Current Research Research Articles

Addressing the issue of microparticle size Pyrolysis Carbon Black(PCB) by adding to the concrete mixture

MAX 250 words Tire waste is one of the world's major environmental solid waste problems. Used tires cannot be handled in landfills or burned because they create noxious vapors that are harmful. Therefore, a variety of methods for the treatment of used tires have been proposed. The most advantageous method for disposing of garbage is thought to be tire pyrolysis. By pyrolyzing waste tires, carbon black (PCB) is produced as a byproduct as well as gases, fuel oil, steel, and other materials. Another problem with solid waste is caused by PCB, which accounts for 30-35 weight percent of waste tire materials. In this experimental investigation, PCB inclusion in construction-grade concrete was attempted. The effect of black carbon particle size on concrete was examined in the current research. The compression test, which was performed in the testing, used six different PCB particle sizes. The results showed that the strength in the 28-day compression test could be organized in an increasing fashion, with the smallest particle size (75 m) yielding the highest compressive strength. The seven-day exam is also devoid of the usual arrangement.

Depression-reminiscent Behavior Induced by Chronic Unpredictable Mild Stress Paradigm in Mice Substantially Abrogated by Diosmin

Background: Diosmin has already been described and documented to be neuroprotective, antioxidant and anti-inflammatory. It may possess or hold depressionalleviating activity. Therefore, the purpose of the current research protocol is to investigate the depression-relieving proficiency of diosmin in stressed and unstressed mice. Methods: Male mice (Swiss albino) were imperiled to an unpredictable chronic stress paradigm every day for three sequential weeks, and depression-resembling behavioral despair was induced. Imipramine 15 mg/kg and diosmin (25, 50 and 100 mg/kg) were dispensed for 21 successive days to discrete groups of stressed and unstressed mice. Results: Both diosmin (100 mg/kg) and 15 mg/kg imipramine administration for 3 consecutive weeks substantially or significantly diminished the immobility period of mice imperiled to stress in comparison to stressed mice gauzed with the vehicle. Diosmin (25, 50 and 100 mg/kg) and imipramine considerably reinstated the diminished sucrose proclivity (sucrose preference percentage; %) in stressed mice, demonstrating their considerable or substantial depression-relieving effects. The locomotor activities of mice were not considerably altered by these drugs. Antidepressant-like activity of diosmin for immobility periods and preference for sucrose was observed to be analogous to imipramine. Diosmin (100 mg/kg) and imipramine substantially quashed CUMS- persuaded escalation of plasma corticosterone and nitrite levels, malondialdehyde levels and MAO-A activity in the brain of stressed mice. Both drugs also substantially reversed CUMS-prompted reduction in catalase activity and brain glutathione levels. Conclusion: Accordingly, diosmin revealed significant anti-depressive activity in mice imperiled to chronic mild unpredictable stress paradigm conceivably via mitigation of nitrosative and oxidative stress, reticence of brain MAO-A action, and sink drop of plasma corticosterone degrees.

TRIP13 Activates Glycolysis to Promote Cell Stemness and Strengthen Doxorubicin Resistance of Colorectal Cancer Cells.

Chemotherapy resistance is one of the main causes of clinical chemotherapy failure. Current cancer research explores the drug resistance mechanism and new therapeutic targets. This work aims to elucidate the mechanism of thyroid hormone receptor interactor 13 (TRIP13) affecting doxorubicin (DOX) resistance in colorectal cancer (CRC). Bioinformatics analyses were employed to clarify TRIP13 expression in CRC tissues and predict the correlation of the TRIP13 enrichment pathway with glycolysis-related genes and stemness index mRNAsi. Quantitative real-time polymerase chain reaction and western blot were adopted to analyze the expression of TRIP13 and glycolysis- related genes. Cell Counting Kit-8 was utilized to determine the cell viability and IC50 value. Western blot was employed to measure the expression of stemness-related factors. Cell function assays were performed to detect cells' sphere-forming ability and glycolysis level. Animal models were constructed to determine the effects of TRIP13 expression on CRC tumor growth. TRIP13 was significantly overexpressed in CRC, concentrated in the glycolysis signaling pathway, and positively correlated with stemness index mRNAsi. High expression of TRIP13 facilitated DOX resistance in CRC. Further mechanistic studies revealed that overexpression of TRIP13 could promote cell stemness through glycolysis, which was also confirmed in animal experiments. TRIP13 was highly expressed in CRC, which enhanced the DOX resistance of CRC cells by activating glycolysis to promote cell stemness. These findings offer new insights into the pathogenesis of DOX resistance in CRC and suggest that TRIP13 may be a new target for reversing DOX resistance in CRC.

Factor structure of the Impact of Events Scale-Revised in Latin American young adults.

More than 550 million people speak Spanish and, yet, psychometric data on psychological instruments in Spanish lags. Given evidence of significant traumatic exposure and distress among Spanish speakers, the aim of the current study was to examine the factor structure of the Impact of Events Scale-Revised (IES-R), in a large sample of Spanish-speaking adults. Participants (n = 725) were university students living in Latin America (M = 21.02; SD = 3.12). Most were born in Mexico (77.6%) and the next largest subgroup was from Ecuador (18.9%). Respondents completed the 22-item IES-R. The IES-R mean score was 20.08 (SD = 21.34) and 26.6% of the sample met the cutoff score for clinically significant symptoms. Regarding factor structure, eight different factor structures that have demonstrated a good fit in the extant literature were examined. The one-factor model demonstrated an acceptable fit, χ²(209) = 839.13, p < .0001; root-mean-square error (RMSEA) = 0.06, 95% confidence interval (CI) [0.06, 0.07]; comparative fit index (CFI) = 0.91, Tucker-Lewis index (TLI) = 0.90. The two-factor model demonstrated good fit, χ²(208) = 746.70, p < .0001; RMSEA = 0.06, 95% CI [0.05, 0.06]; CFI = 0.92, TLI = 0.91, and nested model comparisons of the two-factor and one-factor models using the chi-square difference test supported the two-factor model. The most parsimonious of the multifactor models, a two-factor model with Avoidance symptoms as one factor and Intrusions and Hyperarousal combined into a second may be of greatest use for this particular version of the IES-R. The current research demonstrates strong psychometric support for Intrusion/Hyperarousal and Avoidance subscales when measuring traumatic stress in Spanish speakers and underscores the need for culturally and contextually sensitive assessment in this population, in which posttraumatic stress is prevalent. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Synthetic Data in Human Analysis: A Survey.

Deep neural networks have become prevalent in human analysis, boosting the performance of applications, such as biometric recognition, action recognition, as well as person re-identification. However, the performance of such networks scales with the available training data. In human analysis, the demand for large-scale datasets poses a severe challenge, as data collection is tedious, time-expensive, costly and must comply with data protection laws. Current research investigates the generation of synthetic data as an efficient and privacy-ensuring alternative to collecting real data in the field. This survey introduces the basic definitions and methodologies, essential when generating and employing synthetic data for human analysis. We summarise current state-of-the-art methods and the main benefits of using synthetic data. We also provide an overview of publicly available synthetic datasets and generation models. Finally, we discuss limitations, as well as open research problems in this field. This survey is intended for researchers and practitioners in the field of human analysis.

Assessment of Ergonomic Risk Factors among Metal Sculpture Workers and Future Scope of AI Applications in Ergonomic Evaluation

Background: Handicraft workers usually carry out daily activities by adopting awkward postures. The most prevailing health issues among handicraft workers are musculoskeletal disorders (MSDs). Objective: The current research aims to assess the occurrence of musculoskeletal symptoms and investigate risk factors associated with musculoskeletal disorders among metal sculpture artisans. Subsequently, the study highlighted the future scope of AI applications in ergonomic evaluation. Methods: 144 male metal sculpture workers participated in the study. A modified Nordic questionnaire was adopted to determine the musculoskeletal problems among metal sculpture workers. The probable risk elements for MSD symptoms were identified by applying binary logistic regression. Results: Most workers faced discomfort in various body parts, particularly the wrist, lower back, and shoulders. The outcome of the logistic regression model revealed that job-related factors have significantly contributed to the development of MSD symptoms. Conclusion: This study concedes that awkward working postures for prolonged periods highly affect the health of metal sculpture workers, and there is a need for ergonomic intervention to minimize the risks of musculoskeletal disorders. The study also emphasizes the future scope of Artificial Intelligence (AI) applications that can be used in ergonomically assessing working postures.

Potential Antidiabetic Activity of β-sitosterol from Zingiber roseum Rosc. via Modulation of Peroxisome Proliferator-activated Receptor Gamma (PPARγ).

To evaluate the antidiabetic potential of β-sitosterol from Zingiber roseum. Diabetes mellitus is a cluster of metabolic disorders, and 90% of diabetic patients are affected with Type II diabetes (DM2). For the treatment of DM2, thiazolidinedione drugs (TZDs) were proposed, but recent studies have shown that TZDs have several detrimental effects, such as weight gain, kidney enlargement (hypertrophy), fluid retention, increased risk of bone fractures, and potential harm to the liver (hepatotoxicity). That is why a new molecule is needed to treat DM2. The current research aimed to assess the efficacy of β-Sitosterol from methanolic extract of Zingiber roseum in managing diabetes via PPARγ modulation. Zingiber roseum was extracted using methanol, and GC-MS was employed to analyze the extract. Through homology modeling, PPARγ structure was predicted. Molecular docking, MD simulation, free binding energies, QSAR, ADMET, and bioactivity and toxicity scores were all used during the in-depth computer-based research. Clinically, agonists of synthetic thiazolidinedione (TZDs) have been used therapeutically to treat DM2, but these TZDs are associated with significant risks. Hence, GC-MS identified phytochemicals to search for a new PPAR-γ agonist. Based on the in-silico investigation, β-sitosterol was found to have a higher binding affinity (-8.9 kcal/mol) than standard drugs. MD simulations and MMGBSA analysis also demonstrated that β-sitosterol bound to the PPAR-γ active site stably. It can be concluded that β-sitosterol from Z. roseum attenuates Type-II diabetes by modulating PPARγ activity.

Innovative costume design within the framework of the folklore of the State of Iraq

This current research to the date of the start of the issue to the current version of clothes for girls from the Iraqi folk heritage in line with the values and customs of the community in addition to the possibility of designing costumes. Fashionable for girls at that stage Accordingly, (10) proposed designs of (8) models of the folklore costume of the State of Iraq were prepared to achieve the objectives of the research using the CLO 3D program, and the research followed the experimental and descriptive method. The proposed designs were presented to a group of specialized professors. and female consumers with the aim of evaluating them, through a questionnaire for specialists consisting of (23) phrases divided into four axes to know the extent to which each of (the characteristics of the Iraqi folklore according to the elements and foundations of design, the innovative and aesthetic side, the functional side have been achieved, The economic and marketing aspect), while the questionnaire for female consumers is composed of (10) phrases for the proposed designs. The results of the study indicated the success of using design elements inspired by the concepts of Iraqi folklore as a design source according to the limits of the study. Where the functional, innovative, aesthetic and marketing aspect of the proposed designs for girls was achieved, and the best-proposed designs were identified, which achieved the highest transactions according to the results of the study and the opinions of arbitrators and consumers.

Designing for health: A study of architecturally oriented models of public space

AbstractIn the post-pandemic period, cities are committed to creating healthier and more healing urban environments. In high-density urban environments, urban complexes are increasingly assuming the function of enriching the external space and activating the vitality of cities, and their architecturally oriented public spaces have great potential for the promotion of residents' health. However, current research on public space and health has focused on green spaces and neighborhoods, and has not yet systematically sorted out the pathways that influence how building-oriented public space can contribute to health. In order to fill the gap, this study attempt to establish a model of health-promoting architecturally oriented public space, which can provide a reference for the similar projects.

Cube-Evo: A Query-Efficient Black-Box Attack on Video Classification System

The current progressive research in the domain of black-box adversarial attack enhances the reliability of deep neural network (DNN)-based video systems. Recent works mainly carry out black-box adversarial attacks on video systems by query-based parameter dimension reduction. However, the additional temporal dimension of video data leads to massive query consumption and low attack success rate. In this article, we embark on our efforts to design an effective adversarial attack on popular video classification systems. We deeply root the observations that the DNN-based systems are sensitive to adversarial perturbations with high frequency and reconstructed shape. Specifically, we propose a systematic attack pipeline Cube-Evo, aiming to reduce the search space dimension and obtain the effective adversarial perturbation via the optimal parameter group updating. We evaluate the proposed attack pipeline on two popular datasets: UCF101 and JESTER. Our attack pipeline reduces query consumption and achieves a high success rate on various DNN-based video classification systems. Compared with the state-of-the-art method Geo-Trap-Att, our pipeline averagely reduces 1.6× query consumption in untargeted attacks and 2.9× in targeted attacks. Besides, Cube-Evo improves 13% attack success rate on average, achieving new state-of-the-art results over diverse video classification systems.

Alzheimer's Disease and Cancer: Common Targets.

There is growing epidemiologic evidence of an inverse association between cancer and AD. In addition, both cell survival and death are regulated by the same signaling pathways, and their abnormal regulation may be implicated in the occurrence and development of cancer and AD. Research shows that there may be a common molecular mechanism between cancer and AD. This review will discuss the role of GSK3, DAPK1, PP2A, P53 and CB2R in the pathogenesis of cancer and AD and describe the current research status of drug development based on these targets.

Herbal Medicine- A Friend or a Foe of Cardiovascular Disease.

Herbal remedies are used by 80% of the Asian population in primary health care as per WHO. According to current research, the herbal medicine market was valued at nearly USD 166 billion in 2021 and is expected to reach approximately USD 348 billion by 2028. Increased incidence of chronic conditions such as diabetes, asthma, coronary artery disease, osteoarthritis, has fueled the growing interest in traditional herbal and plant-derived treatments among researchers. In addition, rural communities in developing nations have renewed interest in herbal treatments due to lower cost and easy availability. Aim of the paper is to highlight the role of five of more commonly used herbal medicines that are Ginkgo biloba, Garlic, Flaxseed, Ginseng, Salvia miltiorrhiza in cardiovascular disorders. A PubMed search was done using the keywords Herbal Medicine, Ginkgo biloba, Garlic, Flaxseed, Ginseng, Salvia miltiorrhiza. Articles which were available for free access were utilized. No formula inclusion or exclusion criteria was followed. A total of 42 papers were included for the study. Although there have been encouraging outcomes with the use of these herbal medications, many of these products are poorly monitored and are yet to be studied in detail regarding their adverse effects. Moreover, these medicinal products are known to interact with various drugs. To compete with the expanding pharmaceutical industry, more medicinally helpful herbal items must be used and scientifically validated.

A Review of Current Research on Traditional Medicines for the Treatment of Gastrointestinal and Biliary Disorders

Abstract: Gastrointestinal (GI) and biliary disorders are the most commonly known health issues for people in the present time as a consequence of modern lifestyle, eating habits, stress, and many other conditions. The usage of traditional substances has been phased out over time, resulting in an increase in the occurrence of numerous diseases and a decrease in immunity. Therefore, in the current scenario, traditional medicine is increasingly being used to treat and manage diseases worldwide. Traditional medical systems of India, China, and Africa are the most frequently used today. Indian medicinal system includes the Ayurveda, Siddha, and Unani systems of medicine. Ayurveda is the most antique system of medicine, which relies on the usage of plant-based formulations. Herbal medicines are used nowadays by up to half of the world's population. Phytomedicines isolated from plants contain a wide variety of bioactive components that can have both negative and positive effects. Many herbal plants, such as Acacia, Aloe, Carum, Rose, Funnel, etc., are proven to be effective as phytomedicines that are effective for the cure of gastrointestinal and biliary problems. The available pharmacological therapeutic drugs often have efficacy but are associated with many adverse effects. To minimize the adverse effects, the use of phytomedicines can be the best possible alternative. In this study, a review of some of the most frequently used traditional herbal medicine isolates with their proven pharmacological activity and novel drug delivery systems for the proper delivery of isolates is presented. Moreover, currently available herbal-marketed formulations are also highlighted.

Consumer experience and outcomes of insertion, removal, and management practices of short and midline peripheral intravenous catheters in acute health care: a mixed methods systematic review protocol.

This review will synthesize and integrate current research on the practices relating to the insertion, removal, and management of short and midline peripheral intravenous catheters on consumer experiences and outcomes in acute health care. The aim is to provide consolidated evidence to support policy decision-makers and health care workers in overcoming peripheral intravenous catheter device management challenges. Implementing the evidence provided by this review could increase positive consumer outcomes and reduce the gap between research evidence and clinical practice. Peripheral intravenous catheterization is a process in which a device is inserted into a patient's peripheral vein to administer medication, blood products, and therapeutic fluids. Recent studies have demonstrated the positive and negative impacts of peripheral intravenous catheter site placement, pain relief for insertion, complications, consumer engagement, and routine versus clinically indicated removal of these devices on consumers and the health care system. Managing these impacts in relation to research-practice gaps and conflicting evidence remains challenging. Moreover, consumer experiences and outcomes concerning these challenges are unclear. This review will consider quantitative, qualitative, and mixed methods studies on consumer experiences and outcomes in acute health care. The quantitative component will consider outcomes of patients' pain, satisfaction, anxiety, distress, preferences, fear, and comfort. The qualitative component will consider consumer experiences, including perceptions, preferences, perspectives, attitudes, expectations, and satisfaction. This study will follow JBI's convergent segregated approach for mixed method systematic reviews. A search of 11 databases will be conducted for peer-reviewed published articles, theses, and dissertations. There will be no age, date, or language limitations. PROSPERO CRD42023410214.

Recent Advances on PKM2 Inhibitors and Activators in Cancer Applications.

Metabolic reprogramming of cells, from the normal mode of glucose metabolism named glycolysis, is a pivotal characteristic of impending cancerous cells. Pyruvate kinase M2 (PKM2), an important enzyme that catalyzes the final rate-limiting stage during glycolysis, is highly expressed in numerous types of tumors and aids in development of favorable conditions for the survival of tumor cells. Increasing evidence has suggested that PKM2 is one of promising targets for innovative drug discovery, especially for the developments of antitumor therapeutics. Herein, we systematically summarize the recent advancement on PKM2 modulators including inhibitors and activators in cancer applications. We also discussed the classifications of pyruvate kinases in mammals and the biological functions of PKM2 in this review. We do hope that this review would provide a comprehensive understanding of the current research on PKM2 modulators, which may benefit the development of more potent PKM2-related drug candidates to treat PKM2-associated diseases including cancers in future.

Role of TBK1 Inhibition in Targeted Therapy of Cancer.

TANK-binding kinase 1 (TBK1) is a serine/threonine protein that plays a crucial role in various biological processes like immunity, autophagy, cell survival, and proliferation. The level and kinase activity of the TBK1 protein is regulated through post-translational modifications (PTMs). TBK1 mainly mediates the activation of IRF3/7 and NF-κB signaling pathways while also participating in the regulation of cellular activities such as autophagy, mitochondrial metabolism, and cell proliferation. TBK1 regulates immune, metabolic, inflammatory, and tumor occurrence and development within the body through these cellular activities. TBK1 kinase has emerged as a promising therapeutic target for tumor immunity. However, its molecular mechanism of action remains largely unknown. The identification of selective TBK1 small molecule inhibitors can serve as valuable tools for investigating the biological function of TBK1 protein and also as potential drug candidates for tumor immunotherapy. The current research progress indicates that some TBK1 inhibitors (compounds 15,16 and 21) exhibit certain antitumor effects in vitro culture systems. Here, we summarize the mechanism of action of TBK1 in tumors in recent years and the progress of small molecule inhibitors of TBK1.

The Therapeutic Effect of Natural Compounds on Osteoporosis through Ferroptosis.

Ferroptosis is a newly discovered non-apoptotic cell death whose key is lipid peroxidation. It has been reported that ferroptosis is involved in the occurrence and development of tumors and nervous system and musculoskeletal diseases. Cellular ferroptosis contributes to the imbalance of bone homeostasis and is involved in the development of osteoporosis; however, the detailed mechanism of which is still unclear though it may provide a new direction for anti-osteoporosis. The current drugs used in the treatment of osteoporosis, such as bisphosphonates and teriparatide, have many side effects, increasing people's search for natural compounds to treat osteoporosis. This review paper briefly summarizes the current research regarding the mechanisms of ferroptosis and natural anti-osteoporosis compounds targeting its pathway.

Nerolidol inhibited U-251 human glioblastoma cell proliferation and triggered apoptosis via the upregulation of the p38 MAPK signaling pathway.

Glioblastoma multiforme (GBM) is a lethal brain tumor with high mortality and morbidity. Nerolidol (NRD) is a sesquiterpene alcohol sequestered from the essential oils of aromatic florae with potent antioxidant, antiviral, anticancer, cardioprotective, and neuroprotective activity. The aim of the study was to investigate the underlying cell-cycle mechanisms of NRD-mediated antiproliferative and apoptosis activities in GBM using human U-251 cells. The current research investigated the antiproliferative and apoptotic activities of NRD on U-251 cells. The effects of NRD were measured using a Cell Counting Kit-8 (CCK-8) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, messenger ribonucleic acid (mRNA) level assessment, and western blot assay. Nerolidol decreased U-251 viability in a dose-dependent manner, as well as induced apoptotic activity, reduced B-cell lymphoma-2 (BCL-2) levels, and increased mRNA expression of BCL-2-associated X (Bax), caspase-3 and caspase-9. The attenuation of the cyclin-D1, cyclin-dependent kinase 4 (CDK4) and CDK6 mRNA expression confirmed cell cycle regulation. Western blot analysis of CDK1 indicated reductions in cyclin-B1 and p21. Furthermore, NRD prompted apoptosis through p38 amelioration and increased phosphorylated extracellular signal-related kinase 1 (p-ERK1) and phosphorylated c-Jun N-terminal protein kinase 1 (p-JNK1) levels. Nerolidol inhibited GBM cell viability and induced apoptosis through the regulation of cell-cycle proteins via p38 mitogen-activated protein kinase (MAPK) signaling pathways. Thus, NRD could be developed as a potential natural therapeutic agent for GBM.

D-Optimal Mixture Design Enabled Development of Lyophilized Nanoemulsifying Drug Delivery System of Paliperidone

Background: Schizophrenia is a chronic disease with acute psychotic symptoms, which is having frequent recurrence. Paliperidone palmitate (PP) is a second-generation antipsy-chotic drug to treat schizophrenia. Aims: The aim of the study was to prepare lyophilized nanoemulsifying drug delivery system (NEDDS) of paliperidone (PD). Objective: The primary objective of the current research work was to develop a lyophilized nanoemulsifying drug delivery system (NEDDS) of paliperidone (PD) to improve its oral bioa-vailability and stability. Methods: Optimization using D-Optimal Mixture Design DMD) was conducted, and optimized NEDDS was further lyophilized to improve stability. The lyophilized optimized NEDDS was fur-ther evaluated for biopharmaceutical evaluation. Result: A saturation solubility study revealed Peceol, Tween 80, and Plurol Olique CC497 as suitable candidates for oil, surfactant, and co-surfactant, respectively. Optimized NEDDS of PD showed mean globule size (MGS) of 185 nm, PDI of 0.27 and cumulative % drug release within 15 min Q15 of 86.6%. Lyophilized optimized NEDDS was found to have no significant change in quality attributes within the stability study period. A pharmacokinetic study revealed more than two-fold increases in bioavailability for lyophilized optimized NEDDS. Conclusion: Hence, lyophilized NEDDS of PD can be used as an effective approach for the im-provement of oral bioavailability and stability.

Emotion dysregulation and family functioning moderate family caregiving burden during the pandemic.

Since the onset of COVID-19 pandemic, additional risk factors affecting family caregivers' mental health have arisen. Therefore, personal stress coping strategies and family dynamics became important factors in reducing the impact of the pandemic on family caregivers' mental health. The present research aimed to estimate the association between COVID-19 stressors and family caregiving burden. Moreover, moderating effects of emotion dysregulation and family functioning on this association were investigated. This study analyzed data collected in April 2021 from 154 family caregivers (Mage=38.79, SDage=9.36, range=22-64) recruited through Amazon's Mechanical Turk (MTurk). The impact of COVID-19 stressors on family caregiving burden was tested, and moderating impacts of emotion dysregulation and family functioning were also investigated. Both COVID-19 stress exposure and stress appraisal were positively associated with family caregiving burden. Emotion dysregulation and problematic family functioning were also positively associated with family caregiving burden. A significant moderating effect of emotion dysregulation was found, such that family caregivers with higher emotion dysregulation were likely to feel more caregiving burden when they experienced more COVID-19 stressors. The current research highlighted the role of emotion regulation in reducing the negative impact of COVID-19 stressors on family caregiving burden. The research also emphasizes the need for intervention programs to improve emotion regulation strategies to decrease family caregiving burden during the pandemic.