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The field of phenomics is experiencing unprecedented advances thanks to the rapid growth of morphological quantification based on three-dimensional (3D) imaging, online data repositories, team-oriented collaborations, and open data-sharing policies. In line with these progressions, we present an extensive primate phenotypic dataset comprising >6,000 3D scans (media) representing skeletal morphologies of 386 individual specimens covering all hominoid genera (except humans) and other selected primates. The digitized specimens are housed in physical collections at the American Museum of Natural History, the National Museum of Natural History, the Royal Museum for Central Africa (Belgium), the Cleveland Museum of Natural History, and Stony Brook University. Our technical validation indicates that despite the diverse digitizing devices used to produce the scans, the final 3D models (meshes) can be safely combined to collect comparable morphometric data. The entire dataset (and detailed associated metadata) is freely available through MorphoSource. Hence, these data contribute to empowering the future of primate phenomics and providing a roadmap for future digitization and archiving of digital data from other collections. [ABSTRACT FROM AUTHOR]

Many children with autism spectrum disorder experience feeding difficulties that can lead to increased health risks (e.g., severe nutrition deficiencies, obesity-related illnesses) if left untreated. Intensive feeding programs that use behavior-analytic interventions have reported positive outcomes for treating challenging behavior associated with pediatric feeding disorders at discharge and up to 1 year post discharge. Whether these children achieve and maintain long-term goals is unknown. The purpose of the current study was to evaluate outcomes of behavior-analytic intervention for pediatric feeding disorders among children with and without autism spectrum disorder in an intensive feeding program post discharge. Caregivers of former patients reported on the positive and negative impact of the program and their child's growth and diet variety at follow-up. 85% of caregivers reported the program had a positive impact. Increases in height-for-age z scores were significant from admission to discharge from the intensive program, and progress in growth and diet variety remained the same or improved for most children at follow-up. Results suggest that behavior-analytic intervention in an intensive feeding program produced positive short- and long-term outcomes for children and their families. [ABSTRACT FROM AUTHOR]

Purpose: Sleep disturbances are common in patients with breast cancer, but comprehensive evaluations with patient-reported outcomes (PRO) and sleep evaluation with polysomnography (PSG) are lacking. This study describes sleep disruption using PROs and PSG to identify underlying sleep disorders. Methods: A retrospective review of patients with breast cancer undergoing formal sleep evaluation from 4/1/2009 to 7/31/2014 was performed. Clinical characteristics, PROs using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), and PSG data were reviewed. Results: 404 patients were identified with 43% early, 30% locally advanced and 17% metastatic disease. PSQI revealed poor sleep in 75%, and ESS demonstrated daytime sleepiness in 55%. Sleep aid use was reported by 39%, and pain medication use in 22%. Most patients (50.2%) had multiple sleep disorders. Insomnia (54.5%) was the most frequent sleep disorder, followed closely by obstructive sleep apnea (OSA) (53.7%). PSG was performed in 74%. Multivariate analysis linked poor sleep to use of sleep aids [OR 7.7, 95% CI 3.9 to 15.2], anxiety disorder [OR 4.8, 95% CI 1.7 to 14.0], and metastatic disease [OR 2.8, 95% CI 1.1 to 6.6]. Daytime sleepiness correlated with known diagnosis of OSA [OR 1.9, 95% CI 1.0 to 3.3] and sleep aid use [OR 0.6, 95% CI 0.4 to 0.9]. Conclusions: Poor sleep was associated with sleep aid use, anxiety disorder and metastatic disease. Insomnia was the most common sleep disorder, followed by OSA (mostly mild). Education about sleep health and proactive screening for sleep symptoms would be beneficial in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have improved patient survival in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC) in clinical trials and real-world studies. However, investigations of survival gains in broader HR+/HER2− mBC populations using epidemiological approaches are limited. Methods: This retrospective study used SEER registry data to assess breast cancer-specific survival (BCSS) in patients diagnosed with HR+/HER2− de novo mBC from 2010 to 2019. Kaplan–Meier and Cox proportional hazards models were used to compare BCSS in patients diagnosed before (2010‒2013 with follow-up to 2014) and after (2015‒2018 with follow-up to 2019) the 2015 guideline recommendations for CDK4/6i use. A comparison was made to patients with HR+/HER2-positive (HER2+) de novo mBC, for which no major guideline changes occurred during 2015–2018. Results: Data from 11,467 women with HR+/HER2− mBC and 3260 women with HR+/HER2+ mBC were included. After baseline characteristic adjustment, patients with HR+/HER2− mBC diagnosed post-2015 (n = 6163), had an approximately 10% reduction in risk of BC-specific death compared with patients diagnosed pre-2015 (n = 5304; HR = 0.895, p < 0.0001). Conversely, no significant change was observed in HR+/HER2+ BCSS post-2015 (n = 1798) versus pre-2015 (n = 1462). Similar results were found in patients aged ≥ 65 years. Conclusion: Using one of the largest US population-based longitudinal cancer databases, significant improvements in BCSS were noted in patients with HR+/HER2− mBC post-2015 versus pre-2015, potentially due to the introduction of CDK4/6i post-2015. No significant improvement in BCSS was observed in patients with HR+/HER2+ mBC post-2015 versus pre-2015, likely due to the availability of HER2-directed therapies in both time periods. [ABSTRACT FROM AUTHOR]

The human otolithic system (utricle and saccule), housed within the bony vestibule of the inner ear, establishes our sense of balance in conjunction with the semicircular canals. Yet, while the morphological evolution of the semicircular canals is actively explored, comparative morphological analyses of the otolithic system are lacking. This is regrettable because functional links with head orientation suggest the otolithic system could be used to track postural change throughout human evolution and across primates more broadly. In this context, we present the first analysis of the evolution of the human otolithic system within an anthropoid primate setting. Using the vestibule as a morphological proxy for the utricle and saccule, we compare humans to 13 other extant anthropoid species, and use phylogenetically-informed methods to find correlations with body size, endocranial flexion, and head-neck posture. Our results, obtained through micro-CT of 136 inner ears, reveal two major evolutionary transitions in hominoids, leading to distinctive vestibular morphology in humans, characterized by otolithic morphology resembling squirrel monkeys (possibly due to reversal), with a pronounced supraovalic fossa. Finally, we find a positional signal embedded in the anthropoid bony vestibule, providing the foundation to further explore the evolution of human head-neck posture using inner ear morphology. Morphometric modeling reveals evolutionary divergences of the otolithic inner ear in humans and apes, with a possible link to the evolution of postural behavior. [ABSTRACT FROM AUTHOR]

While surgery, when possible, remains the mainstay of pediatric low-grade glioma (pLGG) management, adjuvant therapy has significantly evolved over time. Radiation therapy was commonly used in the late 1990s for tumors that could not be resected or recurred. This resulted in significant late morbidity in this population and mortality related to secondary malignancies and chronic health conditions. Chemotherapy became the mainstay of adjuvant therapy but children still experienced late morbidity secondary to exposure to multiple lines of treatment over time. Targeted therapies emerged after the identification of frequent genetic alterations in the mitogen activated protein kinase (MAPK) pathway including KIAA1549-BRAF fusions and BRAF-V600 mutations and the near universal upregulation of the MAPK pathway in these tumors. Both BRAF and MEK inhibitors have shown efficacy in the treatment of pLGG and have led to prolonged stability in some cases. Multiple phase III clinical trials are now comparing targeted therapy to standard-of-care chemotherapy regimens setting the stage for targeted therapy to replace chemotherapy as the first-line treatment in some cases. Targeted therapy, however, is not without its challenges. There are clear examples of resistance and mechanisms of resistance have not been fully elucidated. There is also no clear duration for these therapies and rebound growth is a well-known phenomenon especially in BRAF-V600 mutant tumors. Targeted therapies are also fairly recent developments and long-term toxicities and functional outcomes are still being monitored. Very young and adolescent/young adult LGGs also carry molecular features that may not be addressed by inhibition of the MAPK pathway. Adjuvant therapy for pLGG has evolved from radiation for all unresectable or residual tumors to molecularly driven targeted therapies with improved quality of life, late effects, and less off-target toxicities. While there is still much to learn in regard to newer targeted therapies for pLGG, the era of targeted therapies for pediatric LGG is upon us. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to compare maternal and neonatal outcomes when the diagnosis of FGR was based on isolated abdominal circumference < 10th percentile for gestational age (GA) (iAC group) versus overall estimated fetal weight < 10th percentile (EFW group). Methods: This was a retrospective cohort study of singleton gestations who underwent growth ultrasounds and delivered at a single health system from 1/1/19–9/4/20. The study group was comprised of patients with AC < 10th percentile and EFW ≥ than the 10th percentile (iAC group). The control group included patients with overall EFW < 10th percentile (EFW group). Outcomes evaluated included GA at delivery, mode of delivery, fetal and neonatal outcomes. Data was analyzed using Mann Whitney U, X2, and Fisher exact tests with significance defined as p < 0.05. Results: 635 women met the inclusion criteria, 259 women in the iAC group and 376 women in the EFW group. The iAC group was noted to have a later GA at diagnosis and delivery. iAC was associated with lower rates of preterm birth (PTB), NICU admission, SGA at delivery and umbilical artery cord gas < 7.0. Conclusion: Using iAC as a definition of FGR increased the number of FGR cases by 1.69-fold over EFW criteria alone. However, obstetrical and neonatal outcomes for the iAC group appear to be significantly better than those in the EFW group, with low rates of PTB, NICU admission, and umbilical artery cord gas < 7.0. [ABSTRACT FROM AUTHOR]

The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from four crew members longitudinally before (Launch: L-92, L-44, L-3 days), during (Flight Day: FD1, FD2, FD3), and after (Return: R + 1, R + 45, R + 82, R + 194 days) spaceflight, spanning a total of 289 days across 2021-2022. The collection process included venous whole blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies. Venous whole blood was further processed to obtain aliquots of serum, plasma, extracellular vesicles and particles, and peripheral blood mononuclear cells. In total, 2,911 sample aliquots were shipped to our central lab at Weill Cornell Medicine for downstream assays and biobanking. This paper provides an overview of the extensive biospecimen collection and highlights their processing procedures and long-term biobanking techniques, facilitating future molecular tests and evaluations.As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can aid future human spaceflight and space biology experiments. Here the authors provide the biospecimen collection methodology from the SpaceX Inspiration4 mission, including venous blood, capillary blood, saliva, urine, stool, skin biopsy, body swab, and environmental swab samples. [ABSTRACT FROM AUTHOR]

Freshwater gastropods are among the most imperiled organisms on Earth. Yet, they are among the most understudied freshwater taxa. Numerous freshwater gastropod species have gone extinct in the last 100 years, but recent rediscoveries indicate that some species were prematurely declared extinct. Such premature extinction declarations remove legal protections, which could facilitate actual extinction. Thus, research and policy recommendations are needed so surveys provide the best information possible for conservation. Here, we examined the case of Lithasia hubrichti, a freshwater gastropod endemic to the Big Black River in Mississippi that was last seen in 1965. In 2022, a freshwater mollusk survey resulted in finding L. hubrichti alive. An additional survey effort in 2023 that prioritized sampling as many sites as possible in a single day clarified the current range of L. hubrichti. Genomic analyses indicated that the species has persisted with a large population size for thousands of years, rather than ever falling below a survey detection limit. When considering the case of L. hubrichti and other recent freshwater gastropod rediscoveries, we conclude that freshwater gastropod surveys should emphasize sampling as many sites as possible under favorable sampling conditions when targeting rare species, rather than expending high sampling effort at a small number of sites or when stream conditions may impact ability to detect target species. We also advocate for policies that encourage partnerships with landowners, which was required to rediscover L. hubrichti. [ABSTRACT FROM AUTHOR]

Purpose: Black women often experience poorer breast cancer-related outcomes and higher mortality than white women. A contributor to this disparity may relate to the disproportionate burden of cancer treatment-related cardiovascular (CV) toxicities. The objective of this review is to identify studies that report racial differences in CV toxicity risk. Methods: Medline and Embase were searched for studies that assessed CV toxicities as the outcome(s) and included Black and White women with breast cancer. Studies were selected based on inclusion/exclusion criteria and through the use of multiple reviewers. Results: The review included 13 studies following a review of 409 citations and 49 full-text articles. All studies were retrospective and 8/13 utilized data from the Surveillance, Epidemiology, and End Results–Medicare linked database. Trastuzumab was the most frequently studied treatment. The proportion of Black women in these studies ranged from 5.5 to 63%. A majority of studies reported a higher risk of CV toxicity amongst Black women when compared to white women (93%). Black women had up to a two times higher risk of CV toxicity (HR, 2.73 (CI, 1.24 to 6.01)) compared to white women. Only one study evaluated the role of socioeconomic factors in explaining racial differences in CV toxicity; however, the disparity remained even after adjusting for these factors. Conclusions: There is a critical need for more longitudinal studies that evaluate multilevel factors (e.g., psychosocial, biological) that may help to explain this disparity. Implications for Cancer Survivors: Black cancer survivors may require additional surveillance and mitigation strategies to decrease disproportionate burden of CV toxicities. [ABSTRACT FROM AUTHOR]

Purpose: Obesity and health behaviors are the major modifiable contributors to cancer and health disparities. We examined the differences in obesity-related health behaviors, and health outcomes by rural and Appalachian residency in Ohio. Methods: Cross-sectional survey data from the 2011–2019 Behavioral Risk Factor Surveillance System were obtained from the Ohio Department of Health. County-level identifiers were used to classify urban non-Appalachian, urban Appalachian, rural non-Appalachian, and rural Appalachian residency. Self-reported weight, height, health behaviors, and health conditions were used. Logistic regression was used to assess the difference in health behaviors and health outcomes by rural and Appalachian residency. All analyses incorporated with sample weights. Results: Among Ohio residents, compared to urban non-Appalachian residents, urban Appalachian and rural Appalachian residents had a higher prevalence of obesity, hypertension, high cholesterol, and cardiovascular diseases, as well as lower rates of healthy diet and physical activity. No difference was found in trends of obesity and obesity-related health outcomes in 2011–2019 by rural and Appalachian residency. However, rural Appalachian residents had a greater increase in obesity, hypertension, and diabetes, whereas rural non-Appalachian had favorable changes in obesity-related health behaviors. Additionally, associations between health behaviors and obesity-related health outcomes differed by rural and Appalachian residency. Conclusions: Findings underscore the importance of distinguishing between urban non-Appalachian, urban Appalachian, rural non-Appalachian, and rural Appalachian populations when assessing health disparities. While the trends of obesity and obesity-related health outcomes did not differ, the association between health behaviors and obesity-related outcomes differed by rural and Appalachian residency. [ABSTRACT FROM AUTHOR]

Adolescent mothers frequently encounter pregnancy-related stigma which increases their risk for depression and this risk is comparatively greater than for adult mothers. The current study investigated the relationship between stigma and depression in adolescent mothers including the role that household composition played in the adolescents' experience of stigma and depression. A sample of 85 adolescent mothers, aged 14–18 years, enrolled at multiple sites of a national school program in Jamaica, completed an interviewer-administered questionnaire that assessed different types of perceived stigma, depression risk, and varying forms of household composition for the adolescent mothers. After adapting the Berger's HIV Stigma Scale for use with adolescent pregnancy, correlational analyses revealed that higher scores on the Personalized Stigma and Negative Self-Image subscales and the overall stigma scale were associated with higher depression scores. Adolescent mothers living in a single-parent household were at increased risk for experiencing stigma while those living in multigenerational households were protected from depression risk. Regression analyses identified exposure to sexual violence during pregnancy as an independent predictor of feeling stigmatized, and depression risk was independently predicted by internalized stigma resulting in a negative self-image. We discuss conceptualizing stigma as heterogenous and bi-directional in its relationship with depression and suggest that more research is needed to evaluate the link between stigma, mental health risk and protective factors for adolescent mothers. Highlights: Perceived stigma was influenced by household composition as adolescent mothers in a single-parent household were most likely to report high levels of stigma while stigma risk was reduced for those in a relationship with an intimate partner Stigma experienced in close personal relationships increased depression risk but not stigma linked to public attitudes on adolescent pregnancy Depression risk was reduced for adolescent mothers living in a multigenerational household when the home included a biological mother. [ABSTRACT FROM AUTHOR]

Pregnancy on a rudimentary uterine horn is a rare condition that can lead to a catastrophic outcome when it ruptures. The majority of cases are diagnosed late, after the rupture has occurred. We present the case of a 29-year-old female G2 P1 who complained of abdominal pain. She consulted a medical practitioner who prescribed her analgesics. In the next day, she was found dead in her bedroom. The pregnancy was undiagnosed as she was not aware that she was in a gravid state. At autopsy, there was massive haemoperitoneum and a 24-week gestation foetus lying outside the uterus. The uterus revealed an anomaly in keeping with a non- communicating rudimentary horn. Forensic pathologists do encounter undiagnosed ectopic pregnancies in practice. However, abdominal ectopic pregnancy with a uterine anomaly remains uncommon. These cases are often associated with a high maternal and foetal mortality. [ABSTRACT FROM AUTHOR]

Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8+ and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data.Nasally delivered live attenuated influenza vaccines (LAIV) have been shown to be effective in vaccine trials yet immune responses are mostly measured in blood. Here the authors report a clinical trial in young adults and measure immune responses in the mucosa and blood to identify compartmentalised responses. [ABSTRACT FROM AUTHOR]

Purpose: Infertility affects one in four female physicians, yet current availability of fertility benefits within Accreditation Council for Graduate Medical Education (ACGME) accredited residency programs in the United States (US) is unknown. Our objective was to examine publicly available fertility benefits information for residents and fellows. Methods: The top 50 medical schools in the US for research were identified using US News & World Report 2022. In April 2022, we reviewed fertility benefits available to residents and fellows at these medical schools. Websites of their associated graduate medical education (GME) websites were queried for details surrounding fertility benefits. Two investigators collected data from GME and publicly available institutional websites. The primary outcome was fertility coverage and rates are reported as percentages. Results: Within the top 50 medical schools, 66% of institutional websites included publicly available medical benefits, 40% included any mention of fertility benefits, and 32% had no explicit information on fertility or medical benefits. Fertility benefit coverage included infertility diagnostic workup (40%), intrauterine insemination (32%), prescription coverage (12%), and in vitro fertilization (IVF, 30%). No information on coverage for third party reproduction or LGBT family building was available on public websites. Most programs with fertility benefits were in the South (40%) or Midwest (30%). Conclusion: To support the reproductive autonomy of physicians in training, it is critical to ensure access to information on fertility care coverage. Given the prevalence of infertility among physicians and the impact of medical training on family planning goals, more programs should offer and publicize coverage for fertility care. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the preferred regimen for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced or metastatic breast cancer. However, the optimal treatment sequencing for CDK4/6i with other available therapeutic options is unclear. We conducted a targeted literature review to identify the current evidence on CDK4/6i treatment patterns in patients with breast cancer. The search was initially conducted in October 2021 and subsequently updated in October 2022. Biomedical databases and gray literature were searched, and bibliographies of included reviews were screened for relevant studies. The search identified ten reviews published since 2021 and 87 clinical trials or observational studies published since 2015. The included reviews discussed CDK4/6i usage with or without endocrine therapy (ET) in first-line and second-line treatment for patients with HR+/HER2− advanced or metastatic breast cancer, followed by ET, chemotherapy, or targeted therapy with ET. Clinical studies reported similar treatment sequences consisting of ET, chemotherapy, or targeted therapy with ET prior to CDK4/6i with ET, followed by ET monotherapy, chemotherapy, targeted therapy with ET, or continued CDK4/6i with ET. Current evidence suggests CDK4/6i are effective for HR+/HER2− advanced or metastatic breast cancer in earlier lines of therapy. Efficacy of CDK4/6i as measured by progression-free survival and overall survival was similar within a line of therapy regardless of the type of prior therapy. Survival on different post-CDK4/6i treatments was also similar within the same line of therapy. Additional research is needed to investigate the optimal place in therapy of CDK4/6i and the sequencing of treatments following progression on CDK4/6i. [ABSTRACT FROM AUTHOR]

Purpose: Endometrial cancer (EC) is the most common gynecological cancer among women in the United States. Despite well-documented racial/ethnic disparities in EC incidence and mortality rates, limited data exist regarding disparities in hysterectomy surgical outcomes. We evaluated associations of race/ethnicity with postoperative complications, serious adverse events (SAEs), and length of hospital stay among women undergoing EC-related hysterectomy. Methods: Using National Surgical Quality Improvement Program (NSQIP) data, we identified women (≥18 years) undergoing hysterectomy to treat EC between 2014 and 2020. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of race/ethnicity (white, black, and Latina) with postoperative complications and SAEs. We used Poisson regression with robust standard errors to calculate incidence rate ratios (IRRs) and 95% CIs for the association of race/ethnicity with length of hospital stay. Results: Of 22,778 women undergoing EC-related hysterectomy, 3.1% developed postoperative complications. Black (adjusted OR: 1.62; 95% CI 1.05–2.48) and Latina women (adjusted OR: 1.79; 95% CI 1.04–3.09) had higher postoperative complication risks than white women. The overall SAE incidence was 5.0%. Black women (adjusted OR: 1.55, 95% CI 1.13–2.15) had higher SAE risks than white women. Length of hospital stay was significantly longer for black women than white women (IRR: 1.18; 95% CI 1.07–1.30). Conclusions: We observed racial/ethnic disparities in EC-related hysterectomy surgical outcomes in a large, diverse sample of U.S. women between 2014 and 2020. Studies to elucidate the underlying mechanisms of these racial disparities, with a focus on social context remain necessary. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Surveys that prioritize site number over time per site will result in better gastropod status assessments: a case study on the rediscovery of Big Black Rocksnail" published in the journal Biodiversity & Conservation. The correction addresses an error in the affiliation details of authors Paul D. Hartfield, Ashley S. Ruppel, and Matthew D. Wagner, which were incorrectly listed as 'Mississippi Ecological Services Field Office, U.S. Fish and Wildlife Service, Warm Springs, GA, USA' instead of 'Mississippi Ecological Services Field Office, U.S. Fish and Wildlife Service, Jackson, MS, USA'. The correction has been made to the original article. The publisher, Springer Nature, maintains neutrality regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Melanoma is the most aggressive form of skin cancer, with tendency to spread to any organ of the human body, including the gastrointestinal tract (GIT). The diagnosis of metastases to the GIT can be difficult, as they may be clinically silent for somewhile and may occur years after the initial melanoma diagnosis. CT imaging remains the standard modality for staging and surveillance of melanoma patients, and in most cases, it will be the first imaging modality to identify GIT lesions. However, interpretation of CT studies in patients with melanoma can be challenging as lesions may be subtle and random in distribution, as well as sometimes mimicking other conditions. Even so, early diagnosis of GIT metastases is critical to avoid emergency hospitalisations, whilst surgical intervention can be curative in some cases. In this review, we illustrate the various imaging presentations of melanoma metastases within the GIT, discuss the clinical aspects and offer advice on investigation and management. We offer tips intended to aid radiologists in their diagnostic skills and interpretation of melanoma imaging scans. [ABSTRACT FROM AUTHOR]

Background: Pediatric intra-cranial germ cell tumors (iGCTs) occur at an incidence of 0.6–1.2 cases/million/year in Western countries. The incidence is reported up to 5 times higher in Japan. It is unknown whether this increased incidence is due to genetic predisposition or environment. Methods: The incidence of iGCTs in children ages 0–19 years was evaluated from December 1st, 1996-December 1st, 2016 in stable Japanese immigrant populations living abroad and compared to current native Japanese registry data. The incidence of medullobblastoma was used as a control to account for assumptions in the data. Sites were identified based on historical and population data of known large scale emigration from Japan during a period of industrialization from 1868–1912 which resulted in large, stable Japanese immigrant populations abroad. These three representative sites included Lima, Peru, San Paolo, Brazil, and Vancouver, Canada. Data was collected from registry and hospital-based resources within each region. Results: A review of the Brain Tumor Registry of Japan from 1984–2004 revealed an incidence of 2.5 cases/million/year, lower than previously reported, and a lower incidence of medulloblastoma at 1.2 cases/million/year. Data from Vancouver, Canada, Lima, Peru, and San Paolo, Brazil included a total population of 731,174 Japanese persons. The ratio of all medulloblastoma to iGCT cases in Japan was identified as 1:2 while the ratio was 2:1, 6.5:1, and 5:1, respectively, in the other three locations. The data suggests increased incidence in native Japan may not translate to higher incidence in immigrant Japanese populations abroad and a clear genetic component was not found in our data set. Conclusions: A more precise and comprehensive study is needed to determine the cause of this difference in incidence. This study also emphasizes the importance of national and state registries and is a call to collaborate on state and country level epidemiology studies. [ABSTRACT FROM AUTHOR]

Escape extinction has been identified as an effective treatment for feeding problems. However, negative side effects, such as extinction bursts and emotional responding, may occur with escape extinction. In some cases, treatment without escape extinction may be unsuccessful. Therefore, the purpose of this study was to evaluate modifications that may optimize the effects of escape extinction while keeping inappropriate mealtime behavior low. First, an assessment was conducted to determine the starting point for treatment, which was different for each participant. The condition that produced higher levels of acceptance and lower levels of inappropriate mealtime behavior (low response effort) was identified as the starting point for the stimulus (bolus) fading plus escape extinction treatment. Acceptance increased for all three participants with a variety of foods using an antecedent-based intervention in combination with escape extinction. Although escape extinction was part of the final treatment, inappropriate mealtime behavior was relatively low at the onset of treatment. These data are discussed in relation to motivating operations and negative reinforcement. [ABSTRACT FROM AUTHOR]

Purpose: Racial disparities in cardiovascular disease and cardiac dysfunction exist amongst breast cancer survivors. This study examined the prevalence of cardioprotective medication use in survivors and identified factors associated with use by race. Methods: The analysis included women enrolled in the Women's Hormonal Initiation and Persistence study, a longitudinal observational trial of breast cancer survivors. The study outcome, angiotensin converting enzyme inhibitor (ACEi) or ß-Blocker (BB) use, were ascertained from pharmacy records. Demographic, psychosocial, healthcare, and quality of life factors were collected from surveys and clinical data were abstracted from medical records. Bivariate associations by race and ACEi/BB use were tested using chi square and t tests; logistic regression evaluated multivariable-adjusted associations. Results: Of the 246 survivors in the sample, 33.3% were Black and most were < 65 years of age (58.4%). Most survivors were hypertensive (57.6%) and one-third received ACEi/BBs. In unadjusted analysis, White women (vs. Black) (OR 0.33, 95% 0.19–0.58) and women with higher ratings of functional wellbeing (OR 0.94, 95% 0.89–0.99) were less likely to use ACEi/BBs. Satisfaction with provider communication was only significant for White women. In multivariable-adjusted analysis, ACEi/BB use did not differ by race. Correlates of ACEi/BB use included hypertension among all women and older age for Black women only. Conclusions: After adjusting for age and comorbidities, no differences by race in ACEi/BB use were observed. Hypertension was a major contributor of ACEi/BB use in BC survivors. [ABSTRACT FROM AUTHOR]

While positive teacher–student relationships are at the heart of teaching and learning, it is no easy task to improve these relationships and cultivate caring classroom communities. This study drew on key elements of improvement science. Three 9th grade language arts teachers and one researcher collaborated to plan, implement, study and revise an instructional routine for improving relationships with and among students. As part of this collaboration, the group created a survey to learn about students' experiences in teachers' classrooms. Through qualitative data collection and analysis, I examined teachers' talk when collectively examining and discussing student survey data. Teachers' talk turned towards and away from deeper investigations of pedagogical practice and the student survey. I describe patterns of teacher talk and analyse two episodes for which teachers collectively investigated their pedagogical practice and the routine as it related to their classroom environment. These episodes revealed that talking about survey results encouraged teachers to assess their classroom communities formatively, led to the creation of a teacher learning environment, influenced teachers' practices, and evoked emotional and personal responses from teachers when looking at data connected to their classroom environments. [ABSTRACT FROM AUTHOR]

The sodium-iodide symporter (NIS) mediates the uptake of iodide into the thyroid. Inhibition of NIS function by xenobiotics has been demonstrated to suppress circulating thyroid hormones and perturb related physiological functions. Until recently, few environmental chemicals had been screened for NIS inhibition activity. We previously screened over 1000 chemicals from the ToxCast Phase II (ph1v2 and ph2) libraries using an in vitro radioactive iodide uptake (RAIU) with the hNIS-HEK293T cell line to identify NIS inhibitors. Here, we broaden the chemical space by expanding screening to include the ToxCast e1k library (804 unique chemicals) with initial screening for RAIU at 1 × 10–4 M. Then 209 chemicals demonstrating > 20% RAIU inhibition were further tested in multiple-concentration, parallel RAIU and cell viability assays. This identified 55 chemicals as active, noncytotoxic RAIU inhibitors. Further cytotoxicity-adjusted potency scoring (with NaClO4 having a reference score of 200) revealed five chemicals with moderate to strong RAIU inhibition (scored > 100). These data were combined with our previous PhII screening data to produce binary hit-calls for ~ 1800 unique chemicals (PhII + e1k) with and without cytotoxicity filtering. Results were analyzed with a ToxPrint chemotype-enrichment workflow to identify substructural features significantly enriched in the NIS inhibition hit-call space. We assessed the applicability of enriched PhII chemotypes to prospectively predict NIS inhibition in the e1k dataset. Chemotype enrichments derived for the combined ~ 1800 dataset also identified additional enriched features, as well as chemotypes affiliated with cytotoxicity. These enriched chemotypes provide important new information that can support future data interpretation, structure–activity relationship, chemical use, and regulation. [ABSTRACT FROM AUTHOR]

The KNM-ER 2598 occipital is among the oldest fossils attributed to Homo erectus but questions have been raised about whether it may derive from a younger horizon. Here we report on efforts to relocate the KNM-ER 2598 locality and investigate its paleontological and geological context. Although located in a different East Turkana collection area (Area 13) than initially reported, the locality is stratigraphically positioned below the KBS Tuff and the outcrops show no evidence of deflation of a younger unit, supporting an age of >1.855 Ma. Newly recovered faunal material consists primarily of C4 grazers, further confirmed by enamel isotope data. A hominin proximal 3rd metatarsal and partial ilium were discovered <50 m from the reconstructed location where KNM-ER 2598 was originally found but these cannot be associated directly with the occipital. The postcrania are consistent with fossil Homo and may represent the earliest postcrania attributable to Homo erectus. KNM-ER 2598 is one of the oldest known Homo erectus fossils but there are doubts about its age. Here, Hammond et al. trace the original location of the specimen, confirming an age >1.85 million years, and locating additional hominin fossils situated in a paleohabitat dominated by C4 grazers. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder where alpha-synuclein plays a central role in the death and dysfunction of neurons, both, in central, as well as in the peripheral nervous system. Besides the neuronal events observed in patients, PD also includes a significant immune component. It is suggested that the PD-associated immune response will have consequences on neuronal health, thus opening immunomodulation as a potential therapeutic strategy in PD. The immune changes during the disease occur in the brain, involving microglia, but also in the periphery with changes in cells of the innate immune system, particularly monocytes, as well as those of adaptive immunity, such as T-cells. This realization arises from multiple patient studies, but also from data in animal models of the disease, providing strong evidence for innate and adaptive immune system crosstalk in the central nervous system and periphery in PD. Here we review the data showing that alpha-synuclein plays a crucial role in the activation of the innate and adaptive immune system. We will also describe the studies suggesting that inflammation in PD includes early changes in innate and adaptive immune cells that develop dynamically through time during disease, contributing to neuronal degeneration and symptomatology in patients. This novel finding has contributed to the definition of PD as a multisystem disease that should be approached in a more integratory manner rather than a brain-focused classical approach. [ABSTRACT FROM AUTHOR]

The alkylating agent, temozolomide (TMZ), is the most commonly used chemotherapeutic for the treatment of glioblastoma (GBM). The anti-glioma effect of TMZ involves a complex response that includes G2-M cell cycle arrest and cyclin-dependent kinase 1 (CDK1) activation. While CDK1 phosphorylation is a well-described consequence of TMZ treatment, we find that TMZ also robustly induces CDK1 expression. Analysis of this pathway demonstrates that CDK1 is regulated by NF-κB via a putative κB-site in its proximal promoter. CDK1 was induced in a manner dependent on mature p50 and the atypical inhibitor κB protein, BCL-3. Treatment with TMZ induced binding of NF-κB to the κB-site as assessed by gel shift analysis and chromatin immunoprecipitation. Examination of a CDK1 promoter-reporter demonstrated the functional relevance of the κB-site and underlined the requirement of p50 and BCL-3 for activation. Targeted knockdown of CDK1 or chemical inhibition with the selective CDK1 inhibitor, RO-3306, potentiated the cytotoxic effect of TMZ. These results identify CDK1 as an NF-κB target gene regulated by p50 and BCL-3 and suggest that targeting CDK1 may be a strategy to improve the efficacy of TMZ against GBM. [ABSTRACT FROM AUTHOR]

Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction1, although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms B–E (H1B, H1C, H1D and H1E; also known as H1-5, H1-2, H1-3 and H1-4, respectively) are highly recurrent in B cell lymphomas, but the pathogenic relevance of these mutations to cancer and the mechanisms that are involved are unknown. Here we show that lymphoma-associated H1 alleles are genetic driver mutations in lymphomas. Disruption of H1 function results in a profound architectural remodelling of the genome, which is characterized by large-scale yet focal shifts of chromatin from a compacted to a relaxed state. This decompaction drives distinct changes in epigenetic states, primarily owing to a gain of histone H3 dimethylation at lysine 36 (H3K36me2) and/or loss of repressive H3 trimethylation at lysine 27 (H3K27me3). These changes unlock the expression of stem cell genes that are normally silenced during early development. In mice, loss of H1c and H1e (also known as H1f2 and H1f4, respectively) conferred germinal centre B cells with enhanced fitness and self-renewal properties, ultimately leading to aggressive lymphomas with an increased repopulating potential. Collectively, our data indicate that H1 proteins are normally required to sequester early developmental genes into architecturally inaccessible genomic compartments. We also establish H1 as a bona fide tumour suppressor and show that mutations in H1 drive malignant transformation primarily through three-dimensional genome reorganization, which leads to epigenetic reprogramming and derepression of developmentally silenced genes. Mutations in histone H1 induce the remodelling of chromatin architecture to a more relaxed state, which leads to malignant transformation through changes in histone modifications and the expression of stem cell genes. [ABSTRACT FROM AUTHOR]

Science, propelled forward by noble aspirations and, at times, human hubris, has the capacity to affect lives and alter the world in unanticipated ways. Even seemingly minor discoveries have repeatedly proven to have far reaching implications that experts within their respective fields could not have predicted. Nuclear technology is both a source of energy and a potential means of annihilation. The internet has both seamlessly connected the world but has also opened society to the misuse and manipulation of information. Both exemplify how new technologies have the potential for positive and negative outcomes that often go beyond what was initially intended. This is not a fault of science and innovation but rather an inherent occupational hazard as new discoveries exist within a gray zone between ignorance and comprehension. These gaps in our knowledge can only be filled over time as our knowledge expands. Innovations that were once seen as fringe, over time, become mainstream and that which was once revolutionary becomes a part of everyday life. Occasionally, a scientific advancement comes along that challenges societal norms and causes us to question what is feasible, acceptable, and ethical. Nowhere in the twenty-first century has this been more evident than within the fields of genetics and genetic engineering. As we gain a deeper understanding of the source code of life, from individual base pairs to epigenetic influences, the implications of new discoveries will go far beyond curing genetic diseases, and the possibilities will be endless. Reproductive endocrinology and infertility (REI) specialists utilize many tools including expanded carrier screening, preimplantation genetic testing, and embryo selection and have become some of the experts at the forefront of the ongoing genetic revolution. Now more than ever, there is a need for REIs to be trained in the fundamentals of genetics, exposed to novel gene sequencing and editing techniques, and involved in the coming ethical discussions in order to be prepared for the genetically engineered future. [ABSTRACT FROM AUTHOR]

This paper presents a case study of long-term post-retraction citation to falsified clinical trial data (Matsuyama et al. in Chest 128(6):3817–3827, 2005. https://doi.org/10.1378/chest.128.6.3817), demonstrating problems with how the current digital library environment communicates retraction status. Eleven years after its retraction, the paper continues to be cited positively and uncritically to support a medical nutrition intervention, without mention of its 2008 retraction for falsifying data. To date no high quality clinical trials reporting on the efficacy of omega-3 fatty acids on reducing inflammatory markers have been published. Our paper uses network analysis, citation context analysis, and retraction status visibility analysis to illustrate the potential for extended propagation of misinformation over a citation network, updating and extending a case study of the first 6 years of post-retraction citation (Fulton et al. in Publications 3(1):7–26, 2015. https://doi.org/10.3390/publications3010017). The current study covers 148 direct citations from 2006 through 2019 and their 2542 second-generation citations and assesses retraction status visibility of the case study paper and its retraction notice on 12 digital platforms as of 2020. The retraction is not mentioned in 96% (107/112) of direct post-retraction citations for which we were able to conduct citation context analysis. Over 41% (44/107) of direct post-retraction citations that do not mention the retraction describe the case study paper in detail, giving a risk of diffusing misinformation from the case paper. We analyze 152 second-generation citations to the most recent 35 direct citations (2010–2019) that do not mention the retraction but do mention methods or results of the case paper, finding 23 possible diffusions of misinformation from these non-direct citations to the case paper. Link resolving errors from databases show a significant challenge in a reader reaching the retraction notice via a database search. Only 1/8 databases (and 1/9 database records) consistently resolved the retraction notice to its full-text correctly in our tests. Although limited to evaluation of a single case (N = 1), this work demonstrates how retracted research can continue to spread and how the current information environment contributes to this problem. [ABSTRACT FROM AUTHOR]

For species that do not provide parental care after birth, excess maternal provisioning during development, beyond what is required for embryogenesis, provides offspring with resources to increase their chances of survival. Maternally derived resources are expected to be important for buffering offspring against limited food resources at birth or time needed to learn how to properly feed. Young-of-the-year (YOY) cryptic Scalloped Hammerheads (Sphyrna lewini) and Carolina Hammerheads (Sphyrna gilberti) were sampled from nurseries along the US Atlantic Coast and compared for a number of biological condition metrics across three developmental stages. Large declines in liver lipid content and hepatosomatic indices were found in neonatal sharks, using umbilical scar healing as a proxy for time since birth. Feeding commenced quickly as 96% of sharks had prey remnants in their stomachs. The combination of rapid exhaustion of maternally provided resources and high occurrence of stomachs with prey contents indicate that nursery quality, with respect to prey availability, may be important for YOY hammerhead survivorship. While externally the two species are morphologically similar, longer length-at-birth in S. lewini and higher hepatic condition in neonatal S. gilberti suggest that aspects of reproductive biology, including physiology, may differ between species. While more information is needed to distinguish life history differences between these two species, data collected from YOY may serve as a useful proxy to inform management when adult samples of cryptic species are difficult to collect. [ABSTRACT FROM AUTHOR]

Integrins are important for mechanosensation in tissue and play, together with nutrition, a role in regulating extracellular matrix (ECM) in skeletal muscle and tendon. Integrin receptors are dimers that consist of an α and β subunit and bridge extracellular and intracellular signals. The present study investigates whether the deletion of the integrin receptor α1 subunit influences collagen and other matrix proteins in the musculotendinous tissue and whether it causes any compensatory changes in other integrin subunits in C57BL/6J mice. In addition, we study whether a high-fat diet (HFD) influences these responses in muscle or tendon. Mice on a HFD had a higher number of non-enzymatic cross-links in skeletal muscle ECM and increased gene expression of collagen and other extracellular matrix proteins. In contrast to gene expression, total collagen protein content was decreased by HFD in the muscle with no change in tendon. Integrin α1 subunit knockout resulted in a decrease of collagen type I and III, TGF-β1 and IGF-1 gene expression in muscle of HFD mice but did not affect total collagen protein compared with wild-type (WT) littermates in either muscle or tendon. There was no compensatory increase in the genes that express other integrin subunits. In conclusion, HFD induced a significant increase in expression of ECM genes in muscle. On the protein level, HFD resulted in a lower collagen content in muscle. Tendons were unaffected by the diet. Deletion of the integrin α1 subunit did not affect collagen protein or gene expression in muscle or tendon. [ABSTRACT FROM AUTHOR]

The life-history patterns that animals display are a product of their ability to maximize reproductive performance while concurrently balancing numerous metabolic demands. For example, the energetic costs of reproduction may reduce an animal's ability to support self-maintenance and longevity. In this work, we evaluated the impact of parity on mitochondrial physiology in laboratory mice. The theory of mitohormesis suggests that modest exposure to reactive oxygen species can improve performance, while high levels of exposure are damaging. Following this theory, we hypothesized that females that experienced one bout of reproduction (primiparous) would display improved mitochondrial capacity and reduced oxidative damage relative to non-reproductive (nulliparous) mice, while females that had four reproductive events (multiparous) would have lower mitochondrial performance and greater oxidative damage than both nulliparous and primiparous females. We observed that multiple reproductive events enhanced the mitochondrial respiratory capacity of liver mitochondria in females with high body mass. Four-bout females showed a positive relationship between body mass and mitochondrial capacity. In contrast, non-reproductive females showed a negative relationship between body mass and mitochondrial capacity and primiparous females had a slope that did not differ from zero. Other measured variables, too, were highly dependent on body mass, suggesting that a female's body condition has strong impacts on mitochondrial physiology. We also evaluated the relationship between how much females allocated to reproduction (cumulative mass of all young weaned) and mitochondrial function and oxidative stress in the multiparous females. We found that females that allocated more to reproduction had lower basal respiration (state 4), lower mitochondrial density, and higher protein oxidation in liver mitochondria than females that allocated less. These results suggest that, at least through their first four reproductive events, female laboratory mice may experience bioenergetic benefits from reproduction but only those females that allocated the most to reproduction appear to experience a potential cost of reproduction. [ABSTRACT FROM AUTHOR]

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by abnormal accumulation of alpha-synuclein (α-syn) in oligodendrocytes accompanied by inflammation, demyelination, and subsequent synapse and neuronal loss. Little is known about the mechanisms of neurodegeneration in MSA. However, recent work has highlighted the important role of the immune system to the pathophysiology of other synuclein-related diseases such as Parkinson's disease. In this study, we investigated postmortem brain tissue from MSA patients and control subjects for evidence of immune activation in the brain. We found a significant increase of HLA-DR+ microglia in the putamen and substantia nigra of MSA patient tissue compared to controls, as well as significant increases in CD3+, CD4+, and CD8+ T cells in these same brain regions. To model MSA in vivo, we utilized a viral vector that selectively overexpresses α-syn in oligodendrocytes (Olig001-SYN) with > 95% tropism in the dorsal striatum of mice, resulting in demyelination and neuroinflammation similar to that observed in human MSA. Oligodendrocyte transduction with this vector resulted in a robust inflammatory response, which included increased MHCII expression on central nervous system (CNS) resident microglia, and infiltration of pro-inflammatory monocytes into the CNS. We also observed robust infiltration of CD4 T cells into the CNS and antigen-experienced CD4 T cells in the draining cervical lymph nodes. Importantly, genetic deletion of TCR-β or CD4 T cells attenuated α-syn-induced inflammation and demyelination in vivo. These results suggest that T cell priming and infiltration into the CNS are key mechanisms of disease pathogenesis in MSA, and therapeutics targeting T cells may be disease modifying. [ABSTRACT FROM AUTHOR]

Emphasizing customer satisfaction as a strategic lever for enhancing business performance is a widespread business practice. However, just over 25 years of empirical studies by academic researchers has produced evidence that is sometimes contradictory. Hence, greater academic clarity and improved managerial understanding could result from a meta-analysis of the customer satisfaction-business performance relationship. To that end, the authors analyzed 251 correlations from 96 studies published between 1991 and 2017. While the satisfaction-performance relationship is positive and statistically significant on average (r =.101), more meaningful insights emerge from the explication of moderating and mediating relationships. Illustrative of these insights is the finding that satisfaction is more appropriately depicted as mediating the effects of selected marketing strategy variables on firm performance outcomes. Moreover, when satisfaction is viewed in the right setting using the right satisfaction and performance measures, a most favorable contingencies (MFC) perspective, the estimated correlation is reasonably strong (r =.349). [ABSTRACT FROM AUTHOR]

Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3). Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts. [ABSTRACT FROM AUTHOR]

We conducted two experiments to investigate how crossing a single naturalistic event boundary impacted two different types of temporal estimation involving the same target duration – one where participants directly compared marked temporal durations and another where they judged the temporal proximity of stimuli. In Experiment 1, participants judged whether time intervals presented during movies of everyday events were shorter or longer than a previously encoded 5-s reference interval. We examined how the presence of a transition between events (event boundary) in the movie influenced people's judgments about the length of the comparison interval. Comparison intervals presented during a portion of the movie containing an event boundary were judged as shorter than the reference interval more often than comparison intervals that contained no boundary. Working-memory updating at the event boundary may have directed attention away from the concurrent timing task. In Experiment 2, participants judged whether the second of three tones presented during everyday movies was closer to the first or the third tone presented. Tones separated by an event boundary were judged as farther apart than tones contained within the same event. When judging temporal proximity, attention directed to processing information at an event boundary between two stimuli may disrupt the formation of temporal associations between those stimuli. Overall, these results demonstrate that crossing a single event boundary can impact people's prospective perceptions of the temporal characteristics of their experience and suggest that the episodic memory updating that occurs during an event boundary both captures timing-relevant attentional resources and plays a role in the temporal binding of information. [ABSTRACT FROM AUTHOR]

A boronic acid-based anthracene fluorescent probe was functionalised with an acrylamide unit to incorporate into a hydrogel system for monosaccharide detection. In solution, the fluorescent probe displayed a strong fluorescence turn-on response upon exposure to fructose, and an expected trend in apparent binding constants, as judged by a fluorescence response where d–fructose > d–galactose > d–mannose > d–glucose. The hydrogel incorporating the boronic acid monomer demonstrated the ability to detect monosaccharides by fluorescence with the same overall trend as the monomer in solution with the addition of d–fructose resulting in a 10-fold enhancement (⩽ 0.25 mol/L). [ABSTRACT FROM AUTHOR]

The Fischer rat thyroid follicular cell line (FRTL-5) endogenously expresses the sodium-iodide symporter (NIS) and has been used to identify environmental chemicals that perturb thyroid hormone homeostasis by disruption of NIS-mediated iodide uptake. Previously, a high-throughput radioactive iodide uptake (RAIU) screening assay incorporating the hNIS-HEK293T-EPA cell line was used to identify potential human NIS (hNIS) inhibitors in 1028 ToxCast Phase I (ph1_v2) and Phase II chemicals. In this study, the FRTL-5 cell line was evaluated and applied as a secondary RAIU assay coupled with cell viability assays to further prioritize highly active NIS inhibitors from the earlier screening. Assay validation with ten reference chemicals and performance assessment by chemical controls suggest the FRTL-5 based assays are robust and highly reproducible. Top-ranked chemicals from the ToxCast screening were then evaluated in both FRTL-5 and hNIS RAIU assays using newly sourced chemicals to strengthen the testing paradigm and to enable a rat vs. human species comparison. Eighteen of 29 test chemicals showed less than 1 order of magnitude difference in IC50 values between the two assays. Notably, two common perfluorinated compounds, perfluorooctanesulfonic acid (PFOS) and perfluorohexane sulfonate (PFHxS), demonstrated strong NIS inhibitory activity [IC50 − 6.45 (PFOS) and − 5.70 (PFHxS) log M in FRTL-5 RAIU assay]. In addition, several chemicals including etoxazole, methoxyfenozide, oxyfluorfen, triclocarban, mepanipyrim, and niclosamide also exhibited NIS inhibition with minimal cytotoxicity in both assays and are proposed for additional testing using short-term in vivo assays to characterize effects on thyroid hormone synthesis. [ABSTRACT FROM AUTHOR]

Houben et al. acknowledged this difference, although Lee, de Jongh, and Hase ([19]) claimed that Houben et al. ([17]) had ignored the incompatible results of Parker et al. ([25]). Additionally, Houben et al. ([17]) had participants retrieve their memory of the video while performing eye movements or the control task, whereas Parker et al. ([25]) did not. Working memory explanations of EMDR suggest that eye movements should tax working memory and reduce the vividness and emotionality of memories. 18 Houben STL, Otgaar H, Roelofs J, Merckelbach H. EMDR and false memories: A response to Lee, de Jongh, and Hase (2019). [Extracted from the article]

Purpose: To compare self-rated health among the United States general population in 2002 and 2017.Methods: Secondary data were analyzed from two EQ-5D valuation studies conducted in 2002 and 2017. Both studies included the EQ-5D-3L self-classifier and visual analog scale (VAS), where health is rated from 0 (worst imaginable health) to 100 (best imaginable health). VAS scores were compared between time points using regression models, adjusting for sociodemographic factors (Model 1), plus illness (Model 2), and health problems according to the EQ-5D classifier (Model 3).Results: Mean VAS scores in 2002 [84.4 (SD = 16.1)] were not different from 2017 [84.6 (SD = 14.5)] (p = 0.63), nor different after adjusting for demographics (Model 1) or illness (Model 2). However, 2017 VAS mean scores were significantly higher than 2002 [2.2 (95% CI 1.36-3.10)] upon adjusting for the presence of dimension-specific health problems.Conclusions: Self-rated health of the general US adult population in 2017 was similar to 2002, but after adjusting for health problems, scores were slightly higher in 2017. Sociodemographic shifts in age and education explain some of the differences in scores, and by removing health and sociodemographic factors, we found the VAS reveals self-rated health is slightly better in 2017 than 2002. [ABSTRACT FROM AUTHOR]

Purpose: Irradiation-avoiding strategies have been used with relative success in the treatment of infants and young children with medulloblastoma. While advances in cancer genomics have significantly improved our understanding of the tumor biology of medulloblastoma allowing for improved prognostication and risk-stratification, the molecular subgroup-specific outcomes of infants and young children with medulloblastoma treated with irradiation-avoiding strategies remains unknown. Methods: Molecular and clinical features of children with medulloblastoma treated with irradiation-avoiding strategies at Children's Hospital Los Angeles were analyzed. Molecular subgrouping of these patients was determined using a 31-gene TaqMan Low Density Array signature. Survival analyses were conducted based on 3 molecular subgroups (SHH, Group 3, and Group 4). Results: Twenty-eight patients with medulloblastoma received irradiation-sparing regimens and were included in this analysis. Patients were divided into SHH (n = 16), Group 3 (n = 3) and Group 4 subgroups (n = 9). Subgroup specific 5-year progression-free and overall survival was 81.2% (95% CI 52.5–93.5) and 93.7% (95% CI 63.2–99.1) for SHH, 0% and 0% for Group 3 and 0% and 44.4% (95% CI 13.6–71.9) for Group 4. Conclusion: The majority of young children with SHH-subgroup medulloblastoma can be treated effectively with irradiation-sparing regimens. Our results support the use of chemotherapy-only strategies for upfront treatment of young children with SHH medulloblastoma, while demonstrating the urgent need for intensification/augmentation of treatment for patients with group 3/4 medulloblastoma. [ABSTRACT FROM AUTHOR]