bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early outcomes and predictors of patient satisfaction after TKA: a prospective study of 200 cases with a contemporary cemented rotating platform implant design
Authors: van Loon Corné , Baas Niels , Huey Verdonna , Lesko James , Meermans Geert , Vergroesen Diederik 
Published: April 2021

Abstract
Purpose
The purpose of the study was to identify the earliest time point where subjects realized the greatest clinical improvement after TKA, and the time when post-operative scores became superior to pre-operative scores. Post-hoc exploratory analyses were conducted to investigate predictors of early post-operative outcomes and patient satisfaction.

Methods
Six investigators across 4 sites in the Netherlands prospectively implanted 200 subjects with a contemporary cemented rotating platform device. Patient Reported Outcome Measurements (PROMs) KOOS-PS, PKIP, and EQ-5D were collected pre-operatively and post-operatively through 2-years. PROMs change from pre-operative baseline were summarized, along with radiographic outcomes and adverse events (AEs). Pre-operative patient characteristics were explored for correlation with patient outcomes, and patient satisfaction for correlation with KOOS-PS.

Results
Follow-up compliance was 99% at 6-months, and 95.5% at 2-years. The percentage with higher KOOS-PS compared to baseline was 81.3% at 6-months. KOOS-PS, PKIP, and PKIP subscore means were all better at 6-weeks versus baseline. Gender, BMI, hypertension, and pre-operative KOOS-PS were weakly correlated with 6-week KOOS-PS (multivariate R-squared = 14.1%), but only pre-operative KOOS-PS demonstrated correlation with post-operative KOOS-PS at 6-months or later (R-squared < 5% at 6-months and 2 years). Satisfaction was moderately correlated with concurrent KOOS-PS at each post-operative time point, with (R-squared = 35.3% at 6-months, and 37.5% at 2 years).

Conclusion
The greatest mean clinical improvement occurred within the first 6-weeks. Although some pre-operative factors were correlated with higher early post-operative KOOS-PS outcomes, these advantages disappeared by 6-months aside from weak correlation with pre-operative KOOS-PS. Post-operative KOOS-PS was moderately correlated with concurrent post-operative satisfaction. These results may be used for pre-operative counseling and management of patient’s postoperative expectations.

Trial registration
Clinicaltrials.gov, NCT02339610. Registered 15 January 2015.
Anti-VEGF therapy prevents Müller intracellular edema by decreasing VEGF-A in diabetic retinopathy
Authors: Wang Tianqin , Zhang Chaoyang , Xie Hai , Jiang Mengmeng , Tian Haibin , Lu Lixia , Xu Guo-Tong , Liu Lin , Zhang Jingfa 
Published: April 2021

Abstract
Background
Although vascular endothelial growth factor A (VEGF-A) is known to play a key role in causing retinal edema, whether and how VEGF-A induces intracellular edema in the retina still remains unclear.

Methods
Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin. Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset. rMC-1 cells (rat Müller cell line) were treated with glyoxal for 24 h with or without ranibizumab. The expression levels of inwardly rectifying K+ channel 4.1 (Kir4.1), aquaporin 4 (AQP4), Dystrophin 71 (Dp71), VEGF-A, glutamine synthetase (GS) and sodium-potassium-ATPase (Na+-K+-ATPase) were examined using Western blot. VEGF-A in the supernatant of the cell culture was detected with ELISA. The intracellular potassium and sodium levels were detected with specific indicators.

Results
Compared with normal control, protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas, which were prevented by ranibizumab. The above changes were recapitulated in vitro. Similarly, the intracellular potassium level in glyoxal-treated rMC-1 cells was increased, while the intracellular sodium level and Na+-K+-ATPase protein level remained unchanged, compared with control. However, ranibizumab treatment decreased intracellular sodium, but not potassium.

Conclusion
Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A. It also caused a reduction in intracellular osmotic pressure.
Complete atrio-ventricular block with coronary artery spasm due to direct laryngoscopy in a pediatric patient with laryngeal papillomatosis: a case report
Authors: Matsushita Katsuyuki , Arai Risa , Nakayama Tetsuzo , Nakagaki Toshiaki , Kandabashi Tadashi , Yamaura Ken 
Published: April 2021

Abstract
Background
Coronary artery spasm has rarely been reported in pediatric patients. Previous studies have reported comorbidities and risk factors for coronary artery spasms. We present the case of a complete atrio-ventricular (AV) block that occurred in the absence of other risk factors immediately after direct laryngoscopy.

Case presentation
A 2-year-old girl developed severe coronary artery spasm after direct laryngoscopy for elective laryngeal papillomatosis resection. Immediately after the initiation of laryngoscopy, complete AV block and ST elevation on lead II of the electrocardiogram were observed. These findings indicated that the complete AV block was caused by a right coronary artery spasm.

Conclusion
Coronary artery spasm resulting in lethal arrhythmia rarely occurs in healthy pediatric patients. To the best of our knowledge, this is the first pediatric case of a severe coronary artery spasm resulting in a complete AV block due to direct laryngoscopy in a healthy patient.
Identification of metabolism genes related to hepatocarcinogenesis and progression in type 2 diabetes mellitus via co-expression networks analysis
Authors: Bi Yiming , Yin Bei , Fan Guanjie 
Published: April 2021

Abstract
Background
Type 2 Diabetes Mellitus (T2DM) is an independent risk factor of hepatocellular carcinoma (HCC). However, the related genes and modules to hepatocarcinogenesis and progression in T2DM remain unclear.

Methods
The microarray data from Gene Expression Omnibus (GEO) were analyzed to screen differentially expressed genes (DEGs) of T2DM and HCC dataset. Then, weighted gene co-expression network analysis (WGCNA) was performed on these DEGs to detect the modules and genes, respectively. Common genes in modules with clinical interests of T2DM and HCC were obtained and annotated via GOSemSim package and Metascape. Genes related to late-stage HCC and high glycated haemoglobin (HbA1c) were also identified. These genes were validated by UALCAN analysis and univariate cox regression based on The Cancer Genome Atlas (TCGA). Finally, another two independent datasets were applied to confirm the results of our study.

Results
A total of 1288 and 1559 DEGs of T2DM and HCC were screened, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed several shared pathways in two diseases, such as pathways in cancer and metabolism. A total of 37 common genes correlated with T2DM and HCC were then identified with WGCNA. Furthermore, 12 genes from modules associated with late-stage HCC and high HbA1c were regarded as hub genes. Among these genes, 8 genes associated with tumor invasion and metastasis were validated by UALCAN analysis. Moreover, downregulations of ACAT1, SLC2A2, PCK1 and ABAT were significantly associated with poorer prognosis in HCC patients with elevated HbA1c. Additionally, the expressions of PCK1 and ABAT were raised in HepG2 cells pre-treated with metformin and phenformin.

Conclusions
The present study confirmed several metabolic genes related to hyperglycemia and malignant tumor, which may provide not only new insights into the pathogenesis of hepatocarcinogenesis and progression in T2DM, but also novel therapeutic targets for T2DM patients with HCC in the future.
In vitro antifungal activity of endophytic bacteria isolated from date palm (Phoenix doctylifera L.) against fungal pathogens causing leaf spot of date palm
Authors: Al-Nadabi H. H. , Al-Buraiki N. S. , Al-Nabhani A. A. , Maharachchikumbura S. N. , Velazhahan R. , Al-Sadi A. M. 
Published: April 2021

Abstract
Background
Date palm ((Phoenix doctylifera L.) suffers from several fungal diseases. The endophytic microorganisms present in higher plants generally offer protection to their host plants against invading phytopathogenic fungi and bacteria. In the present study, endophytic bacteria associated with date palm leaves were isolated and their in vitro antagonistic potential against fungal pathogens causing leaf spots in date palm was demonstrated.

Results
Endophytic bacteria were isolated from date palm leaves of 3 different cultivars viz., Nighal, Khalas and Khinaizi and evaluated for their inhibitory activity against leaf spot pathogens of date palm viz., Fusarium solani, Alternaria sp., Nigrospora sp., Thieloviopsis sp., Curvularia subpapendrofii and Tilletiopsis minor using an in vitro dual culture assay. Of the 24 endophytic bacterial strains tested, the endophytes designated B1, B7, B8 and B9 obtained from cv. Nighal showed inhibitory activities (more than 55% mycelial growth inhibition) against F. solani and Alternaria sp. None of the bacterial endophytes inhibited the growth of other fungal pathogens tested. These antagonistic bacterial strains were identified as Pantoea septica on the basis of 16S rRNA gene sequence analysis. The hyphae of F. solani and Alternaria sp. exhibited morphological abnormalities such as shrinkage and disintegration when grown in the presence of antagonistic bacterial endophytes. The cell-free culture filtrates of the bacterial endophytes caused inhibition of mycelial growth and induced leakage of electrolytes from the mycelia of F. solani and Alternaria sp. This is the first study that describes inhibition of the date palm pathogens F. solani and Alternaria sp. by P. septica.

Conclusion
Endophytic Pantoea septica strains isolated from date palm leaves inhibited the mycelial growth of F. solani and Alternaria sp. and induced morphological changes in their mycelia. The culture filtrates of these bacterial strains also inhibited the mycelial growth and caused leakage of electrolytes from the mycelia of F. solani and Alternaria sp. These promising bacterial strains can be exploited as biocontrol agents to control F. solani and Alternaria sp.-induced leaf spot diseases of date palm.
Development of screening criteria for microplastic particles in air and atmospheric deposition: critical review and applicability towards assessing human exposure
Authors: Wright Stephanie L. , Gouin Todd , Koelmans Albert A. , Scheuermann Lisa 
Published: April 2021

AbstractOver the last several years there has been an increase in studies reporting the presence of microplastic particles (MPs) in both indoor and outdoor air. Data reported reflect a variety of different types of air samples, which have helped to demonstrate the ubiquity of MPs in the atmosphere and their potential contribution to atmospheric particulate matter (PM). The relative quality of the data reporting on MPs in air has not been evaluated, but represents an important step towards improving our overall understanding of the human health implications in relation to inhalation exposure to MPs. Adopting recent approaches that have been proposed to assess the quality of data for those studies reporting concentrations in biota and water samples, we identify a suite of criteria used to screen studies reporting MPs in air for the purposes of evaluating their usefulness in assessing human exposure. Here we review and summarize data from 27 studies reporting MPs in various types of air samples and evaluate each of the studies against 11 separate criteria representing four main categories (sampling; contamination mitigation; sample purification / handling; characterization and application towards assessing human exposure). On average, studies scored 48.6% (range 18.2–81.8%) of the maximum score. Only one study received a positive score for all criteria, implying that there remains a need for future studies to consider strengthening implementation and reporting of QA/QC protocol. The most urgent areas requiring attention relate to the need for studies to avoid and verify background contamination and to strengthen the quantification of method recovery efficiencies. The majority of studies report data for particulates > 10 μm. Due to the associations between exposure to particles < 10 μm and human health effects, we recommend that prioritization efforts that develop standard protocols, based on existing air sampling methods capable of characterizing MPs < 10 μm are progressed.
Soluble Alpha Klotho in Acromegaly: Comparison With Traditional Markers of Disease Activity
Authors: Schweizer Júnia R O L , Schilbach Katharina , Haenelt Michael , Giannetti Alexandre V , Bizzi Mariana F , Soares Beatriz S , Paulino Eduardo , Schopohl Jochen , Störmann Sylvère , Ribeiro-Oliveira Antônio , Bidlingmaier Martin 
Published: April 2021

Abstract

Context
Soluble alpha klotho (sαKL) has been linked to growth hormone (GH) action, but systematic evaluation and comparisons with traditional biomarkers in acromegaly are lacking.

Objective
To evaluate the potential of sαKL to aid classification of disease activity.

Methods
This retrospective study at 2 academic centers included acromegaly patients before surgery (A, n = 29); after surgery (controlled, discordant, or uncontrolled) without (B1, B2, B3, n = 28, 11, 8); or with somatostatin analogue treatment (C1, C2, C3, n = 17, 11, 5); nonfunctioning pituitary adenomas (n = 20); and healthy controls (n = 31). sαKL was measured by immunoassay and compared with traditional biomarkers (random and nadir GH, insulin-like growth factor I [IGF-I], IGF binding protein 3). Associations with disease activity were assessed.

Results
sαKL was correlated to traditional biomarkers, particularly IGF-I (rs=0.80, P &lt;0.0001). High concentrations before treatment (A, median, interquartile range: 4.04 × upper limit of normal [2.26-8.08]) dropped to normal after treatment in controlled and in most discordant patients. A cutoff of 1548 pg/mL for sαKL discriminated controlled (B1, C1) and uncontrolled (B3, C3) patients with 97.8% (88.4%-99.9%) sensitivity and 100% (77.1%-100%) specificity. sαKL was below the cutoff in 84% of the discordant subjects. In the remaining 16%, elevated sαKL and IGF-I persisted, despite normal random GH. Sex, age, body mass index, and markers of bone and calcium metabolism did not significantly affect sαKL concentrations.

Conclusion
Our data support sαKL as a biomarker to assess disease activity in acromegaly. sαKL exhibits close association with GH secretory status, large dynamic range, and robustness toward biological confounders. Its measurement could be helpful particularly when GH and IGF-I provide discrepant information.
SGLT2 Inhibitors as Calorie Restriction Mimetics: Insights on Longevity Pathways and Age-Related Diseases
Authors: Hoong Caroline W S , Chua Marvin W J 
Published: April 2021

Abstract
Sodium-glucose cotransporter-2 (SGLT2) inhibitors induce glycosuria, reduce insulin levels, and promote fatty acid oxidation and ketogenesis. By promoting a nutrient deprivation state, SGLT2 inhibitors upregulate the energy deprivation sensors AMPK and SIRT1, inhibit the nutrient sensors mTOR and insulin/IGF1, and modulate the closely linked hypoxia-inducible factor (HIF)-2α/HIF-1α pathways. Phosphorylation of AMPK and upregulation of adiponectin and PPAR-α favor a reversal of the metabolic syndrome which have been linked to suppression of chronic inflammation. Downregulation of insulin/IGF1 pathways and mTOR signaling from a reduction in glucose and circulating amino acids promote cellular repair mechanisms, including autophagy and proteostasis which confer cellular stress resistance and attenuate cellular senescence. SIRT1, another energy sensor activated by NAD+ in nutrient-deficient states, is reciprocally activated by AMPK, and can deacetylate and activate transcription factors, such as PCG-1α, mitochondrial transcription factor A (TFAM), and nuclear factor E2-related factor (NRF)-2, that regulate mitochondrial biogenesis. FOXO3 transcription factor which target genes in stress resistance, is also activated by AMPK and SIRT1. Modulation of these pathways by SGLT2 inhibitors have been shown to alleviate metabolic diseases, attenuate vascular inflammation and arterial stiffness, improve mitochondrial function and reduce oxidative stress-induced tissue damage. Compared with other calorie restriction mimetics such as metformin, rapamycin, resveratrol, and NAD+ precursors, SGLT2 inhibitors appear to be the most promising in the treatment of aging-related diseases, due to their regulation of multiple longevity pathways that closely resembles that achieved by calorie restriction and their established efficacy in reducing cardiovascular events and all-cause mortality. Evidence is compelling for the role of SGLT2 inhibitors as a calorie restriction mimetic in anti-aging therapeutics.
Estrogen Regulation of the Molecular Phenotype and Active Translatome of AVPV Kisspeptin Neurons
Authors: Stephens Shannon B Z , Kauffman Alexander S 
Published: April 2021

AbstractIn females, ovarian estradiol (E2) exerts both negative and positive feedback regulation on the neural circuits governing reproductive hormone secretion, but the cellular and molecular mechanisms underlying this remain poorly understood. In rodents, estrogen receptor α–expressing kisspeptin neurons in the hypothalamic anteroventral periventricular region (AVPV) are prime candidates to mediate E2 positive feedback induction of preovulatory gonadotropin-releasing hormone and luteinizing hormone (LH) surges. E2 stimulates AVPV Kiss1 expression, but the full extent of estrogen effects in these neurons is unknown; whether E2 stimulates or inhibits other genes in AVPV Kiss1 cells has not been determined. Indeed, understanding of the function(s) of AVPV kisspeptin cells is limited, in part, by minimal knowledge of their overall molecular phenotype, as only a few genes are currently known to be co-expressed in AVPV Kiss1 cells. To provide a more detailed profiling of co-expressed genes in AVPV Kiss1 cells, including receptors and other signaling factors, and test how these genes respond to E2, we selectively isolated actively translated mRNAs from AVPV Kiss1 cells of female mice and performed RNA sequencing (RNA-seq). This identified &gt;13 000 mRNAs co-expressed in AVPV Kiss1 cells, including multiple receptor and ligand transcripts positively or negatively regulated by E2. We also performed RNAscope to validate co-expression of several transcripts identified by RNA-seq, including Pdyn (prodynorphin), Penk (proenkephalin), Vgf (VGF), and Cartpt (CART), in female AVPV Kiss1 cells. Given the important role of AVPV kisspeptin cells in positive feedback, E2 effects on identified genes may relate to the LH surge mechanism and/or other physiological processes involving these cells.
Hormone Therapy in Menopause: Concepts, Controversies, and Approach to Treatment
Authors: Flores Valerie A , Pal Lubna , Manson JoAnn E 
Published: April 2021

AbstractHormone therapy (HT) is an effective treatment for menopausal symptoms, including vasomotor symptoms and genitourinary syndrome of menopause. Randomized trials also demonstrate positive effects on bone health, and age-stratified analyses indicate more favorable effects on coronary heart disease and all-cause mortality in younger women (close proximity to menopause) than in women more than a decade past menopause. In the absence of contraindications or other major comorbidities, recently menopausal women with moderate or severe symptoms are appropriate candidates for HT. The Women’s Health Initiative (WHI) hormone therapy trials—estrogen and progestin trial and the estrogen-alone trial—clarified the benefits and risks of HT, including how the results differed by age. A key lesson from the WHI trials, which was unfortunately lost in the posttrial cacophony, was that the risk:benefit ratio and safety profile of HT differed markedly by clinical characteristics of the participants, especially age, time since menopause, and comorbidity status. In the present review of the WHI and other recent HT trials, we aim to provide readers with an improved understanding of the importance of the timing of HT initiation, type and route of administration, and of patient-specific considerations that should be weighed when prescribing HT.
An Approach to Nonsuppressed Testosterone in Transgender Women Receiving Gender-Affirming Feminizing Hormonal Therapy
Authors: Maheshwari Arvind , Nippoldt Todd , Davidge-Pitts Caroline 
Published: April 2021

AbstractNonsuppressed levels of testosterone are seen in up to a quarter of transgender women on gender-affirming feminizing hormonal treatment. Multiple factors contribute to this situation, including patient, medication, laboratory, and organ-specific concerns. We propose a stepwise approach to determine the etiology of nonsuppressed levels of testosterone in transgender women. This may lead to an appropriate feminizing hormonal therapy regimen and diagnosis of manageable medical conditions.
The PRKAR1B p.R115K Variant is Associated with Lipoprotein Profile in African American Youth with Metabolic Challenges
Authors: Bloyd Michelle , Settas Nikolaos , Faucz Fabio Rueda , Sinaii Ninet , Bathon Kerstin , Iben James , Coon Steven , Caprio Sonia , Stratakis Constantine A , London Edra 
Published: April 2021

Abstract

Context
High childhood obesity rates coincide with increased incidence of nonalcoholic fatty liver disease (NAFLD) and other comorbidities. Understanding the genetics of susceptibility to obesity and its comorbidities could guide intervention. The cyclic adenosine monophosphate (cAMP)–dependent protein kinase (PKA) signaling pathway regulates energy balance, glucose homeostasis, and lipid metabolism.

Objective
We hypothesized that PKA-related gene variants may be associated with obesity or associated metabolic conditions.

Methods
We included 457 youths from the Yale Obesity Clinic into the Pathogenesis of Youth-Onset Diabetes cohort (NCT01967849); a variety of clinical tests were performed to characterize NAFLD. Exon sequencing of 54 PKA pathway genes was performed. Variants were confirmed by Sanger sequencing. Clinical data were analyzed, correcting for NAFLD status and body mass index z-score with adjustments for multiple comparisons. Fluorescence resonance energy transfer (FRET) and PKA enzymatic assays were performed in HEK293 cells transfected with the PRKAR1B p.R115K construct. In silico structural analysis for this variant was done.

Results
We identified the variant PRKAR1B p.R115K in 4 unrelated, African American patients. Analyses compared this variant group to other African American patients in the cohort. PRKAR1B p.R115K was associated with favorable circulating lipoprotein levels. Analysis of FRET and PKA enzymatic assay showed stronger interaction between the R1β mutant and PKA catalytic subunit Cα and decreased basal PKA activity compared with the wildtype (P &lt; .0001). Structural analysis revealed that p.R115K may hinder conformational changes resulting from cAMP binding at cAMP binding domain A.

Conclusion
Data suggest PRKAR1B p.R115K affects cAMP signaling and may favorably modulate lipoprotein profile in African American youth, protecting them from some adverse metabolic outcomes.