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ical activity had 30% slower decline (β, -0.031; 95% CI, -0.048 to -0.014) than did those who participated in low physical activity (β, -0.046; 95% CI, -0.066 to -0.025).

The findings suggest that physical activity is associated with diminished cognitive decline among older adults with increased serum NfL concentrations. The results support the potential use of blood biomarkers in measuring the benefits of health behaviors, such as physical activity, and early intervention for older adults at risk for cognitive decline.

The findings suggest that physical activity is associated with diminished cognitive decline among older adults with increased serum NfL concentrations. The results support the potential use of blood biomarkers in measuring the benefits of health behaviors, such as physical activity, and early intervention for older adults at risk for cognitive decline.

The Centers for Medicare & Medicaid Services requires health care organizations to report the National Clinical Trial (NCT) identifier on claims for items and services related to clinical trials that qualify for coverage. This same NCT identifier is used to identify clinical trials in the ClinicalTrials.gov registry. If linked, this information could facilitate population-based analyses of clinical trial participation and outcomes.

To evaluate the validity of a linkage between fee-for-service (FFS) Medicare claims and ClinicalTrials.gov through the NCT identifier for patients with cancer enrolled in clinical trials.

This cohort study included 2 complementary retrospective analyses for a validation assessment. First, billing data from 3 health care institutions were used to estimate the missingness of the NCT identifier in claims by calculating the proportion of known participants in cancer clinical trials with no NCT identifier on any submitted Medicare claims. Second, the Surveillance Epidemiology th cancer on a population level. The presence of the NCT identifiers in claims for Medicare patients participating in clinical trials is likely to improve over time with increasing adherence with the Centers for Medicare & Medicaid Services mandate.Solid tumors possess heterogeneous metabolic microenvironments where oxygen and nutrient availability are plentiful (fertile regions) or scarce (arid regions). While cancer cells residing in fertile regions proliferate rapidly, most cancer cells in vivo reside in arid regions and exhibit a slow-cycling state that renders them chemoresistant. Here, we developed an in vitro system enabling systematic comparison between these populations via transcriptome analysis, metabolomic profiling, and whole-genome CRISPR screening. Metabolic deprivation led to pronounced transcriptional and metabolic reprogramming, resulting in decreased anabolic activities and distinct vulnerabilities. Reductions in anabolic, energy-consuming activities, particularly cell proliferation, were not simply byproducts of the metabolic challenge, but rather essential adaptations. Mechanistically, Bcl-xL played a central role in the adaptation to nutrient and oxygen deprivation. In this setting, Bcl-xL protected quiescent cells from the lethal effects of cell-cycle entry in the absence of adequate nutrients. Moreover, inhibition of Bcl-xL combined with traditional chemotherapy had a synergistic antitumor effect that targeted cycling cells. Bcl-xL expression was strongly associated with poor patient survival despite being confined to the slow-cycling fraction of human pancreatic cancer cells. These findings provide a rationale for combining traditional cancer therapies that target rapidly cycling cells with those that target quiescent, chemoresistant cells associated with nutrient and oxygen deprivation.

The majority of pancreatic cancer cells inhabit nutrient- and oxygen-poor tumor regions and require Bcl-xL for their survival, providing a compelling antitumor metabolic strategy.

The majority of pancreatic cancer cells inhabit nutrient- and oxygen-poor tumor regions and require Bcl-xL for their survival, providing a compelling antitumor metabolic strategy.In this issue of JEM, Diny et al. (2022. J. Selleck EN460 Exp. Med.https//doi.org/10.1084/jem.20210970) identify the aryl hydrocarbon receptor (AHR) as a key orchestrator of eosinophil tissue adaptation in the small intestine, controlling their lifespan, degranulation, and tissue-remodeling activities.Hematopoietic differentiation is controlled by both genetic and epigenetic regulators. Long noncoding RNAs (lncRNAs) have been demonstrated to be important for normal hematopoiesis, but their function in erythropoiesis needs to be further explored. We profiled the transcriptomes of 16 murine hematopoietic cell populations by deep RNA sequencing and identified a novel lncRNA, Gm15915, that was highly expressed in erythroid-related progenitors and erythrocytes. For this reason, we named it lncEry. We also identified a novel lncEry isoform, which was the principal transcript that has not been reported before. lncEry depletion impaired erythropoiesis, indicating the important role of the lncRNA in regulating erythroid differentiation and maturation. Mechanistically, we found that lncEry interacted with WD repeat-containing protein 82 (WDR82) to promote the transcription of Klf1 and globin genes and thus control the early and late stages of erythropoiesis, respectively. These findings identified lncEry as an important player in the transcriptional regulation of erythropoiesis.

Neonatal hypoglycemia is associated with increased risk of poor executive and visual-motor function, but implications for later learning are uncertain.

To test the hypothesis that neonatal hypoglycemia is associated with educational performance at age 9 to 10 years.

Prospective cohort study of moderate to late preterm and term infants born at risk of hypoglycemia. Blood and masked interstitial sensor glucose concentrations were measured for up to 7 days. Infants with hypoglycemic episodes (blood glucose concentration <47 mg/dL [2.6 mmol/L]) were treated to maintain a blood glucose concentration of at least 47 mg/dL. Six hundred fourteen infants were recruited at Waikato Hospital, Hamilton, New Zealand, in 2006-2010; 480 were assessed at age 9 to 10 years in 2016-2020.

Hypoglycemia was defined as at least 1 hypoglycemic event, representing the sum of nonconcurrent hypoglycemic and interstitial episodes (sensor glucose concentration <47 mg/dL for ≥10 minutes) more than 20 minutes apart.

The primsk, 0.72 [95% CI, 0.53-0.99; P = .04]). Groups were not significantly different for other secondary end points.

Among participants at risk of neonatal hypoglycemia who were screened and treated if needed, exposure to neonatal hypoglycemia compared with no such exposure was not significantly associated with lower educational achievement in mid-childhood.

Among participants at risk of neonatal hypoglycemia who were screened and treated if needed, exposure to neonatal hypoglycemia compared with no such exposure was not significantly associated with lower educational achievement in mid-childhood.

Prophylactic oral dextrose gel reduces neonatal hypoglycemia, but later benefits or harms remain unclear.

To assess the effects on later development of prophylactic dextrose gel for infants born at risk of neonatal hypoglycemia.

Prospective follow-up of a multicenter randomized clinical trial conducted in 18 Australian and New Zealand hospitals from January 2015 to May 2019. Participants were late preterm or term at-risk infants; those randomized in 9 New Zealand centers (n = 1359) were included and followed up between January 2017 and July 2021.

Infants were randomized to prophylactic 40% dextrose (n = 681) or placebo (n = 678) gel, 0.5 mL/kg, massaged into the buccal mucosa 1 hour after birth.

The primary outcome of this follow-up study was neurosensory impairment at 2 years' corrected age. There were 44 secondary outcomes, including cognitive, language, and motor composite Bayley-III scores (mean [SD], 100 [15]; higher scores indicate better performance).

Of eligible infants, 1197 (91%) were as the other 27 secondary outcomes.

Among late preterm and term infants born at risk of neonatal hypoglycemia, prophylactic oral 40% dextrose gel at 1 hour of age, compared with placebo, resulted in no significant difference in the risk of neurosensory impairment at 2 years' corrected age. However, the study may have been underpowered to detect a small but potentially clinically important increase in risk, and further research including longer-term follow-up is required.

anzctr.org.au Identifier ACTRN12614001263684.

anzctr.org.au Identifier ACTRN12614001263684.

Atrial myopathy-characterized by alterations in left atrial (LA) function and size-is associated with ischemic stroke, independent of atrial fibrillation (AF). Electrocardiographic markers of atrial myopathy are associated with dementia, but it is unclear whether 2-dimensional echocardiographic (2DE)-defined LA function and size are associated with dementia.

To examine the association of LA function and size with incident dementia.

The Atherosclerosis Risk in Communities (ARIC) study is a community-based prospective cohort. An exploratory, retrospective analysis was conducted. ARIC centers are located in Forsyth County, North Carolina; Jackson, Mississippi; Washington County, Maryland; and suburban Minneapolis, Minnesota. For this analysis, visit 5 (2011-2013) served as the baseline. Participants without prevalent AF and stroke and who had 2DEs in 2011-2013 were included and surveilled through December 31, 2019.

LA function (reservoir strain, conduit strain, contractile strain, emptying fraction, pass function may be a risk factor associated with dementia.

In this exploratory analysis of a US community-based cohort, several echocardiographic measures of lower LA function were significantly associated with an increased risk of subsequent dementia. Measures of LA size were not significantly associated with dementia risk. These findings suggest that impaired LA function may be a risk factor associated with dementia.The US Preventive Services Task Force (USPSTF) works to improve the health of people nationwide by making evidence-based recommendations for preventive services. Patient-centered care is a core value in US health care. Shared decision-making (SDM), in which patients and clinicians make health decisions together, ensures patients' rights to be informed and involved in preventive care decisions and that these decisions are patient-centered. SDM has a role across the spectrum of USPSTF recommendations. For A or B recommendations (judged by the USPSTF to have high or moderate certainty of a moderate or substantial net benefit at the population level), SDM allows individual patients to decide whether to accept such services based on their personal values and preferences. For C recommendations (indicating at least moderate certainty of a small net benefit at the population level), SDM is critical for individual patients to decide whether the net benefit for them is worthwhile. For D recommendations (reflecting at least moderate certainty of a zero or negative net benefit) or I statements (low certainty of net benefit), clinicians should be prepared to discuss these services if patients ask. More evidence is needed to determine if, in addition to promoting patient-centeredness, SDM reduces inequities in preventive care, as well as to define new strategies to find time for discussion of preventive services in primary care.