Integrating cervical cancer screening into routine Human Immunodeficiency Virus (HIV) care has been endorsed as an effective strategy for increasing uptake of cervical cancer screening, facilitating early detection and treatment of pre-cancerous lesions among HIV-infected women. In Uganda, this strategy has not been implemented yet in most HIV clinics. Assessing acceptability of this intervention among HIV-infected women is of great relevance to inform implementation. We assessed acceptability of integration of cervical cancer screening into routine HIV care, associated factors and perceptions among HIV-infected women enrolled in the HIV clinic at Mbarara Regional Referral Hospital.p-value <0.05. Thematic analysis utilizing inductive coding was applied to analyse qualitative data.A mixed methods study utilizing explanatory sequential approach was conducted among 327 eligible HIV-infected women. Acceptability of integration of cervical cancer screening into routine HIV care was measured based on Theoretical Framework of Acceptability. Quantitative data was collected using a pre-tested questionnaire. We conducted focus group discussions to explore perceptions regarding the intervention among purposively selected HIV-infected women. Modified Poisson regression with robust variance analysis was utilized to determine factors associated with acceptability of the intervention. Statistical significance was determined at The majority of HIV-infected women (64.5%) accepted integration of cervical cancer screening into routine HIV care. Religion, perceived risk of developing cervical cancer and ever screened for cervical cancer were statistically significantly associated with acceptability of integration of cervical cancer screening into routine HIV care. Perceived benefits of the proposed intervention were: convenience to seek for cervical cancer screening, motivation to undergo cervical cancer screening, improved archiving of cervical cancer screening results, confidentiality of HIV patient information, and preference to interact with HIV clinic health workers. Shame to expose their privacy to HIV clinic health workers and increased waiting time were the only perceived challenges of the integrated strategy.Study findings highlight the need to take advantage of this acceptability to prioritize implementation of integration of cervical cancer screening into routine HIV care. HIV-infected women should be reassured of confidentiality and reduced waiting time to increase uptake of integrated cervical cancer screening and HIV services among HIV-infected women along the continuum of HIV care and treatment services. Globally, cervical cancer is the fourth most frequently diagnosed cancer and fourth leading cause of cancer death in women with an estimated 570,000 incident cases and 311,000 deaths . In low Human Immunodeficiency Virus (HIV) has been associated with high vulnerability of developing cervical cancer, a great public health challenge. Since 1989, research studies have reported an increased incidence of cervical cancer among HIV-infected women . HIV-infIntegration of cervical cancer screening into routine HIV care has been endorsed as an effective strategy to increase uptake of cervical cancer screening, achieve early detection and treatment of pre-cancerous lesions among HIV-infected women in Sub Saharan Africa where cervical cancer burden parallels that of HIV , 15–22. HIV-infected women enrolled in the HIV clinic are either referred or voluntarily undergo cervical cancer screening conducted by health workers in the cervical cancer screening department at Mbarara Regional Referral Hospital. Despite establishing referral or client-initiated cervical cancer screening system at Mbarara Regional Referral Hospital for the last 10 years, only 11.3% of HIV-infected women enrolled in the HIV clinic at Mbarara Regional Referral Hospital had undergone cervical cancer screening by September 30, 2019. HIV-infected women miss cervical cancer screening opportunities for early detection of pre-cancerous cervical lesions at enrolment and during subsequent annual intervals despite their frequent visits to HIV clinics for medical reviews, viral load monitoring, and monthly Anti–Retroviral Treatment (ART) refills. Such missed opportunities increase risk of presenting late with advanced cervical cancer and poor prognosis among this vulnerable population. Implementation of integration of cervical cancer screening into routine HIV care is expected to increase uptake of cervical cancer screening services at enrolment and during subsequent annual HIV clinic visits among HIV-infected women enrolled in the HIV clinic at Mbarara Regional Referral Hospital compared to currently practiced referral or client-initiated cervical cancer screening system. We assessed acceptability of integration of cervical cancer screening into routine HIV care, associated factors and perceptions among HIV-infected women enrolled in the HIV clinic at Mbarara Regional Referral Hospital.The study was conducted in the HIV clinic at Mbarara Regional Referral Hospital in Mbarara District, South Western Uganda. Cervical cancer is the leading gynaecological cancer at Mbarara Regional Referral Hospital . With a Mixed methods study design utilizing explanatory sequential approach was used to assess acceptability of integration of cervical cancer screening into routine HIV care, associated factors and perceptions among HIV-infected women. Using explanatory sequential approach, the quantitative phase of the study was first conducted followed by analysis of data. HIV-infected women were then selected based on generated quantitative results of acceptability of integration of cervical cancer screening into routine HIV care; to participate in qualitative investigations.This study was conducted among HIV-infected women receiving HIV care and treatment services from the HIV clinic at Mbarara Regional Referral Hospital. Only HIV-infected women aged 18 and above who turned up for ART refills at the HIV clinic on interview dates were included in the study. HIV-infected women aged 18 and above who turned up for ART refills on unscheduled dates were excluded based on electronic appointment lists generated for the respective appointment dates. HIV-infected women who turned up on unscheduled dates were excluded because they were not on the appointment list from which study respondents were systematically selected to participate in the study.The dependent variable for this study was acceptability of integration of cervical cancer screening into routine HIV care. The Theoretical Framework of Acceptability was adapted to measure acceptability of integration of cervical cancer screening into routine HIV care. The Theoretical Framework of Acceptability was proposed as a multi-component framework and systematic approach to assess intervention acceptability across prospective, concurrent, and retrospective temporal perspectives . QuestioInformation on sociodemographic characteristics, awareness of cervical cancer, knowledge of risk factors of cervical cancer, knowledge of symptoms of cervical cancer, cervical cancer screening awareness, uptake of cervical cancer screening, and perceived risk of cervical cancer was obtained. Sociodemographic characteristics included age, marital status, highest education level, religion, area of residence, number of living biological children, and duration of HIV disease.To assess knowledge of risk factors and symptoms of cervical cancer, participants were requested to select from response options “1. Yes” “2. No” for each item. A correct answer was awarded “1” whereas a wrong answer was awarded “0”. According to the African Women Awareness of CANcer tool, codes to response options were assigned without any meaning. So, out of two options, if the participant selected an appropriate answer, one received an award of "1" for the item because it was the correct answer. If the participant selected an inappropriate answer, one received an award of "0" for the item because it was the wrong answer. A summated score was obtained for variables: knowledge of risk factors and knowledge of signs and symptoms of cervical cancer.Knowledge of risk factors of cervical cancer was categorised into two categories: “1. Poor Knowledge” and “2. Good Knowledge”; based on the mean score as evidenced in recent published studies , 28. “1.Knowledge of signs and symptoms of cervical cancer was also categorised into two categories: “1. Poor Knowledge” and “2. Good Knowledge”; based on the mean score as demonstrated in recent published studies , 28. “1.For the quantitative component, sample size was calculated using sample size estimation formula , 30. TheQuantitative data were collected using administered questionnaires. The pre-coded questionnaire was pre-tested at Kawaala Health Centre IV to check for suitability of various aspects such as translations, skip procedures, filtering questions and modifications were made thereafter. The questionnaire was translated into Runyankole/Rukiiga. Selection and recruitment of experienced research assistants was based on competence, quantitative data collection skills and qualifications. Research assistants received training on how to administer study questions before data collection. After meeting selected participants to take part in the study, research assistants introduced themselves and explained the purpose of the study. Eligible participants provided written informed consent before the interview was conducted. Each questionnaire was completed within 15 - 20 minutes. During data collection, questionnaires were reviewed on completion of each interview so that corrections are made in addition to checking for completeness before departure of participants. Supervision was conducted to ensure compliance throughout the study.Data capture screens with in-built checks for consistency, logical flow, range and accuracy of data were designed in EpiData version 3.0 for data entry. Data were cleaned and stored daily. Double-entry of data was done to check for any errors. Stored data was backed up on different flash discs. Questionnaires were kept securely throughout the study and thereafter.Linear regression analysis was the recommended method of modelling since the dependent variable, acceptability of integration of cervical cancer screening into routine HIV care, was a continuous variable. Summated scores of acceptability of integration of cervical cancer screening into routine HIV care were converted into percentages. The regression modelling predicting acceptability of integration of cervical cancer screening into routine HIV care from all independent variables was conducted. Residuals were generated followed by testing assumptions of linear regression: normality of residuals and homogeneity of variance. Linear regression analysis was not utilised for this study because both assumptions of normality and homogeneity of variance of residuals were violated.th percentile of the highest possible summated score of 35 from seven constructs of Theoretical Framework of Acceptability. The 75th percentile was recommended as the cut-off value based on a published study which utilised likert-type scale responses assessing constructs to measure composite dependent variable  …” HIV-infected women in the majority of focus group discussions argued that delivering cervical cancer screening comprehensively with other routine HIV care services during scheduled HIV clinic visits would be very time consuming hence increasing waiting time at the HIV clinic. With increased numbers of HIV-infected women enrolled into HIV care at the HIV clinic, participants were worried of potential delay at the HIV clinic attributed to integration of cervical cancer screening into routine HIV care.This study assessed acceptability of integration of cervical cancer screening into routine HIV care, associated factors and perceptions among HIV-infected women enrolled in the HIV clinic at Mbarara Regional Referral Hospital. Analysis of data showed that 64.5% of HIV-infected women enrolled in the HIV clinic at Mbarara Regional Referral Hospital accepted integration of cervical cancer screening into routine HIV care. This study finding is lower than acceptance among HIV-infected women to undergo cervical cancer screening procedure reported at 87.6% after incorporating Visual Inspection with Acetic acid into the routine clinical services offered at Family AIDS Care and Education Services clinics in Kisumu, Kenya .Acceptability of the proposed intervention at 64.5% is lower than cervical cancer screening acceptance of 79.8% among HIV-infected women at the HIV treatment centre, Nigerian Institute of Medical Research (NIMR), Lagos, Nigeria who participated in the study assessing acceptability of integration of cervical cancer screening into HIV care . This coResults of multivariable regression analysis indicated that religion, perceived risk of developing cervical cancer and ever screened for cervical cancer were statistically significantly associated with acceptability of integration of cervical cancer screening into routine HIV care among HIV-infected women. Despite the fact that Muslims accepted integration of cervical cancer screening into routine HIV care compared to Protestants, a study conducted among HIV-infected women reported that religion was not significantly associated with acceptability of integration of cervical cancer screening into routine HIV care . AdditioHIV-infected women with “Much Above Average” perceived risk of developing cervical cancer accepted integration of cervical cancer screening into routine HIV care. This study finding highly correlates with findings from the systematic review conducted in Ethiopia where perceived susceptibility to acquiring cervical cancer  was significantly associated with cervical cancer screening acceptability among HIV-positive women . HoweverIt was also found out HIV-infected women who had not undergone cervical cancer screening were less likely to accept integration of cervical cancer screening into routine HIV care compared to HIV-infected women who had undergone cervical cancer screening. A study conducted among HIV-infected women at the HIV treatment centre, Nigerian Institute of Medical Research, Lagos, Nigeria reported that ever screened for cervical cancer was not significantly associated with acceptability of integration of cervical cancer screening into routine HIV care . HIV-infPerceived benefits of the proposed intervention were: convenience to seek for cervical cancer screening, motivation to undergo cervical cancer screening, improved archiving of cervical cancer screening results, confidentiality of HIV patient information, and preference to interact with HIV clinic health workers. In all FGDs, HIV-infected women acknowledged that integration of cervical cancer screening into routine HIV care would grant them an opportunity to receive both cervical cancer screening in addition to HIV services conveniently from the HIV clinic compared to currently practiced referral or client-initiated cervical cancer screening. This study finding is in agreement with findings from other studies which reported that convenience of seeking for integrated HIV and cervical cancer screening services from one point without forgetting an added advantage of one off relief of anxiety was attributed to the integrated strategy compared to stand alone screening services , 24. TheHIV-infected women in all FGDs reported that integration of cervical cancer screening would motivate HIV infected women to undergo cervical cancer screening services. Furthermore, HIV-infected women in the majority of FGDs alleged that integration of cervical cancer screening into routine HIV care would inspire HIV-infected women, targeted recipients for the proposed intervention, to comply and adhere to recommended annual cervical cancer screening. Researchers, community members, health care providers and policy makers were also optimistic that intervention would improve uptake of initial and annual cervical cancer screening among HIV-infected women , 15–24. HIV-infected women in the majority of FGDs claimed that the proposed intervention would promote confidentiality of HIV status and any other health related information due to interaction with only health workers and fellow HIV-infected women. This study finding was also reported in a study conducted in Uganda where women reported that the integrated model would promote confidentiality of HIV and any other health related information due to being accessed and confined to limited teams of health care practitioners in HIV clinics . In mostShame to expose their privacy to HIV clinic health workers and increased waiting time were the only perceived challenges of integration of cervical cancer screening into routine HIV care among HIV-infected women. HIV-infected women in only “Very Unacceptable and Unacceptable” FGD reported that they would prefer undergoing cervical cancer screening conducted by health workers at the cervical cancer screening unit of Mbarara Regional Referral Hospital as opposed to HIV clinic health workers. Based on a study conducted in Uganda, discomfort and invasion of privacy expressed by HIV-infected women due to genital illnesses, menstrual periods, and fear to expose their private parts was one of the challenges to undergo cervical cancer screening integrated into routine HIV services at Mildmay Uganda . HIV-infHIV-infected women in the majority of the FGDs argued that delivering cervical cancer screening comprehensively with other routine HIV care services during scheduled HIV clinic visits would be very time consuming hence increasing waiting time at the HIV clinic. This study finding was consistent with findings from other studies where long waiting time was cited as one of the potential challenges HIV-infected women would have to endure through to undergo cervical cancer screening integrated into comprehensive HIV services , 24, 37.The mixed methods study design using explanatory sequential approach increased rigor and internal validity of the study. Utilisation of systematic sampling method for selection of HIV-infected women to participate in the quantitative phase of the study was an added strength to the conduct of the study. However, the Theoretical Framework of Acceptability adapted to measure acceptability of integration of cervical cancer screening into routine HIV care had not yet been validated among Ugandan populations. HIV-infected women who turned up on unscheduled dates were excluded from participating in the study; increasing potential for information bias. Furthermore, this study was conducted in only one HIV clinic in the entire country due to limited funding; hence affecting generalisability of study findings to all HIV-infected women in Uganda.Study findings highlight the need to take advantage of this acceptability to prioritize implementation of integration of cervical cancer screening into routine HIV care. Ministry of Health should prioritise implementation of integration of cervical cancer screening into routine HIV care to increase uptake of cervical cancer screening among HIV-infected women along the continuum of HIV care and treatment services. Health workers delivering HIV care and treatment services should endeavour to conduct intensified health education and awareness about increased risk of developing cervical cancer among HIV-infected women. HIV-infected women should be reassured of reduced waiting time, confidentiality and optimisation of privacy by HIV clinic health workers during provision of integrated HIV care and cervical cancer screening services. Furthermore, a nationally representative study should be conducted to assess acceptability of integration of cervical cancer screening into routine HIV care, associated factors, and perceptions among HIV-infected women enrolled in HIV clinics in Uganda.


Cancer cells that remain viable despite treatment constitute a persister condition that is implicated in residual diseases and a source from which resistant clones and relapses can emerge. Unlike resistant cells that are capable of cycling under therapy, persister cancer cells stay viable but assume a quiescent or non-proliferating state that is reversible upon treatment discontinuation. A source of persisters that has been under extensive study is drug-tolerant persisters, a small cancer cell population that can withstand the selection pressure of cytotoxic treatment and have been attributed to failure in achieving complete response. It is well recognized that many targeted therapeutic agents possess cytostatic effects that suppress growth without directly inducing cell death. While representing favorable responses, treatment-mediated cytostatic conditions require continual maintenance and intrinsically confer an obligate persister population throughout therapy. However, few efforts have focused on understanding the properties of such cytostatic persisters and exploring their therapeutic potentials.A recent study  from ourThese initial findings prompted us to investigate the general effects of oncogenic AKT signaling on non-proliferating cells. To do that, we undertook a bottom-up approach and devised a platform amendable for engineering cell signaling in cytostatic states using three-dimensional culture of quiescent mammary organoids. Quantitative proteomic analysis showed that hyperactive AKT signaling alters the homeostatic control in cytostatic state and promotes an oxidative and proteotoxic environment. Screening a small set of pharmacologic agents that further perturb redox and proteostasis identified an efficacy of proteasome inhibitors in inducing apoptosis in the cytostatic persister cancer cells with selectivity over quiescent normal cells. Mechanistically, this induction of apoptosis is dependent on p70S6K, redox, and ASK1 [+, Her2+, and triple negative), epithelial tissue origins , and drug-mediated cytostatic conditions (CDK4/6 and EGFR/Her2 inhibitors). Furthermore, tumor spheroids and xenograft models of lung and breast cancer showed that targeting cytostatic persisters could significantly reduce and delay cancer recurrence after treatment discontinuation.Notably, this targeting approach shows efficacy in cytostatic persisters harboring PTEN/PI3K pathway mutations independent of breast cancer subtypes (ERFindings from this study have shed light into the cellular controls in cytostatic persisters and highlighted that treatment-mediated cytostatic condition before resistance emerges is a viable targeting venue to reduce cancer recurrence. This study also raised insights into the complexity and challenges of targeting persister cancer cells in therapy. Investigating oncogenic AKT signaling under cytostatic conditions has suggested a different homeostatic environment between cytostatic and drug-tolerant persisters despite similar non-proliferating status, which may contribute to the distinct approaches for targeting. Inhibiting the pro-survival oncogenic AKT signals have broad efficacy in targeting drug-tolerant persisters , 8. We sThe synthetic-lethal approach for targeting is dependent on the effects of specific oncogenic signaling on the cytostatic state homeostasis, suggesting that distinct approaches may be necessary for targeting cytostatic persisters harboring different oncogenic alterations. This notion emphasizes a value of identifying sustained oncogenic signals and their effects in cytostatic persisters, which could facilitate the development of targeting strategies. More broadly, given the pharmacokinetic limitations and the dose-dependent cytostatic and cytotoxic effects of many cancer therapeutic agents, we anticipate that heterogeneous persister populations are inevitable in treatment. The distinct vulnerabilities of cytostatic and drug-tolerant persisters imply that administering multiple targeted regimens would be necessary to effectively deplete the persister reservoirs in patients under cancer treatments.


Cognitive impairment is a well-recognized key feature of schizophrenia. However, these cognitive impairments may be worsened by alcohol consumption. Up to 80% of patients with alcohol use disorders (AUD) display cognitive impairments. Screening for those impairments with a full neuropsychological assessment may be difficult. The Brief Evaluation Alcohol-Related Neuropsychological Impairments (BEARNI) is a specific tool for screening those impairments easy to implement in in clinical practice . To our knowledge, no previous studies have assessed the alcohol-related cognitive impairments using the BEARNI test in schizophrenia patients.The objective of the study was to compare BEARNI mean scores between a group of schizophrenia patients with alcohol use disorders and a group of schizophrenia patients without alcohol use disorder.39 patients with schizophrenia and AUD (SCZ/AUD +)  and 49 patients with schizophrenia without AUD (SCZ/AUD-)  consecutively included in the study, were assessed using the BEARNI test. All patients met DSM-5 criteria for schizophrenia and AUD. Demographic and clinical variables were also collected, using the Alcohol Use Disorders Identification Test (AUDIT) and the Positive and Negative Syndrome Scale (PANSS). The primary endpoint of the study was the difference in BEARNI cognitive mean scores between the SCZ/AUD+ and SCZ/AUD- groups.There was no difference between the two groups regarding demographic variables or PANSS mean scores . The AUDIT mean score was higher in the group of patients SCZ/AUD+ . Total BEARNI and cognitive BEARNI mean scores were significantly lower in the group of patients SCZ/AUD+ compared to the group of patients SCZ/AUD- . The mean subscores of delayed verbal memory, alphabetical ordination, and alternating verbal fluency subtests were also significantly lower in the group of patients SCZ/+ group .The present study found cognitive impairments using BEARNI test in schizophrenia patients with AUD compared to their counterparts without AUD. Screening alcohol related cognitive impairments using BEARNI could be easier in patients in schizophrenia patients with AUD than usual neurocognitive assessmentsNone Declared


Cancer diagnosis, prognosis, and treatment stand as pivotal factors in enhancing patient outcomes. Recent advances in AI, deep learning, and genomics are reshaping cancer research . The intResearch in this domain has spotlighted predictive modeling and cancer biomarkers, demonstrating the application of machine learning in predicting malignancy and metastasis across various cancers, including lung and colorectal cancers . FurtherMachine learning and whole-evidence analysis have facilitated comprehensive evaluation in cancer research. Studies focusing on lung cancer screening and hepatocellular carcinoma prognosis have enhanced screening and prognostic accuracy . AdditioThe investigation of cancer stem cells and their involvement in tumorigenesis has gained significant attention. Studies in this field have delved into the exploration of prognostic long non-coding RNAs (lncRNAs) and the development of deep learning models for early cancer diagnosis. These efforts underscore the critical importance of integrating both physical and genomic markers in treatment planning .Huang et al. pioneered a novel approach integrating low-rank matrix completion for missing value imputation. Their work not only enhanced the accuracy of intratumor heterogeneity analysis but also laid a foundation for precise interpretations within the intricate landscape of cancer biology.In a stride toward addressing technical challenges in single-cell RNA-Seq data analysis, Zhou et al. illuminated the significance of an immune-related prognostic signature in predicting the clinical outcomes and tumor immunity of stomach adenocarcinomas (STAD). Their findings underscored the pivotal role of immune cell infiltration, unveiling distinctive clusters of “hot” and “cold” tumors with divergent clinical trajectories, while identifying key genes, such as PEG10, DKK1, and RGS1, as critical prognostic markers.A pivotal study by Chuang et al. delved into the genetic nuances of diabetic retinopathy, shedding light on the influence of genetic variants of the lncRNA LINC00673 on disease susceptibility. Their exploration unveiled associations between specific LINC00673 single nucleotide polymorphisms (SNPs) and the development of non-proliferative diabetic retinopathy (NPDR), providing crucial insights into the genetic underpinnings of this complex ocular condition.Genes exert a significant impact not only on cancer but also on the development of various other diseases. Hsieh and Li harnessed the potential of image recognition techniques to rectify data imbalances in genetic disease research, spotlighting the transformative role of Synthetic Minority Oversampling Technique (SMOTE) in restoring data integrity within human biobanks. Their study streamlined data processing and facilitated more robust analysis and interpretation of genetic datasets.In parallel, In summary, these groundbreaking studies demonstrate the transformative potential of integrating physical and genomic markers into intelligent therapy systems, fortified by cutting-edge computational technologies. By fostering a collaborative and interdisciplinary approach that promotes scientific excellence, societal inclusivity, and ethical healthcare practices, we pave the way for a future where personalized medicine is not just a vision but a tangible reality accessible to all.


Drosophila revealed two different mechanisms to regulate synapse formation. In photoreceptor neurons, autophagosome formation in synaptogenic filopodia destabilizes presumptive synaptic contacts and thereby restricts incorrect synaptic partnerships. In dorsal cluster neurons, autophagy is actively suppressed to keep mature synapses stable during axonal branching. These findings indicate that different neuron types can require activation or suppression of synaptic autophagy during the same developmental period to ensure proper synapse formation and brain connectivity.A recent characterization of the role of autophagy in two different neuron types during brain development in  Atg5 or Atg7. This seminal work revealed that functional neurons develop in the absence of autophagy, but are at increased risk for adult-onset degeneration. However, subsequent studies revealed that autophagy-deficient neurons, although functional, exhibit hallmarks of neurodevelopmental defects. Loss of autophagy during mouse brain development leads to increased spine density due to defective pruning after synapse formation, a hallmark of neurodevelopmental autism spectrum disorders. Conversely, in worms and flies, loss of neuronal autophagy can lead to reduced synapse formation. These findings suggest developmental roles for autophagy at the level of synapses, yet there is currently no coherent picture about a single, shared mechanism by which autophagy functions during brain development and synapse formation.The role of macroautophagy/autophagy in the brain was initially characterized in mice with neuron-specific loss of the core autophagy genes Our labs have recently studied the role of neuronal autophagy during fly brain development in two different neuronal cell types. Loss of autophagy in photoreceptor neurons leads to a stabilization of synaptogenic filopodia, which in turn leads to increased synapse formation, similar to what has been suggested for spine stabilization in mice . Importasuppression of autophagy. The signaling mechanism underlying this suppression requires Egfr  function, which had previously been shown to function in DCN axon branching during early axon development. The new study now revealed an independent second, later role for Egfr signaling in axonal branches during synapse formation. However, loss of Egfr signaling does not affect the initial trafficking of presynaptic proteins to synaptogenic filopodia at the time synaptogenesis commences in these branches. Instead, Egfr function is specifically required to stabilize newly formed presynaptic active zones by preventing their turnover through membrane degradation . Correspondingly, a reduction of endomembrane degradation through Presynaptic active zones form concomitantly with the elaborate axonal branch morphogenesis of DCN axons. A role for synapse formation in axonal and dendritic branching is well known as “synaptotropic growth”. During synaptotropic growth synapse formation stabilizes branches and provides a local basis for new probabilistic branch formation. Correspondingly, suppression of autophagy during DCN synapse formation secondarily leads to branch destabilization and a deterioration of the stereotypic axonal branching pattern . The conWe conclude that autophagy can restrict synapse formation through different mechanisms in two different neuron types of the fly visual system during the development of synaptic connectivity. In the non-branched axon terminals of photoreceptor neurons autophagy is actively induced at the tips of synaptogenic filopodia to restrict synapse formation and partner choice; in the highly branched axons of DCNs autophagy is actively suppressed to allow synaptotropic growth of an axonal branching pattern. Furthermore, the autophagic cargo in photoreceptor filopodia include the presynaptic seeding factors Liprin-a and RhoGAP100F/Syd-1, but not the mature active zone marker Brp ; by contThe observation that activation versus suppression of autophagy can be required in two different neuron types in the same brain region and during the same critical window of brain development may also affect how we view brain-wide autophagic up- or downregulation as a therapeutic opportunity. If neighboring neurons employ opposite autophagic regulation to develop proper synaptic connectivity, then levels of autophagy must be controlled at the level of individual neurons to ensure normal development.In summary, we have identified two very different neuron types in the fly visual system that employ the spatial and temporal regulation of autophagy for the fine-tuning of synaptic connectivity through selective restriction of synapse formation, albeit through different mechanisms. In both cases cell type-specific modulation of presynaptic autophagy during synapse formation represents a quantitative contribution to brain wiring that is selectable at the level of animal behavior. Based on the diversity of autophagy-dependent synapse development in the few neuron types analyzed thus far, we speculate that more cell-specific roles of autophagy will emerge as more neuron types are investigated during brain development.


Atmospheric heavy metal pollution presents a severe threat to public health and environmental stability. Transition metal catalysts have emerged as a potent solution for the selective capture and removal of these pollutants. This review provides a comprehensive summary of current advancements in the field, emphasizing the efficiency and specificity of nanostructured transition metals, including manganese, iron, cobalt, nickel, copper, and zinc. Looking forward, we delve into the prospective trajectory of catalyst development, underscoring the need for materials with enhanced stability, regenerability, and environmental compatibility. We project that advancements in computational materials science, nanotechnology, and green chemistry will be pivotal in discovering innovative catalysts that are economically and environmentally sustainable. The integration of smart technologies for real-time monitoring and adaptive control is anticipated to revolutionize heavy metal remediation, ensuring efficient and responsive pollution abatement strategies in the face of evolving industrial scenarios and regulatory landscapes. Atmospheric heavy metal pollution, a critical public health concern, has intensified with industrialization, emitting toxic elements like arsenic and lead . IndustrThese metals undergo atmospheric transformations, influencing their environmental persistence and human bioaccumulation, with significant health impacts . They coHeterogeneous catalysis with transition metals has become a key approach for removing atmospheric heavy metals, supported by advancements in catalyst design for improved specificity and cost effectiveness . ResearcTransition metals are exceptionally well suited as catalysts for highly selective capture and removal of atmospheric heavy metals. The variable oxidation states, coordination modes and tunable active sites of transition metals like iron, manganese, cobalt, nickel, copper and zinc facilitate specific binding with heavy metal contaminants . The nanThis review discusses recent advances in emerging transition metal catalytic systems for atmospheric heavy metal removal. The sources, toxicity and environmental impacts of key heavy metal pollutants are first outlined. Progress in the rational design and development of nanostructured transition metal catalysts using synthesis strategies to optimize selective removal performance is then reviewed. Key mechanisms including adsorption, reduction, photocatalytic degradation and vapor-phase catalytic oxidation are examined. Finally, current challenges and future prospects for transition metal catalysts as solutions for real-world atmospheric heavy metal abatement are discussed.Transition metal nanoparticles (NPs) supported over porous materials have been widely explored as promising catalysts for adsorptive removal and reduction in atmospheric heavy metals. Nanostructuring enhances reactive surface area and metal dispersion while supports like silica and activated carbon provide stability and prevent aggregation . By modu2) with sizes of 10–30 nm via a microemulsion technique  (MOF-2)) which showed excellent As(III) and As(V) removal capacity from simulated flue gas . The thi0 vapor under visible light [0 to Hg2+, which was captured in the MOF pores, preventing volatilization.Semiconductor MOFs containing photoactive metal clusters like Ti, Fe, and Zr can generate reactive oxygen species under light irradiation to oxidize toxic heavy metals. MIL-125-NH2, a Ti-based MOF, was able to completely oxidize harmful Hgle light . The phoMOFs selectivity for target heavy metals can be improved through rational functionalization of the organic linkers. Amino-functionalized MOFs are promising for capturing acidic oxoanions of toxic metals like Cr(VI) and As(V). Li et al. synthesized an ethylenediamine-modulated MOF which showed excellent Cr(VI) removal capacity of 199 mg/g . The amiIn summary, MOFs offer a versatile platform for atmospheric heavy metal capture through highly porous structures, tunable functionality and photocatalytic activity. Further development of visible light responsive, durable MOFs through modular synthesis and advanced characterization will drive progress in atmospheric heavy metal remediation.Porous coordination polymers (PCPs), also known as metal–organic polyhedra (MOPs), have attracted interest as selective sorbents for separating toxic heavy metals like mercury and arsenic from flue gas streams. PCPs consist of multimetallic nodes bridged by organic ligands to create crystalline porous architectures . The tun2+ compared to lower adsorption of Pb2+, Cd2+ and Zn2+. This high Hg2+ selectivity was attributed to complementary interactions between the pore size and the ionic diameter. The porous coordination polymers for heavy metal removal are given in The ultrafine micropores (<2 nm) and open metal sites in PCPs promote capture of heavy metal ions and particles. Yuan et al. synthesized a series of PCPs with pore sizes ranging from 0.5 to 2.5 nm and demonstrated size selective adsorption of metal ions . The PCPIncorporating coordinatively unsaturated metal sites in PCPs facilitates strong binding with heavy metals. Zhang et al. synthesized an aluminum methylphosphonate PCP containing open Al(III) sites which demonstrated a remarkable arsenic adsorption capacity of 1025 mg/g . XPS and0 and photoreduction of Cr(VI) under UV irradiation [0 was oxidized to HgO while Cr(VI) was reduced to less toxic Cr(III) species by photoexcited electrons. The local coordination environment around the Ti(IV) sites facilitated the photocatalytic activity.The reactive open metal sites in PCPs also enable redox transformations of toxic metals like Hg(II) and Cr(VI). A Ti(IV)-based PCP synthesized by Boorboor et al. exhibited selective oxidation of Hgadiation . XPS anaOverall, precise modulation of pores sizes, functional groups, and metal binding sites make PCPs promising selective sorbents for removing toxic heavy metal contaminants from industrial flue gas emissions. Future development of durable PCPs with optimized pore structures and active sites will help advance practical heavy metal remediation applications.Metal oxides are a versatile class of catalysts that have shown immense potential for removing toxic heavy metals from industrial flue gas emissions. Redox-active transition metal oxides, especially manganese, iron, cobalt, nickel, copper and zinc oxides, exhibit favorable properties like high stability, good adsorptivity, and multiple oxidation states that facilitate catalytic abatement of atmospheric heavy metals .Nanostructuring enhances the performance of metal oxide catalysts by providing increased reactive surface area, surface defects, and nanoscale interactions that augment heavy metal adsorption and catalytic activity . Common Metal oxides demonstrate excellent adsorption capacity for heavy metals due to surface hydroxyl groups, oxygen vacancies, and labile lattice oxygen that can trap metal ions and particles . Nanosiz2, ZnO and α-Fe2O3 catalyze the photooxidation of toxic metals upon band gap excitation under UV or solar irradiation [0 and As(III) into less volatile higher oxidation states that are readily captured [2O3 nanoparticles prepared using a sol–gel method achieved a 98% photooxidation of Hg0 to HgO, enabling flue gas purification [Semiconducting metal oxides like TiOadiation . Photoexcaptured . For exafication .The variable oxidation states of transition metals like Cu, Fe and Co in metal oxides facilitate catalytic reduction in toxic metals like Hg(II), Cr(VI) and As(V) . Redox cOverall, metal oxide catalysts present versatile, high-performance platforms for removing heavy metals from industrial flue gas emissions through combinations of adsorption, photooxidation and redox catalytic mechanisms. Advances in morphology and interface engineering, visible light harvesting, and multi-functional composite fabrication offer exciting opportunities to leverage these mechanisms for efficient atmospheric heavy metal abatement.Bimetallic catalysts comprised of coupled transition metals have emerged as promising materials for removing airborne heavy metal contaminants. The synergistic effects between the constituent metals in bimetallic nanoparticles and porous materials augment their adsorption capacity, redox activity and stability compared to their monometallic counterparts . Strateg0 while Cu provided abundant binding sites. The combined effect significantly exceeded their individual performances.Bimetallic catalysts often demonstrate increased heavy metal adsorption capacity owing to the combination of favorable properties from the two metals. Pd-Cu bimetallic nanoparticles supported on multiwalled carbon nanotubes showed excellent capture of elemental mercury, achieving a 96% removal from simulated flue gas . The Pd 0 which was then oxidized by interfacial Cu(II) sites [0.Incorporating two transition metals with different reduction potentials generates bifunctional sites that can catalyze sequential conversion of heavy metals between multiple oxidation states. Fe-Cu bimetallic nanoparticles synthesized by Liu et al. displayed cooperative redox activity where Fe(III) centers first adsorbed gaseous HgI) sites . This tw0 under visible light irradiation [0 oxidation.The distinct electronic structures of constituent metals in bimetallic catalysts allow modulating band alignment, charge transfer and surface reactivity. Au-Ag bimetallic nanoclusters exhibited plasmon-enhanced photocatalytic oxidation of Hgadiation . The Ag In summary, bimetallic catalysts present opportunities to strategically couple the unique properties of transition metals to develop multifunctional materials with synergistically enhanced activity, selectivity and lifespan for removing harmful atmospheric heavy metals.Zeolites are crystalline aluminosilicate materials comprised of intersecting channels and cavities that make them promising catalysts for capturing airborne heavy metal pollutants. The porous structure, high surface area, and ion exchange capacity of zeolites facilitate adsorption of heavy metal ions and particles . FunctioThe microporous channels and cavities in zeolites promote physical adsorption and trapment of heavy metal contaminants. Zeolite Y with a faujasite structure demonstrated high capacity adsorption of 215 mg/g for Cd(II) ions owing to the porous supercages . EnhanciThe aluminosilicate framework of zeolites contains abundant charge balancing cations that can be readily exchanged with heavy metal ions. Zeolite NaY exhibited reversible ion exchange with Pb(II) and Cd(II), enabling cyclic heavy metal removal from simulated flue gas . The cat0 [0 to HgO along with high thermal stability, achieving near complete mercury removal [Incorporating redox-active transition metals like Fe, Ti and Ce introduces reactive sites in zeolites that chemisorb and catalytically oxidize elemental metals like Hg0 . Fe-exch removal .Graphene and graphene oxide (GO) are emerging support materials for metal and metal oxide nanocatalysts owing to their high surface area, thermal/chemical stability, and mechanical durability . GraphenGraphene is an ideal support for dispersing metal and metal oxide nanocatalysts while preventing aggregation and leaching during high-temperature operation . Ni nano3O4 nanoparticles grown on graphene nanosheets exhibited potent low-temperature catalytic oxidation of Hg0 to HgO [3O4-graphene interface to boost Hg0 oxidation kinetics.The high conductivity of graphene facilitates electron transfer to supported catalysts, improving redox conversion of absorbed heavy metals. CO0 to HgO . GraphenOxygen functional groups in GO enable selective coordination with heavy metal ions, while restoration of conjugation in reduced GO improves electron mobility . Thiol-fIn summary, graphene-based materials present versatile supports to augment metal/metal oxide nanocatalysts for atmospheric heavy metal removal through carrier, binding site and electron transfer effects.Understanding the kinetics of heavy metal adsorption on MOFs is fundamental to the design of efficient removal processes. Kinetic studies shed light on the rate at which heavy metal ions are immobilized on the MOF surface, impacting overall removal efficiency.In this section, key aspects of kinetics and modeling applied to MOFs photocatalysis for removing heavy metal ions, organic pollutants and microbes from water are reviewed. The discussion illustrates the multifaceted reaction networks involved and highlights recent efforts to develop integrated kinetics models incorporating coupled adsorption, interfacial transfer, light absorption, contaminant degradation and mass transport effects that influence overall treatment rates and efficiencies.Langmuir–Hinshelwood model: The Langmuir–Hinshelwood model is a widely used kinetic model that describes the adsorption and reaction kinetics of surface-catalyzed reactions. Recent advancements in Langmuir–Hinshelwood modeling for MOFs have focused on integrating factors such as photonic efficiency, active site availability, intermediates, and competitive adsorption between multiple contaminants. These refinements enhance the model’s accuracy in describing the kinetics of heavy metal adsorption on MOF surfaces .Pseudo-first-order model: The pseudo-first-order kinetic model is a simplified approach used to describe the kinetics of adsorption reactions. It assumes that the rate of adsorption is directly proportional to the concentration of the adsorbate on the surface. Recent studies applying the pseudo-first-order model have explored its applicability to heavy metal adsorption on MOFs. These investigations have provided insights into the initial stages of adsorption and the factors that influence it, such as temperature and initial concentration .Pseudo-second-order model: The pseudo-second-order kinetic model is an alternative approach for modeling adsorption kinetics. It suggests that the rate of adsorption is related to the square of the concentration of the adsorbate on the surface. Recent developments in the pseudo-second-order model have extended its application to heavy metal adsorption on MOFs. This model accounts for the interactions between heavy metal ions and MOF surfaces and provides insights into the kinetics of adsorption processes, including factors like dosage and initial concentration .Elovich model: The Elovich model is a kinetic model commonly used to describe chemisorption processes. It considers the exponential decrease in adsorption rate over time. Recent studies have applied the Elovich model to investigate the kinetics of heavy metal adsorption on MOFs. This model has been refined to account for factors influencing the rate of adsorption, including temperature and the presence of intermediates .Intraparticle diffusion model: The intraparticle diffusion model focuses on the diffusion of adsorbate molecules within the adsorbent particles. It considers the role of particle size in affecting adsorption kinetics. Recent research has incorporated intraparticle diffusion effects into kinetic models for heavy metal adsorption on MOFs. These studies have provided insights into how particle size influences the rate of adsorption and overall removal efficiency .Chick–Watson model: The Chick–Watson model is commonly applied to describe the kinetics of microbial inactivation through photocatalysis. It considers the reduction in microbe concentration over time. Recent advancements in the Chick–Watson model have focused on its application to MOFs-based photocatalytic disinfection. This model has been adapted to describe multi-step damage processes, shedding light on the kinetics of microbe inactivation .Hom model: The Hom model is an empirical approach used to model the kinetics of microbial inactivation during photocatalysis. It relates the reduction in microbe concentration to reaction time. Recent research has applied the Hom model to investigate the kinetics of microbial inactivation using MOFs-based photocatalysis. This model has been adapted to consider factors such as photonic utilization efficiency and transport effects that influence disinfection rates . The kinThe application of transition metal catalysts for atmospheric heavy metal removal has made significant strides in recent years. As we evaluate the innovations and advances in this field, it becomes apparent that conducting a comprehensive Life Cycle Assessment (LCA) is indispensable. LCA, a systematic evaluation of the environmental impacts associated with a product, process, or technology throughout its entire life cycle, offers a holistic perspective on the sustainability of transition metal catalysts for heavy metal removal .Advancements in LCA methodologies: One of the pivotal advancements lies in the refinement and diversification of LCA methodologies tailored to this niche. Researchers are increasingly adopting hybrid and consequential LCA approaches, allowing for a more accurate assessment of the cradle-to-grave environmental implications of heavy metal removal processes. These approaches enable the integration of local environmental factors, temporal dynamics, and indirect consequences into the evaluation, resulting in a more comprehensive understanding of the technology’s sustainability .Materials selection and sourcing: LCA has played a crucial role in optimizing the selection and sourcing of materials used in transition metal catalysts. Evaluations encompass aspects such as the extraction of raw materials, the energy-intensive production of catalysts, and the management of waste streams generated during the life cycle. As a result, researchers are better equipped to identify environmentally favorable materials and minimize the ecological footprint of catalyst production .Energy efficiency and emission reduction: Transition metal catalysts are continually evolving to enhance energy efficiency and reduce emissions during heavy metal removal. LCA studies have been instrumental in quantifying the environmental benefits of these innovations. The assessment of energy consumption, greenhouse gas emissions, and other pollutants provides valuable insights into the catalyst’s ecological performance and guides further research into sustainable design .End-of-life considerations: The disposal and recycling of transition metal catalysts have gained prominence within the context of LCA. Understanding the fate of catalysts at the end of their life cycle, including potential reclamation and recycling processes, is vital. LCA has facilitated a more complete evaluation of the environmental implications associated with the disposal of catalysts, thereby promoting strategies for sustainable end-of-life management.Socioeconomic and health impacts: Beyond environmental considerations, recent LCA studies have increasingly incorporated socioeconomic and health impacts into the assessment framework. Researchers are examining the potential effects of heavy metal removal processes on local communities and workers, as well as the broader societal implications. This holistic approach ensures that the assessment extends beyond environmental boundaries to encompass the broader spectrum of sustainability.In summary, the integration of Life Cycle Assessment into the evaluation of transition metal catalysts for atmospheric heavy metal removal marks a pivotal advancement in this field. LCA provides a multidimensional view of the technology’s sustainability, encompassing environmental, socioeconomic, and health aspects. As innovation continues to drive this field forward, LCA remains an invaluable tool for guiding research and development efforts towards more sustainable, efficient, and responsible heavy metal removal technologies. The key impact metrics for life cycle assessment of transition metal catalysts are given in The deployment of transition metal catalysts for atmospheric heavy metal removal brings forth several complex challenges that necessitate careful consideration as we move forward. These encompass environmental, societal, and technological dimensions, demanding innovative solutions for sustainable progress.Environmental challenges: The environmental challenges are paramount, as they directly relate to the core goal of mitigating heavy metal pollution. While transition metal catalysts offer substantial promise, their production and deployment must be carefully managed to minimize ecological impacts. Issues such as the environmental footprint of catalyst manufacturing, energy consumption, and greenhouse gas emissions during operation require vigilant attention. Furthermore, the potential release of nanoscale catalyst particles into the environment demands rigorous study to ensure long-term ecological safety.Societal and health concerns: Transition metal catalysts for heavy metal removal often operate in urban and industrial settings. Consequently, the health and safety of nearby communities and workers emerge as vital considerations. Ensuring that these technologies do not inadvertently introduce health risks or disproportionately affect vulnerable populations is of paramount importance. Assessing potential socioeconomic disparities and addressing them proactively is a challenge that the field must confront.Scaling up and integration: Transitioning from laboratory-scale experimentation to real-world application remains a significant challenge. Scaling up catalyst production, maintaining performance consistency, and integrating these technologies into existing industrial processes require innovative engineering solutions. Addressing issues like catalyst stability under varying conditions, efficient mass transport, and reactor design are paramount to success.Long-term stability: The durability and stability of transition metal catalysts in harsh environmental conditions are essential for sustained heavy metal removal. Overcoming issues related to catalyst degradation and ensuring long-term functionality pose notable technological hurdles. Strategies involving materials engineering and advanced coatings are being explored to enhance catalyst longevity.Resource availability: Many transition metal catalysts rely on critical or scarce elements for their functionality. Ensuring a stable supply of these materials is crucial. The development of alternative catalysts with reduced reliance on rare resources or the implementation of effective recycling and reclamation strategies is essential for long-term viability.Outlook for Transition Metal Catalysts:The future of transition metal catalysts in the context of atmospheric heavy metal removal is poised at the cusp of transformative advancements. As we navigate towards more sustainable and efficient environmental remediation technologies, several key development trajectories are anticipated to shape the evolution of these catalysts.Material Innovation and Synthesis:Future research is expected to focus on the discovery and synthesis of novel materials with enhanced catalytic properties. The use of high-throughput computational screening and machine learning will accelerate the identification of catalysts with superior adsorption capacities, selectivity, and stability. Green synthesis routes, employing biological or recycled feedstocks, are projected to gain traction, minimizing the environmental impact associated with catalyst production.Catalyst Architecture and Nano-engineering:Advancements in nanotechnology will enable the precise engineering of catalysts at the atomic level, controlling their morphology, surface properties, and porosity. Such nano-engineered catalysts will exhibit higher efficiencies and targeted action, ensuring the rapid and selective removal of heavy metals from complex atmospheric matrices.Stability and Regeneration:Ensuring the long-term stability of catalysts under operational conditions remains a critical objective. Research will likely advance towards the development of self-healing and regenerative catalyst systems that maintain their activity over extended periods, reducing the need for replacement and minimizing waste generation.Integration with Sensing and Monitoring Technologies:The convergence of catalysis with sensor technology will lead to the advent of intelligent remediation systems. These systems will dynamically adjust to fluctuating pollution levels, optimizing heavy metal capture in real time and providing continuous monitoring to ensure compliance with environmental regulations.Scalability and Process Integration:Translating benchtop innovations to industrial-scale applications will be a significant focus. Addressing the challenges of catalyst scalability, including manufacturing and deployment costs, will be key to their widespread adoption. Modular and adaptable catalyst designs will facilitate seamless integration into existing industrial infrastructures.Holistic Environmental Impact Assessments:Life Cycle Assessments (LCAs) will become integral in evaluating the environmental footprint of catalysts throughout their lifecycle. Emphasis on the sustainable procurement of raw materials, energy efficient production processes, and end-of-life recycling or disposal will guide the development of environmentally benign catalyst systems.Policy-Driven Catalyst Development:Evolving environmental policies and regulations will continue to drive the innovation of transition metal catalysts. Catalyst development will increasingly align with regulatory frameworks aimed at mitigating heavy metal pollution, fostering the creation of compliant and future-proof technologies.In the foreseeable future, transition metal catalysts will likely emerge as more than mere agents for pollution mitigation; they will become integral components of a broader ecosystem aimed at fostering sustainable industrial practices and promoting public health and environmental conservation. The progressive integration of these catalysts into global efforts to combat atmospheric pollution will exemplify the harmonious intersection of science, technology, and policy, crafting a cleaner and safer environment.In conclusion, our review synthesizes the significant strides made in employing transition metal catalysts for the remediation of atmospheric heavy metals, delineating their operational mechanisms, efficiency, and current technological standing. As we peer into the future, we envision a landscape where the development of transition metal catalysts is propelled by breakthroughs in material science, with a pronounced emphasis on sustainability and environmental stewardship. The advent of smart remediation systems, powered by the confluence of catalytic technology and IoT, is set to provide adaptive and precise pollution control. Furthermore, the adoption of green synthesis approaches and life cycle assessments will ensure that catalyst production aligns with global sustainability targets. The challenges of scalability and integration with existing infrastructures will necessitate a collaborative effort across scientific disciplines and industries. By embracing these future directions, transition metal catalysts will not only continue to mitigate the perils of heavy metal pollution, but also pave the way for a cleaner, safer, and more sustainable future.


Fueled by support from the National Cancer Institute’s “Cancer Moonshot” program, the past few years have witnessed a renewed interest in the canine spontaneous cancer model as an invaluable resource in translational oncology research. Increasingly, there is awareness that pet dogs with cancer provide an accessible bridge to improving the efficiency of cancer drug discovery and clinical therapeutic development. Canine tumors share many biological, genetic, and histologic features with their human tumor counterparts, and most importantly, retain the complexities of naturally occurring drug resistance, metastasis, and tumor-host immune interactions, all of which are difficult to recapitulate in induced or genetically engineered murine tumor models. The utility of canine models has been particularly apparent in sarcoma research, where the increased incidence of sarcomas in dogs as compared to people has facilitated comparative research resulting in treatment advances benefitting both species. Although there is an increasing awareness of the advantages in using spontaneous canine sarcoma models for research, these models remain underutilized, in part due to a lack of more permanent institutional and cross-institutional infrastructure to support partnerships between veterinary and human clinician-scientists. In this review, we provide an updated overview of historical and current applications of spontaneously occurring canine tumor models in sarcoma research, with particular attention to knowledge gaps, limitations, and growth opportunities within these applications. Furthermore, we propose considerations for working within existing veterinary translational and comparative oncology research infrastructures to maximize the benefit of partnerships between veterinary and human biomedical researchers within and across institutions to improve the utility and application of spontaneous canine sarcomas in translational oncology research. Sarcomas are a heterogeneous group of neoplasms which arise from mesenchymal cells within tissues derived from the embryonic mesoderm. Sarcomas are rare in people and account for only about 1% of all cancers, though pediatric patients are disproportionately burdened by this tumor type as sarcomas represent greater than 20% of pediatric solid tumors  is the most common primary malignant bone tumor in both dogs and people , 8. HoweAppendicular OS arising from the metaphysis of long bones is the most common and best researched form in both people and dogs and has a remarkably similar clinical presentation in both species, including a similar bimodal age distribution , 13–15. The molecular landscape of canine OS has been relatively well characterized compared with other canine sarcomas. Comparative genomic analysis of OS from dogs and people consistently identifies striking similarities between these tumors, with one study finding them indistinguishable by global gene expression signature . The genWhile further exploration is warranted (and ongoing), the genetic similarities between the canine and human tumors suggest rich opportunities for utilization of canine OS models in the development of new prognostication methods and personalized, targeted therapeutics. Indeed, comparison of the genetic signatures of canine and human OS have led to identification of a pair of genes (CXCL8 and SLC1A3) for which high expression in human tumors was linked with poorer clinical outcome . The cliAngiosarcoma (AS) refers to a group of sarcomas which exhibit differentiation toward vascular or lymphatic endothelial cells. These are among the rarest of the sarcoma types in humans, comprising less than 1% of all soft tissue sarcomas . The incThe clinical presentations of AS and HSA are similar with both tumors diagnosed predominantly in older patients , 47. HowAS and HSA exhibit similarly aggressive biologic behavior with highly infiltrative and invasive patterns of local growth and a high risk of metastasis contributing to the poor clinical outcomes seen in both species , 48–50. The cellular origins of both AS and HSA remain incompletely understood, but recent genomic profiling of canine HSA has driven paradigm shifts regarding the histogenesis of this tumor. Though classically thought of as arising from transformed endothelial cells, these data suggest a pluripotent bone marrow progenitor cell of origin for HSA , 68. WhiIn canine patients, multiple histologic subtypes of sarcomas arising from cutaneous and subcutaneous connective tissues are grouped under a shared grading system and are referred to collectively as soft tissue sarcomas (STS) , 76. DesWhile the general histologic features are similar between canine STS and human sSTS the distribution of histologic subtypes varies between these species. In dogs, fibrosarcoma, peripheral nerve sheath tumors, and perivascular wall tumors are most common among STS for which subtype is reported. In contrast, liposarcoma and undifferentiated pleomorphic sarcoma are the most commonly reported sSTS in people , 80. As Molecular characterization of canine STS represents an area where increased focus could overcome challenges posed by differences in current classification and nomenclature schemes to facilitate inclusion of these tumors in translational studies. For example, dermatofibrosarcoma protuberans in people is characterized by a pathognomonic COL1A1-PDGFB gene fusion , and thoThe genetic landscape of human malignant peripheral nerve sheath tumors (MPNST) reveals recurrent themes of Ras/Raf pathway activation and impairment of DNA repair and P53 regulation resulting from mutations in NF1 , BRAF and CDKN2A/B –91. LimiLiposarcoma is an uncommonly reported STS subtype in dogs, but one for which histologic classification closely parallels human classification. Several immunohistochemical studies in canine liposarcoma demonstrate some similarities with the human disease, including overexpression of MDM2 in well-differentiated and de-differentiated variants. However these studies fail to provide evidence for other histotype-characteristic genetic alterations used in the diagnosis of myxoid and pleomorphic liposarcoma variants in people , 96. Morc-kit gene are implicated in the pathogenesis of many GIST and contribute to remarkable sensitivity of these tumors to tyrosine kinase inhibitors  and leiomyosarcomas) and rhabdomyosarcoma, require further investigation but may also have potential applications as models for human disease. GIST and leiomyosarcoma are primary gastrointestinal sarcomas which account for only around 1% of GI malignancies in people , 98 but hibitors . As withine GIST . LimitedRhabdomyosarcoma refers to a group of malignant mesenchymal neoplasms which exhibit varying degrees of skeletal muscle differentiation. These neoplasms are rare in the veterinary literature, though this apparent low prevalence may be partially due to diagnostic challenges posed by the extreme variation in phenotype, age of presentation, and cellular morphology in these tumors . In peopin vivo biological complexity of human tumors.The conception and implementation of co-clinical trials approaches in translational oncology research has significantly expanded over the last decade. This expansion has been driven by technological advances which continue to provide an ever-increasing understanding of the mutational landscape and key genetic drivers of human cancer types. Our expanded understanding of this genetic complexity has led to an increasingly granular stratification of patients with a common cancer histology into diverse molecular subtypes. Personalized medicine through tailored therapeutic approaches targeting each individual patient’s actionable molecular drivers will no doubt led to additional clinical advances. However, the breadth and depth of these advances, and the time it takes to achieve them, continues to hinge entirely on effective pre-clinical modeling of the in vivo models allow an almost exact recapitulation of treatment protocols for human clinical trial cancer patients in their GEMM or PDX counterpart. This type of mirrored approach can inform strategies and biomarkers for patient stratification, lead to the identification of mechanisms of de novo and acquired drug resistance, and rapidly evaluate drug combinations that overcome this resistance. For certain tumor types, the success of this approach has surmounted increasing cynicism of the basic and clinical oncology research communities around small animal pre-clinical cancer models. Still, these models are not without inherent challenges and disadvantages. PDX models require the use of immunodeficient mice, thus failing to recapitulate tumor-immune interactions and evolution and precluding investigation of anti-metastatic or immunomodulatory therapies. GEMMs alleviate some of these issues via de novo tumor development in the presence of an intact immune system, subsequent establishment of a microenvironment with tumor-host interactions, and in some models, spontaneous metastasis, but GEMMs can be limited in the number of concurrent mutations, limiting their ability to fully recapitulate the molecular heterogeneity of human tumors  accessibility and feasibility of obtaining, expanding, and utilizing patient-derived xenograft (PDX) mouse models, and 2) insightful development and refinement of compelling genetically engineered mouse models (GEMMs) of human cancers. These pre-clinical n tumors , 113.Spurred from these challenges is an increasingly renewed interest in employing a similar comparative dog-human co-clinical approach Table 1.Thus, enhancing engagement and collaboration between academic physician-veterinarian research teams and the pharmaceutical industry is something that must be increasingly addressed in the comparative sarcoma research community. One potential solution to this pressure point is the National Cancer Institute’s (NCI) Cancer Therapy Evaluation Program (CTEP). The long-established NCI Comparative Oncology Trials Consortium (COTC) could work internally with the NCI Division of Cancer Treatment and Diagnosis to develop a secondary function wherein COTC could enter into collaborative agreements with pharmaceutical companies similar to those of CTEP. This could allow COTC, perhaps through CTEP's already established “Non-clinical Use Request” avenue, to supply academic investigators of human-canine veterinary cancer center consortium institutions (e.g. The V Foundation Canine Oncology Research Consortium – CORC) with investigator brochure canine pharmacokinetic and toxicity data and the desired investigational agent or active pharmaceutical ingredient for compounding.Despite these challenges, co-clinical trial designs in dogs with spontaneous sarcomas can still significantly aid in pharmacokinetic and pharmacodynamic based vetting of pre-clinical therapies Figure 2A prime example of the type of “high-risk high-reward” investigations that may best leverage dogs with spontaneous sarcoma is metastasis biology research in osteosarcoma. Metastasis accounts for greater than 90% of all cancer-related mortality , and in Stephen Paget’s 1889 “seed and soil” hypothesis on metastatic organotropism continues to foresee one of the most intensive areas of cancer research over the last two decades –130. Deshttps://caninecommons.cancer.gov/#/home), a centralized, open access repository of clinical and genomic data from spontaneous canine cancers, and by private biotechnology companies such as nanoString® who have made significant investments in canine comparative oncology research (https://www.precinctnetwork.org/). Through an NIH-hosted workshop, these groups of comparative oncology investigators could provide a list of prioritized canine targets for which antibody reagents are needed. Subsequently, working through the channels of the Comparative Oncology Program or Canine Cancer Immunotherapy Network, NCI could produce a Small Business Innovation Research (SBIR) request for proposals for companies to produce these antibody reagents. Once produced, competitive supplemental funding could then be provided to NCI PRECINCT members who submit detailed proposals for validating the specificity and functionality of these antibodies in a variety of immune assays.While remarkable clinical and biological similarities of human and canine OS have been previously demonstrated, increasing knowledge of the genomic complexity in human OS obtained through investigations leveraging technological advances is beginning to widen the gap between these parallel patient populations. If not addressed, this widening gap in the molecular understanding of human vs. canine OS could undermine the predictability of the canine model for testing novel preclinical candidates more so than in studies focused on the fundamental biology of sarcoma progression and metastasis. However, work on addressing this knowledge gap has already begun through establishment of the NCI’s Integrated Canine Data Commons . Additional opportunities in areas such as advanced molecular imaging, cross disciplinary training in human molecular pathology and human investigative new drug trial design would allow veterinary clinician scientists to bring these skills back to our patients and better inform comparative oncology trial design and laboratory correlative studies to maximize extraction of data from these trials and increase their impact on clinical sarcoma patient management.Continued efforts in diversification of our cancer research workforce training infrastructure is an indispensable prerequisite for enhancing the quantity and quality of comparative sarcoma research. To be successful in this approach, the next generation of cancer researchers must include veterinary biomedical scientists with training backgrounds in medical, surgical, and radiation oncology, pharmacology, pathology, and immunology Figure 1Sustaining and bolstering cross-veterinary and -medical institutional support in the form of expanded financial and faculty training investment into specialized and clinically relevant comparative and translational biomedical research fellowship training programs for veterinary scientists would provide more than just a pipeline of well-trained, diverse clinician scientists to foster co-clinical trial approaches in large animal models. Specifically, these fellowship programs would be separate from the already successfully established, and in some cases National Institutes of Health training grant funded, DVM-PhD and post-DVM residency/PhD programs established at veterinary schools across the USA. Instead, these fellowships could more closely mirror MD post-residency clinical fellowships programs, which often contain a multi-year research intensive component and in many cases lead the trainee to pursue further post-doctoral research following fellowship completion. In veterinary medicine, establishment of these fellowship programs would serve to further develop and fortify a more integrated veterinary and medical oncology research landscape from its current partially siloed state, into one that effectively blends and aligns the comparative oncology trials work of veterinary clinicians and scientists with their human colleague counterparts. Veterinary clinicians and scientists completing these fellowships would likely emerge with strong established collaborations with their human oncology research counterparts, a key benefit that circumvents an otherwise not infrequent barrier for junior veterinary clinician scientist faculty looking to establish independent comparative oncology research programs.Similar to their medical counterparts, veterinary clinician-scientists are invaluable members of increasingly necessary multi-disciplinary cancer research teams. If and when these types of translational research fellowships are established, recruiting, retaining, and growing the number of clinically trained veterinarians entering into these programs would in part require a paradigm shift in how veterinary medical institutions themselves value these post-DVM trainees. Based on the latest American Veterinary Medical Association (AVMA) compensation report, veterinarians entering academic residency or PhD programs immediately after graduation would likely receive 40-50% of the starting salary of their fellow classmates entering into private clinical practice despite comparably high educational loan burdens. When considering post-residency DVMs entering PhD or the fellowship programs proposed here, this compensation gap exponentially widens. Post-residency academic fellowship programs that provide compensation at the NIH-specified post-doctoral stipend levels, regardless of whether or not the program holds, or the individual successfully competes for, an NIH institutional training grant, would provide the necessary institutional commitment needed to broaden the veterinary clinician-scientist pipeline.V foundation for Cancer Research), and 4) inclusion of members of both groups in monthly grant progress and update meetings of these consortia. Additionally, non-profit groups such as Ethos Discovery, the Osteosarcoma Institute, and Make It Better (MIB) Agents are fully invested in engaging academic investigators, leveraging their collaborative networks, and raising funds to support both human and canine sarcoma research.There exists already a strengthening network of key academic, government, and non-profit stakeholders with an expanding intellectual and financial investment in comparative sarcoma research. For example, opportunities are already arising to share ideas and data from members of canine clinical trials and comparative oncology research consortia such as the Comparative Oncology Trials Consortium, the Consortium for Canine Comparative Oncology (c3o) between Duke Cancer Institute and North Carolina State University College of Veterinary Medicine, and NCI PRECINCT (which was created through the aforementioned NCI Cancer Moonshot funding opportunities), with that of their human counterparts such as the Children’s Oncology Group Osteosarcoma Biology and Bone Tumor Steering Committees. These collaborative opportunities occur through 1) focused comparative oncology scientific sessions at national meetings, 2) joint national meetings between canine and human cancer moonshot grant awardees, 3) funding opportunities requiring veterinary and medical scientist co-PI submissions (Although clear gaps in the comparative molecular characterization of the canine sarcoma types reviewed herein remain, these temporary limitations should not preclude the cancer research community’s embracement of these valuable translational models. Leveraging dogs with spontaneous sarcomas in co-clinical trial approaches will undoubtedly provide a valuable and complementary source of high predictive value data to inform clinical practice, and ultimately, improve both human and canine sarcoma patient outcomes. Fully realizing the potential of this comparative approach requires fortifying veterinary and human medical oncology research partnerships alongside continued and enhanced investment in training the next generation of diverse, cross-disciplinary cancer researchers.MK, LH, LA, AM, ML and DR all drafted and edited the manuscript. MK and DR generated the figures and table. All authors contributed to the article and approved the submitted version.


Minimal (or measurable) residual disease (MRD) negativity has emerged as one of the most important prognostic tools in multiple myeloma (MM) and is associated with significant improvements in progression-free survival (PFS) and overall survival . Much ofMRD negativity is associated with improved outcomes for older adults with MM . Table 1Older adults with MM have traditionally had inferior outcomes compared to younger patients . A signiThe ideal treatment for older adults should be highly effective, safe and with no enduring toxicity. Moreover, it should aim to minimize treatment burden, ideally with a finite duration, while improving patient quality of life. Even low-grade symptoms such as protracted fatigue from continuous immunomodulatory drugs can have a major impact on quality of life. The ideal treatment strategy should target not only specific disease characteristics but also patient specific characteristics, including frailty. A precise evaluation of disease response should allow for treatment titration including dose escalation, dose de-escalation or treatment discontinuation altogether.MRD testing represents one of the most powerful prognostic tools in MM, offering the potential for a more precise approach to treatment. This approach applies across the entire spectrum of treatment options, including bispecific and CAR-T therapies. Moreover, insights from clinical trials suggest that treatments with a higher likelihood of achieving MRD negativity, along with agents adding only modest or minimal toxicity , shouldFor instance, in an older adult receiving daratumumab–lenalidomide–dexamethasone therapy, achieving MRD negativity, especially sustained MRD negativity with a complete response, could prompt de-escalation of one of the agents or even therapy discontinuation, particularly if the current treatment is symptomatically burdensome. During this off-treatment phase, close monitoring would be essential, and if MRD resurgence occurs, therapy could be re-initiated, either with dara-len-dex or an alternative regimen. Proper tailoring using MRD testing should enhance quality of life, reduce treatment burden, and minimize the ongoing risk of treatment-related toxicity.Despite its potential value, numerous key unanswered questions remain regarding the role of MRD testing in older adults with MM. We need further evidence to demonstrate that tailoring treatment based on MRD results improves patient outcomes, including quality of life among older adults. This evidence generation is necessary not only for fit older adults but also for the frail patient population. Among the frail group, low-intensity continuous treatments are often used, typically yielding low rates of MRD negativity. Thus, given the already high rates of toxicity among frail patients, thoughtful consideration and data are required to justify treatment escalation with potentially more potent agents to achieve higher rates of MRD negativity, while balancing the impact of treatment modification on the risk of treatment-related toxicity and quality of life.Designing clinical trials involving older adults with MM to demonstrate the utility of MRD testing will pose unique challenges. It will be crucial to ensure that the eligibility criteria of these trials accurately reflect the real-world diversity of these patients, encompassing variations in comorbidities and functional status. Adequate sample sizes in these designed trials will also be essential to detect meaningful differences in MRD status and outcomes among older adults. Lastly, as MRD assessments often require long-term follow-up to assess their impact on patient outcomes, strategies to reduce attrition and maintain consistent follow-up over longer periods will be important. Ultimately, overcoming the challenges of designing trials in older adults, particularly to demonstrate the utility of MRD testing, demands a multidisciplinary approach involving geriatric specialists, oncologists, statisticians, and patient advocates. Striking a balance between scientific rigor and the unique needs and characteristics of real-world older adult patients is essential for obtaining clinically relevant results.−5 vs 10−6) also remains to be defined and may differ for fit older adults who may require dose escalation for MRD positivity versus among frail older adults where dose de-escalation is being considered for MRD negativity. Lastly, given that the risk of progression is dynamic, the role and feasibility of repeat bone marrow aspiration measurements for MRD testing in the context of dynamic frailty status [Additional challenges in MRD testing for older adults with MM include determining the optimal timing for MRD measurement. Unlike transplant-eligible patients with defined treatment blocks , many current treatment regimens for older adults are continuous, making it unclear when the ideal time for MRD assessment would be. This needs to be further analyzed with respect to the intended use of the MRD result. Discontinuation likely requires the establishment of durable MRD negativity while dose intensification may require more frequent testing at time points where an intervention would be re-planned. The optimal threshold 10− vs 10−6 In summary, MRD testing stands as an exciting advancement in the field of MM, offering valuable insights into prognosis for older adults with MM. Additionally, while data remains somewhat limited, in specific scenarios such as discontinuing maintenance therapy, especially for patients encountering treatment-related toxicity, MRD-negative results could serve as a valuable tool in treatment decision-making. As emerging data continue to evolve, MRD testing holds the potential to help us fine-tune treatment strategies, optimizing both under- and over-treatment for the diverse population of older adults with MM.


Apathy and goal-oriented behaviors are key dimensions of late-life depression (LLD) and are iteratively associated with cognitive decline in most neuropsychiatric disorders. However, scales and criteria remains insufficient to provide robust individual biomarkers that could foster personalized therapeutic approaches. Therefore, dimensional and digital phenotyping offer new possibilities of stratifying LLD population. This presentation will show our recent results of functional connectivity cerebral networks associated with multidimensional paper-and-pen measures of apathy, including the default mode and the cingulo-opercular networks. We will also show how dimensional reduction  of 3 days actimetry measures are associated with both FC and inflammatory measures (diffusion and multicompartment indices such as free water and neurite orientation dispersion), providing arguments for different pathophysiological mechanisms underlying goal-oriented behaviors and reinforcing actimetry as a good candidate for individual biomarker of cognitive decline in LLD. Finally, machine learning approaches using combination of different, yet correlated, indices of actimetry will be presented and discussed with their corresponding classifying accuracies . Altogether, this presentation aims at bridging the gap between cerebral imaging and digital phenotyping to enhance personalized medicine in the field of old-age psychiatry and cognitive decline prevention.None Declared


Mops condylurus bats in Kenya, indicating the virus is well-tolerated. Our findings indicate M. condylurus bats may be a reservoir host for Bombali virus. Increased surveillance of these bats will be important to reduce potential virus spread. We found similar mild perivascular inflammation in lungs of Bombali virus–positive and –negative  Despite extensive research since the first documented human Ebola virus (EBOV) disease outbreak in 1976, animal species involved and mechanisms by which ebolaviruses spillover to humans remains enigmatic. Bats have been implicated as reservoir hosts , the sixth and most recent ebolavirus identified. First reported in M. condylurus bats; the BOMV-negative bats were used as negative controls  as described previously  support bats as a chronic subclinical BOMV reservoir with the potential for infection and sporadic virus excretion. However, the small number of samples, absence of recovery of infectious virus, and lack of longitudinal data make interpretation of our results difficult. As for all wildlife-borne ebolaviruses, no direct evidence currently exists regarding the transmission route of BOMV between susceptible hosts. Our findings suggest the mode of transmission involves activation of replication in either macrophages or other cells and virus dispersal through saliva droplets or feces. The identification of BOMV infection in lungs and occasional virus presence in intestines further supports this hypothesis (M. condylurus bats and an absence of substantial concurrent pathologic findings. Our results support M. condylurus bats as reservoir hosts for ebolaviruses and highlight the importance of bat surveillance to understand and mitigate potential emerging disease risks.In summary, we showed EBOV-VP40 immunolabeling, acting as a cross-reactive surrogate for BOMV antigen, in pulmonary macrophages of wild BOMV RT-PCR–positive Mops condylurus bats naturally infected with Bombali virus, Kenya. Additional information for no substantial histopathologic changes in


Daucus carota L.), resulting in reduced crop yields and quality. Drought stress induces a range of physiological and biochemical changes in carrots, including reduced germination, hindered cell elongation, wilting, and disrupted photosynthetic efficiency, ultimately leading to stunted growth and decreased root development. Recent research has focused on understanding the molecular mechanisms underlying carrot's response to drought stress, identifying key genes and transcription factors involved in drought tolerance. Transcriptomic and proteomic analyses have provided insights into the regulatory networks and signaling pathways involved in drought stress adaptation. Among biochemical processes, water scarcity alters carrot antioxidant levels, osmolytes, and hormones. This review provides an overview of the effects of drought stress on carrots and highlights recent advances in drought stress-related studies on this crop. Some recent advances in understanding the effects of drought stress on carrots and developing strategies for drought stress mitigation are crucial for ensuring sustainable carrot production in the face of changing climate conditions. However, understanding the mechanisms underlying the plant's response to drought stress is essential for developing strategies to improve its tolerance to water scarcity and ensure food security in regions affected by drought.Drought stress is a significant environmental factor that adversely affects the growth and development of carrot ( Daucus carota L. is an important vegetable, grown in a cool climate and globally used for its edible taproot  enhanced the physio-biochemical stress response of carrot plants  and total phenolics exhibit higher levels of accumulation   and proline dehydrogenase genes (PDH) are involved in drought stress tolerance in carrot cultivars. Furthermore, proline dehydrogenase is the first enzyme involved in the proline oxidation pathway and they are associated with cellular homeostasis. The same study also described the role of catalase (CAT) and proline transporter genes (PRT) under drought stress in carrot plants, these genes are involved in the transportation of proline among organs and cells  and 20.058 SNPs (single nucleotide polymorphisms) in carrots  involved in different processes in carrot plants including stress tolerance  might also be beneficial. There is still a significant research gap in understanding drought effects and its mechanisms in carrot crop and developing tolerant carrot cultivars. Therefore, it is needed to incorporate both conventional and modern techniques to acquire fruitful results.


The overall health care costs for managing patients with community-acquired pneumonia (CAP) in U.S. hospitals is burdensome.While pharmacy costs comprise only a minor proportion of these costs,hospital length of stay (LOS) is the greatest contributor. Infections due to antimicrobial-resistant pathogens are also associated with increased overall health care cost. Therefore, strategies that aim to minimize antimicrobial resistance and reduce hospital LOS may have the greatest impact in reducing overall health care costs in managing patients with CAP.To evaluate how antimicrobial resistance can impact healthcare costs associated with CAP and review strategies to minimize the risk of resistance development while promoting appropriate antimicrobial therapy (including optimized dosing) and decreasing hospital LOS.Antimicrobial resistance can increase the risk of clinical failure and result in higher overall health care costs. Further development of antimicrobial resistance during therapy should, therefore, be minimized.This can be achieved through optimized antimicrobial dosing strategies—using a higher dose of concentration-dependent agents or prolonged infusion of time-dependent agents—that increase the probability of attaining pharmacokinetic-pharmacodynamic targets for eradication of the pathogen and hence successful clinical outcomes. Decreasing LOS must be a priority when attempting to reduce hospital costs. Active intravenous-to-oral switch therapy has been shown to effectively reduce LOS. Appropriate short-course regimens may also offer the opportunity for effective treatment while reducing or eliminating unnecessary antimicrobial exposure that not only reduces the potential for drug-related adverse events, but may also minimize the selection of resistant organisms.Clinical failure and antimicrobial resistance can significantly increase the cost of managing patients with CAP, primarily by increasingLOS. Therefore, strategies should be employed to minimize the risk of resistance development and reduce LOS. These include early appropriate therapy, optimized dosing based on pharmacodynamic principles, and efficient IV-to-PO switch therapy when appropriate.


Patients' willingness to pay (WTP) is a subject of interest, particularly in these times of consumer-directed health care and benefit designs that involve multiple copayment tiers. Since tiered copayment products have been found to reduce premium costs, the continued proliferation of tiered copayment benefits can be expected.