bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of dietary patterns and components with atherosclerosis risk biomarkers in familial hypercholesterolemia
Authors: Antoniazi Luiza , Arroyo-Olivares Raquel , Mata Pedro , Santos Raul D. 
Published: December 2021

Purpose of review
Familial hypercholesterolemia (FH) is a relatively common genetic disorder associated with elevated atherosclerotic risk. Dietary interventions can modulate processes associated with cardiovascular risk and potentiate the impact of pharmacological lipid-lowering therapies. This review evaluates recent findings of dietary patterns and their components on risk biomarkers in people with FH.

Recent findings
Diets lower in saturated fatty acids (SFA) may reduce low-density lipoprotein-cholesterol (LDL-C); however, their effects seem to be modest. A Mediterranean style diet apparently exerts more robust effects on plasma LDL-C, apolipoprotein B and C reactive protein concentrations than one restricted in SFA. Supplementation of plant sterols and stanols reduces LDL-C especially in children with FH. Caloric restricted diets may reduce weight and improve triglyceride levels in individuals with FH and excess body weight.

Summary
Despite the strong impact of genetic variants, dietary patterns mostly low in SFA and especially the Mediterranean diet may influence risk biomarkers in FH. However, most available studies are limited by cross-sectional design, small number of study subjects and short-term follow-ups. Robust interventional studies are necessary to test the impact of dietary patterns in people with FH.
Pediatric immune deficiencies: current treatment approaches
Authors: Gonzalez Corina 
Published: December 2021

Purpose of review
To summarize the currently available definitive therapies for patients with inborn errors of immunity (IEIs) with a strong focus on recent advances in allogeneic hematopoietic cell transplantation (HCT) and gene therapy, including the use of alternative donors, graft manipulation techniques, less toxic approaches for pretransplant conditioning and gene transfer using autologous hematopoietic stem cells.

Recent findings
In the absence of a matched sibling or a matched related donor, therapeutic alternatives for patients with IEIs include alternative donor transplantation or autologous gene therapy, which is only available for selected IEIs. In recent years, several groups have published their experience with haploidentical hematopoietic cell transplantation (HHCT) using different T-cell depletion strategies. Overall survival and event free survival results, although variable among centers, are encouraging. Preliminary results from autologous gene therapy trials with safer vectors and low-dose busulfan conditioning have shown reproducible and successful results. Both strategies have become valid therapeutic options for patients with IEIs. A new promising and less toxic conditioning regimen strategy is also discussed.

Summary
Definitive therapies for IEIs with HCT and gene therapy are in stage of evolution, not only to refine their efficacy and safety but also their reach to a larger number of patients.
Non‐Invasive Approaches to Estimate Liver Steatosis and Stiffness in Children With Non‐Alcoholic Fatty Liver Disease
Authors: Yodoshi Toshifumi , Orkin Sarah , Trout Andrew T. , Arce‐Clachar Ana Catalina , Bramlage Kristin , Liu Chunyan , Fei Lin , Dillman Jonathan R. , Xanthakos Stavra A. , Mouzaki Marialena 
Published: December 2021

ABSTRACTObjectives:To develop pediatric‐specific models that predict liver stiffness and hepatic steatosis in non‐alcoholic fatty liver disease (NAFLD), based on clinical and laboratory data.Methods:Children with NAFLD, who had undergone magnetic resonance imaging with proton density fat fraction (MRI‐PDFF) for steatosis quantification and/or magnetic resonance elastography (MRE) for liver stiffness assessment were included. We used data from patients imaged between April 2009 to July 2018 to develop a predictive model for fat fraction and stiffness. We validated the performance of the models using data from a second cohort, imaged between 2018 and 2019.Results:The first cohort (n = 344) consisted of predominantly non‐Hispanic (80%), male (67%) adolescents. MRE data were available for 343 children, while PDFF data were available for 130. In multivariable regression, ethnicity, insulin levels, platelet count, and aspartate aminotransferase independently predicted liver stiffness and these variables were used to develop the predictive model. Similarly, sex, ethnicity, alanine aminotransferase, and triglycerides levels independently predicted liver PDFF and were used in the PDFF model. The AUC of the optimal cutoff for the model that predicted a stiffness of >2.71 kPa was 0.70 and for the model that predicted PDFF >5% was 0.78. The validation group (n = 110) had similar characteristics. The correlation coefficient of the model with the measured liver stiffness was 0.30 and with the measured liver PDFF was 0.26.Conclusions:Pediatric‐specific models perform poorly at predicting exact liver stiffness and steatosis; however, in the absence of magnetic resonance imaging can be used to predict the presence of significant steatosis (>5%) and/or significant stiffness (>2.71). Thus, imaging remains an invaluable adjunct to laboratory investigations in determining disease severity.
Is Roux‐en‐Y Feeding Jejunostomy a Safe and Effective Operation in Children? A Systematic Review Exploring Outcomes
Authors: Cullis Paul S. , Buckle Rheanan E. , Losty Paul D. 
Published: December 2021

ABSTRACTObjectives:Roux‐en‐Y jejunostomy (REYJ) may establish feeding in children with foregut dysmotility or severe gastro‐esophageal reflux disease (GERD). Nevertheless, concerns have been raised about safety and efficacy. We, therefore, evaluated outcomes of REYJ by systematic review to determine if this was a satisfactory option for achieving enteral autonomy in children with complex nutritional needs.Methods:A PRISMA‐adherent systematic review was conducted of studies reporting children undergoing feeding REYJ. Two authors performed processes independently; the senior author resolved disagreements. Embase, CINAHL and Medline were searched (inception—01/21). Additional databases, references, and ‘grey’ literature were searched. Methodological Index for Non‐randomized Studies (MINORS) and a bespoke system assessed methodological quality.Results:Of 362 articles, 10 met eligibility criteria (9 retrospective series; 1 conference proceeding). Unpublished data were also attained. Interobserver agreement for MINORS (kappa = 0.47) and bespoke scoring (kappa = 0.58) were moderate. After consensus, median MINORS score was 37.5% (IQR 6.3%) and bespoke 50% (IQR 20.8%), indicating poor methodological quality. One hundred sixty‐four patients were reported (age range: 2 months to 19 years). Time to full feeds and length of stay were inadequately reported but most achieved enteral autonomy. No studies reported patient/caregiver‐questionnaires. Seventy‐six complications were documented (Clavien‐Dindo grading was infeasible). Morbidity included peristomal leakage (N = 26), internal hernia/volvulus (N = 8), and SSI (N = 7). Thirty‐eight patients died (2 procedure‐attributable) during follow‐up (range: 1 month to 15 years).Conclusions:Up to 50% patients experience complications after REYJ (often minor) with 23% patients dying during follow‐up, often comorbidity‐attributable. REYJ can achieve enteral autonomy although parents/caregivers of children should be counselled accordingly.
EZH2 Protein Expression in Triple-negative Breast Cancer Treated With Neoadjuvant Chemotherapy: An Exploratory Study of Association With Tumor Response and Prognosis
Authors: Fineberg Susan , Tian Xuejun , Makower Della , Harigopal Malini , Lo Yungtai 
Published: December 2021

Introduction:
Neaodjuvant chemotherapy is used to treat high risk triple-negative breast cancer (TNBC). Residual cancer burden (RCB) is used to predict risk of relapse after neoadjuvant chemotherapy (NAC); however, it cannot predict disease recurrence with certainty. EZH2 is a targetable oncogenic protein overexpressed in TNBC and associated with metastasis and stem cell expansion. We quantified EZH2 protein expression in TNBC before NAC to examine potential utility as a predictive and prognostic biomarker.

Materials and Methods:
We retrospectively identified 63 patients with localized TNBC treated with NAC. We quantified EZH2 nuclear expression in pretherapy biopsies using a score which included intensity and percent of positive cells at each intensity. EZH2 expression was evaluated as a continuous variable and dichotomized at a score of 210. Logistic regression analysis was used to determine association between EZH2 expression and RCB, tumor-infiltrating lymphocytes, clinicopathologic features and disease-free survival.

Results:
There was no significant association between EZH2 score and posttreatment RCB class evaluated as a continuous variable (P=0.831) or dichotomized at 210 (P=0.546). On multivariable logistic regression, adjusted for covariates including RCB, EZH2 >210 was associated with development of metastasis (odds ratio=14.35, 95% confidence interval: 2.69-76.66; P=0.002). Logistic regression was run with EZH2 scores as a continuous variable and increased EZH2 score was associated with metastasis (odds ratio=1.10, 95% confidence interval: 1.00-1.03; P=0.047).

Conclusion:
In our study of TNBC treated with NAC, high EZH2 expression in pretherapy core biopsies was significantly associated with metastatic recurrence independent of RCB. The potential value of EZH2 as a biomarker to improve stratification of outcome after NAC should be explored further.
Improving Equity of Care for Patients with Limited English Proficiency Using Quality Improvement Methodology
Authors: Martinez Elizabeth M. , Carr Daniel Timothy , Mullan Paul C. , Rogers Lakisha E. , Howlett-Holley Wendy L. , McGehee Coleman A. , Mangum Christopher D. , Godambe Sandip A. 
Published: December 2021

Introduction:
Disparate clinical outcomes have been reported for patients with Limited English Proficiency (LEP) in the emergency department setting, including increased length of stay, diagnostic error rates, readmission rates, and dissatisfaction. Our emergency department had no standard processes for LEP patient identification or interpreter encounter documentation and a higher rate of 48-hour LEP return visits (RV) than English proficient patients. The aim was to eliminate gaps by increasing appropriate interpreter use and documentation (AIUD) for Spanish-speaking LEP (LEP-SS) patients from 35.7% baseline (10/17-05/18) to 100% by October 2020.

Methods:
LEP-SS patient data were reviewed in the electronic medical record to determine the AIUD and RV rates. Using the Model for Improvement and multiple Plan-Do-Study-Act (PDSA) cycles, a multi-disciplinary team encouraged stakeholder engagement and identified improvement opportunities, implemented an electronic tracking board LEP icon (PDSA1), standardized documentation using an LEP Form linked to the icon (PDSA2), and included color changes to the icon for team situational awareness (PDSA3).

Results:
The mean of LEP-SS patients with AIUD improved from 35.7% to 64.5% without significant changes in balancing measures. During the postintervention period (6/1/2018-10/31/2020), no special cause variation was noted from the baseline 48-hour emergency department RV rates for LEP patients (3.1%) or English proficient patients (2.6%).

Conclusions:
While the RV rate was not affected, this project is part of a multi-faceted approach aiming to positively impact this outcome measure. Significant improvements in AIUD were achieved without affecting balancing measures.
Infection in Hospitalized Patients With Systemic Lupus Erythematosus
Authors: Carvalho Joana S. , Carvalho Maria G. , Reis Edna A. , Alves Luan Carlos V. , Ferreira Gilda A. 
Published: December 2021

Background
Identification of infection in patients with systemic lupus erythematosus (SLE) is a major challenge in clinical practice.

Objective
This medical records review study evaluated clinical markers, including the performance of C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) in the diagnosis of infection in SLE patients.

Methods
One hundred four SLE patients hospitalized between 2014 and 2018 were allocated into 3 groups, namely, infection, infection and disease activity, and isolated disease activity. Groups were compared in relation to clinical and laboratory variables. Accuracy measures were calculated for CRP, NLR, and PLR.

Results
C-reactive protein, NLR, and PLR differed between the groups with higher values observed in the infected group, intermediate values in the mixed group, and lower values in the group with isolated activity—CRP (56 vs 26 vs 15 mg/dL, p = 0.002), NLR (7.9 vs 4.0 vs 3.1, p = 0.005), and PLR (270 vs 227 vs 134, p = 0.025). Fever, tachypnea, and PLR were independently associated with infection. The cutoff points of the CRP of 20 mg/L, NLR of 3.5, and PLR of 151.4 presented values of sensitivity and specificity for the prediction of infection equal to 67% and 67%, 65% and 58%, and 71% and 53%, respectively. The developed algorithm showed a sensitivity of 86.6% and specificity of 81% for the diagnosis of infection.

Conclusions
The combined use of clinical and laboratory markers presented superior accuracy than their isolated use, suggesting a great potential for the application of the algorithm in clinical practice.
Unrecognized Fracture of a Silicone Implant During Closed Rhinoplasty
Authors: Lee Sae Bin , Kim Kyung Soo , Min Hyun Jin 
Published: December 2021

Abstract:
Rhinoplasty via a closed approach is rarely performed due to provide limited exposure and inadequate operative field. Nevertheless, there are some cases in which closed approach is performed using L-shaped silicone implants. The authors recently encountered an interesting complication in a 33-year-old woman who had previously undergone rhinoplasty via a closed approach and who sought revision rhinoplasty at our institution. The authors accidently found a fractured silicone implant on lateral nasal x-ray. She had no nasal trauma history since previous rhinoplasty. The authors assumed that the silicone implant can be fractured as 1 of complications during the rhinoplasty via a closed approach.
Development and Application of a Semi quantitative Scoring Method for Ultrastructural Assessment of Acute Stress in Pancreatic Islets
Authors: Dyson Nicola J. , Kattner Nicole , Honkanen-Scott Minna , Hunter Bethany , Doyle Jennifer A. , White Kathryn , Davey Tracey S. , Ploeg Rutger J. , Bury Yvonne A. , Tiniakos Dina G. , Shaw James A. M. , Scott William E. 
Published: December 2021

Background.
Pancreas and islet transplantation outcomes are negatively impacted by injury to the endocrine cells from acute stress during donor death, organ procurement, processing, and transplant procedures. Here, we report a novel electron microscopy scoring system, the Newcastle Pancreas Endocrine Stress Score (NPESS).

Methods.
NPESS was adapted and expanded from our previously validated method for scoring pancreatic exocrine acinar cells, yielding a 4-point scale (0–3) classifying ultrastructural pathology in endocrine cell nuclei, mitochondria, endoplasmic reticulum, cytoplasmic vacuolization, and secretory granule depletion, with a maximum additive score of 15. We applied NPESS in a cohort of deceased organ donors after brainstem (DBD) and circulatory (DCD) death with a wide range of cold ischemic times (3.6–35.9 h) including 3 donors with type 1 and 3 with type 2 diabetes to assess islets in situ (n = 30) in addition to pancreata (n = 3) pre- and postislet isolation.

Results.
In DBD pancreata, NPESS correlated with cold ischemic time (head: r = 0.55; P = 0.02) and mirrored exocrine score (r = 0.48; P = 0.01). When stratified by endocrine phenotype, cells with granules of heterogeneous morphology had higher scores than α, β, and δ cells (P < 0.0001). Cells of mixed endocrine-exocrine morphology were observed in association with increased NPESS (P = 0.02). Islet isolation was associated with improved NPESS (in situ: 8.39 ± 0.77 [Mean ± SD]; postisolation: 5.44 ± 0.31; P = 0.04).

Conclusions.
NPESS provides a robust method for semiquantitative scoring of subcellular ultrastructural changes in human pancreatic endocrine cells in situ and following islet isolation with utility for unbiased evaluation of acute stress in organ transplantation research.
Investigating climate tipping points under various emission reduction and carbon capture scenarios with a stochastic climate model
Authors: Mendez Alexander , Farazmand Mohammad 
Published: December 2021

We study the mitigation of climate tipping point transitions using an energy balance model. The evolution of the global mean surface temperature is coupled with the

CO
2

concentration through the green-house effect. We model the

CO
2

concentration with a stochastic delay differential equation (SDDE), accounting for various carbon emission and capture scenarios. The resulting coupled system of SDDEs exhibits a tipping point phenomena: if

CO
2

concentration exceeds a critical threshold (around

478

ppm

), the temperature experiences an abrupt increase of about six degrees Celsius. We show that the

CO
2

concentration exhibits a transient growth which may cause a climate tipping point, even if the concentration decays asymptotically. We derive a rigorous upper bound for the

CO
2

evolution which quantifies its transient and asymptotic growths, and provides sufficient conditions for evading the climate tipping point. Combining this upper bound with Monte Carlo simulations of the stochastic climate model, we investigate the emission reduction and carbon capture scenarios that would avert the tipping point.
The alopecia areata phenotype is induced by the water avoidance stress test incchcr1-deficient mice
Authors: Zhao Qiao-Feng , Yoshihara Nagisa , Takagi Atsushi , Komiyama Etsuko , Oka Akira , Ikeda Shigaku 
Published: December 2021

ABSTRACTBackgroundWe recently discovered a nonsynonymous variant in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene within the alopecia areata (AA) risk haplotype; mice engineered to carry the risk allele displayed a hair loss phenotype.ObjectiveTo further investigate the involvement of theCCHCR1gene in AA pathogenesis.MethodsWe developed an AA model using C57BL/6Ncchcr1gene knockout mice. Mice (6-8 weeks) were divided into two groups:cchcr1-/-mice and wild-type (WT) mice. Both groups were subjected to a water avoidance stress (WAS) test.ResultsEight weeks after the WAS test, 25% ofcchcr1mice exhibited noninflammatory foci of alopecia on the dorsal skin. The foci resembled human AA in terms of gross morphology, trichoscopic findings and histological findings.ConclusionsOur results strongly suggest thatCCHCR1is associated with AA pathogenesis and thatcchcr1-/-mice are a good model for investigating AA.Author summaryAlopecia areata is thought to affect 1-2% of the population. In severe alopecia areata, changes in appearance significantly reduce the patient’s quality of life, but there is no established treatment. Its pathogenic mechanism is thought to cause an autoimmune disease of the hair bulb of growing hair. Many genes and factors associated with AA onset form a background that easily causes such an immune reaction, and the causative genes related to alopecia areata are being elucidated worldwide. We were able to identify theCCHCR1gene as one of the causative genes by genome analysis. In this study, we createdCCHCR1-deficient mice using Cre/loxP technology and confirmed that 25% ofCCHCR1-deficient mice that underwent the WAS test for psychological stimulation developed hair loss similar to that observed in human alopecia areata. This suggests that theCCHCR1gene is a disease susceptibility gene for alopecia areata.
A measure of concurrent neural firing activity based on mutual information
Authors: Mijatovic Gorana , Loncar-Turukalo Tatjana , Bozanic Nebojsa , Faes Luca 
Published: December 2021

AbstractMultiple methods have been developed in an attempt to quantify stimulus-induced neural coordination and to understand internal coordination of neuronal responses by examining the synchronization phenomena in neural discharge patterns. In this work we propose a novel approach to estimate the degree of concomitant firing between two neural units, based on a modified form of mutual information (MI) applied to a two-state representation of the firing activity. The binary profile of each single unit unfolds its discharge activity in time by decomposition into the state of neural quiescence/low activity and state of moderate firing/bursting. Then, the MI computed between the two binary streams is normalized by their minimum entropy and is taken as positive or negative depending on the prevalence of identical or opposite concomitant states. The resulting measure, denoted as Concurrent Firing Index based on MI (CFIMI), relies on a single input parameter and is otherwise assumption-free and symmetric. Exhaustive validation was carried out through controlled experiments in three simulation scenarios, showing that CFIMIis independent on firing rate and recording duration, and is sensitive to correlated and anti-correlated firing patterns. Its ability to detect non-correlated activity was assessed using ad-hoc surrogate data. Moreover, the evaluation of CFIMIon experimental recordings of spiking activity in retinal ganglion cells brought insights into the changes of neural synchrony over time. The proposed measure offers a novel perspective on the estimation of neural synchrony, providing information on the co-occurrence of firing states in the two analyzed trains over longer temporal scales compared to existing measures.
NIH Funding of COVID-19 Research in 2020: a Cross Sectional Study
Authors: Balaguru Logesvar , Dun Chen , Meyer Andrea , Hennayake Sanuri , Walsh Christi M. , Kung Christopher , Cary Brittany , Migliarese Frank , Dai Tinglong , Bai Ge , Sutcliffe Kathleen , Makary Martin A. 
Published: December 2021

AbstractObjectiveThis study aims to characterize and evaluate the NIH’s grant allocation pattern of COVID-19 research.DesignCross sectional studySettingCOVID-19 NIH RePORTER Dataset was used to identify COVID-19 relevant grants.Participants1,108 grants allocated to COVID-19 research.Main Outcomes and MeasuresThe primary outcome was to determine the number of grants and funding amount the NIH allocated for COVID-19 by research type and clinical/scientific area. The secondary outcome was to calculate the time from the funding opportunity announcement to the award notice date.ResultsThe NIH awarded a total of 56,169 grants in 2020, of which 2.0% (n=1,108) were allocated for COVID-19 research. The NIH had a $42 billion budget that year, of which 5.3% ($2.2 billion) was allocated to COVID-19 research. The most common clinical/scientific areas were social determinants of health (n=278, 8.5% of COVID-19 funding), immunology (n=211, 25.8%), and pharmaceutical interventions research (n=208, 47.6%). There were 104 grants studying COVID-19 non-pharmaceutical interventions, of which 2 grants studied the efficacy of face masks and 6 studied the efficacy of social distancing. Of the 83 COVID-19 funded grants on transmission, 5 were awarded to study airborne transmission of COVID-19, and 2 grants on transmission of COVID-19 in schools. The average time from the funding opportunity announcement to the award notice date was 151 days (SD: ±57.9).ConclusionIn the first year of the pandemic, the NIH diverted a small fraction of its budget to COVID-19 research. Future health emergencies will require research funding to pivot in a timely fashion and funding levels to be proportional to the anticipated burden of disease in the population.