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It has become increasingly important for microbiology educators to help students learn critical concepts of the discipline. This is particularly true in virology, where current challenges include increasing rates of vaccine hesitancy, misinformation about the COVID-19 pandemic, and controversy surrounding research on pathogens with pandemic potential. Having students learn virology can attract more people to the field and increase the number of people who can engage in meaningful discourse about issues relating to the discipline. However, the limited number of virologists who teach undergraduates, combined with the fact that many institutions lack stand-alone virology courses, results in virology often being taught as a limited number of lectures within an undergraduate microbiology course (if it is covered at all), which may or may not be taught by an individual trained as a virologist. To provide a framework to teach virology to undergraduate students, a team of virology educators, with support from the American Society for Virology (ASV), developed curriculum guidelines for use in a stand-alone undergraduate virology course or a virology section within another course (D. B. Kushner et al., J Virol 96:e01305-22, 2022, https://doi.org/10.1128/jvi.01305-22). These guidelines are available at the ASV website (https://asv.org/curriculum-guidelines/). To assist educators in implementing these guidelines, we created examples of measurable learning objectives. This perspective provides details about the virology curriculum guidelines and learning objectives and accompanies the perspective by Boury et al. in this issue of the "Journal of Microbiology & Biology Education" (25:e00126-24, 2024, https://doi.org/10.1128/jmbe.00126-24) about the recent revision of the microbiology curriculum guidelines overseen by the American Society for Microbiology.

BACKGROUND: To evaluate whether infectious illness symptoms (IIS) are associated with generalized anxiety symptoms during the COVID-19 pandemic in sexual/gender (SGM) minority young adults assigned male at birth (AMAB). METHOD: Four hundred eighteen participants (median age = 25; range, 20-40) were recruited through RADAR, an ongoing Chicago-based cohort study of SGM-AMAB between September 2020 and February 2021. Participants completed online surveys. A subset (n = 145) provided dried blood spot samples to assess SARS-CoV-2 serostatus. RESULTS: One hundred twenty participants (28.7%) had GAD-7 scores of 10 or greater, which indicates generalized anxiety symptoms that may be clinically significant. In a binomial logistic regression model adjusting age, gender identity, race/ethnicity, substance use, and HIV status, the authors found that having a higher IIS count since March 1, 2020, was associated with greater odds of having a GAD-7 score of 10 or greater (OR = 1.14; 95% CI, 1.04, 1.25; P = 0.007). This effect was more pronounced in a binomial logistic regression model adjusting for the same covariates but using current IIS count as the independent variable (OR = 1.39; 95% CI, 1.13, 1.74; P = 0.002). CONCLUSION: Among SGM-AMAB young adults, those who experienced ISS reported higher scores on the GAD-7, a widely used and validated screening measure for generalized anxiety symptoms. These findings highlight the importance of screening for anxiety disorders when patients present with IIS in clinical settings and psychobehavioral health follow-ups when indicated.

The Mirandese language is a Romance language and form of Astur-Leonese that is spoken in a border region of rural northeastern Portugal. Mirandese owes its existence to the southward expansion of the medieval kingdoms of Asturias and Leon into territory later incorporated into the Portuguese kingdom. For most of its history Mirandese has been an essentially oral language, though in recent decades this has changed, and in 1999 an Orthographic Convention for the Mirandese Language was published. That same year, the Portuguese parliament recognized the existence of Mirandese and the linguistic rights of the Mirandese community. Despite these advances, spoken Mirandese is in decline, and it currently has an estimated 3,500 active speakers. This decline is due to factors including language stigmatization, particularly during the latter half of the twentieth century, improved transportation links between the northeast and the rest of Portugal, and rural-to-urban migration. Mirandese may go extinct as a spoken language by the mid-twenty-first century. On September 8, 2023, Cristina Martins (Associate Professor, Department of Languages, Literatures, and Cultures, Faculty of Letters, Arts and Humanities, University of Coimbra) gave a keynote address, “Mirandese, quo vadis?” at the 44th Annual Conference of the Association for Contemporary Iberian Studies, at the University of Porto. Professor Martins provided an overview of the history, present, and possible futures of Mirandese. She also described her linguistic research on and personal relationship with the language. I invited her to participate in this interview, conducted by email, to introduce Mirandese to a primarily North American academic audience, and to expand on the themes of her address.

Medical students with disabilities constitute 7.6% of allopathic (MD) and 4.3% of osteopathic (DO) programs, and they are entitled to reasonable accommodation, per the Americans with Disabilities Act. However, research has demonstrated that disabled medical students often encounter barriers when accessing accommodations. In response to these barriers, Medical Students with Chronic Illness and Disability (MSDCI) National created the MSDCI Guide to Accessing Disability Accommodations During Undergraduate Medical Education (the Guide). We conducted a program evaluation to evaluate the efficacy of the Guide as a resource to the members of MSDCI, a program evaluation was conducted. A Qualtrics survey was distributed though the MSDCI listserv, and 29 complete responses were received. Responses were analyzed with descriptive statistics. All respondents agreed or strongly agreed with the statement "I would recommend this guide to other medical students with disability and/or chronic illness." The sections rated "most useful" were "Accessing USMLE Accommodations" and "Understanding Materials for Accommodation." The section rated "least useful" was "Accessing CASPer Accommodations." Freeform comments highlighted a need for greater inclusion of DO-specific topics, and a more detailed explanation of the rights of disabled medical students. This feedback demonstrates that the Guide is a good resource for the disabled and chronically ill medical students in the MSDCI community. Future editions of the Guide will include more DO-related topics and exclude pre-medical topics.

BackgroundThe legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis.MethodsA total of 12 NCI-Designated Cancer Centers, across states with varied cannabis-access legal status, conducted surveys with a core questionnaire to assess cannabis use among recently diagnosed cancer patients. Data were collected between September 2021 and August 2023 and pooled across 12 cancer centers. Frequencies and 95% confidence intervals for core survey measures were calculated, and weighted estimates are presented for the 10 sites that drew probability samples.ResultsOverall reported cannabis use since cancer diagnosis among survey respondents was 32.9% (weighted), which varied slightly by state legalization status. The most common perceived benefits of use were for pain, sleep, stress and anxiety, and treatment side effects. Reported perceived risks were less common and included inability to drive, difficulty concentrating, lung damage, addiction, and impact on employment. A majority reported feeling comfortable speaking to health-care providers though, overall, only 21.5% reported having done so. Among those who used cannabis since diagnosis, the most common modes were eating in food, smoking, and pills or tinctures, and the most common reasons were for sleep disturbance, followed by pain and stress and anxiety with 60%-68% reporting improved symptoms with use.ConclusionThis geographically diverse survey demonstrates that patients use cannabis regardless of its legal status. Addressing knowledge gaps concerning benefits and harms of cannabis use during cancer treatment is critical to enhance patient-provider communication.

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with limited treatment options. Endothelial dysfunction plays a central role in the development and progression of PAH, yet the underlying mechanisms are incompletely understood. The endosome-lysosome system is important to maintain cellular health, and the small GTPase RAB7 regulates many functions of this system. Here, we explored the role of RAB7 in endothelial cell (EC) function and lung vascular homeostasis. We found reduced expression of RAB7 in ECs from patients with PAH. Endothelial haploinsufficiency of RAB7 caused spontaneous pulmonary hypertension (PH) in mice. Silencing of RAB7 in ECs induced broad changes in gene expression revealed via RNA-Seq, and RAB7-silenced ECs showed impaired angiogenesis and expansion of a senescent cell fraction, combined with impaired endolysosomal trafficking and degradation, suggesting inhibition of autophagy at the predegradation level. Furthermore, mitochondrial membrane potential and oxidative phosphorylation were decreased, and glycolysis was enhanced. Treatment with the RAB7 activator ML-098 reduced established PH in rats with chronic hypoxia/SU5416. In conclusion, we demonstrate for the first time to our knowledge the fundamental impairment of EC function by loss of RAB7, causing PH, and show RAB7 activation to be a potential therapeutic strategy in a preclinical model of PH.

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and pre-operative PSA levels. More importantly, we demonstrate that elevated Trop2 expression at radical prostatectomy predicts worse overall survival in men undergoing radical prostatectomy. Additionally, we detect shed Trop2 in urine from men with clinically significant prostate cancer. Our study identifies Trop2 as a novel tissue prognostic biomarker and a candidate non-invasive marker for prostate cancer.

Derek P Lindsey,1 Luis Perez-Orribo,2 Nestor Rodriguez-Martinez,2 Phillip M Reyes,2 Anna Newcomb,2 Alexandria Cable,2 Grace Hickam,2 Scott A Yerby,1 Neil R Crawford21SI-BONE, Inc., San Jose, CA, USA; 2Spinal Biomechanics Research Laboratory, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ, USAIntroduction: Sacroiliac (SI) joint pain has become a recognized factor in low back pain. The purpose of this study was to investigate the effect of a minimally invasive surgical SI joint fusion procedure on the in vitro biomechanics of the SI joint before and after cyclic loading.Methods: Seven cadaveric specimens were tested under the following conditions: intact, posterior ligaments (PL) and pubic symphysis (PS) cut, treated (three implants placed), and after 5,000 cycles of flexion–extension. The range of motion (ROM) in flexion–extension, lateral bending, and axial rotation was determined with an applied 7.5 N • m moment using an optoelectronic system. Results for each ROM were compared using a repeated measures analysis of variance (ANOVA) with a Holm–Šidák post-hoc test.Results: Placement of three fusion devices decreased the flexion–extension ROM. Lateral bending and axial rotation were not significantly altered. All PL/PS cut and post-cyclic ROMs were larger than in the intact condition. The 5,000 cycles of flexion–extension did not lead to a significant increase in any ROMs.Discussion: In the current model, placement of three 7.0 mm iFuse Implants significantly decreased the flexion–extension ROM. Joint ROM was not increased by 5,000 flexion–extension cycles.Keywords: biomechanics, iliosacral, arthrodesis, cadaver

Abstract Background We previously reported that increases in circulating sphingolipids are associated with elevated risk of biopsy Gleason grade group (GG) upgrading in men on Active Surveillance (AS) for prostate cancer. Here, we aimed to validate these findings and establish a blood-based sphingolipid biomarker panel for identifying men on AS who are at high-risk of biopsy GG upgrading. Methods Men diagnosed with low- or intermediate-risk prostate cancer in one of two AS cohorts (CANARY PASS and MDACC) were followed for GG upgrading after diagnostic and confirmatory biopsy. The PASS cohort consisted of 544 patients whereas the MDACC Cohort consisted of 697 patients. The number of patients with GG upgrading during course of study follow-up in the PASS and MDACC cohorts were 98 (17.7%) and 133 (19.1%), respectively. Plasmas collected prior to confirmatory biopsy were used for mass spectrometry-based quantitation of 87 unique sphingolipid species. A neural network layer based on 21 sphingolipids was developed in the CANARY PASS cohort for predicting biopsy GG upgrading. Tertile-based thresholds for low-, intermediate-, and high-risk strata were subsequently developed for the sphingolipid panel as well as a model that combined the sphingolipid panel with PSA density and rate of core positivity on diagnostic biopsy. The resultant models and risk thresholds for GG upgrading were validated in the MDACC cohort. Performance was assessed using Cox proportional hazard models, C-index, AUC, and cumulative incidence curves. Results The sphingolipid panel had a HR (per unit standard deviation increase) of 1.36 (95% CI: 1.07–1.70) and 1.35 (95% CI: 1.11–1.64) for predicting GG biopsy upgrading in the PASS and MDACC cohort, respectively. The model that combined the sphingolipid panel with PSA density and rate of core positivity achieved a HR of 1.63 (95% CI: 1.33-2.00) and 1.44 (1.25–1.66), respectively. Tertile-based thresholds, established in the PASS cohort, were applied to the independent MDACC cohort. Compared to the low-risk group, MDACC patients in the high-risk strata had a GG biopsy upgrade HR of 3.65 (95% CI: 2.21–6.02), capturing 50% of the patients that had biopsy upgrading during study follow-up. Conclusions The sphingolipid panel is independently associated with GG biopsy upgrading among men in two independent AS cohorts who have previously undergone diagnostic and confirmatory biopsy. The sphingolipid panel, together with clinical factors, provides a potential means for risk stratification to better guide clinical management of men on AS.

Trigger warnings have become a hotly contested practice in higher education, including within the field of social work. Learning to become a social worker can be a demanding process that requires in-depth study about often socially taboo and traumatic topics. The learning process can, understandably, cause discomfort that may result in a disconcerting or anxiety-provoking experience for social work students. However, the inclusion of challenging topics in social work education, including human rights violations, domestic violence, sexual abuse, racism, sexism, and many other social injustices is essential in the development of competency in social work practice. What remains unclear is the role and responsibility of universities and subsequently educators, in how we include or exclude trigger warnings, their relevance to social work education, and how we manage the expectations of students and their responses to the exposure of sensitive material. This article argues that trigger warnings may contribute to the pathologization of the experience of discomfort while simultaneously silencing oppressed students who may not identify with the language or experience of being triggered. This article investigates trigger warnings from a critical social work perspective and considers if the use of trigger warnings may potentially be more harmful than helpful.

Purpose: This study aims to promote sustainability-based education in fashion design and merchandising program to enhance students' knowledge, skills and attitude about sustainability development, organizational responsibility and personal responsibility from the cotton industry perspective. Design/methodology/approach: To conduct this study, three learning components were considered: learning from experts, learning by doing and outreach activity. Sustainability-related topics were strategically incorporated in different courses for one year; project-based learning approach was adopted; and pre-posttest survey was conducted to study the impact of sustainability-based education on student learning outcome. Rand's principles-attributes matrix was applied to analyze the impact of sustainable education on student learning outcomes. Findings: The results of course projects indicated enhanced student's abilities on using use different types of cotton materials in product development, creative use of cotton in visual merchandising and development of business plans focused on sustainability. The two-group mean comparisons showed a significant positive impact on students' knowledge in cotton and sustainability, followed by students' skills and attitudes. Originality/value: In response to the lack of systematic approach to incorporate sustainability-related topics in textile and apparel design discipline, this study offered an opportunity to involve approximately 110 students in various sustainability-based teaching and learning projects.

Although decades of behavior-analytic studies have focused on decreasing the aggressive behavior of clients, relatively little research has been conducted on preventing injuries for the staff members who implement treatment plans. In this study, three direct-care staff members working with clients presenting with aggressive behavior were taught targeted blocking and distance management techniques designed to keep the clients safe while preventing injuries to the participants. Findings indicated that all staff members acquired the target skills in simulations, after which the skills for two participants generalized to the natural work environment.

BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folates role in CRC. OBJECTIVES: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Phosphatase and tensin homolog (PTEN) loss is associated with adverse outcomes in prostate cancer and can be measured via immunohistochemistry. The purpose of the study was to establish the clinical application of an in-house developed artificial intelligence (AI) image analysis workflow for automated detection of PTEN loss on digital images for identifying patients at risk of early recurrence and metastasis. Postsurgical tissue microarray sections from the Canary Foundation (n = 1264) stained with anti-PTEN antibody were evaluated independently by pathologist conventional visual scoring (cPTEN) and an automated AI-based image analysis pipeline (AI-PTEN). The relationship of PTEN evaluation methods with cancer recurrence and metastasis was analyzed using multivariable Cox proportional hazard and decision curve models. Both cPTEN scoring by the pathologist and quantification of PTEN loss by AI (high-risk AI-qPTEN) were significantly associated with shorter metastasis-free survival (MFS) in univariable analysis (cPTEN hazard ratio [HR], 1.54; CI, 1.07-2.21; P = .019; AI-qPTEN HR, 2.55; CI, 1.83-3.56; P < .001). In multivariable analyses, AI-qPTEN showed a statistically significant association with shorter MFS (HR, 2.17; CI, 1.49-3.17; P < .001) and recurrence-free survival (HR, 1.36; CI, 1.06-1.75; P = .016) when adjusting for relevant postsurgical clinical nomogram (Cancer of the Prostate Risk Assessment [CAPRA] postsurgical score [CAPRA-S]), whereas cPTEN does not show a statistically significant association (HR, 1.33; CI, 0.89-2; P = .2 and HR, 1.26; CI, 0.99-1.62; P = .063, respectively) when adjusting for CAPRA-S risk stratification. More importantly, AI-qPTEN was associated with shorter MFS in patients with favorable pathological stage and negative surgical margins (HR, 2.72; CI, 1.46-5.06; P = .002). Workflow also demonstrated enhanced clinical utility in decision curve analysis, more accurately identifying men who might benefit from adjuvant therapy postsurgery. This study demonstrates the clinical value of an affordable and fully automated AI-powered PTEN assessment for evaluating the risk of developing metastasis or disease recurrence after radical prostatectomy. Adding the AI-qPTEN assessment workflow to clinical variables may affect postoperative surveillance or management options, particularly in low-risk patients.

The Trauma Survivors Network (TSN), a program of the American Trauma Society (ATS), has a unique history spanning decades with a vision to continue expanding and strengthening services to support survivors and families impacted by traumatic injury. Since the COVID-19 pandemic, the ATS has adapted TSN services to provide both virtual and in-person services for trauma survivors, increasing equity and inclusion for many survivors to access TSN services for the first time. The recent policy changes in the American College of Surgeons Committee on Trauma New Standards for Care of the Injured Patient provide an impetus for the TSN to grow and expand services in support of a diverse group of trauma survivors and their loved ones. This paper highlights the collateral impact of traumatic injury, the history and ongoing growth of the TSN and its services to date, the challenges encountered in establishing and maintaining the TSN program, and the equity and inclusion that the TSN offers internationally to support a diverse range of survivors with various forms of trauma and polytrauma.

Background: Meniscotibial ligament disruption and medial meniscal extrusion may represent early and predisposing events contributing to medial meniscal root tears. If left untreated, these extruded tears may result in loss of medial compartment cartilage. As a result, multiple approaches have been developed to centralize the extruded meniscus. Indications: In this case, we present a 45-year-old man who sustained a left medial meniscal root tear with extrusion while playing tennis. Indications for root repair with meniscal centralization include extrusion >3 mm seen on magnetic resonance imaging after an acute meniscal root tear or subjective meniscal extrusion seen intraoperatively. Technique Description: The medial meniscal root tear is first repaired arthroscopically per surgeon preference. Then a medial incision is made along the proximal tibia and a submeniscal arthrotomy performed. Two double-loaded 3.0-mm anchors are placed along the proximal medial tibial edge. Sutures are passed in a Mason-Allen configuration through the meniscal body and capsule. Tightening of the sutures results in meniscal centralization. The root repair sutures are then tensioned and fixed along the medial proximal tibia. Results: Recent data have shown meniscal root repair with centralization is associated with significant improvements in pain, function, and quality of life and no significant progression of osteoarthritis. Discussion/Conclusion: Medial meniscal centralization can be safely performed with an open approach. An open approach may allow for more accurate anchor placement and more near-anatomic replication of meniscotibial ligaments. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Rationale: To identify barriers and opportunities for Ph.D., basic and translational scientists to be fully integrated into clinical units. Objectives: In 2022, an ad hoc committee of the American Thoracic Society developed a project proposal and workshop to identify opportunities and barriers for scientists who do not practice medicine to develop successful careers and achieve tenure-track faculty positions in clinical departments and divisions within academic medical centers (AMCs) in the United States. Methods: This document focuses on results from a survey of adult and pediatric pulmonary, critical care, and sleep medicine division chiefs as well as a survey of workshop participants, including faculty in departmental and school leadership roles in both basic science and clinical units within U.S. AMCs. Results: We conclude that full integration of non-clinically practicing basic and translational scientists into the clinical units, in addition to their traditional placements in basic science units, best serves the tripartite mission of AMCs to provide care, perform research, and educate the next generation. Evidence suggests clinical units do employ Ph.D. scientists in large numbers, but these faculty are often hired into non-tenure track positions, which do not provide the salary support, start-up funds, research independence, or space often associated with hiring in basic science units within the same institution. These barriers to success of Ph.D. faculty in clinical units are largely financial. Conclusions: Our recommendation is for AMCs to consider and explore some of our proposed strategies to accomplish the goal of integrating basic and translational scientists into clinical units in a meaningful way.

Abstract Prostate cancer (PCa) is the second leading cause of cancer-related death in American men. PCa that relapses after hormonal therapies, referred to as castration resistant PCa (CRPC), often presents with metastases (mCRPC) that are the major cause of mortality. The few available therapies for mCRPC patients include taxanes docetaxel (DTX) and cabazitaxel (CBZ). However, development of resistance limits their clinical use. Mechanistically, resistance arises through upregulation of multidrug resistance (MDR) proteins such as MDR1/ABCB1, making ABCB1 an attractive therapeutic target. Yet, ABCB1 inhibitors failed to be clinically useful due to low specificity and toxicity issues. To study taxanes resistance, we produced CBZ resistant C4-2B cells (RC4-2B) and documented resistance to both CBZ and DTX in cell culture and in 3D prostaspheres settings. RNAseq identified increased expression of ABCB1 in RC4-2B, that was confirmed by immunoblotting and immunofluorescent analysis. ABCB1-specific inhibitor elacridar reversed CBZ and DTX resistance in RC4-2B cells, confirming ABCB1-mediated resistance mechanism. In a cell-based screen using a curated library of cytotoxic drugs, we found that DNA damaging compounds Camptothecin (CPT) and Cytarabine (Ara-C) overcame resistance as seen by similar cytotoxicity in parental C4-2B and resistant RC4-2B. Further, these compounds were cytotoxic to multiple PC cells resistant to taxanes with high ABCB1 expression and, therefore, can be used to conquer the acquired resistance to taxanes in PCa. Finally, inhibition of cyclin-dependent kinases 4/6 (CDK4/6) with small molecule inhibitors (CDK4/6i) potentiated cytotoxic effect of CPT or Ara-C in both parental and resistant cells. Overall, our findings indicate that DNA damaging agents CPT and Ara-C alone or in combination with CDK4/6i can be suggested as a new treatment regimen in CRPC patients, including those that are resistant to taxanes.