bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial hypercholesterolaemia in pregnancy: Australian case series and review
Authors: Nangrahary Mary , Graham Dorothy F. , Pang Jing , Barnett Wendy , Watts Gerald F. 
Published: March 2023

BackgroundFamilial hypercholesterolaemia (FH) is associated with a significant increase in the risk of premature coronary artery disease. Pregnancy is likely a vulnerable time for atherosclerosis progression, with a physiological rise in low‐density lipoprotein cholesterol (LDL‐C) further exaggerated by the discontinuation of cholesterol‐lowering therapy.Materials and MethodsA retrospective review was undertaken of 13 women with familial hypercholesterolemia who were managed during pregnancy between 2007 and 2021 by a multidisciplinary team following individualised risk assessment.ResultsOverall, pregnancy outcomes were good, with no maternal or fetal complications, including congenital abnormalities, maternal cardiac events or hypertensive complications. Loss of statin treatment time ranged between 12 months and 3.5 years resulting from the accumulation of the preconception, pregnancy and lactation periods and was magnified in women having more than one pregnancy. Of seven women treated with cholestyramine, one developed abnormal liver function with an elevated international normalisation ratio which was corrected with vitamin K.ConclusionPregnancy is associated with prolonged cessation of cholesterol‐lowering therapy, a concern with respect to the risk of coronary artery disease in FH. Continuation of statin therapy up to conception and even during pregnancy in patients at higher risk of cardiovascular disease may be justified, especially with increasing evidence supporting the safety of statin therapy during pregnancy. However, more long‐term maternal and fetal data are required for the routine use of statins during pregnancy. Guideline‐informed models of care covering family planning and pregnancy should be implemented for all women with FH.
Acute and chronic impacts of heat stress on planetary health
Authors: Sampath Vanitha , Shalakhti Omar , Veidis Erika , Efobi Jo Ann Ifeoma , Shamji Mohamed H. , Agache Ioana , Skevaki Chrysanthi , Renz Harald , Nadeau Kari C. 
Published: March 2023

AbstractHeat waves are increasing in intensity, frequency, and duration causing significant heat stress in all living organisms. Heat stress has multiple negative effects on plants affecting photosynthesis, respiration, growth, development, and reproduction. It also impacts animals leading to physiological and behavioral alterations, such as reduced caloric intake, increased water intake, and decreased reproduction and growth. In humans, epidemiological studies have shown that heat waves are associated with increased morbidity and mortality. There are many biological effects of heat stress (structural changes, enzyme function disruption, damage through reactive oxygen or nitrogen species). While plants and animals can mitigate some of these effects through adaptive mechanisms such as the generation of heat shock proteins, antioxidants, stress granules, and others, these mechanisms may likely be inadequate with further global warming. This review summarizes the effects of heat stress on plants and animals and the adaptative mechanisms that have evolved to counteract this stress.
Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: Results from a German real‐world cohort
Authors: Jost‐Brinkmann Fabian , Demir Münevver , Wree Alexander , Luedde Tom , Loosen Sven H. , Müller Tobias , Tacke Frank , Roderburg Christoph , Mohr Raphael 
Published: March 2023

SummaryBackground and AimsPhase III trials have established atezolizumab plus bevacizumab as the novel standard of care for patients with unresectable hepatocellular carcinoma (HCC). However, these trials raised concerns regarding treatment efficacy in non‐viral HCC, and it remains unclear whether combination immunotherapy is safe and effective in patients with advanced cirrhosis.MethodsOne hundred patients with unresectable HCC initiated therapy with atezolizumab plus bevacizumab at our centre between January 2020 and March 2022. The control cohort consisted of 80 patients with advanced HCC who received either sorafenib (n = 43) or lenvatinib (n = 37) as systemic treatment.ResultsOverall survival (OS) and progression‐free survival (PFS) were significantly longer within the atezolizumab/bevacizumab group and comparable to phase III data. The benefits in terms of increased objective response rate (ORR), OS and PFS were consistent across subgroups, including non‐viral HCC (58%). The ROC‐optimised neutrophil‐to‐lymphocyte ratio (NLR) cut‐off of 3.20 was the strongest independent predictor of ORR and PFS. In patients with advanced cirrhosis Child–Pugh B, liver function was significantly better preserved with immunotherapy. Patients with Child–Pugh B cirrhosis showed similar ORR but shorter OS and PFS compared to patients with preserved liver function.ConclusionsAtezolizumab plus bevacizumab showed good efficacy and safety in patients with unresectable HCC and partially advanced liver cirrhosis in a real‐world setting. Moreover, the NLR was able to predict response to atezolizumab/bevacizumab treatment and may guide patient selection.
COVID‐19 infection‐associated platelet and neutrophil activation is blunted by previous anti‐SARS‐CoV‐2 vaccination
Authors: Petito Eleonora , Franco Laura , Falcinelli Emanuela , Guglielmini Giuseppe , Conti Chiara , Vaudo Gaetano , Paliani Ugo , Becattini Cecilia , Mencacci Antonella , Tondi Francesca , Gresele Paolo ,   COVIR‐Study Investigators
Published: March 2023

SummaryThe effectiveness of vaccination against SARS‐CoV‐2 in preventing COVID‐19 or in reducing severe illness in subjects hospitalized for COVID‐19 despite vaccination has been unequivocally shown. However, no studies so far have assessed if subjects who get COVID‐19 despite vaccination are protected from SARS‐CoV‐2‐induced platelet, neutrophil and endothelial activation, biomarkers associated with thrombosis and worse outcome. In this pilot study, we show that previous vaccination blunts COVID‐19‐associated platelet activation, assessed by circulating platelet‐derived microvesicles and soluble P‐selectin, and neutrophil activation, assessed by circulating neutrophil extracellular trap (NET) biomarkers and matrix metalloproteinase‐9, and reduces COVID‐19‐associated thrombotic events, hospitalization in intensive‐care units and death.
Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T‐cell therapy
Authors: Kitamura Wataru , Asada Noboru , Naoi Yusuke , Abe Masaya , Fujiwara Hideaki , Ennishi Daisuke , Nishimori Hisakazu , Fujii Keiko , Fujii Nobuharu , Matsuoka Ken‐ichi , Yoshino Tadashi , Maeda Yoshinobu 
Published: March 2023

SummaryMechanisms of prolonged cytopenia (PC) after chimeric antigen receptor (CAR) T‐cell therapy, an emerging therapy for relapsed or refractory diffuse large B‐cell lymphoma, remain elusive. Haematopoiesis is tightly regulated by the bone marrow (BM) microenvironment, called the ‘niche’. To investigate whether alterations in the BM niche cells are associated with PC, we analysed CD271+ stromal cells in BM biopsy specimens and the cytokine profiles of the BM and serum obtained before and on day 28 after CAR T‐cell infusion. Imaging analyses of the BM biopsy specimens revealed that CD271+ niche cells were severely impaired after CAR T‐cell infusion in patients with PC. Cytokine analyses after CAR T‐cell infusion showed that CXC chemokine ligand 12 and stem cell factor, niche factors essential for haematopoietic recovery, were significantly decreased in the BM of patients with PC, suggesting reduced niche cell function. The levels of inflammation‐related cytokines on day 28 after CAR T‐cell infusion were consistently high in the BM of patients with PC. Thus, we demonstrate for the first time that BM niche disruption and sustained elevation of inflammation‐related cytokines in the BM following CAR T‐cell infusion are associated with subsequent PC.
Cutaneous reactions following COVID‐19 vaccination assessed by dermatologists: a single‐institutional study in Germany
Authors: Wang Rosi , Mathes Sonja , Claussen Carla , Biedermann Tilo , Brockow Knut 
Published: March 2023

SummaryBackground and objectivesCutaneous reactions following COVID‐19 vaccination have been frequently described, whereas larger case series by dermatologists are lacking. This study assesses SARS‐CoV‐2 vaccination‐associated skin reactions, severity, treatment, course, eliciting vaccines, allergy test results and tolerance to revaccination.Patients and methodsSingle‐institutional, non‐interventional study of dermatologists assessing cutaneous manifestations in 83 patients in Germany.Results93 reactions were presented. Manifestations clustered into immediate (n = 51, 54.8%) and delayed hypersensitivity reactions (n = 10, 10.8%), chronic inflammatory skin diseases (n = 13, 14.0%), reactivation of latent herpes virus infection (pityriasis rosea/herpes zoster; n = 9; 9.7%) and others (n = 10, 10.8%). Vaccination was associated with new (76.3%) – mostly hypersensitivity reactions – or exacerbation of known skin diseases (23.7%), in this case predominantly chronic inflammatory skin diseases. Reactions occurred primarily within the first week (72.8%) and after first vaccination (62.0%). Treatment was required in 83.9% and hospitalization in 19.4%. In 48.8% revaccination led to recurrence of the same reactions. Disease was ongoing at last consultation in 22.6%, primarily in chronic inflammatory skin diseases. Allergy tests were performed in 15 patients (18.1%) and resulted negative.ConclusionsIt can be assumed that vaccination may trigger immune activation‐related reactions especially in those patients predisposed to develop respective skin diseases.
Association between serum calcium level and type 2 diabetes: An NHANES analysis and Mendelian randomization study
Authors: Zhai Zhiyu , Deng Yun , He Yunbiao , Chen Li , Chen Xia , Zuo Lei , Liu Mingliang , Mao Minzhi , Li Sha , Hu Haiping , Chen Haiyan , Wei Yuan , Zhou Qin , Hao Guang , Peng Shuang 
Published: March 2023

AbstractAimsThis study investigated the association between serum calcium levels and the prevalence of T2D using a cross‐sectional study and Mendelian randomization analysis.MethodsCross‐sectional data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Serum calcium levels were divided into three groups (low, medium and high groups) according to the tertiles. Logistic regression was used to estimate the association between serum calcium levels and T2D prevalence. Instrumental variables for serum calcium levels were obtained from the UK Biobank and a two‐sample MR analysis was performed to examine the causal relationship between genetically predicted serum calcium levels and the risk of T2D.ResultsA total of 39,645 participants were available for cross‐sectional analysis. After adjusting for covariates, participants in the high serum calcium group had significantly higher odds of T2D (OR = 1.18, 95% CI = 1.07, 1.30, p = 0.001) than those in the moderate group. Restricted cubic spline plots showed a J‐shaped curve relationship between serum calcium level and prevalence of T2D. Consistently, Mendelian randomization analysis showed that higher genetically predicted serum calcium levels were causally associated with a higher risk of T2D (OR = 1.16, 95% CI: 1.01, 1.33, p = 0.031).ConclusionsThe results of this study suggest that higher serum calcium levels are causally associated with a higher risk of T2D. Further studies are needed to clarify whether intervening in high serum calcium could reduce the risk of T2D.
Rate of change of J‐integral in creep‐fatigue condition
Authors: Tiwari Abhishek 
Published: March 2023

AbstractThe operational conditions in next generation power plants and other high temperature applications such as turbine blades in jet engines demand the component to perform under extreme conditions where metallic materials show time dependent deformation under cyclic loading conditions. Under creep‐fatigue loading condition, the crack tip is exposed to both time dependent and independent plastic deformation. Conventional crack characterizing parameters such as (C
)
has shown good correlation with dominant damage‐based crack velocity, (d
/d
)
. However, the true definition or prediction of crack driving forces under such scenario are vague due to limited theoretical validity of the conventional crack tip characterizing parameters, such as
or C
. In this work, the concept of configurational forces are applied for the first time to understand the creep‐fatigue crack growth behavior. The crack growth is simulated using node‐release technique and the configurational forces are calculated using post processing the finite element results for calculation of d
/d
.
The predictive value of the dynamic risk outcome scales (DROS) for recidivism in (forensic) clients with mild intellectual disabilities or borderline intellectual functioning
Authors: Delforterie M. J. , Hesper B. L. , Nijman H. L. I. , Korzilius H. P. L. M. , Turhan A. , Didden R. 
Published: March 2023

AbstractBackgroundThe dynamic risk outcome scales (DROS) was developed to assess treatment progress of clients with mild intellectual disability or borderline intellectual functioning using dynamic risk factors. We studied the predictive value of the DROS on various classifications and severity levels of recidivism.MethodData of 250 forensic clients with intellectual disabilities were linked to recidivism data from the Judicial Information Service in the Netherlands. Receiver operating characteristics (ROC) analyses were used to determine the predictive values.ResultsThe DROS total score could not significantly predict recidivism. A DROS recidivism subscale predicted general, violent and other recidivism. These predictive values were comparable to those of a Dutch tool validated for risk assessment in the general forensic population.ConclusionsThe DROS recidivism subscale predicted various classifications of recidivism better than chance. At present, the DROS appears to have no added value beyond the HKT‐30 for the purpose of risk assessment.
Genome‐wide association studies for additive and dominance effects for body composition traits in commercial crossbred Piétrain pigs
Authors: Heidaritabar Marzieh , Bink Marco C. A. M. , Dervishi Elda , Charagu Patrick , Huisman Abe , Plastow Graham S. 
Published: March 2023

AbstractFat depth (FD) and muscle depth (MD) are economically important traits and used to estimate carcass lean content (LMP), which is one of the main breeding objectives in pig breeding programmes. We assessed the genetic architectures of body composition traits for additive and dominance effects in commercial crossbred Piétrain pigs using both 50 K array and sequence genotypes. We first performed a genome‐wide association study (GWAS) using single‐marker association analysis with a false discovery rate of 0.1. Then, we estimated the additive and dominance effects of the most significant variant in the quantitative trait loci (QTL) regions. It was investigated whether the use of whole‐genome sequence (WGS) will improve the QTL detection (both additive and dominance) with a higher power compared with lower density SNP arrays. Our results showed that more QTL regions were detected by WGS compared with 50 K array (n = 54 vs. n = 17). Of the novel associated regions associated with FD and LMP and detected by WGS, the most pronounced peak was on SSC13, situated at ~116–118, 121–127 and 129–134 Mbp. Additionally, we found that only additive effects contributed to the genetic architecture of the analysed traits and no significant dominance effects were found for the tested SNPs at QTL regions, regardless of panel density. The associated SNPs are located in or near several relevant candidate genes. Of these genes, GABRR2, GALR1, RNGTT, CDH20 and MC4R have been previously reported as being associated with fat deposition traits. However, the genes on SSC1 (ZNF292, ORC3, CNR1, SRSF12, MDN1, TSHZ1, RELCH and RNF152) and SSC18 (TTC26 and KIAA1549) have not been reported previously to our best knowledge. Our current findings provide insights into the genomic regions influencing composition traits in Piétrain pigs.
Development and validation of the fall‐related injury risk in nursing homes (INJURE‐NH) prediction tool
Authors: Duprey Matthew S. , Zullo Andrew R. , Gouskova Natalia A. , Lee Yoojin , Capuano Alyssa , Kiel Douglas P. , Daiello Lori A. , Kim Dae Hyun , Berry Sarah D. 
Published: March 2023

AbstractBackgroundExisting models to predict fall‐related injuries (FRI) in nursing homes (NH) focus on hip fractures, yet hip fractures comprise less than half of all FRIs. We developed and validated a series of models to predict the absolute risk of FRIs in NH residents.MethodsRetrospective cohort study of long‐stay US NH residents (≥100 days in the same facility) between January 1, 2016 and December 31, 2017 (n = 733,427) using Medicare claims and Minimum Data Set v3.0 clinical assessments. Predictors of FRIs were selected through LASSO logistic regression in a 2/3 random derivation sample and tested in a 1/3 validation sample. Sub‐distribution hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated for 6‐month and 2‐year follow‐up. Discrimination was evaluated via C‐statistic, and calibration compared the predicted rate of FRI to the observed rate. To develop a parsimonious clinical tool, we calculated a score using the five strongest predictors in the Fine‐Gray model. Model performance was repeated in the validation sample.ResultsMean (Q1, Q3) age was 85.0 (77.5, 90.6) years and 69.6% were women. Within 2 years of follow‐up, 43,976 (6.0%) residents experienced ≥1 FRI. Seventy predictors were included in the model. The discrimination of the 2‐year prediction model was good (C‐index = 0.70), and the calibration was excellent. Calibration and discrimination of the 6‐month model were similar (C‐index = 0.71). In the clinical tool to predict 2‐year risk, the five characteristics included independence in activities of daily living (ADLs) (HR 2.27; 95% CI 2.14–2.41) and a history of non‐hip fracture (HR 2.02; 95% CI 1.94–2.12). Performance results were similar in the validation sample.ConclusionsWe developed and validated a series of risk prediction models that can identify NH residents at greatest risk for FRI. In NH, these models should help target preventive strategies.
Intracellular glucose starvation inhibits osteogenic differentiation in human periodontal ligament cells
Authors: Deng Xin , Kato Hirohito , Taguchi Yoichiro , Nakata Takaya , Umeda Makoto 
Published: March 2023

AbstractBackgroundPeriodontal ligament cells (PDLCs), as mesenchymal cells in the oral cavity, are closely linked to periodontal tissue regeneration. However, the effect of local glucose deficiency on periodontal tissue regeneration, such as immediately post‐surgery, remains unknown.ObjectiveIn the present study, we investigated the effect of a low‐glucose environment on the proliferation and osteogenic differentiation of PDLCs.Materials and MethodsWe used media with five glucose concentrations (100, 75, 50, 25, and 0 mg/dL) and focused on the effects of a low‐glucose environment on the proliferation, osteogenic differentiation, and autophagy of PDLCs. Additionally, we focused on changes in lactate production in a low‐glucose environment and investigated the involvement of lactate with AZD3965, a monocarboxylate transporter‐1 (MCT‐1) inhibitor.ResultsThe low‐glucose environment inhibited PDLCs proliferation, migration, and osteogenic differentiation, and induced the expression of the autophagy‐related factors LC3 and p62. Lactate and ATP production were decreased under low‐glucose conditions. The addition of AZD3965 (MCT‐1 inhibitor) in normal glucose conditions caused a similar trend as in low‐glucose conditions on PDLCs.ConclusionOur results suggest lactate production through glucose metabolism in the osteogenic differentiation of PDLCs. A low‐glucose environment decreased lactate production, inhibiting cell proliferation, migration, and osteogenic differentiation and inducing autophagy in PDLCs.
Concentrations, pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites following oral administration to horses
Authors: Poth Meghan K. M. , McKemie Daniel S. , Traynham Megan , Kass Philip H. , Knych Heather K. 
Published: March 2023

AbstractThe metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6‐glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2 mg/kg morphine and oral doses of 0.2, 0.6, and 0.8 mg/kg of morphine in a four‐way balanced crossover design, with a 2‐week washout period between doses. Concentrations of morphine and metabolites were determined, and pharmacokinetic parameters determined. Physiologic and behavioral outcomes including the number of steps taken, changes in heart rate, and gastrointestinal borborygmi were assessed. Oral administration of morphine resulted in higher concentrations of morphine metabolites, including M6G (Cmax: 11.6–37.8 ng/mL (0.6 mg/kg); 15.8–42.6 ng/mL (0.8 mg/kg)), compared with i.v. Bioavailability was 36.5%, 27.6% and 28.0% for 0.2, 0.6 and 0.8 mg/kg, respectively. Behavioral and physiologic changes were noted in all groups but were less prominent with oral compared with i.v. administration. Results of the current study are encouraging for further study, specifically anti‐nociceptive effects of morphine following oral administration.
Technologies, strategies, and cautions when deconvoluting genome‐wide association signals: FTO in focus
Authors: Pahl Matthew C. , Grant Struan F. A. , Leibel Rudolph L. , Stratigopoulos George 
Published: March 2023

SummaryGenome‐wide association studies have revealed a plethora of genetic variants that correlate with polygenic conditions. However, causal molecular mechanisms have proven challenging to fully define. Without such information, the associations are not physiologically useful or clinically actionable. By reviewing studies of the FTO locus in the genetic etiology of obesity, we wish to highlight advances in the field fueled by the evolution of technical and analytic strategies in assessing the molecular bases for genetic associations. Particular attention is drawn to extrapolating experimental findings from animal models and cell types to humans, as well as technical aspects used to identify long‐range DNA interactions and their biological relevance with regard to the associated trait. A unifying model is proposed by which independent obesogenic pathways regulated by multiple FTO variants and genes are integrated at the primary cilium, a cellular antenna where signaling molecules that control energy balance convene.