Specific Time Points Research Articles

New Strategies of Canine Post-Adoption Support: Methods for a Prospective Longitudinal Cohort Study.

In 2018, Dogs Trust (UK) launched the Post Adoption Support project, the largest known prospective cohort study investigating behavioural and health problems post-rehoming of dogs. Individuals adopting a dog from any UK Dogs Trust Rehoming Centre are eligible to receive phone calls regarding their dog's health and behaviour at specific timepoints after adoption (2 days, 2 weeks, 4 months). Alongside providing an early and proactive framework to support the wellbeing of the adopter and dog, the project collects rich longitudinal data on dog health and behaviour following adoption to assess the development of issues, the impact of support given, and re-relinquishment risk. This paper details the methodology and study design of the Post Adoption Support project and describes a cohort profile of adoptions over an initial 6-month period. In the cohort, behaviour and health data were collected from 5498 adopters, with call success for those eligible ranging from 72% (4 months) to 89% (2 days). Data from these calls will provide significant insights into canine welfare during the first 4 months post-adoption, which can be used to inform strategies for effective and impactful rehoming and post-adoption support.

Abstract 5492: Application of Optim.AI™ platform for predictive evaluation of immunotherapy combinations in breast cancer

Abstract PURPOSE: Successful pre-clinical evaluation of immunotherapy within ex vivo settings require complex systems to accurately represent tumor heterogeneity and the surrounding tumor microenvironment (TME). With expanding immunotherapy combinations being investigated in clinical trials, particularly for breast cancer (BC), there is a growing need for reliable methodologies for functional immune-oncology drug testing in a patient- and subtype-specific manner. We have developed Optim.AI™, a hybrid experimental-analytics platform designed to predict and rank actionable treatment options, with successful application in clinical settings to guide cytotoxic and targeted therapies. However, its potential for evaluating immunotherapy responses remains underexplored. In this study, we present an integrated platform that combines short-term 3D tumor-immune cell co-culture with high content imaging and Optim.AI™ to evaluate immunotherapy-focused drug sets in HER2-positive and triple-negative BC subtypes. METHODS: BC cells were pre-labeled with cell tracker and seeded in a 384-well format for 3-4 days to allow spheroid formation, and co-cultured with PBMCs. Optim.AI™ combinatorial drug testing was then applied to the co-culture system with up to 12 FDA-approved chemotherapies, targeted agents, monoclonal antibodies, and antibody-drug conjugates. Utilizing real-time fluorescent apoptosis signal as the phenotypic readout, high-content analysis of tumor-specific cell death was evaluated at specific timepoints and used for Optim.AI™ analytics and predictive ranking of combinatorial immunotherapy sensitivities. RESULTS: Quantitative, real-time, image-based analysis allowed for phenotypic measurement of complex tumor-immune cell interactions within the 3D co-culture system, including immune cell migration, infiltration into spheroids, and subsequent tumor-specific killing. Co-culturing BC spheroids with PBMCs at an optimized effector-to-target ratio induced significant antibody-dependent cellular cytotoxicity, with measurable responses observed within 72 hours post-treatment. Through Optim.AI™, we observed distinct sensitivities towards the different antibody-based therapies, in HER2-positive and triple-negative BC spheroids. These findings underscore the potential of Optim.AI™ to effectively evaluate and rank immunotherapy-based treatment combinations in a physiologically relevant, 3D TME model. CONCLUSIONS: We present an integrated platform combining high-content screening of a 3D tumor-immune cell co-culture system with Optim.AI™ and demonstrated both visualization and quantification of tumor-specific responses in the context of the TME. Future applications to ex vivo patient samples hold promise for personalized treatment regimens and identifying more effective immunotherapy combinations for BC and other solid malignancies. Citation Format: Sharon Pei Yi Chan, Jhin Jieh Lim, Masturah Mohamed Abdul Rashid, Edward Kai-Hua Chow. Application of Optim.AI™ platform for predictive evaluation of immunotherapy combinations in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5492.

Probabilistic Forecasting of Irregularly Sampled Time Series with Missing Values via Conditional Normalizing Flows

Probabilistic forecasting of irregularly sampled multivariate time series with missing values is crucial for decision-making in various domains, including health care, astronomy, and climate. State-of-the-art methods estimate only marginal distributions of observations in single channels and at single timepoints, assuming a Gaussian distribution for the data. In this work, we propose a novel model, ProFITi using conditional normalizing flows to learn multivariate conditional distribution: joint distribution of the future values of the time series conditioned on past observations and specific channels and timepoints, without assuming any fixed shape of the underlying distribution. As model components, we introduce a novel invertible triangular attention layer and an invertible non-linear activation function on and onto the whole real line. Through extensive experiments on 4 real-world datasets, ProFITi demonstrates significant improvement, achieving an average log-likelihood gain of 2.0 compared to the previous state-of-the-art method.

Patient-Reported Outcome Measures in Benign Esophageal Disorders.

Patient-Reported Outcome Measures in Benign Esophageal Disorders.

Myths at Work: Taming Imperial Histories with Tea

ABSTRACT This article analyzes a day-long tea service at Yasukuni Shrine in Tokyo to unpack how people can uncritically replicate myths that subdue recognition of imperialist aggression. Extending the work of Roland Barthes, it identifies how myths can operate through objects grouped as a set, deployed in space, and used in interaction. Meanings attributed to objects both in their singularity and as members of a collection – a dual layering of semiotic interactions – can collude to vivify a myth that, in this case, emphasizes the peaceful essence of Japanese culture and depoliticizes a history of imperial violence. In doing so, the myth rides on a translocal connection that links the nation and the former empire to Asia today. The analysis reveals the ways that the material arrangement and physical enactment of a tea performance at a particular point in time suppressed a violent history of Japanese imperialism fought under the banner “Asian universalism” and invoked in its place a narrative of spreading peace through a bowl of tea.

Are different types of childhood adversities correlated within and across time? A comparison of data on adversity co-occurrence from three longitudinal birth cohort studies.

Are different types of childhood adversities correlated within and across time? A comparison of data on adversity co-occurrence from three longitudinal birth cohort studies.

Maximum Isometric Hip Adduction Squeeze and Abduction Press Strength Values in Men's Rugby Union Players at Select Timepoints Throughout a Competitive Season.

O' Connor, C, Mc Intyre, M, Delahunt, E, and Thorborg, K. Maximum isometric hip adduction squeeze and abduction press strength values in men's rugby union players at select timepoints throughout a competitive season. J Strength Cond Res 39(4): e569-e580, 2025-The purpose of this research was to report hip adduction and abduction strength values in men's rugby union players at select timepoints throughout a competitive season and to examine if differences exist between time of season and hip-testing positions. This cross-sectional repeated measures study design consisted of 15 male rugby union players competing at senior club level. Maximum isometric hip adduction and abduction strength were measured using a ForceFrame in 3 testing positions at specific timepoints: start of preseason (T1), start of competitive season (T2), mid-season period 1 (T3), and mid-season period 2 (T4). At group level, hip adduction strength (N·kg -1 ) increased from T1 to T2 in all testing positions, with significant increases observed in the 0° hip-flexion short-lever position ( p = 0.048), and 45° hip-flexion position ( p = 0.032). No significant changes occurred in hip abduction strength (N·kg -1 ). Hip adduction:abduction strength ratio increased from T1 to T2, with a significant increase observed in the 0° hip-flexion short-lever position ( p = 0.008). At individual level, large variations from baseline strength (N·kg -1 ) were observed between timepoints for hip adduction strength, abduction strength, and adduction:abduction strength ratio. In conclusion, the present study shows increases in hip adduction strength and hip adduction:abduction strength ratio from the start of preseason to the beginning of the competitive season, with no other significant changes in hip strength observed throughout the season. Individual and frequent hip strength monitoring throughout the season and a more individualized exercise prescription approach may be needed for rugby union players, in addition to a more generalized focus on improving adductor and abductor strength.

Blood Virome After Allogeneic Hematopoietic Stem Cell Transplantation.

Haploidentical allogeneic hematopoietic cell transplant recipients (allo-HCTr) receiving posttransplant cyclophosphamide (haplo-PTCy) are at higher risk for infectious complications, including viral infections. We performed a retrospective, single-center, propensity-score matched-pair study including adult haplo-PTCy and allo-HCTr from human leukocyte antigen (HLA)-matched donors, undergoing transplantation in our institution between 2016 and 2022. For each patient, 4 blood samples (day [D] 0, D30, D90, and D180 posttransplantation) were extracted from the biobank and tested with metagenomic next-generation sequencing (mNGS) to describe the blood virome and identify viral RNA/DNA signatures potentially unrecognized by routinely available tests. Routine and symptom-driven polymerase chain reaction (PCR) test results performed during the study period were reviewed. Twenty-five matched pairs of haplo-PTCy and HLA-matched allo-HCTr were included in the analysis. Plasma mNGS detected a total of 155 and 190 different viral RNA/DNA signatures in haplo-PTCy and HLA-matched allo-HCTr, respectively between D0 and D180. The number of viral signatures was significantly lower in the haplo-PTCy group compared to HLA-matched allo-HCTr at D90 (-1.0 [95% confidence interval {CI}, -1.7 to -.3]; P = .01) and during the period between D30 and D180 (-1.9 [95% CI, -3.3 to -.5]; P = .01). Certain viral species (Anelloviridae, Epstein-Barr virus) were more prevalent in HLA-matched patients. Symptom-driven PCR tests showed higher infection rates of usual viral pathogens in haplo-PTCy versus HLA-matched allo-HCTr (P = .02). Frequently deployed, targeted PCR tests showed increased viral infection prevalence in haplo-PTCy patients. Conversely, mNGS testing applied at specific timepoints revealed a lower number of commensal viruses in this patient group. More studies on routine use of mNGS are needed to further assess its clinical relevance and value.

Factors Affecting Psychosocial Distress in Adolescents and Young Adults with Cancer: BRIGHTLIGHT Cross-Sectional and Longitudinal Cohort Study Results.

AYAs face unique psychosocial challenges compared to younger children and older adults. Little published data exists about symptoms of psychological distress in AYAs, particularly in large cohorts over time. This study aimed to (1) explore relationships between distress and variables known to impact mental health, (2) examine distress over time, and (3) consult with a patient and public involvement group (Young Advisory Panel, YAP) to contextualize the results. Secondary data analyses were conducted from a multicentre longitudinal cohort study, which recruited 830 participants aged 13-24 years newly diagnosed with different cancers. The mean age was 20.1 (SD 3.3) and 45% were female. Bespoke surveys, including a validated measure of psychosocial distress, were administered five times over 3 years following diagnosis. Participatory workshops were conducted with the YAP to gather their impressions of the study results and inform conclusions. At the first time point, higher social support was associated with higher distress scores (β = 0.202, p < 0.001) and AYAs with higher depressive symptoms were more likely to see a mental health professional (p < 0.01). Over time, anxiety symptoms remained stable (p = 0.090); however, depressive symptoms improved (p < 0.001). The YAP highlighted the mixed effects of social support and the under-recognition and undertreatment of distress. This information identifies key targets, such as social support, that can inform the design of personalized screening and intervention tools. It also highlights specific timepoints at which these efforts can be directed to mitigate distress and improve quality of life. Future research should include longer-term follow-up, qualitative explorations of distress along the disease trajectory, and ongoing co-production efforts.

Effect of immunonutrition during concurrent chemoradiotherapy on acute oral mucositis in head and neck cancer patients: A prospective randomized study.

Immunonutrition (IN) supplements, designed to modulate immune system, may help reduce treatment-related toxicities. This study aimed to evaluate the efficacy of IN in reducing acute oral mucositis (OM) and other side effects in head and neck cancer patients undergoing concurrent chemoradiotherapy (CCRT). A multicenter, prospective, open-label randomized controlled study was conducted to assess the impact of IN on reducing OM and other side effects in head and neck cancer patients undergoing CCRT. Patients were randomized into either IN or control arms. Those in the IN arm received IN sachets starting one week before radiotherapy until treatment completion, while the control arm received no supplement. Treatment outcomes were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) version 5 and patient-reported outcomes via National Cancer Institute's Patient-Reported Outcomes of CTCAE (NCI-PRO-CTCAE). Mixed-effects logistic regression was performed to analyze outcomes between the groups, adjusting for chemotherapy regimens, while Chi-squared tests were used for group comparisons at specific timepoints. A total of 87 patients were analyzed with 46 in IN arm and 41 in control arm. Physician evaluations showed similar rates of grade 2 or higher OM, dermatitis, esophagitis, and hematologic toxicities across both arms. Patient-reported outcomes also showed no significant differences in the severity of oral mucositis or its interference with daily activities. A significant reduction of dermatitis was observed at week 3 in the IN arm (9.8% vs. 34.8%, p = 0.03), but this effect was not sustained in later weeks. IN supplementation during CCRT did not result in statistically significant reductions in acute oral mucositis and other radiation toxicities. Further research with larger sample sizes, compliance monitoring, and optimized supplementation protocols is warranted to better understand the potential benefits of IN.

Abstract A049: Application of a combinatorial functional precision medicine platform to predict immunotherapy response in DLBCL

Abstract PURPOSE: With expanding immunotherapy options available in many cancers, particularly diffuse large B-cell lymphoma (DLBCL), methods for identifying individualized and subtype-specific immunotherapy sensitivity are increasingly important. Evaluation of immunotherapy within ex vivo settings is challenging due to the complexity in conserving tumor heterogeneity and its surrounding tumor microenvironment (TME). We have developed a combinatorial functional precision medicine platform, Optim.AI, a hybrid experimental-analytics platform that predictively ranks all actionable treatments within a drug set of interest. In prior clinical studies, Optim.AI has been demonstrated to guide cytotoxic and targeted treatments in lymphomas, including DLBCL. However, these clinical studies did not interrogate immunotherapy responses. In this study, we explored the integration of high-content screening workflows with Optim.AI to evaluate immunotherapy-focused drug sets in physiologically relevant multicellular models of DLBCL. METHODS: PBMCs and DLBCL cells were fluorescently labelled to facilitate multicellular tracking for high-content analysis. Optim.AI combinatorial drug sensitivity testing plates were then used to evaluate DLBCL cells, co-cultured with PBMCS, with up to 12 FDA-approved chemotherapies, immunomodulatory agent, monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies. Utilizing real-time fluorescent apoptosis signal as the phenotypic readout, high-content analysis of tumor-specific cell death and apoptosis was evaluated at specific timepoints and used as the dataset of Optim.AI analytics and predictive ranking of combinatorial immunotherapy sensitivities in DLBCL cells. RESULTS: Optim.AI could confirm rituximab (CD20 mAb) sensitivity and optimal antibody-dependent cellular cytotoxicity (ADCC) lysis on CD20+ DLBCL cells at an Effector to Target ratio of 5:1 with a quantifiable phenotypic output at 48h post-treatment. Cytotoxicity studies performed across PBMCs from four different donors also showed negligible potential toxicity from drug candidates on immune cells, indicating that the platform can effectively and stably quantify ADCC. Furthermore, low ranking of tafasitamab (CD19 mAb) based combinations in a CD20+ cell line with low CD19 expression showed low target engagement with tafasitamab, confirming the platform’s ability to detect appropriate immunotherapy specificity. These findings collectively demonstrate the feasibility of pairing Optim.AI with an integrated co-culture model and image analysis pipeline to evaluate and rank immunotherapy-based combinations. CONCLUSIONS: We have demonstrated the integration of a high-content screening cancer-immune cell co-culture system with Optim.AI to evaluate immune-based combination therapies. Application of this approach towards ex vivo patient samples as well as appropriate cancer models will allow for guided immunotherapy-based treatment as well as identification of more effective cancer-specific and subtype-specific immunotherapy combinations. Citation Format: Sharon Pei Yi Chan, Jhin Jieh Lim, Masturah Rashid, Edward Kai-Hua Chow. Application of a combinatorial functional precision medicine platform to predict immunotherapy response in DLBCL [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A049.

Parenting Styles, Self Compassion and Unstable Relationships in University Students

Aim of the Study: This study sets to explore out the relationship between parenting styles, self-compassion, and unstable relationship in university students. Methodology: Data was collected by using a cross-sectional research design, which successfully catches a population at a particular point in time. By using the purposive sampling technique, data was collected from selected university students who met the specific criteria, and willing to provide relevant detail regarding parenting styles, self-compassion, and unstable relationships. By using cross-sectional research design and purposive sampling, the study enhanced the quality of the collected data. Findings: The study’s finding indicated the strong positive correlation between an authoritative parenting style and self-compassion. Other results showed the positive correlation between authoritarian parenting style and self-compassion. The connection between unstable relationships and authoritarian parenting was weakly positive. There was a weak positive association between self-compassion and permissive parenting. There was a weak positive association between unstable relationships and permissive parenting. Regression analysis results indicate that parenting practices were a significant predictor of unstable relationships and a significant positive predictor of self-compassion. Findings suggest a positive relationship between parenting styles, self-compassion, and relationships in university students. Conclusion: Study concluded that authoritative parenting style was positively associated with self-compassion in university students. University students' self-compassion, authoritarian, permissive parenting, and unstable relationship were not negative correlate. It was found that parenting styles positively predict unstable relationships; they also positively predict self-compassion.

"Are you ready?" A longitudinal interpretative phenomenological analysis of couples' experiences with breast reconstruction decision-making.

In this study, we aimed to explore women's and their male partners' experiences with breast reconstruction (BR) decision and to study the evolution of their experiences since undergoing mastectomy to one year after. Unstructured individual interviews with four couples facing mastectomy for breast cancer and BR decision-making were conducted following mastectomy (T1) and one year after mastectomy (T2). Longitudinal interpretative phenomenological analysis (LIPA) was conducted on the data. A total of 16 interviews were conducted, revealing seven group experiential themes: six applicable across time and one related to a specific timepoint. The results highlight two critical aspects: the ambivalence surrounding BR and the perceived importance of moving forward. Women and their partners expressed mixed feelings about BR, weighing the potential for improved quality of life and body image against fears of surgery and medical complications. The decision to undergo BR evolved over time, influenced by experiences related to body acceptance, aesthetic considerations, practical concerns, and societal norms for femininity. Partners played a significant role in the decision-making process, offering emotional support and influencing the decision both directly and indirectly. Moreover, the interpretative accounts underline how couples may see BR as a strategy for repairing both physical and psychological damage. Our findings emphasize the importance of understanding BR not only as a medical procedure but also as a deeply psychosocial process shaped by individual and relational factors. Furthermore, we provide reflections on the use of LIPA since it is a rarely used method.

Breast cancer risk assessment tool: Observations from an Indian cohort

Abstract Introduction: Breast cancer is now the most common cancer in Indian women and a major health problem. It is multifactorial in causation and the risk is dynamic and changeable over time. A risk assessment tool helps to evaluate an individual’s risk at a particular point in time. The Gail model, available as an online risk calculator, is the most widely used and studied tool for the risk assessment of nonhereditary breast cancer. However, the Gail model was developed for the American population and its applicability and accuracy for the Indian population are not definitely known. Since race is an important risk determinant and it could change with migration of different ethnic groups to different geographical and socio-cultural environments. This observational study highlights the findings regarding Gail model for breast cancer risk in an urban cohort of Indian women. Materials and Methods: Prospectively collected data of women attending the preventive health check-up department of western India were analyzed retrospectively. The online breast cancer risk assessment tool was used to calculate the immediate 5-year risk, lifetime risk, and relative risk (RR) of each individual. Individual risk factors of age at menarche and age at first child were analyzed additionally using the same data set to know their relevance in the Indian setting. Results: The online risk calculator performs more accurately when the resident Indian women are categorized as “Asian American” in the tool even rather than as “unknown” which could be used since they are not resident Americans; categorizing them of “unknown” race doubles the risk score generally. An early menarche and later age of over 30 years at first childbirth remain determinants of higher risk for breast cancer in Indian women. A significantly high risk, defined as RR of more than 1.61 was found in only about 6% in this cohort. Conclusion: In the absence of an algorithm, especially developed for resident Indian women, the online breast cancer risk calculator based on the Gail model was more suitable for risk assessment with race chosen and entered as “Asian American” in the model.

Children with autistic spectrum disorder can imagine actions- what can this reveal about the Broken Mirror Hypothesis?

This study investigated whether children with Autistic Spectrum Disorder (ASD) can imagine object directed actions similarly to their typically developed (TD) peers. We tested the ability to imagine goal directed actions in children with ASD (n = 18) and TD (n = 18) peers by means of VMIQ-2 questionnaire and a novel behavioral task, in which children were requested to imagine some daily actions, after seeing them through videoclips presented on a computer screen. Observed actions lasted 4 s and children were requested to follow the same time course during imagination. During this motor imagery (MI) task, children were interrupted at a specific timepoint (e.g., at 1.5 s) from the beginning of the task. Afterwards, they had to select one of two frames extracted from the videoclips: one showed the correct timepoint at which the imagined action was stopped, the other depicted an earlier or later timepoint. Children had to press the key associated to the correct frame to provide their responses. Both groups performed similarly in the questionnaire and in the novel MI task, where they showed the same error rate. Errors distribution suggests that all children exploited a similar strategy to solve the task, being errors mainly distributed in judging the later frame. These findings support the view that children with ASD can imagine actions similarly to their TD peers. These results do not fully support the Broken Mirror Hypothesis and may encourage the use of MI as a cognitive strategy in the rehabilitation of autism.

Optimal Timing for Intraocular Pressure Measurement Following Femtosecond Laser-Assisted Cataract Surgery: A Systematic Review and Meta-Analysis.

Femtosecond laser-assisted cataract surgery (FLACS) has increasingly been adopted worldwide. Lagging behind is evidence-based consensus regarding optimal timing for intraocular pressure (IOP) measurement following FLACS. The purpose of this study was to determine if enough evidence currently exists to guide best practice. A comprehensive literature search was performed on MEDLINE and EMBASE until February 6th, 2023. Articles reporting IOP measurements following uncomplicated FLACS were screened. For change in IOP at various post-operative timepoints, standardized mean difference (SMD) was calculated as the mean difference in IOP from baseline. Risk of Bias Assessment was conducted following data extraction. The meta-analysis incorporated six randomized clinical studies involving a total of 1356 eyes from 1032 participants. Post-operative day one was the only timepoint with a non-significant increase in IOP (SMD = -0.08 [95% CI: -0.41 to +0.24]) compared to the 7-days, 30-days, 60 to 90-days, and 180-days follow-up periods. All studies except one utilized an ophthalmic viscosurgical device (OVD) in their procedure; this was the only publication that reported a decrease in IOP from baseline within the 1-day follow-up period. The results suggest that the optimal time to measure IOP is within the first 24hours after FLACS. However, these findings are limited by a small study sample. Future prospective clinical trials may be beneficial to determine if specific timepoints within the first 24hours exist to optimize outcomes and patient reported experiences.

Residential Load Forecasting Based on Long Short-Term Memory, Considering Temporal Local Attention

Accurate residential load forecasting is crucial for the stable operation of the energy internet, which plays a significant role in advancing sustainable development. As the construction of the energy internet progresses, the proportion of residential electricity consumption in end-use energy consumption is increasing, the peak load on the grid is growing year on year, and seasonal and regional peak power supply tensions, mainly for household electricity consumption, grow into common problems across countries. Residential load forecasting can assist utility companies in determining effective electricity pricing structures and demand response operations, thereby improving renewable energy utilization efficiency and reducing the share of thermal power generation. However, due to the randomness and uncertainty of user load data, forecasting residential load remains challenging. According to prior research, the accuracy of residential load forecasting using machine learning and deep learning methods still has room for improvement. This paper proposes an improved load-forecasting model based on a time-localized attention (TLA) mechanism integrated with LSTM, named TLA-LSTM. The model is composed of a full-text regression network, a date-attention network, and a time-point attention network. The full-text regression network consists of a traditional LSTM, while the date-attention and time-point attention networks are based on a local attention model constructed with CNN and LSTM. Experimental results on real-world datasets show that compared to standard LSTM models, the proposed method improves R2 by 14.2%, reduces MSE by 15.2%, and decreases RMSE by 8.5%. These enhancements demonstrate the robustness and efficiency of the TLA-LSTM model in load forecasting tasks, effectively addressing the limitations of traditional LSTM models in focusing on specific dates and time-points in user load data.

Therapeutic Drug Monitoring of Antimicrobial Drugs in Children with Cancer: A New Tool for Personalized Medicine.

The risk of fungal, bacterial, and viral infections is higher in children with hematological and solid malignancies, particularly during periods of profound neutropenia. Although early administration of antimicrobial agents is common, optimizing pharmacological therapy in pediatric patients with cancer is challenging because of their variable pharmacokinetics compared with adults, including differences in body mass and augmented renal clearance, as well as chemotherapy-induced organ toxicity. Therapeutic drug monitoring, which involves measuring drug concentrations in serum or plasma at specific timepoints and adjusting doses accordingly, can be applied to various medications. While standardized targets for all antimicrobial agents in children are lacking, therapeutic drug monitoring appears to be beneficial in preventing serious toxicity and addressing treatment failure or non-compliance. This narrative review aims to analyze current perspectives on therapeutic drug monitoring for antimicrobial drugs in the special population of children with hematological or oncological diseases, including those undergoing hematopoietic cell transplantation. The review provides evidence on the clinical benefits of this method and explores potential future developments in this area.

Spatial Transcriptomics Reveals the Temporal Architecture of the Seminiferous Epithelial Cycle and Precise Sertoli-Germ Synchronization.

Spermatogenesis is characterized by the seminiferous epithelial cycle, a periodic pattern of germ cell differentiation with a wave-like progression along the length of seminiferous tubules. While key signaling and metabolic components of the cycle are known, the transcriptional changes across the cycle and the correlations between germ cell and somatic lineages remain undefined. Here, we use spatial transcriptomics via RNA SeqFISH+ to profile 2,638 genes in 216,090 cells in mouse testis and identify a periodic transcriptional pattern across tubules that precisely recapitulates the seminiferous epithelial cycle, enabling us to map cells to specific timepoints along the developmental cycle. Analyzing gene expression in somatic cells reveals that Sertoli cells exhibit a cyclic transcriptional profile closely synchronized with germ cell development while other somatic cells do not demonstrate such synchronization. Remarkably, in mouse testis with drug-induced ablation of germ cells, Sertoli cells independently maintain their cyclic transcriptional dynamics. By analyzing expression data, we identify an innate retinoic acid cycle, a network of transcription factors with cyclic activation, and signaling from germ cells that could interact with this network. Together, this work leverages spatial geometries for mapping the temporal dynamics and reveals a regulatory mechanism in spermatogenesis where Sertoli cells oscillate and coordinate with the cyclical progression of germ cell development.

Association between autonomic dysfunction, 12-year mortality and 10-year incident cardiovascular disease

Abstract Background Standing from a supine position requires a co-ordinated response in peripheral and central haemodynamic signals to protect the brain and body from sudden drops in blood pressure (BP) and has previously been shown to be an important measure of neuro-cardiovascular health (1-3). Previous studies have found an association between BP and heart rate recovery (HRR) to standing with all-cause mortality, cardiovascular disease and other health outcomes (4-8). However, almost all of these studies have exclusively investigated the association of consensus-defined HR/BP phenotypes measured at specific timepoints during standing. Purpose We hypothesised that assessing information from the entire haemodynamic response to orthostasis - instead of discrete timepoints or consensus definitions - may uncover novel associations between BP/HR responses to active stand and neuro-cardiovascular health in older adults. This may afford better physiological understanding of the longitudinal relationships between the response to standing and both Cardiovascular Disease (CVD) and mortality. Methods We used functional Principal Components Analysis (FPCA) to examine the determinants of variability in the complete haemodynamic response to active stand and examine which components were related to mortality and incident CVD in &amp;gt;4500 community-dwelling adults aged 50+. Results Figure 1 shows the mean response curve according to mortality status and Figure 2 the mean curve for participants free of CVD at baseline who later have CVD vs those who remain CVD-free during 10 year follow-up. All-cause mortality was associated with functional principal components which discriminate higher baseline HR, blunted HR peak and impaired HRR up to ~25 seconds after standing. Components that discriminated high baseline and impaired recovery of SBP from the post-stand nadir to 60 seconds post stand were also associated with all-cause mortality. This association remained even after covariate adjustment. Interestingly, neither baseline SBP nor orthostatic hypotension (OH) were associated with mortality. Components which discriminate high baseline and blunted HR peak; elevated stroke volume index and impaired recovery of DBP from ~25 seconds post stand were associated with 10-year incident CVD. Conclusions To our knowledge this is the first study to incorporate data driven information over the entire trace of the haemodynamic response to standing to investigate associations with incident CVD and mortality. The fact that components which discriminated high BP and impaired recovery of BP were associated with 12-year mortality and 10-year incident CVD when traditional summary measures of OH and baseline BP were not; suggests that incorporating information across the entire response to standing allows for richer and more flexible associations with health outcomes to be uncovered and allows for a better understanding of the underlying physiology leading to such associations.Figure 1:Mean trace of Mortality StatusFigure 2:Mean Trace of CVD Status