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Abstract Background While people with substance use disorders, including people who inject drugs (PWID), experience increased risk for COVID-19 infection and adverse outcomes, COVID-19 vaccination rates among PWID are consistently lower than those observed in the general population. Offering COVID-19 vaccines at syringe services programs (SSPs) has been proposed as a critical strategy to increase vaccine uptake among this population. We explored the experiences of frontline staff at an SSP in Miami, Florida implementing onsite COVID-19 vaccines. Methods Between June and July 2022, we conducted in-depth semi-structured interviews with 17 staff members of an SSP in Miami, Florida. Data collection and codebook thematic analysis of transcribed interviews were guided by the Consolidated Framework for Implementation Research (CFIR). Results Facilitators and barriers of COVID-19 vaccine implementation at the SSP aligned with all major CFIR domains. Key facilitators included the SSP’s established partnership with the local health department for vaccine distribution, its existing funding sources which could be leveraged for vaccine-related expenses, consensus among staff about the need for new strategies to increase vaccine uptake among PWID, and PWID’s trust in the SSP. Major—but largely modifiable—barriers included lack of participant compensation, limited internal collaboration and communication regarding the vaccine initiative beyond implementation leads and innovation deliverers due to competing priorities and segmented roles and responsibilities, and insufficient involvement of the most participant-facing staff (i.e., the SSP’s peer navigators and outreach workers). Conclusions Implementing onsite COVID-19 vaccines was perceived as feasible and acceptable by frontline staff at the SSP, however contextual factors impeded optimal implementation. Multilevel strategies, such as participant compensation for vaccine completion and internal educational meetings with staff to improve vaccine implementation and reach, are required. As a trusted source of preventative services for PWID, SSPs are an underutilized venue for increasing vaccine uptake among this population, and findings from this study could inform the expansion of low-barrier vaccine services at SSPs nationwide.

Abstract Despite progress towards malaria reduction in Peru, measuring exposure in low transmission areas is crucial for achieving elimination. This study focuses on two very low transmission areas in Loreto (Peruvian Amazon) and aims to determine the relationship between malaria exposure and proximity to health facilities. Individual data was collected from 38 villages in Indiana and Belen, including geo-referenced households and blood samples for microscopy, PCR and serological analysis. A segmented linear regression model identified significant changes in seropositivity trends among different age groups. Local Getis-Ord Gi* statistic revealed clusters of households with high (hotspots) or low (coldspots) seropositivity rates. Findings from 4000 individuals showed a seropositivity level of 2.5% (95%CI: 2.0%-3.0%) for P. falciparum and 7.8% (95%CI: 7.0%-8.7%) for P. vivax, indicating recent or historical exposure. The segmented regression showed exposure reductions in the 40–50 age group (β1 = 0.043, p = 0.003) for P. vivax and the 50–60 age group (β1 = 0.005, p = 0.010) for P. falciparum. Long and extreme distance villages from Regional Hospital of Loreto exhibited higher malaria exposure compared to proximate and medium distance villages (p

To determine the effects of SARS-CoV-2 infection on cellular metabolism, we conducted an exhaustive survey of the cellular metabolic pathways modulated by SARS-CoV-2 infection and confirmed their importance for SARS-CoV-2 propagation by cataloging the effects of specific pathway inhibitors. This revealed that SARS-CoV-2 strongly inhibits mitochondrial oxidative phosphorylation (OXPHOS) resulting in increased mitochondrial reactive oxygen species (mROS) production. The elevated mROS stabilizes HIF-1α which redirects carbon molecules from mitochondrial oxidation through glycolysis and the pentose phosphate pathway (PPP) to provide substrates for viral biogenesis. mROS also induces the release of mitochondrial DNA (mtDNA) which activates innate immunity. The restructuring of cellular energy metabolism is mediated in part by SARS-CoV-2 Orf8 and Orf10 whose expression restructures nuclear DNA (nDNA) and mtDNA OXPHOS gene expression. These viral proteins likely alter the epigenome, either by directly altering histone modifications or by modulating mitochondrial metabolite substrates of epigenome modification enzymes, potentially silencing OXPHOS gene expression and contributing to long-COVID.

The mangrove ecosystems of the Department of Atlántico (Colombian Caribbean) are seriously threatened by problems of hypersalinization and contamination, especially by heavy metals from the Magdalena River. The mangrove plants have developed various mechanisms to adapt to these stressful conditions, as well as the associated microbial populations that favor their growth. In the present work, the tolerance and detoxification capacity to heavy metals, especially to mercury, of a halotolerant endophytic bacterium isolated from the species Avicennia germinans located in the Balboa Swamp in the Department of Atlántico was characterized. Diverse microorganisms were isolated from superficially sterilized A. germinans leaves. Tolerance to NaCl was evaluated for each of the obtained isolates, and the most resistant was selected to assess its tolerance to Pb2+, Cu2+, Hg2+, Cr3+, Co2+, Ni2+, Zn2+, and Cd2+, many of which have been detected in high concentrations in the area of study. According to the ANI and AAI percentages, the most halotolerant strain was identified as Priestia flexa, named P. flexa 7BS3110, which was able to tolerate up to 12.5% (w/v) NaCl and presented a minimum inhibitory concentrations (MICs) of 0.25 mM for Hg, 10 mM for Pb, and 15 mM for Cr3+. The annotation of the P. flexa 7BS3110 genome revealed the presence of protein sequences associated with exopolysaccharide (EPS) production, thiol biosynthesis, specific proteins for chrome efflux, non-specific proteins for lead efflux, and processes associated with sulfur and iron homeostasis. Scanning electron microscopy (SEM) analysis showed morphological cellular changes and the transmission electron microscopy (TEM) showed an electrodense extracellular layer when exposed to 0.25 mM Hg2+. Due to the high tolerance of P. flexa 7BS3110 to Hg2+ and NaCl, its ability to grow when exposed to both stressors was tested, and it was able to thrive in the presence of 5% (w/v) NaCl and 0.25 mM of Hg2+. In addition, it was able to remove 98% of Hg2+ from the medium when exposed to a concentration of 14 mg/L of this metalloid. P. flexa 7BS3110 has the potential to bioremediate Hg2+ halophilic contaminated ecosystems.

Spinocerebellar ataxia type 3 (SCA3) is the most common type of disease related to poly-glutamine (polyQ) repeats. Its hallmark pathology is related to the abnormal accumulation of ataxin 3 with a longer polyQ tract (polyQ-ATXN3). However, there are other mechanisms related to SCA3 progression that require identifying trait and state biomarkers for a more accurate diagnosis and prognosis. Moreover, the identification of potential pharmacodynamic targets and assessment of therapeutic efficacy necessitates valid biomarker profiles. The aim of this review was to identify potential trait and state biomarkers and their potential value in clinical trials. Our results show that, in SCA3, there are different fluid biomarkers involved in neurodegeneration, oxidative stress, metabolism, miRNA and novel genes. However, neurofilament light chain NfL and polyQ-ATXN3 stand out as the most prevalent in body fluids and SCA3 stages. A heterogeneity analysis of NfL revealed that it may be a valuable state biomarker, particularly when measured in plasma. Nonetheless, since it could be a more beneficial approach to tracking SCA3 progression and clinical trial efficacy, it is more convenient to perform a biomarker profile evaluation than to rely on only one.

Abstract Introduction: Community-Engaged Research (CEnR) and Community-Based Participatory Research (CBPR) require validated measures and metrics for evaluating research partnerships and outcomes. There is a need to adapt and translate existing measures for practical use with diverse and non-English-speaking communities. This paper describes the Spanish translation and adaptation of Engage for Equity’s Community Engagement Survey (E2 CES), a nationally validated and empirically-supported CEnR evaluation tool, into the full-length “Encuesta Comunitaria,” and a pragmatic shorter version “Fortaleciendo y Uniendo EsfueRzos Transdisciplinarios para Equidad de Salud” (FUERTES). Methods: Community and academic partners from the mainland US, Puerto Rico, and Nicaragua participated in translating and adapting E2 CES, preserving content validity, psychometric properties, and importance to stakeholders of items, scales, and CBPR constructs (contexts, partnership processes, intervention and research actions, and outcomes). Internal consistency was assessed using Cronbach’s alpha and convergent validity was assessed via a correlation matrix among scales. Results: Encuesta Comunitaria respondents (N = 57) self-identified as primarily Latinos/as/x (97%), female (74%), and academics (61%). Cronbach’s alpha values ranged from 0.72 to 0.88 for items in the context domain to 0.90–0.92 for items in the intervention/research domain. Correlations were found as expected among subscales, with the strongest relationships found for subscales within the same CBPR domain. Results informed the creation of FUERTES. Conclusions: Encuenta Comunitaria and FUERTES offer CEnR/CBPR practitioners two validated instruments for assessing their research partnering practices, and outcomes. Moreover, FUERTES meets the need for shorter pragmatic tools. These measures can further strengthen CEnR/CBPR involving Latino/a/x communities within the US, Latin America, and globally.

'How did you fall into science?' It is a simple enough question, with a usually straightforward answer. What drew you in, and why did you stay? But the question makes [...]

OBJECTIVES/GOALS: Analyze how the Endowment HIREC ‘s Mentoring and Career Coach Model A productive mentoring relationship is essential to advance researchers into being independent and bring extramural funds. METHODS/STUDY POPULATION: Provide Hispanic researchers mentoring and career coaching to strengthen their pathway as researcher. The HiREC’s Career Coach and Mentoring Component (CCMC) is an innovated approach to support long-lasting research mentoring relationships in our institution. This approach was developed to advance research to eliminate health disparities, promote multidisciplinary translational research in a Minority Institution and sustain research infrastructure and services, career, and workforce development initiatives. Promising Faculty are target and early and mid-career investigators interested in pursuing a research career. To implement the CCMC with the Visiting Endowed Chair a HiREC Advisory Leadership Group in Mentoring will be established, with researchers from Puerto Rico, and US mainland. RESULTS/ANTICIPATED RESULTS: Three Hispanic mid-career women from the School of Medicine and one from the School of Health Professions from the University of Puerto Rico received a HiREC Advanced Research Award of $50,000. The awardees achieved their goals; completed their research plan, research infrastructure needs, peer-reviewed publications, and submission of a competitive grant. They also provided successful perspectives on mentoring relationships in a Minority institution. Each one showed the mentor’s and mentee’s experiences as fundamental for their research advancements, productivity, leadership, and successful results. HiIREC’s mentoring component with the Visiting Endowed Chairs improves a healthy work environment and expands the research agenda for each awardee sustaining the institutional research culture. DISCUSSION/SIGNIFICANCE: A productive mentoring relationship is essential to advance researchers into being independent and bring extramural funds. Four mentees received formal, long-term guidance and endowment funds for their research infrastructure requirements with successful outcomes. HiREC contributes to building up an institutional mentoring program.

Aim: To estimate the rate of preterm delivery (PTD) and mean latency period to delivery in asymptomatic women with no history of preterm delivery and cervical length (CL) ≤10.0 mm undergoing or not cerclage and who were not treated with vaginal progesterone., Methods: Retrospective analysis of asymptomatic patients with singleton pregnancies and no history of preterm delivery, with an incidental finding of a CL ≤10.0 mm measured with transvaginal ultrasound during the mid-trimester scan, 56 of them (63.6%) underwent cerclage placement and 32 (36.4%) did not, none of them received vaginal progesterone. Those with evidence of advanced dilation, prolapsing, membranes, ruptured membranes, or positive signs of infection were not candidates for cerclage placement were excluded from the analysis. Differences in the prevalence of preterm birth, mean gestational age at delivery, and mean latency from very short cervix identification to delivery between the two groups were calculated. Associations between cerclage and preterm delivery adjusted for maternal characteristics and fetal weight, were estimated., Results: Median (range) gestational age at time of CL measurement in the cerclage group was (weeks/days) 20w6d (17w5d-23w3d) vs. 21w5d (17w6d-23w6d) in the no-cerclage group (p=0.02). No differences in CL were observed between those who had a cerclage (5.9 mm (SD 3.1 mm)) vs. those who did not (6.5 mm (SD 3.2 mm); p=0.4). The prevalence of preterm delivery (PTD) in women with cerclage vs. women without cerclage was: PTD <37 weeks 31/56 (55.3%) vs. 28/32 (87.5%); adjusted (a) OR 0.17 (95% CI; 0.05-0.62 p=0.008); PTD ≤34 weeks 27/56 (48.2%) vs. 24/32 (75.0%); aOR 0.16 (95% CI 0.05-0.55; p=0.02); PTD ≤28 weeks 19/56 (33.9%) vs. 22/32 (68.7%); aOR 0.15 (95% CI 0.05-0.51; p=0.002). The mean (range) gestational age at delivery was 32w6d (19w1d-40w1d) for the cerclage group, and 28w1d (20w1d-40w2d) for the no-cerclage group (p =0.001). The median (range) latency from the time of CL measurement to delivery in the cerclage group was 84 (8-144) vs. 43 (1-146) days in the no-cerclage group (p=0.003)., Conclusion: Among low-risk asymptomatic women with a very short cervix (≤10.0 mm) in the midtrimester scan, those treated with cerclage have increased latency to delivery and lower prevalence of preterm birth as compared to expectant management., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

HER2-positive breast cancer accounts for 10% to 20% of all breast cancer diagnoses. The mAb trastuzumab is crucial in treating this disease, significantly improving survival outcomes. Despite its inclusion in the World Health Organization's Model List of Essential Medicines, access to trastuzumab remains limited worldwide. In this issue of the journal, Norris and colleagues report that only 45% of eligible patients with HER2-positive breast cancer in the United Kingdom received trastuzumab between 2012 and 2017. This finding in a high-income country with universal health care is worrisome and points toward even greater barriers to access in developing nations. Some solutions to improve accessibility, which we discuss, include shorter durations of trastuzumab treatment and encouraging the registration and availability of biosimilars. The data presented by Norris and colleagues point toward a disconnect between the academic oncology landscape, focused on expensive drugs with marginal benefits, and everyday practice in which even essential interventions may not be available. Ensuring the accessibility to proven, essential medicines should be as relevant as innovation to improve patient outcomes and create a more sustainable healthcare system. See related article by Norris et al., p. 1298., (©2024 American Association for Cancer Research.)

Purpose: To develop and implement a continuing professional development (CPD) activity focused on geriatric assessment (GA) in oncology for oncologists and geriatricians. We evaluated the impact of this activity on knowledge, skills, and performance regarding GA in oncology, as well as its feasibility and acceptability., Methods: We included teams composed of an oncologist and a geriatrician working in Mexico. Curriculum content was selected from geriatric oncology guidelines. We used Project Extension for Community Healthcare Outcome (ECHO)'s model to create a 12-week online course. A one-group pretest post-test quasi-experimental design was used to evaluate the intervention's effectiveness. At baseline, participants answered a multiple-choice knowledge assessment, a survey on self-perceived competence in GA, and an adaptation of the Association for Community Cancer Centers Geriatric Oncology Gap Assessment Tool, evaluating self-perceived performance in conducting geriatric interventions. These assessments and a satisfaction questionnaire were also completed postintervention. Baseline and postintervention scores were compared using paired t -tests., Results: We included 40 participants (20 oncologists and 20 geriatricians). Median attendance was 10 sessions (range 2-12). Thirty-eight participants completed the satisfaction questionnaire, with a median score of 10/10 (range 8-10). The mean baseline and postintervention knowledge scores were 59.5 ± 12.8 and 74.4 ± 9.7, respectively ( P < .001, effect size 1.14). The mean baseline and postintervention competence scores were 6.42 ± 2.5 and 9.02 ± 0.8, respectively ( P < .001, effect size 1.03). The mean baseline and postintervention performance scores were 2.58 ± 0.65 and 3.29 ± 0.5, respectively ( P < .001, effect size 1.64)., Conclusion: A CPD activity for oncologists and geriatricians on the basis of the Project ECHO model was feasible and acceptable, leading to increased knowledge, competence, and performance in geriatric oncology. This could represent a novel method for increasing the geriatric competence of the cancer care workforce in Latin America and globally.

Introduction: Tissue expansion is a commonly used breast reconstructive strategy. Although the procedure is regarded as safe, tissue expander to implant-based breast reconstruction is reported to have the highest rates of postoperative infection among plastic surgery operations. During the COVID-19 pandemic, face masks were required at all hospital facilities at our institution. The purpose of this study is to investigate the effects of COVID-19 mask mandate on in-office breast tissue expansion procedures., Methods: An institutional review board-approved, retrospective review was completed on all patients who underwent unilateral or bilateral tissue expansion following mastectomy at a single institution in 2017 (prior to the COVID-19 mask mandate) and 2021 (following implementation of the mandate). Variables included were demographics, procedure information, and postoperative outcomes., Results: The analysis included 118 patients in the premandate group and 147 patients in the postmandate group. There was no difference in age, body mass index, smoking status, or diabetes mellitus between the 2 groups (P > 0.05). More patients in the postmandate group underwent bilateral reconstruction as opposed to unilateral when compared with the premandate group (70.7% vs 55.9%, P = 0.014). There were no differences in major complication rate (26.3% vs 30.6%, P = 0.495) or minor complication rate 30.5% vs 26.5%, P = 0.495) between the pre-mask and post-mask mandate groups., Conclusion: Our results demonstrated that the use of face masks did not play a significant role in complication rates relating to in-office tissue expansion procedures. It remains up to the discretion and comfortability of the provider if masks should be worn during the procedure., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The objective of this study was to evaluate the potential of novel poloxamer thermosensitive hydrogels (PTHs) formulations for prolonged release of iron dextran particles (IDP) for intramuscular (IM) injection. The thermosensitive behaviour helps to avoid hepcidin overexpression and toxicity by releasing IDPs without iron accumulation in injection or deposit sites. We hypothesized that novel PTH formulation would prolong iron liberation compared to the commercial iron dextran formulation (FEDEX). PTHs loaded with IDPs were developed with increasing iron content (0.1, 0.2 and 0.4 g of iron/g of poloxamer) and characterized as a prolonged release IM iron supplement. The PTHs had a biocompatible pH for IM injection (6.4) and thermosensitive viscosity, increasing from ∼50 (4 °C) to ∼3000 mPa.s (37 °C). PTHs were successfully injected in the sol state (at 4 °C) into pork meat at 37 °C, transitioning to the gel state in situ (in ∼60-190 s). Structural characterization indicated that there were no PTH-IDP chemical interactions, suggesting that IDP entrapment in PTHs was physical upon gelation. In vitro release studies revealed that iron release from PTH (0.4 g of iron/g of poloxamer) reached 100 % by day 10, whereas 100 % release from FEDEX was complete in 4 h. This novel iron PTH formulation achieved a 60 times long iron release compared to the commercial product. In conclusion, the reported strategy shows adequate IDP entrapment/release properties for prolonged iron release following ex vivo IM injection using biocompatible materials. These results provide a strong basis for future preclinical evaluation to elucidate aspects such as drug release, local irritation, biocompatibility, and efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Edwardsiella piscicida is an emerging bacterial pathogen and the aetiological agent of edwardsiellosis among cultured and wild fish species globally. The increased frequency of outbreaks of this Gram-negative, facultative intracellular pathogen pose not only a threat to the aquaculture industry but also a possible foodborne/waterborne public health risk due to the ill-defined zoonotic potential. Thus, understanding the role of temperature on the virulence of this emerging pathogen is essential for comprehending the pathogenesis of piscine edwardsiellosis in the context of current warming trends associated with climate change, as well as providing insight into its zoonotic potential. In this study, significant temperature-dependent alterations in bacterial growth patterns were observed, with bacterial isolates grown at 17°C displaying higher peak growth sizes, extended lag times, and slower maximal growth rates than isolates grown at 27or 37°C. When E. piscicida isolates were grown at 37°C compared to 27 and 17°C, mass spectrometry analysis of the E. piscicida proteome revealed significant downregulation of crucial virulence proteins, such as Type VI secretion system proteins and flagellar proteins. Although in vivo models of infection are warranted, this in vitro data suggests possible temperature-associated alterations in the virulence and pathogenic potential of E. piscicida in poikilotherms and homeotherms., (© 2024 The Author(s). Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The ability to impact the immune response of the host has been recognized as essential for the success of a virus during infection. A few groups of viruses can combine these immunomodulatory mechanisms with specific patterns of their own transcriptional and replication regulation to achieve persistence within the host long term. The Herpesvirales order is one of those groups and the resultant state is known as latency. Throughout the years, latency has been studied in many host-herpesvirus models to attempt to understand the complex and profound effects of this state on the host's systems, and in the hopes of deciphering a way to eliminate the latent state from survivors of the primary infection. Most studies of herpesvirus latency have been conducted on mammalian host species, but this review summarizes the data available regarding herpesviruses in fish species and their latent state. As the field of aquatic animal health research continues to advance, the elucidation of these complex mechanisms will be crucial for disease control, prevention, and treatment., (© 2024 The Author(s). Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Background: The global cancer burden is rising, particularly in low- and middle-income countries (LMIC), highlighting a critical research gap in understanding disparities in supportive care access. To address this, the Multinational Association of Supportive Care in Cancer (MASCC) Health Disparities Committee initiated a global survey to investigate and delineate these disparities. This study aims to explore and compare supportive care access disparities between LMIC and High-Income Countries (HIC)., Methods: An online cross-sectional survey was conducted among active members of MASCC. Members, representing diverse healthcare professions received email invitations. The survey, available for 3 weeks, comprised sections covering (1) sociodemographic information; (2) clinical service/practice-related disparities in their region/nation; (3) population groups facing disparities within their region or country. Chi-squared or Fisher's exact test for cross-sectional analyses, and a multivariable logistic regression model was employed for statistical analysis., Results: A total of 218 active members participated, with one-quarter (26.6%) from LMIC and 18.4% ethnic minorities, timely cancer care (43.7%) and timely supportive care (45.0%) emerged as the most pressing disparities globally. Notably, participants from LMIC underscored cancer drug affordability (56.4%) and supportive care guideline implementation (56.4%) as critical issues. Economically disadvantaged populations were noted as more likely to face disparities by both LMIC and HIC (non-US-based) respondents, while US-based respondents identified racial/ethnic minorities as facing more disparities., Conclusion: This global survey reveals significant disparities in cancer supportive care between LMIC and HIC, with a particular emphasis on medication affordability and guideline implementation in LMIC. Addressing these disparities requires targeted intervention, considering specific regional priorities., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

As the global population ages, so does the number of older people being diagnosed, treated and surviving cancer. Challenges to providing appropriate healthcare management stem from the heterogeneity common in this population. Although malnutrition is highly prevalent in older people with cancer, ranging between 30 % and 80 % according to some analyses, is associated with frailty, and has been shown to be a major risk factor for poor treatment response and worse overall survival, addressing nutrition status is not always a priority among oncology healthcare providers. Evaluation of nutritional status is a two-step process: screening identifies risk factors for reduced nutritional intake and deficits that require more in-depth assessment. Screening activities can be as simple as taking weight and BMI measurements or using short nutritional questionnaires and asking the patient about unintentional weight loss to identify potential nutritional risk. Using geriatric assessment, deficits in the nutritional domain as well as in others reveal potentially reversible geriatric and medical problems to guide specific therapeutic interventions. The authors of this paper are experts in the fields of geriatric medicine, oncology, and nutrition science and believe that there is not only substantial evidence to support regularly performing screening and assessment of nutritional status in older patients with cancer, but that these measures lead to the planning and implementation of patient-centered approaches to nutrition management and thus enhanced geriatric-oncology care. This paper presents rationale for systematic nutrition screening and assessment in older adults with cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.M.B. - Advisor to the following companies: Nutricia DANONE; Nestlé ; Fresenius; Pfizer; Novartis; Rejuvenate Biomed. Lecturer for: Nutricia DANONE; Nestlé ; Fresenius; Pfizer; Novartis. All income from the above activities goes to the institution he is working for. M.P. - Boards & Committees: BDA Prehab Sub-Group Committee. Travel grants: BDA GET Fund, RMH Charity, SIOG. Speaker fees: Fresenius Kabi, SPCC & SIOG. Research grants: Nutricia. R.B. – has participated to Advisory Boards for Nutricia Research, Eli Lilly, Novo Nordisk, Pfizer. N.M.L.B. – Advisory board: Pfizer, Abbott, Sanofi, Astellas; Travel grants: Exact Sciences, Pfizer, Lilly, Novartis; Speaker fees: Pfizer, AbbVie, Roche, Sanofi, Novartis, Servier, Gilead, AstraZeneca, Lilly. E.S-P-D-C. – Speaker fees: Amgen, Synapsis. F.S. – BMS, Sanofi, Roche, MSD, Prostrakan, Leo pharma, Janssen, Pfizer, Amgen, Pierre Fabre Oncologie, Pharmanovia, Vifor Pharma, GSK, Viatris, Helsinn. P.S. – BMS: Member of Advisory Board on cancer in the elderly (2018–2019), GSK: Conference with honoraria (2020), EISAI: Member of Advisory Board on Management of older patients with thyroid cancer (2021), AbbVie: Member of Advisory Board on Geriatric oncology in hematological malignancies (2023). The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Older adults with cancer facing competing treatments must prioritize between various outcomes. This study assessed health outcome prioritization among older adults with cancer starting chemotherapy., Methods: Secondary analysis of a randomized trial addressing vulnerabilities in older adults with cancer. Patients completed three validated outcome prioritization tools: 1) Health Outcomes Tool: prioritizes outcomes (survival, independence, symptoms) using a visual analog scale; 2) Now vs. Later Tool: rates the importance of quality of life at three times-today versus 1 or 5 years in the future; and 3) Attitude Scale: rates agreement with outcome-related statements. The authors measured the proportion of patients prioritizing various outcomes and evaluated their characteristics., Results: A total of 219 patients (median [range] age 71 [65-88], 68% with metastatic disease) were included. On the Health Outcomes Tool, 60.7% prioritized survival over other outcomes. Having localized disease was associated with choosing survival as top priority. On the Now vs. Later Tool, 50% gave equal importance to current versus future quality of life. On the Attitude Scale, 53.4% disagreed with the statement "the most important thing to me is living as long as I can, no matter what my quality of life is"; and 82.2% agreed with the statement "it is more important to me to maintain my thinking ability than to live as long as possible"., Conclusion: Although survival was the top priority for most participants, some older individuals with cancer prioritize other outcomes, such as cognition and function. Clinicians should elicit patient-defined priorities and include them in decision-making., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: The time toxicity of anticancer therapy, defined as days spent with healthcare contact during treatment, represents a critical but understudied outcome. This study aims to quantify time toxicity among older patients with cancer receiving palliative systemic treatment., Methods: All patients aged ≥ 65 years with metastatic cancer receiving cytotoxic chemotherapy, immunotherapy, or targeted therapy at a single center in Mexico were selected from a prospective patient navigation cohort. Patients completed a baseline assessment, including the G8 screening and quality of life measures. Physical healthcare contact days within the first 6 months were extracted from medical records and divided by days alive during the same period. Beta regression models were used to identify predictors of time toxicity., Results: We identified 158 older patients (median age 71 years); 86% received cytotoxic chemotherapy. Seventy-three percent had an impaired G8 score and were considered vulnerable/frail. Six-month overall survival was 74%. Within the first 6 months, patients spent a mean of 21% (95% confidence interval (CI) 19-23%) of days with healthcare contact. Concurrent radiotherapy (odds ratio (OR) 1.55; 95%CI 1.21-1.97), cytotoxic chemotherapy versus targeted therapy (OR 1.64; 95%CI 1.13-2.37), and an impaired G8 (OR 1.27; 95%CI 1.01-1.60) were associated with increased time toxicity., Conclusion: Older adults with metastatic cancer spend 1 in 5 days with healthcare contact during treatment, with a higher burden of time toxicity for patients receiving radiotherapy or cytotoxic chemotherapy and those with potential frailty. These findings underscore the importance of informing patients about their expected healthcare contact days within the context of a limited life expectancy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Molecular and cellular characterization of tumors is essential due to the complex and heterogeneous nature of cancer. In recent decades, many bioinformatic tools and experimental techniques have been developed to achieve personalized characterization of tumors. However, sample handling continues to be a major challenge as limitations such as prior treatments before sample acquisition, the amount of tissue obtained, transportation, or the inability to process fresh samples pose a hurdle for experimental strategies that require viable cell suspensions. Here, we present an optimized protocol that allows the recovery of highly viable cell suspensions from breast cancer primary tumor biopsies. Using these cell suspensions we have successfully characterized genome architecture through Hi-C. Also, we have evaluated single-cell gene expression and the tumor cellular microenvironment through single-cell RNAseq. Both technologies are key in the detailed and personalized molecular characterization of tumor samples. The protocol described here is a cost-effective alternative to obtain viable cell suspensions from biopsies simply and efficiently., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Stephenson-Gussinye, Rendón-Bautista, Ruiz-Medina, Blanco-Olais, Pérez-Molina, Marcial-Medina, Chavarri-Guerra, Soto-Pérez-de-Celis, Morales-Alfaro, Esquivel-López, Candanedo-González, Gamboa-Domínguez, Cortes-González, Alfaro-Goldaracena, Vázquez-Manjarrez, Grajales-Figueroa, Astudillo-Romero, Ruiz-Manriquez, Poot-Hernández, Licona-Limón and Furlan-Magaril.)

Piscine francisellosis is one of the most important bacterial diseases affecting various fish species worldwide. Francisella orientalis, F. noatunensis, and F. salimarina (F. marina) have been reported as etiological agents of disease in fish. A Francisella sp. was isolated from several diseased red drum Sciaenops ocellatus experiencing morbidity in Florida, USA, in 2008. In this study, molecular and phenotypic characterization of the recovered isolate was conducted. Phenotypically, the isolate showed a biochemical reaction profile distinct from that of F. orientalis and F. salimarina. Although the 16S rRNA sequence of this isolate shared 99.61% identity to the type strain of F. philomiragia O#319LT, whole genome analysis (average nucleotide identity <95%; digital DNA-DNA hybridization <70%) and a multilocus sequence analysis of 8 concatenated housekeeping genes in comparison with other Francisella spp. indicated that this isolate was a novel Francisella species, more closely related to F. orientalis. Immersion, intracoelomic injection, and co-habitation challenges using a Nile tilapia Oreochromis niloticus fingerling model of infection were done to investigate virulence in a piscine model. Variably pigmented granulomas and pigmented macrophage aggregates were observed in the kidneys and spleens of the challenged fish, but no mortality was recorded during the 15 d challenge period, suggesting that this novel Francisella sp. might be an opportunistic pathogen of fish. Based on the phenotypic and genotypic differences from other Francisella spp. observed in this study, we propose the name Francisella sciaenopsi sp. nov. for this novel isolate.

Skin microbiomes in amphibians are complex systems that can be influenced by biotic and abiotic factors. In this study, we examined the effect of host species and environmental conditions on the skin bacterial and fungal microbiota of four obligate paedomorphic salamander species, commonly known as axolotls (Ambystoma andersoni, A. dumerilii, A. mexicanum, and A. taylori), all of them endemic to the Trans-Mexican Volcanic Belt. We found that despite their permanent aquatic lifestyle, these species present a host-specific skin microbiota that is distinct from aquatic communities. We identified skin-associated taxa that were unique to each host species and that differentiated axolotl species based on alpha and beta diversity metrics. Moreover, we identified a set of microbial taxa that were shared across hosts with high relative abundances across skin samples. Specifically, bacterial communities were dominated by Burkholderiales and Pseudomonadales bacterial orders and Capnodiales and Pleosporales fungal orders. Host species and environmental variables collectively explained more microbial composition variation in bacteria (R2 = 0.46) in comparison to fungi (R2 = 0.2). Our results contribute to a better understanding of the factors shaping the diversity and composition of skin microbial communities in Ambystoma. Additional studies are needed to disentangle the effects of specific host associated and environmental factors that could influence the skin microbiome of these endangered species., (© 2024. The Author(s).)

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection inhibits mitochondrial oxidative phosphorylation (OXPHOS) and elevates mitochondrial reactive oxygen species (ROS, mROS) which activates hypoxia-inducible factor-1alpha (HIF-1α), shifting metabolism toward glycolysis to drive viral biogenesis but also causing the release of mitochondrial DNA (mtDNA) and activation of innate immunity. To determine whether mitochondrially targeted antioxidants could mitigate these viral effects, we challenged mice expressing human angiotensin-converting enzyme 2 (ACE2) with SARS-CoV-2 and intervened using transgenic and pharmacological mitochondrially targeted catalytic antioxidants. Transgenic expression of mitochondrially targeted catalase (mCAT) or systemic treatment with EUK8 decreased weight loss, clinical severity, and circulating levels of mtDNA; as well as reduced lung levels of HIF-1α, viral proteins, and inflammatory cytokines. RNA-sequencing of infected lungs revealed that mCAT and Eukarion 8 (EUK8) up-regulated OXPHOS gene expression and down-regulated HIF-1α and its target genes as well as innate immune gene expression. These data demonstrate that SARS-CoV-2 pathology can be mitigated by catalytically reducing mROS, potentially providing a unique host-directed pharmacological therapy for COVID-19 which is not subject to viral mutational resistance., Competing Interests: Competing interests statement:D.C.W. is on the scientific advisory boards of Pano Therapeutics, Inc. and Medical Excellent Capital, and published a manuscript with S.E. Schriner in 2022.

Addressing ageism in clinical practice & research: #awareness #education #language and #geriassessment.

Broadly neutralizing antibodies (bNAbs) have shown great promise for prevention and treatment of HIV infection. Breadth of bNAb neutralization, measured in vitro across panels of diverse viral isolates, is often used as a predictor of clinical potential. However, recent prevention studies demonstrate that the clinical efficacy of a broad and potent bNAb (VRC01) is undermined by neutralization resistance of circulating strains. Using HIV-infected humanized mice, we find that therapeutic efficacy of bNAbs delivered as Vectored ImmunoTherapy (VIT) is a function of both the fitness cost and resistance benefit of mutations that emerge during viral escape, which we term 'escapability'. Applying this mechanistic framework, we find that the sequence of the envelope V5-loop alters the resistance benefits of mutants that arise during escape, thereby impacting the therapeutic efficacy of VIT-mediated viral suppression. We also find that an emtricitabine-based antiretroviral drug regimen dramatically enhances the efficacy of VIT, by reducing the fitness of mutants along the escape path. Our findings demonstrate that bNAb escapability is a key determinant to consider in the rational design of antibody regimens with maximal efficacy and illustrates a tractable means of minimizing viral escape from existing bNAbs., Competing Interests: DECLARATION OF INTERESTS A.B.B. is a founder of Cure Systems LLC.

Spliced leader trans-splicing of pre-mRNAs is a critical step in the gene expression of many eukaryotes. How the spliced leader RNA and its target transcripts are brought together to form the trans-spliceosome remains an important unanswered question. Using immunoprecipitation followed by protein analysis via mass spectrometry and RIP-Seq, we show that the nematode-specific proteins, SNA-3 and SUT-1, form a complex with a set of enigmatic non-coding RNAs, the SmY RNAs. Our work redefines the SmY snRNP and shows for the first time that it is essential for nematode viability and is involved in spliced leader trans-splicing. SNA-3 and SUT-1 are associated with the 5' ends of most, if not all, nascent capped RNA polymerase II transcripts, and they also interact with components of the major nematode spliced leader (SL1) snRNP. We show that depletion of SNA-3 impairs the co-immunoprecipitation between one of the SL1 snRNP components, SNA-2, and several core spliceosomal proteins. We thus propose that the SmY snRNP recruits the SL1 snRNP to the 5' ends of nascent pre-mRNAs, an instrumental step in the assembly of the trans-spliceosome., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: The study aims to explore unmet social needs and sources of financial toxicities in patients as noted by health care professionals and researchers in cancer supportive care, shedding light on potential health disparities., Methods: In this cross-sectional survey, we anonymously surveyed active members of the Multinational Association of Supportive Care in Cancer (MASCC). The survey, structured in three sections, included questions regarding the routine assessment of social needs during patient consultations, sociodemographic aspects, factors influencing financial toxicity (FT), perceived support for managing FT, and available/desirable resources., Results: A total of 218 MASCC members were included, predominantly from high-income countries (HIC, 73.4%), with many age 41-60 years (56.5%) and female (56.9%). Drug/treatment cost and insurance coverage were the main sources for FT among the HIC, whereas participants from low-middle-income countries (LMIC) considered transportation cost, loss of employment because of cancer diagnosis, and unavailability of return-to-work services as the top three sources of FT. Respondents from LMIC (adjusted odds ratio [aOR], 3.01 [95% CI, 1.15 to 7.93]) and physicians (aOR, 2.67 [95% CI, 1.15 to 6.21]) were more likely to routinely assess financial coverages. Socioeconomic status was consistently ranked as one of the top three sources of financial toxicities by participants from LMIC (34%), HIC excluding the United States (38%), those who do not self-identify as racial/ethnic minority (36%), and physicians (40%)., Conclusion: This global survey of health care professionals and researchers in HIC and LMIC revealed varying approaches to assessing financial coverage and social needs. Socioeconomic status emerged as a consistent concern across countries, affecting financial toxicities. The study highlights the need for tailored approaches and improved resource visibility while emphasizing clinicians' pivotal role in addressing financial aspects of cancer care.

Introduction: Current management of metastatic prostate cancer (mPC) includes androgen receptor axis-targeted therapy (ARATs), which is associated with substantial toxicity in older adults. Geriatric assessment and management and remote symptom monitoring have been shown to reduce toxicity and improve quality of life in patients undergoing chemotherapy, but their efficacy in patients being treated with ARATs has not been explored. The purpose of this study is to examine whether these interventions, alone or in combination, can improve treatment tolerability and quality of life (QOL) for older adults with metastatic prostate cancer on ARATs., Materials and Methods: TOPCOP3 is a multi-centre, factorial pilot clinical trial coupled with an embedded process evaluation. The study includes four treatment arms: geriatric assessment and management (GA + M); remote symptom monitoring (RSM); geriatric assessment and management plus remote symptom monitoring; and usual care and will be followed for six months. The aim is to recruit 168 patients between two cancer centres in Toronto, Canada. Eligible participants will be randomized equally via REDCap. Participants in all arms will complete a comprehensive baseline assessment upon enrollment following the Geriatric Core dataset, as well as follow-up assessments at 1.5, 3, 4.5, and 6 months. The co-primary outcomes will be grade 3-5 toxicity and QOL. Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. QOL will be measured by patient self-reporting using the EuroQol 5 dimensions of health questionnaire. Secondary outcomes include fatigue, insomnia, and depression. Finally, four process evaluation outcomes will also be observed, namely feasibility, fidelity, and acceptability, along with implementation barriers and facilitators., Discussion: Data will be collected to observe the effects of GA + M and RSM on QOL and toxicities experienced by older adults receiving ARATs for metastatic prostate cancer. Data will also be collected to help the design and conduct of a definitive multicentre phase III randomized controlled trial. This study will extend supportive care interventions for older adults with cancer into new areas and inform the design of larger trials., Trial Registration: The trial is registered at clinicaltrials.gov (registration number: NCT05582772)., Competing Interests: Declaration of Competing Interest Dr. Krzyzanowska reports grants and personal fees from Eisai, grants and personal fees from Lilly, personal fees from Ipsen, personal fees from Bayer, grants from Exelixis, all outside the submitted work. Dr. Glicksman reports grants from Astellas Pharma, grants and personal fees from TreSera, personal fees from Bayer, personal fees from Tolmar, personal fees from Knight Therapeutics, all outside the submitted work. Dr. Emmenegger reports personal fees from Amgen, personal fees from AstraZeneca, grants and personal fees from Astellas, grants and personal fees from Bayer, grants and personal fees from Janssen, grants and personal fees from Merck, grants and personal fees from Novartis, personal fees from Pfizer, grants from Clovis, grants from Roche-Genentech, all outside the submitted work., (Copyright © 2023. Published by Elsevier Ltd.)

Infectious diseases are a leading cause of losses in the aquaculture industry and conservation programs globally. Simultaneously, infectious diseases pose a substantial risk to fish being hatchery-reared and released into natural habitats for conservation purposes, including the Great Lakes lake sturgeon ( Acipenser fulvescens , i.e., GL-LST). Recently, an alloherpesvirus (lake sturgeon herpesvirus 2, i.e., LSHV-2) capable of inducing disease and/or mortality in adult and juvenile GL-LSTs was detected in two adult GL-LST populations. To begin developing disease prevention and/or control methods, in vitro experiments were designed to determine the susceptibility of LSHV-2 to disinfectants commonly used in hatchery and aquaculture facilities (Virkon ® -Aquatic: potassium peroxymonosulfate; Ovadine ® : polyvinylpyrrolidone iodine complex; and Perox-Aid ® : hydrogen peroxide). Cultured LSHV-2 was exposed to each disinfectant at two concentrations (Virkon ® -Aquatic: 0.5% and 1%; Ovadine ® : 50 and 100 ppm; and Perox-Aid ® : 500 and 1000 ppm) in duplicate for durations of 1, 10, and 30 min. Following exposure, the disinfectant was neutralized, and after a 14-day incubation period on a white sturgeon × lake sturgeon hybrid cell line (WSxLS), percent reduction was calculated by comparing the 50% tissue culture infectious doses (TCID 50 /mL) of the virus with and without disinfectant exposure. When exposed to Perox-Aid ® , LSHV-2 percent reduction ranged from 58.7% to 99.5%. When exposed to Ovadine ® , the percent reduction ranged from 99.4% to 100%. Lastly, the percent reduction when exposed to Virkon ® -Aquatic was 100% for both concentrations and all timepoints. The results herein provide evidence that both Virkon ® -Aquatic and Ovadine ® are virucidal to LSHV-2 and may represent a means to reduce virus transmission risk under field settings.

Information on BMI and risk of developing hypertension in type 1 diabetes (T1D) is scarce, and it comes mostly from cross-sectional analyses. This study underscores a risk of developing hypertension in T1D individuals with high BMI, and this risk appears to be higher than in those with type 2 diabetes., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest relevant to this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The guppy, Poecilia reticulata, is one of the most common cultured ornamental fish species, and a popular pet fish highly desired by hobbyists worldwide due to its availability of many brilliantly coloured fish of many varieties. The susceptibility of guppies to diseases presents a remarkable concern for both breeders and hobbyists. In this study, we report the emergence of disease in fancy guppies caused by a previously uncharacterized virus in the USA. This virus was isolated from moribund guppies in two separate outbreaks in California and Alabama, from December 2021 to June 2023. The infected guppies presented with acute morbidity and mortality shortly after shipping, displaying nonspecific clinical signs and gross changes including lethargy, anorexia, swimming at the water surface, gill pallor, mild to moderate coelomic distension and occasional skin lesions including protruding scales, skin ulcers and hyperaemia. Histological changes in affected fish were mild and nonspecific; however, liver and testes from moribund fish were positive for Tilapia lake virus (TiLV), the single described member in the family Amnoonviridae, using immunohistochemistry and in situ hybridization, although the latter was weak. A virus was successfully recovered following tissue inoculation on epithelioma papulosum cyprini and snakehead fish cell lines. Whole genome sequencing and phylogenetic analyses revealed nucleotide and amino acid homologies from 78.3%-91.2%, and 78.2%-97.7%, respectively, when comparing the guppy virus genomes to TiLV isolates. Based on the criteria outlined herein, we propose the classification of this new virus, fancy tailed guppy virus (FTGV), as a member of the family Amnoonviridae, with the name Tilapinevirus poikilos (from the Greek 'poikilos', meaning of many colours; various sorts, akin to 'poecilia')., (© 2024 The Authors. Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Introduction: Supportive care needs may vary according to age. The purpose of this research is to describe and compare supportive care needs between older adults with metastatic cancer (age ≥ 65 years) and their younger counterparts., Materials and Methods: We conducted a retrospective secondary analysis of a cohort of patients with newly diagnosed metastatic solid tumors. Supportive care needs were assessed at baseline and at a three-month follow-up. Patients were divided into two groups (aged ≥65/<65 years). Differences in clinical characteristics and supportive care needs were compared utilizing descriptive statistics. Multivariate logistic regression models were employed to identify patient characteristics associated with specific supportive care needs., Results: Between 2018 and 2022, 375 patients were enrolled. Median age was 66 years (interquartile range 19-94). At baseline, older adults had a higher number of supportive care needs (4.8 vs. 4.2, p = 0.01) and were at higher risk of malnutrition (75 vs. 65%, p = 0.05). Increasing age (odds ratio [OR] 1.02 (95% confidence interval [CI] 1.0-1.04, p = 0.03) and an estimated life expectancy <6 months (OR 3.0, 95%CI 1.5-6.1; p < 0.01) were associated with higher odds of malnutrition, while a higher educational level was associated with decreased odds (OR 0.68, 95%CI 0.5-0.8; p < 0.01). At three-month follow-up, older adults still had a higher number of supportive care needs (3.8 vs.2.6, p < 0.01) and were more likely to have fatigue (62 vs. 47%, p = 0.02). An estimated life expectancy of <6 months was associated with increased odds of fatigue (OR 3.0, 95%CI 1.5-6.3; p < 0.01)., Discussion: Older adults reported significantly more supportive care needs, particularly risk of malnutrition and fatigue. This information can help in the creation of supportive care services tailored to the needs of older individuals., (Copyright © 2023. Published by Elsevier Ltd.)

The increasing rate of the older adult population across the world over the next 20 years along with significant developments in the treatment of oncology will require a more granular understanding of the older adult population with cancer. The ASCO Geriatric Oncology Community of Practice (COP) herein provides an outline for the field along three fundamental pillars: education, research, and implementation, inspired by ASCO's 5-Year Strategic Plan. Fundamental to improving the understanding of geriatric oncology is research that intentionally includes older adults with clinically meaningful data supported by grants across all career stages. The increased knowledge base that is developed should be conveyed among health care providers through core competencies for trainees and continuing education for practicing oncologists. ASCO's infrastructure can serve as a resource for fellowship programs interested in acquiring geriatric oncology content and provide recommendations on developing training pathways for fellows interested in pursuing formalized training in geriatrics. Incorporating geriatric oncology into everyday practice is challenging as each clinical setting has unique operational workflows with barriers that limit implementation of valuable geriatric tools such as Geriatric Assessment. Partnerships among experts in quality improvement from the ASCO Geriatric Oncology COP, the Cancer and Aging Research Group, and ASCO's Quality Training Program can provide one such venue for implementation of geriatric oncology through a structured support mechanism. The field of geriatric oncology must continue to find innovative strategies using existing resources and partnerships to address the pressing needs of the older adult population with cancer to improve patient outcomes.

Communication in oncology has always been challenging. The new era of precision oncology creates prognostic uncertainty. Still, person-centered care requires attention to people and their care needs. Living with cancer portends an experience that is life-altering, no matter what the outcome. Supporting patients and families through this unique experience requires careful attention, honed skills, an understanding of process and balance measures of innovation, and recognizing that supportive care is a foundational element of cancer medicine, rather than an either-or approach, an and-with approach that emphasizes the regular integration of palliative care (PC), geriatric oncology, and skilled communication.

While some recent drug treatments have been transformative for patients with cancer, many treatments offer small benefits despite high clinical toxicity, time toxicity and financial toxicity. Moreover, treatments that do provide substantial clinical benefits are not available to many patients globally due to issues with availability and affordability. The Common Sense Oncology's vision is that patients will have access to treatments that provide meaningful improvements in outcomes that matter, regardless of where they live. In recognition of the growing challenges in the field of oncology, Common Sense Oncology seeks to achieve this vision by improving evidence generation, evidence interpretation and evidence communication.

Piscine lactococcosis is a significant threat to cultured and wild fish populations worldwide. The disease typically presents as a per-acute to acute hemorrhagic septicemia causing high morbidity and mortality, recalcitrant to antimicrobial treatment or management interventions. Historically, the disease was attributed to the gram-positive pathogen Lactococcus garvieae . However, recent work has revealed three distinct lactococcosis-causing bacteria (LCB)- L. garvieae, L. petauri, and L. formosensis- which are phenotypically and genetically similar, leading to widespread misidentification. An update on our understanding of lactococcosis and improved methods for identification are urgently needed. To this end, we used representative isolates from each of the three LCB species to compare currently available and recently developed molecular and phenotypic typing assays, including whole-genome sequencing (WGS), end-point and quantitative PCR (qPCR) assays, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), API 20 Strep and Biolog systems, fatty acid methyl ester analysis (FAME), and Sensititre antimicrobial profiling. Apart from WGS, sequencing of the gyrB gene was the only method capable of consistent and accurate identification to the species and strain level. A qPCR assay based on a putative glycosyltransferase gene was also able to distinguish L. petauri from L. garvieae/formosensis . Biochemical tests and MALDI-TOF MS showed some species-specific patterns in sugar and fatty acid metabolism or protein profiles but should be complemented by additional analyses. The LCB demonstrated overlap in host and geographic range, but there were relevant differences in host specificity, regional prevalence, and antimicrobial susceptibility impacting disease treatment and prevention., Importance: Lactococcosis affects a broad range of host species, including fish from cold, temperate, and warm freshwater or marine environments, as well as several terrestrial animals, including humans. As such, lactococcosis is a disease of concern for animal and ecosystem health. The disease is endemic in European and Asian aquaculture but is rapidly encroaching on ecologically and economically important fish populations across the Americas. Piscine lactococcosis is difficult to manage, with issues of vaccine escape, ineffective antimicrobial treatment, and the development of carrier fish or biofilms leading to recurrent outbreaks. Our understanding of the disease is also widely outdated. The accepted etiologic agent of lactococcosis is Lactococcus garvieae . However, historical misidentification has masked contributions from two additional species, L. petauri and L. formosensis , which are indistinguishable from L. garvieae by common diagnostic methods. This work is the first comprehensive characterization of all three agents and provides direct recommendations for species-specific diagnosis and management., Competing Interests: The authors declare no conflict of interest.

Deficiencies in the BRCA1 tumor suppressor gene are the main cause of hereditary breast and ovarian cancer. BRCA1 is involved in the Homologous Recombination DNA repair pathway and, together with BARD1, forms a heterodimer with ubiquitin E3 activity. The relevance of the BRCA1/BARD1 ubiquitin E3 activity for tumor suppression and DNA repair remains controversial. Here, we observe that the BRCA1/BARD1 ubiquitin E3 activity is not required for Homologous Recombination or resistance to Olaparib. Using TULIP2 methodology, which enables the direct identification of E3-specific ubiquitination substrates, we identify substrates for BRCA1/BARD1. We find that PCNA is ubiquitinated by BRCA1/BARD1 in unperturbed conditions independently of RAD18. PCNA ubiquitination by BRCA1/BARD1 avoids the formation of ssDNA gaps during DNA replication and promotes continuous DNA synthesis. These results provide additional insight about the importance of BRCA1/BARD1 E3 activity in Homologous Recombination., (© 2024. The Author(s).)

Captive fish populations, such as those encompassing aquarium and pet fish, offer significant economic value and are integral to conservation, research, and education. However, these ornamental fish exhibit a reduced ability to protect their ocular surfaces, and our understanding of the ocular diseases that affect them remains limited. Although corneal neoplasms in carp are uncommon, identifying their distinct characteristics is crucial in selecting appropriate therapeutic interventions that aim to preserve vision, prevent the ocular loss, and ultimately ensure the survival of the affected fish. This study provides clinical and histopathological details of various proliferative corneal masses in Cyprininae species, including five koi (Cyprinus carpio) and four goldfish (Carassius auratus). It discusses a spectrum of neoplasms, including soft tissue sarcoma, spindle cell sarcoma, chromatophoroma, and papilloma, in addition to conditions like exuberant granulation tissue and proliferative carp pox. These findings bear significant implications for clinical decision-making and treatment, offering valuable insights into the incidence and characteristics of corneal tumors in captive fish, which could inform further studies in this area., (© 2023 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Background: In low-risk pregnancies, a third-trimester ultrasound examination is indicated if fundal height measurement and gestational age discrepancy are observed. Despite potential improvement in the detection of ultrasound abnormality, prior trials to date on universal third-trimester ultrasound examination in low-risk pregnancies, compared with indicated ultrasound examination, have not demonstrated improvement in neonatal or maternal adverse outcomes., Objective: The primary objective was to determine if universal third-trimester ultrasound examination in low-risk pregnancies could attenuate composite neonatal adverse outcomes. The secondary objectives were to compare changes in composite maternal adverse outcomes and detection of abnormalities of fetal growth (fetal growth restriction or large for gestational age) or amniotic fluid (oligohydramnios or polyhydramnios)., Study Design: Our pre-post intervention study at 9 locations included low-risk pregnancies, those without indication for ultrasound examination in the third trimester. Compared with indicated ultrasound in the preimplementation period, in the postimplementation period, all patients were scheduled for ultrasound examination at 36.0-37.6 weeks. In both periods, clinicians intervened on the basis of abnormalities identified. Composite neonatal adverse outcomes included any of: Apgar score ≤5 at 5 minutes, cord pH <7.00, birth trauma (bone fracture or brachial plexus palsy), intubation for >24 hours, hypoxic-ischemic encephalopathy, seizure, sepsis (bacteremia proven with blood culture), meconium aspiration syndrome, intraventricular hemorrhage grade III or IV, periventricular leukomalacia, necrotizing enterocolitis, stillbirth after 36 weeks, or neonatal death within 28 days of birth. Composite maternal adverse outcomes included any of the following: chorioamnionitis, wound infection, estimated blood loss >1000 mL, blood transfusion, deep venous thrombus or pulmonary embolism, admission to intensive care unit, or death. Using Bayesian statistics, we calculated a sample size of 600 individuals in each arm to detect >75% probability of any reduction in primary outcome (80% power; 50% hypothesized risk reduction)., Results: During the preintervention phase, 747 individuals were identified during the initial ultrasound examination, and among them, 568 (76.0%) met the inclusion criteria at 36.0-37.6 weeks; during the postintervention period, the corresponding numbers were 770 and 661 (85.8%). The rate of identified abnormalities of fetal growth or amniotic fluid increased from between the pre-post intervention period (7.1% vs 22.2%; P<.0001; number needed to diagnose, 7; 95% confidence interval, 5-9). The primary outcome occurred in 15 of 568 (2.6%) individuals in the preintervention and 12 of 661 (1.8%) in the postintervention group (83% probability of risk reduction; posterior relative risk, 0.69 [95% credible interval, 0.34-1.42]). The composite maternal adverse outcomes occurred in 8.6% in the preintervention and 6.5% in the postintervention group (90% probability of risk; posterior relative risk, 0.74 [95% credible interval, 0.49-1.15]). The number needed to treat to reduce composite neonatal adverse outcomes was 121 (95% confidence interval, 40-200). In addition, the number to reduce composite maternal adverse outcomes was 46 (95% confidence interval, 19-74), whereas the number to prevent cesarean delivery was 18 (95% confidence interval, 9-31)., Conclusion: Among low-risk pregnancies, compared with routine care with indicated ultrasound examination, implementation of a universal third-trimester ultrasound examination at 36.0-37.6 weeks attenuated composite neonatal and maternal adverse outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Members of the genus Erysipelothrix are emergent pathogens of cultured eels, as well as several characid and cyprinid species. Since 2013, E. rhusiopathiae has been reported from diseased barramundi ( Lates calcarifer ) cultured in North America; we recovered 8 E. rhusiopathiae isolates from diseased fish during different outbreaks from the same farm. The E. rhusiopathiae isolates from barramundi were compared phenotypically and genetically to E. piscisicarius isolates characterized from ornamental fish and E. rhusiopathiae recovered from aquatic and terrestrial animals. All barramundi isolates were PCR-positive for the surface protective antigen type B ( spaB ) gene, and shared ≥ 99.7% sequence similarity among concatenated multilocus sequence analysis gene sequences, indicating a high degree of genetic homogeneity. These isolates were > 99% similar to other spaB- positive isolates from marine invertebrates and marine mammals, consistent with findings for other spa types. The spaA and spaB isolates shared < 98% similarity, as well as < 90% similarity with spaC- positive E. piscisicarius . Similar clonality among the spaB isolates was observed using repetitive element palindromic PCR. In experimental intracoelomic injection challenges conducted to fulfill Koch postulates, 67% of exposed tiger barbs ( Puntigrus tetrazona ) died within 14 d of challenge. Our study supports previous work citing the genetic variability of Erysipelothrix spp. spa types and the emergence of members of the genus Erysipelothrix as nascent fish pathogens., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.