Study of behavioral and psychosocial factors relating to needle stick injuries in nursing staff of a tertiary care cancer hospital of Punjab, India.

Background and Objectives: Needle stick injury (NSI) is the most dreaded occupational health hazard affecting a healthcare worker (HCW) psychologically and physically. The risk of infection post needle stick injury ranges between 1.9% to greater than 40% for HBV infections, 2.7-10% for HCV and 0.2-0.44% for HIV infections. As per National AIDS Control Organisation (NACO) records, nursing staff is at highest risk (43%) followed by physicians (28%). The main objective of this study was to evaluate knowledge of nursing staff about needle stick injuries and to study factors leading to such incidents in their working areas, impart them knowledge regarding the same and fill gaps in knowledge. Materials and Methods: This is a cross-sectional retrospective analysis involving nursing staff and students. p values were calculated using SPSS software. Results: Overall NSI prevalence among nursing staff and students was 51.6% whereas in more exposed and less exposed group was 47.45% and 10.16% respectively (p=0.2056). The most common cause of NSI incident was recapping of needle (38.5%) followed by transferring needle to sharp container (35%). Conclusion: Consequences of NSI are serious and this study has tried to emphasize on the need to study the factors leading to NSI.

Stromal mediated DNA damage promotes high grade serous ovarian cancer initiation.

The fundamental steps in high-grade serous ovarian cancer (HGSOC) initiation are unclear, thus providing critical barriers to the development of prevention or early detection strategies for this deadly disease. Increasing evidence demonstrates most HGSOC starts in the fallopian tube epithelium (FTE). Current models propose HGSOC initiates when FTE cells acquire increasing numbers of mutations allowing cells to evolve into serous tubal intraepithelial carcinoma (STIC) precursors and then to full blown cancer. Here we report that epigenetically altered mesenchymal stem cells (termed high risk MSC-hrMSCs) can be detected prior to the formation of ovarian cancer precursor lesions. These hrMSCs drive DNA damage in the form of DNA double strand breaks in FTE cells while also promoting the survival of FTE cells in the face of DNA damage. Indicating the hrMSC may actually drive cancer initiation, we find hrMSCs induce full malignant transformation of otherwise healthy, primary FTE resulting in metastatic cancer in vivo . Further supporting a role for hrMSCs in cancer initiation in humans, we demonstrate that hrMSCs are highly enriched in BRCA1/2 mutation carriers and increase with age. Combined these findings indicate that hrMSCs may incite ovarian cancer initiation. These findings have important implications for ovarian cancer detection and prevention.

Companies inadvertently fund online misinformation despite consumer backlash.

The financial motivation to earn advertising revenue has been widely conjectured to be pivotal for the production of online misinformation1-4. Research aimed at mitigating misinformation has so far focused on interventions at the user level5-8, with little emphasis on how the supply of misinformation can itself be countered. Here we show how online misinformation is largely financed by advertising, examine how financing misinformation affects the companies involved, and outline interventions for reducing the financing of misinformation. First, we find that advertising on websites that publish misinformation is pervasive for companies across several industries and is amplified by digital advertising platforms that algorithmically distribute advertising across the web. Using an information-provision experiment9, we find that companies that advertise on websites that publish misinformation can face substantial backlash from their consumers. To examine why misinformation continues to be monetized despite the potential backlash for the advertisers involved, we survey decision-makers at companies. We find that most decision-makers are unaware that their companies' advertising appears on misinformation websites but have a strong preference to avoid doing so. Moreover, those who are unaware and uncertain about their company's role in financing misinformation increase their demand for a platform-based solution to reduce monetizing misinformation when informed about how platforms amplify advertising placement on misinformation websites. We identify low-cost, scalable information-based interventions to reduce the financial incentive to misinform and counter the supply of misinformation online.

Metabolically active neutrophils represent a permissive niche for Mycobacterium tuberculosis.

Mycobacterium tuberculosis- (Mtb) infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection. Using single-cell metabolic and transcriptional analyses, we found that neutrophils in the Mtb-infected lung displayed elevated mitochondrial metabolism, which was largely attributed to the induction of activated neutrophils with enhanced metabolic activities. The activated neutrophil subpopulation was also identified in the lung granulomas from Mtb-infected non-human primates. Functionally, activated neutrophils harbored more viable bacteria and displayed enhanced lipid uptake and accumulation. Surprisingly, we found that IFNγ promoted the activation of lung neutrophils during Mtb infection. Lastly, perturbation of lipid uptake pathways selectively compromised Mtb survival in activated neutrophils. These findings suggest that neutrophil heterogeneity and metabolic diversity are key to their permissiveness for Mtb, and that metabolic pathways in neutrophils represent potential host-directed therapeutics in TB.

Covalent Organic Frameworks as Potential Drug Carriers and Chemotherapeutic Agents for Ovarian Cancers.

Anticancer drugs are often associated with limitations such as poor stability in aqueous solutions, limited cell membrane permeability, nonspecific targeting, and irregular drug release when taken orally. One possible solution to these problems is the use of nanocarriers of drug molecules, particularly those with targeting ability, stimuli-responsive properties, and high drug loading capacity. These nanocarriers can improve drug stability, increase cellular uptake, allow specific targeting of cancer cells, and provide controlled drug release. While improving the therapeutic efficacy of cancer drugs, contemporary researchers also aim to reduce their associated side effects, such that cancer patients are offered with a more effective and targeted treatment strategy. Herein, a set of nine porous covalent organic frameworks (COFs) were tested as drug delivery nanocarriers. Among these, paclitaxel loaded in COF-3 was most effective against the proliferation of ovarian cancer cells. This study highlights the emerging potential of COFs in the field of therapeutic drug delivery. Due to their biocompatibility, these porous COFs provide a viable substrate for controlled drug release, making them attractive candidates for improving drug delivery systems. This work also demonstrates the potential of COFs as efficient drug delivery agents, thereby opening up new opportunities in the field of sarcoma therapy.

Oral health assessment and treatment needs of 12- and 15-year-old children residing in tribal welfare and private hostels - A comparative study.

Background and Objectives: Oral health is an integral part of general health. Providing oral health care facilities and creating awareness about the oral health problem in under-served children and communities may lead to a better oral-health-related quality of life of the individual. The present study aims to assess and compare the oral health status and treatment needs of 12- and 15-year-old children residing in tribal welfare hostels and other private hostels of Bhopal district, Madhya Pradesh. Materials and Methods: The present descriptive cross-sectional study consisted of a total sample size of 800 children, 400 in each group (tribal welfare hostel and private hostel groups). Oral health status and treatment needs were assessed using World Health Organization proforma 1997. Oral health behavior including health of teeth and gums, oral hygiene aids, brushing frequency, consumption of sweets in between meals, and present general and oral health was assessed. Utilization of dental services was also assessed using a pre-designed questionnaire, which was completed by the study participants. Results: Statistical analysis was carried out using Chi-square test. Significant differences were noted between the groups in regarding oral health behaviors and visit to a dentist during the past 12 months (P = 0.002*), which were lower in tribal children. Tribal children were having higher dental fluorosis as compared to the private hostel children (P = 0.043*). Decay in permanent teeth (P = 0.006*) and missing of permanent teeth (P = 0.05*) were higher among tribal children. Conclusion: The present study revealed a poor oral health status and treatment needs of tribal children. Tribal children were having higher dental fluorosis as compared to the private hostel children. Decay in permanent teeth and missing of permanent teeth were higher among tribal children. Oral health behaviors and utilization of dental services were lower in tribal children. Good oral health has a definitive influence on general health and thus contributes to self-image and social interaction.

Incidence, Risk, and Clinical Course of New-Onset Diabetes in Long COVID: Protocol for a Systematic Review and Meta-Analysis of Cohort Studies.

BACKGROUND: COVID-19, an infectious disease pandemic, affected millions of people globally, resulting in high morbidity and mortality. Causing further concern, significant proportions of COVID-19 survivors endure the lingering health effects of SARS-CoV-2, the pathogen that causes COVID-19. One of the diseases manifesting as a postacute sequela of COVID-19 (also known as "long COVID") is new-onset diabetes. OBJECTIVE: The aim of this study is to examine the incidence of new-onset diabetes in patients with long COVID and assess the excess risk compared with individuals who tested negative for COVID-19. The study also aims to estimate the population-attributable fraction for COVID-19 as a risk factor for new-onset diabetes in long COVID and investigate the clinical course of new-onset diabetes cases. METHODS: This is a protocol for a systematic review and meta-analysis. PubMed, MEDLINE, Embase, Scopus, and Web of Science databases will be systematically searched to identify articles published between December 2019 and July 2024. A comprehensive search strategy for each database will be developed using a combination of Medical Subject Headings terms, subject headings, and text words to identify eligible studies. Cohort studies and randomized controlled trials (only control arms) involving patients with COVID-19 of any age, with follow-up data on new-onset diabetes in long COVID, will be considered for inclusion. Controls will comprise individuals who tested negative for COVID-19, with or without other respiratory tract infections. Three independent reviewers (AST, NB, and TT) will perform article selection, data extraction, and quality assessment of the studies. A fourth reviewer (ST) will review the identified studies for final inclusion in the analysis. The random-effects DerSimonian-Laird models will be used to estimate the pooled incidence proportion (%), incidence rate of diabetes (per 1000 person-years), and risk ratio (with 95% CIs) for diabetes incidence. RESULTS: A total of 1972 articles were identified through the initial search conducted in August 2023. After excluding duplicates, conducting title and abstract screening, and completing full-text reviews, 41 articles were found to be eligible for inclusion. The search will be updated in July 2024. Currently, data extraction is underway, and the meta-analysis is expected to be completed in August 2024. Publication of the study findings is anticipated by the end of 2024. CONCLUSIONS: The study findings should provide valuable insights to inform both clinical practice and public health policies regarding the effective management of new-onset diabetes in patients with long COVID. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54853.

Factors associated with immune responses to SARS-CoV-2 vaccination in autoimmune disease individuals.

Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 autoimmune subjects, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti-spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell-depleted multiple sclerosis (MS) subjects were associated with higher CD8 T cell responses. By contrast, subjects taking mycophenolate mofetil exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low IgG anti-spike response included B cell depletion within the last year, fingolimod, and combination treatment with mycophenolate mofetil (MMF) and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine, is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of pre-existing anti-type I interferon antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2-related deaths suggest that T cell immunity contributes to protection in autoimmune disease.

Increased endothelial sclerostin caused by elevated DSCAM mediates multiple trisomy 21 phenotypes.

Trisomy 21 (T21), a recurrent aneuploidy occurring in 1:800 births, predisposes to congenital heart disease (CHD) and multiple extracardiac phenotypes. Despite a definitive genetic etiology, the mechanisms by which T21 perturbs development and homeostasis remain poorly understood. We compared the transcriptome of CHD tissues from 49 patients with T21 and 226 with euploid CHD (eCHD). We resolved cell lineages that misexpressed T21 transcripts by cardiac single-nucleus RNA sequencing and RNA in situ hybridization. Compared with eCHD samples, T21 samples had increased chr21 gene expression; 11-fold-greater levels (P = 1.2 × 10-8) of SOST (chr17), encoding the Wnt inhibitor sclerostin; and 1.4-fold-higher levels (P = 8.7 × 10-8) of the SOST transcriptional activator ZNF467 (chr7). Euploid and T21 cardiac endothelial cells coexpressed SOST and ZNF467; however, T21 endothelial cells expressed 6.9-fold more SOST than euploid endothelial cells (P = 2.7 × 10-27). Wnt pathway genes were downregulated in T21 endothelial cells. Expression of DSCAM, residing within the chr21 CHD critical region, correlated with SOST (P = 1.9 × 10-5) and ZNF467 (P = 2.9 × 10-4). Deletion of DSCAM from T21 endothelial cells derived from human induced pluripotent stem cells diminished sclerostin secretion. As Wnt signaling is critical for atrioventricular canal formation, bone health, and pulmonary vascular homeostasis, we concluded that T21-mediated increased sclerostin levels would inappropriately inhibit Wnt activities and promote Down syndrome phenotypes. These findings imply therapeutic potential for anti-sclerostin antibodies in T21.

Overexpression of TSPAN8 in consensus molecular subtype 3 colorectal cancer.

BACKGROUND: Recently, consensus molecular subtypes (CMSs) have been proposed as a robust transcriptome-based classification system for colorectal cancer (CRC). Tetraspanins (TSPANs) are transmembrane proteins. They have been associated with the development of numerous malignancies, including CRC, through their role as "master organizers" for multi-molecular membrane complexes. No previous study has investigated the correlation between TSPANs and CMS classification. Herein, we investigated the expression of TSPANs in patient-derived primary CRC tissues and their CMS classifications. METHODS: RNA samples were derived from primary CRC tissues (n = 100 patients diagnosed with colorectal adenocarcinoma) and subjected to RNA sequencing for transcriptome-based CMS classification and TSPAN-relevant analyses. Immunohistochemistry (IHC) and immunofluorescence (IF) stains were conducted to observe the protein expression level. To evaluate the relative biological pathways, gene-set enrichment analysis was performed. RESULTS: Of the highly expressed TSPAN genes in CRC tissues (TSPAN8, TSPAN29, and TSPAN30), TSPAN8 was notably overexpressed in CMS3-classified primary tissues. The overexpression of TSPAN8 protein in CMS3 CRC was also observed by IHC and IF staining. As a result of gene-set enrichment analysis, TSPAN8 may potentially play a role in organizing signaling complexes for kinase-based metabolic deregulation in CMS3 CRC. CONCLUSIONS: The present study reports the overexpression of TSPAN8 in CMS3 CRC. This study proposes TSPAN8 as a subtype-specific biomarker for CMS3 CRC. This finding provides a foundation for future CMS-based studies of CRC, a complex disease and the second leading cause of cancer mortality worldwide.

Paper-based sensing of phytotoxicant gossypol in aqueous media through turn-on visible-light emitting lanthanide-luminescence.

Gossypol, a phytotoxicant in cotton-seed oil, has been found to sensitize Tb(III)-luminescence in a supramolecular hydrogel. Based on this observation, a paper-based sensor has been developed to detect gossypol with a limit of detection (LOD) of 2.9 nM. This is the first report of water-based detection with the highest sensitivity involving turn-on time-gated luminescence. This method was also able to sense gossypol in commercial crude cotton-seed oil.

Dose escalation of tolinapant (ASTX660) in combination with standard radical chemoradiotherapy in cervical cancer : a study protocol for a phase 1b TiTE-CRM clinical trial (CRAIN) in UK secondary care centres.

BACKGROUND: Cervical cancer is the fourth most common cancer in women, with an estimated 342,000 deaths worldwide in 2020. Current standard of care in the UK for locally advanced cervical cancer is concurrent chemoradiotherapy with weekly cisplatin, yet 5-year overall survival rates are only 65% with a distant relapse rate of 50%. Inhibitors of Apoptosis Proteins (IAPs) are often overexpressed in cancer cells and associated with tumour progression and resistance to treatment. Tolinapant, developed by Astex Pharmaceuticals, is an IAP antagonist with an additional mechanism of action via down-regulation of NF-kB, an important regulator in cervical cancer. Preclinical studies performed using tolinapant in combination with cisplatin and radiotherapy showed inhibition of tumour growth and enhanced survival. There is therefore a strong rationale to combine tolinapant with chemoradiotherapy (CRT). METHODS: CRAIN is a phase Ib open-label, dose escalation study to characterise the safety, tolerability and initial evidence for clinical activity of tolinapant when administered in combination with cisplatin based CRT. Up to 42 patients with newly diagnosed cervix cancer will be recruited from six UK secondary care sites. The number of participants and the duration of the trial will depend on toxicities observed and dose escalation decisions, utilising a TiTE-CRM statistical design. Treatment will constist of standard of care CRT with 45 Gy external beam radiotherapy given in 25 daily fractions over 5 weeks with weekly cisplatin 40mg/m2. This is followed by brachytherapy for which common schedules will be 28 Gy in 4 fractions high-dose-rate or 34 Gy in 2 fractions pulsed-dose-rate. Tolinapant will be administered in fixed dose capsules taken orally daily for seven consecutive days as an outpatient on alternate weeks (weeks 1, 3, 5) during chemoradiation. Dose levels for tolinapant which will be assessed are: 60 mg; 90 mg (starting level); 120 mg; 150 mg; 180 mg. Escalation will be guided by emerging safety data and decisions by the Safety Review Committee. DISCUSSION: If this trial determines a recommended phase II dose and shows tolinapant to be safe and effective in combination with CRT, it would warrant future phase trials. Ultimately, we hope to provide a synergistic treatment option for these patients to improve outcome. TRIAL REGISTRATIONS: EudraCT Number: 2021-006555-34 (issued 30th November 2021); ISRCTN18574865 (registered 30th August 2022).

High temperature and solar radiation in the Red Sea enhance the dissolution of crude oil from surface films.

The Red Sea is a hotspot of biodiversity susceptible to oil pollution. Besides, it is one of the warmest seas on the Earth with highly transparent waters. In this study, we estimated the oil dissolution rates under natural sunlight spectra and temperature conditions using coastal oil slicks collected after the 2019 Sabiti oil spill in the Red Sea. Optical analyses revealed the significant interactive effect of sunlight and temperature in enhancing the dissolution of oil into dissolved organic matter (DOM). The highest oil dissolution rate (38.68 g C m-3 d-1) was observed in full-spectrum sunlight. Oil dissolution significantly enhanced total organic carbon (TOC) and polycyclic aromatic hydrocarbons (PAHs) in seawater. High nucleic acid (HNA) bacteria, likely the oil degraders, proliferated from 30 to 70 - 90% after 4 days. The heavier stable carbon isotopic composition of methane (δ13C-CH4) and lighter stable carbon isotopic composition of carbon dioxide (δ13C-CO2) indicate the putative role of bacterial processes in the natural degradation of crude oil. The results indicated that the combined effect of temperature and solar radiation enhanced the biological and photochemical dissolution of oil on the Red Sea surface.

Eating behaviours, social media usage, and its association: A cross-sectional study in Indian medical undergraduates.

Background: Despite increasing incidence, there is little data on abnormal eating behaviours or disorders in Indian youth, especially medical students. Additionally, little literature exists measuring the association of social media use with abnormal eating behaviours. Aim: To assess the prevalence of abnormal eating behaviours amongst medical students, social media usage, and any association of social media usage with eating behaviours. Materials and Methods: An online cross-sectional questionnaire-based study was conducted with 272 participants at a medical college, and two scales: the Three-Factor Eating Questionnaire-Revised 21items (TFEQ-R21) and the Scale of Effects of social media on Eating Behaviour (SESMEB) were used. Results: 22% of the participants reported abnormal eating behaviours. A significant difference in the effect of social media on eating behaviour according to the year of study [f = 3.08, P = 0.02] was seen with the final years having the lowest and the first years having the highest SESMEB scores. Students using more than 4 social media platforms had a higher SESMEB score [t = -2.02, P < 0.04]. A positive correlation was seen between TFEQ domains such as uncontrolled eating [r = 0.38, P = 0.01], emotional eating [r = 0.30, P = 0.01], and TFEQ total score [r = 0.40, P = 0.01] with SESMEB scores. Conclusion: This study finds a significant correlation between increased social media usage and developing abnormal eating behaviours in medical students. It highlights the need for the creation of policies regulating social media use with eating behaviours in mind.

Understanding the Role of Large Language Models in Personalizing and Scaffolding Strategies to Combat Academic Procrastination.

Traditional interventions for academic procrastination often fail to capture the nuanced, individual-specific factors that underlie them. Large language models (LLMs) hold immense potential for addressing this gap by permitting open-ended inputs, including the ability to customize interventions to individuals' unique needs. However, user expectations and potential limitations of LLMs in this context remain underexplored. To address this, we conducted interviews and focus group discussions with 15 university students and 6 experts, during which a technology probe for generating personalized advice for managing procrastination was presented. Our results highlight the necessity for LLMs to provide structured, deadline-oriented steps and enhanced user support mechanisms. Additionally, our results surface the need for an adaptive approach to questioning based on factors like busyness. These findings offer crucial design implications for the development of LLM-based tools for managing procrastination while cautioning the use of LLMs for therapeutic guidance.

Understanding and Managing Metabolic Deficiencies Post Bariatric and Esophagectomy Surgeries: A Narrative Review of the Literature.

Gastrectomy and esophagectomy are the most performed surgeries in the treatment of both esophageal and gastric cancers. The type of esophagectomy depends on the type of malignancy, site of the tumor, criteria of resection, and field of resection. The three standard approaches to esophagectomy are the transhiatal approach, the left thoracoabdominal approach, and a three-stage procedure. The transhiatal approach involves abdominal and cervical incisions, while the left thoracoabdominal approach is a one-stage procedure that utilizes a single incision exposing the dissection field. The Ivor Lewis and McKeown esophagectomies are two-stage and three-stage surgeries that include laparotomy with right thoracotomy. Malabsorption often emerges as a significant postoperative complication following esophagectomy and gastrectomy surgeries. Malnutrition linked with these cancers has detrimental effects, including heightened rates of postoperative complications, elevated infection risks, delayed wound healing, reduced tolerance to treatment, diminished quality of life, and heightened mortality rates. Our narrative review summarizes and sheds light on solutions to treat malabsorption disorders and malnutrition after gastric bypass surgery. These solutions include methods such as adjustments, supplements, and treatment. Although more research is needed to confirm their effectiveness, these methods indicate potential for lowering the impact on patients' diets. By considering the beneficial implications of these effects and considering solutions, we aim to improve the management of these adverse effects, ultimately improving the overall health and postoperative outcomes of patients.

Protocol for measuring labile cytosolic Zn2+ using an in situ calibration of a genetically encoded FRET sensor.

Zinc (Zn2+) plays roles in structure, catalysis, and signaling. The majority of cellular Zn2+ is bound by proteins, but a fraction of total Zn2+ exists in a labile form. Here, we present a protocol for measuring labile cytosolic Zn2+ using an in situ calibration of a genetically encoded Förster resonance energy transfer (FRET) sensor. We describe steps for producing buffered Zn2+ solutions for performing an imaging-based calibration and analyzing the imaging data generated to determine labile Zn2+ concentration in single cells. For complete details on the use and execution of this protocol, please refer to Rakshit and Holtzen et al.1.