bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-Induced Cyr61/CCN1 Production in Infantile Hemangioma
Authors: Wu Pinru , Xu Hui , Li Ningli , Huo Rongfen , Shen Baihua , Lin Xiaoxi , Ma Gang 
Published: February 2021

Background:
Hypoxia may play a role in the pathogenesis of infantile hemangioma. Cysteine-rich angiogenic inducer 61 (Cyr61), or CCN1, can be induced under hypoxic conditions in several types of cells. However, whether CCN1 has any impact on infantile hemangioma remains unknown. This study aims to explore the expression of CCN1 in infantile hemangioma and to investigate the effect of hypoxia on CCN1 and vascular endothelial growth factor-A (VEGF-A) production.

Methods:
Hemangioma-derived endothelial cells and hemangioma-derived stem cells were isolated from surgical specimens of proliferative infantile hemangioma. RNA extracted from infantile hemangioma tissue, hemangioma-derived endothelial cells, and hemangioma-derived stem cells was used to analyze gene expression by real-time polymerase chain reaction. The effects of CCN1 blockade were examined in hemangioma-derived stem cells. Immunostaining, immunoblotting, and enzyme-linked immunosorbent assays were used to assess protein expression.

Results:
By double-label immunofluorescence staining, the authors first identified that CCN1 was abundant in proliferative infantile hemangioma lesions and colocalized well with immature microvessels. The authors found that the mRNA level of CCN1 in proliferative infantile hemangioma was significantly higher than in healthy controls, as was involuting infantile hemangioma. Treatment with the hypoxia inducer cobalt chloride dramatically increased CCN1 production in hemangioma-derived endothelial cells in a time-dependent manner. Furthermore, blocking or knockdown of CCN1 expression reduced the expression of VEGF-A in hemangioma-derived stem cells. Lastly, the signaling pathway study showed that CCN1 up-regulation of VEGF-A synthesis in hemangioma-derived stem cells depends on nuclear factor-κB and JNK activation.

Conclusions:
These findings provide new evidence that CCN1 participates in the crosstalk between hemangioma-derived endothelial cells and hemangioma-derived stem cells through promoting VEGF-A expression in the hypoxic environment of infantile hemangioma angiogenesis and vasculogenesis. Targeting of CCN1 might be a novel therapeutic strategy for infantile hemangioma.
Variation in Payment per Work Relative Value Unit for Breast Reconstruction and Nonbreast Microsurgical Reconstruction: An All-Payer Claims Database Analysis
Authors: Shamsunder Meghana G. , Sheckter Clifford C. , Sheinin Avraham , Rubin David , Berlin Nicholas L. , Mehrara Babak , Matros Evan 
Published: February 2021

Background:
Commercial payments for implant-based breast reconstruction have increased within the past decade, whereas reimbursements have stagnated for microsurgical techniques. The physician payment–to–work relative value unit ratio allows for standardization when comparing procedures of differing complexity. This study aimed to characterize payment per work relative value unit for common breast and nonbreast microsurgical procedures.

Methods:
The Massachusetts All-Payer Claims Database was queried from 2010 to 2014 for Current Procedural Terminology (CPT) codes related to microsurgical and breast reconstruction. International Classification of Diseases codes were further used to categorize procedures by anatomical region, including head and neck, breast, trunk, and extremities. Physician payments, both commercial and governmental, were aggregated by anatomical region and CPT code. Payment distributions were described with means and medians and compared using statistical tests.

Results:
Among 3435 commercial claims, distributions of physician payments per work relative value unit for microsurgical and common breast procedures differed only for breast free flaps billed through S codes (p < 0.001). Microsurgical breast procedures (CPT code 19364) had significantly greater median payments per work relative value unit compared to microsurgery of the head and neck, trunk, and upper extremities (p = 0.004). Payment per work relative value unit for common breast and nonbreast microsurgical procedures did not differ significantly among governmental claims (p = 0.103).

Conclusions:
Adjustment of physician payments by work relative value units did not show significant variability across common breast procedures, except for S codes, suggesting that payments are mostly driven by differences in work relative value units and individual contractual negotiations. Lower payments per work relative value unit for other regions compared to breast suggests an opportunity for negotiation with commercial payers.
Women in Leadership and Their Influence on the Gender Diversity of Academic Plastic Surgery Programs
Authors: Keane Alexandra M. , Larson Ellen L. , Santosa Katherine B. , Vannucci Bianca , Waljee Jennifer F. , Tenenbaum Marissa M. , Mackinnon Susan E. , Snyder-Warwick Alison K. 
Published: February 2021

Background:
Women seldom reach the highest leadership positions in academic plastic surgery. Contributing factors include lack of female role models/mentors and lack of gender diversity. Studies show that female role models and mentors are critical for recruiting and retaining female surgeons and that gender diversity within organizations more strongly influences women’s career choices. The authors therefore sought to determine the current gender diversity of academic plastic surgery programs and investigate influences of gender and leadership on program gender composition.

Methods:
A cross-sectional study of U.S. plastic surgery residency programs was performed in December of 2018. Genders of the leadership were collected, including medical school dean, department of surgery chair, department/division of plastic surgery chair/chief, plastic surgery program director, plastic surgery faculty, and plastic surgery residents. Gender relationships among these groups were analyzed.

Results:
Ninety-nine residency programs were identified (79 integrated with or without independent and 20 independent). Women represented a smaller proportion of academic plastic surgeons in more senior positions (38 percent residents, 20 percent faculty, 13 percent program directors, and 8 percent chairs). Plastic surgery chair gender was significantly correlated with program director gender, and plastic surgery faculty gender was significantly associated with plastic surgery resident gender. Although not statistically significant, female plastic surgery chair gender was associated with a 45 percent relative increase in female plastic surgery residents.

Conclusions:
Women in leadership and gender diversity influence the composition of academic plastic surgery programs. Gender disparity exists at all levels, worsening up the academic ladder. Recruitment, retention, and promotion of women is critical, as such diversity is required for continued progress in innovation and problem-solving within plastic surgery.
A Comparison of Pulsatile Hypothermic and Normothermic Ex Vivo Machine Perfusion in a Porcine Kidney Model
Authors: Vallant Natalie , Wolfhagen Nienke , Sandhu Bynvant , Hamaoui Karim , Cook Terence , Pusey Charles , Papalois Vassilios 
Published: February 2021

Background.
Hypothermic machine perfusion (HMP) is a well-established method for deceased donor kidney preservation. Normothermic machine perfusion (NMP) might offer similar or greater advantages. We compared the 2 methods in an ex vivo perfusion model using 34 porcine kidneys.

Methods.
Thirty kidneys were stored on ice for 24 h before undergoing 4 h of HMP (n = 15) or NMP (n = 15) followed by 2 h of normothermic ex vivo reperfusion with whole blood. Four kidneys underwent 28 h of cold static storage followed by 2 h of normothermic ex vivo reperfusion. During the 2 h of normothermic ex vivo reperfusion, perfusate flow rates, urinary output, and oxygen consumption rates were compared between all groups.

Results.
Porcine kidneys after HMP showed significantly higher urinary output (5.31 ± 2.06 versus 2.44 ± 1.19 mL/min; P = 0.002), oxygen consumption (22.71 ± 6.27 versus 11.83 ± 1.29 mL/min; P = 0.0016), and perfusate flow rates (46.24 ± 12.49 versus 26.16 ± 4.57 mL/min; P = 0.0051) than kidneys after NMP. TUNEL staining of tissue sections showed significantly higher rates of apoptosis in kidneys after NMP (P = 0.027).

Conclusions.
In our study, the direct comparison of HMP and NMP kidney perfusion in a translational model demonstrated superiority of HMP; however, further in vivo studies would be needed to validate those results.
What have we learned from cognition in the oldest-old
Authors: Kawas Claudia H. , Legdeur Nienke , Corrada María M. 
Published: February 2021

Purpose of review
People over 90 are the fastest growing segment of the population with the highest rates of dementia. This review highlights recent findings that provide insight to our understanding of dementia and cognition at all ages.

Recent findings
Risk factors for Alzheimer's disease (AD) and dementia differ by age, with some factors, like the development of hypertension, actually becoming protective in the oldest-old. At least half of all dementia in this age group is due to non AD pathologies, including microinfarcts, hippocampal sclerosis and TDP-43. The number of pathologic changes found in the brain is related to both risk and severity of dementia, but many people in this age group appear to be ‘resilient’ to these pathologies. Resilience to Alzheimer pathology, in part, may be related to absence of other pathologies, and imaging and spinal fluid biomarkers for AD have limited utility in this age group.

Summary
Studies of dementia in the oldest-old are important for our understanding and eventual treatment or prevention of dementia at all ages.
Abnormal synaptic pruning during adolescence underlying the development of psychotic disorders
Authors: Germann Monique , Brederoo Sanne G. , Sommer Iris E.C. 
Published: February 2021

Purpose of review
Excessive synaptic pruning has first been suggested by Irwin Feinberg (1982) as an important pillar in the pathophysiology in schizophrenia (SCZ). This article reviews recent developments highlighting factors implicated in aberrant synaptic pruning and its contribution to disease onset and emergence of cognitive symptoms in SCZ. Unraveling these factors provides new insights for potential prevention and treatment strategies for psychotic disorders.

Recent findings
Increased pruning in SCZ was recently confirmed by a positron emission tomography-study employing the novel tracer [11C]UCB-J, demonstrating the consequential loss of synaptic density. Recent evidence supports the contributing role of astrocytes and increased complement-mediated microglial pruning in disease onset and cognitive symptoms in SCZ. Increased microglial pruning is mediated specifically by C4. Furthermore, environmental factors (e.g., infections and stress) can lead to dysbiosis which was recently linked to microglial activation and pruning in SCZ.

Summary
Recent findings render the pruning machinery a potential target for early treatment and prevention in individuals at high risk for SCZ. Minocycline can improve cognition in SCZ, probably by reducing excessive pruning. Probiotics might also have beneficial effects on cognition, although recent findings are not encouraging. N-acetyl-cysteine recovers functional connectivity in SCZ both in vitro and in vivo, making it an interesting candidate.
Lack of latent tuberculosis screening in HIV patients and delay in Anti-Retroviral Therapy initiation in HIV-TB co-infection: A 11-year study in an intermediate TB-burden country
Authors: Teng Vannesa Yue May , Chua Yan Ting , Lai Eunice En Ni , Mukherjee Shilpa , Michaels Jessica , Wong Chen Seong , Leo Yee Sin , Young Barnaby , Archuleta Sophia , Ong Catherine W.M. 
Published: February 2021

ABSTRACTObjectivesTuberculosis (TB) is a common infection in HIV patients. Our study aims to determine the prevalence and characteristics of HIV-TB co-infected patients in Singapore, a high-income, intermediate TB-burden country.MethodsRetrospective data of 11-years was obtained from the National University Hospital (NUH), a quaternary care hospital and the National Centre for Infectious Diseases, the national HIV centre.ResultsFrom December 2005 to December 2016, 48 out of 819 HIV patients and 272 out of 3,196 HIV patients who were managed in NUH and TTSH respectively, were diagnosed with TB. 89.1% (n=285) were males and 2 (0.6%) were screened for latent TB on HIV diagnosis. The median age at TB diagnosis was 47.3 years old (Interquartile range, IQR 41-57). Mean CD4 count at TB diagnosis was 125.0 ± 153.9 cells/mm3. 124 (38.6%) patients had CD4 < 50 cells/mm3. 41.3% (n=132) of patients had HIV diagnosed at least 6 weeks before TB diagnosis, indicating an opportunity to initiate latent TB preventive therapy. 55.0% (n=176) had HIV and TB concomitantly diagnosed within 6 weeks whilst 2.25% (n=7) had TB diagnosed before HIV. Of those HIV-TB co-infected patients with CD4 ≤ 50 cells/mm3, 18 (14.2%) had anti-retroviral therapy (ART) started <2 weeks. TB-related mortality was 5.3% (n=17) and 3.75% (n=12) were lost to follow-up.ConclusionThere is a lack of latent TB screening in HIV patients and a delay in initiation of ART in HIV-TB patients with low CD4 counts in our study. Clinical practices can be further improved for the benefit of outcomes in HIV-TB patients.
The effect of special educational assistance in early childhood education and care on psycho-social difficulties in elementary school children
Authors: Biele Guido , Lekhal Ratib , Overgaard Kristin R. , Wang Mari Vaage , Brandlistuen Ragnhild Eek , Friis Svein , Zeiner Paal 
Published: February 2021

AbstractThree to seven percent of preschoolers have developmental problems or child psychiatric disorders. Randomized controlled trials (RCTs) indicate that interventions in early childhood education and care improve long-term outcomes of children from disadvantaged backgrounds. It is unknown if effects generalize beyond the well-structured context of RCTs and to children who may not have a disadvantaged background but have developmental problems or psychiatric disorders. We use data from the population-based Norwegian Mother, Father and Child Cohort Study, recruiting pregnant women from 1999 to 2008, with child follow-up from ages 6, 18, and 36 months to ages 5, 7, and 8 years. This sub-study included 2499 children with developmental problems or psychiatric disorders at age five. We investigate the effects of special educational assistance at age five on mother-reported internalizing, externalizing, and communication problems at age eight. We analyze bias due to treatment by indication with directed acyclic graphs, adjust for treatment predictors to reduce bias, and estimate effects in different patient groups and outcome domains with a hierarchical Bayesian model. In the adjusted analysis, preschoolers with special educational assistance had on average by 0.1 (0.03-0.16) standardized mean deviation weaker psycho-social difficulties in elementary school. Mean effect sizes varied between groups and outcomes. We estimate positive effects of educational assistance during the transition from preschool to the school years. It should therefore be considered as an intervention for preschoolers with developmental or behavior problems. More research with improved measurements of treatment and outcomes is needed to identify success factors for their implementation.
The utility of homologous recombination deficiency biomarkers across cancer types
Authors: Takamatsu Shiro , Brown J.B. , Yamaguchi Ken , Hamanishi Junzo , Yamanoi Koji , Takaya Hisamitsu , Kaneyasu Tomoko , Mori Seiichi , Mandai Masaki , Matsumura Noriomi 
Published: February 2021

AbstractBackgroundGenomic alterations in BRCA1/2 and genomic scar signatures are associated with homologous recombination DNA repair deficiency (HRD) and serve as therapeutic biomarkers for platinum and PARP inhibitors in breast and ovarian cancers. However, the clinical significance of these biomarkers in other homologous recombination repair-related genes or other cancer types is not fully understood.ResultsWe analyzed the datasets of all solid cancers from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia, and found that the association between biallelic alterations in the homologous recombination pathway genes and genomic scar signatures differed greatly depending on gender and the presence of somatic TP53 mutation. Additionally, HRD cases identified by a combination of these indicators showed higher sensitivity to DNA-damaging drugs than non-HRD cases both in clinical samples and cell lines.ConclusionOur work provides novel proof of the utility of HRD analysis for all cancer types and will improve the precision and efficacy of chemotherapy selection in clinical oncology.
Applicability of Neighborhood and Building Scale Wastewater-Based Genomic Epidemiology to Track the SARS-CoV-2 Pandemic and other Pathogens
Authors: Spurbeck Rachel R. , Minard-Smith Angela T. , Catlin Lindsay A. 
Published: February 2021

AbstractThe benefits of wastewater-based epidemiology (WBE) for tracking the viral load of SARS-CoV-2, the causative agent of COVID-19, have become apparent since the start of the pandemic. However, most sampling occurs at the wastewater treatment plant influent and therefore can only monitor SARS-CoV-2 concentration and spread within the entire catchment, which can encompass multiple municipalities. Furthermore, most WBE only quantifies the virus, and therefore miss crucial information that can be gained by sequencing SARS-CoV-2. Here we demonstrate feasibility of sampling at the neighborhood or building complex level using a mix of quantitative polymerase chain reaction (qPCR) and targeted sequencing to provide a more refined understanding of the local dynamics of SARS-CoV-2 strains. When coupled with the higher-level treatment plant samples, this creates an opportunity for health officials to monitor the spread of the virus at different spatial and temporal scales to inform policy decisions.Here we demonstrate the feasibility of tracking SARS-CoV-2 at the neighborhood, hospital, and nursing home level with the ability to detect one COVID-19 positive out of 60 nursing home residents. The viral load obtained was correlative with the number of COVID-19 patients being treated in the hospital. Sequencing of the samples over time demonstrated that nonsynonymous mutations fluctuate in the viral population, and wastewater-based sequencing could be an efficient approach to monitor for vaccine or convalescent plasma escape mutants, as well as mutations that could reduce the efficacy of diagnostics. Furthermore, while SARS-CoV-2 was detected by untargeted RNA sequencing, qPCR and targeted whole genome amplicon sequencing were more reliable methods for tracking the pandemic. From our sequencing data, clades and shifts in mutation profiles within the community were traceable and could be used to determine if vaccine or diagnostics need to be adapted to ensure continued efficacy.Graphical AbstractHighlightsNeighborhood or building level wastewater analysis accurately detects SARS-CoV-2SARS-CoV-2 was detected in wastewater from one infected person out of 60 residentsTotal RNAseq did not accurately detect SARS-CoV-2 in wastewater samples.Targeted whole genome sequencing of wastewater samples identified Spike mutations.
A glomerular transcriptomic landscape of APOL1 in Black patients with focal segmental glomerulosclerosis
Authors: McNulty Michelle M. , Fermin Damian , Eichinger Felix , Jang Dongkeun , Kretzler Matthias , Burtt Noel , Pollak Martin R. , Flannick Jason , Friedman David J. ,   Nephrotic Syndrome Study Network (NEPTUNE), Sampson Matthew G. 
Published: February 2021

AbstractApolipoprotein L1 (APOL1)-associated focal segmental glomerulosclerosis (FSGS) is the dominant form of FSGS in Black people. There are no targeted therapies for this condition, in part because the molecular mechanisms underlying APOL1’s pathogenic contribution to FSGS are incompletely understood. Studying the transcriptomic landscape of APOL1 FSGS in patient kidneys is an important way to discover genes and molecular behaviors that are unique or most relevant to the human disease. With the hypothesis that the pathology driven by the high-risk (HR) APOL1 genotype is reflected in alteration of gene expression across the glomerular transcriptome, we compared expression and co-expression profiles of 15,703 genes in 16 Black FSGS patients with a HR vs 14 with a low-risk (“LR”) APOL1 genotype. Expression data from APOL1-inducible HEK293 cells and normal human glomeruli were used to pursue genes and molecular pathways illuminated in these studies.We discovered (1) increased expression of APOL1 in HR and nine other significant differentially expressed genes, including stanniocalcin (STC1), which has a role in mitochondrial and calcium-related processes, (2) differential correlations between HR and LR APOL1 and metabolism pathway genes, but similar correlations with extracellular matrix- and immune-related genes, (3) significant loss of co-expression of mitochondrial genes in HR FSGS, and (4) an NF-κB -down-regulating gene, NKIRAS1, as the most significant hub gene with strong differential correlations with NDUF family and immune-related genes. Overall, differences in mitochondrial gene regulation appear to underlie many differences observed between HR and LR FSGS. All data are available for secondary analysis through the “APOL1 Portal” (http://APOL1portal.org).
Cognitive, emotional, and social functioning of preschoolers with attention deficit hyperactivity problems
Authors: Biele Guido , Overgaard Kristin R. , Friis Svein , Zeiner Pal , Aase Heidi 
Published: February 2021

AbstractAttention Deficit Hyperactivity Disorder (ADHD) is associated with deficits in a number of functional domains, which have been described both as causes and effects of ADHD. It remains unclear if deficits in different domains are equally strong in early childhood, and which deficits are specific to ADHD. Here, we describe functional domains in preschoolers and assess deficits in children with ADHD problems, by comparing them to preschoolers who have other mental health problems or who develop typically. The ADHD Study assessed 1195 ca. 3.5 years old preschoolers through a semi-structured parent interview, parent questionnaires, and with neuropsychological tests. We determined functional domains by applying factor analytic methods to a broad set of questionnaire- and test-scales. Using resulting factor scores, we employed a Bayesian hierarchical regression to estimate functional deficits in children with ADHD. We found that preschoolers’ functioning could be described along the seven relatively independent dimensions activity level and regulation, executive function, cognition, language, emotion regulation, introversion, and sociability. Compared to typically developing preschoolers, those with ADHD had deficits in all domains except introversion and sociability. Only deficits in activity level and regulation and executive functions were larger than 0.5 standardized mean deviations and larger than deficits of children with other mental health problems. Preschoolers with ADHD have deficits in multiple functional domains, but only impairments in activity level and regulation and executive functions are specific for ADHD and large enough to be clinically significant. Research on functioning in these domains will likely be central for understanding the development of ADHD in later the childhood, and for improving treatment and prevention approaches.