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Introduction: AI technologies have led to transformative changes in various industries across medicine and healthcare, environmental assessments, smart cities, smart surveillance and security etc. In this article, the dual nature of AI has been investigated. Material and Methods: It is a review article that described the ethical concerns of societies in AI. Conclusion: Despite of the many amazing prospective applications, there are ethical and dual use issues of AI which necessitates enhanced governance and vigilance. Addressing these issues requires adherence to the basic ethical principles. Herein, we present the various concerning dimensions of the AI and discuss them under the lens of ethical concepts.

Despite growing interest in the health-related consequences of racially discriminatory institutional policies and practices, public health scholars have yet to reach a consensus on how to measure and analyze exposure to institutional racism. The purpose of this paper is to provide an overview of the conceptualization, measurement, and analysis of institutional racism in the context of quantitative research on minority health and health disparities in the United States. We begin by providing definitions of key concepts (e.g., racialization, racism, racial inequity) and describing linkages between these ideas. Next, we discuss the hypothesized mechanisms that link exposure to institutional racism with health. We then provide a framework to advance empirical research on institutional racism and health, informed by a literature review that summarizes measures and analytic approaches used in previous studies. The framework addresses six considerations: (1) policy identification, (2) population of interest, (3) exposure measurement, (4) outcome measurement, (5) study design, and (6) analytic approach. Research utilizing the proposed framework will help inform structural interventions to promote minority health and reduce racial and ethnic health disparities.

In this study, we report the mutational profiles, pathogenicity, and their association with different clinicopathologic and sociogenetic factors in patients with Pashtun ethnicity for the first time. A total of 19 FFPE blocks of invasive ductal carcinoma (IDC) from the Breast Cancer (BC) tissue and 6 normal FFPE blocks were analyzed by whole-exome sequencing (WES). Various somatic and germline mutations were identified in cancer-related genes, i.e., ATM, CHEK2, PALB2, and XRCC2. Among a total of 18 mutations, 14 mutations were somatic and 4 were germline. The ATM gene exhibited the maximum number of mutations (11/18), followed by CHEK2 (3/18), PALB2 (3/18), and XRCC2 (1/18). Except one frameshift deletion, all other 17 mutations were nonsynonymous single-nucleotide variants (SNVs). SIFT prediction revealed 7/18 (38.8%) mutations as deleterious. PolyPhen-2 and MutationTaster identified 5/18 (27.7%) mutations as probably damaging and 10/18 (55.5%) mutations as disease-causing, respectively. Mutations like PALB2 p.Q559R (6/19; 31.5%), XRCC2 p.R188H (5/19; 26.31%), and ATM p.D1853N (4/19; 21.05%) were recurrent mutations and proposed to have a biomarker potential. The protein network prediction was performed using GeneMANIA and STRING. ISPRED-SEQ indicated three interaction site mutations which were further used for molecular dynamic simulation. An average increase in the radius of gyration was observed in all three mutated proteins revealing their perturbed folding behavior. Obtained SNVs were further correlated with various parameters related to the clinicopathological status of the tumors. Three mutation positions (ATMp. D1853N, CHEK2 p.M314I, and PALB2 p.T1029S) were found to be highly conserved. Finally, the wild- and mutant-type proteins were screened for two drugs: elagolix (DrugBank ID: DB11979) and LTS0102038 (a triterpenoid, isolated from the anticancer medicinal plant Fagonia indica). Comparatively, a higher number of interactions were noted for normal ATM with both compounds, as compared to mutants.

Background: CCHFV is well recognized as a major public health threat and its prevalence and epidemiological distribution in Pakistan and specifically in KP province is not well documented. Methods: We used a gold-standard PCR-based diagnostic assay for confirmation of CCHFV among suspected patients. A total of 150 patients were enrolled from June 2022 to September 2022 and their blood samples were collected for PCR confirmation. Results: The overall positivity rate for CCHFV was 26.67 %, with the virus mostly prevalent in the middle-aged group (21–40 years). In the July of 2022, a significant spike in the prevalence of CCHFV was observed in provincial capital Peshawar with the highest burden (31.57 %). Conclusion: Our findings indicate the necessity of strengthening CCHFV monitoring programs and intensifying efforts to identify hotspot regions for effective surveillance and control of CCHFV. The months before the Eid-ul-Adha are crucial in the context of CCHFV control.

Gene mutations are a source of genetic instability which fuels the progression of cancer. Mutations in BRCA1 and BRCA2 are considered as major drivers in the progression of breast cancer and their detection indispensable for devising therapeutic and management approaches. The current study aims to identify novel pathogenic and recurrent mutations in BRCA1 and BRCA2 in Pakhtun population from the Khyber Pakhtunkhwa. To determine the BRCA1 and BRCA2 pathogenic mutation prevalence in Pakhtun population from KP, whole exome sequencing of 19 patients along with 6 normal FFPE embedded blocks were performed. The pathogenicity of the mutations were determined and they were further correlated with different hormonal, sociogenetic and clinicopathological features. We obtained a total of 10 mutations (5 somatic and 5 germline) in BRCA1 while 27 mutations (24 somatic and 3 germline) for BRCA2. Five and seventeen pathogenic or deleterious mutations were identified in BRCA1 and BRCA2 respectively by examining the mutational spectrum through SIFT, PolyPhen-2 and Mutation Taster. Among the SNVs, BRCA1 p.P824L, BRCA2 p. P153Q, p.I180F, p.D559Y, p.G1529R, p.L1576F, p.E2229K were identified as mutations of the interaction sites as predicted by the deep algorithm based ISPRED-SEQ prediction tool. SAAFEQ-SEQ web-based algorithm was used to calculate the changes in free energy and effect of SNVs on protein stability. All SNVs were found to have a destabilizing effect on the protein. ConSurf database was used to determine the evolutionary conservation scores and nature of the mutated residues. Gromacs 4.5 was used for the molecular simulations. Ramachandran plots were generated using procheck server. STRING and GeneMania was used for prediction of the gene interactions. The highest number of mutations (BRCA1 7/10, 70 %) were on exon 9 and (BRCA2, 11/27; 40 %) were on exon 11. 40 % and 60 % of the BRCA2 mutations were associated Grade 2 and Grade 3 tumors respectively. The present study reveals unique BRCA1 and BRCA2 mutations in Pakhtun population. We further suggest sequencing of the large cohorts for further characterizing the pathogenic mutations.

Abstract Hyphaene thebaica fruits were used for the fabrication of spherical erbium oxide nanoparticles (HT-Er2O3 NPS) using a one-step simple bioreduction process. XRD pattern revealed a highly crystalline and pure phase with crystallite size of ~ 7.5 nm, whereas, the W–H plot revealed crystallite size of 11 nm. FTIR spectra revealed characteristic Er-O atomic vibrations in the fingerprint region. Bandgap was obtained as 5.25 eV using K-M function. The physicochemical and morphological nature was established using Raman spectroscopy, reflectance spectroscopy, SAED and HR-TEM. HT-Er2O3 NPS were further evaluated for antidiabetic potential in mice using in-vivo and in-vitro bioassays. The synthesized HT-Er2O3 NPS were screened for in vitro anti-diabetic potentials against α-glucosidase enzyme and α-amylase enzyme and their antioxidant potential was evaluated using DPPH free radical assay. A dose dependent inhibition was obtained against α-glucosidase (IC50 12 μg/mL) and α-amylase (IC50 78 μg/mL) while good DPPH free radical scavenging potential (IC50 78 μg mL−1) is reported. At 1000 μg/mL, the HT-Er2O3 NPS revealed 90.30% and 92.30% inhibition of α-amylase and α-glucosidase enzymes. HT-Er2O3 NPs treated groups were observed to have better glycemic control in diabetic animals (503.66 ± 5.92*** on day 0 and 185.66 ± 2.60*** on day 21) when compared with positive control glibenclamide treated group. Further, HT-Er2O3 NPS therapy for 21 days caused a considerable effect on serum total lipids, cholesterol, triglycerides, HDL and LDL as compared to untreated diabetic group. In conclusion, our preliminary findings on HT-Er2O3 NPS revealed considerable antidiabetic potential and thus can be an effective candidate for controlling the post-prandial hyperglycemia. However, further studies are encouraged especially taking into consideration the toxicity aspects of the nanomaterial.

Abstract Plants from genus Ephedra are commonly used by the Chinese people as folk medicine for treatment of various diseases. The current study was designed to explore the ethno-pharmacological based pharmacological potentials of Ephedra intermedia Schrenk & C.A. Mey. (E. intermedia). Plant aerial parts were extracted using ten solvent systems with increasing order of polarity. Samples were analyzed for total phenolic and flavonoid contents, HPLC-DAD analysis, antibacterial, antifungal, HepG2 cell line cytotoxicity, hemolysis and antioxidant potentials following standard procedures. Highest percent extract recovery was observed in Eth+WT (25.55 % w/w) solvent system. Flavonoid and phenolic contents were higher in chloroform and Met+WT fractions respectively. Considerable antibacterial activity was shown by Eth+Met extract against B. subtilis and K. pneumonia (MIC of 11.1μg/mL for each). Eth extract exhibited high antifungal activity against A. fumigates (15±0.31 mm DIZ). Met+WT extract showed significant cytotoxicity against HepG2 cell lines with IC50 of 13.51+0.69 μg/mL. Substantial free radical scavenging activity (74.9%) was observed for Met+Eth extract. In the current study, several solvent systems were used for more effective extraction of fractions and can be useful in the isolation of phytochemicals. Various fractions exhibited considerable antimicrobial, antioxidant and cytotoxic potentials. Biological potentials of E. intermedia signify its potential uses in microbial, cancer and degenerative disorders and thus warrant further detailed studies.

Objective: Aging-related changes and caregiver burden may increase the risk for sleep disturbances among older caregivers, yet few studies have examined the prevalence of insomnia and daytime sleepiness in this group. We examined the relationship of caregiver status with insomnia and daytime sleepiness among persons of advanced age (>75 years of age). Design: Cross-sectional. Setting: Community. Participants: Yale Precipitating Events Project participants (n=383, mean age 84.4 years, 67% female, 12% African American, 25% caregivers). Measurements: Caregivers were persons who reported caring for another person in the past week or caring for/helping a friend or relative >4 times in the past month. We examined the correlates of caregiver status, including demographic (age, sex, race/ethnicity, education, marital status), psychosocial (living alone, Medicaid eligibility, depressive symptoms, social support, hours volunteered), and physical (obesity, chronic conditions, medication use, self-rated health status, physical activity, functional disability, cognitive impairment) factors. We used the Insomnia Severity Index (ISI) to establish insomnia severity (ISI score 0-28) or clinically significant insomnia symptoms (ISI ≥8). We used the Epworth Sleepiness Scale to establish daytime sleepiness (ESS score 0-24) or hypersomnia (ESS ≥10). In nonparametric multivariable regression analyses, we examined the relationship of caregiver status with insomnia or daytime sleepiness. Results: Compared to non-caregivers, caregivers were younger, more educated, less likely to be Medicaid eligible and had lower rates of depression, obesity, poor self-rated health, low physical activity, functional disability, and cognitive impairment. Mean ISI and ESS scores were in the normal range and similar among non-caregivers and caregivers (ISI scores of 6.9±5.6 and 6.9±5.4, and ESS scores of 6.4±4.7 and 6.1±4.3, in non-caregivers and caregivers, respectively). Multivariable-adjusted models demonstrated no significant differences in ISI and ESS scores between non-caregivers and caregivers (regression coefficients for ISI and ESS scores of -0.01 [95% CI = -1.58, 1.21] and -0.10 [-1.05, 1.21], respectively). Conclusion: When compared to older non-caregivers, older caregivers had more advantageous demographic, psychosocial, and physical profiles and had similar levels of insomnia and daytime sleepiness on standardized questionnaires. Future research is needed to elucidate contextual factors (e.g., caregiving intensity and care partner disease) that may increase the risk of sleep disturbances among caregivers of advanced age [ABSTRACT FROM AUTHOR]

This contribution insight on the cytotoxic and anticancer activities and molecular mechanism of phyto‐reduced silver nanoparticles (AgNPs) in MCF‐7 breast cancer cell lines. A simple, entirely green synthesis process was optimized for the phyto‐reduction of AgNP (~12.7 nm) using aqueous leaf extracts of Indigofera heterantha. The structural and vibrational properties of biosynthesized AgNPs were extensively characterized using UV–Vis spectrophotometer, x‐ray diffraction (XRD), dynamic light scattering (DLS), and Fourier transform Infrared spectroscopy (FTIR), while their shape and morphology was studied through scanning electron microscopy (SEM). The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) cell viability assay indicates concentration dependent inhibition with IC50, 27.93 ± 2.10 μg/mL against MCF‐7 cells and 294.38 ± 3.87 μg/mL against L929 cells. The manifested anticancer mechanism in MCF‐7 cells was extensively studied using Acridine orange/ethidium bromide (AO/EB), 4′,6‐diamidino‐2‐phenylindole (DAPI) and Annexin‐V/propedium iodide fluorescence microscopic assays. The level of reactive oxygen species (ROS) was measured using DCFH‐DA fluorescent spectroscopy. Overall, the results show that AgNPs exhibit cytotoxic and apoptotic effect on breast cancer MCF‐7 cells by damaging membrane integrity and nuclear fragmentation due to oxidative stress generated by elevated level of ROS. Research Highlights: Biomimetic synthesis of nano dimension size silver nanoparticles (AgNPs).Characterization of AgNPs through UV–Vis, DLS, XRD, FTIR, and SEM.Cytotoxic and anticancer effects of the biosynthesized AgNPs in L929 fibroblast cells and MCF7 breast cancer respectively.Determination of morphological, and nuclear changes triggered by AgNPs in MCF 7 breast cancer cells using fluorescent microscopy and flow cytometry.Apoptosis induction by AgNPs in cancer cells through oxidative stress generated by reactive oxygen species (ROS). [ABSTRACT FROM AUTHOR]

Transformation of science by embracing the concepts of open science presents a very attractive strategy to enhance the reliability of science. Open science policies embody the concepts of open data and open access that encompass sharing of resources, dissemination of ideas, and synergizing the collaborative forums of research. Despite the opportunities in openness, however, there are grave ethical concerns too, and they present a dual-use dilemma. Access to sensitive information is seen as a security risk, and it also possesses other concerns such as confidentiality, privacy, and affordability. There are arguments that open science can be harmful to marginalized groups. Through this study, we aim to discuss the opportunities of open science, as well as the ethical and security aspects, which require further deliberation before full-fledged acceptance in the science community.

Abstract COVID-19 which started in Wuhan, China and swiftly expanded geographically worldwide, including to Low to Middle Income Countries (LMICs). This in turn raised numerous ethical concerns in preparedness, knowledge sharing, intellectual property rights, environmental health together with the serious constraints regarding readiness of health care systems in LMICs to respond to this enormous public health crisis. From the restrictions on public freedom and burgeoning socio-economic impacts to the rationing of scarce medical resources, the spread of COVID-19 is an extraordinary ethical dilemma for resource constrained nations with less developed health and research systems. In the current crisis, scientific knowledge and technology has an important role to play in effective response. Emergency preparedness is a shared responsibility of all countries with a moral obligation to support each other. This review discusses the ethical concerns regarding the national capacities and response strategies in LMICs to deal with the COVID-19 pandemic as well as the deep link between the environment and the increasing risk of pandemics.

Dengue is a growing mosquito-borne viral disease prevalent in 128 countries, while 3.9 billion people are at high risk of acquiring the infection. With no specific treatment available, the only way to mitigate the risk of dengue infection is through controlling of vector, i.e., Aedes aegypti. Nanotechnology-based prevention strategies like biopesticides with nanoformulation are now getting popular for preventing dengue fever. Metal nanoparticles (NPs) synthesized by an eco-friendly process, through extracts of medicinal plants have indicated potential anti-dengue applications. Green synthesis of metal NPs is simple, cost-effective, and devoid of hazardous wastes. The recent progress in the phyto-synthesized multifunctional metal NPs for anti-dengue applications has encouraged us to review the available literature and mechanistic aspects of the dengue control using green-synthesized NPs. Furthermore, the molecular bases of the viral inhibition through NPs and the nontarget impacts or hazards with reference to the environmental integrity are discussed in depth. Till date, major focus has been on green synthesis of silver and gold NPs, which need further extension to other innovative composite nanomaterials. Further detailed mechanistic studies are required to critically evaluate the mechanistic insights during the synthesis of the biogenic NPs. Likewise, detailed analysis of the toxicological aspects of NPs and their long-term impact in the environment should be critically assessed.

Cobalt oxide nanoparticles were successfully biosynthesized by complete green process using aqueous leaf extracts of Sageretia thea as chelating agent. Diverse techniques were applied for characterization. Antibacterial (with and without UV illumination), antileishmanial, antioxidant and enzyme inhibition applications were assessed, while freshly isolated macrophages and red blood cells were used for biocompatibility studies. Good antibacterial nature and enhancement of bactericidal nature upon UV modulation is reported. Staphylococcus aureus and Escherichia coli are indicated as most susceptible bacterial strains. Significant cytotoxic potential is revealed with IC50 calculated as 12.82 µg/ml and 3.16 µg/ml against the axenic leishmanial promastigote and amastigote cultures respectively. Biogenic cobalt oxide nanoparticles indicated DPPH free radical scavenging potential, while moderate antioxidant capacity and reducing power was demonstrated. Bioinspired cobalt oxide also demonstrated alpha amylase and protein kinase inhibition at higher concentrations. Biogenic cobalt oxide was found as more cytotoxic to macrophages (IC50 = 58.55 µg/ml) then to RBC’s (IC50 >200 µg/ml). Our results indicate green synthesis as an alternative, effective and eco-friendly method for the biosynthesis of cobalt oxide nanoparticles with numerous biological applications. Keywords: Biosynthesis, Cobalt oxide, Nanoparticles, Antimicrobial, Antileishmanial, Antioxidant

Green and ecofriendly route for biosynthesis of lead oxide nanoparticles has been successfully demonstrated using aqueous leaf extracts of Sageretia thea (Osbeck.). Biosynthesized PbO (∼27 nm) nanoparticles were extensively characterized using XRD, FTIR, Raman, EDS etc. Morphology was studied through HR-TEM/SEM. As synthesized nanoparticles were investigated for their iv-vitro biological properties. Antibacterial activities revealed enhancement upon modulation by UV in a concentration dependent manner. Pseudomonas aeruginosa was found to be the most resistant strain (MIC = 250 µg/mL and MICuv = 31.25 µg/ml). MTT cytotoxicity on leishmania promastigotes and amastigotes revealed significant inhibition as indicated by their IC50 values of 14.7 µg/mL and 11.95 µg/m respectively. Cytotoxicity was also confirmed using brine shrimp lethality (IC50 = 27.7 µg/mL). Bio-compatibility evaluation indicated cytotoxicity to freshly isolated human macrophages (IC50 = 57.1 µg/mL). Insignificant alpha-amylase inhibition and moderate protein kinase inhibition was revealed. Antioxidant activities indicated free radical scavenging activity (58 ± 2.45) at 200 µg/mL. Moderate total reducing power and total antioxidant activity was also indicated. Overall, we conclude lead oxide as a potential candidate for biological applications, however further studies are recommended on their in vitro and in vivo cytotoxicity. Keywords: Lead oxide, Nanoparticles, Bioinspired, Antileishmanial, Antimicrobial

Abstract Biosynthesis of bismuth vanadate (BiVO4) nanorods was performed using dried fruit extracts of Hyphaene thebaica as a cost effective reducing and stabilizing agent. XRD, DRS, FTIR, zeta potential, Raman, HR-SEM, HR-TEM, EDS and SAED were used to study the main physical properties while the biological properties were established by performing diverse assays. The zeta potential is reported as − 5.21 mV. FTIR indicated Bi–O and V–O vibrations at 640 cm−1 and 700 cm−1/1120 cm−1. Characteristic Raman modes were observed at 166 cm−1, 325 cm−1 and 787 cm−1. High resolution scanning and transmission electron micrographs revealed a rod like morphology of the BiVO4. Bacillus subtilis, Klebsiella pneumonia, Fusarium solani indicated highest susceptibility to the different doses of BiVO4 nanorods. Significant protein kinase inhibition is reported for BiVO4 nanorods which suggests their potential anticancer properties. The nanorods revealed good DPPH free radical scavenging potential (48%) at 400 µg/mL while total antioxidant capacity of 59.8 µg AAE/mg was revealed at 400 µg/mL. No antiviral activity is reported on sabin like polio virus. Overall excellent biological properties are reported. We have shown that green synthesis can replace well established processes for synthesizing BiVO4 nanorods.

Purpose: To examine how former caregivers for parents living with dementia engage in personal health planning. Design: An inductive, qualitative study. Setting: Virtual, audio-recorded, semi-structured interviews. Participants: Thirty-two midlife former primary caregivers for parents who died following advanced dementia 3 months to 3 years prior. Method: Participants responded to a series of open-ended interview prompts. Interview recordings were transcribed and evaluated by a trained, diverse team to generate Consensual Qualitative Research (CQR) domains and categories. Results: Caregivers developed health planning outlooks (ie, mindsets regarding willingness and ability to engage in personal health planning) that guided health planning activities (ie, engaging in a healthy lifestyle, initiating cognitive/genetic testing, maintaining independence and aging in place, ensuring financial and legal security). An agentic outlook involved feeling capable of engaging in health planning activities and arose when caregivers witnessed the impact and feasibility of their parents' health planning. Anxiety-inducing and present-focused outlooks arose when caregivers faced barriers (eg, low self-efficacy, lack of social support, perception that parent's health planning did not enhance quality of life) and concluded that personal health planning would not be valuable or feasible. Conclusion: Caregiving for a parent living with dementia (PLWD) shapes former caregivers' personal health planning. Interventions should support former caregivers who have developed low self-efficacy or pessimistic views on healthy aging to support them in addressing health planning activities. [ABSTRACT FROM AUTHOR]

To characterize core themes conveyed by caregivers when sharing narratives of high and low caregiving points and to describe how caregivers structured these narratives. Using consensual qualitative research and thematic analysis, high and low point narratives from 32 former caregivers of persons living with dementia were examined. High point narrative themes involved strengthening relationships with care partners, fulfillment derived from care, lighthearted moments, and fostering the care partners' joy and dignity. Low point narratives involved family conflict and lack of support, personal deficiencies, loss of the caregivers' 'pre-caregiving' life, health system failures, and alienation from their care partner. Across high and low points, caregivers' narratives were structured by three types of narrative elaborations; details unnecessary for factual recall but which enriched narrative sharing. Themes across high and low point narratives encompassed relational issues, how caregiving shaped the caregiver's self-efficacy, and factors that made navigating caregiving easier or more difficult. Both high point and low point narration often involved describing positive aspects of caregiving (PAC). Narrative elaborations may be used by former caregivers to engage in deeper evaluation of their caregiving experiences. We consider how psychotherapeutic techniques can help former caregivers reframe maladaptive narratives, supporting their mental health. [ABSTRACT FROM AUTHOR]

Green synthesis of nanoparticles is an emerging field of nanotechnology, preferred over physical and chemical synthesis owing to their safety, cost-effectiveness nature, bio-compatibility, eco-friendly and scalable properties. The present study includes Seripheidium quettense aqueous extract mediated green synthesis, optimization of silver nanoparticles (Sq-AgNPs) and their pharmacological evaluations. Synthesis was done considering various optimization parameters including concentrations of AgNO3, pH of the reaction mixture, extract to precursor ratio and temperature. Biosynthesis was carried out using our already optimized conditions. UV–visible spectrophotometer, FTIR, XRD and SEM analysis were used for characterization of Sq-AgNPs. The synthesized Sq-AgNPs (49.96–54.36 nm) were evaluated for their antibacterial, antifungal, anticancer and hemolytic potentials. The maximum antibacterial activity was found against Escherichia coli, Klebsiella pneumonia and Bacillus subtilis with their MICs of 11.1, 33.3 and 33.3 μg/mL, respectively. Aspergillus nigar was found as the most susceptible fungal strain with the highest zone of inhibition (13.2 ± 0.72 mm). Sq-AgNPs inhibited proliferation of human liver cancer cell lines (HepG2) with median lethal concentration (IC50s) of 62.5 µg/mL. Results of the hemolytic assay showed that SqNPs are bio-compatible and have less effect on erythrocytes even at high concentration of 100 µg/mL.