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Atypical Scrapie, which is not linked to epidemics, is assumed to be an idiopathic spontaneous prion disease in small ruminants. Therefore, its occurrence is unlikely to be controlled through selective breeding or other strategies as it is done for classical scrapie outbreaks. Its spontaneous nature and its sporadic incidence worldwide is reminiscent of the incidence of idiopathic spontaneous prion diseases in humans, which account for more than 85% of the cases in humans. Hence, developing animal models that consistently reproduce this phenomenon of spontaneous PrP misfolding, is of importance to study the pathobiology of idiopathic spontaneous prion disorders. Transgenic mice overexpressing sheep PrP C with I112 polymorphism (TgShI112, 1-2 × PrP levels compared to sheep brain) manifest clinical signs of a spongiform encephalopathy spontaneously as early as 380 days of age. The brains of these animals show the neuropathological hallmarks of prion disease and biochemical analyses of the misfolded prion protein show a ladder-like PrP res pattern with a predominant 7-10 kDa band. Brain homogenates from spontaneously diseased transgenic mice were inoculated in several models to assess their transmissibility and characterize the prion strain generated: TgShI112 (ovine I112 ARQ PrP C ), Tg338 (ovine VRQ PrP C ), Tg501 (ovine ARQ PrP C ), Tg340 (human M129 PrP C ), Tg361 (human V129 PrP C ), TgVole (bank vole I109 PrP C ), bank vole (I109I PrP C ), and sheep (AHQ/ARR and AHQ/AHQ churra-tensina breeds). Our analysis of the results of these bioassays concludes that the strain generated in this model is indistinguishable to that causing atypical scrapie (Nor98). Thus, we present the first faithful model for a bona fide, transmissible, ovine, atypical scrapie prion disease., (© 2022. The Author(s).)

The emergence of COVID-19 as a global pandemic forced researchers worldwide in various disciplines to investigate and propose efficient strategies and/or technologies to prevent COVID-19 from further spreading. One of the main challenges to be overcome is the fast and efficient detection of COVID-19 using deep learning approaches and medical images such as Chest Computed Tomography (CT) and Chest X-ray images. In order to contribute to this challenge, a new dataset was collected in collaboration with "S.E.S Hospital Universitario de Caldas" ( https://hospitaldecaldas.com/ ) from Colombia and organized following the Medical Imaging Data Structure (MIDS) format. The dataset contains 7,307 chest X-ray images divided into 3,077 and 4,230 COVID-19 positive and negative images. Images were subjected to a selection and anonymization process to allow the scientific community to use them freely. Finally, different convolutional neural networks were used to perform technical validation. This dataset contributes to the scientific community by tackling significant limitations regarding data quality and availability for the detection of COVID-19., (© 2022. The Author(s).)

Background: Fine-needle aspiration cytology (FNAC) is generally the initial sampling method for salivary gland neoplasms. The cytomorphologic features of acinic cell carcinoma (AciCC) of salivary gland can overlap with other neoplastic and nonneoplastic entities. AciCCs harbor a recurrent t(4;9) rearrangement with upregulation of nuclear receptor subfamily 4 group A member 3 (NR4A3). NR4A3 protein overexpression has been shown to be highly sensitive and specific for the diagnosis of AciCC in histologic specimens and cell block preparations. However, data on NR4A3 immunocytochemistry (ICC) on conventional smears or liquid-based cytology are limited., Methods: The authors identified 18 FNAC of histologically proven AciCC cases between 2013 and 2019. FNAC samples of diagnostic mimickers were likewise retrieved and included in the study cohort for comparison. The NOR1/NR4A3 mouse monoclonal antibody was applied directly to FNAC slides using a standard ICC technique., Results: The cohort included ethanol-fixed Papanicolaou-stained cytologic smears and liquid-based preparations from 18 AciCC, one secretory carcinoma, four mucoepidermoid carcinomas, four salivary duct carcinomas, five pleomorphic adenomas (PA), five Warthin tumors, five oncocytomas, one oncocytic hyperplasia, and five nonneoplastic salivary gland cases. Strong nuclear staining for NR4A3 was present in all AciCC, weak nuclear staining was present in one PA, and all other non-AciCC were negative (sensitivity, 100%; specificity, 97%)., Conclusions: NR4A3 ICC can be used directly on FNAC conventional smears and liquid-based cytology to reliably distinguish AciCC from its mimickers. This marker may be useful in cases where a cell block preparation is unavailable or inadequate., (© 2022 American Cancer Society.)

Urine cytology of urinary tract condylomas has not been systematically studied. We analyzed cytologic features of urinary tract condylomas and evaluated potential diagnostic challenges and pitfalls. We retrospectively reviewed urine cytology of urinary tract condylomas from 2 academic institutions (2015-2022). Among 20 patients with urinary tract condylomas, 6 had urine cytology (2 samples in 1 patient), including 3 men and 3 women (mean age, 74.3 years; range, 65-86 years). Original interpretations were negative for high-grade urothelial carcinoma (NHGUC; n = 4), atypical urothelial cells (n = 1), reactive urothelial cells (n = 1), and negative for malignancy (n = 1). Squamous cells were noted in 3 cases, atypical squamous cells (ASC) consistent with low-grade squamous intraepithelial lesion (LSIL) were noted in 1 case, and in 3 cases, the presence of squamous cells was not mentioned. All urines were reclassified according to The Paris System as NHGUC. Specimens were composed of benign urothelial cells and groups or isolated ASC consistent with LSIL (n = 4), atypical keratinized squamous cells (n = 2), and ASC that did not meet LSIL criteria (n = 1). The LSIL cells showed nuclear enlargement (n = 4), hyperchromasia (n = 4), perinuclear halo (n = 3), nuclear membrane irregularity (n = 4), orangeophilic cytoplasm (n = 3), and binucleation (n = 4). The atypical keratinized squamous cells showed hyperchromasia (n = 2), nuclear membrane irregularity (n = 2), keratin pearls (n = 2), and binucleation (n = 1). The ASC that did not meet LSIL criteria showed nuclear enlargement and orangeophilic cytoplasm. Many urinary tract condylomas (57%) demonstrate classic LSIL features in urine cytology. Less frequent cases can mimic keratinizing squamous cell carcinoma (28%) or demonstrate ASC not diagnostic of LSIL (15%)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Statistics show that an estimated 64 million people worldwide suffer from glaucoma. To aid in the detection of this disease, this paper presents a new public dataset containing eye fundus images that was developed for glaucoma pattern-recognition studies using deep learning (DL). The dataset, denoted Brazil Glaucoma, comprises 2000 images obtained from 1000 volunteers categorized into two groups: those with glaucoma (50%) and those without glaucoma (50%). All images were captured with a smartphone attached to a Welch Allyn panoptic direct ophthalmoscope. Further, a DL approach for the automatic detection of glaucoma was developed using the new dataset as input to a convolutional neural network ensemble model. The accuracy between positive and negative glaucoma detection, sensitivity, and specificity were calculated using five-fold cross-validation to train and refine the classification model. The results showed that the proposed method can identify glaucoma from eye fundus images with an accuracy of 90.0%. Thus, the combination of fundus images obtained using a smartphone attached to a portable panoptic ophthalmoscope and artificial intelligence algorithms yielded satisfactory results in the overall accuracy of glaucoma detection tests. Consequently, the proposed approach can contribute to the development of technologies aimed at massive population screening of the disease.

We performed collapsing analyses on 454,796 UK Biobank (UKB) exomes to detect gene-level associations with diabetes. Recessive carriers of nonsynonymous variants in MAP3K15 were 30% less likely to develop diabetes ( P = 5.7 × 10 -10 ) and had lower glycosylated hemoglobin (β = -0.14 SD units, P = 1.1 × 10 -24 ). These associations were independent of body mass index, suggesting protection against insulin resistance even in the setting of obesity. We replicated these findings in 96,811 Admixed Americans in the Mexico City Prospective Study ( P < 0.05)Moreover, the protective effect of MAP3K15 variants was stronger in individuals who did not carry the Latino-enriched SLC16A11 risk haplotype ( P = 6.0 × 10 -4 ). Separately, we identified a Finnish-enriched MAP3K15 protein-truncating variant associated with decreased odds of both type 1 and type 2 diabetes ( P < 0.05) in FinnGen. No adverse phenotypes were associated with protein-truncating MAP3K15 variants in the UKB, supporting this gene as a therapeutic target for diabetes.

Purpose: Immune checkpoint inhibitors are one of the most effective treatments available in advanced non-small cell lung cancer. However, at present, there are no clinical or analytical biomarkers that define which patients benefit with certainty from these treatments. In our study, we evaluated whether excess weight could be a good predictive biomarker of benefit from these drugs., Methods: We studied a population of 79 patients, divided into a study group with 39 patients diagnosed with non-small cell lung cancer treated with immunotherapy and 40 patients in a control group, diagnosed with different advanced cancers, treated with non-immunotherapy treatment. We analyzed according to the presence of excess weight or not, the treatment's outcome in the study group and in the control group (objective response, and progression-free and overall survival)., Results: In our study, we detected a better response rate to immunotherapy in patients with excess weight (62.50 vs 26.08%, OR 4.72, p = 0.02), and a better median progression-free survival (14.19 vs 5.03 months, HR 0.50, p = 0.058) and median overall survival (33.84 months vs 20.76 months, HR 0.43, p = 0.01) in the study group. These findings were specific to the immunotherapy group since in the control group, with patients who did not receive immune checkpoint inhibitors, these findings were not found., Conclusion: Our study suggests that patients with excess weight who receive anti-PD-1 immune checkpoint inhibitors diagnosed with non-small cell lung cancer have a better outcome. This effect is specific to patients receiving immunotherapy., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

DEK::AFF2 carcinoma of the sinonasal tract is an emerging entity. The tumor is typically characterized by papillary proliferation of non-keratinizing squamous epithelial cells with monotonous cytologic features, which may mimic other sinonasal tumors. The confirmation of this gene fusion has thus far relied solely on next-generation sequencing, fluorescence in situ hybridization (FISH), or reverse transcription polymerase chain reaction (RT-PCR). This current study aimed to validate an immunohistochemical assay for AFF2 C-terminus as an ancillary marker. We first analyzed publicly available RNA sequencing data of sinonasal tumors from the national center for biotechnology information (NCBI) sequence read archive and identified 3 DEK::AFF2 carcinomas out of 28 sinonasal tumors. The gene expression of AFF2 was significantly higher in the fusion-positive cases compared to the wild-type tumors (p < 0.001), while DEK was not. We then optimized an immunohistochemical assay with an anti-AFF2 C-terminus antibody for ancillary diagnosis. Seventeen DEK::AFF2 carcinomas, including 11 cases with predominantly low-grade morphology and one showing glandular differentiation, as well as 78 DEK FISH-negative sinonasal tumors were evaluated by AFF2 immunohistochemistry (IHC). Sixteen of the 17 DEK::AFF2 carcinomas showed nuclear AFF2 expression in ≥30% of tumor cells, including one decalcified case that failed FISH and RT-PCR confirmation. The one case that was negative for AFF2 IHC in the tumor cells also lacked expression in the internal positive control. It was thus considered a failure of the IHC rather than a truly negative case and was excluded from the statistical analysis. All DEK FISH-negative sinonasal tumors were negative for nuclear AFF2 expression. The nuclear expression of AFF2 IHC showed 100% sensitivity and specificity for DEK::AFF2 carcinoma. Accordingly, AFF2 IHC is a highly sensitive and specific ancillary marker that distinguishes DEK-AFF2 carcinoma from the other sinonasal tumors with overlapping morphological features and may be an especially useful alternative for decalcified specimens., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Background: ThyroSeq assesses the probability of malignancy (POM) in thyroid fine-needle aspiration cytology specimens diagnosed as atypia of undetermined significance (AUS). The authors investigated whether defined AUS subcategories are associated with specific molecular alterations, the molecular-derived risk of malignancy (MDROM), and the risk of malignancy (ROM)., Methods: Fine-needle aspiration cytology reports of AUS and corresponding results from the ThyroSeq version 3 genomic classifier results were retrieved and subcategorized as follicular cells with either cytologic atypia (FC-C), architectural atypia (FC-A), both cytologic and architectural atypia (FC-CA), or a predominance of Hurthle cells (PHC). The MDROM, ROM, and frequency of molecular alterations by subcategory were computed and analyzed, and p &lt; .05 was considered significant., Results: The final analysis included 541 cases subdivided into 233 with FC-A, 104 with FC-C, 116 with FC-CA, and 88 with PHC. The benign call rate and positive call rate for the AUS category were 72% and 28%, respectively, which varied between AUS subcategories. The MDROM by subcategory was 15.9% FC-A, 20.5% FC-C, 33.8% FC-CA, and 14.4% PHC. Histologic follow-up was available for 155 (28%) AUS cases with a follow-up period ≥12 months. The 95% confidence intervals of the MDROMs overlapped with the ROMs. The highest MDROM and ROM were in the FC-CA subcategory. RAS mutations were present in all subcategories. BRAF V600E mutations and papillary thyroid carcinoma were most frequent in the FC-CA subcategory. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features was significantly more frequent in the FC-C subcategory., Conclusions: The current results demonstrated that AUS subcategories are associated with specific genetic alterations, the MDROM, and the ROM. Molecular results and an awareness of various cancer probabilities within AUS subcategories can allow for a more tailored management., (© 2022 American Cancer Society.)

A growing body of research suggests that adult child educational attainment benefits older parents' cognitive outcomes via financial (e.g., direct monetary transfers) and nonfinancial (e.g., psychosocial) mechanisms. Quasi-experimental studies are needed to circumvent confounding bias. No such quasi-experimental studies have been completed in higher-income countries, where financial transfers from adult children to aging parents are rare. Using data on 8,159 adults aged ≥50 years in the Survey for Health, Aging and Retirement in Europe (2004/2005), we leveraged changes in compulsory schooling laws as quasi-experiments. Each year of increased schooling among respondents' oldest children was associated with better verbal fluency (β = 0.07, 95% CI: 0.02, 0.12) scores; overall associations with verbal memory scores were null, with mixed and imprecise evidence of association in models stratified by parent gender. We also evaluated associations with psychosocial outcomes as potentially important mechanisms. Increased schooling among respondents' oldest children was associated with higher quality-of-life scores and fewer depressive symptoms. Our findings present modest albeit inconsistent evidence that increases in schooling may have an "upward" influence on older parents' cognitive performance even in settings where financial transfers from adult children to their parents are uncommon. Associations with parents' psychosocial outcomes were more robust., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study analyzed changes in the psychological health of students who were in the final year of their nursing degree during the COVID-19 pandemic and later served as nursing professionals in hospitals. Methods: A prospective longitudinal study was conducted over two periods of time (the first in April 2020 and the second 6 months later, in December 2020) with 296 students for a T0 baseline (rate response 68.83%) and 92 students for a T1 post-test sample (response rate 31.08%). The data were electronically collected using the Hospital Anxiety and Depression Scale, the Life Satisfaction Questionnaire, the Resilience Scale, and a post-traumatic stress questionnaire. The mean age of the sample participants was 24.17 years (SD = 5.51), and 89.11% were female. During the pandemic, 14.11% of students showed scores that indicated depression, and 32.61% showed scores that indicated anxiety. In December 2020, 86.5% of the participants were working as nurses, and the percentages of those with anxiety (12%) and depression (4.3%) were significantly lower than in the first sample period. A total of 20.7% of the participants had post-traumatic stress. High scores for resilience were significantly associated with better quality of life and lower levels of anxiety, depression, and post-traumatic stress. Conclusions: Although the percentages of participants with anxiety and depression decreased, they still presented with mental health problems.

The role of the glycosylation status of PrPC in the conversion to its pathological counterpart and on cross-species transmission of prion strains has been widely discussed. Here, we assessed the effect on strain characteristics of bovine spongiform encephalopathy (BSE) isolates with different transmission histories upon propagation on a model expressing a non-glycosylated human PrPC. Bovine, ovine and porcine-passaged BSE, and variant Creutzfeldt-Jakob disease (vCJD) isolates were used as seeds/inocula in both in vitro and in vivo propagation assays using the non-glycosylated human PrPC-expressing mouse model (TgNN6h). After protein misfolding cyclic amplification (PMCA), all isolates maintained the biochemical characteristics of BSE. On bioassay, all PMCA-propagated BSE prions were readily transmitted to TgNN6h mice, in agreement with our previous in vitro results. TgNN6h mice reproduced the characteristic neuropathological and biochemical hallmarks of BSE, suggesting that the absence of glycans did not alter the pathobiological features of BSE prions. Moreover, back-passage of TgNN6h-adapted BSE prions to BoTg110 mice recovered the full BSE phenotype, confirming that the glycosylation of human PrPC is not essential for the preservation of the human transmission barrier for BSE prions or for the maintenance of BSE strain properties., Competing Interests: The authors have declared that no competing interests exist.

Background . Metastatic clear cell renal cell carcinoma (RCC) is one of the most common secondary thyroid malignancies. Diagnosis can be challenging, particularly if presenting many years after initial diagnosis. We reviewed clinicopathologic features and immunoprofile of metastatic clear cell RCC in thyroid. Design. We identified 17 patients from 2003-2021. Clinical data were obtained from medical records, and slides were retrieved and reviewed. Results . Seventeen patients (12 male and 5 female) included 12 thyroidectomies, 3 core biopsies, 1 excisional biopsy, and 1 fine-needle aspiration. The average patient age was 68.7 years (range, 45-88 years). Sixteen patients had history of clear cell RCC, and in 1 patient, the clear cell RCC was discovered after the thyroid metastasis was found. Thyroid gland metastases were on average diagnosed 90.7 months after the diagnosis of the renal primary (range, 24-240 months). Patients presented with a new palpable mass (n = 11) or dyspnea/stridor (n = 1). Five tumors were incidentally found via surveillance imaging. In 2 patients, metastases occurred within follicular thyroid neoplasms. All metastases showed conspicuous sinusoidal vasculature between the tumor nests and areas of myxoid degeneration. A prominent thick fibromuscular pseudocapsule was evident in 10 resections. Immunohistochemistry (n = 5) showed that the metastases were positive for PAX8, CA9, and CD10, while negative for keratin 7, thyroglobulin, and TTF1. Conclusions . Metastatic clear cell RCC involving the thyroid gland is infrequent and typically occurs remotely after the initial diagnosis. Cytologic and histologic features may show significant overlap with primary thyroid lesions. Immunohistochemistry can help reliably distinguish metastases from primary thyroid neoplasms.

Objective: This study examines how onset of chronic pain affects characteristics of personal social networks among adults aged 51+ across Europe., Methods: We used population-based data from the Survey of Health, Ageing and Retirement in Europe (SHARE; 2011-2015; n = 12,647). Using a change score analysis approach, we tracked changes in personal social networks of respondents experiencing new-onset chronic pain (n = 3803) compared to pain-free counterparts (n = 8844) in 11 European countries over four years., Results: Overall, consistent with network activation theory, respondents with new-onset mild-to-moderate chronic pain reported increases in sizes and diversity of their personal social networks, compared to their pain-free counterparts. However, consistent with the "pain as threat to the social self" theory, respondents with new-onset moderate pain or mild-to-moderate pain reported a decrease over time in perceived satisfaction and closeness with networks, respectively. Estimates from interactions between new-onset pain severity and sex show that men with new-onset pain experienced greater decreases in network satisfaction (mild pain) and closeness (severe pain) than did women., Discussion: This study highlights the complex social consequences of chronic pain, which may vary based on pain severity, gender, and type of social outcome considered., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Health professionals predict that the number of people who will suffer and die from oncological diseases will continue to increase. It is vitally important to provide comprehensive care to these patients and prescribe physical exercise programs as adjuvant therapy. The objective of this systematic review was to determine the impact of physical exercise on advanced-stage cancer patients. A literature search was performed in eight different databases. This search focused on randomized controlled trials (RCTs) published during the last 10 years. To assess the methodological quality of the sample of 15 RCTs finally obtained, the PEDro scale was used. Aerobic and strength training methods were used. The combination of both aerobic and strength training methods was the most frequently reported. Likewise, different physical and psychological variables were recorded, from which improvements were seen in fatigue, independence, quality of life and sleep, among others. The participation in physical exercise programs by advanced-stage cancer patients has a positive impact on health. Providing these programs serves as adjuvant therapy, facilitating the comprehensive care of patients. Similarly, aerobic, strength or mixed training programs increase the muscle mass of patients and therefore reduce hypotonia, the main side effect during the advanced-stages of cancer., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Biomarkers are becoming increasingly important for the differential diagnosis of neurodegenerative diseases. Previous observations indicated neurofilament light chain (NfL) as a potential blood-based biomarker for sporadic Creutzfeldt-Jakob disease (sCJD). Here, we investigated the stability, inter-assay/intra-assay variation and the regulation of NfL levels in CSF and plasma in a large cohort of sCJD patients by using a single-molecule array (SIMOA). We defined cutoffs for an accurate diagnosis and measured plasma NfL level in prion-infected mice models at different time points to identify the potential dynamics throughout the disease. Our analyses confirmed CSF and plasma NfL as stable and consistent marker for sCJD. Receiver operating characteristic (ROC) curve analysis showed an AUC of 0.92-0.93 to distinguish sCJD from control groups. Newly defined cutoffs revealed good diagnostic accuracies of CSF and plasma NfL, indicated by a sensitivity of 80-83.5% and a specificity of 87.4-91%. Studies on two humanized prion-infected mice lines (Tg340-PRNP 129MM and Tg361-PRNP 129VV) revealed increased plasma NfL levels in a late pre-clinical or very early clinical stage between 120-150 days post-inoculation. In conclusion, our work supports the potential use of CSF and plasma NfL as a very early biomarker in sCJD diagnostic with good diagnostic accuracies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The synergetic effect of estrogens and androgens is known to play a crucial role in the physiopathology of the prostate gland. Bisphenol A (BPA) is an endocrine disrupting compound that can interfere with endocrine hormone functioning and thereby influence prostate development. The objective of this study was to examine the impact on prostate expression of aromatase, 5α-R isozymes, and prostate cancer-related genes of exposure to low doses of BPA from perinatal period to adulthood. Vehicle or BPA (2.5 μg/kg b.w./day) was administered to gestating Wistar rats from gestational day 12 (GD12) to parturition and then to their male pups from postnatal day 1 (PND1) until euthanization on PND90. Their prostate glands were examined by qRT-PCR, Western blot, PCR array, and morphological study. mRNA and protein levels of 5α-R2 were significantly reduced and mRNA and protein levels of aromatase were significantly increased in BPA-treated animals, which also showed modifications of 8 out of the 84 key genes implicated in the development of prostate cancer. Because BPA interferes with genes involved in intraprostatic androgen and estrogen production and others implicated in prostate cancer, research is warranted into the prostate disease risk associated with chronic low-dose BPA exposure throughout life., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Risk assessment behaviors are necessary for gathering risk information and guiding decision-making. Risky decision-making heightens during adolescence, possibly as a result of low risk awareness and an increase in sensitivity to reward-associated cues and experiences. Higher adolescent engagement in high-risk behaviors may be, in part, due to developing circuits that contribute to risk assessment behaviors. Nucleus accumbens (NAc) activity is linked to risky decision-making and receives inputs carrying sensory and emotional information. Namely, the medial orbitofrontal cortex (MO) contributes to behavior guided by reward probability and sends direct projections to the NAc (MO→NAc), which may permit risk assessment in a mature circuit. Here, we evaluated risk assessment behaviors in adult and adolescent rats during elevated plus maze (EPM) exploration, including stretch and attend postures, head dips, and rears. We found that adolescents exhibited fewer EPM risk assessment behaviors than adults. We also quantified MO→NAc projections using a fluorescent anterograde tracer, Fluoro-Ruby, in both age groups. Labeled MO→NAc pathways exhibited greater total fluorescence in adults than in adolescents, indicating MO→NAc fibers increase over development. Using a disconnection approach to measure the contribution of the MO-NAc pathway in adults, we found that ipsilateral inactivation of the MO-NAc did not alter risk assessment behavior; however, MO-NAc disconnection reduced the number of stretch-and-attend postures. Together, this work suggests that the development of MO-NAc pathways can contribute to age-dependent differences in risk assessment., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism. We describe an association with favorable fat distribution (p = 1.8 × 10 -09 ), favorable metabolic profile and protection from type 2 diabetes (~28% lower odds; p = 0.004) for heterozygous protein-truncating mutations in INHBE, which encodes a circulating growth factor of the activin family, highly and specifically expressed in hepatocytes. Our results suggest that inhibin βE is a liver-expressed negative regulator of adipose storage whose blockade may be beneficial in fat distribution-associated metabolic disease., (© 2022. The Author(s).)

Evidence shows that state-level restrictive immigrant policies are associated with health disparities between noncitizens and citizens. Most research has focused on Latinos and there is limited knowledge of the relationship between restrictive policies and citizenship status among other groups, particularly Asian and Pacific Islanders (API). We examined whether state-level criminalization policy contexts (e.g., law enforcement collaboration with immigration authorities, E-Verify employment authorization) were associated with self-rated health (SRH) by citizenship, with a focus on Latinos and APIs. We expected that criminalization policies would be associated with worse health for noncitizens and citizens, but with a more negative influence for noncitizens; and that this pattern would be the same for Latinos and APIs. We merged a state-level immigrant criminalization policy database with a multi-racial/ethnic sample from 2014 to 2015 National Health Interview Survey (NHIS, n = 70,335). We tested the association between SRH and the number of state-level criminalization policies and generated predicted probabilities of noncitizens and citizens reporting excellent health in states with the most and fewest criminalization policies for the full sample, Latino, and API respondents. In states with the most criminalization policies, all noncitizens had a higher and all US-born citizens had a lower probability of excellent health. In states with the fewest criminalization policies there were no differences by citizenship status. Findings provide new evidence that state-level immigrant policies may harm the health of US-born citizens. As immigrant policymaking at the state level continues, understanding the relationship between state-level immigrant policies and health inequities across citizenship statuses will continue to be critical to improving population health., Competing Interests: None., (© 2022 The Authors.)

Latino construction workers in the U.S. have faced a disproportionate risk for COVID-19 infection in the workplace. Prior studies have focused on quantifying workplace risk for COVID-19 infection; few have captured workers' experiences and perspectives. This study describes COVID-19-related workplace risks from the perspectives of Latino construction workers. We conducted a qualitative study using semi-structured phone interviews with Latino construction workers from the Fruitvale District of Oakland, California. Twenty individuals were interviewed from December 2020 to March 2021. Nearly all participants (19/20) were Spanish-speaking men; mean age 42.6 years. The majority were low-income and over one-third did not have health insurance. Participants worked in varied construction-related jobs ranging from demolition to office work; additionally, four were day laborers, and three belonged to a labor union. We identified four major themes with public health policy and workplace safety implications: (1) Major concern about the risk of SARS-CoV-2 infection for family health and economic wellbeing; (2) Clarity about mask use and social distancing but not disclosure; (3) Variability in access to additional resources provided by employers; and (4) Uncertainty around structural support for SARS-CoV-2 quarantine/isolation. Our findings provide further evidence from workers' own perspectives of the major gaps experienced during the pandemic in workplace protections and resources.

Proteomics methods can identify amino acid sequences in fossil proteins, thus making it possible to determine the ascription or proximity of a fossil to other species. Before mass spectrometry was used to study fossil proteins, earlier studies used antibodies to recognize their sequences. Lowenstein and colleagues, at the University of San Francisco, pioneered the identification of fossil proteins with immunological methods. His group, together with Olivares's group at the University of Granada, studied the immunological reactions of proteins from the controversial Orce skull fragment (VM-0), a 1.3-million-year-old fossil found at the Venta Micena site in Orce (Granada province, southern Spain) and initially assigned to a hominin. However, discrepancies regarding the morphological features of the internal face of the fossil raised doubts about this ascription. In this article, we review the immunological analysis of the proteins extracted from VM-0 and other Venta Micena fossils assigned to hominins and to other mammals, and explain how these methods helped to determine the species specificity of these fossils and resolve paleontological controversies.

Background: The Deferred Action for Childhood Arrivals (DACA) program provides temporary relief from deportation and work permits for previously undocumented immigrants who arrived as children. DACA faced direct threats under the Trump administration. There is select evidence of the short-term impacts of DACA on population health, including on birth outcomes, but limited understanding of the long-term impacts., Methods: We evaluated the association between DACA program and birth outcomes using California birth certificate data (2009-2018) and a difference-in-differences approach to compare post-DACA birth outcomes for likely DACA-eligible mothers to birth outcomes for demographically similar DACA-ineligible mothers. We also separately compared birth outcomes by DACA eligibility status in the first 3 years after DACA passage (2012-2015) and in the subsequent 3 years (2015-2018) - a period characterized by direct threats to the DACA program - as compared to outcomes in the years prior to DACA passage., Results: In the 7 years after its passage, DACA was associated with a lower risk of small-for-gestational age (- 0.018, 95% CI: - 0.035, - 0.002) and greater birthweight (45.8 g, 95% CI: 11.9, 79.7) for births to Mexican-origin individuals that were billed to Medicaid. Estimates were consistent but of smaller magnitude for other subgroups. Associations between DACA and birth outcomes were attenuated to the null in the period that began with the announcement of the Trump U.S. Presidential campaign (2015-2018), although confidence intervals overlapped with estimates from the immediate post-DACA period., Conclusions: These findings suggest weak to modest initial benefits of DACA for select birthweight outcomes during the period immediately following DACA passage for Mexican-born individuals whose births were billed to Medicaid; any benefits were subsequently attenuated to the null. The benefits of DACA for population health may not have been sufficient to counteract the impacts of threats to the program's future and heightened immigration enforcement occurring in parallel over time., (© 2022. The Author(s).)

There is growing evidence that adult child educational attainment is associated with older parents' physical health and longevity. Scholars have hypothesized that these associations may be driven by health-behavior pathways, whereby adult children with more education may share information about healthy lifestyles, role-model healthier behaviors, and/or have more economic resources to support leisure-based physical activity or the purchase of healthy foods for older parents. However, this relationship has not been comprehensively evaluated with methods capable of addressing the confounding bias expected for observational studies on this topic. We estimated the association between increased adult child schooling and older parents' health behaviors using data from the Survey for Health, Aging and Retirement in Europe (SHARE) (n = 8195). We leveraged changes to compulsory schooling laws that would have impacted respondents' adult children as quasi-experiments and estimated the association between increased schooling among oldest adult children and respondents' (parents') body mass index, obesity, physical inactivity, excessive drinking, and current smoking using two-stage least squares regression. Each year of increased schooling among oldest adult children was associated with a lower risk of current smoking ( β : -0.029, 95% CI: -0.056, -0.003), physical inactivity ( β : -0.034, 95% confidence interval [CI]: -0.077, 0.009), obesity ( β : -0.038, 95% CI: -0.065, -0.011) and lower body mass index ( β : -0.37, 95% CI: -0.73, -0.02). The direction of associations with excessive drinking varied by parent gender ( β : -0.027, 95% CI: -0.046, -0.007 for mothers; β : 0.068, 95% CI: -0.011, 0.148 for fathers). Increases in adult child schooling may have upward influences on parents' late-life health behaviors, although there may be some differences by parent gender. Findings should be replicated across other global settings and studies should directly evaluate parent health behaviors as mediators of the relationship between increased adult child schooling and older parents' longevity., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (© 2022 Published by Elsevier Ltd.)

Background: Optimal control of acute postoperative pain and prevention of chronic persistent pain in total knee arthroplasty (TKA) remain a challenge., Methods: A randomized, non-inferiority clinical trial (385 patients) evaluated every hour immediate postoperative pain during 24 h, using a verbal rating 11-point scale for patient self-reporting of pain (VRS11). All patients received subarachnoid anesthesia and were randomly allocated in four groups: single shots femoral (FNB) or adductor canal blocks (ACB), both with dexamethasone (dex) and buprenorphine (bup). Patients received intravenous analgesia (metamizole magnesium, dexketoprofen) and rescue analgesia when needed: intravenous (paracetamol and morphine) and/or regional (femoral and sciatic nerve blocks). Demographics and adverse effects were also recorded., Results: A 45.7% of patients had pain: bupACB 56.3%, bupFNB 50.0%, dexACB 40.6% and dexFNB 36.1% (P=0.022). Rescue analgesia was needed in 37.7% of patients (P=0.128). There were statistical differences in percentage of timepoints without pain (95.0±7.9%, P=0.014) and mean VRS11 (0.18±0.3, P=0.012) but no differences in distribution of intensity periods of pain. There were no significant differences in the need of rescue analgesia excepting the use of intravenous morphine (P=0.025)., Conclusions: Buprenorphine is in the present trial inferior to dexamethasone by less than the established non-inferiority limit when used as perineural adjuvant in femoral nerve or adductor canal blocks in total knee arthroplasty analgesia. So, it could be considered an alternative in patients where dexamethasone is contraindicated, such as diabetics.

Catheter ablation is useful for reducing drug refractory ventricular tachycardia (VT) episodes and can be life-saving when VT is incessant or arrhythmic storm. Left ventricular hemodynamic support may be required in patients with VT and hemodynamic instability. Extracorporeal membrane oxygenation (ECMO) support is an alternative to achieve ventricular tachycardia mapping and ablation over long periods of time. We present a case of successful catheter ablation of substrate in a patient with ischemic heart disease and ventricular tachycardia with hemodynamic instability performed using venous- arterial ECMO support. There were not episodes of ventricular tachycardia after 2 years of follow-up.

Background: Individuals with autism spectrum disorder (ASD) exhibit frequent behavioral deficits in facial emotion recognition (FER). It remains unknown whether these deficits arise because facial emotion information is not encoded in their neural signal or because it is encodes but fails to translate to FER behavior (deployment). This distinction has functional implications, including constraining when differences in social information processing occur in ASD, and guiding interventions (i.e., developing prosthetic FER vs. reinforcing existing skills)., Methods: We utilized a discriminative and contemporary machine learning approach-deep convolutional neural networks-to classify facial emotions viewed by individuals with and without ASD (N = 88) from concurrently recorded electroencephalography signals., Results: The convolutional neural network classified facial emotions with high accuracy for both ASD and non-ASD groups, even though individuals with ASD performed more poorly on the concurrent FER task. In fact, convolutional neural network accuracy was greater in the ASD group and was not related to behavioral performance. This pattern of results replicated across three independent participant samples. Moreover, feature importance analyses suggested that a late temporal window of neural activity (1000-1500 ms) may be uniquely important in facial emotion classification for individuals with ASD., Conclusions: Our results reveal for the first time that facial emotion information is encoded in the neural signal of individuals with (and without) ASD. Thus, observed difficulties in behavioral FER associated with ASD likely arise from difficulties in decoding or deployment of facial emotion information within the neural signal. Interventions should focus on capitalizing on this intact encoding rather than promoting compensation or FER prostheses., (Published by Elsevier Inc.)

This retrospective observational study analyzed the clinical characteristics, treatment patterns and outcomes of 120 patients with advanced ALK-positive non-small-cell lung cancer (ALK+ NSCLC) according to data collected between November 2019 and October 2020 in 38 Spanish hospitals. Patients had progressed after 1-5 prior treatment lines (which included crizotinib in any prior line) and received subsequent therapy with alectinib in a local expanded access program. Median age was 58.7 years, 50% of patients were female, 64.1% had ECOG PS of 0-1, 85% presented stage IV, 95% had adenocarcinoma histology and 20.8% had brain metastases. After a median 9.6 months of alectinib treatment, objective response rate (ORR) was 54.5%, disease control rate (DCR) was 80%, median progression-free survival (PFS) was 9.4 months and median overall survival (OS) was 24.1 months. Patients with brain metastases achieved an intracranial DCR of 71.4%. Adverse events (AEs) were reported in 35.8% of patients (14.2% of AEs were grade ≥3). Over 40% of patients received some treatment after alectinib, most frequently lorlatinib (65.2%) and brigatinib (32.6%). This study provides information on real-world treatment patterns and confirms the tolerability and prolonged PFS and OS observed with alectinib in clinical trials, in unselected pretreated patients with advanced ALK+ NSCLC., Competing Interests: CONFLICTS OF INTEREST R. B.-C. reports advisory honoraria from Roche, Bristol-Myers Squibb, and AstraZeneca; speaker honoraria from Roche, Bristol-Myers Squibb, and Amgen; and grants from Roche. P. G. reports consultancy fees from Abbvie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Lilly, Merck-Sharp-Dome, Medscape, Novartis, Pfizer, Roche, Takeda and Sanofi, and speaker honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck-Sharp-Dome, Novartis, Pfizer, Roche, and Takeda. R. G.-C. reports consultancy fees and speaker honoraria from Merck-Sharp-Dome, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda, Bayer and Janssen. R. P. reports speaker honoraria from Guardant Health, Pfizer, Roche, Boehringer-Ingelheim, Eli-Lilly, Bristol-Myers Squibb, AstraZeneca, and Merck-Sharp-Dome; travel/meeting attendance expenses from Merck-Sharp-Dome and Roche, and membership of data safety monitoring from Boehringer-Ingelheim and Roche. A. A. reports consultancy fees from Roche, Takeda, AstraZeneca, and Bristol-Myers Squibb. C. B. reports consultancy fees from Boehringer-Ingelheim and AstraZeneca; speaker honoraria from Pfizer, Merk, Roche, Bristol-Myers Squibb, Takeda, Merck-Sharp-Dome, and Amgen; meeting and courses attendance expenses from Merck-Sharp-Dome, Roche, Merk, AstraZeneca and Boehringer-Ingelheim. D. R.-A. reports honoraria for lectures and consultancy fees from Bristol-Myers Squibb, MSD and Hoffmann-La Roche. M. L.-B. reports travel grants from Bristol-Myers Squibb, Roche, Pfizer, and Merck-Sharp-Dome; speaker honoraria, consulting fees and continuing medical education expenses from Roche, Bristol-Myers Squibb, Merck-Sharp-Dome, Pfizer, AstraZeneca, and Takeda. A. P. declares no conflicts of interests. D. V. reports speaker honoraria from Merck-Sharp-Dome, Pfizer, and AstraZeneca; and travel/accommodation expenses from Merck-Sharp-Dome, Pfizer, and AstraZeneca. J. M. S.-T. reports consultancy fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Pfizer, Roche, and Takeda; and travel/accommodation expenses from Boehringer-Ingelheim, Merck-Sharp-Dome, and Roche. M. M. reports grants from Bristol-Myers Squibb, Roche, and AstraZeneca; personal fees from Bristol-Myers Squibb, AstraZeneca, Roche, Merck-Sharp-Dome, Boehringer-Ingelheim, Takeda, Sanofi-Aventis, Novartis, Vifor and Bayer. P. D. reports speaker honoraria and consultancy fees from Bristol-Myers Squibb, AstraZeneca, Boehringer-Ingelheim, Roche, Merck-Sharp-Dome, and Takeda; speaker honoraria from Pfizer and Amgen; institutional research grants from AstraZeneca and Mirati, and personal and institutional research grants from AstraZeneca and Roche. R. G. and M. G. are Roche Farma employees. J. d. C. reports educational fees from Astra Zeneca, Bristol-Myers Squibb, Merck-Sharp-Dome, and Roche; consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen-Cilag, Lilly, Merck-Sharp-Dome, Novartis, Pfizer, Roche, and Takeda. All potential conflicts of interests were outside of the submitted work., (Copyright: © 2022 Bernabé-Caro et al.)

In lung cancer immunotherapy, biomarkers to guide clinical decisions are limited. We now explore whether the detailed immunophenotyping of circulating peripheral blood mononuclear cells (PBMCs) can predict the efficacy of anti-PD-1 immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC). We determined 107 PBMCs subpopulations in a prospective cohort of NSCLC patients before starting single-agent anti-PD-1 immunotherapy (study group), analyzed by flow cytometry. As a control group, we studied patients with advanced malignancies before initiating non-immunotherapy treatment. The frequency of PBMCs was correlated with treatment outcome. Patients were categorized as having either high or low expression for each biomarker, defined as those above the 55th or below the 45th percentile of the overall marker expression within the cohort. In the study group, three subpopulations were associated with significant differences in outcome: high pretreatment levels of circulating CD4+CCR9+, CD4+CCR10+, or CD8+CXCR4+ T cells correlated with poorer overall survival (15.7 vs. 35.9 months, HR 0.16, p = 0.003; 22.0 vs. NR months, HR 0.10, p = 0.003, and 22.0 vs. NR months, HR 0.29, p = 0.02). These differences were specific to immunotherapy-treated patients. High baseline levels of circulating T cell subpopulations related to tissue lymphocyte recruitment are associated with poorer outcomes of immunotherapy-treated advanced NSCLC patients.

Salivary gland neoplasms are uncommon, and most exhibit epithelial differentiation. Mesenchymal neoplasms of the salivary gland are rare, and the incidence ranges from 1.9% to 5%. The aim of this study is to identify the types and clinical-pathological features of mesenchymal salivary neoplasm and review their differential diagnosis. A retrospective search for mesenchymal neoplasms of salivary glands from our institution's pathology archives from the 2004-2021 period and consultation files of one of the authors (AER) was performed. The clinical data were obtained from available medical records, and the histological slides and ancillary studies were retrieved and reviewed. We identified a total of 68 cases that form the study cohort. Thirty-five patients were male, and thirty-three patients were female, with a mean age of 48 years (range, 7 months-79 years), and the male to female ratio was 1:.94. Sixty-three (92.6%) of sixty-eight tumors were benign and included: 38 (56%) lipomas, 9 (13%) hemangiomas, 7 (10.3%) schwannomas, 3 (4.4%) neurofibromas, 3 (4.4%) lymphangioma, 2 (3%) solitary fibrous tumors, 1 (1.5%) myofibroma. Five of sixty-eight (7.4%) were malignant and included: 3 (4.4%) Adamantinoma-like Ewing sarcomas, 1 (1.5%) malignant peripheral nerve sheath tumor (MPNST), and 1 (1.5%) malignant solitary fibrous tumor. The involved sites included: parotid (55), submandibular gland (5), parapharyngeal space (5), buccal mucosa minor salivary gland (2), and sublingual gland (1). Sixty-seven patients underwent surgical resection. One patient with lymphangioma manifested a recurrence/persistence a week post-surgery. One patient with a parotid hemangioma developed post-operative numbness, and another patient developed chronic postauricular pain after surgery. Two patients with MPNST and one patient with adamantinoma-like Ewing sarcoma underwent neoadjuvant chemoradiation and were disease-free after treatment. The remaining 37 patients with available follow-up ranging from 7 days to 96 months (mean, 18 months) had a favorable outcome and were disease-free after treatment. Mesenchymal neoplasms of salivary gland are rare; most are benign and demonstrate adipocytic, endothelial, and schwannian differentiation; awareness of their development is important for adequate diagnosis. The mainstay of treatment is surgical excision, with the extent determined by tumor type. Adjuvant therapy is reserved for high-grade sarcomas and may be given in a neoadjuvant or adjuvant setting., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

(1) Background: A United States national policy advisory group (PAG) was convened to identify barriers and facilitators to expand formal long-term services and support (LTSS) for people living alone with cognitive impairment (PLACI), with a focus on equitable access among diverse older adults. The PAG's insights will inform the research activities of the Living Alone with Cognitive Impairment Project, which is aimed at ensuring the equitable treatment of PLACI. (2) Methods: The PAG identified barriers and facilitators of providing effective and culturally relevant LTSS to PLACI via one-on-one meetings with researchers, followed by professionally facilitated discussions among themselves. (3) Results: The PAG identified three factors that were relevant to providing effective and culturally relevant LTSS to PLACI: (i) better characterization of PLACI, (ii) leveraging the diagnosis of cognitive impairment, and (iii) expanding and enhancing services. For each factor, the PAG identified barriers and facilitators, as well as directions for future research. (4) Conclusions: The barriers and facilitators the PAG identified inform an equity research agenda that will help inform policy change.

Aims and Objectives: To investigate nurses' intention in accepting COVID-19 vaccination and the factors affecting their decision., Background: COVID-19 vaccination has started in most European countries with healthcare personnel being the first group receiving the vaccine shots. Their attitude towards vaccination is of paramount significant as their role in the frontline could help in the awareness of general population., Methods: A study was conducted in Albania, Cyprus, Greece, Spain and Kosovo with the use of an online questionnaire. The Fear of COVID-19 Scale was used. The STROBE checklist was followed for this cross-sectional study., Results: Study population consisted of 1135 nurses. Mean age of the participants was 38.3 years, while most of them were female gender (84.7%) and married (53.1%). Acceptance of a safe and effective COVID-19 vaccine was higher among Greek (79.2%) and Spanish (71.6%) nurses, followed by Cypriot (54%), Albanian (46.3%) and Kosovo (46.2%) nurses. Key factors for willingness to get vaccinated were male gender, living in a country with a high mortality rate in comparison with low mortality, being not infected with COVID-19, having high level of knowledge about COVID-19 vaccines and having been vaccinated for influenza in the last 2 years. Moreover, trusting the government and doctors regarding the information about the COVID-19 and having high level of fear about this virus were key factors for willingness to get vaccinated., Conclusion: Vaccination of healthcare personnel is a crucial issue not only for their own safety but also for their patients'. Healthcare acceptance to get vaccinated can work as a role model for general population., Relevance to Clinical Practice: Gender, country, mortality rate, trust in government and health professionals and the level of fear were key factors that should be managed in clinical practice., (© 2021 John Wiley & Sons Ltd.)

Objective: Despite some progress in recent years, colorectal cancer (CRC) screening adherence in the United States is still suboptimal, particularly among disadvantaged groups. In this study, we assessed the association between socioeconomic status (SES) and self-reported screening non-adherence (SNA) in a sample of racial/ethnic minorities living in San Francisco, California., Design/methods: A total of 376 participants of the San Francisco version of the Health Information National Trends Survey (SF-HINTS) with ages 50-75 years were included in this cross-sectional study. SNA was defined as not reporting blood stool test within the past year and not reporting sigmoidoscopy/colonoscopy within the past 10 years. Poisson regression models with robust variance estimators were used to evaluate the relation of SES with SNA, adjusting for measured confounders. Results are reported as prevalence ratios (PR) and 95% confidence intervals (95% CI)., Results: Overall SNA was 40%. In multivariable models including all respondents, retired participants had significantly lower SNA prevalence than employed participants (PR = 0.46, 95% CI = 0.26 0.83). In stratified analyses by race/ethnicity, Black respondents with less than high school (PR = 1.93, 95% CI = 1.09, 3.43) and those with high school or equivalent (PR = 1.88, 95% CI = 1.16, 3.04) had significantly higher SNA prevalence than those with at least some college. Among non-Hispanic Asian/Pacific Islanders, those disabled had significantly higher prevalence of SNA as compared to employed people (PR = 4.26, 95% CI = 2.11, 8.60). None of the SES indicators were significantly associated to SNA among Hispanics., Conclusions: Participants with lower SES characteristics were less likely to adhere to CRC screening guidelines and being retired was a predictor of compliance. There was evidence of heterogeneity in associations between SES and CRC screening by race/ethnicity. Life circumstances of retired people could provide insights for designing interventions aimed to improve CRC screening uptake in these priority groups. Future efforts should consider mechanisms underlying differences by race/ethnicity.

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10 -9 ), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: The objective of this study was to evaluate the efficacy and safety of intranasal midazolam as part of a paediatric sedation and analgesic procedure during the suturing of traumatic lacerations in paediatric emergency departments., Methodology: A systematic review of clinical trials was completed in July 2021. The databases consulted were PUBMED, SCOPUS, WEB OF SCIENCE, NICE and Virtual Health Library., Eligibility Criteria: randomised and nonrandomised clinical trials. Two independent, blinded reviewers performed the selection and data extraction. The participants were 746 children, of whom, 377 received intranasal midazolam. All of the children were admitted to an emergency department for traumatic lacerations that required suturing. The quality of the articles was evaluated with the Jadad scale. This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines., Results: Nine studies were included in the review. The intranasal administration of midazolam in healthy children produces anxiolysis and minimal/moderate sedation without serious side effects. Although there are combinations of parenteral drugs that produce deeper sedation, they also have greater adverse effects. No significant differences in the initiation of sedation and the suture procedure were found between the intranasal route and the parenteral route., Conclusions: The use of intranasal midazolam in healthy children produces sufficiently intense and long-lasting sedation to allow for the suturing of traumatic lacerations that do not present other complications; therefore, this drug can be used effectively in paediatric emergency departments.

Background: Gender violence among adolescents is a global problem. In the context of public healthcare, nursing professionals play an important role., Objective: The aim of this study was to determine awareness, information, and beliefs regarding gender violence in adolescents and identify their educational needs., Participants and Setting: Data from a study conducted by the Spanish Centre for Sociological Research and the Government Office for Gender Violence in 2013 are used. The sample contained 698 adolescents aged 15-19 years., Methods: This is a secondary analysis of a data survey. Strengthening the Reporting of Observational Studies in Epidemiology guidelines are followed. Sociodemographic variables and seven topics of interest were analyzed: gender inequality, intimate relationships, definition of abuse, identification of abuse, awareness of cases of abuse in women, and informal and formal support networks., Results: The results show that adolescents are well informed, are aware of informal and formal support networks, use the word "respect," identify abuse and consider it unacceptable, and believe media coverage is useful in giving visibility to gender violence. No significant differences were found in gender, social class, or education, and their idea of romantic love remains intact., Conclusions: The researchers conclude that, in Spain, adolescents' awareness of gender violence is strongly influenced by environmental and cultural factors, because of the prevalence of gender and intimate partner violence in the country. Formal interventions such as health education provided by either nursing professionals in schools or the broader community can have a positive effect on adolescent health. Primary care nurses should use these findings to support the development of health promotion programs for young adults., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 International Association of Forensic Nurses.)

In the absence of effective pharmacological treatment to halt or reverse the course of Alzheimer's disease and related dementias (ADRDs), population-level research on the modifiable determinants of dementia risk and outcomes for those living with ADRD is critical. The Harmonized Cognitive Assessment Protocol (HCAP), fielded in 2016 as part of the U.S. Health and Retirement Study (HRS) and multiple international counterparts, has the potential to play an important role in such efforts. The stated goals of the HCAP are to improve our ability to understand the determinants, prevalence, costs, and consequences of cognitive impairment and dementia in the U.S. and to support cross-national comparisons. The first wave of the HCAP demonstrated the feasibility and value of the more detailed cognitive assessments in the HCAP compared to the brief cognitive assessments in the core HRS interviews. To achieve its full potential, we provide eight recommendations for improving future iterations of the HCAP. Our highest priority recommendation is to increase the representation of historically marginalized racial/ethnic groups disproportionately affected by ADRDs. Additional recommendations relate to the timing of the HCAP assessments; clinical and biomarker validation data, including to improve cross-national comparisons; dropping lower performing items; enhanced documentation; and the addition of measures related to caregiver impact. We believe that the capacity of the HCAP to achieve its stated goals will be greatly enhanced by considering these changes and additions., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The evidence about the best body position to prevent ventilator-associated pneumonia (VAP) is unclear. The aim of this study was to know what the best body position is to prevent VAP, shorten the length of intensive care unit (ICU) and hospital stay, and reduce mortality among patients undergoing mechanical ventilation (MV)., Methods: We performed a network meta-analysis of randomized controlled trials including intubated patients undergoing MV and admitted to an ICU. The assessed interventions were different body positions (i.e., lateral, prone, semi-recumbent) or alternative degrees of positioning in mechanically ventilated patients., Results: Semi-recumbent and prone positions showed a risk reduction of VAP incidence (RR: 0.38, 95% CI: 0.25-0.52) and mortality (RR: 0.70, 95% CI: 0.50-0.91), respectively, compared to the supine position. The ranking probabilities and the surface under the cumulative ranking displayed as the first best option of treatment the semi-recumbent position to reduce the incidence of VAP (71.4%), the hospital length of stay (68.9%), and the duration of MV (67.6%); and the prone position to decrease the mortality (89.3%) and to reduce the ICU length of stay (59.3%)., Conclusions: Cautiously, semi-recumbent seems to be the best position to reduce VAP incidence, hospital length of stay and the duration of MV. Prone is the most effective position to reduce the risk of mortality and the ICU length of stay, but it showed no effect on the VAP incidence. Registration PROSPERO CRD42021247547., (© 2022. The Author(s).)

Objective: The characteristics of the residence environment seem to be closely related to the health status of its residents, and the infrastructure linked to the practice of physical activity may have a direct influence on health. The objective of the study was to analyze the physical activity practice environment, evaluating in adolescents their relationship with various lifestyle habits and indicators of physical and psychosocial health, academic performance, as well as the influence of various sociodemographic variables., Methods: The study was carried out in a sample of 761 students (14.51±1.63 years) from 25 educational centers in a region of northern Spain. The environment for the practice of physical activity, physical activity engagement, the hours of night sleep, the adherence to the Mediterranean diet, the maximum oxygen uptake, the body mass index, the health-related quality of life were assessed, self-esteem, academic performance and various sociodemographic factors., Results: The residence in more favorable environments for the realization of physical activity was associated with higher physical activity engagement, adherence to the Mediterranean diet, maximum oxygen uptake, self-esteem and health-related quality of life. In addition, the rates of residence in more favorable environments for the realization of physical activity were lower on the part of migrants and those with low/medium socioeconomic status., Conclusions: The infrastructure linked to the practice of physical activity is associated with the well-being of its residents, so interventions aimed at child and adolescent health should take into account the promotion of residential spaces that facilitate access to said practice., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance., Patients and Methods: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs)., Results: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively., Conclusions: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination., Competing Interests: Disclosure RAS reports advisory role for Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Lily, Merck, Novartis, Pfizer, Roche, Taiho, Takeda and Yuhan and grants from AstraZeneca, Boehringer Ingelheim, outside the submitted work. UD reports honorarium as Member of the Tumor Agnostic Evidence Generation working Group of Roche, outside the submitted work. BCC reports grants from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, Abbvie, Medpacto, GI Innovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp, personal fees from Novartis, AstraZeneca, Champions Oncology, Janssen, Yuhan, Ono, MSD, Medpacto, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp, Boehringer Ingelheim, Roche, BMS, Pfizer, Takeda, KANAPH Therapeutic Inc., Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Joseah BIO, Gencurix Inc., and other from Interpark Bio Convergence Corp, KANAPH Therapeutic Inc., Bridgebio therapeutics, Cyrus therapeutics, Gencurix Inc, DAAN, TheraCanVac Inc., outside the submitted work. EN reports grants, personal fees and non-financial support from Roche, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Bristol-Myers-Squibb, personal fees and non-financial support from Merck Sharp Dohme, grants and personal fees from Merck Serono, personal fees from Takeda, grants, personal fees and non-financial support from Pfizer, personal fees from Lilly, personal fees from Bayer, personal fees from Amgen, personal fees from Boehringer Ingelheim, outside the submitted work. EC reports personal fees from AstraZeneca, Amgen, BMS, MSD and Roche, outside the submitted work. JdC reports grants and personal fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme and Hoffmann-La Roche, personal fees from Bayer, Boehringer Ingelheim, Glaxosmithkline, Jansen-Cilag, Lilly, Novartis, Pfizer and Takeda, outside the submitted work. MAS reports advisory role for Roche and Boehringer Ingelheim, speaker role for Pierre Fabre and travel grants from Roche and PharmaMar, outside the submitted work. RB reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Roche, AstraZeneca, BMS, AMGEN and MSD, participation on Data Safety Monitoring Board or Advisory Board for AstraZeneca, BMS and Roche. LC reports advisory role for AstraZeneca, Roche and Daichi, outside the submitted work. MPP reports grants, personal fees and non-financial support from AstraZeneca, BMS and ROCHE, personal fees from MSD and TAKEDA, outside the submitted work. RGC reports Advisory Board, Consultancy or Speaker honoraria from MSD, Bristol-Myers Squibb, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda, Janssen and Sanofi. SC reports non-financial support from Pfizer, Roche, MSD and BMS, outside the submitted work. MF reports grants from Astra Zeneca and BMS and other support from AstraZeneca, BMS, Boehringer Ingelheim, Janssen, MSD, Pfizer, Roche and Takeda, outside the submitted work. JGS reports grants for consulting or advisory role from Roche, Boehringer Ingelheim, EUSA Pharma, research funding from Roche and travel, and accommodation expenses from Roche, BMS, Merck Sharp & Dohme and Pfizer, outside the submitted work. MD reports personal fees from AstraZeneca, BMS, Boehringer Ingelheim, MSD, Pfizer, Roche and Takeda, outside the submitted work. MM reports grants and personal fees from Bristol-Myers Squibb, Pierre Fabre, personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, F. Hoffman – La Roche, Merck Sharp and Dohme, and personal fees from Kyowa Kirin, outside the submitted work. JMST reports personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Roche, Takeda and MSD, outside the submitted work. CB reports consulting or advisory role for AstraZeneca, Pfizer, Roche, Takeda, Janssen-Cilag and Boehringer Ingelheim, as well as travel support from AstraZeneca and Takeda, outside the submitted work. MP reports grants from AstraZeneca, BMS, Boehringer Ingelheim, Roche, Takeda, Vifor, and personal fees from Abbvie, AstraZeneca, BMS, Boehringer Ingelheim, Eisei, MSD, Novartis, Pfizer, Roche, Takeda, Merck and Janssen, outside the submitted work. RAS reports consultant or advisory role for AstraZeneca, BMS, Janssen, MSD, Pfizer, Regeneron, Roche, Seattle Genetics and Takeda, speaker honoraria from Amgen, AstraZeneca, Blueprint, Eli Lilly, GSK, MSD, Novartis, Roche and Sandoz, DMC role from Genentech/Roche and Takeda, and financial support for ETOP and IBCSG trials, where he is president and scientific chair, from AstraZeneca, BMS, Ipsen, MSD, Novartis, Pierre Fabre, Roche and Pfizer. SP reports grants from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffman – La Roche, Illumina, Novartis, Pfizer, Merck Sharp and Dohme, personal fees from Amgen, Abbvie, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffman – La Roche, Foundations Medicine, Illumina, Janssen, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Merck Sharp and Dohme, Merck Serono, Merrimack, Medscape, Phosphoplatin Therapeutics, Beigene and Imedex, outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2021 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Background: Levels of fear have increased since the COVID-19 pandemic outbreak. The absence of a safe and effective vaccine for mass-vaccination deteriorates this situation, which has a significant impact on mental health. This study aimed to assess the feelings of fear among nurses and nursing students in five European countries., Methods: A multicenter cross-sectional study was conducted in five European countries (Greece, Albania, Cyprus, Spain, and Kosovo) before the start of mass vaccination in Europe. Data collection was conducted in December 2020-January 2021 using an online questionnaire for nursing students and professional nurses. Fear of COVID-19 Scale (FCV-19S) was used for measuring levels of fear. IBM SPSS version 21.0 was used for statistical analysis., Results: The study population included 1135 nurses and 1920 nursing students from Kosovo ( n = 1085), Spain ( n = 663), Greece ( n = 534), Albania ( n = 529), and Cyprus ( n = 244). According to multivariable analysis, females (OR = 2.53, 95% CI = 1.89-3.15), married (OR = 0.86, 95% CI = 0.24-1.48), nurses (OR = 0.87, 95% CI = 0.28-1.45) and those with a chronic disease (OR = 0.86, 95% CI = 0.11-1.62) were more fearful of COVID-19., Conclusions: It is important to decrease fear in the population of nurses who are at the frontlines of the pandemic. The provision of appropriate education and training activities for nurses and students to manage their stress levels is of high importance. Future studies should focus on levels of fear after the administration of several safe and effective vaccines worldwide.

Background: US preterm-birth rates are 1.6 times higher for Black mothers than for White mothers. Although traffic-related air pollution (TRAP) may increase the risk of preterm birth, evaluating its effect on preterm birth and disparities has been challenging because TRAP is often measured inaccurately. This study sought to estimate the effect of TRAP exposure, measured at the street level, on the prevalence of preterm birth by race/ethnicity., Methods: We linked birth-registry data with TRAP measured at the street level for singleton births in sampled communities during 2013-2015 in Oakland and San Jose, California. Using logistic regression and marginal standardization, we estimated the effects of exposure to black carbon, nitrogen dioxide and ultrafine particles on preterm birth after confounder adjustment and stratification by race/ethnicity., Results: There were 8823 singleton births, of which 760 (8.6%) were preterm. Shifting black-carbon exposure from the 10th to the 90th percentile was associated with: 6.8%age point higher risk of preterm birth (95% confidence interval = 0.1 to 13.5) among Black women; 2.1%age point higher risk (95% confidence interval = -1.1 to 5.2) among Latinas; and inconclusive null findings among Asian and White women. For Latinas, there was evidence of a positive association between the other pollutants and risk of preterm birth, although effect sizes were attenuated in models that co-adjusted for other TRAP., Conclusions: Exposure to TRAP, especially black carbon, may increase the risk of preterm birth for Latina and Black women but not for Asian and White women., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Hemoplasmas have already been detected in bats in the United States of America, Spain, Australia, Chile, Brazil, Peru, Belize, Nigeria, Costa Rica, Germany, Switzerland and New Caledonia. The recent detection of hemoplasmas closely related to Mycoplasma haematohominis, an agent causing disease in humans, emphasizes the need for additional studies on the diversity of hemoplasmas in bats. The present work aimed to investigate the occurrence and assess the phylogenetic positioning and genetic diversity of hemoplasmas in bats and associated ectoparasites sampled in central-western Brazil. Overall, 43% (58/135) sampled bats and 1.56% (1/64) bat flies (Megistopoda aranea) were positive for hemoplasmas, however, twenty-four and two hemoplasma sequences were obtained from PCR assays targeting 16S and 23S rRNA genes, respectively, since the majority of the obtained amplicons showed faint bands in agarose gel electrophoresis. The obtained 16S rRNA sequences showed to be broadly distributed along the phylogenetic tree, albeit positioned within the 'Haemofelis group' and clustering with other bat-associated hemoplasmas. Twelve 16S rRNA hemoplasma genotypes were found among the 24 obtained sequences. When compared to other bat-related hemoplasmas sequences retrieved from the Genbank, 52 genotypes were found. The two 23S rRNA sequences obtained were positioned as a sister clade to "Candidatus Mycoplasma haematohydrochaerus", M. haemofelis and M. haemocanis. High genetic diversity was found among 16S rRNA hemoplasma sequences detected in non-hematophagous bats from central-western Brazil and previously detected in other regions of the world. Even though the genotype analysis showed that hemoplasmas from the same genus tend to group together, the results from the unipartite and bipartite analyses did not robustly support the hypothesis. Further studies addressing the specificity of hemoplasma genotypes according to bat species and genera should be performed., (Copyright © 2021. Published by Elsevier B.V.)

Background: Evaluation of salivary gland lesions is routinely done preoperatively by fine-needle aspiration cytology (FNAC). The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), with diagnostic categories I-VI, has been recommended to standardize the reporting of salivary gland lesions by FNAC. We aimed to reclassify archival salivary gland FNAC samples using MSRSGC, correlate the samples with surgical resections, and calculate the risk of malignancy (ROM) for each category., Methods: A total of 354 salivary gland FNAC samples (2013-2018) were reviewed. All FNAC results were retrospectively classified according to the MSRSGC. All cases had surgical follow-up. Histology was used to calculate the ROM, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy., Results: The 354 aspirates were classified as: nondiagnostic (ND) 17.0% (60), non-neoplastic (NN) 1.4% (5), atypia of undetermined significance (AUS) 11.0% (39), benign neoplasm (BN) 49.4% (175), salivary gland neoplasms of unknown malignant potential (SUMP) 10.7% (38), suspicious for malignancy (SM) 3.4% (12), and malignant (M) 7.1% (25). The ROM was as follows: ND 22%, NN 20%, AUS 15%, BN 2%, SUMP 53%, SM 75%, and M 96%. The diagnostic accuracy for separating benign versus malignant neoplasms was 96%. Cytologic-histologic correlation yielded a false-negative rate of 2.7%, false-positive rate of 10.5%, PPV of 89%, NPV of 97%, sensitivity of 87%, and specificity of 98%., Conclusion: MSRSGC helps standardize cytology reports, provides useful information for appropriate clinical management, and ensures the best care of patients with salivary gland lesions., (© 2022 S. Karger AG, Basel.)

COVID-19 global pandemic affects health care and lifestyle worldwide, and its early detection is critical to control cases' spreading and mortality. The actual leader diagnosis test is the Reverse transcription Polymerase chain reaction (RT-PCR), result times and cost of these tests are high, so other fast and accessible diagnostic tools are needed. Inspired by recent research that correlates the presence of COVID-19 to findings in Chest X-ray images, this papers' approach uses existing deep learning models (VGG19 and U-Net) to process these images and classify them as positive or negative for COVID-19. The proposed system involves a preprocessing stage with lung segmentation, removing the surroundings which does not offer relevant information for the task and may produce biased results; after this initial stage comes the classification model trained under the transfer learning scheme; and finally, results analysis and interpretation via heat maps visualization. The best models achieved a detection accuracy of COVID-19 around 97%., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: Low socioeconomic status (SES) has been associated with a higher risk of aggressive breast cancer (BC) subtypes, but few studies have examined the independent effects of both neighborhood-level socioeconomic status (nSES) and individual-level SES measures., Methods: This study included 5547 women from the Pathways and Life After Cancer Epidemiology cohorts who were diagnosed with invasive BC. Generalized estimating equation models were used to examine associations of nSES (a composite score based on income, poverty, education, occupation, employment, rent, and house value) and individual-level SES (income and education) with BC subtypes: luminal B (LumB), Her2-enriched (Her2-e), and triple-negative breast cancer (TNBC) relative to luminal A (LumA). Models controlled for age, race, nativity, stage, days from diagnosis to survey, and study cohort and simultaneously for nSES and individual-level SES., Results: In fully adjusted models, low nSES was significantly associated with the LumB (odds ratio for quartile 1 vs quartile 4 [OR Q1vQ4 ], 1.31; 95% confidence interval [CI], 1.11-1.54; P for trend = .005) and TNBC subtypes (OR Q1vQ4 , 1.32; 95% CI, 1.02-1.71; P for trend = .037) relative to LumA. Conversely, individual education was significantly associated with only the Her2-e subtype (odds ratio for high school degree or less vs postgraduate, 1.68; 95% CI, 1.03-2.75; P for trend = .030) relative to LumA. Individual income was not significantly associated with any BC subtype., Conclusions: nSES and individual-level SES are independently associated with different BC subtypes; specifically, low nSES and individual-level education are independent predictors of more aggressive BC subtypes relative to LumA., (© 2021 American Cancer Society.)