Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation of PD-L1 expression on tumor cell and tumor infiltrating immune cell with 18F-fluorodeoxyglucose uptake on PET/computed tomography in surgically resected pulmonary adenocarcinoma

Supplemental Digital Content is available in the text. Objective The uptake of 18F-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) is known to be linked to programmed death ligand 1 (PD-L1) expression on tumor cells (TC). However, the association between PD-L1 expression on immune cells (IC) and 18F-FDG accumulation is still unclear. Here, we conducted a clinicopathological study to investigate the relationship between PD-L1 expression on TC/IC and 18F-FDG uptake in patients with surgically resected pulmonary adenocarcinoma (ADC). Methods A total of 450 ADC patients who underwent preoperative 18F-FDG-PET/CT imaging were analyzed retrospectively. Immunohistochemistry analysis was performed for PD-L1 expression on TC and IC in ADC specimens with SP142. PD-L1 expression was performed on whole-tissue sections and given scores (0/1/2/3) according to percent of PD-L1+ cells in TC and IC. Results Compared to TC0 and IC0, PD-L1 positive expression was 90.4% (407/450) in ADC specimens. Both PD-L1 expression score on TC and IC were associated with maximum standardized uptake (SUVmax). SUVmax augmented with increasing PD-L1 expression (TC0 and IC0, 4.3 ± 3.4; TC or IC1/2/3, 7.7 ± 5.6; TC or IC2/3, 8.1 ± 5.6; TC or IC3, 8.4 ± 5.4). The best cut-off value of PD-L1 expression, determined by receiver operating characteristic curve, was 5.1 for TC or IC1/2/3 [area under the curve (AUC) = 0.713, sensitivity 62.2%, specificity 72.1%]. Multivariate analysis demonstrated that TC or IC1/2/3 subset was correlated with histological subtype, PD-1 expression on IC and SUVmax. Conclusion High SUVmax is associated with PD-L1 expression on TC and IC in surgically resected pulmonary ADC. 18F-FDG-PET/CT imaging can be a potential tool to evaluate PD-L1 expression in pulmonary ADC.
The European Vulvovaginal Epidemiological Survey (EVES): impact on sexual function of vulvovaginal atrophy of menopause.

OBJECTIVE To estimate the impact of vulvovaginal atrophy (VVA) on sexual function in a clinical population of postmenopausal women. METHODS Women 45 to 75 years old and more than 12 months after the last menstruation, who attended menopausal/gynecological centers in Italy and Spain, were included. Women with at least one VVA symptom completed the following questionnaires: Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI), and Female Sexual Distress Scale revised (FSDS-R). A physical gynecological examination was performed to confirm the VVA diagnosis. Data were analyzed by chi-square and Student's t tests. RESULTS In all, 2,160 evaluable women were included in the study. VVA was confirmed in 90% of the included participants. The negative impact on sexual function was significantly higher in women with than in women without confirmed VVA, as evaluated with the sexual function component (DIVA-C) of the DIVA questionnaire (P = 0.013). Statistically significant differences (P < 0.0005) were also detected in the scores of overall FSDS-R, the overall FSFI, and of all the FSFI subdomains (desire, arousal, lubrication, orgasm, satisfaction, and pain). CONCLUSION For postmenopausal women with at least one VVA symptom, the presence of physician-confirmed VVA is associated with significant impaired sexual function, as shown by unadjusted analyses. Given the impact on quality of life and the prevalence of VVA, further research to improve and reduce VVA is warranted.
DNA inhibitors for the treatment of brain tumors

ABSTRACT Introduction: The worldwide incidence of central nervous system (CNS) primary tumors is increasing. Most of the chemotherapeutic agents used for treating these cancer types induce DNA damage, and their activity is affected by the functional status of repair systems involved in the detection or correction of DNA lesions. Unfortunately, treatment of malignant high-grade tumors is still an unmet medical need. Areas covered: We summarize the action mechanisms of the main DNA inhibitors used for the treatment of brain tumors. In addition, studies on new agents or drug combinations investigated for this indication are reviewed, focusing our attention on clinical trials that in the last 3 years have been completed, terminated or are still recruiting patients. Expert opinion: Much still needs to be done to render aggressive CNS tumors curable or at least to transform them from lethal to chronic diseases, as it is possible for other cancer types. Drugs with improved penetration in the CNS, toxicity profile, and activity against primary and recurrent tumors are eagerly needed. Targeted agents with innovative mechanisms of action and ability to harness the cells of the tumor microenvironment against cancer cells represent a promising approach for improving the clinical outcome of CNS tumors.
Personalized models of psychopathology as contextualized dynamic processes: An example from individuals with borderline personality disorder.

OBJECTIVE Psychopathology research has relied on discrete diagnoses, which neglects the unique manifestations of each individual's pathology. Borderline personality disorder combines interpersonal, affective, and behavioral regulation impairments making it particularly ill-suited to a "one size fits all" diagnosis. Clinical assessment and case formulation involve understanding and developing a personalized model for each patient's contextualized dynamic processes, and research would benefit from a similar focus on the individual. METHOD We use group iterative multiple model estimation, which estimates a model for each individual and identifies general or shared features across individuals, in both a mixed-diagnosis sample (N = 78) and a subsample with a single diagnosis (n = 24). RESULTS We found that individuals vary widely in their dynamic processes in affective and interpersonal domains both within and across diagnoses. However, there was some evidence that dynamic patterns relate to transdiagnostic baseline measures. We conclude with descriptions of 2 person-specific models as an example of the heterogeneity of dynamic processes. CONCLUSIONS The idiographic models presented here join a growing literature showing that the individuals differ dramatically in the total patterning of these processes, even as key processes are shared across individuals. We argue that these processes are best estimated in the context of person-specific models, and that so doing may advance our understanding of the contextualized dynamic processes that could identify maintenance mechanisms and treatment targets. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Mechanical strain promotes proliferation of ADSCs through the integrin β1-mediated RhoA/MLC pathway.

External volume expansion (EVE) promotes proliferation of adipose-derived stem cells (ADSCs) during adipose tissue regeneration. However, the mechanism by which EVE is translated into biochemical signals and subsequently induces proliferation of ADSCs is poorly understood. Here, we investigated the strain in adipose tissue and mechanochemical signaling upon EVE in rats. In addition, the effect of mechanical strain on proliferation of ADSCs was assessed using a custom-built Flexcell device. The level of strain in adipose tissue upon EVE peaked at week 1 and then decreased over time, and the cell proliferation rate was similarly affected. Mechanical strain-dependent activation of integrin β1 and the RhoA/myosin light chain (MLC) pathway was involved in cell proliferation. The proliferation rate of ADSCs was higher under 12% mechanical strain than under 6% and 0% mechanical strain in vitro. Mechanical strain-dependent activation of integrin β1 promoted activation of the small GTPase RhoA and phosphorylation of MLC. Furthermore, knockdown of integrin β1 attenuated activation of the RhoA/MLC pathway and proliferation of ADSCs in response to mechanical strain. Taken together, this study provides the first evidence of mechanochemical signaling in response to EVE. These data may help to elucidate the effects of different strain levels on adipose tissue regeneration.
Altered renal hemodynamics is associated with glomerular lipid accumulation in obese Dahl salt-sensitive leptin receptor mutant rats.

The current study examined whether the development of renal injury in the obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) strain is associated with elevations in GFR and renal lipid accumulation. Baseline MAP at 6 weeks of age was similar between SSWT and SSLepRmutant rats. However, by 18 weeks of age, the SSLepRmutant strain developed hypertension while the elevation in MAP was not as severe in SSWT rats (192±4 vs 149±6 mmHg, respectively). At baseline, proteinuria was 4-fold higher in the SSLepRmutant strain compared to SSWT rats and remained elevated throughout the study. The early development of progressive proteinuria was associated with renal hyperfiltration followed by a decline in renal function over the course of study in the SSLepRmutant strain compared to SSWT rats. Kidneys from the SSLepRmutant strain displayed more glomerulosclerosis and glomerular lipid accumulation in comparison to SSWT rats. Glomeruli were isolated from the renal cortex of both strains at 6 and 18 weeks of age and RNA sequencing was performed to identify genes and pathways driving glomerular injury. We observed significant increases in Cxcl16 and Cd36 (scavenger receptor and fatty acid translocase - influx lipid transporters, respectively) expression and a significant decrease in Abca2 (cholesterol efflux regulatory protein 2 - efflux lipid transporter) in SSLepRmutant rats versus SSWT rats at 6 and 18 weeks of age, which were validated by RT-PCR analysis. These data provide evidence that there may be an association between glomerular hyperfiltration and glomerular lipid accumulation during the early development of proteinuria associated with obesity.
Higher-risk myelodysplastic syndromes with del(5q): does the del(5q) matter?

ABSTRACT Introduction: Myelodysplastic Syndrome (MDS) represents a group of cancers characterized by abnormal blood cell formation and maturation, leading to various degrees of cytopenias and potential transformation to acute myeloid leukemia. Deletion of the long arm of chromosome 5 (del(5q)) is the most common clonal chromosomal anomaly in MDS, yet the population in this disease subtype is quite heterogeneous. This manuscript analyzes literature on high-risk MDS with del(5q) abnormalities. Areas covered: The paper will review outcomes with lenalidomide among high-risk MDS patients with del(5q). It will discuss the implications of harboring TP53 gene mutations, and share the data for allogeneic hematopoietic stem cell transplantations in this setting. Finally, the report evaluates the risk of disease progression in these patients. Expert commentary: Improved characterization of MDS has enhanced our understanding of patients with anomalies involving del(5q). Emerging literature is exploring combination therapy beyond lenalidomide, and next-generation sequencing may identify secondary mutations that could be an additional avenue for treatment.
Weekly variation in diet and physical activity among 4–75-year-old Danes

Abstract Objective: To compare dietary intake and physical activity (PA) between days of the week in a large sample of the Danish population; furthermore, to investigate the influence of gender and age as determinants for weekly variation. Design: Analysis was based on cross-sectional data from the Danish National Survey of Diet and Physical Activity 2011–2013. Dietary intake and PA were assessed by 7 d of pre-coded food diaries and pedometer-determined step counts. Dietary intake and PA on weekdays (Monday–Thursday), Friday, and weekend days (Saturday and Sunday) were compared using linear mixed models. Setting: Survey with national representation, conducted in Denmark between 2011 and 2013. Participants: A random sample of 4–75-year-old Danes, n 3934 and n 3530 in analysis of dietary intake and PA, respectively. Results: Energy intake during Friday and weekend days was 7–20 % higher compared with weekdays, while step counts were 10 and 17 % lower on Saturday and Sunday, respectively (all P < 0·001). Energy density of liquids and solids, consumption of added sugar, alcohol, discretionary foods, beer, wine and sugar-sweetened beverages were substantially higher, and consumption of dietary fibre, vegetables, fruit and wholegrain products were lower, during Friday and weekend days compared with weekdays (all P < 0·001). The observed patterns were present across gender and age, although weekly variation was most pronounced among children and relatively modest among the elderly. Conclusions: Weekend health behaviours of Danes display less favourable eating and PA behaviour compared with weekdays, making the weekend an important target for public health interventions aiming to improve dietary intake and PA behaviour.
Community Pharmacy Medicare Part D Consultations: Plan-Switching Decisions and Chronic Medication Adherence

Objectives: (1)To compare Part D plan switching for users and nonusers of a pharmacy-led Medicare Part D consultation service and (2) to evaluate the effect of service use on chronic medication adherence. Methods: This was a longitudinal study, occurring in one independently owned community pharmacy in Iowa. Medicare Part D beneficiaries who used the service were compared to nonusers. Dispensing data were used to compare planswitching and the effect of service use on chronic medication adherence between service users and nonusers. Proportion of days covered (PDC) was used to evaluate medication adherence. Results: In the 2017 and 2018 plan year, 79 and 138 Medicare beneficiaries used the service, respectively. These individuals were compared to 849 Medicare beneficiaries and a random sample of 101 beneficiaries in respective years. The respective switching rates for service users in 2018 and 2019 plan year were 43% and 15.9%, compared to 4% switching rates in both years for nonusers. Using the Medicare Part D consultation yielded a statistically significant positive effect on switching in both plan years (P values < .05) and a statistically significant positive effect on PDC between years (P value <.05). Conclusion: The use of a pharmacist-led Medicare Part D consultation resulted in increased plan switching and improved chronic medication adherence.
Quality of work life and work-family conflict: a cross-sectional study among nurses in teaching hospitals.

BACKGROUND The nursing profession is known to induce high levels of stress, and being simultaneously engaged in a stressful professional occupation and having a family life can lead to work-family conflict. Healthcare providers require recruitment and retention strategies that preserve nurses' quality of work-life and mitigate work-family conflict. AIM To investigate the relationship between quality of work-life and work-family conflict among hospital nurses in Iran, as well as the relationships between work-family conflict and quality of work life, and between age, professional experience, type of employment, work shift and marital status. METHOD This cross-sectional study was conducted among 378 nurses working in six Iranian teaching hospitals, who were selected using random quota sampling. Data on age, professional experience, type of employment, work shift and marital status was collected. The study questionnaire was based on the 53-item Quality of Work Life scale and the 18-item Work-Family Conflict scale. Correlations were established using Pearson's chi-squared and eta-squared tests. RESULTS A total of 93% of participants experienced moderate or high levels of work-family conflict and 83% had a low or moderate quality of work life. On average, the levels of work-family conflict and quality of work life were moderate. Quality of work life decreased with increasing work-family conflict. CONCLUSION Healthcare providers can use these results to inform their recruitment and retention strategies. Nurse managers can mitigate any adverse effects of work-family conflict on quality of work life by offering staff interventions such as short training courses on how to manage work-family conflict.
Risk stratification for multidrug-resistant bacteria in patients with skin and soft tissue infection.

PURPOSE OF REVIEW This article summarizes the available evidence enabling a stratification of risk for multidrug-resistant bacteria (MDRB) in patients with skin and soft tissue infection (SSTI). RECENT FINDINGS MDRB are increasingly reported in both healthcare-associated (HCA) and community-acquired (CA)-SSTI, including in patients with life-threatening presentations for whom early initiation of adequate antimicrobial therapy is pivotal to improve outcomes. Community-associated methicillin-resistant Staphylococcus aureus (MRSA) is now endemic in several geographical areas and may cause outbreaks in frail populations or other at-risk clusters. Pseudomonas aeruginosa and other nonfermenting Gram-negative pathogens are involved in CA-SSTI on an occasional basis, especially in patients with chronic wounds or recent antimicrobial exposure. The burden of HCA-SSTI because of MRSA, MR P. aeruginosa, MR Acinetobacter baumannii, extended-spectrum β-lactamase-producing Enterobacterales and vancomycin-resistant enterococci is amplifying in endemic settings. Severe comorbidities, prolonged hospitalization, invasive procedures, prior colonization or infection and antimicrobial exposure stand as the main risk factors for these conditions. Worryingly, carbapenemase-producing Enterobacterales are emerging as causative pathogens in HCA-SSTI. SUMMARY The choice of empirical agents depends on the type and location of SSTI, place of onset, initial severity and whether the patient presents or not with risk factors for MDRB, with local epidemiology and prior antimicrobial use being among the main features to consider.
Prevalence of substance use disorder and psychiatric comorbidity burden among pregnant women with opioid use disorder in a large administrative database, 2009–2014

Abstract Objectives Using data from the Healthcare Cost and Utilization Project (HCUP), we estimated prevalence of individual substance use disorders (SUDs) and psychiatric comorbidities among pregnant women with opioid use disorder (OUD) in the New York State from 2009 to 2014. Methods In this cross-sectional study, pregnancy outcome and gestational age at delivery were estimated, and OUD diagnosis during pregnancy or at delivery discharge was identified. Prevalence of SUDs and psychiatric comorbidities were then calculated. Results Among 1,463,302 pregnant women, 8324 (0.57%) were diagnosed with OUD during pregnancy or at delivery. The most frequent SUDs or psychiatric comorbidities among pregnant women with OUD were non-opioid SUD (78.2%), followed by tobacco use disorder (74.9%), generalized anxiety disorder (38.0%), major depressive disorder (36.9%), cannabis use disorder (28.3%) and cocaine use disorder (27.4%). Conclusions Most pregnant women with OUD were diagnosed with at least one non-opioid SUD and tobacco use disorder. Generalized anxiety disorder and major depressive disorder were also common, suggesting that mental health screenings should be prioritized for pregnant women with OUD.
Survey Item Response Rates by Survey Modality, Language, and Sociodemographic Factors in a Large U.S. Cohort

Background: Large-scale prospective cohorts traditionally use English, paper-based, mailed surveys, but Web-based surveys can lower costs and increase data quality, and multi-language surveys may aid in capturing diverse populations. Little evidence exists examining item response for multiple survey modalities or languages in epidemiologic cohorts. Methods: A total of 254,475 men and women completed a comprehensive lifestyle and medical survey at enrollment (2006–2013) for the Cancer Prevention Study-3, a U.S.-based prospective cohort. Web-based (English only) or paper (Spanish or English) surveys were offered. Using generalized linear models, differences in item response rates overall and by topical areas (e.g., reproductive history) by modality and language were examined. We further examined whether differences in response quality by sociodemographic characteristics within each survey modality existed. Results: Overall, English Web-based surveys had the highest average item response rate (97.6%), followed by English paper (95.5%) and Spanish paper (83.1%). Lower item response rates were seen among nonwhite, lower income, or less-educated participants. When examining individual survey sections by topic, results varied the most for residential history, with the lowest item response rate among Spanish language respondents (women, 62.7% and men, 64.3%) and the highest in English language Web-based, followed by paper respondents (women, 94.6% and men, 95.3%; and women, 92.8% and men, 92.1%, respectively). Conclusions: This study supports that utilizing multimodal survey approaches in epidemiologic studies does not differentially affect data quality. However, for some topic areas, further analysis should be considered for assessing data quality differences in Spanish language surveys. Impact: Multimodal survey administration is effective in nondifferentially capturing high-quality data. See all articles in this CEBP Focus section, “Modernizing Population Science. ”
Platelet‐derived transforming growth factor‐β1 promotes keratinocyte proliferation in cutaneous wound healing

Platelets are a recognised potent source of transforming growth factor‐β1 (TGFβ1), a cytokine known to promote wound healing and regeneration by stimulating dermal fibroblast proliferation and extracellular matrix deposition. Platelet lysate has been advocated as a novel personalised therapeutic to treat persistent wounds, although the precise platelet‐derived growth factors responsible for these beneficial effects have not been fully elucidated. The aim of this study was to investigate the specific role of platelet‐derived TGFβ1 in cutaneous wound healing. Using a transgenic mouse with a targeted deletion of TGFβ1 in megakaryocytes and platelets (TGFβ1fl/fl.PF4‐Cre), we show for the first time that platelet‐derived TGFβ1 contributes to epidermal and dermal thickening and cellular turnover after excisional skin wounding. In vitro studies demonstrate that human dermal fibroblasts stimulated with platelet lysate containing high levels of platelet‐derived TGFβ1 did not exhibit enhanced collagen deposition or proliferation, suggesting that platelet‐derived TGFβ1 is not a key promoter of these wound healing processes. Interestingly, human keratinocytes displayed enhanced TGFβ1‐driven proliferation in response to platelet lysate, reminiscent of our in vivo findings. In summary, our novel findings define and emphasise an important role of platelet‐derived TGFβ1 in epidermal remodelling and regeneration processes during cutaneous wound healing.