Larger cerebral cortex is genetically correlated with greater frontal area and dorsal thickness.

Human cortical expansion has occurred non-uniformly across the brain. We assessed the genetic architecture of cortical global expansion and regionalization by comparing two sets of genome-wide association studies of 24 cortical regions with and without adjustment for global measures (i.e., total surface area, mean cortical thickness) using a genetically informed parcellation in 32,488 adults. We found 393 and 756 significant loci with and without adjusting for globals, respectively, where 8% and 45% loci were associated with more than one region. Results from analyses without adjustment for globals recovered loci associated with global measures. Genetic factors that contribute to total surface area of the cortex particularly expand anterior/frontal regions, whereas those contributing to thicker cortex predominantly increase dorsal/frontal-parietal thickness. Interactome-based analyses revealed significant genetic overlap of global and dorsolateral prefrontal modules, enriched for neurodevelopmental and immune system pathways. Consideration of global measures is important in understanding the genetic variants underlying cortical morphology.

Effect of Phase Encoding Direction on Image Quality in Single-Shot EPI Diffusion-Weighted Imaging of the Breast.

BACKGROUND: In breast diffusion-weighted imaging (DWI), distortion and physiologic artifacts affect clinical interpretation. Image quality can be optimized by addressing the effect of phase encoding (PE) direction on these artifacts. PURPOSE: To compare distortion artifacts in breast DWI acquired with different PE directions and polarities, and to discuss their clinical implications. STUDY TYPE: Prospective. POPULATION: Eleven healthy volunteers (median age: 47 years old; range: 22-74 years old) and a breast phantom. FIELD STRENGTH/SEQUENCE: Single-shot echo planar DWI and three-dimensional fast gradient echo sequences at 3 T. ASSESSMENT: All DWI data were acquired with left-right, right-left, posterior-anterior, and anterior-posterior PE directions. In phantom data, displacement magnitude was evaluated by comparing the location of landmarks in anatomical and DWI images. Three breast radiologists (5, 17, and 23 years of experience) assessed the presence or absence of physiologic artifacts in volunteers' DWI datasets and indicated their PE-direction preference. STATISTICAL TESTS: Analysis of variance with post-hoc tests were used to assess differences in displacement magnitude across DWI datasets and observers. A binomial test and a chi-squared test were used to evaluate if each in vivo DWI dataset had an equal probability (25%) of being preferred by radiologists. Inter-reader agreement was evaluated using Gwet's AC1 agreement coefficient. A P-value <0.05 was considered statistically significant. RESULTS: In the phantom study, median displacement was the significantly largest in posterior-anterior data. While the displacement in the anterior-posterior and left-right data were equivalent (P = 0.545). In the in vivo data, there were no physiological artifacts observed in any dataset, regardless of PE direction. In the reader study, there was a significant preference for the posterior-anterior datasets which were selected 94% of the time. There was good agreement between readers (0.936). DATA CONCLUSION: This study showed the impact of PE direction on distortion artifacts in breast DWI. In healthy volunteers, the posterior-to-anterior PE direction was preferred by readers. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Using functional principal component analysis (FPCA) to quantify sitting patterns derived from wearable sensors.

BACKGROUND: Sedentary behavior (SB) is a recognized risk factor for many chronic diseases. ActiGraph and activPAL are two commonly used wearable accelerometers in SB research. The former measures body movement and the latter measures body posture. The goal of the current study is to quantify the pattern and variation of movement (by ActiGraph activity counts) during activPAL-identified sitting events, and examine associations between patterns and health-related outcomes, such as systolic and diastolic blood pressure (SBP and DBP). METHODS: The current study included 314 overweight postmenopausal women, who were instructed to wear an activPAL (at thigh) and ActiGraph (at waist) simultaneously for 24 hours a day for a week under free-living conditions. ActiGraph and activPAL data were processed to obtain minute-level time-series outputs. Multilevel functional principal component analysis (MFPCA) was applied to minute-level ActiGraph activity counts within activPAL-identified sitting bouts to investigate variation in movement while sitting across subjects and days. The multilevel approach accounted for the nesting of days within subjects. RESULTS: At least 90% of the overall variation of activity counts was explained by two subject-level principal components (PC) and six day-level PCs, hence dramatically reducing the dimensions from the original minute-level scale. The first subject-level PC captured patterns of fluctuation in movement during sitting, whereas the second subject-level PC delineated variation in movement during different lengths of sitting bouts: shorter (< 30 minutes), medium (30 -39 minutes) or longer (> 39 minute). The first subject-level PC scores showed positive association with DBP (standardized ß ^ : 2.041, standard error: 0.607, adjusted p = 0.007), which implied that lower activity counts (during sitting) were associated with higher DBP. CONCLUSION: In this work we implemented MFPCA to identify variation in movement patterns during sitting bouts, and showed that these patterns were associated with cardiovascular health. Unlike existing methods, MFPCA does not require pre-specified cut-points to define activity intensity, and thus offers a novel powerful statistical tool to elucidate variation in SB patterns and health. TRIAL REGISTRATION: ClinicalTrials.gov NCT03473145; Registered 22 March 2018; https://clinicaltrials.gov/ct2/show/NCT03473145 ; International Registered Report Identifier (IRRID): DERR1-10.2196/28684.

Structural connectome quantifies tumour invasion and predicts survival in glioblastoma patients.

Glioblastoma is characterized by diffuse infiltration into the surrounding tissue along white matter tracts. Identifying the invisible tumour invasion beyond focal lesion promises more effective treatment, which remains a significant challenge. It is increasingly accepted that glioblastoma could widely affect brain structure and function, and further lead to reorganization of neural connectivity. Quantifying neural connectivity in glioblastoma may provide a valuable tool for identifying tumour invasion. Here we propose an approach to systematically identify tumour invasion by quantifying the structural connectome in glioblastoma patients. We first recruit two independent prospective glioblastoma cohorts: the discovery cohort with 117 patients and validation cohort with 42 patients. Next, we use diffusion MRI of healthy subjects to construct tractography templates indicating white matter connection pathways between brain regions. Next, we construct fractional anisotropy skeletons from diffusion MRI using an improved voxel projection approach based on the tract-based spatial statistics, where the strengths of white matter connection and brain regions are estimated. To quantify the disrupted connectome, we calculate the deviation of the connectome strengths of patients from that of the age-matched healthy controls. We then categorize the disruption into regional disruptions on the basis of the relative location of connectome to focal lesions. We also characterize the topological properties of the patient connectome based on the graph theory. Finally, we investigate the clinical, cognitive and prognostic significance of connectome metrics using Pearson correlation test, mediation test and survival models. Our results show that the connectome disruptions in glioblastoma patients are widespread in the normal-appearing brain beyond focal lesions, associated with lower preoperative performance (P < 0.001), impaired cognitive function (P < 0.001) and worse survival (overall survival: hazard ratio = 1.46, P = 0.049; progression-free survival: hazard ratio = 1.49, P = 0.019). Additionally, these distant disruptions mediate the effect on topological alterations of the connectome (mediation effect: clustering coefficient -0.017, P < 0.001, characteristic path length 0.17, P = 0.008). Further, the preserved connectome in the normal-appearing brain demonstrates evidence of connectivity reorganization, where the increased neural connectivity is associated with better overall survival (log-rank P = 0.005). In conclusion, our connectome approach could reveal and quantify the glioblastoma invasion distant from the focal lesion and invisible on the conventional MRI. The structural disruptions in the normal-appearing brain were associated with the topological alteration of the brain and could indicate treatment target. Our approach promises to aid more accurate patient stratification and more precise treatment planning.

National norms for the obstetric nurses' and midwives' health education competence, and its influencing factors: a nationwide cross-sectional study.

BACKGROUND: Strengthening obstetric nurses' and midwives' health education competence is the investment and guarantee for the population's future health. The purpose of study is to establish national norms for their health education competence, and explore possible influencing factors for providing an uniform criterion identifying levels and weaknesses. METHODS: An online questionnaire with a standard process was used to collect data. Three normative models were constructed, and multiple linear regression analysis analyzed possible influencing factors. RESULTS: The sample respondents (n = 3027) represented obstetric nurses and midwives nationally. Three health education competency normative norms (mean, percentile and demarcation norm) were constructed separately. Locations, hospital grade, department, marital status, training times and satisfaction with health education training influenced obstetrical nurses' and midwives' health education competence (P<0.05). CONCLUSION: This study constructed the first national standard for assessing obstetric nurses' and midwives' health education competence, providing a scientific reference to evaluate the degree of health education competence directly. These known factors could help clinical and policy managers designate practice improvement measures. In future research, Grade I hospitals should be studied with larger sample sizes, and indicators need to improve to reflect health education's effect better.

Low movement, deep-learned sitting patterns, and sedentary behavior in the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE).

BACKGROUND/OBJECTIVES: Sedentary behavior (SB) has both movement and postural components, but most SB research has only assessed low movement, especially in children. The purpose of this study was to compare estimates and health associations of SB when derived from a standard accelerometer cut-point, a novel sitting detection technique (CNN Hip Accelerometer Posture for Children; CHAP-Child), and both combined. METHODS: Data were from the International Study of Childhood Obesity, Lifestyle, and the Environment (ISCOLE). Participants were 6103 children (mean ± SD age 10.4 ± 0.56 years) from 12 countries who wore an ActiGraph GT3X+ accelerometer on the right hip for approximately one week. We calculated SB time, mean SB bout duration, and SB breaks using a cut-point (SBmovement), CHAP-Child (SBposture), and both methods combined (SBcombined). Mixed effects regression was used to test associations of SB variables with pediatric obesity variables (waist circumference, body fat percentage, and body mass index z-score). RESULTS: After adjusting for MVPA, SBposture showed several significant obesity associations favoring lower mean SB bout duration (b = 0.251-0.449; all p < 0.001) and higher SB breaks (b = -0.005--0.052; all p < 0.001). Lower total SB was unexpectedly related to greater obesity (b = -0.077--0.649; p from <0.001-0.02). For mean SB bout duration and SB breaks, more associations were observed for SBposture (n = 5) than for SBmovement (n = 3) or SBcombined (n = 1), and tended to have larger magnitude as well. CONCLUSIONS: Using traditional measures of low movement as a surrogate for SB may lead to underestimated or undetected adverse associations between SB and obesity. CHAP-Child allows assessment of sitting posture using hip-worn accelerometers. Ongoing work is needed to understand how low movement and posture are related to one another, as well as their potential health implications.

Validation of NRG Oncology's prognostic nomograms for oropharyngeal cancer in the Veterans Affairs database.

BACKGROUND: To test whether nomograms developed by NRG Oncology for oropharyngeal squamous cell carcinoma (OPSCC) patients could be validated in an independent population-based sample. METHODS: The authors tested nomograms for estimating progression-free survival (PFS) and overall survival (OS) in patients from the Veterans Health Administration with previously untreated locoregionally advanced OPSCC, diagnosed between 2008 and 2017, managed with definitive radiotherapy with or without adjuvant systemic therapy. Covariates were age, performance status, p16 status, T/N category, smoking history, education history, weight loss, marital status, and anemia. We used multiple imputation to handle missing data and performed sensitivity analyses on complete cases. Validation was assessed via Cox proportional hazards models, log-rank tests, and c-indexes. RESULTS: A total of 4007 patients met inclusion criteria (658 patients had complete data). Median follow-up time was 3.20 years, with 967 progression events and 471 noncancer deaths. Each risk score was associated with poorer outcomes per unit increase (PFS score, hazard ratio [HR], 1.42 [1.37-1.47]; OS score, HR, 1.40 [1.34-1.45]). By risk score quartile, 2-year PFS estimates were 89.2%, 78.5%, 65.8%, and 48.3%; OS estimates were 92.6%, 83.6%, 73.9%, and 51.3%, respectively (P < .01 for all comparisons). C-indices for models of PFS and OS were 0.65 and 0.67, for all patients, respectively (0.69 and 0.73 for complete cases). The nomograms slightly overestimated PFS and OS in the overall cohort but exhibited high agreement in complete cases. CONCLUSIONS: NRG nomograms were effective for predicting PFS and OS for patients with OPSCC, supporting their broader applicability in the OPSCC population undergoing definitive radiotherapy.

CHAP-child: an open source method for estimating sit-to-stand transitions and sedentary bout patterns from hip accelerometers among children.

BACKGROUND: Hip-worn accelerometer cut-points have poor validity for assessing children's sedentary time, which may partly explain the equivocal health associations shown in prior research. Improved processing/classification methods for these monitors would enrich the evidence base and inform the development of more effective public health guidelines. The present study aimed to develop and evaluate a novel computational method (CHAP-child) for classifying sedentary time from hip-worn accelerometer data. METHODS: Participants were 278, 8-11-year-olds recruited from nine primary schools in Melbourne, Australia with differing socioeconomic status. Participants concurrently wore a thigh-worn activPAL (ground truth) and hip-worn ActiGraph (test measure) during up to 4 seasonal assessment periods, each lasting up to 8 days. activPAL data were used to train and evaluate the CHAP-child deep learning model to classify each 10-s epoch of raw ActiGraph acceleration data as sitting or non-sitting, creating comparable information from the two monitors. CHAP-child was evaluated alongside the current practice 100 counts per minute (cpm) method for hip-worn ActiGraph monitors. Performance was tested for each 10-s epoch and for participant-season level sedentary time and bout variables (e.g., mean bout duration). RESULTS: Across participant-seasons, CHAP-child correctly classified each epoch as sitting or non-sitting relative to activPAL, with mean balanced accuracy of 87.6% (SD = 5.3%). Sit-to-stand transitions were correctly classified with mean sensitivity of 76.3% (SD = 8.3). For most participant-season level variables, CHAP-child estimates were within ± 11% (mean absolute percent error [MAPE]) of activPAL, and correlations between CHAP-child and activPAL were generally very large (> 0.80). For the current practice 100 cpm method, most MAPEs were greater than ± 30% and most correlations were small or moderate (≤ 0.60) relative to activPAL. CONCLUSIONS: There was strong support for the concurrent validity of the CHAP-child classification method, which allows researchers to derive activPAL-equivalent measures of sedentary time, sit-to-stand transitions, and sedentary bout patterns from hip-worn triaxial ActiGraph data. Applying CHAP-child to existing datasets may provide greater insights into the potential impacts and influences of sedentary time in children.

Compensation or Aggravation: Pb and SO2 Copoisoning Effects over Ceria-Based Catalysts for NOx Reduction.

Severe catalyst deactivation caused by multiple poisons, including heavy metals and SO2, remains an obstinate issue for the selective catalytic reduction (SCR) of NOx by NH3. The copoisoning effects of heavy metals and SO2 are still unclear and irreconcilable. Herein, the unanticipated differential compensated or aggravated Pb and SO2 copoisoning effects over ceria-based catalysts for NOx reduction was originally unraveled. It was demonstrated that Pb and SO2 exhibited a compensated copoisoning effect over the CeO2/TiO2 (CT) catalyst with sole active CeO2 sites but an aggravated copoisoning effect over the CeO2-WO3/TiO2 (CWT) catalyst with dual active CeO2 sites and acidic WO3 sites. Furthermore, it was uniquely revealed that Pb preferred bonding with CeO2 among CT while further being combined with SO2 to form PbSO4 after copoisoning, which released the poisoned active CeO2 sites and rendered the copoisoned CT catalyst a recovered reactivity. In comparison, Pb and SO2 would poison acidic WO3 sites and active CeO2 sites, respectively, resulting in a seriously degraded reactivity of the copoisoned CWT catalyst. Therefore, this work thoroughly illustrates the internal mechanism of differential compensated or aggravated deactivation effects for Pb and SO2 copoisoning over CT and CWT catalysts and provides effective solutions to design ceria-based SCR catalysts with remarkable copoisoning resistance for the coexistence of heavy metals and SO2.

Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study. / ä½é™¢æžæ—©äº§å„¿å®«å¤–ç”Ÿé•¿è¿Ÿç¼“åŠç›¸å ³å› ç´ çš„å¤šä¸­å¿ƒå‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Deubiquitylation and stabilization of ARMC5 by ubiquitin-specific processing protease 7 (USP7) are critical for RCC proliferation.

The ubiquitin-proteasome system is an essential regulator of ARMC5, which serves as a new tumour suppressor protein for inhibiting meningiomas and hereditary adrenocortical tumorigenesis. However, the precise mechanism for the deubiquitination of ARMC5 is still not fully understood. A Western blot analysis of ARMC5 was performed and showed that the expression of ARMC5 was decreased in the renal cancer cell tissues and lines. By screening a deubiquitinase library, we identified USP7 as a potential ARMC5 associated deubiquitinase. In this paper, we demonstrated that there was an interaction between USP7 and ARMC5 in vivo and in vitro. Employing the overexpression and knockdown assay indicated that USP7 could greatly increase the steady state of ARMC5 through the ubiquitin-proteasome pathway and regulate ARMC5 ubiquitination. Moreover, USP7 altered cell cycle G1/S phases and regulated renal cancer cell proliferation by targeting ARMC5. Together, these results suggest that USP7 plays an important role in the RCC proliferation through modulating ARMC5 stability.

Correction of Artifacts Induced by B0 Inhomogeneities in Breast MRI Using Reduced-Field-of-View Echo-Planar Imaging and Enhanced Reversed Polarity Gradient Method.

BACKGROUND: Diffusion-weighted (DW) echo-planar imaging (EPI) is prone to geometric distortions due to B0 inhomogeneities. Both prospective and retrospective approaches have been developed to decrease and correct such distortions. PURPOSE: The purpose of this work was to evaluate the performance of reduced-field-of-view (FOV) acquisition and retrospective distortion correction methods in decreasing distortion artifacts for breast imaging. Coverage of the axilla in reduced-FOV DW magnetic resonance imaging (MRI) and residual distortion were also assessed. STUDY TYPE: Retrospective. POPULATION/PHANTOM: Breast phantom and 169 women (52.4 ± 13.4 years old) undergoing clinical breast MRI. FIELD STRENGTH/SEQUENCE: A 3.0 T/ full- and reduced-FOV DW gradient-echo EPI sequence. ASSESSMENT: Performance of reversed polarity gradient (RPG) and FSL topup in correcting breast full- and reduced-FOV EPI data was evaluated using the mutual information (MI) metric between EPI and anatomical images. Two independent breast radiologists determined if coverage on both EPI data sets was adequate to evaluate axillary nodes and identified residual nipple distortion artifacts. STATISTICAL TESTS: Two-way repeated-measures analyses of variance and post hoc tests were used to identify differences between EPI modality and distortion correction method. Generalized linear mixed effects models were used to evaluate differences in axillary coverage and residual nipple distortion. RESULTS: In a breast phantom, residual distortions were 0.16 ± 0.07 cm and 0.22 ± 0.13 cm in reduced- and full-FOV EPI with both methods, respectively. In patients, MI significantly increased after distortion correction of full-FOV (11 ± 5% and 18 ± 9%, RPG and topup) and reduced-FOV (8 ± 4% both) EPI data. Axillary nodes were observed in 99% and 69% of the cases in full- and reduced-FOV EPI images. Residual distortion was observed in 93% and 0% of the cases in full- and reduced-FOV images. DATA CONCLUSION: Minimal distortion was achieved with RPG applied to reduced-FOV EPI data. RPG improved distortions for full-FOV images but with more modest improvements and limited correction near the nipple. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

A point-of-care chemiluminescence immunoassay for pepsinogen I enables large-scale community health screening.

Pepsinogen I (PGI) can reflect the morphology and function of the gastric mucosa. Accordingly, the large-scale community health screening of PGI can dramatically increase the early diagnosis rate of gastric cancer. However, PGI testing can only be carried out in comprehensive hospitals and health examination centers. To ameliorate this issue, a point-of-care chemiluminescent immunoassay for PGI was developed in a fully automated miniaturized instrument. This instrument was especially developed for health check-ups in the grassroots communities; its volume of which is only 0.18 m3. Critically, the entire detection process for a single sample only requires 20 min, and the samples can be loaded continuously, making the method suitable for high-throughput analysis. The assay displayed an excellent detection limit of 0.048 ng/mL with a broad detection range of 0-200 ng/mL. Furthermore, this assay exhibited high sensitivity and specificity, had low intra- and inter-assay coefficients of variation (<10%), and was not affected after storage at 37 °C for 7 days. The assay was used to detect PGI in 95 clinical serum samples, and the results were highly correlated with those that were clinically tested (correlation coefficient, R2 = 0.998). Hence, the method established in this work has great application value and can be broadly applied for the large-scale screening of gastric cancer in resource-limited areas.

Bifidobacterium adolescentis protects against necrotizing enterocolitis and upregulates TOLLIP and SIGIRR in premature neonatal rats.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disorder that is often seen in premature infants. Probiotics decrease the risk of NEC; however, the mechanism by which probiotics work is not clear. The goal of this study was to evaluate the preventive effect of Bifidobacterium adolescentis in an NEC rat model. METHODS: Sprague-Dawley neonatal rats were obtained by caesarean section after 20-21 d gestation and randomly divided into the following 3 groups: dam fed (DF), formula fed (FF), and formula + B. adolescentis (FB). Those in the FF and FB groups developed NEC after exposure to asphyxia and cold stress. All rats were sacrificed 72 h after birth and intestinal injury and mRNA expression of TLR4, TOLLIP and SIGIRR were assessed. RESULTS: B. adolescentis significantly increased the 72-h survival rate from 56.3% in the FF group to 86.7% in the FB group. B. adolescentis significantly reduced the histological score from a median of 3.0 in the FF group to a median of 1.0 in the FB group,and significantly decreased the rate of NEC-like intestinal injury from 77.8% in the FF group to 23.1% in the FB group. The mRNA expression of TLR4 increased 3.6 fold in the FF group but decreased by 2 fold from B. adolescentis treatment. mRNA expression of TOLLIP and SIGIRR decreased 4.3 and 3.7 fold, respectively, in the FF group. B. adolescentis significantly increased mRNA expression of TOLLIP and SIGIRR by 3.7 fold and 2.6 fold, respectively. CONCLUSIONS: This study demonstrated B. adolescentis prevents NEC in preterm neonatal rats and that the mechanism for this action might be associated with the alteration of TLR4, TOLLIP, and SIGIRR expression.

Resistance training improves hyperglycemia and dyslipidemia, highly prevalent among nonelderly, nondiabetic, chronically disabled stroke patients.

OBJECTIVE: To test the effect of 8 weeks of lower body resistance training on hyperglycemia and dyslipidemia, which may be prevalent among nonelderly, nondiabetic, chronically disabled stroke patients. DESIGN: Randomized controlled study. SETTING: Outpatient clinics of rehabilitation centers. PARTICIPANTS: Nonelderly, nondiabetic, chronically disabled stroke subjects (N=56) were enrolled and randomly assigned to an experimental group (n=28) and a control group (n=28). INTERVENTIONS: Lower body resistance training was performed by subjects in the experimental group 3 times a week for 8 weeks. The control group was given duration-matched stretch exercises. MAIN OUTCOME MEASURES: Fasting glucose level, fasting insulin level, 2-hour blood glucose level during oral glucose tolerance test, homeostasis model assessment of insulin resistance (HOMA-IR), glycosylated hemoglobin (Hb A1c), total triglyceride level, total cholesterol level, high-density lipoprotein (HDL) cholesterol level, low-density lipoprotein (LDL) cholesterol level, body mass index, lower limb muscle strength, and Fugl-Meyer motor score. RESULTS: Before the intervention, 34 subjects (60.7%) had hyperglycemia and 38 (67.9%) had dyslipidemia. Fifty-one subjects finished the study. Subjects in the experimental group (n=26) showed significant improvements in fasting insulin and 2-hour blood glucose levels; HOMA-IR; total cholesterol, HDL cholesterol, and LDL cholesterol levels; and muscle strength compared with control subjects (n=25) after the intervention (P<.05). CONCLUSIONS: Resistance training may play a significant role in improving hyperglycemia and dyslipidemia, which are frequently present among nonelderly, nondiabetic, chronically disabled stroke patients.

Confronting fear using exposure and response prevention for anorexia nervosa: A randomized controlled pilot study.

OBJECTIVE: Anorexia nervosa (AN) is a severe illness with high rates of relapse. Exposure and Response Prevention for AN (AN-EXRP) is a new approach that specifically addresses maladaptive eating behavior by targeting eating-related fear and anxiety. The aim of this study was to evaluate AN-EXRP as an adjunctive strategy to improve eating behavior during weight restoration, at a pivotal moment when treatment goals shift toward relapse prevention. METHOD: A randomized controlled trial was conducted to compare AN-EXRP with a comparison condition, Cognitive Remediation Therapy (CRT). Hospitalized patients with AN (n = 32) who had achieved weight restoration to a BMI > 18.5 kg/m(2) received 12 sessions of either AN-EXRP or CRT. Outcome was assessed by change in caloric intake in an objective assessment of eating behavior. RESULTS: The average test meal caloric intake of participants who received AN-EXRP increased from 352 ± 263 kcal at baseline to 401 ± 215 kcal post-treatment, while that of participants who received CRT decreased from 501 ± 232 kcal at baseline to 424 ± 221 kcal post-treatment [t(28) = 2.5, p = .02]. Improvement in intake was significantly associated with improvement in eating-related anxiety (Spearman's ρ = 0.40, p = .03). DISCUSSION: These data demonstrate that AN-EXRP, compared to a credible comparison intervention, is associated with better caloric intake in a laboratory meal over time in AN. Additional studies are required to determine whether incorporation of these techniques into a longer treatment program leads to enduring and clinically significant change.

Sociodemographic correlates of parent and youth-reported eating disorder symptoms in the Adolescent Brain Cognitive Development Study.

PURPOSE: Eating Disorders (EDs) often start in adolescence, though ED-related concerns in diverse youth samples remain understudied. We leveraged data from the Adolescent Brain Cognitive Development (ABCD) Study to identify the prevalence of parent- and youth-reported ED symptoms and their sociodemographic characteristics. METHODS: Data were drawn from baseline (ages 9-11 years, n=11,868) and 2-year follow-up (ages 11-14 years; n=10,908) from the ABCD Study. A tetrachoric factor analysis summarized clusters of ED symptoms, which were compared between parent and youth reports and across sociodemographic variables. RESULTS: Three factors emerged reflecting "weight distress", "weight control", and "binge eating" (prevalence range: 1.5-7.3%). Symptoms loaded onto similar factors between reporters. Rates of symptom endorsement were similar between sexes, with disproportionately higher endorsement rates for youth who self-identified as sexual minority, Hispanic, Black, or Mixed race participants, and those from a disadvantaged socioeconomic background, compared to the reference ABCD sample. Youth and parent reports at 2-year showed ~12% overlap. CONCLUSIONS: ED-related concerns among historically understudied racial and sexual minority groups call for greater attention to the detection and treatment of these symptoms in these groups. Applying a transdiagnostic approach to ED symptoms can inform effective detection and intervention efforts.

The effect of extracellular matrix on the precision medicine utility of pancreatic cancer patient-derived organoids.

The use of patient-derived organoids (PDOs) to characterize therapeutic sensitivity and resistance is a promising precision medicine approach, and its potential to inform clinical decisions is now being tested in several large multiinstitutional clinical trials. PDOs are cultivated in the extracellular matrix from basement membrane extracts (BMEs) that are most commonly acquired commercially. Each clinical site utilizes distinct BME lots and may be restricted due to the availability of commercial BME sources. However, the effect of different sources of BMEs on organoid drug response is unknown. Here, we tested the effect of BME source on proliferation, drug response, and gene expression in mouse and human pancreatic ductal adenocarcinoma (PDA) organoids. Both human and mouse organoids displayed increased proliferation in Matrigel compared with Cultrex and UltiMatrix. However, we observed no substantial effect on drug response when organoids were cultured in Matrigel, Cultrex, or UltiMatrix. We also did not observe major shifts in gene expression across the different BME sources, and PDOs maintained their classical or basal-like designation. Overall, we found that the BME source (Matrigel, Cultrex, UltiMatrix) does not shift PDO dose-response curves or drug testing results, indicating that PDO pharmacotyping is a robust approach for precision medicine.

Let's TOC Fertility: A stepped wedge cluster randomized controlled trial of the Telehealth Oncofertility Care (TOC) intervention in children, adolescent and young adult cancer survivors.

INTRODUCTION: Children, adolescent, and young adult cancer survivors experience overall increased risks of infertility that are preventable through effective fertility preservation services prior to starting cancer treatment. Oncofertility care is the evidence-based practice of informing newly diagnosed cancer patients about their reproductive risks and supporting shared decision-making on fertility preservation services. Despite longstanding clinical guidelines, oncofertility care delivery continues to be limited and highly variable across adult and pediatric oncology settings. MATERIALS AND METHODS: We describe the design of a stepped wedge cluster randomized clinical trial to evaluate the effectiveness of the multi-component Telehealth Oncofertility Care (TOC) intervention conducted in 20 adult and pediatric oncology clinics across three health systems in Southern California. Intervention components are: 1) electronic health record-based oncofertility needs screen and referral pathway to a virtual oncofertility hub; 2) telehealth oncofertility counseling through the hub; and 3) telehealth oncofertility financial navigation through the hub. We hypothesize the intervention condition will be associated with increased proportions of patients who engage in goal-concordant oncofertility care (i.e., engagement in reproductive risk counseling and fertility preservation services that meet the patient's fertility goals) and improved patient-reported outcomes, compared to the usual care control condition. We will also evaluate intervention implementation in a mixed-methods study guided by implementation science frameworks. DISCUSSION: Our overall goal is to speed implementation of a scalable oncofertility care intervention at cancer diagnosis for children, adolescent and young adult cancer patients to improve their future fertility and quality of life. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05443737.