Search

ObjectiveTo evaluate differences based on intrauterine device (IUD) frame geometry in force, and stress, and strain at the stem/arms junction during simulated IUD removal.Study designWe manufactured injection-molded frame models for three Nova-T IUDs (Mirena [model M]; Liletta [model L]; Kyleena [model K]) and a Tatum-T IUD (Paragard [model P]) at two-times scaling. We created a custom fixture to simulate the uterus and used a screw-driven machine to pull models at various displacement rates through the 10 cm fixture cavity to measure force and strain and calculate stress at the IUD stem/arms junction. We tested models at 30 mm/min and higher displacement rates for exploratory analyses. We used Mann-Whitney U test for statistical testing.ResultsWe completed testing at 30 mm/min using five of each Nova-T model and nine model P samples. Resistance against the cavity walls created significantly more force on model P (11.83, interquartile range [IQR] 11.61-12.31) than any Nova-T model samples (p

Research misconduct refers to deliberate or accidental manipulation or misrepresentation of research data, findings, or processes. It can take many forms, such as fabricating data, plagiarism, or failing to disclose conflicts of interest. Data falsification is a serious problem in the field of medical research, as it can lead to the promotion of false or misleading information. Researchers might engage in p-hacking - the practice of using someone else's research results or ideas without giving them proper attribution. Conflict of interest (COI) occurs when an individual's personal, financial, or professional interests could potentially influence their judgment or actions in relation to their research. Nondisclosure of COI can be considered research misconduct and can damage the reputation of the authors and institutions. Hypothesis after results are known can lead to the promotion of false or misleading information. Cherry-picking data is the practice of focusing attention on certain data points or results that support a particular hypothesis, while ignoring or downplaying results that do not. Researchers should be transparent about their methods and report their findings honestly and accurately. Research institutions should have clear and stringent policies in place to address scientific misconduct. This knowledge must become widespread, so that researchers and readers understand what approaches to statistical analysis and reporting amount to scientific misconduct. It is imperative that readers and researchers alike are aware of the methods of statistical analysis and reporting that constitute scientific misconduct. Keywords: Conflict of interest, data fabrication, misconduct, p-hacking, plagiarism, Author(s): Karthik N. Rao (corresponding author) [1]; Manish Mair [2]; Ripu D. Arora [3]; Prajwal Dange [3]; Nitin M. Nagarkar [4] Introduction Research misconduct refers to the deliberate or accidental [...]

Background: The second wave of the COVID-19 pandemic led to a very dreaded complication of mucormycosis. Immunosuppressive action of the COVID-19 virus, co-morbidities, for example, diabetes mellitus (DM), hypertension, use of steroids, and humidified oxygen, are among the important factors that make the patients susceptible to developing mucormycosis. Objective: The present study was conducted to identify and understand all the significant histological changes including the type and extent of tissue involvement, the pattern of inflammation, the volume of fungal hyphae, hemorrhage, etc., in patients with COVID-19 associated mucormycosis (CAM) and correlate with clinical outcome. Method: It was a retrospective cross-sectional observational study involving all the patients of CAM, who underwent debridement or biopsy over a period of 5 months, from April 01, 2021, to August 31, 2021. CAM was classified based on the radiological evaluation, clinical features, and organs involved. Different demographic, clinical, laboratory, and histologic parameters were recorded. The variables were assessed for their association with poor clinical outcomes using multiple logistic regression. P < 0.05 was considered statistically significant. Results: A total of 146 patients were included in the study with a mean age of 49.4 years and 71.2% were male. Sino-naso-palatal was the most common type of CAM (32.9%), while sino-naso-cerebral was the least common (14.3%). DM was present in 54.1% of patients, out of which 26.6% were recently diagnosed. The death occurred in 21.9% of patients. Maximum mortality was observed in CAM of sino-naso-cerebral involvement (42.9%). Total leucocyte count (TLC) [OR = 0.87; 95%CI: 0.76-0.97; P = 0.02] and C-reactive protein (CRP) [OR = 0.97; 95%CI: 0.96-0.99; P = 0.008] were significantly associated with poor outcomes. Other factors, that is, high prothrombin time, DM, ferritin, and the involvement of muscle, skin, and cartilage, were also associated with poor clinical outcomes but were not statistically significant. Similarly, high fungal volume and the presence of thrombosis were also associated with poor outcomes but were not statistically significant. Conclusion: CAM more commonly affects males with co-morbidities. TLC and CRP were significantly associated with poor outcomes. Histologically, the involvement of skin, muscle, and cartilage and the presence of excessive fungal hyphae and thrombosis were also associated with poor outcomes.

Predictability of the various financial instruments can lead to more trust and investment. The study examines the long-term and causal relationship between various Nifty indices and the Ethereum cryptocurrency. This study considers the data from April 2015 to December 2022 in two phases, pre-covid and post-covid. Johansen’s cointegration test was used to determine if the vectors in the data set are cointegrated, using the Max-Eigen and Trace tests for evaluation. The Granger causality test was also used to explore the short-term causal relationship between Ethereum and the five Nifty indices. The study found that post-pandemic daily returns of stock market indices have developed a significant cointegration with the cryptocurrency over time. The Granger causality test results showed bi-directional relationships of Nifty 50, Nifty 200 and Nifty Next 50 with Ethereum and a unidirectional relationship between Nifty Auto and Ethereum. The non-linear results reveal a one-way relationship pre-covid and a bi-directional relationship post-covid except for Nifty Banks. Johansen’s cointegration test, both in the pre-and post-covid-era, indicated that these indices had a substantial long-term cointegration with cryptocurrencies. This study also offers guidance to investors in making long-term investment decisions and to regulatory authorities. This implied that the investing decisions resulted in developing a causal relationship between the equity market and cryptocurrencies, which seemed very unlikely before 2020. This indicates that a new and young investor also considered cryptocurrencies a viable alternate investment option compared to traditional options such as fixed deposits, gold, and other fixed-income instruments.

ABSTRACT Background Detection of cancer at the early stage currently offers the only viable strategy for reducing disease‐related morbidity and mortality. Various approaches for multi‐cancer early detection are being explored, which largely rely on capturing signals from circulating analytes shed by tumors into the blood. The fact that biomarker concentrations are limiting in the early stages of cancer, however, compromises the accuracy of these tests. We, therefore, adopted an alternate approach that involved interrogation of the serum metabolome with machine learning‐based data analytics. Here, we monitored for modulations in metabolite patterns that correlated with the presence or absence of cancer. Results obtained confirmed the efficacy of this approach by demonstrating that it could detect a total of 15 cancers in women with an average accuracy of about 99%. Aims To further increase the scope of our test, we conducted an investigator‐initiated clinical trial involving a total of 6445 study participants, which included both cancer patients and non‐cancer volunteers. Our goal here was to maximize the number of cancers that could be detected, while also covering cancers in both females and males. Methods and Results Metabolites extracted from individual serum samples were profiled by ultra‐performance liquid chromatography coupled to a high‐resolution mass spectrometer using an untargeted protocol. After processing, the data were analyzed by our cancer detection machine‐learning algorithm to differentiate cancer from non‐cancer samples. Results revealed that our test platform could indeed detect a total of 30 cancers, covering both females and males, with an average accuracy of ~98%. Importantly, the high detection accuracy remained invariant across all four stages of the cancers. Conclusion Thus, our approach of integrating untargeted metabolomics with machine learning‐powered data analytics offers a powerful strategy for early‐stage multi‐cancer detection with high accuracy. Trial Registration: Registration No: CTRI/2023/03/050316

DYRK1A, a ubiquitously expressed kinase, is linked to the dominant intellectual developmental disorder, microcephaly, and Down syndrome in humans. It regulates numerous cellular processes such as cell cycle, vesicle trafficking, and microtubule assembly. DYRK1A is a critical regulator of organ growth; however, how it regulates organ growth is not fully understood. Here, we show that the knockdown of DYRK1A in mammalian cells results in reduced cell size, which depends on mTORC1. Using proteomic approaches, we found that DYRK1A interacts with the tuberous sclerosis complex (TSC) proteins, namely TSC1 and TSC2, which negatively regulate mTORC1 activation. Furthermore, we show that DYRK1A phosphorylates TSC2 at T1462, a modification known to inhibit TSC activity and promote mTORC1 activity. We also found that the reduced cell growth upon knockdown of DYRK1A can be rescued by overexpression of RHEB, an activator of mTORC1. Our findings suggest that DYRK1A inhibits TSC complex activity through inhibitory phosphorylation on TSC2, thereby promoting mTORC1 activity. Furthermore, using the Drosophila neuromuscular junction as a model, we show that the mnb, the fly homologs of DYRK1A, is rescued by RHEB overexpression, suggesting a conserved role of DYRK1A in TORC1 regulation.

The basic concepts of research are learned through systematic literature searches which form the basis of a research statement and research topic. Then the research question, hypothesis, aim, and objectives, as well as the experimental design, are developed. Given the context provided, the primary focus is on the importance of adequately training postgraduates and young research investigators in research methodology and project development. It is evident that there is a lack of proper training in these areas, and the rapid expansion of colleges in India exacerbates this issue. To address this, research students must receive comprehensive instruction in scientific research methodology, experimental design, statistics, scientific writing, publishing, and research ethics. Our team has been conducting workshops and symposia for more than two decades to improve the current teaching methods in these areas. Most recently, we organized a series of national and international workshops and seminars in multiple states across India to fortify the core concepts of scientific research for students and faculty members. This report highlights the key aspects of these workshops and the positive outcomes experienced by participants.

Abstract Background Airborne environmental and engineered nanoparticles (NPs) are inhaled and deposited in the respiratory system. The inhaled dose of such NPs and their deposition location in the lung determines their impact on health. When calculating NP deposition using particle inhalation models, a common approach is to use the bulk material density, ρ b , rather than the effective density, ρ eff . This neglects though the porous agglomerate structure of NPs and may result in a significant error of their lung-deposited dose and location. Results Here, the deposition of various environmental NPs (aircraft and diesel black carbon, wood smoke) and engineered NPs (silica, zirconia) in the respiratory system of humans and mice is calculated using the Multiple-Path Particle Dosimetry model accounting for their realistic structure and effective density. This is done by measuring the NP ρ eff which was found to be up to one order of magnitude smaller than ρ b . Accounting for the realistic ρ eff of NPs reduces their deposited mass in the pulmonary region of the respiratory system up to a factor of two in both human and mouse models. Neglecting the ρ eff of NPs does not alter significantly the distribution of the deposited mass fractions in the human or mouse respiratory tract that are obtained by normalizing the mass deposited at the head, tracheobronchial and pulmonary regions by the total deposited mass. Finally, the total deposited mass fraction derived this way is in excellent agreement with those measured in human studies for diesel black carbon. Conclusions The doses of inhaled NPs are overestimated by inhalation particle deposition models when the ρ b is used instead of the real-world effective density which can vary significantly due to the porous agglomerate structure of NPs. So the use of realistic ρ eff , which can be measured as described here, is essential to determine the lung deposition and dosimetry of inhaled NPs and their impact on public health. Graphical abstract

In India, the incidence of mucormycosis reached high levels during 2021–2022, coinciding with the COVID-19 pandemic. In response to this, we established a multicentric ambispective cohort of patients hospitalised with mucormycosis across India. In this paper, we report their baseline profile, clinical characteristics and outcomes at discharge. Patients hospitalized for mucormycosis during March–July 2021 were included. Mucormycosis was diagnosed based on mycological confirmation on direct microscopy (KOH/Calcofluor white stain), culture, histopathology, or supportive evidence from endoscopy or imaging. After consent, trained data collectors used medical records and telephonic interviews to capture data in a pre-tested structured questionnaire. At baseline, we recruited 686 patients from 26 study hospitals, of whom 72.3% were males, 78% had a prior history of diabetes, 53.2% had a history of corticosteroid treatment, and 80% were associated with COVID-19. Pain, numbness or swelling of the face were the commonest symptoms (73.3%). Liposomal Amphotericin B was the commonest drug formulation used (67.1%), and endoscopic sinus surgery was the most common surgical procedure (73.6%). At discharge, the disease was stable in 43.3%, in regression for 29.9% but 9.6% died during hospitalization. Among survivors, commonly reported disabilities included facial disfigurement (18.4%) and difficulties in chewing/swallowing (17.8%). Though the risk of mortality was only 1 in 10, the disability due to the disease was very high. This cohort study could enhance our understanding of the disease’s clinical progression and help frame standard treatment guidelines.

Background: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. Materials and Methods: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. Results: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. Conclusion: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846]

Rajnish Nagarkar,1 Mamillapalli Gopichand,2 Suparna Kanti Pal,3 Ankur Gupta,4,5 Najmuddin Mohd Saquib,4,5 Ganga Sagar,4 Kanury VS Rao,4,5 Zaved Siddiqui,4,5 Imliwati Longkumer6 1Surgical Oncology, HCG Manavta Cancer Centre, Nashik, Maharashtra, India; 2Surgical Oncology, HealthCare Global Enterprises Limited, Vijayawada, India; 3Radiotherapy, Indoriv Clinical, Kolkata, India; 4Research and Development Section, PredOmix Technologies Private Limited, Gurugram, India; 5Research and Development Section, PredOmix Health Sciences Private Limited, Singapore; 6Biochemistry, North East Cancer Hospital and Research Institute, Guwahati, Assam, IndiaCorrespondence: Imliwati Longkumer; Zaved Siddiqui, Email ilongkumer@yahoo.co.in; zaved@predomix.comAbstract: We evaluated the potential relevance of our multi-cancer detection test, OncoVeryx-F, for ovarian cancer screening. For this, we compared its accuracy with that of CA125-based screening. We demonstrate here that, in contrast to CA125-based detection, OncoVeryx-F detected ovarian cancer with very high sensitivity and specificity. Importantly here, Stage I cancers too could be detected with an accuracy of > 98%. Furthermore, again unlike CA 125, the detection accuracy of OncoVeryx-F remained comparable in both Caucasian and South Asian/Indian women. Thus, the robustness and accuracy of OncoVeryx-F, particularly for early-stage detection, underscores its potential utility for ovarian cancer screening.Keywords: CA 125, Oncoveryx-F, OvC, NoC, LC-MS/MS