Interactive CLV3, CLE16 and CLE17 signaling mediates stem cell homeostasis in the Arabidopsis shoot apical meristem.

The ability of plants to grow and form organs throughout their lifetime is dependent on their sustained stem cell activity. These stem cell populations are maintained by intricate networks of intercellular signaling pathways. In Arabidopsis thaliana, the small secreted peptide CLAVATA3 (CLV3) controls shoot apical meristem (SAM) maintenance by activating a signal transduction pathway that modulates the expression of the homeodomain transcription factor WUSCHEL (WUS). Here, we demonstrate that two CLV3-related peptides, CLE16 and CLE17, restrict stem cell accumulation in the absence of CLV3. CLE16 and CLE17 contribute independently to SAM maintenance and organ production in clv3 plants at all stages of development. We show that CLE16 and CLE17 signal through a subset of CLV3 receptors, the BARELY ANY MERISTEM (BAM) receptor kinases, and act upstream of WUS. Our study reveals that CLE16 and CLE17 function in a mechanism that partially compensates for CLV3 to maintain stem cell homeostasis and plant resiliency, and expands the potential targets for enhancing yield traits in crop species.

Community Pharmacy Chlamydia and Gonorrhea Test-To-Treat Program: Development of an Implementation Toolkit.

BACKGROUND: Sexually transmitted infection (STI) surveillance showed more than 2.5 million cases of chlamydia, gonorrhea, and syphilis nationally in the United States in 2022. Individuals often seek out non-emergency medical care at pharmacies. This makes community pharmacies well-positioned to address rising STI rates by offering services to screen and treat common STIs. A local health department, an independent pharmacy, and a school of pharmacy in Pennsylvania partnered to implement a test-to-treat service for chlamydia and gonorrhea within a pharmacy. This pilot program utilized: (1) patient self-collected test kits for chlamydia and gonorrhea screening and; (2) standing orders for treatment at the pharmacy. One goal of this pilot was to develop resources others can use to implement similar pharmacy-based chlamydia and gonorrhea testing and treatment services. OBJECTIVE: Develop an expert-informed implementation toolkit for a chlamydia and gonorrhea test-to-treat program at a community pharmacy. METHODS: The "How to Build an Implementation Toolkit from Start to Finish" framework from the University of California at Berkeley was used to design the initial toolkit outline. Toolkit content was triangulated from three sources: (1) comprehensive literature review; (2) pilot program implementation team meetings; and (3) feedback from public health and other experts. Pilot program partners met regularly to review and edit the toolkit. The draft toolkit was then reviewed by outside experts and potential end-users . RESULTS: An 11-item toolkit was developed. Toolkit contents were reviewed by 11 outside experts and potential end-users. Toolkit resources included STI training resources for pharmacy teams, testing and treatment standing orders, pharmacy treatment screening form, marketing strategies, patient education materials, sample workflow, essential supply list, and other key resources. CONCLUSION: Pharmacies may need additional resources for STI testing and treatment program implementation. Toolkit resources developed from this pilot program may help pharmacies overcome implementation barriers for similar programs.

IKKß promotes metabolic adaptation to glutamine deprivation via phosphorylation and inhibition of PFKFB3.

Glutamine is an essential nutrient for cancer cell survival and proliferation. Enhanced utilization of glutamine often depletes its local supply, yet how cancer cells adapt to low glutamine conditions is largely unknown. Here, we report that IκB kinase ß (IKKß) is activated upon glutamine deprivation and is required for cell survival independently of NF-κB transcription. We demonstrate that IKKß directly interacts with and phosphorylates 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase isoform 3 (PFKFB3), a major driver of aerobic glycolysis, at Ser269 upon glutamine deprivation to inhibit its activity, thereby down-regulating aerobic glycolysis when glutamine levels are low. Thus, due to lack of inhibition of PFKFB3, IKKß-deficient cells exhibit elevated aerobic glycolysis and lactate production, leading to less glucose carbons contributing to tricarboxylic acid (TCA) cycle intermediates and the pentose phosphate pathway, which results in increased glutamine dependence for both TCA cycle intermediates and reactive oxygen species suppression. Therefore, coinhibition of IKKß and glutamine metabolism results in dramatic synergistic killing of cancer cells both in vitro and in vivo. In all, our results uncover a previously unidentified role of IKKß in regulating glycolysis, sensing low-glutamine-induced metabolic stress, and promoting cellular adaptation to nutrient availability.

Development of a Pharmacy Point-of-Dispensing Toolkit for Anthrax Post-Exposure Prophylaxis for Allegheny County Postal Workers.

CONTEXT: The Centers for Disease Control and Prevention (CDC) and the US Postal Service (USPS) consider anthrax to be a potential threat to USPS workers. A county health department-owned pharmacy supports local USPS response in the event of an exposure. The pharmacy team identified the need to review and update the local anthrax response plan. PROGRAM/POLICY: A Pharmacy Point-of-Dispensing Toolkit and response plan for initial 10-day post-exposure antibiotic prophylaxis was developed for use by a local health department in the event of a mass anthrax exposure at a US Post Office sorting facility. The pharmacist's role in medical countermeasures planning for anthrax exposure is also discussed to illustrate how pharmacists' medication expertise can be utilized. EVALUATION: The CDC's Public Health Preparedness Capabilities: National Standards for State and Local Planning framework and inputs from an interprofessional stakeholder team were used to develop a Medical Countermeasures Response Plan and Implementation Toolkit for mass point-of-dispensing (POD) in the event of an anthrax exposure. IMPLEMENTATION AND DISSEMINATION: Stakeholders attended a USPS Community Partner Training event where additional revisions to the toolkit were made. The toolkit and standing order are now implemented at the local health department to be reviewed and updated on a yearly basis by health department leadership. DISCUSSION: Pharmacists can use their medication expertise and experience with patient education to design emergency response plans focused on increasing patient safety and medication adherence. Pharmacists should be involved in emergency response and medical countermeasures planning that involve medications.

The B56α subunit of PP2A is necessary for mesenchymal stem cell commitment to adipocyte.

Adipose tissue plays a major role in maintaining organismal metabolic equilibrium. Control over the fate decision from mesenchymal stem cells (MSCs) to adipocyte differentiation involves coordinated command of phosphorylation. Protein phosphatase 2A plays an important role in Wnt pathway and adipocyte development, yet how PP2A complexes actively respond to adipocyte differentiation signals and acquire specificity in the face of the promiscuous activity of its catalytic subunit remains unknown. Here, we report the PP2A phosphatase B subunit B56α is specifically induced during adipocyte differentiation and mediates PP2A to dephosphorylate GSK3ß, thereby blocking Wnt activity and driving adipocyte differentiation. Using an inducible B56α knock-out mouse, we further demonstrate that B56α is essential for gonadal adipose tissue development in vivo and required for the fate decision of adipocytes over osteoblasts. Moreover, we show B56α expression is driven by the adipocyte transcription factor PPARγ thereby establishing a novel link between PPARγ signaling and Wnt blockade. Overall, our results reveal B56α is a necessary part of the machinery dictating the transition from pre-adipocyte to mature adipocyte and provide fundamental insights into how PP2A complex specifically and actively regulates unique signaling pathway in biology.

Pitx genes in development and disease.

Homeobox genes encode sequence-specific transcription factors (SSTFs) that recognize specific DNA sequences and regulate organogenesis in all eukaryotes. They are essential in specifying spatial and temporal cell identity and as a result, their mutations often cause severe developmental defects. Pitx genes belong to the PRD class of the highly evolutionary conserved homeobox genes in all animals. Vertebrates possess three Pitx paralogs, Pitx1, Pitx2, and Pitx3 while non-vertebrates have only one Pitx gene. The ancient role of regulating left-right (LR) asymmetry is conserved while new functions emerge to afford more complex body plan and functionalities. In mouse, Pitx1 regulates hindlimb tissue patterning and pituitary development. Pitx2 is essential for the development of the oral cavity and abdominal wall while regulates the formation and symmetry of other organs including pituitary, heart, gut, lung among others by controlling growth control genes upon activation of the Wnt/ß-catenin signaling pathway. Pitx3 is essential for lens development and migration and survival of the dopaminergic neurons of the substantia nigra. Pitx gene mutations are linked to various congenital defects and cancers in humans. Pitx gene family has the potential to offer a new approach in regenerative medicine and aid in identifying new drug targets.

Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes.

Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON) or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.

Internal quantum efficiency of AlGaN/AlN quantum dot superlattices for electron-pumped ultraviolet sources.

In this paper, we describe the growth and characterization of ≈530 nm thick superlattices (100 periods) of AlxGa1-xN/AlN (0 ⩽ x ⩽ 0.1) Stranski-Krastanov quantum dots (QDs) for application as the active region of electron-beam pumped ultraviolet lamps. Highly dense (>1011 cm-2) QD layers are deposited by molecular beam epitaxy, and we explore the effect of the III/V ratio during the growth process on their optical performance. The study considers structures emitting in the 244-335 nm range at room temperature, with a relative linewidth in the 6%-11% range, mainly due to the QD diameter dispersion inherent in self-assembled growth. Under electron pumping, the emission efficiency remains constant for acceleration voltages below ≈9 kV. The correlation of this threshold with the total thickness of the SL and the penetration depth of the electron beam confirms the homogeneity of the nanostructures along the growth axis. Below the threshold, the emission intensity scales linearly with the injected current. The internal quantum efficiency (IQE) is characterized at low injection, which reveals the material properties in terms of non-radiative processes, and high injection, which emulates carrier injection in operation conditions. In QDs synthesized with III/V ratio <0.75, the IQE remains around 50% from low injection to pumping power densities as high as 200 kW cm-2, being the first kind of nanostructure that present such stable behaviour.

Is There Gender Bias on the American Board of Surgery General Surgery Certifying Examination?

BACKGROUND: When oral examinations are administered, examiner subjectivity may possibly affect ratings, particularly when examiner severity is influenced by examinee characteristics (e.g., gender) that are independent of examinee ability. This study explored whether the ratings of the general surgery oral certifying examination (CE) of the American Board of Surgery and likelihood of passing the CE were influenced by the gender of examinees or examiners. MATERIALS AND METHODS: Data collected from examinees who attempted the general surgery CE in the 2016-2017 academic year were analyzed. There were 1341 examinees (61% male) and 216 examiners (82% male). Factorial analysis of variance and logistic regression analyses were used to evaluate the effect of examinee and examiner gender on CE ratings and likelihood of passing the CE. RESULTS: Examinees received similar ratings and had similar likelihood of passing the CE regardless of examinee or examiner genders and different combinations of examiner gender pairs (all P values > 0.05). CONCLUSIONS: These results indicate that CE ratings of examinees are not influenced by examinee or examiner gender. There was no evidence of examiner bias due to gender on the CE.

Reduced Anti-Histone Antibodies and Increased Risk of Rheumatoid Arthritis Associated with a Single Nucleotide Polymorphism in PADI4 in North Americans.

Autoantibodies against citrullinated proteins are a hallmark of rheumatoid arthritis, a destructive inflammatory arthritis. Peptidylarginine deiminase 4 (PAD4) has been hypothesized to contribute to rheumatoid arthritis by citrullinating histones to induce neutrophil extracellular traps (NETs), which display citrullinated proteins that are targeted by autoantibodies to drive inflammation and arthritis. Consistent with this theory, PAD4-deficient mice have reduced NETs, autoantibodies, and arthritis. However, PAD4's role in human rheumatoid arthritis is less clear. Here, we determine if single nucleotide polymorphism rs2240335 in PADI4, whose G allele is associated with reduced PAD4 in neutrophils, correlates with NETs, anti-histone antibodies, and rheumatoid arthritis susceptibility in North Americans. Control and rheumatoid arthritis subjects, divided into anti-cyclic citrullinated peptide (CCP) antibody positive and negative groups, were genotyped at rs2240335. In homozygotes, in vitro NETosis was quantified in immunofluorescent images and circulating NET and anti-histone antibody levels by enzyme linked immunosorbent assay (ELISA). Results were compared by t-test and correlation of rheumatoid arthritis diagnosis with rs2240335 by Armitage trend test. NET levels did not significantly correlate with genotype. G allele homozygotes in the CCP- rheumatoid arthritis group had reduced anti-native and anti-citrullinated histone antibodies. However, the G allele conferred increased risk for rheumatoid arthritis diagnosis, suggesting a complex role for PAD4 in human rheumatoid arthritis.

SiGe nano-heteroepitaxy on Si and SiGe nano-pillars.

In this paper, SiGe nano-heteroepitaxy on Si and SiGe nano-pillars was investigated in a 300 mm industrial reduced pressure-chemical vapour deposition tool. An integration scheme based on diblock copolymer patterning was used to fabricate nanometre-sized templates for the epitaxy of Si and SiGe nano-pillars. Results showed highly selective and uniform processes for the epitaxial growth of Si and SiGe nano-pillars. 200 nm thick SiGe layers were grown on Si and SiGe nano-pillars and characterised by atomic force microscopy, x-ray diffraction and transmission electron microscopy. Smooth SiGe surfaces and full strain relaxation were obtained in the 650 °C-700 °C range for 2D SiGe layers grown either on Si or SiGe nano-pillars.

Delineating the Relationship Between Leptin, Fat Mass, and Bone Mineral Density: A Mediation Analysis.

To test the hypothesis that the relationship between fat mass (FM) and bone mineral density (BMD) is mediated by leptin. The study involved 611 individuals aged 20-89 years who were randomly sampled from Ho Chi Minh City (Vietnam). BMD at the femoral neck (FN), lumbar spine (LS), and whole body (WB) was measured by DXA. Lean mass and FM were derived from the WB DXA scan. Leptin was measured by ELISA (DRG Diagnostics, Germany). The regression method was used to partition the variance of leptin and FM on BMD. The mediated effect of leptin was analyzed by the mediation analysis model. In the multiple linear regression, leptin, FM, and age collectively accounted for ~34 % variation in FNBMD in men and women. However, only 0.5 % of this explained variance was due to leptin. Of the total effect of FM on FNBMD, the mediated effect of leptin accounted for 6.1 % (P = 0.38) in men and 7.1 % (P = 0.99) in women. The same trend was observed for LS and WBBMD. These data suggest that greater FM is associated with greater BMD, but the association is not mediated by leptin, and that leptin has a non-significant influence on bone mass.

α-Glucosidase Inhibitory Xanthones from the Roots of Garcinia fusca.

Two new compounds, fuscaxanthones J (1) and K (2), together with eight known xanthones (3 - 10) were isolated from an ethyl acetate extract of the roots of Garcinia fusca. Their structures were determined using spectroscopic methods, mainly 1D- and 2D-NMR. α-Glucosidase inhibitory activity of the isolated compounds was evaluated and fuscaxanthone J (1) showed the most significant effect with an IC50 value of 8.3 ± 1.8 µm (compared with acarbose, IC50 = 214.5 ± 2.3 µm).

Body Composition in Individuals with Asymptomatic Osteoarthritis of the Knee.

Greater body mass index (BMI) is associated with a greater risk of osteoarthritis (OA). This study sought to investigate whether the association is mediated by fat mass or lean mass. The study involved 170 men and 488 women aged between 20 and 90 (average age: 55) who were randomly recruited from Ho Chi Minh City, Vietnam. The presence of knee OA was radiographically diagnosed based on the Kellgren-Lawrence criteria. Lean mass (LM) and fat mass (FM) were obtained from the DXA whole body scan (Hologic QDR-4500). The relationship between OA, LM, and FM was analyzed by a series of multiple linear regression models which take into account the effects of gender and age. As expected, men and women with knee OA were older than those without OA (65 vs 51 year in men, and 64 vs 52 year in women). After adjusting for age, OA was associated with greater FM and percent body fat (PBF), but the association was only observed in women, not in men. There was no statistically significant difference in LM between OA and non-OA individuals. Moreover, after adjusting for age and BMI or PBF, bone density in OA patients was not significantly different from non-OA individuals. Women with OA of the knee have greater fat mass than non-OA individuals, and that there is no significant difference in bone density between OA and non-OA individuals. Thus, the association between body mass index and OA is mainly mediated by fat mass.

Vemurafenib resistance reprograms melanoma cells towards glutamine dependence.

BACKGROUND: (V600) BRAF mutations drive approximately 50% of metastatic melanoma which can be therapeutically targeted by BRAF inhibitors (BRAFi) and, based on resistance mechanisms, the combination of BRAF and MEK inhibitors (BRAFi + MEKi). Although the combination therapy has been shown to provide superior clinical benefits, acquired resistance is still prevalent and limits the overall survival benefits. Recent work has shown that oncogenic changes can lead to alterations in tumor cell metabolism rendering cells addicted to nutrients, such as the amino acid glutamine. Here, we evaluated whether melanoma cells with acquired resistance display glutamine dependence and whether glutamine metabolism can be a potential molecular target to treat resistant cells. METHODS: Isogenic BRAFi sensitive parental (V600) BRAF mutant melanoma cell lines and resistant (derived by chronic treatment with vemurafenib) sub-lines were used to assess differences in the glutamine uptake and sensitivity to glutamine deprivation. To evaluate a broader range of resistance mechanisms, isogenic pairs where the sub-lines were resistant to BRAFi + MEKi were also studied. Since resistant cells demonstrated increased sensitivity to glutamine deficiency, we used glutaminase inhibitors BPTES [bis-2-(5 phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide] and L-L-DON (6-Diazo-5-oxo-L-norleucine) to treat MAPK pathway inhibitor (MAPKi) resistant cell populations both in vitro and in vivo. RESULTS: We demonstrated that MAPKi-acquired resistant cells uptook greater amounts of glutamine and have increased sensitivity to glutamine deprivation than their MAPKi-sensitive counterparts. In addition, it was found that both BPTES and L-DON were more effective at decreasing cell survival of MAPKi-resistant sub-lines than parental cell populations in vitro. We also showed that mutant NRAS was critical for glutamine addiction in mutant NRAS driven resistance. When tested in vivo, we found that xenografts derived from resistant cells were more sensitive to BPTES or L-DON treatment than those derived from parental cells. CONCLUSION: Our study is a proof-of-concept for the potential of targeting glutamine metabolism as an alternative strategy to suppress acquired MAPKi-resistance in melanoma.

Prevalence and pattern of radiographic intervertebral disc degeneration in Vietnamese: a population-based study.

Intervertebral disc degeneration (IDD) is one of the most common skeletal disorders, yet few data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic IDD in a Vietnamese population. This population-based cross-sectional investigation involved 170 men and 488 women aged ≥40 years, who were randomly sampled from the Ho Chi Minh City (Vietnam). Anthropometric data, clinical history and self-reported back and neck pain were ascertained by a questionnaire. Plain radiographs (from the cervical spine, thoracic spine to the lumbar spine) were examined for the presence of disc space narrowing and/or osteophytosis using the Kellgren-Lawrence (KL) grading system. The presence of radiographic IDD was defined if the KL grade was 2 or greater in at least one disc. The prevalence of radiographic IDD was 62.4% (n = 106) in men and 54.7% (n = 267) in women. The most frequently affected site was the lumbar spine with prevalence being 50.6 and 43.2% in men and women, respectively. The prevalence of IDD increased with advancing age: 18.8% among those aged 40-49 years, and increased to 83.4% in those aged ≥60 years. Self-reported neck pain and lower back pain were found in 30 and 44% of individuals, respectively. There was no statistically significant association between self-reported neck pain and cervical spine OA. These data suggest that radiographic IDD is highly prevalent in the Vietnamese population, and that self-reported back pain is not a sensitive indicator of IDD.

Integrated clinical and quality improvement coaching in Son La Province, Vietnam: a model of building public sector capacity for sustainable HIV care delivery.

BACKGROUND: The global scale-up of antiretroviral therapy included extensive training and onsite support to build the capacity of HIV health care workers. However, traditional efforts aimed at strengthening knowledge and skills often are not successful at improving gaps in the key health systems required for sustaining high quality care. METHODS: We trained and mentored existing staff of the Son La provincial health department and provincial HIV clinic to work as a provincial coaching team (PCT) to provide integrated coaching in clinical HIV skills and quality improvement (QI) to the HIV clinics in the province. Nine core indicators were measured through chart extraction by clinic and provincial staff at baseline and at 6 month intervals thereafter. Coaching from the team to each of the clinics, in both QI and clinical skills, was guided by results of performance measurements, gap analyses, and resulting QI plans. RESULTS: After 18 months, the PCT had successfully spread QI activities, and was independently providing regular coaching to the provincial general hospital clinic and six of the eight district clinics in the province. The frequency and type of coaching was determined by performance measurement results. Clinics completed a mean of five QI projects. Quality of HIV care was improved throughout all clinics with significant increases in seven of the indicators. Overall both the PCT activities and clinic performance were sustained after integration of the model into the Vietnam National QI Program. CONCLUSIONS: We successfully built capacity of a team of public sector health care workers to provide integrated coaching in both clinical skills and QI across a province. The PCT is a feasible and effective model to spread and sustain quality activities and improve HIV care services in a decentralized rural setting.

A Comparison of Remote vs In-Person Proctored In-Training Examination Administration for Internal Medicine.

PURPOSE: In response to COVID-19, the American College of Physicians provided residents the option to complete the 2020 Internal Medicine In-Training Examination (IM-ITE) via in-person and remote proctoring. This study evaluated the extent to which scores obtained from both testing modalities were comparable. METHOD: Data were analyzed from residents from all U.S.-based Accreditation Council for Graduate Medical Education-accredited IM residency programs and participating Canadian and international programs who completed the IM-ITE in 2020. The final sample contained 27,115 IM residents: 9,205 postgraduate year (PGY) 1, 9,332 PGY-2, and 8,578 PGY-3. Testing modality, gender, PGY, time spent on assessment, and native language were used to predict percent-correct scores in a multilevel regression model. This model included all main effects and all 2-way interactions between testing modality and each resident-level demographic variable, allowing those effects to be controlled for. RESULTS: Of 27,115 residents studied, 11,354 (42%) tested remotely and 15,761 (58%) in person. Across the parameters of interest (main effect of testing modality and 2-way interactions), the only statistically significant effects were the interaction effects between testing mode (interaction effect: -0.61; 95% confidence interval [CI], -1.01 to -0.21) and PGY (interaction effect: -0.54; 95% CI, -0.95 to -0.13) ( P = .002). Differences between in-person and remote predicted scores were slightly larger for PGY-1 than for PGY-2 and PGY-3 residents, but the magnitude of these differences across residency training was well under one percentage point. Because these statistically significant effects were deemed educationally nonsignificant, the study concluded that performance did not substantively differ across in-person and remote examinees. CONCLUSIONS: Residents taking the 2020 IM-ITE performed similarly across in-person and remote proctoring. This study provides evidence of score comparability across the 2 testing modalities and supports continued use of remote proctoring for the IM-ITE.

Vaccination equity and the role of community pharmacy in the United States: A qualitative study.

OBJECTIVES: To identify strategies community pharmacists utilized to support equitable vaccination in their communities. STUDY DESIGN: Qualitative, descriptive design. METHODS: Key informant interviews were conducted virtually via teleconference using a mix of purposeful and snowball sampling of Pennsylvania community pharmacy personnel who participated in COVID-19 vaccination efforts. Interviews were conducted from March until August 2022 when thematic saturation was reached. A qualitative, inductive thematic data analysis was utilized to identify major themes and strategies that emerged from the data. RESULTS: Pharmacists utilized three philosophies: (1) prioritizing trust, (2) meeting people where they are at, and (3) building capacity within their teams and communities to create "safe spaces" for people to receive vaccinations. Nine discrete strategies used in practice exemplify how respondents implemented these philosophies: (1) Build Community Partnerships; (2) Establish Trust to Build Credibility; (3) Address Transportation Issues; (4) Provide Patient Education and Address Health Literacy Barriers; (5) Address Language Barriers; (6) Create a Safe and Accessible Space for Those with Individualized Needs; (7) Provide Patient-Centered and Culturally-Sensitive Care; (8) Train Staff on Health Equity and Patient Engagement; and (9) Advocate for Community Pharmacy Policy and Payment Reform. Definitions for these philosophies and key examples that illustrate how each strategy was employed in practice are provided. CONCLUSION: The findings highlight unique strategies respondent community-based pharmacy teams use to contribute to equitable vaccination efforts in communities and further emphasizes the importance of their role in public health initiatives.

Oncolytic virus V937 in combination with PD-1 blockade therapy to target immunologically quiescent liver and colorectal cancer.

V937 is an investigational, genetically unmodified Kuykendall strain of coxsackievirus A21, which has been evaluated in the clinic for advanced solid tumor malignancies. V937 specifically infects and lyses tumor cells that overexpress intercellular adhesion molecule-1 (ICAM-1). Intratumoral V937 as a monotherapy and in combination with anti-PD-1 antibody pembrolizumab has shown clinical response in patients with metastatic melanoma, which overexpresses ICAM-1. Here, we investigate in preclinical studies the potential bidirectional cross-talk between hepatocellular carcinomas (HCC) or colorectal carcinomas (CRC) and immune cells when treated with V937 alone or in combination with pembrolizumab. We show that while V937 treatment of tumor cell lines or organoids or peripheral blood mononuclear cells (PBMCs) alone induced a minimal immunological response, V937 treatment of non-contact co-cultures of tumor cell lines or CRC organoids with PBMCs led to robust production of proinflammatory cytokines and immune cell activation. In addition, both recombinant interferon-gamma and pembrolizumab increased ICAM-1 on tumor cell lines or organoids and, in turn, amplified V937-mediated oncolysis and immunogenicity. These findings provide critical mechanistic insights on the cross-talk between V937-mediated oncolysis and immune responses, demonstrating the therapeutic potential of V937 in combination with PD-1 blockade to treat immunologically quiescent cancers.