Microbiology of bloodstream infections in Ontario, Canada during COVID-19 pandemic.

Background: Bloodstream infections (BSI) caused by a wide range of bacterial and fungal pathogens are associated with high rates of morbidity and mortality. Based on an estimate in 2017, the number of BSI incidences in Ontario is 150 per 100,000 population. The epidemiology of BSIs may be affected by many factors, including the social and travel restrictions and increased rates of hospitalizations in Ontario during the coronavirus disease 2019 (COVID-19) pandemic. Objectives: This study aimed to assess the changes in the microbiology of BSIs in Ontario during the COVID-19 pandemic compared to the pre-pandemic period. Methods: Retrospective blood culture data (n=189,106) from LifeLabs Ontario (July 2018 to December 2021) were analyzed. Blood culture positivity rates for common bacterial pathogens were compared between pre-COVID-19 (July 2018 to March 2020) and COVID-19 (April 2020 to December 2021) periods in community and hospital settings, using the chi-square test for significance. Results: During the COVID-19 period, blood culture positivity rates in the community remained the same, while hospital rates increased by approximately threefold (p=0.00E-00). In the community, the isolation rates of most bacterial species remained unchanged, except for an increase in Enterococcus spp. and a decrease in Salmonella spp. The rates of antibiotic-resistant organisms (AROs) also significantly decreased in the community. In hospitals, all bacterial species, including AROs, showed significant increases in isolation rates during the COVID-19 period. Conclusion: The study revealed shifts in the microbiology of BSIs and suggests changes in the epidemiology of BSIs during the COVID-19 pandemic in Ontario, both in hospitals and in the community.

The Association of Cytokines IL-2, IL-6, TNF-α, IFN-γ, and IL-10 With the Disease Severity of COVID-19: A Study From Bangladesh.

Introduction Clinically, the early prediction of the severity of COVID-19 is often challenging, as a dramatic change in severity can occur without warning. The severity of COVID-19 disease is associated with an increased level of inflammatory mediators, including cytokines. This study aimed to evaluate the association of the levels of cytokines interleukin (IL)-2, IL-6, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and IL-10 with the severity of COVID-19 in Bangladesh. Materials and methods This cross-sectional study included a total of 60 confirmed cases of COVID-19, comprising 30 severe cases (Group A) and 30 non-severe cases (Group B), and 10 healthy individuals (Group C) attending Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2021 to February 2022. The cytokine assay was performed using the human Th1/Th2/Th17 cytokine kit BD cytometric bead array (CBA) on the BD Accuri C6 Plus flow cytometer. Statistical analysis was conducted using IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York). Results The mean ages of the patients in Groups A, B, and C were 60.73±5.97, 57.13±7.68, and 48.10±9.13 years, respectively, with a male predominance in all groups. The mean IL-2, IL-6, IL-10, and TNF-α levels had a positive correlation with the increased age group and male gender, although it was not statistically significant. The mean IL-6 and IFN-γ levels were significantly higher among severe cases (216.95±147.78 and 0.98±0.95 pg/mL, respectively) compared to non-severe cases (94.29±128.79 and 0.41±0.61 pg/mL, respectively) and healthy individuals (1.08±1.97 and 0.15±0.28 pg/mL, respectively). Furthermore, the anti-inflammatory cytokine IL-10 was also significantly higher among severe cases (17.92±21.87 pg/mL) compared to non-severe cases (5.38±6.73 pg/mL) and healthy individuals (1.62±1.65 pg/mL). Conclusion IL-6, IFN-γ, and IL-10 have a significant association with the severity of COVID-19 disease. Clinicians treating patients with COVID-19 can consider the level of these cytokines as biomarkers of severity.

Ultra-high-resolution CT vs. invasive angiography for detecting hemodynamically significant coronary artery disease: Rationale and methods of the CORE-PRECISION multicenter study.

BACKGROUND: Direct coronary arterial evaluation via computed tomography (CT) angiography is the most accurate noninvasive test for the diagnosis of coronary artery disease (CAD). However, diagnostic accuracy is limited in the setting of severe coronary calcification or stents. Ultra-high-resolution CT (UHR-CT) may overcome this limitation, but no rigorous study has tested this hypothesis. METHODS: The CORE-PRECISION is an international, multicenter, prospective diagnostic accuracy study testing the non-inferiority of UHR-CT compared to invasive coronary angiography (ICA) for identifying patients with hemodynamically significant CAD. The study will enroll 150 patients with history of CAD, defined as prior documentation of lumen obstruction, stenting, or a calcium score ≥400, who will undergo UHR-CT before clinically prompted ICA. Assessment of hemodynamically significant CAD by UHR-CT and ICA will follow clinical standards. The reference standard will be the quantitative flow ratio (QFR) with <0.8 defined as abnormal. All data will be analyzed in independent core laboratories. RESULTS: The primary outcome will be the comparative diagnostic accuracy of UHR-CT vs. ICA for detecting hemodynamically significant CAD on a patient level. Secondary analyses will focus on vessel level diagnostic accuracy, quantitative stenosis analysis, automated contour detection, in-depth plaque analysis, and others. CONCLUSION: CORE-PRECISION aims to investigate if UHR-CT is non-inferior to ICA for detecting hemodynamically significant CAD in high-risk patients, including those with severe coronary calcification or stents. We anticipate this study to provide valuable insights into the utility of UHR-CT in this challenging population and for its potential to establish a new standard for CAD assessment.

"Jordanian Nurses' Perceptions of Disaster Preparedness and Core Competencies".

OBJECTIVE: This study aims to identify the Jordanian nurses' perception of their disaster preparedness and core competencies. METHODS: A descriptive, cross-sectional research design was used. The data was collected via an online self-reported questionnaire using the disaster preparedness evaluation tool and the core disaster competencies tool. RESULTS: A total of 126 nurses participated in the study. Jordanian nurses had moderate to high levels of core disaster competencies and moderate levels of disaster preparedness. Core disaster competencies and disaster preparedness levels differed based on previous training on disaster preparedness and the availability of an established emergency plan in their hospitals. Lastly, a previous training on disaster preparedness and core disaster competencies were statistically significant predictors of disaster preparedness among Jordanian nurses. CONCLUSIONS: Organizational factors and environmental contexts play a role in the development of such capabilities. Future research should focus on understanding the barriers and facilitators of developing core disaster competencies and disaster preparedness among nurses.

Deep phenotyping of dementia in a multi-ethnic cardiovascular cohort: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Our understanding of the specific aspects of vascular contributions to dementia remains unclear. OBJECTIVES: We aim to identify the correlates of incident dementia in a multi-ethnic cardiovascular cohort. METHODS: A total of 6806 participants with follow-up data for incident dementia were included. Probable dementia diagnoses were identified using hospitalization discharge diagnoses according to the International Classification of Diseases Codes (ICD). We used Random Forest analyses to identify the correlates of incident dementia and cognitive function from among 198 variables collected at the baseline MESA exam entailing demographic risk factors, medical history, anthropometry, lab biomarkers, electrocardiograms, cardiovascular magnetic resonance imaging, carotid ultrasonography, coronary artery calcium and liver fat content. Death and stroke were considered competing events. RESULTS: Over 14 years of follow-up, 326 dementia events were identified. Beyond age, the top correlates of dementia included coronary artery calcification, high sensitivity troponin, common carotid artery intima to media thickness, NT-proBNP, physical activity, pulse pressure, tumor necrosis factor-α, history of cancer, and liver to spleen attenuation ratio from computed tomography. Correlates of cognitive function included income and physical activity, body size, serum glucose, glomerular filtration rate, measures of carotid artery stiffness, alcohol use, and inflammation indexed as IL-2 and TNF soluble receptors and plasmin-antiplasmin complex. CONCLUSION: In a deeply phenotyped cardiovascular cohort we identified the key correlates of dementia beyond age as subclinical atherosclerosis and myocyte damage, vascular function, inflammation, physical activity, hepatic steatosis, and history of cancer.

Ovoselenol, a Selenium-containing Antioxidant Derived from Convergent Evolution.

Selenium is an essential micronutrient, but its presence in biology has been limited to protein and nucleic acid biopolymers. The recent identification of the first biosynthetic pathway for selenium-containing small molecules suggests that there is a larger family of selenometabolites that remains to be discovered. Using a bioinformatic search strategy that relies on mapping of composite active site motifs, we identify a recently evolved branch of abundant and uncharacterized metalloenzymes that we predict are involved in selenometabolite biosynthesis. Biochemical studies confirm this prediction and show that these enzymes form an unusual C-Se bond onto histidine, thus giving rise to a novel selenometabolite and potent antioxidant that we have termed ovoselenol. Aside from providing insights into the evolution of this enzyme class and the structural basis of C-Se bond formation, our work offers a blueprint for charting the microbial selenometabolome in the future.

Ti3C2Tx Filled in EMIMBF4 Semi-Solid Polymer Electrolytes for the Zinc-Metal Battery.

Zinc-ion batteries (ZIBs) are promising candidates for safe energy storage applications. However, undesirable parasitic reactions such as dendrite growth, gas evaluation, anode corrosion, and structural damage to the cathode under an acidic microenvironment severely affected cell performance. To resolve these issues, an MXene entrapped in an ionic liquid semi-solid gel polymer electrolyte (GPE) composite was explored. The molecular-level mixing of poly(vinylidene fluoride-co-hexafluoropropylene) (PVHF), zinc trifluoromethanesulfonate (Zn(OTF)2), 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIBF4) ionic liquid, and Ti3C2Tx MXene provided a controlled Zn2+ shuttle toward the anode/cathode. Ti3C2Tx/EMIBF4/Zn(OTF)2/PVHF exhibited a breaking strength of 0.36 MPa with an associated extension of 23%. The Zn//Ti3C2Tx/EMIBF4/Zn(OTF)2/PVHF//Zn symmetric cell with continuous zinc plating/stripping exhibited excellent Zn2+ ion mobility toward the anode and cathode without undesired reactions. This was confirmed by post-mortem analysis after a symmetric cell compatibility test. The as-prepared GPE with a Na3V2(PO4)3 (NVP) cathode exhibited a high chemical diffusion coefficient of 1.14 × 10-7. It also showed an outstanding reversible capacity of 89 mAh g-1 at C/10 with an average discharge plateau voltage of 1.45 V, cycle durability, and controlled self-discharge. These results suggested that the Zn2+ ions in the Ti3C2Tx/EMIBF4/Zn(OTF)2/PVHF composite are reversibly labile in the anode and cathode directions.

DL_POLY Quantum 2.0: A modular general-purpose software for advanced path integral simulations.

DL_POLY Quantum 2.0, a vastly expanded software based on DL_POLY Classic 1.10, is a highly parallelized computational suite written in FORTRAN77 with a modular structure for incorporating nuclear quantum effects into large-scale/long-time molecular dynamics simulations. This is achieved by presenting users with a wide selection of state-of-the-art dynamics methods that utilize the isomorphism between a classical ring polymer and Feynman's path integral formalism of quantum mechanics. The flexible and user-friendly input/output handling system allows the control of methodology, integration schemes, and thermostatting. DL_POLY Quantum is equipped with a module specifically assigned for calculating correlation functions and printing out the values for sought-after quantities, such as dipole moments and center-of-mass velocities, with packaged tools for calculating infrared absorption spectra and diffusion coefficients.

Lamina Cribrosa Insertions Into the Sclera Are Sparser, Narrower, and More Slanted in the Anterior Lamina.

Purpose: The lamina cribrosa (LC) depends on the sclera for support. The support must be provided through the LC insertions. Although a continuous insertion over the whole LC periphery is often assumed, LC insertions are actually discrete locations where LC collagenous beams meet the sclera. We hypothesized that LC insertions vary in number, size, and shape by quadrant and depth. Methods: Coronal cryosections through the full LCs from six healthy monkey eyes were imaged using instant polarized light microscopy. The images were registered into a stack, on which we manually marked LC insertion outlines, nothing their position in-depth and quadrant (inferior, superior, nasal, or temporal). From the marks, we determined the insertion number, width, angle to the canal wall (90 degrees = perpendicular), and insertion ratio (fraction of LC periphery represented by insertions). Using linear mixed effect models, we determined if the insertion characteristics were associated with depth or quadrant. Results: Insertions in the anterior LC were sparser, narrower, and more slanted than those in deeper LC (P values < 0.001). There were more insertions spanning a larger ratio of the canal wall in the middle LC than in the anterior and posterior (P values < 0.001). In the nasal quadrant, the insertion angles were significantly smaller (P < 0.001). Conclusions: LC insertions vary substantially and significantly over the canal. The sparser, narrower, and more slanted insertions of the anterior-most LC may not provide the robust support afforded by insertions of the middle and posterior LC. These variations may contribute to the progressive deepening of the LC and regional susceptibility to glaucoma.

Educational Paradigms in Islamic Medical History: A Review.

The rise of Islam in Arabia witnessed a scientific pursuit from 8th CE to 14th CE in its vast dominion. Medicine was one among many disciplines that was reshaped during the golden ages of Islamic world. Physicians and scholars from diverse faiths and background flocked in learning centers of Baghdad, Cordoba, and other cities. A multicultural environment of medical research was evolved with fundings from state. From medical teaching and clinical training to the licensing of physicians, many of the modern attributes of medical education were pioneered in Islamic world. The scholarly transfusion from European territories of Islamic world to the Western world in medieval era laid the foundation of modern medical education.

Protection of natural infection against reinfection with SARS-CoV-2 JN.1 variant.

Overall effectiveness of infection in preventing reinfection with SARS-CoV-2 JN.1 variant was estimated at 1.8% (95% CI: -9.3-12.6%), and demonstrated rapid decline over time since the previous infection, decreasing from 82.4% (95% CI: 40.9 to 94.7%) within 3 to less than 6 months, to a negligible level after one year.

Effectiveness of two and three doses of COVID-19 mRNA vaccines against infection, symptoms, and severity in the pre-omicron era: A time-dependent gradient.

BACKGROUND: Vaccines were developed and deployed to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to characterize patterns in the protection provided by the BNT162b2 and mRNA-1273 mRNA vaccines against a spectrum of SARS-CoV-2 infection symptoms and severities. METHODS: A national, matched, test-negative, case-control study was conducted in Qatar between January 1 and December 18, 2021, utilizing a sample of 238,896 PCR-positive tests and 6,533,739 PCR-negative tests. Vaccine effectiveness was estimated against asymptomatic, symptomatic, severe coronavirus disease 2019 (COVID-19), critical COVID-19, and fatal COVID-19 infections. Data sources included Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalization, and death. RESULTS: Effectiveness of two-dose BNT162b2 vaccination was 75.6% (95% CI: 73.6-77.5) against asymptomatic infection and 76.5% (95% CI: 75.1-77.9) against symptomatic infection. Effectiveness against each of severe, critical, and fatal COVID-19 infections surpassed 90%. Immediately after the second dose, all categories-namely, asymptomatic, symptomatic, severe, critical, and fatal COVID-19-exhibited similarly high effectiveness. However, from 181 to 270 days post-second dose, effectiveness against asymptomatic and symptomatic infections declined to below 40%, while effectiveness against each of severe, critical, and fatal COVID-19 infections remained consistently high. However, estimates against fatal COVID-19 often had wide 95% confidence intervals. Analogous patterns were observed in three-dose BNT162b2 vaccination and two- and three-dose mRNA-1273 vaccination. Sensitivity analyses confirmed the results. CONCLUSION: A gradient in vaccine effectiveness exists and is linked to the symptoms and severity of infection, providing higher protection against more symptomatic and severe cases. This gradient intensifies over time as vaccine immunity wanes after the last vaccine dose. These patterns appear consistent irrespective of the vaccine type or whether the vaccination involves the primary series or a booster.

The Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) versus Transcranial Direct-Current Stimulation (tDCS) on Migraine Headaches: A Randomized Clinical Trial.

Background: Non-pharmacologic prophylactic methods for chronic migraine have been developed, including the promising non-invasive techniques of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). This study aimed to compare the efficacy of rTMS and tDCS on pain intensity, the impact of headaches on daily life, anxiety, and depression in migraine headaches patients. Materials and Methods: This randomized clinical trial was conducted on 72 patients with migraine headaches, randomly allocated to the rTMS and tDCS groups. Participants received 3 and 12 sessions of stimulation over the left dorsolateral prefrontal cortex (DLPFC), respectively. Follow-up measurements, including pain intensity, anxiety, depression, and impact on daily life, were performed one month after the last sessions. Analyses were done by IBM SPSS statistics version 26 software. Results: Of 72 patients enrolled in the study, 19 were male (8 in the rTMS group and 11 in the tDCS group). There was no significant difference in baseline characteristics between groups. During the follow-up visit, both groups showed a decrease in anxiety levels (P values = 0.005 and 0.015), while only the rTMS group displayed a significant improvement in depression (P value = 0.01). However, no statistically significant difference was found among the groups regarding changes in pain intensity, anxiety, and the impact of headaches on daily life (P values >0.05). Conclusion: Our findings suggest that both rTMS and tDCS may be effective in reducing pain intensity and improving the impact of headaches on daily life and anxiety in patients with chronic migraine. However, significant improvement in depression was only observed in the rTMS group patients.

Addressing bias in the definition of SARS-CoV-2 reinfection: implications for underestimation.

Introduction: Reinfections are increasingly becoming a feature in the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, accurately defining reinfection poses methodological challenges. Conventionally, reinfection is defined as a positive test occurring at least 90 days after a previous infection diagnosis. Yet, this extended time window may lead to an underestimation of reinfection occurrences. This study investigated the prospect of adopting an alternative, shorter time window for defining reinfection. Methods: A longitudinal study was conducted to assess the incidence of reinfections in the total population of Qatar, from February 28, 2020 to November 20, 2023. The assessment considered a range of time windows for defining reinfection, spanning from 1 day to 180 days. Subgroup analyses comparing first versus repeat reinfections and a sensitivity analysis, focusing exclusively on individuals who underwent frequent testing, were performed. Results: The relationship between the number of reinfections in the population and the duration of the time window used to define reinfection revealed two distinct dynamical domains. Within the initial 15 days post-infection diagnosis, almost all positive tests for SARS-CoV-2 were attributed to the original infection. However, surpassing the 30-day post-infection threshold, nearly all positive tests were attributed to reinfections. A 40-day time window emerged as a sufficiently conservative definition for reinfection. By setting the time window at 40 days, the estimated number of reinfections in the population increased from 84,565 to 88,384, compared to the 90-day time window. The maximum observed reinfections were 6 and 4 for the 40-day and 90-day time windows, respectively. The 40-day time window was appropriate for defining reinfection, irrespective of whether it was the first, second, third, or fourth occurrence. The sensitivity analysis, confined to high testers exclusively, replicated similar patterns and results. Discussion: A 40-day time window is optimal for defining reinfection, providing an informed alternative to the conventional 90-day time window. Reinfections are prevalent, with some individuals experiencing multiple instances since the onset of the pandemic.

Perceptual Thresholds for Radial Optic Flow Distortion in Near-Eye Stereoscopic Displays.

We provide the first perceptual quantification of user's sensitivity to radial optic flow artifacts and demonstrate a promising approach for masking this optic flow artifact via blink suppression. Near-eye HMOs allow users to feel immersed in virtual environments by providing visual cues, like motion parallax and stereoscopy, that mimic how we view the physical world. However, these systems exhibit a variety of perceptual artifacts that can limit their usability and the user's sense of presence in VR. One well-known artifact is the vergence-accommodation conflict (VAC). Varifocal displays can mitigate VAC, but bring with them other artifacts such as a change in virtual image size (radial optic flow) when the focal plane changes. We conducted a set of psychophysical studies to measure users' ability to perceive this radial flow artifact before, during, and after self-initiated blinks. Our results showed that visual sensitivity was reduced by a factor of 10 at the start and for ~70 ms after a blink was detected. Pre- and post-blink sensitivity was, on average, ~O.15% image size change during normal viewing and increased to ~1.5- 2.0% during blinks. Our results imply that a rapid (under 70 ms) radial optic flow distortion can go unnoticed during a blink. Furthermore, our results provide empirical data that can be used to inform engineering requirements for both hardware design and software-based graphical correction algorithms for future varifocal near-eye displays. Our project website is available at https://gamma.umd.edu/ROF/.

SIRT4 as a novel interactor and candidate suppressor of C-RAF kinase in MAPK signaling.

Cellular responses leading to development, proliferation, and differentiation depend on RAF/MEK/ERK signaling, which integrates and amplifies signals from various stimuli for downstream cellular responses. C-RAF activation has been reported in many types of tumor cell proliferation and developmental disorders, necessitating the discovery of potential C-RAF protein regulators. Here, we identify a novel and specific protein interaction between C-RAF among the RAF kinase paralogs, and SIRT4 among the mitochondrial sirtuin family members SIRT3, SIRT4, and SIRT5. Structurally, C-RAF binds to SIRT4 through the N-terminal cysteine-rich domain, whereas SIRT4 predominantly requires the C-terminus for full interaction with C-RAF. Interestingly, SIRT4 specifically interacts with C-RAF in a pre-signaling inactive (serine 259-phosphorylated) state. Consistent with this finding, the expression of SIRT4 in HEK293 cells results in an up-regulation of pS259-C-RAF levels and a concomitant reduction in MAPK signaling as evidenced by strongly decreased phospho-ERK signals. Thus, we propose an additional extra-mitochondrial function of SIRT4 as a cytosolic tumor suppressor of C-RAF-MAPK signaling, besides its metabolic tumor suppressor role of glutamate dehydrogenase and glutamate levels in mitochondria.

In silico clinical studies for optimal COVID-19 vaccination schedules in patients with cancer.

This study introduces a tailored COVID-19 model for patients with cancer, incorporating viral variants and immune-response dynamics. The model aims to optimize vaccination strategies, contributing to personalized healthcare for vulnerable groups.

Compliance to personal hygiene habits in response to COVID-19 pandemic.

OBJECTIVE: This study aimed to evaluate the Jordanians' compliance rates in terms of personal hygiene habits in response to the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A descriptive cross-sectional design was utilized to collect data from 651 Jordanians via an electronic self-report questionnaire. Data was analyzed using Statistical Package for Social Sciences software Results: The overall compliance rate for personal hygiene habits among Jordanians was 79 percent (11.85/15, SD = 9). Personal hygiene practices differ significantly across age groups (F = 2, 89, p = .04), gender (t = 5.18, p = .003), marital status (F = 3.09, p = .029), and being a member of a healthcare specialty (t = -2.20, p = .028). Gender, educational level, occupation, and living place were statistically significant predictors for compliance with personal hygiene habits. Compliance rates increased drastically (82 percent) in response to the COVID-19 pandemic. CONCLUSION: Compliance with personal hygiene habits among Jordanians was encouraging in response to the COVID-19 pandemic. Still, there is a chance for more improvement to reach optimum levels of safe and healthy per-sonal hygiene habits. Healthcare authorities shall adopt change management programs and theories to target personal hygiene habits where opportunities for improvement are found.

Public Attitudes and Beliefs About Organ Donation: Development and Validation of a New Instrument.

Background and Purpose: The number of patients in need of lifesaving organ transplants continues to exceed the number of available. One of the most critical factors influencing peoples' practices and rates of organ donation is their attitude and beliefs. This study aimed to develop and validate an instrument that evaluates peoples' attitudes and beliefs about organ donation. Methods: A cross-sectional methodological study was used to guide the development of a questionnaire after reviewing the literature. Results: The initial items (n = 45) were evaluated by 15 nonexperts pilot to verify face validity; then, content validity was established by three experts, and exploratory factorial analysis established construct validity. Afterward, internal consistency was checked using Cronbach's α analysis. Eventually, 31 items were included in the questionnaire, comprising four subscales. Conclusion: According to the results, we found that the "Public Attitudes and Beliefs about Organ Donation" questionnaire has adequate validity and reliability to assess peoples' attitudes and beliefs about organ donation.

Psychological challenges of female caregivers in providing home-based palliative care for patients with advanced cancer: A descriptive-exploratory study.

BACKGROUND: Family caregivers play a key role in providing care for patients with advanced cancer. Most of this care burden is shouldered by female caregivers in the family. Compared to their male counterparts, female caregivers face numerous psychological challenges in the process of caregiving. The aim of this study was to identify the psychological challenges of female caregivers in providing care to patients with advanced cancer. MATERIALS AND METHODS: This descriptive-exploratory study began with purposive sampling method in 2020-2021 in Isfahan and continued until data saturation was reached. Twenty semi-structured interviews were conducted with female caregivers of patients with advanced cancer and 18 more interviews with providers of health services and supportive-palliative care. The interviews were recorded, transcribed, and analyzed using conventional qualitative content analysis. DISCUSSION: The results were classified into three categories. The first category was psychological reactions that included the four subcategories of depression and anxiety, aggression, mental exhaustion, and death anxiety; the second category was psychological needs which included the three subcategories of need for professional counseling, need for emotional support, and need to prepare for mourning; and the third category was mental occupations which consisted of the two subcategories of feeling of regret and remorse. CONCLUSION: Assessment of psychological challenges is a prerequisite for planning psychological interventions, providing high-quality care, and improving quality of life and satisfaction of caregivers. The findings of this study will contribute to the development of guidelines and empowerment programs for female caregivers providing palliative care.