An integrated framework for the study of exercise across the postdiagnosis cancer continuum.

Exercise plays many important roles across the entire cancer continuum that have been described in previous frameworks. These frameworks, however, have generally provided a simplified description of the roles of exercise postdiagnosis. The modern cancer treatment landscape has become complex and often consists of multiple lines of multimodal treatments combined concurrently and/or sequentially and delivered over many months or years. This complexity requires a more multifaceted and targeted approach to the study of exercise after a cancer diagnosis. Here, we propose a new integrated framework-Exercise Across the Postdiagnosis Cancer Continuum (EPiCC)-that highlights the distinct roles of exercise for disease treatment and supportive care from diagnosis until death. We also propose new terminology to clarify the distinct roles of exercise that emerge in the context of the modern cancer treatment landscape. The EPiCC Framework is structured around multiple sequential cancer treatments that highlight six distinct cancer treatment-related time periods for exercise-before treatments, during treatments, between treatments, immediately after successful treatments, during longer term survivorship after successful treatments, and during end of life after unsuccessful treatments. The EPiCC Framework proposes that the specific roles of exercise as a disease treatment and supportive care intervention will vary depending on its positioning within different cancer treatment combinations. As a cancer treatment, exercise may serve as a "priming therapy", primary therapy, neoadjuvant therapy, induction therapy, "bridging therapy", adjuvant therapy, consolidation therapy, maintenance therapy, and/or salvage therapy. As a supportive care intervention, exercise may serve as prehabilitation, intrahabilitation, interhabilitation, rehabilitation, "perihabilitation", health promotion/disease prevention, and/or palliation. To date, exercise has been studied during all of the cancer treatment-related time periods but only in relation to some cancer treatments and combinations. Moreover, fewer studies have examined exercise across multiple cancer treatment-related time periods within any cancer treatment combination. Future research is needed to study exercise as a disease treatment and supportive care intervention within and across the distinct cancer treatment-related time periods contained within different cancer treatment combinations. The aim of the EPiCC Framework is to stimulate a more targeted, integrated, and clinically-informed approach to the study of exercise after a cancer diagnosis.

Outcomes associated with Healthcare-associated Respiratory Syncytial Virus in Children's Hospitals.

To determine if healthcare-associated (HA)-RSV is associated with worse outcomes, this multicenter cohort study studied 26 children with HA-RSV and 78 matched non-HA-RSV patients of whom 58% and 55%, respectively, had >2 comorbidities. Overall, 39% of HA-RSV versus 18% of non-HA-RSV patients required respiratory support escalation (aOR 5.1, CI95 1.4,19.1).

Continuity of care during severe civil unrest with a model of community-based HIV care: a retrospective cohort study from Haiti.

Background: There are limited data on the effectiveness of differentiated service delivery (DSD) for HIV care during sociopolitical turmoil. We assessed outcomes with a DSD model of care that includes patient choice between community-based antiretroviral therapy (ART) centres, home-based ART dispensing, or facility-based care at GHESKIO clinic during a period of severe civil unrest in Port-au-Prince, Haiti. Methods: This retrospective analysis included data on patients with at least one HIV visit at GHESKIO between May 1, 2019, and December 31, 2021. Multivariable logistic regression models were used to assess predictors of attending ≥1 community visit during the study period, and failure to attend timely visits. HIV-1 RNA test results were reported among patients who had been ART for ≥3 months at last visit. Findings: Of the 18,625 patients included in the analysis, 9659 (51.9%) attended at least one community visit. The proportion of community visits ranged from 0.3% (2019) to 44.1% (2021). Predictors of ≥1 community visit included male sex (aOR: 1.13; 95% CI: 1.06, 1.20), secondary education (aOR: 1.07; 95% CI: 1.01, 1.14), income > $USD 1.00/day (aOR: 1.24; 95% CI: 1.14, 1.35), longer duration on ART (aOR: 1.08 per additional year; 95% CI: 1.07, 1.09), and residence in Carrefour/Gressier (p < 0.0001 in comparisons with all other zones). Younger age and shorter time on ART were associated with late visits and loss to follow-up. Among 12,586 patients with an on-time final visit who had been on ART for ≥3 months, 11,131 (88.4%) received a viral load test and 9639 (86.6%) had HIV-1 RNA < 1000 copies/mL. Interpretation: The socio-political situation in Haiti has presented extraordinary challenges to the health care system, but retention and viral suppression rates remain high with a model of community-based HIV care. Additional interventions are needed to improve outcomes for younger patients, and those with shorter time on ART. Funding: No funding.

ALDH1A3 is the switch that determines the balance of ALDH+ and CD24-CD44+ cancer stem cells, EMT-MET, and glucose metabolism in breast cancer.

Plasticity is an inherent feature of cancer stem cells (CSCs) and regulates the balance of key processes required at different stages of breast cancer progression, including epithelial-to-mesenchymal transition (EMT) versus mesenchymal-to-epithelial transition (MET), and glycolysis versus oxidative phosphorylation. Understanding the key factors that regulate the switch between these processes could lead to novel therapeutic strategies that limit tumor progression. We found that aldehyde dehydrogenase 1A3 (ALDH1A3) regulates these cancer-promoting processes and the abundance of the two distinct breast CSC populations defined by high ALDH activity and CD24-CD44+ cell surface expression. While ALDH1A3 increases ALDH+ breast cancer cells, it inversely suppresses the CD24-CD44+ population by retinoic acid signaling-mediated gene expression changes. This switch in CSC populations induced by ALDH1A3 was paired with decreased migration but increased invasion and an intermediate EMT phenotype. We also demonstrate that ALDH1A3 increases oxidative phosphorylation and decreases glycolysis and reactive oxygen species (ROS). The effects of ALDH1A3 reduction were countered with the glycolysis inhibitor 2-deoxy-D-glucose (2DG). In cell culture and tumor xenograft models, 2DG suppresses the increase in the CD24-CD44+ population and ROS induced by ALDH1A3 knockdown. Combined inhibition of ALDH1A3 and glycolysis best reduces breast tumor growth and tumor-initiating cells, suggesting that the combination of targeting ALDH1A3 and glycolysis has therapeutic potential for limiting CSCs and tumor progression. Together, these findings identify ALDH1A3 as a key regulator of processes required for breast cancer progression and depletion of ALDH1A3 makes breast cancer cells more susceptible to glycolysis inhibition.

Using Dual-Coil TMS-EEG to Probe Bilateral Brain Mechanisms in Healthy Aging and Mild Cognitive Impairment.

Background: A widespread observation in the cognitive neuroscience of aging is that older adults show a more bilateral pattern of task-related brain activation. These observations are based on inherently correlational approaches. The current study represents a targeted assessment of the role of bilaterality using repetitive transcranial magnetic stimulation (rTMS). Objective: We used a novel bilateral TMS-stimulation paradigm, applied to a group of healthy older adults (hOA) and older adults with mild cognitive impairment (MCI), with two aims: First, to elucidate the neurophysiological effects of bilateral neuromodulation, and second to provide insight into the neurophysiological basis of bilateral brain interactions. Methods: Electroencephalography (EEG) was recorded while participants received six forms of transcranial magnetic stimulation (TMS): unilateral and bilateral rTMS trains at an alpha (8 Hz) and beta (18 Hz) frequency, as well as two sham conditions (unilateral, bilateral) mimicking the sounds of TMS. Results: First, time-frequency analyses of oscillatory power induced by TMS revealed that unilateral beta rTMS elicited rhythmic entrainment of cortical oscillations at the same beta-band frequency. Second, both bilateral alpha and bilateral beta stimulation induced a widespread reduction of alpha power. Lastly, healthy older adults showed greater TMS-related reductions in alpha power in response to bilateral rTMS compared to the MCI cohort. Conclusion: Overall, these results demonstrate frequency-specific responses to bilateral rTMS in the aging brain, and provide support for inhibitory models of hemispheric interaction across multiple frequency bands.

Encoding spatiotemporal asymmetry in artificial cilia with a ctenophore-inspired soft-robotic platform.

A remarkable variety of organisms use metachronal coordination (i.e. numerous neighboring appendages beating sequentially with a fixed phase lag) to swim or pump fluid. This coordination strategy is used by microorganisms to break symmetry at small scales where viscous effects dominate and flow is time-reversible. Some larger organisms use this swimming strategy at intermediate scales, where viscosity and inertia both play important roles. However, the role of individual propulsor kinematics-especially across hydrodynamic scales-is not well-understood, though the details of propulsor motion can be crucial for the efficient generation of flow. To investigate this behavior, we developed a new soft robotic platform using magnetoactive silicone elastomers to mimic the metachronally coordinated propulsors found in swimming organisms. Furthermore, we present a method to passively encode spatially asymmetric beating patterns in our artificial propulsors. We investigated the kinematics and hydrodynamics of three propulsor types, with varying degrees of asymmetry, using Particle Image Velocimetry and high-speed videography. We find that asymmetric beating patterns can move considerably more fluid relative to symmetric beating at the same frequency and phase lag, and that asymmetry can be passively encoded into propulsors via the interplay between elastic and magnetic torques. Our results demonstrate that nuanced differences in propulsor kinematics can substantially impact fluid pumping performance. Our soft robotic platform also provides an avenue to explore metachronal coordination at the meso-scale, which in turn can inform the design of future bioinspired pumping devices and swimming robots.

Plasma Circulating HPV DNA Surveillance in a Patient With Nasopharyngeal Cancer.

Nearly one third of nasopharyngeal carcinomas (NPCs) in the United States are associated with human papillomavirus (HPV). Surveillance for Epstein-Barr virus (EBV)-negative subtypes is customarily based solely on imaging and physical examinations. We present a case of HPV-positive NPC using serial circulating tumor HPV DNA (ctHPVDNA) as a biomarker of disease status. A 58-year-old Caucasian female initially presented with T1N1M0 EBV-negative p16-positive squamous cell carcinoma of the nasopharynx and was treated with concurrent chemoradiation. Regional nodal recurrence identified 7 months post-radiotherapy was treated with salvage left neck dissection. Surveillance was supplemented using a commercially available polymerase chain reaction (PCR)-based ctHPVDNA assay. Rising ctHPVDNA levels at 9 and 10 months post salvage surgery prompted positron emission tomography (PET). Biopsy confirmed recurrence in avid right hilar and paraoesophageal lymph nodes. Following definitive radiotherapy to the involved nodes and concurrent pembrolizumab, posttreatment ctHPVDNA decreased to baseline, but then increased after 6 cycles of pembrolizumab. Follow-up PET found left mediastinal recurrence outside of the prior treatment field, which was treated with concurrent chemoradiation with cetuximab. Again, ctHPVDNA level dropped to baseline but increased 3 months postradiation. PET scan showed a left lung nodule, and the patient received systemic therapy. Plasma ctHPVDNA monitoring correlated well with disease activity in our patient with HPV-positive NPC. ctHPVDNA detected disease earlier than standard surveillance methods and allowed for earlier intervention. Larger studies are needed to validate the utility of HPV biomarker surveillance in NPC.

Propulsive efficiency of spatiotemporally asymmetric oscillating appendages at intermediate Reynolds numbers.

Many organisms use flexible appendages for locomotion, feeding, and other functional behaviors. The efficacy of these behaviors is determined in large part by the fluid dynamics of the appendage interacting with its environment. For oscillating appendages at low Reynolds numbers, viscosity dominates over inertia, and appendage motion must be spatially asymmetric to generate net flow. At high Reynolds numbers, viscous forces are negligible and appendage motion is often also temporally asymmetric, with a fast power stroke and a slow recovery stroke; such temporal asymmetry does not affect the produced flow at low Reynolds numbers. At intermediate Reynolds numbers, both viscous and inertial forces play non-trivial roles---correspondingly, both spatial and temporal asymmetry can strongly affect overall propulsion. Here we perform experiments on three robotic paddles with different material flexibilities and geometries, allowing us to explore the effects of motion asymmetry (both spatial and temporal) on force production. We show how a flexible paddle's time-varying shape throughout the beat cycle can reorient the direction of the produced force, generating both thrust and lift. We also evaluate the propulsive performance of the paddle by introducing a new quantity, which we term "integrated efficiency". This new definition of propulsive efficiency can be used to directly evaluate an appendage's performance independently from full-body swimming dynamics. Use of the integrated efficiency allows for accurate performance assessment, generalization, and comparison of oscillating appendages in both robotic devices and behaving organisms. Finally, we show that a curved flexible paddle generates thrust more efficiently than a straight paddle, and produces spatially asymmetric motion---thereby improving performance---without the need for complex actuation and controls, opening new avenues for bioinspired technology development.

Horse Sector Participants' Attitudes towards Anthropomorphism and Animal Welfare and Wellbeing.

Anthropomorphizing can misinform the making of inferences about animal mental experiences. This is a consideration when implementing the Five Domains Model for animal welfare assessment. An online survey run in 2021 captured horse sector participants' perspectives about anthropomorphism and wellbeing in relation to horses. Most respondents, 82.9% (n = 431/520), believed that anthropomorphism could influence horse welfare and wellbeing. These respondents were then asked how, in their opinion, anthropomorphism might relate to horse welfare. A thematic analysis identified two themes: (1) 'Anthropomorphism can influence how people relate to horses' and (2) 'Anthropomorphism can have consequences for horse welfare and wellbeing'. The results suggested that experienced respondents were aware of the complexities surrounding anthropomorphic attitudes and that anthropomorphism can have beneficial and detrimental consequences on horse welfare and wellbeing. Benefits include a sense of relatedness to a horse, while detriments include the potential to misinterpret horse behaviors. The authors propose that anthropomorphism has a place in horse welfare and wellbeing when used critically and with caution. This study recommends that there is a need to actively manage anthropomorphism when organizations update policies and practices and implement the Five Domains Model. More research is required to understand the effects of anthropomorphism on horse-related practices.

Using Systems Engineering and Implementation Science to Design an Implementation Package for Preoperative Comprehensive Geriatric Assessment Among Older Adults Having Major Abdominal Surgery: Protocol for a 3-Phase Study.

BACKGROUND: Older Americans, a growing segment of the population, have an increasing need for surgical services, and they experience a disproportionate burden of postoperative complications compared to their younger counterparts. A preoperative comprehensive geriatric assessment (pCGA) is recommended to reduce risk and improve surgical care delivery for this population, which has been identified as vulnerable. The pCGA optimizes multiple chronic conditions and factors commonly overlooked in routine preoperative planning, including physical function, polypharmacy, nutrition, cognition, mental health, and social and environmental support. The pCGA has been shown to decrease postoperative morbidity, mortality, and length of stay in a variety of surgical specialties. Although national guidelines recommend the use of the pCGA, a paucity of strategic guidance for implementation limits its uptake to a few academic medical centers. By applying implementation science and human factors engineering methods, this study will provide the necessary evidence to optimize the implementation of the pCGA in a variety of health care settings. OBJECTIVE: The purpose of this paper is to describe the study protocol to design an adaptable, user-centered pCGA implementation package for use among older adults before major abdominal surgery. METHODS: This protocol uses systems engineering methods to develop, tailor, and pilot-test a user-centered pCGA implementation package, which can be adapted to community-based hospitals in preparation for a multisite implementation trial. The protocol is based upon the National Institutes of Health Stage Model for Behavioral Intervention Development and aligns with the goal to develop behavioral interventions with an eye to real-world implementation. In phase 1, we will use observation and interviews to map the pCGA process and identify system-based barriers and facilitators to its use among older adults undergoing major abdominal surgery. In phase 2, we will apply user-centered design methods, engaging health care providers, patients, and caregivers to co-design a pCGA implementation package. This package will be applicable to a diverse population of older patients undergoing major abdominal surgery at a large academic hospital and an affiliate community site. In phase 3, we will pilot-test and refine the pCGA implementation package in preparation for a future randomized controlled implementation-effectiveness trial. We anticipate that this study will take approximately 60 months (April 2023-March 2028). RESULTS: This study protocol will generate (1) a detailed process map of the pCGA; (2) an adaptable, user-centered pCGA implementation package ready for feasibility testing in a pilot trial; and (3) preliminary pilot data on the implementation and effectiveness of the package. We anticipate that these data will serve as the basis for future multisite hybrid implementation-effectiveness clinical trials of the pCGA in older adults undergoing major abdominal surgery. CONCLUSIONS: The expected results of this study will contribute to improving perioperative care processes for older adults before major abdominal surgery. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59428.

Pubic Hair Removal Practices and Motivations Among a Nationally Representative Sample of U.S. Men.

Understanding current pubic hair removal (PHR) practices is vital for public health, given the prevalence among U.S. adults. This study updates the understanding of PHR practices, motivations, and correlates in a nationally representative sample of adult men. In April 2023, through a probability-based internet panel survey (Ipsos KnowledgePanel®), we found that nearly half (46.7%) of respondents reported lifetime PHR, with 29.2% reporting PHR in the past 30 days. Statistically significant differences were observed in sexual orientation, age, socioeconomic status, sexual activity, and social media use. A higher proportion of Gay and Bisexual men (GBM) reported lifetime PHR (76.5%) compared with heterosexual men (44.6%), with GBM having nearly 3 times greater odds of reporting lifetime PHR (OR = 2.891, 95%CI [1.2, 6.7]). Being sexually active in the past month statistically significantly predicted both lifetime PHR (OR = 1.884, 95%CI [1.2, 2.9]) and past 30-day PHR (OR = 2.849, 95%CI [1.8, 4.6]). Age also emerged as a significant predictor, as men aged 25 to 34 years (OR = 2.275, 95%CI [1.0, 5.0]) and 45 to 54 years (OR = 2.493, 95%CI [1.1, 5.6]) had higher odds of reporting lifetime PHR compared with those aged 18 to 24 years. This study provides valuable insights and updated national data on the prevalence, methods, and frequency of PHR among men in the United States. Given the correlations between PHR practices and factors such as sexual orientation, sexual activity, and age, these findings can equip educators and health care providers with data to foster better health outcomes through acknowledging and addressing the interplay between individual choices and broader social and cultural factors.

Implications of the 2022 lung function update and GLI global reference equations among patients with interstitial lung disease.

BACKGROUND: Lung function testing remains a cornerstone in the assessment and management of interstitial lung disease (ILD) patients. The clinical implications of the Global Lung function Initiative (GLI) reference equations and the updated interpretation strategies remain uncertain. METHODS: Adult patients with ILD with baseline forced vital capacity (FVC) were included from the Australasian ILD registry and the National Healthcare Group ILD registry, Singapore.The European Coal and Steel Community and Miller reference equations were compared with the GLI reference equations to assess (a) differences in lung function percent predicted values; (b) ILD risk prediction models and (c) eligibility for ILD clinical trial enrolment. RESULTS: Among 2219 patients with ILD, 1712 (77.2%) were white individuals. Idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD and unclassifiable ILD predominated.Median FVC was 2.60 (2.01-3.36) L, forced expiratory volume in 1 s was 2.09 (1.67-2.66) L and diffusing capacity of the lungs for carbon monoxide (DLCO) was 13.60 (10.16-17.60) mL/min/mm Hg. When applying the GLI reference equations, the mean FVC percentage predicted was 8.8% lower (87.7% vs 78.9%, p<0.01) while the mean DLCO percentage predicted was 4.9% higher (58.5% vs 63.4%, p<0.01). There was a decrease in 19 IPF and 119 non-IPF patients who qualified for the nintedanib clinical trials when the GLI reference equations were applied. Risk prediction models performed similarly in predicting mortality using both reference equations. CONCLUSION: Applying the GLI reference equations in patients with ILD leads to higher DLCO percentage predicted values and smaller lung volume percentage predicted values. While applying the GLI reference equations did not impact on prognostication, fewer patients met the clinical trial criteria for antifibrotic agents.

Telehealth in Home Visiting for New Mothers: Are Outcomes Different if the First Visits Are in Person?

Home visiting programs for new parents have a broad range of goals, including improvements in maternal and child health, reductions in child maltreatment, and improvements in child development. Before 2020, few home visits were conducted through phone or video encounters, i.e., telehealth home visiting (teleHV). However, rapid adoption of teleHV was required by the coronavirus disease 2019 (COVID-19) pandemic. To understand how conducting initial visits via teleHV was associated with outcomes, we performed a secondary data analysis to make use of the natural experiment created by COVID-19. Utilizing data from the Nurse-Family Partnership, a US national evidence-based model, we compared outcomes for families whose initial home visits were in person (enrolled 10/2019 to 1/2020; n = 7066) to those whose first visits were through teleHV (enrolled 4/2020 to 12/2020; n = 14,587). TeleHV at intake was associated with a higher likelihood of elevated depressive symptoms at 12 months (OR = 1.37; 95% CI 1.07, 1.76), a lower likelihood of retention to child's age 12 months (OR = 0.67; 95% CI 0.58, 0.78), a higher likelihood of early drop from the program (OR = 1.77; 95% CI 1.48, 2.12), and fewer screening assessments completed (b = - 0.06; 95% CI - 0.07, - 0.04). No differences were detected between groups for the likelihood of breastfeeding at child's age 6 months, elevated intimate partner violence (IPV) risk, 90% of attempted visits completed, or time to attrition. COVID-19 may have led families in different groups to have different experiences during key points of child development; however, as both groups' involvement in the program occurred primarily during the pandemic, they were both subject to comparable influences. These findings suggest that in-person visits have some advantages in the first months of program involvement.

Parental Reflective Capacities: A Scoping Review of Mindful Parenting and Parental Reflective Functioning.

Objectives: Two key parental reflective capacities-mindful parenting (MP) and parental reflective functioning (PRF) - have been shown to promote healthy parent-child relationships through parents' increased sensitivity and responsiveness to their children's needs in spite of parenting stressors. Despite the theoretical overlap between these two constructs, researchers have continued to examine them independently. Therefore, the purpose of this scoping review was to review the overlapping and distinctive outcomes and correlates in the empirical MP and PRF literatures. Method: A comprehensive literature search across the MP and PRF literature for studies published from 2005 through early 2020 (pre-COVID-19 pandemic) was conducted. Results: A review of 301 articles (n = 180 MP and n = 121 PRF) revealed overlapping study outcomes and correlates, including improvement in parent and child well-being, parenting behaviors, and attachment. Both MP and PRF literatures suggest MP and PRF are amenable to intervention-induced changes, although mostly documented in White mothers, which results may not be generalizable to diverse populations. Conclusions: Researchers should consider the impact MP and PRF have on positive family relationships. Results suggest that scholars should consider investigating and intervening on MP and PRF simultaneously. Specifically, results identified MP and PRF convergent associations and perhaps synergistic impacts on positive parenting behaviors. Limitations and future directions are discussed. Preregistration: This review was not preregistered.

Health workforce needs in Malawi: analysis of the Thanzi La Onse integrated epidemiological model of care.

BACKGROUND: To make the best use of health resources, it is crucial to understand the healthcare needs of a population-including how needs will evolve and respond to changing epidemiological context and patient behaviour-and how this compares to the capabilities to deliver healthcare with the existing workforce. Existing approaches to planning either rely on using observed healthcare demand from a fixed historical period or using models to estimate healthcare needs within a narrow domain (e.g., a specific disease area or health programme). A new data-grounded modelling method is proposed by which healthcare needs and the capabilities of the healthcare workforce can be compared and analysed under a range of scenarios: in particular, when there is much greater propensity for healthcare seeking. METHODS: A model representation of the healthcare workforce, one that formalises how the time of the different cadres is drawn into the provision of units of healthcare, was integrated with an individual-based epidemiological model-the Thanzi La Onse model-that represents mechanistically the development of disease and ill-health and patients' healthcare seeking behaviour. The model was applied in Malawi using routinely available data and the estimates of the volume of health service delivered were tested against officially recorded data. Model estimates of the "time needed" and "time available" for each cadre were compared under different assumptions for whether vacant (or established) posts are filled and healthcare seeking behaviour. RESULTS: The model estimates of volume of each type of service delivered were in good agreement with the available data. The "time needed" for the healthcare workforce greatly exceeded the "time available" (overall by 1.82-fold), especially for pharmacists (6.37-fold) and clinicians (2.83-fold). This discrepancy would be largely mitigated if all vacant posts were filled, but the large discrepancy would remain for pharmacists (2.49-fold). However, if all of those becoming ill did seek care immediately, the "time needed" would increase dramatically and exceed "time supply" (2.11-fold for nurses and midwives, 5.60-fold for clinicians, 9.98-fold for pharmacists) even when there were no vacant positions. CONCLUSIONS: The results suggest that services are being delivered in less time on average than they should be, or that healthcare workers are working more time than contracted, or a combination of the two. Moreover, the analysis shows that the healthcare system could become overwhelmed if patients were more likely to seek care. It is not yet known what the health consequences of such changes would be but this new model provides-for the first time-a means to examine such questions.

Cortico-hippocampal interactions underlie schema-supported memory encoding in older adults.

Although episodic memory is typically impaired in older adults (OAs) compared to young adults (YAs), this deficit is attenuated when OAs can leverage their rich semantic knowledge, such as their knowledge of schemas. Memory is better for items consistent with pre-existing schemas and this effect is larger in OAs. Neuroimaging studies have associated schema use with the ventromedial prefrontal cortex (vmPFC) and hippocampus (HPC), but most of this research has been limited to YAs. This fMRI study investigated the neural mechanisms underlying how schemas boost episodic memory in OAs. Participants encoded scene-object pairs with varying congruency, and memory for the objects was tested the following day. Congruency with schemas enhanced object memory for YAs and, more substantially, for OAs. FMRI analyses examined how cortical modulation of HPC predicted subsequent memory. Congruency-related vmPFC modulation of left HPC enhanced subsequent memory in both age groups, while congruency-related modulation from angular gyrus (AG) boosted subsequent memory only in OAs. Individual differences in cortico-hippocampal modulations indicated that OAs preferentially used their semantic knowledge to facilitate encoding via an AG-HPC interaction, suggesting a compensatory mechanism. Collectively, our findings illustrate age-related differences in how schemas influence episodic memory encoding via distinct routes of cortico-hippocampal interactions.

Utility of the 52-Gene Risk Score to Identify Patients with Idiopathic Pulmonary Fibrosis at Greater Risk of Mortality in the Era of Antifibrotic Therapy.

PURPOSE: We investigated whether a 52-gene signature was associated with transplant-free survival and other clinically meaningful outcomes in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry, which enrolled patients who were and were not taking antifibrotic therapy. METHODS: The 52-gene risk signature was implemented to classify patients as being at "high risk" or "low risk" of disease progression and mortality. Transplant-free survival and other outcomes were compared between patients with a low-risk versus high-risk signature. RESULTS: The 52-gene signature classified 159 patients as at low risk and 86 as at high risk; in these groups, respectively, 56.6% and 51.2% used antifibrotic therapy at enrollment. Among those taking antifibrotic therapy, patients with a low-risk versus high-risk signature were at decreased risk of death, a composite of lung transplant or death, and a composite of decline in DLco % predicted > 15%, lung transplant, or death. Similar results were observed in the overall cohort. CONCLUSIONS: These data suggest that the 52-gene signature can be used in patients with IPF treated with antifibrotic therapy to distinguish patients at higher risk of disease progression and mortality.