross-orthographic (or cross-script) bilingual participants of this study performed the semantic judgment of visually presented words in a masked priming paradigm in each of their languages while we simultaneously collected the event-related potentials (ERPs). The primes were either translations (different phonology & orthography: P–O–; phonologically incongruent) or transliterations (same phonology & different orthography: P + O–; phonologically congruent) of the target. Overall, the results showed no difference between the two prime conditions. We discuss our findings in light of the BIA and BIA + models of bilingual visual word processing and discuss the relevance of the former model in orthographically distinct bilingual language dyads.

IntroductionThe BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine.MethodsHere, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine.Results and discussionOverall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P

Hannah Whittaker,1 Annalisa Rubino,2 Hana Müllerová,2 Tamsin Morris,3 Precil Varghese,4 Yang Xu,3 Enrico De Nigris,5 Jennifer K Quint1 1National Heart and Lung Institute, Imperial College London, London, UK; 2Epidemiology, AstraZeneca, Cambridge, UK; 3Medical and Scientific Affairs, AstraZeneca, Luton, UK; 4Biopharmaceuticals Medical, Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA; 5Health Economics, AstraZeneca, Cambridge, UKCorrespondence: Hannah Whittaker, Email h.whittaker@imperial.ac.ukBackground: Studies have shown that chronic obstructive pulmonary disease (COPD) exacerbation events are related to future events; however, previous literature typically reports frequent vs infrequent exacerbations per patient-year and no studies have investigated increasing number of severe exacerbations in relation to COPD outcomes.Objective: To investigate the association between baseline frequency and severity of exacerbations and subsequent mortality and exacerbation risk in a COPD cohort.Methods: Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics data were used to identify patients registered at general practices in the UK, who had a diagnosis of COPD, were over the age of 40 years, were smokers or ex-smokers and had data recorded from 2004 onwards. Frequency and severity of exacerbations in the baseline year were identified as moderate exacerbations (general practice events) and severe exacerbations (hospitalised events). Patients were categorised as having: none, 1 moderate only, 2 moderate only, 3+ moderate only, 1 severe (and any moderate), 2 severe (and any moderate), and 3+ severe (and any moderate exacerbations). Poisson regression was used to investigate the association between baseline exacerbation frequency/severity and exacerbation events and mortality over follow-up.Results: Overall, 340,515 COPD patients were included. Patients had higher rates of future exacerbations with increasing frequency and severity of baseline exacerbations compared to no baseline exacerbations. Adjusted incidence rate ratios (IRR) for patients with 1, 2, and 3+ moderate exacerbations compared to 0 exacerbations were 1.70 (95% CI 1.66– 1.74), 2.31 (95% CI 2.24– 2.37), and 3.52 (95% CI 3.43– 3.62), respectively. Patients with increased frequency of baseline exacerbations were more likely to die from all-cause, COPD-related, and cardiovascular-related mortality in a graduated fashion.Conclusion: Increasing number and severity of exacerbations were associated with increasing risk of subsequent exacerbations, all-cause mortality and COPD-related mortality. Even a single moderate event increases the risk of future events, illustrating that every exacerbation counts.Keywords: COPD, exacerbations of COPD

Abstract Colorectal cancer (CRC) is one of the most common cancers worldwide. The diagnosis, prognosis and therapeutic monitoring of CRC depends largely on tissue biopsy. However, due to tumor heterogeneity and limitations such as invasiveness, high cost and limited applicability in longitudinal monitoring, liquid biopsy has gathered immense attention in CRC. Liquid biopsy has several advantages over tissue biopsy including ease of sampling, effective monitoring, and longitudinal assessment of treatment dynamics. Furthermore, the importance of liquid biopsy is signified by approval of several liquid biopsy assays by regulatory bodies indicating the powerful approach of liquid biopsy for comprehensive CRC screening, diagnostic and prognostics. Several liquid biopsy biomarkers such as novel components of the microbiome, non-coding RNAs, extracellular vesicles and circulating tumor DNA are extensively being researched for their role in CRC management. Majority of these components have shown promising results on their clinical application in CRC including early detection, observe tumor heterogeneity for treatment and response, prediction of metastases and relapse and detection of minimal residual disease. Therefore, in this review, we aim to provide updated information on various novel liquid biopsy markers such as a) oral microbiota related bacterial network b) gut microbiome-associated serum metabolites c) PIWI-interacting RNAs (piRNAs), microRNA(miRNAs), Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and d) circulating tumor DNAs (ctDNA) and circulating tumor cells (CTC) for their role in disease diagnosis, prognosis, treatment monitoring and their applicability for personalized management of CRC.

Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. Identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. In this study we evaluated 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines before and after ICIs therapy in 17 NSCLC patients to identify surrogate biomarkers for treatment/monitoring patient stratification for maximum therapeutic benefit. We first confirmed the identity of the isolated exosomes to have their specific markers (CD63, CD81, HSP70 and CD91). We have demonstrated that baseline concentration of exosomal-PD-L1 (p

The rapid worldwide spread of COVID-19 motivated medical professionals to pursue and authenticate appropriate remedies and treatment protocols. This article aims to analyze the potential benefits of one treatment protocol developed by a group of care providers caring for severe COVID-19 patients.

Additive ceramics manufacturing with vat-photopolymerisation (VP) is a developing field, and the need for suitable printing materials hinders its fast growth. Binder mixtures significantly influence the mechanical properties of printed ceramic bodies by VP, considering their rheological properties, curing performances and green body characteristics. Improving mechanical characteristics and reducing cracks during printing and post-processes is mainly related to binder formulations. The study aims to develop a binder formulation to provide the printed ceramic specimens with additional green strength. The impact on mechanical properties (ultimate tensile strength, flexural strength, Young’s and strain at breakpoint), viscosity and cure performance of Urethane Acrylate (UA) and thermoplastic Polyether Acrylate (PEA) oligomers to monofunctional N-Vinylpyrrolidone (NVP), 1,6-Hexanediol Diacrylate (HDDA) and Tri-functional Photocentric 34 (PC34) monomers were investigated under varying concentrations. The best mechanical characteristic was showcased when the PC34 was replaced with 20–30 wt.% of UA in the organic medium. The Thermogravimetric Analysis (TGA) and sintering test outcomes revealed that increasing the content of NVP in the organic medium (above 15 wt.%) leads to uncontrolled thermal degradation during debinding and defects on ceramic parts after sintering. The negative effect of UA on the viscosity of ceramic-loaded mixtures was controlled by eliminating the PC34 compound with NVP and HDDA, and optimum mechanical properties were achieved at 15 wt.% of NVP and 65 wt.% of HDDA. PEA is added to provide additional flexibility to the ceramic parts. It was found that strain and other mechanical parameters peaked at 15 wt.% of PEA. The study formulated the most suitable binder formulation on the green body strength of printing silica ceramics as 50 wt.% HDDA, 20 wt.% Urethane Acrylate, 15 wt.% NVP and 15 wt.% PEA.

John R Hurst,1 Mohd Kashif Siddiqui,2 Barinder Singh,3 Precil Varghese,4 Ulf Holmgren,5 Enrico de Nigris6 1UCL Respiratory, University College London, London, UK; 2HEOR and RWE Analytics, Regulatory Access, Parexel International Ltd, Mohali, India; 3HEOR Evidence Evaluation, Parexel International Ltd, Mohali, India; 4Biopharmaceuticals Medical, Respiratory and Immunology, AstraZeneca, Gothenburg, MD, USA; 5Real World Science and Digital, Biopharmaceutical Medical, AstraZeneca, Gothenburg, Sweden; 6Global Product and Portfolio Strategy, AstraZeneca, Cambridge, UKCorrespondence: John R HurstUCL Respiratory, Royal Free Campus, London, NW3 2QG, UKTel +44 203 108 7761Email j.hurst@ucl.ac.ukBackground: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, causing substantial economic and social burden.Objective: This review assessed the patient-reported humanistic burden associated with moderate to very severe COPD, specifically the impact on health-related quality of life (HRQoL), symptoms, limitations in daily life, and emotional implications, through the use of HRQoL instruments.Methods: A systematic review was conducted to retrieve relevant clinical data from published literature using a representative sample of countries where healthcare systems provide wide availability of COPD medications and/or universal coverage includes respiratory medicines (Australia, Canada, China, France, Germany, Italy, Spain, the UK, and the USA). The primary inclusion criteria were patients with moderate to very severe COPD. HRQoL was quantified with non-disease-specific and disease-specific questionnaires.Results: In total, 82 studies from 95 publications presented HRQoL data from patients with moderate to very severe COPD. Patient-reported HRQoL declined with worsening airflow limitation, advancing GOLD group, and increasing exacerbation frequency. Both increasing frequency of hospitalization for COPD exacerbations and recurrent hospitalization adversely impacted HRQoL. Comorbidity incidence was higher in patients with increased airflow limitation. It was associated with a further decline in HRQoL and increased depression and anxiety, particularly as disease-associated pain worsened. Physical activity improved HRQoL over time.Conclusion: This review highlighted the impact of exacerbations and associated hospitalizations on the humanistic burden of COPD. These findings underline the importance of managing COPD actively, including prompt and appropriate use of pharmacological and non-pharmacological therapies that can improve symptoms and reduce the risk of exacerbations, thereby lessening the humanistic burden. Future reviews could consider a broader range of countries and publications to further assess the humanistic impact of COPD in low- and middle-income economies.Keywords: chronic obstructive pulmonary disease, quality of life, humanistic burden, patient-reported outcomes

Deepa Rajan,1 Vinod G Pillai,2 Patsy Varghese1 1Department of Obstetrics and Gynecology, Believers Church Medical College Hospital, Thiruvalla, Kerala, India; 2Department of Surgery, Believers Church Medical College Hospital, Thiruvalla, Kerala, IndiaCorrespondence: Vinod G PillaiDepartment of Surgery, Believers Church Medical College Hospital, Thiruvalla, Kerala, 689103, IndiaTel/Fax +91 469 3503100Email drvinodpillai@gmail.comIntroduction: The Covid pandemic and social distancing has adversely impacted the conventional apprenticeship method of postgraduate training in laparoscopic surgery. Social media may be a useful adjunct for laparoscopic training, but its utility in developing countries like India has not been studied carefully. This paper describes an observational, cross-sectional study on the educational utility of Facebook groups based in India and which focus on laparoscopic gynecologic surgery.Methods: The most popular Facebook groups involving Indians and focusing on laparoscopic gynecology were identified using appropriate search terms as well as inclusion and exclusion criteria. Demographic data related to the groups, the authors of posts as well as descriptive statistics of all the posts during the study period were collected and appropriate statistical analysis was performed.Results: All the groups in this study were large and growing steadily. Posts related to laparoscopy were more likely to be videos, dealing with operative techniques and having educational value for postgraduate residents (p value < 0.001) compared to posts unrelated to laparoscopic surgery. The majority of posts (88.2%) presented original content created by group members rather than material shared from other sources. Members preferred to share laparoscopic content using links to their personal YouTube channels rather than using institutional YouTube channels, dedicated websites for laparoscopic surgery or direct posts on Facebook. Group members liked educational content and laparoscopic surgery-related content significantly more than other content. Only 16.7% of the laparoscopic surgeons could be identified to be working in academic institutes.Conclusion: Social media for medical education has inherent advantages and disadvantages. This article provides objective data regarding its utilisation in a developing country in the midst of the Covid pandemic, and provides a guide for further research and development of innovative teaching methods.Keywords: online learning, distance learning, surgical education, laparoscopic gynecology, Covid pandemic, social media

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic and its socio-economic consequences have had a significant impact on mental health. A quantifiable data regarding increase of mental health problems as a result of the pandemic is required to take necessary steps in tackling the issue. Aim: To estimate the prevalence of depression, perceived stress and its socio-demographic correlates among general population of South India during COVID-19. Materials and Methods: This cross-sectional survey conducted from 25th August 2021 to 25th October 2021 among the general population of South India during COVID-19. A total of 600 subjects were enrolled into the study. Study subjects included people of either sex between 20-50 years of age who were able to read and understand English and with access to internet. Subjects responded to a questionnaire packet of Patient Health Questionnaire-9 (PHQ-9), Perceived Stress Scale 10 (PSS-10) and a proforma for socio-demographic data. Data was analysed using GNU PSPP version 1. One-way Analysis of Variance (ANOVA) and independent t-test were used to assess associations. A value of p-value

Jennifer K Quint,1 Alessandra Venerus,2 Caroline O’Leary,2 Melissa Myland,2 Ulf Holmgren,3 Precil Varghese,4 Claudia Cabrera3,5 1Imperial College London, London, UK; 2IQVIA, London, UK; 3Real World Science and Digital, BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden; 4Global Medical Affairs, AstraZeneca, Gaithersburg, MD, USA; 5Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, SwedenCorrespondence: Claudia CabreraBioPharmaceuticals Medical, AstraZeneca, Pepparedsleden 1, SE-431 83 Mölndal, Gothenburg, SwedenTel +46 (0)31 776 2890Email claudia.s.cabrera@astrazeneca.comPurpose: Treatment guidance for chronic obstructive pulmonary disease (COPD) recommends inhaled corticosteroid (ICS)+long-acting muscarinic antagonist+long-acting β2-agonist (LABA) triple therapy for patients who experience recurrent exacerbations, persistent breathlessness, or exercise limitation on dual therapy. However, information is limited on pathways to triple therapy in the UK.Patients and Methods: A retrospective cohort study was conducted using de-identified patient-level data from UK primary care electronic medical records from January 1, 2005 to May 1, 2016. Data were included from patients who had their first triple therapy regimen (index date) recorded during the study period and a minimum of 12 months’ pre-index data. Treatment pathways to triple therapy were recorded, and the proportion of patients on triple therapy before their COPD diagnosis was determined. Adherence to triple therapy was estimated using the proportion of days covered (PDC).Results: After applying eligibility criteria, 82,300 patients were included, with a mean age at COPD diagnosis of 64.7 years. The major treatment pathway (27.9%) was the first initiation of ICS+LABA prior to triple therapy. Following COPD diagnosis, the median time to triple therapy was approximately 3.5 years. The estimated mean adherence to triple therapy was 81.8% PDC. Multivariate analysis showed that the following groups were more likely to have received previous therapy prior to triple therapy: females (versus males), patients with asthma (versus those without asthma), severe COPD (versus those with non-severe COPD), or fewer exacerbations (versus those with more exacerbations).Conclusion: Treatment pathways to triple therapy in the UK are diverse, highlighting the need to better understand factors involved in clinical decision-making.Keywords: chronic obstructive pulmonary disease, patient pathways, real-world, retrospective study, treatment initiation, triple therapy

Vitamin C also known as L-ascorbic acid is a nutrient naturally occurring in many fruits and vegetables and widely known for its potent antioxidant activity. Several studies have highlighted the importance of using high dose vitamin C as an adjuvant anti-cancer therapy. Interestingly, it has been shown that vitamin C is able to modulate the anti-cancer immune response and to help to overcome the resistance to immune checkpoints blockade (ICB) drugs such as cytotoxic T-lymphocyte antigen 4 (CLTA-4) and programmed cell death ligand 1 (PD-L1/PD-1) inhibitors. Indeed, it was reported that vitamin C regulates several mechanisms developed by cancer cells to escape T cells immune response and resist ICB. Understanding the role of vitamin C in the anti-tumor immune response will pave the way to the development of novel combination therapies that would enhance the response of cancer patients to ICB immunotherapy. In this review, we discuss the effect of vitamin C on the immune system and its potential role in empowering cancer immunotherapy through its pro-oxidant potential, its ability to modulate epigenetic factors and its capacity to regulate the expression of different cytokines involved in the immune response.

The North Temperate Lakes Long-Term Ecological Research (NTL-LTER) program has been extensively used to improve understanding of how aquatic ecosystems respond to environmental stressors, climate fluctuations, and human activities. Here, we report on the metagenomes of samples collected between 2000 and 2019 from Lake Mendota, a freshwater eutrophic lake within the NTL-LTER site. We utilized the distributed metagenome assembler MetaHipMer to coassemble over 10 terabases (Tbp) of data from 471 individual Illumina-sequenced metagenomes. A total of 95,523,664 contigs were assembled and binned to generate 1,894 non-redundant metagenome-assembled genomes (MAGs) with ≥50% completeness and ≤10% contamination. Phylogenomic analysis revealed that the MAGs were nearly exclusively bacterial, dominated by Pseudomonadota (Proteobacteria, N = 623) and Bacteroidota (N = 321). Nine eukaryotic MAGs were identified by eukCC with six assigned to the phylum Chlorophyta. Additionally, 6,350 high-quality viral sequences were identified by geNomad with the majority classified in the phylum Uroviricota. This expansive coassembled metagenomic dataset provides an unprecedented foundation to advance understanding of microbial communities in freshwater ecosystems and explore temporal ecosystem dynamics.

Brain rhythms provide the timing for recruitment of brain activity required for linking together neuronal ensembles engaged in specific tasks. The γ-oscillations (30 to 120 Hz) orchestrate neuronal circuits underlying cognitive processes and working memory. These oscillations are reduced in numerous neurological and psychiatric disorders, including early cognitive decline in Alzheimers disease (AD). Here, we report on a potent brain-permeable small molecule, DDL-920 that increases γ-oscillations and improves cognition/memory in a mouse model of AD, thus showing promise as a class of therapeutics for AD. We employed anatomical, in vitro and in vivo electrophysiological, and behavioral methods to examine the effects of our lead therapeutic candidate small molecule. As a novel in central nervous system pharmacotherapy, our lead molecule acts as a potent, efficacious, and selective negative allosteric modulator of the γ-aminobutyric acid type A receptors most likely assembled from α1β2δ subunits. These receptors, identified through anatomical and pharmacological means, underlie the tonic inhibition of parvalbumin (PV) expressing interneurons (PV+INs) critically involved in the generation of γ-oscillations. When orally administered twice daily for 2 wk, DDL-920 restored the cognitive/memory impairments of 3- to 4-mo-old AD model mice as measured by their performance in the Barnes maze. Our approach is unique as it is meant to enhance cognitive performance and working memory in a state-dependent manner by engaging and amplifying the brains endogenous γ-oscillations through enhancing the function of PV+INs.

Scrub typhus, a vector-borne bacterial infection, is an important but neglected disease globally. Accurately characterizing the burden is challenging because of nonspecific symptoms and limited diagnostics. Prior seroepidemiology studies have struggled to find consensus cutoffs that permit comparisons of estimates across contexts and time. In this study, we present a novel approach that does not require a cutoff and instead uses information about antibody kinetics after infection to estimate seroincidence. We use data from three cohorts of scrub typhus patients in Chiang Rai, Thailand, and Vellore, India, to characterize antibody kinetics after infection and two population serosurveys in the Kathmandu Valley, Nepal, and Tamil Nadu, India, to estimate seroincidence. The samples were tested for IgM and IgG responses to Orientia tsutsugamushi-derived recombinant 56-kDa antigen using commercial enzyme-linked immunosorbent assay kits. We used Bayesian hierarchical models to characterize antibody responses after scrub typhus infection and used the joint distributions of the peak antibody titers and decay rates to estimate population-level incidence rates in the cross-sectional serosurveys. Median responses persisted above an optical density (OD) of 1.8 for 23.6 months for IgG and an OD of 1 for 4.5 months for IgM. Among 18- to 29-year-olds, the seroincidence was 10 per 1,000 person-years (95% CI, 5-19) in Tamil Nadu, India, and 14 per 1,000 person-years (95% CI: 10-20) in the Kathmandu Valley, Nepal. When seroincidence was calculated with antibody decay ignored, the disease burden was underestimated by more than 50%. The approach can be deployed prospectively, coupled with existing serosurveys, or leverage banked samples to efficiently generate scrub typhus seroincidence estimates.

Abstract Introduction Cancer Immunotherapy has recently emerged as a promising and effective modality to treat different malignancies. Antigenic profiling of cancer tissues and determination of any pre-existing immune responses to cancer antigens may help predict responses to immune intervention in cancer. NY-ESO-1, a cancer testis antigen is the most immunogenic antigen to date. The promise of NY-ESO-1 as a candidate for specific immune recognition of cancer comes from its restricted expression in normal adult tissue but frequent occurrence in multiple tumors including melanoma and carcinomas of lung, esophageal, liver, gastric, prostrate, ovarian, and bladder. Main body This review summarizes current knowledge of NY-ESO-1 as efficient biomarker and target of immunotherapy. It also addresses limitations and challenges preventing a robust immune response to NY-ESO-1 expressing cancers, and describes pre-clinical and clinical observations relevant to NY-ESO-1 immunity, holding potential therapeutic relevance for cancer treatment. Conclusion NY-ESO-1 induces strong immune responses in cancer patients but has limited objective clinical responses to NY-ESO-1 expressing tumors due to effect of competitive negative signaling from immune-checkpoints and immune-suppressive tumor microenvironment. We propose that combination therapy to increase the efficacy of NY-ESO-1 specific immunotherapeutic interventions should be explored to unleash the immune response against NY-ESO-1 expressing tumors.