Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Caloric Restriction with Protein Supplementation on Plasma Protein Profiles in Middle-Aged Women with Metabolic Syndrome—A Preliminary Open Study

Background: Clinical studies have demonstrated that higher protein intake based on caloric restriction (CR) alleviates metabolic abnormalities. However, no study has examined the effects of plasma protein profiles on caloric restriction with protein supplementation (CRPS) in metabolic syndrome (MetS). Therefore, using a proteomic perspective, this pilot study investigated whether CRPS ameliorated metabolic abnormalities associated with MetS in middle-aged women. Methods: Plasma samples of middle-aged women with MetS in CR (n = 7) and CRPS (n = 6) groups for a 12-week intervention were obtained and their protein profiles were analysed. Briefly, blood samples from qualified participants were drawn before and after the dietary treatment. Anthropometric, clinical, and biochemical variables were measured and correlated with plasma proteomics. Results: In results, we found that body mass index, total body fat, and fasting blood glucose decreased significantly after the interventions but were not different between the CR and CRPS groups. After liquid chromatography–tandem mass spectrometry analysis, the relative plasma levels of alpha-2-macroglobulin (A2M), C4b-binding protein alpha chain (C4BPA), complement C1r subcomponent-like protein (C1RL), complement component C6 (C6), complement component C8 gamma chain (C8G), and vitamin K-dependent protein S (PROS) were significantly different between the CRPS and CR groups. These proteins are involved in inflammation, the immune system, and coagulation responses. Moreover, blood low-density lipoprotein cholesterol levels were significantly and positively correlated with C6 plasma levels in both groups. Conclusions: These findings suggest that CRPS improves inflammatory responses in middle-aged women with MetS. Specific plasma protein expression (i.e., A2M, C4BPA, C1RL, C6, C8G, and PROS) associated with the complement system was highly correlated with fasting blood glucose (FBG), blood lipids (BLs), and body fat.
The Potential for Mammographic Breast Density Change as a Biosensor of Adjuvant Tamoxifen Therapy Adherence and Response.

Within this issue of the Journal , Eriksson and colleagues (1) de-scribe the relation of adjuvant therapy with mammographic breast density (MBD) changes among women with breast cancer. Prior studies have demonstrated that tamoxifen-associated MBD decline translates into reduced breast cancer risk in the chemopreventive setting and improved breast cancer outcomes, including reduced risk of recurrence and breast cancer-specific death, in the adjuvant setting (2,3). Previously, this group observed improved prognosis upon MBD decline in the unaffected breast following tamoxifen therapy among breast cancer cases in Sweden (4). This current study builds upon those findings by examining influences of tamoxifen adherence as well as other adjuvant therapy types on MBD decline within 3 years postdiagnosis in a prospective cohort of 2490 Swedish breast cancer patients diagnosed between 2001 and 2015. They show that patients who received adjuvant tamoxifen were more likely than patients not prescribed endocrine therapy to experience MBD decline, consistent with prior reports (2,3). They extend existing knowledge by showing that women who continued tamoxifen were more likely to experience MBD decline compared with discontinuers. They also reported a che-motherapy-associated MBD decline among premenopausal women. Though the relation of MBD decline with prognostic outcomes was not evaluated, these present findings suggest that its assessment holds promise as a biomarker of adjuvant tamoxifen adherence.
Local adaptation in dispersal in multi‐resource landscapes

The distribution of resources in space has important consequences for the evolution of dispersal‐related traits. Dispersal moderates patterns of gene flow and, consequently, the potential for local adaptation to spatially differentiated resource types. We lack both models and experiments that evaluate how dispersal evolves in landscapes with multiple resources. Here, we investigate the evolution of dispersal in landscapes that contain two resource types that differ in their spatial autocorrelations. Individuals may possess ecological traits that give them a fitness advantage on one or the other resource. We find that resources differing in their spatial autocorrelation select for different optimal dispersal strategies and, further, that some multi‐resource landscapes can support the stable coexistence of distinct dispersal strategies. Whether divergence in dispersal strategies between resource specialists occurs depends on the underlying structure of the resources and the degree of linkage between dispersal strategies and ecological specialization. This work indicates that the spatial autocorrelation of resources is an important factor in determining when evolutionary branching is likely to occur, and sheds light on when secondary isolating mechanisms should arise between locally adapted specialists.
High diversity and rapid spatial turnover of integron gene cassettes in soil

Integrons are genetic elements that promote rapid adaptation in bacteria by capturing exogenous, mobile gene cassettes. Recently, a subset of gene cassettes has facilitated the global spread of antibiotic resistance. However, outside clinical settings, very little is known about their diversity and spatial ecology. To address this question, we sequenced integron gene cassettes from soils sampled across Australia and Antarctica. We recovered 44 970 open reading frames that encoded 27 215 unique proteins, representing an order of magnitude more cassettes than previous sequencing efforts. We found that cassettes have extremely high local richness, significantly greater than previously predicted, with estimates ranging from 4000 to 18 000 unique cassettes per 0.3 g of soil. We show that cassettes have a heterogeneous distribution across space, and that they exhibit rapid turnover with distance. Similarity between samples drops to between 0.1% and 10% at distances of as little as 100 m. Together, these data provide key insights into the ecology and size of the gene cassette metagenome.
Type I interferon induces CXCL13 to support ectopic germinal center formation

Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection–induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that resembles a secondary lymphoid organ. Here, we show that type I IFN produced after viral infection can induce CXCL13 expression in a phenotypically distinct population of lung fibroblasts, driving CXCR5-dependent recruitment of B cells and initiating ectopic germinal center formation. This identifies type I IFN as a novel inducer of CXCL13, which, in combination with other stimuli, can promote lung remodeling, converting a nonlymphoid tissue into one permissive to functional tertiary lymphoid structure formation.
Development of a Spanish version of the parent attitudes about childhood vaccines survey

ABSTRACT The Parent Attitudes about Childhood Vaccines (PACV) survey is a validated instrument for identifying vaccine-hesitant parents; however, a Spanish version is not available. Utilizing the WHO framework for translating survey instruments, we used an iterative process for developing the Spanish PACV that included forward translation, expert panel review, back translation and pre-testing that utilized cognitive interviewing. We made revisions to the Spanish PACV at each step, focusing on addressing inclusivity, readability, clarity and conceptual equivalence. The expert panel was comprised of 6 Spanish-speaking medical and research professionals who worked alongside 3 study team members. Pre-testing was conducted using convenience sampling of Spanish-speaking parents (N = 35) who had a child receiving care at the residents’ continuity clinic at Texas Children’s Hospital. Most pre-testing participants were married (80.6%), mothers (97.1%), ≥30 years of age (88.2%) and had a high school education or less (70.6%). While the majority of participants stated the survey was easy to complete, the translation of 5 PACV items was further revised to improve interpretability. We conclude that the final Spanish PACV is conceptually equivalent and culturally appropriate for most Hispanic populations.
Improving HPV vaccine delivery at school-based health centers

ABSTRACT Objective: To identify characteristics associated with human papillomavirus (HPV) vaccination rates, describe barriers and facilitators to vaccine uptake and the potential role for clinician-to-clinician Assessment, Feedback, Incentives, and eXchange (AFIX) visits in school-based health centers (SBHCs). Methods: We conducted clinician-to-clinician AFIX visits at 24 New York City (NYC) high-school and middle-school SBHCs with up-to-date adolescent vaccination rates below 40%. Using NYC’s immunization information system, we assessed HPV initiation and series completion rates at the time of AFIX visit and follow-up three to five months later. We analyzed responses to a questionnaire and summarized interviews to identify barriers and facilitators to HPV immunization practices and quality improvement (QI) implementation. Results: Baseline initiation and completion rates were 76% and 43% for high schools, and 81% and 45% for middle schools. SBHCs that allowed adolescent self-consent or did not require separate vaccine consent had higher baseline rates, but was not statistically significant. Barriers to series completion included challenges with scheduling and appointment compliance. At follow-up, high school SBHCs increased HPV vaccine initiation by 2.9 percentage points (p < 0.01) and series completion by 2.7 percentage points (p < 0.05). There was no statistically significant increase at middle school SBHCs. Most SBHCs (88%) chose reminder/recall systems as a QI strategy. Fewer than half (42%) implemented their QI strategy. Conclusions: We identified barriers to HPV vaccine series completion at our sample of SBHCs. Clinician-to-clinician AFIX visits may help improve vaccination rates and encourage providers to address barriers, including streamlining consent processes for HPV vaccination. Abbreviations: School-based health (SBH); quality improvement (QI)
Non-technical skills assessments in undergraduate medical education: A focused BEME systematic review: BEME Guide No. 54

Abstract Consensus on how to assess non-technical skills is lacking. This systematic review aimed to evaluate the evidence regarding non-technical skills assessments in undergraduate medical education, to describe the tools used, learning outcomes and the validity, reliability and psychometrics of the instruments. A standardized search of online databases was conducted and consensus reached on included studies. Data extraction, quality assessment, and content analysis were conducted per Best Evidence in Medical Education guidelines. Nine papers met the inclusion criteria. Assessment methods broadly fell into three categories: simulated clinical scenarios, objective structured clinical examinations, and questionnaires or written assessments. Tools to assess non-technical skills were often developed locally, without reference to conceptual frameworks. Consequently, the tools were rarely validated, limiting dissemination and replication. There were clear themes in content and broad categories in methods of assessments employed. The quality of this evidence was poor due to lack of theoretical underpinning, with most assessments not part of normal process, but rather produced as a specific outcome measure for a teaching-based study. While the current literature forms a good starting position for educators developing materials, there is a need for future work to address these weaknesses as such tools are required across health education.
County-level estimates of mental health professional shortage in the United States.

OBJECTIVE This study examined shortages of mental health professionals at the county level across the United States. A goal was to motivate discussion of the data improvements and practice standards required to develop an adequate mental health professional workforce. METHODS Shortage of mental health professionals was conceptualized as the percentage of need for mental health visits that is unmet within a county. County-level need was measured by estimating the prevalence of serious mental illness, then combining separate estimates of provider time needed by individuals with and without serious mental illness derived from National Comorbidity Survey Replication, U.S. Census, and Medical Panel Expenditure Survey data. County-level supply data were compiled from professional associations, state licensure boards, and national certification boards. Shortage was measured for prescribers, nonprescribers, and a combination of both groups in the nation's 3,140 counties. Ordinary least-squares regression identified county characteristics associated with shortage. RESULTS Nearly one in five counties (18%) in the nation had unmet need for nonprescribers. Nearly every county (96%) had unmet need for prescribers and therefore some level of unmet need overall. Rural counties and those with low per capita income had higher levels of unmet need. CONCLUSIONS These findings identified widespread prescriber shortage and poor distribution of nonprescribers. A caveat is that these estimates of need were extrapolated from current provider treatment patterns rather than from a normative standard of how much care should be provided and by whom. Better data would improve these estimates, but future work needs to move beyond simply describing shortages to resolving them.
Impact of an Antimicrobial Stewardship Intervention on Within- and Between-Patient Daptomycin Resistance Evolution in Vancomycin-Resistant Enterococcus faecium

Vancomycin-resistant Enterococcus (VRE) is a leading cause of hospital-acquired infection, with limited treatment options. Resistance to one of the few remaining drugs, daptomycin, is a growing clinical problem and has previously been described in this hospital. ABSTRACT Vancomycin-resistant Enterococcus (VRE) is a leading cause of hospital-acquired infection, with limited treatment options. Resistance to one of the few remaining drugs, daptomycin, is a growing clinical problem and has previously been described in this hospital. In response to increasing resistance, an antimicrobial stewardship intervention was implemented to reduce hospital-wide use of daptomycin. To assess the impact of the intervention, daptomycin prescribing patterns and clinically reported culture results from vancomycin-resistant Enterococcus faecium (VREfm) bloodstream infections (BSIs) from 2011 through 2017 were retrospectively extracted and the impact of the intervention was estimated using interrupted time series analysis (ITS). We corrected for a change in MIC determination methodology by retesting 262 isolates using Etest and broth microdilution. Hospital-wide and within-patient resistance patterns of corrected daptomycin MICs are reported. Our data show that daptomycin prescriptions decreased from an average of 287 days of therapy/month preintervention to 151 days of therapy/month postintervention. Concurrently, the proportion of patients experiencing an increase in daptomycin MIC during an infection declined from 14.6% (7/48 patients) in 2014 to 1.9% (1/54 patients) in 2017. Hospital-wide resistance to daptomycin also decreased in the postintervention period, but this was not maintained. This study shows that an antimicrobial stewardship-guided intervention reduced daptomycin use and improved individual level outcomes but had only transient impact on the hospital-level trend.
Diverticulosis and nine connective tissue disorders: epidemiological support for an association

ABSTRACT Purpose: An underlying connective tissue disorder (CTD) may predispose to formation of intestinal diverticula. We assess the association of diverticulosis with nine selected CTDs, to inform the pathophysiology of diverticula. Methods: A population-based period-prevalence study. Individuals (3.5 million New Zealand residents born 1901–1986) with a health system record 1999–2016 were grouped into those with a hospital diagnosis of diverticulosis or diverticulitis (ICD-10-AM K57), and those without. Also recorded were any hospital diagnoses of nine selected CTDs. The association of exposure to diverticulosis and each CTD was assessed using logistic regressions adjusted for age, gender, ethnicity and region. Results: In all, 85,958 (2.4%) people had a hospital diagnosis of diverticulosis. Hospitalisation with diverticulosis was highly significantly associated with rectal prolapse (adjusted odds ratio [OR] = 3.9), polycystic kidney disease (OR = 3.8), heritable syndromes (Marfan or Ehlers-Danlos) (OR = 2.4), female genital prolapse (OR = 2.3), non-aortic aneurysm (OR = 2.3), aortic aneurysm (OR = 2.2), inguinal hernia (OR = 1.9) and dislocations of shoulder and other joints (OR = 1.7), but not subarachnoid haemorrhage (OR = 1.0). Conclusion: People with diverticulosis are more likely to have colonic extracellular matrix (ECM)/connective tissue alterations in anatomical areas other than the bowel, suggesting linked ECM/connective tissue pathology. Although biases may exist, the results indicate large-scale integrated studies are needed to investigate underlying genetic pathophysiology of colonic diverticula, together with fundamental biological studies to investigate cellular phenotypes and ECM changes.
Overview of current and future systemic therapy for metastatic renal cell carcinoma

Since the 2000s, there have been dramatic advances in the treatment of metastatic renal cell carcinoma (mRCC), including drugs targeting vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. The first VEGF inhibitors approved for mRCC were sorafenib and sunitinib. Subsequently, two mTOR inhibitors (everolimus and temsirolimus) and other VEGF inhibitors (pazopanib and axitinib) were approved. Overall survival (OS) of mRCC patients has significantly increased during this period. Two novel VEGF inhibitors have recently been approved overseas, including cabozantinib and lenvatinib. Additionally, the recent advent of immunotherapy with checkpoint inhibitors has led to significant changes in the treatment of mRCC. The PD-1 inhibitor nivolumab improved the OS rate of patients with mRCC following VEGF inhibitors. Moreover, the CheckMate 214 trial demonstrated the benefit of nivolumab plus ipilimumab combination therapy in OS and objective response rate in treatment-naive intermediate- and poor-risk mRCC. In this review, current evidence related to the clinical use of targeted therapies and checkpoint inhibitors for the treatment of patients with mRCC is discussed. In addition, we review ongoing trials investigating combinations of checkpoint inhibitors with targeted agents and the identification of biomarkers to guide patient selection and enable individualization of therapy.
Oocyte donation disclosure decisions: a longitudinal follow-up at middle childhood

Abstract Few studies have captured oocyte donation (OD) parents’ decision processes about intended and actual disclosure over time. Likewise, OD children’s perceptions about their family composition during middle childhood are underexplored. To address these gaps, a longitudinally followed cohort of OD recipient families was invited to participate in a qualitative, follow-up study. With an 86% response rate after 12 years, families were composed of oocyte recipient mothers (n = 6) and biological fathers (n = 6) representing 12 donor-oocyte conceived children (10.33 ± 1.23 years; mean ± SD). Of the 12 children, two that were aware and two that were unaware of their conceptual origins completed conversational interviews. Only one family in the initial cohort had disclosed OD to their children by the 12-year follow-up, despite 43% of parents intending to disclose and another 43% undecided about disclosure during pregnancy. Four parental disclosure patterns emerged at 12 years: (i) wanting to disclose; (ii) conflicted about disclosure; (iii) not planning to disclose; and (iv) having disclosed. Children that were unaware of their conceptual origins displayed no knowledge of their method of conception. There is a need for family-centric interventions to assist ‘wanting to disclose’ parents in their disclosure process and ‘conflicted about disclosure’ parents in their decision-making process post-OD treatment.
Nutritional and productive parameters of Holstein/Zebu cows fed diets containing cactus pear

Objective This study ascertained effects of cactus pear in association with different roughage in the diet of F1 Holstein/Zebu cows on intake, nutrient digestibility, nitrogen balance, ingestive behavior and performance. Methods Eight cows with 72±11 days of lactation were used. The experimental design was simultaneous in two 4×4 Latin squares. Four experimental diets were used: Diet 1, sorghum silage as exclusive roughage; Diet 2, sorghum silage associated with cactus pear in a proportion of 50% of the roughage (dry matter basis); Diet 3, elephant grass (Pennisetum purpureum cv. Roxo) as exclusive roughage; Diet 4, elephant grass associated with cactus pear in a proportion of 50% of the roughage. The roughage:concentrate ratio was 75:25. Results Dry matter intake (p = 0.01) was higher with sorghum silage. There were differences in dry matter intake (p = 0.01), crude protein (p<0.01), ether extract (p = 0.01), non-fibrous carbohydrates (p<0.01) and total digestible nutrients (p = 0.01) among the diets. Cactus pear in the diet reduced water intake by 44.52% (p<0.01). The nitrogen balance was 59.71% and 27.49% lower in animals treated with exclusive sorghum silage and sorghum silage associated with cactus pear in relation to diets with elephant grass and elephant grass associated with cactus pear, respectively (p<0.01). The diets did not influence the milk production (p = 0.70), 3.5% fat corrected milk production (p = 0.72) or feed efficiency (p = 0.61). Conclusion The association of cactus pear with sorghum or elephant grass silage does not alter milk production, reduces the intake of dry matter and water and improves the digestibility of nutrients.