A novel randomized scrambling technique for mean estimation of a finite population.

In recent decades, the randomized response technique has attracted researchers due to its usefulness in sensitive surveys. The randomized response procedure is used for the collection of responses on sensitive issues such as cheating in examination, income earned through illegal sources, expenditure on luxury items, and amount of tax paid, etc. This study introduces a new variant of quantitative randomized response models for use with sample surveys where the variable of interest is quantitative. The properties of a mean estimator based on the new technique have been studied. Further, the combined and separate evaluation metrics for efficiency and privacy level have also been derived and compared with those of the existing methods. Further, a simulation study has been conducted to prove the improvement in the degree of privacy protection and efficiency. The findings reveal that the suggested randomized response technique is not only more efficient than the existing techniques, but also improves the joint measure of efficiency and respondents' privacy, making it preferable over the existing techniques. A real-world example of a sample survey through the suggested model is also presented which illustrates its usefulness in practical surveys on sensitive issues.

NIR-emissive carbon nanodots as a tool to mark ribosomal RNA and nucleolus components using super-resolution microscopy.

Ribosomal RNA (rRNA) plays a key role in protein synthesis and ribosomal biogenesis. The exclusively used commercial dye for RNA staining is SYTO RNASelect, which works in fixed cells only. To overcome this constraint, we synthesized NIR-emissive, highly photostable, and biocompatible carbon nanodots (CNDs) as a fluorescent biomarker for rRNA. The synthesized CNDs could stain rRNA in both live and fixed cells. We were able to visualize rRNA at different sites in eukaryotic cells using super-resolution microscopy (SRM). The CNDs localized rRNA in the dense fibrillar components (DFCs) of the nucleolus, nuclear membrane, and rough endoplasmic reticulum (RER). The super-resolved hollow ring-structured DFC with an FWHM of 140 nm, nuclear membrane with an FWHM of 120 nm, and ER with an FWHM of 115 nm were observed. We further found a marked contrast between the pre-RNA synthesized in cancer cells and normal cells. We believe that these CNDs have great potential in rRNA imaging and comprehending the complex relationships between rRNA dynamics and basic biological processes, disease development, or drug interactions.

Validation of the transcranial Doppler rescue criteria for mechanical thrombectomy.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) identifies acute stroke patients with arterial occlusion where treatment may not effectively open the blocked vessel. This study aimed to examine the clinical utility and prognostic value of TCD flow findings in patients enrolled in a multicenter prospective study (CLOTBUST-PRO). METHODS: Patients enrolled with intracranial occlusion on computed tomography angiography (CTA) who underwent urgent TCD evaluation before intravenous thrombolysis was included in this analysis. TCD findings were assessed using the mean flow velocity (MFV) ratio, comparing the reciprocal ratios of the middle cerebral artery (MCA) depths bilaterally (affected MCA-to-contralateral MCA MFV [aMCA/cMCA MFV ratio]). RESULTS: A total of 222 patients with intracranial occlusion on CTA were included in the study (mean age: 64 ± 14 years, 62% men). Eighty-eight patients had M1 MCA occlusions; baseline mean National Institutes of Health Stroke Scale (NIHSS) score was 16, and a 24-hour mean NIHSS score was 10 points. An aMCA/cMCA MFV ratio of <.6 had a sensitivity of 99%, specificity of 16%, positive predictive value (PV) of 60%, and negative PV of 94% for identifying large vessel occlusion (LVO) including M1 MCA, terminal internal carotid artery, or tandem ICA/MCA. Thrombolysis in Brain Ischemia scale, with (grade ≥1) compared to without flow (grade 0), showed a sensitivity of 17.1%, specificity of 86.9%, positive PV of 62%, and negative PV of 46% for identifying LVO. CONCLUSIONS: TCD is a valuable modality for evaluating arterial circulation in acute ischemic stroke patients, demonstrating significant potential as a screening tool for intravenous/intra-arterial lysis protocols.

Determinants of Stunting in Young Women Age 13-15 Years in South Galesong District, Takalar Regency, Indonesia: a Cross-sectional Study.

Background and Objective: Malnutrition is a serious public health problem in developing countries, including Indonesia. Based on RISKESDAS 2018, the prevalence of stunting aged 13-15 years in Takalar Regency is 24.83%. This study aimed to assess the prevalence of stunting and the determinants of stunting in adolescent girls aged 13-15 years in the South Galesong District, Takalar Regency. Methods: This is a cross-sectional study using purposive sampling method that included 247 adolescent girls in selected junior high schools. Data collection used questionnaires and anthropometric measurements. An anthropometric measurement was converted to the indices of nutritional status using World Health Organization Anthro Plus software. Results: The prevalence of stunting was 25.1%. Bivariate analysis showed determinant factors related significantly to stunting were energy intake (p<0.001), protein intake (p<0.001), iron intake (p<0.005), and zinc intake (p<0.001). Multivariate analysis showed determinant factors related significantly to stunting were zinc intake (p<0.001, OR=7.993), protein intake (p<0.05, OR=2.248), and knowledge level (p<0.05, OR=2.032). Conclusion: The occurrence of stunting is related to the quality and quantity of food and the level of adolescent knowledge about balanced nutrition. It is necessary to hold educational programs and interventions on improving nutrition initiated by stakeholders and the department of health, in this case, the health center is needed to reduce stunting rates, especially among adolescents.

Data mining of arsenic-based small molecules geometrics present in Cambridge structural database.

Arsenic, ubiquitous in various industrial processes and consumer products, presents both essential functions and considerable toxicity risks, driving extensive research into safer applications. Our investigation, drawing from 7182 arsenic-containing molecules in the Cambridge Structural Database (CSD), outlines their diverse bonding patterns. Notably, 51% of these molecules exhibit cyclic connections, while 49% display acyclic ones. Arsenic forms eight distinct bonding types with other elements, with significant interactions observed, particularly with phenyl rings, O3 and F6 moieties. Top interactions involve carbon, nitrogen, oxygen, fluorine, sulfur, and arsenic itself. We meticulously evaluated average bond lengths under three conditions: without an R-factor cut-off, with R-factor ≤0.075, and with R-factor ≤0.05, supporting the credibility of our results. Comparative analysis with existing literature data enriches our understanding of arsenic's bonding behaviour. Our findings illuminate the structural attributes, molecular coordination, geometry, and bond lengths of arsenic with 68 diverse atoms, enriching our comprehension of arsenic chemistry. These revelations not only offer a pathway for crafting innovative and safer arsenic-based compounds but also foster the evolution of arsenic detoxification mechanisms, tackling pivotal health and environmental challenges linked to arsenic exposure across different contexts.

Participants' views of ultra-low dose combination therapy for high blood pressure: a mixed-methods study from the QUARTET trial.

Single-pill combination therapy containing four quarter-dose medications for high blood pressure improves BP control compared to monotherapy, however patient-reported acceptance of the quadpill as a treatment strategy remains undescribed. We collected within-trial feedback and interviewed participants from the quadruple ultra-low-dose treatment for hypertension (QUARTET) trial to characterise patient attitudes to this intervention. All trial participants were asked about ease and preference for the quadpill and provided an opportunity to give further comments on the trial at 12 weeks (trial primary endpoint) and 52 weeks extended follow-up. Separately, we used purposive and quota sampling for the semi-structured telephone interviews, with the resultant verbatim transcripts analysed using an inductive thematic analysis approach. Themes were re-evaluated after each successive interview, and at suspected data saturation, an additional interview conducted for confirmation. At 12 weeks follow-up, 502 of 591 (85%) participants responded to acceptability questions, and 359 of 417 (86%) responded at week 52. Most reported the trial capsule easy or very easy to take. From eight sites, 16 participants were interviewed between 5 August 2020 and 19 November 2020. All described a positive experience, preferred once-daily morning dosing and found routine facilitated adherence. Participants valued individual responsibility for adherence, and involvement of the general practitioner in blood-pressure management. Most reported capsule size did not deter adherence but desired a smaller capsule. Participants described a preference for minimising number and dosage of medications, reduced capsule size, and once-daily morning dosing. These findings suggest a preference for single-pill combination therapy for blood pressure lowering.

Learning the structure of the mTOR protein signaling pathway from protein phosphorylation data.

Statistical learning of the structures of cellular networks, such as protein signaling pathways, is a topical research field in computational systems biology. To get the most information out of experimental data, it is often required to develop a tailored statistical approach rather than applying one of the off-the-shelf network reconstruction methods. The focus of this paper is on learning the structure of the mTOR protein signaling pathway from immunoblotting protein phosphorylation data. Under two experimental conditions eleven phosphorylation sites of eight key proteins of the mTOR pathway were measured at ten non-equidistant time points. For the statistical analysis we propose a new advanced hierarchically coupled non-homogeneous dynamic Bayesian network (NH-DBN) model, and we consider various data imputation methods for dealing with non-equidistant temporal observations. Because of the absence of a true gold standard network, we propose to use predictive probabilities in combination with a leave-one-out cross validation strategy to objectively cross-compare the accuracies of different NH-DBN models and data imputation methods. Finally, we employ the best combination of model and data imputation method for predicting the structure of the mTOR protein signaling pathway.

An efficient estimator of population variance of a sensitive variable with a new randomized response technique.

In sampling theory, a majority of the available estimators of population variance are designed for use with non-sensitive variables only. Such estimators cannot perform efficiently when the variable of interest is of sensitive nature, such as use of drugs, illegal income, abortion, cheating in examination, the amount of income tax payable, and the violation of rules by employees, etc. In the current literature, the shortage of research studies on variance estimators of a sensitive variable has created a big research gap and a room for improvement in the efficiency of such estimators. In this paper, a new randomized scrambling technique is proposed, along with a new estimator of population variance. The new estimator achieves improvement in efficiency over the available variance estimators. The proposed estimator is designed for use with simple random sampling and uses the information on an auxiliary variable. The improvement in efficiency is shown for different choices of constants. Besides efficiency, improvement in the unified measure of estimator quality is also achieved with the proposed estimator under the new randomized response model.

Microplastic contamination in the agricultural soil-mitigation strategies, heavy metals contamination, and impact on human health: a review.

Microplastic pollution has emerged as a critical global environmental issue due to its widespread distribution, persistence, and potential adverse effects on ecosystems and human health. Although research on microplastic pollution in aquatic environments has gained significant attention. However, a limited literature has summarized the impacts of microplastic pollution the agricultural land and human health. Therefore, In the current review, we have discussed how microplastic(s) affect the microorganisms by ingesting the microplastic present in the soil, alternatively affecting the belowground biotic and abiotic components, which further elucidates the negative effects on the above-ground properties of the crops. In addition, the consumption of these crops in the food chain revealed a potential risk to human health throughout the food chain. Moreover, microplastic pollution has the potential to induce a negative impact on agricultural production and food security by altering the physiochemical properties of the soil, microbial population, nutrient cycling, and plant growth and development. Therefore, we discussed in detail the potential hazards caused by microplastic contamination in the soil and through the consumption of food and water by humans in daily intake. Furthermore, further study is urgently required to comprehend how microplastic pollution negatively affects terrestrial ecosystems, particularly agroecosystems which drastically reduces the productivity of the crops. Our review highlights the urgent need for greater awareness, policy interventions, and technological solutions to address the emerging threat of microplastic pollution in soil and plant systems and mitigation strategies to overcome its potential impacts on human health. Based on existing studies, we have pointed out the research gaps and proposed different directions for future research.

Rationale for a New Low-Dose Triple Single Pill Combination for the Treatment of Hypertension.

Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these 'hypertension polypills' were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.

Comparison of Indian clinical practice guidelines for the management of hypertension with the World Health Organization, International Society of Hypertension, American, and European guidelines.

Hypertension is the leading risk factor for preventable cardiovascular diseases and all-cause mortality globally, with majority of the hypertension-attributed deaths occurring in low- and middle-income countries like India. Several international and national clinical practice guidelines (CPGs) provide evidence-informed recommendations to achieve optimal control. CPGs produced by the World Health Organization, International Society for Hypertension, American (AHA/ACC-2017), and European (ESC/ESH-2018) are "major" as they are widely used and are highly cited. We compared the main recommendations for the pharmacological management of hypertension among the major CPGs and the two existing Indian CPGs for similarities and shortcomings. Several deviations from the major CPGs were observed among Indian CPGs. Important shortcomings pertain to Indian CPGs' low priority for initial combination therapy and the use of single pill combinations. Having multiple CPGs providing conflicting recommendations might discourage the adoption of evidence-based practices. There is a need for updating Indian CPGs based on up-to-date evidence.

OsUGE2 Regulates Plant Growth through Affecting ROS Homeostasis and Iron Level in Rice.

BACKGROUND: The growth and development of rice (Oryza sativa L.) are affected by multiple factors, such as ROS homeostasis and utilization of iron. Here, we demonstrate that OsUGE2, a gene encoding a UDP-glucose 4-epimerase, controls growth and development by regulating reactive oxygen species (ROS) and iron (Fe) level in rice. Knockout of this gene resulted in impaired growth, such as dwarf phenotype, weakened root growth and pale yellow leaves. Biochemical analysis showed that loss of function of OsUGE2 significantly altered the proportion and content of UDP-Glucose (UDP-Glc) and UDP-Galactose (UDP-Gal). Cellular observation indicates that the impaired growth may result from decreased cell length. More importantly, RNA-sequencing analysis showed that knockout of OsUGE2 significantly influenced the expression of genes related to oxidoreductase process and iron ion homeostasis. Consistently, the content of ROS and Fe are significantly decreased in OsUGE2 knockout mutant. Furthermore, knockout mutants of OsUGE2 are insensitive to both Fe deficiency and hydrogen peroxide (H2O2) treatment, which further confirmed that OsUGE2 control rice growth possibly through Fe and H2O2 signal. Collectively, these results reveal a new pathway that OsUGE2 could affect growth and development via influencing ROS homeostasis and Fe level in rice.

Super-Resolution Microscopy Unveils Synergistic Structural Changes of Organelles Upon Point Mutation.

Ethyl methanesulphonate (EMS), is a widely used chemical mutagen that causes high-frequency germline null mutation by inserting an alkyl group into the nucleotide guanine in eukaryotic cells. The effect of EMS on the dynamics of the aneuploid genome, increased cellular instability, and carcinogenicity in relation to benign and malignant tumors are reported, but the molecular level understanding of morphological changes of higher-order chromatin structure has poorly been understood. This is due to a lack of sufficient resolution in conventional microscopic techniques to see small structures below the diffraction limit. Here, using super-resolution radial fluctuation, a largely fragmented, decompaction, and less dense heterochromatin structure upon EMS treatment to HEK 293A cells without any change in nuclear DNA domains is observed. This result suggests an early stage of carcinogenicity happened due to the point mutation. In addition, the distinct structural changes with an elongated morphology of lysosomes are also observed. On the other hand, fragmented and increased heterogeneous populations with an increased cytoplasmic occupancy of mitochondria are observed.

Standardized treatment protocols for hypertension: global availability, characteristics, and alignment with the hypertension guideline recommendations.

BACKGROUND: Hypertension control is suboptimal globally. Implementing evidence-based, simple, standardized treatment protocols (STPs) has been instrumental in effectively and efficiently improving treatment and control of hypertension. We aimed to identify, characterize, and critically appraise hypertension STPs. METHODS: We defined STP as a series of steps for the pharmacological treatment of primary hypertension, with information on target population, BP threshold for treatment initiation, target BP, specific drugs/classes/doses, and follow-up frequency. STPs for adult patients were identified from the websites of relevant health organizations, Google search, and through expert consultations (until July 2023). STPs for secondary, gestational, or malignant hypertension or those that were templates/samples were excluded. Included STPs were critically appraised using HEARTS in the Americas Checklist for hypertension management in primary care and compared with the 2021 WHO hypertension management guideline recommendations. RESULTS: Fifty STPs were identified. All STPs had a stepwise treatment approach, involved guideline-recommended first-line drugs, and 98% consisted of at least four steps. Majority (54%) recommended monotherapy with calcium channel blockers as first-line treatment. Only 44% STPs recommended treatment initiation with combination therapy, and 16% recommended single-pill combinations. Most (62%) had dose-intensification as the second step. Most (74%) STPs did not provide complete dosing information. Only one STP mentioned a target time for achieving BP control. On average, STPs scored a performance of 68% on the HEARTS Checklist. CONCLUSION: Several STPs are available globally; however, most of them have enormous scope for improvement through interventions aimed at alignment with the latest evidence-based guidelines and multistakeholder engagement.

Micro/nanoplastics: Critical review of their impacts on plants, interactions with other contaminants (antibiotics, heavy metals, and polycyclic aromatic hydrocarbons), and management strategies.

Microplastic/nanoplastics (MPs/NPs) contamination is not only emerging threat to the agricultural system but also constitute global hazard to the environment worldwide. Recent review articles have addressed the environmental distribution of MPs/NPs and their single-exposure phytotoxicity in various plant species. However, the mechanisms of MPs/NPs-induced phytotoxicity in conjunction with that of other contaminants remain unknown, and there is a need for strategies to ameliorate such phytotoxicity. To address this, we comprehensively review the sources of MPs/NPs, their uptake by and effects on various plant species, and their phytotoxicity in conjunction with antibiotics, heavy metals, polycyclic aromatic hydrocarbons (PAHs), and other toxicants. We examine mechanisms to ameliorate MP/NP-induced phytotoxicity, including the use of phytohormones, biochar, and other plant-growth regulators. We discuss the effects of MPs/NPs -induced phytotoxicity in terms of its ability to inhibit plant growth and photosynthesis, disrupt nutrient metabolism, inhibit seed germination, promote oxidative stress, alter the antioxidant defense system, and induce genotoxicity. This review summarizes the novel strategies for mitigating MPs/NPs phytotoxicity, presents recent advances, and highlights research gaps, providing a foundation for future studies aimed at overcoming the emerging problem of MPs/NPs phytotoxicity in edible crops.

Elucidating arsenic-bound proteins in the protein data bank: data mining and amino acid cross-validation through Raman spectroscopy.

The International Agency for Research on Cancer has unequivocally classified inorganic arsenic as a Group 1 carcinogen, definitively establishing its potential to induce cancer in humans. Paradoxically, despite its well-documented toxicity, arsenic finds utility as a chemotherapeutic agent. Notable examples include melarsoprol and arsenic trioxide, both employed in the treatment of acute promyelocytic leukemia. In both therapeutic and hazardous contexts, arsenic can accumulate within cellular environments, where it engages in intricate interactions with protein molecules. Gaining a comprehensive understanding of how arsenic compounds interact with proteins holds immense promise for the development of innovative inhibitors and pharmaceutical agents. These advancements could prove invaluable in addressing a spectrum of arsenic-related diseases. In pursuit of this knowledge, we undertook a systematic exploration of the Protein Data Bank, with a focus on 902 proteins intricately associated with 26 arsenic compounds. Our comprehensive investigation reveals insights into the interactions between these arsenical compounds and amino acids located within a 4.0 Å molecular distance from arsenic-binding sites. Our findings identify that cysteine, glutamic acid, aspartic acid, serine, and arginine frequently engage with arsenic. In complement to our computational analyses, we conducted rigorous Raman spectroscopy studies on the top five amino acids displaying robust interactions with arsenic. The results derived from experimental Raman spectroscopy were meticulously compared with our computational assessments, thereby enhancing the reliability and depth of our investigations. The current study presents a multidimensional exploration into the elaborate interplay between arsenic compounds and proteins. By elucidating the specific amino acids that preferentially interact with arsenic, this study not only contributes to the fundamental understanding of these molecular associations but also lays the foundation for future endeavors in drug design and therapeutic interventions targeting arsenic-related illnesses. Our work at the convergence of toxicology, medicine, and molecular biology carries profound implications for advancing our knowledge of arsenic's dual nature as both a poison and a potential cure.

The Multifaceted Role of Jasmonic Acid in Plant Stress Mitigation: An Overview.

Plants, being sessile, have developed complex signaling and response mechanisms to cope with biotic and abiotic stressors. Recent investigations have revealed the significant contribution of phytohormones in enabling plants to endure unfavorable conditions. Among these phytohormones, jasmonic acid (JA) and its derivatives, collectively referred to as jasmonates (JAs), are of particular importance and are involved in diverse signal transduction pathways to regulate various physiological and molecular processes in plants, thus protecting plants from the lethal impacts of abiotic and biotic stressors. Jasmonic acid has emerged as a central player in plant defense against biotic stress and in alleviating multiple abiotic stressors in plants, such as drought, salinity, vernalization, and heavy metal exposure. Furthermore, as a growth regulator, JA operates in conjunction with other phytohormones through a complex signaling cascade to balance plant growth and development against stresses. Although studies have reported the intricate nature of JA as a biomolecular entity for the mitigation of abiotic stressors, their underlying mechanism and biosynthetic pathways remain poorly understood. Therefore, this review offers an overview of recent progress made in understanding the biosynthesis of JA, elucidates the complexities of its signal transduction pathways, and emphasizes its pivotal role in mitigating abiotic and biotic stressors. Moreover, we also discuss current issues and future research directions for JAs in plant stress responses.

Tracking the super resolved structure of mitochondria using red emissive carbon nanodots as a fluorescent biomarker.

Herein, we report new red emissive highly photostable and water-soluble carbon nanodots (TPP CNDs) to visualize mitochondrial dynamics using super-resolution radial fluctuations (SRRF) microscopy. The TPP CNDs were synthesized in a one-step method, using 3-(carboxypropyl)triphenylphosphonium bromide (TPP) and o-phenylenediamine (OPDA) as precursors. The obtained crystal structure, NMR, and mass data suggested the presence of [3-(1H-benzimidazol-2-yl)propyl](triphenyl)phosphonium bromide (C28H26N2P+Br-) as a molecular fluorophore (MF) on the surface of the TPP CNDs. The TPP CNDs showed better photostability than the commercially available MitoTracker™ Green and were highly capable for long-term imaging of mitochondrial fission during hyperglycemic conditions and structural changes upon an antidiabetic drug treatment, without altering their fluorescence nature.

Efficacy of zinc-based nanoparticles in alleviating the abiotic stress in plants: current knowledge and future perspectives.

Due to sessile, plants are unable to avoid unfavorable environmental conditions which leads to inducing serious negative effects on plant growth, crop yield, and food safety. Instead, various approaches were employed to mitigate the phytotoxicity of these emerging contaminants from the soil-plant system. However, recent studies based on the exogenous application of ZnO NPs approve of their important positive potential for alleviating abiotic stress-induced phytotoxicity leads to ensuring global food security. In this review, we have comprehensively discussed the promising role of ZnO NPs as alone or in synergistic interactions with other plant growth regulators (PGRs) in the mitigation of various abiotic stresses, i.e., heavy metals (HMs), drought, salinity, cold and high temperatures from different crops. ZnO NPs have stress-alleviating effects by regulating various functionalities by improving plant growth and development. ZnO NPs are reported to improve plant growth by stimulating diverse alterations at morphological, physiological, biochemical, and ultrastructural levels under abiotic stress factors. We have explained the recent advances and pointed out research gaps in studies conducted in earlier years with future recommendations. Thus, in this review, we have also addressed the opportunities and challenges together with aims to uplift future studies toward effective applications of ZnO NPs in stress management.

An improved version of systematic sampling design for use with linear trend data.

In survey sampling, systematic sampling design has attracted survey researchers in recent years due to its simplicity of use. We introduce a modified variant of systematic sampling scheme which improves the efficiency of a recently developed diagonal systematic sampling method. The suggested modification is also found to be more efficient than the other popular sampling designs in circumstances where the units of the population under consideration exhibit an increasing or decreasing perfect or near-perfect linear trend. Moreover, it is observed that the conditions for efficiency are mathematically strong and practically always hold, hence making the suggested sampling design preferable over the available sampling designs.