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Abstract AI image classification algorithms have shown promising results when applied to skin cancer detection. Most public skin cancer image datasets are comprised of dermoscopic photos and are limited by selection bias, lack of standardization, and lend themselves to development of algorithms that can only be used by skilled clinicians. The SLICE-3D (“Skin Lesion Image Crops Extracted from 3D TBP”) dataset described here addresses those concerns and contains images of over 400,000 distinct skin lesions from seven dermatologic centers from around the world. De-identified images were systematically extracted from sensitive 3D Total Body Photographs and are comparable in optical resolution to smartphone images. Algorithms trained on lower quality images could improve clinical workflows and detect skin cancers earlier if deployed in primary care or non-clinical settings, where photos are captured by non-expert physicians or patients. Such a tool could prompt individuals to visit a specialized dermatologist. This dataset circumvents many inherent limitations of prior datasets and may be used to build upon previous applications of skin imaging for cancer detection.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal sentinel surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortiums aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

Introduction: The impact of coronavirus disease 2019 (COVID-19) infection on patients with multiple sclerosis (MS) undergoing various immunomodulating therapies can vary. Individuals on B-cell therapy, such as rituximab, may be more susceptible to infection compared to those treated with natalizumab. Objective: The objective of this study was to determine the incidence and severity of COVID-19 infection in patients receiving rituximab, natalizumab, and healthy controls. Methods: This retrospective multicentric study included data derived from a centralized MS registry of four centers in South India. Data of patients on rituximab and natalizumab recruited between 2020 February and 2022 December were extracted from the registry and analyzed. The outcomes studied were the occurrence of COVID-19 infection, hospitalization, intensive care unit admission, death, post-COVID-19 relapses, and post-vaccine relapses. These outcomes were compared between the treatment groups and the matched controls. Results: COVID-19 infection occurred in 49.1% (26/53) of those on rituximab, 19.2% (5/26) of those on natalizumab, and 11.5% (6/52) of healthy controls. In addition, 8/53 (15.1%) in the rituximab group and 1/26 (3.8%) in the natalizumab group were hospitalized. All 6/52 (11.5%) in the control group had mild infection, and none were hospitalized. No deaths occurred in any group. On statistical analysis, the occurrence of COVID-19 infection in the rituximab group was significantly higher when compared to natalizumab (P = 0.0141) and healthy controls (P < 0.001). Hospitalizations were significantly higher in the rituximab group when compared to healthy controls (P < 0.006). Conclusion: MS patients treated with rituximab were more likely to experience COVID-19 infection compared to those treated with natalizumab and healthy controls. Hospitalization was more frequently seen in patients treated with rituximab compared to healthy controls.

Summary: Background: Dengue shows high geographic heterogeneity within and across endemic countries. In the context of increasing burden and predicted outbreaks due to climate change, understanding the heterogeneity will enable us to develop region specific targeted interventions, including vaccination. World Health Organisation (WHO) suggests standard methodologies to study the burden and heterogeneity at national and subnational levels. Regional studies with robust and standard methodology to capture heterogeneity are scarce. We estimated the seroprevalence of dengue in children aged 9–12 years and the force of infection in Kerala, India, from where Zika cases also have been reported recently. Methods: We conducted a school-based cross-sectional survey in 38 clusters; selected by stratified random sampling, representing rural, urban, high burden and low-burden administrative units. Validation of Indirect IgG ELISA was done by Plaque Reduction Neutralization Test (PRNT90) using the local isolates of all four serotypes. Force of infection (FOI) was estimated using the WHO-FOI calculator. We conducted a follow-up survey among a subsample of seronegative children, to estimate the rate of sero-conversion. Results: Among 5236 children tested, 1521 were positive for anti-dengue IgG antibody. The overall seroprevalence in the state was 29% (95% CI 24.1–33.9). The validity corrected seroprevalence was 30.9% in the overall sample, 46.9% in Thiruvananthapuram, 26.9% in Kozhikkode and 24.9% in Kollam. Age-specific seroprevalence increased with age; 25.7% at 9 years, 29.5% at 10 years, 30.9% at 11 years and 33.9% at 12 years. Seroprevalence varied widely across clusters (16.1%–71.4%). The estimated force of infection was 3.3/100 person-years and the seroconversion rate was 4.8/100 person-years. 90% of children who tested positive were not aware of dengue infection. All the four serotypes were identified in PRNT and 40% of positive samples had antibodies against multiple serotypes. Interpretation: The study validates the WHO methodology for dengue serosurveys and confirms its feasibility in a community setting. The overall seroprevalence in the 9–12 year age group is low to moderate in Kerala; there are regional variations; high burden and low burden clusters co-exist in the same districts. The actual burden of dengue exceeds the reported numbers. Heterogeneity in prevalence, the high proportion of inapparent dengue and the hyperendemic situation suggest the need for region-specific and targeted interventions, including vaccination. Funding: World Health Organization.

Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management. Ocular gene therapies target a range of ocular disorders, but retinal diseases are of particular importance due to the prevalence of retinal disease and the current treatment burden of such diseases on affected patients, as well as the challenge of properly delivering these therapies to the target tissue. The purpose of this review is to provide an update on the most current data available for five different retinal gene therapies currently undergoing clinical trials for use against age-related macular degeneration (AMD) and the development of novel delivery routes for the administration of such therapies. Research has been performed and compiled from PubMed and the select authors of this manuscript on the treatment and effectiveness of five current retinal gene therapies: Luxturna, ADVM-022, RGX-314, GT-005, and HMR59. We present the available data of current clinical trials for the treatment of neovascular and dry age-related macular degeneration with different AAV-based gene therapies. We also present current research on the progress of developing novel routes of administration for ocular gene therapies. Retinal gene therapies offer the potential for life-changing treatment for chronic conditions like age-related macular degeneration with a single administration. In doing so, gene therapies change the landscape of treatment options for these chronic conditions for both patient and provider.

Periungual pyogenic granulomas are benign vascular tumors that present as painful, round, spontaneously bleeding lesions composed of rapidly proliferating capillaries and excess tissue. The vast majority of pyogenic granulomas are caused by physical trauma or infectious agents and they may resolve spontaneously. Herein, we highlight a very rare case of periungual pyogenic granulomas induced by the regularly prescribed oral retinoid acitretin during treatment for congenital palmoplantar keratoderma. This unique case showed that it is feasible to continue acitretin therapy in the presence of pyogenic granuloma development if proper dose reduction and topical therapies are utilized. The patient's lesions resolved within two weeks of this protocol's initiation and the pyogenic granulomas did not recur over the course of a six-month follow-up observation period. In addition, we performed a systematic review of the literature using PubMed databases for the clinical features and treatments in other reported acitretin-induced pyogenic granuloma cases; we compiled a comprehensive list of other prescription drugs known to cause pyogenic granulomas up-to-date.

This paper presents a reflexive analysis of how university educators experience the shift to increasing online teaching in 2019. We explore what it means to be an online educator in contemporary higher education and aim to raise questions about how we approach online education and understand ourselves as educators, informed by a sociomaterial lens. The research utilised collaborative autoethnography (CAE) to facilitate meaning-making and uncover complex perspectives through collaboration and conversation. This enabled us to question what we as educators were losing and what we were gaining as a consequence of shifting to more online modes of teaching via university mandated platforms and processes. Through this methodology, various themes emerged: the role of corporeality; how we constructed ourselves through texts; how others materialised us in virtual spaces; the experience of online time; and our transforming practices and identities. This paper provides a snapshot of a significant cultural milieu in academia as we were afforded time to engage in reflexive practice about teaching online just as the academic world was abruptly mandated to shift almost wholly online. It also provides unique insights into the significance of understanding ourselves as both embodied and social, and the importance of community within academia.

WHO's theme on its 75th year, “Health for All”, is both appropriate and meaningful on account of the unfinished agenda of primary health care (PHC), the Sustainable Development Goals, and the aftermath of the COVID-19 pandemic. The Kerala experience of the pandemic amply demonstrated that the application of these PHC principles helped to address diverse aspects of physical, mental, and social dimensions. The need for 'internalization' of One Health principles and operational strategies cannot be over-emphasized.

Summary: Background: There is a high burden of stroke, including recurrent stroke, in India. We aimed to assess the effect of a structured semi-interactive stroke prevention package in patients with subacute stroke to reduce recurrent strokes, myocardial infarction, and death. Methods: This was a multicentre, randomised, clinical trial conducted in 31 centres of the Indian Stroke Clinical Trial Network (INSTRuCT). Adult patients with first stroke and access to a mobile cellular device were randomly allocated (1:1) to intervention and control groups by the research coordinators at each centre using a central, in-house, web-based randomisation system. The participants and research coordinators at each centre were not masked to group assignment. The intervention group received regular short SMS messages and videos that promoted risk factor control and medication adherence and an educational workbook, in one of 12 languages, and the control group received standard care. The primary outcome was a composite of recurrent stroke, high-risk transient ischaemic attack, acute coronary syndrome, and death at 1 year. The outcome and safety analyses were done in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03228979 and Clinical Trials Registry-India (CTRI/2017/09/009600) and was stopped for futility after interim analysis. Findings: Between April 28, 2018, and Nov 30, 2021, 5640 patients were assessed for eligibility. 4298 patients were randomised to the intervention group (n=2148) or control group (n=2150). 620 patients were not followed up at 6 months and a further 595 patients were not followed up at 1 year because the trial was stopped for futility after interim analysis. 45 patients were lost to follow-up before 1 year. Acknowledgment of receipt of the SMS messages and videos by the intervention group patients was low (17%). The primary outcome occurred in 119 (5·5%) of 2148 patients in the intervention group and 106 (4·9%) of 2150 patients in the control group (adjusted odds ratio 1·12; 95% CI 0·85–1·47; p=0·370). Among the secondary outcome measures, alcohol cessation and smoking cessation were higher in the intervention group than in the control group (alcohol cessation 231 [85%] of 272 in the intervention group vs 255 [78%] of 326 in the control group; p=0·036; smoking cessation 202 [83%] vs 206 [75%]; p=0·035). Medication compliance was better in the intervention group than in the control group (1406 [93·6%] of 1502 vs 1379 [89·8%] of 1536; p

A technique called biofloc technology (BFT) is an environmentally friendly method for aquaculture in which a successful growing cycle depends on the maintenance and monitoring of water quality parameters. Studies have revealed that improving water quality in BFT and maintaining the safety range of the parameters can help to increase the growth performance of cultured species. Following a systematic review of the literature, a meta-analysis was performed to explore how some important water parameters such as pH, dissolved oxygen (DO), nitrite (NO2–N), nitrate (NO3–N), ammonia (NH3–N), total ammonia nitrogen (TAN), total suspended solids (TSS), and alkalinity were influenced by different BFT systems. The PRISMA screening process was followed, and 33 studies were eligible for the meta-analysis. The meta-analyses showed that NO2–N and TSS were significantly affected by BFT, while pH, DO, NO3–N, NH3–N, TAN, and alkalinity were not significantly influenced by this system. The analyses revealed that NO2–N had a significant negative effect size due to BFT, whereas TSS showed a significant positive effect size. The study also revealed some publication bias in which few experiments of some studies showed extremely positive and negative effect sizes due to BFT application in the system. Overall, the findings suggest clear evidence of the profound influence of BFT on the water quality parameters in different aquaculture systems, suggesting the future development of BFT for sustainable and environmentally friendly aquaculture production.

Background: The traditional Neurology exit examination in India has remained unchanged over the last few decades. In developed countries, objective evaluation methods have replaced the traditional ones. A need for such methods has not been explored in India. Objective: We aimed to study the perceptions and key recommendations of Neurology examiners on the existing examination pattern. Material and Methods: We conducted an online survey of examiners perceptions and recommendations using a set of 10 multiple-choice questions and an open-ended question. Results: 46 examiners provided completed responses suitable for analysis. Nearly equal proportions (30%) of the examiners had 10 years, 10–25 years and >25 years' experience. 92% were not satisfied with current system, 95% did not find adequate time for correction of theory scripts, 90% felt that theory questions were random, and 95% had legibility issues. 84% felt that the practical exams do not test true learning, 98% felt the examination stress impairs the performance and 85% felt that there are no objective criteria to pass the candidate. 83% felt the current system-needed changes. The key suggestions provided by the examiners to improve the system included objective assessments like MCQ, OSCE, OSLER and DOPS, inclusion of larger number of short answer type questions and periodic internal assessments of the candidates. Conclusions: A vast majority of examiners favoured changes to the current examination system and provided key recommendations. A larger study is needed to extrapolate these findings to the rest of India.

Purpose: To compare the effectiveness of three root canal irrigants with the influence of activation technique on the depth of sealer penetration into dentinal tubules using a confocal laser scanning microscope (CLSM). Materials and Methods: Sixty recently extracted human mandibular premolars with single straight canals (n = 60) were prepared with ProTaper Next NiTi rotary files up to X3. The samples were divided into three groups according to the final irrigation solution (n = 20), 5.25% sodium hypochlorite, 2% chlorhexidine digluconate, 17% ethylene-diamine-tetraacetic acid (EDTA). Each group was further subdivided into two groups according to the ultrasonic activation protocol and then obturated with a single gutta-percha size X3 and labeled sealer mixed with 0.01% fluorescent rhodamine B after the final irrigation protocol. Transverse sections were obtained at 2, 5, and 8 mm from the apex and observed under CLSM. It recorded the maximum penetration depth of both irrigant and sealer. Data were analyzed using a three-way analysis of variance and Tukey test (P = 0.05). Results: 17% EDTA exhibited significantly higher penetration depth with ultrasonic activation than the other groups and also determined (P < 0.011) statistically significant differences at root canal third (coronal, middle, apical; P < 0.011). Conclusions: The dentinal tubule penetration was significantly affected by selecting a root canal irrigant, an ultrasonic activation protocol, and root canal third. 17% EDTA with ultrasonic activation seemed beneficial in dentinal tubule penetration. Hence, the depth of sealer penetration might influence the outcome or success rate of endodontic therapy.

Purpose: The aim of this study was to compare release from masking (RM) between Mandarin-speaking and English-speaking listeners with normal hearing for competing speech when target-masker sex cues, spatial cues, or both were available. Method: Speech recognition thresholds (SRTs) for competing speech were measured in 21 Mandarin-speaking and 15 English-speaking adults with normal hearing using a modified coordinate response measure task. SRTs were measured for target sentences produced by a male talker in the presence of two masker talkers (different male talkers or female talkers). The target sentence was always presented directly in front of the listener, and the maskers were either colocated with the target or were spatially separated from the target (+90°, -90°). Stimuli were presented via headphones and were virtually spatialized using head-related transfer functions. Three masker conditions were used to measure RM relative to the baseline condition: (a) talker sex cues, (b) spatial cues, or (c) combined talker sex and spatial cues. Results: The results showed large amounts of RM according to talker sex and/or spatial cues. There was no significant difference in SRTs between Chinese and English listeners for the baseline condition, where no talker sex or spatial cues were available. Furthermore, there was no significant difference in RM between Chinese and English listeners when spatial cues were available. However, RM was significantly larger for Chinese listeners when talker sex cues or combined talker sex and spatial cues were available. Conclusion: Listeners who speak a tonal language such as Mandarin Chinese may be able to take greater advantage of talker sex cues than listeners who do not speak a tonal language.

Production of biodiesel together with wastewater treatment and CO2 sequestration is a promising technology. The growing levels of carbon dioxide in the atmosphere increase the amount of dissolved CO2 in natural watercourses, triggering the increase in concentrations of bicarbonate and hydrogen ions while dropping those of carbonate and hydroxyl ions. The active carbon cycling in coastal areas, which can result in periodic and daily fluctuations in pH and CO2 concentrations that may surpass those anticipated for the extensive marine ecosystems, is regarded as one of the consequences of climate change. Studies were conducted to examine the effects of various pH levels on algal growth and lipid production in order to better understand how the growth of algae may be influenced in such conditions. In the present study, the influence of three different pH levels (6, 8, and 10) was studied to evaluate microalgae’s carbohydrate utilisation and lipid accumulation during the operation’s starvation phase (SP). Microalgae, in the study, were cultivated in two modes, namely mixotrophic [growth phase (GP)] and autotrophic [pH-induced (SP)] conditions. Enhancement in biomass formation, and intracellular carbohydrate accumulation were recorded during the GP operation, while noticeable lipid productivities (Total/neutral, 26.93/10.3%) were observed during SP operation at pH 8. Pigment analysis showed variations in both the procedures where higher Chl a concentration was noticed in GP, and higher Chl b was detected during SP. Nile red fluorescent staining strongly supports the existence of intracellular lipid bodies (LB). GC analysis of fatty acid methyl esters (FAME) showed the existence of a substantial amount of saturated fatty acids (SFA) compared with unsaturated fatty acids (USFA). Efficient wastewater treatment with nutrient assimilation was reported during the GP operation, demonstrating the phyco-remediation.

The role and relevance of methanol in the origin and structure of the RNA world is discussed. Methanol is a pivotal, renewable, and regenerable source from which almost all chemical materials, simple or complex, can be accessed. Olefins and carbonyl compounds, amines and amino acids, peptides and polypeptides, and the molecular building blocks in the initial stages of the biological evolution to life’s origin are obtained through methanol as a source material by its chemical transformation. The formation of methanol, whether in stellar and interstellar media, in deep sea-bottom hot hydrothermal vents or from geothermal sources, results from CO2 hydrogenation. It is the basic reaction, setting the stage for the formation of fundamental “organic” building blocks for the formation of simple prebiotic cells to subsequent biological evolution to cells. The important observation of many organics– hydrocarbons and ions including the large expanse of methane and methanol in the interstellar medium and stellar peripheries is a clear indication of “stellar reductive processes” and ensuing reactions shedding light on the probable significant role of extraterrestrial methanol as the basic source material toward a multi-step transformation into complex life molecules such as RNA.

In euryhaline teleost black porgy, Acanthopagrus schlegelii, the glucocorticoid receptor (gr), growth hormone receptor (ghr), prolactin (prl)-receptor (prlr), and sodium–potassium ATPase alpha subunit (α-nka) play essential physiological roles in the osmoregulatory organs, including the gill, kidney, and intestine, during osmotic stress. The present study aimed to investigate the impact of pituitary hormones and hormone receptors in the osmoregulatory organs during the transfer from freshwater (FW) to 4 ppt and seawater (SW) and vice versa in black porgy. Quantitative real-time PCR (Q-PCR) was carried out to analyze the transcript levels during salinity and osmoregulatory stress. Increased salinity resulted in decreased transcripts of prl in the pituitary, α-nka and prlr in the gill, and α-nka and prlr in the kidney. Increased salinity caused the increased transcripts of gr in the gill and α-nka in the intestine. Decreased salinity resulted in increased pituitary prl, and increases in α-nka and prlr in the gill, and α-nka, prlr, and ghr in the kidney. Taken together, the present results highlight the involvement of prl, prlr, gh, and ghr in the osmoregulation and osmotic stress in the osmoregulatory organs (gill, intestine, and kidney). Pituitary prl, and gill and intestine prlr are consistently downregulated during the increased salinity stress and vice versa. It is suggested that prl plays a more significant role in osmoregulation than gh in the euryhaline black porgy. Furthermore, the present results highlighted that the gill gr transcript’s role was solely to balance the homeostasis in the black porgy during salinity stress.

Objective: We aimed to study the long-term association of LV mass index (LVMI) and myocardial fibrosis with ventricular arrhythmia (VA) in a population of patients with confirmed hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance imaging (CMR). Methods: We retrospectively analyzed the data in consecutive HCM patients confirmed on CMR referred to an HCM clinic between January 2008 and October 2018. Patients were followed up yearly following diagnosis. Baseline demographics, risk factors and clinical outcomes from cardiac monitoring and an implanted cardioverter defibrillator (ICD) were analyzed for association of LVMI and LV late gadolinium enhancement (LVLGE) with VA. Patients were then allocated to one of two groups according to the presence of VA (Group A) or absence of VA (Group B) during the follow-up period. The transthoracic echocardiogram (TTE) and CMR parameters were compared between the two groups. Results: A total of 247 patients with confirmed HCM (age 56.2 ± 16.6, male = 71%) were studied over the follow-up period of 7 ± 3.3 years (95% CI = 6.6–7.4 years). LVMI derived from CMR was higher in Group A (91.1 ± 28.1 g/m2 vs. 78.8 ± 28.3 g/m2, p = 0.003) when compared to Group B. LVLGE was higher in Group A (7.3 ± 6.3% vs. 4.7 ± 4.3%, p = 0.001) when compared to Group B. Multivariable Cox regression analysis showed LVMI (hazard ratio (HR) = 1.02, 95% CI = 1.001–1.03, p = 0.03) and LVLGE (HR = 1.04, 95% CI = 1.001–1.08, p = 0.04) to be independent predictors for VA. Receiver operative curves showed higher LVMI and LVLGE with a cut-off of 85 g/m2 and 6%, respectively, to be associated with VA. Conclusions: LVMI and LVLGE are strongly associated with VA over long-term follow-up. LVMI requires more thorough studies to consider it as a risk stratification tool in patients with HCM.