bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of copy number variants with genome sequencing: Clinical experiences from the NYCKidSeq program
Authors: Bonini Katherine E. , Thomas‐Wilson Amanda , Marathe Priya N. , Sebastin Monisha , Odgis Jacqueline A. , Di Biase Miranda , Kelly Nicole R. , Ramos Michelle A. , Insel Beverly J. , Scarimbolo Laura , Rehman Atteeq U. , Guha Saurav , Okur Volkan , Abhyankar Avinash , Phadke Shruti , Nava Caroline , Gallagher Katie M. , Elkhoury Lama , Edelmann Lisa , Zinberg Randi E. , Abul‐Husn Noura S. , Diaz George A. , Greally John M. , Suckiel Sabrina A. , Horowitz Carol R. , Kenny Eimear E. , Wasserstein Melissa , Gelb Bruce D. , Jobanputra Vaidehi 
Published: June 2023

AbstractCopy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first‐tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0–21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype‐driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes.
HIF‐1α promotes astrocytic production of macrophage migration inhibitory factor following spinal cord injury
Authors: Hao Huifei , Hou Yuxuan , Li Aicheng , Niu Li , Li Shaolan , He Bingqiang , Zhang Xingyuan , Song Honghua , Cai Rixin , Zhou Yue , Yao Chun , Wang Yongjun , Wang Yingjie 
Published: June 2023

AbstractBackgroundMacrophage migration inhibitory factor (MIF) is an important mediator of neuropathology in various central nervous system (CNS) diseases. However, little is known about its inducers for production from the nerve cells, as well as the underlying regulatory mechanism. Injury‐induced HIF‐1α has been shown to exacerbate neuroinflammation by activating multiple downstream target molecules. It is postulated that HIF‐1α is involved in the regulation of MIF following spinal cord injury (SCI).MethodsSCI model of Sprague–Dawley rats was established by cord contusion at T8–T10. The dynamic changes of HIF‐1α and MIF protein levels at lesion site of rat spinal cord were determined by Western blot. The specific cell types of HIF‐1α and MIF expression were examined by immunostaining. Primary astrocytes were isolated from the spinal cord, cultured and stimulated with various agonist or inhibitor of HIF‐1α for analysis of HIF‐1α‐mediated expression of MIF. Luciferase report assay was used to determine the relationship between HIF‐1α and MIF. The Basso, Beattie, and Bresnahan (BBB) locomotor scale was used to assess the locomotor function following SCI.ResultsThe protein levels of HIF‐1α and MIF at lesion site were significantly elevated by SCI. Immunofluorescence demonstrated that both HIF‐1α and MIF were abundantly expressed in the astrocytes of the spinal cord. By using various agonists or inhibitors of HIF‐1α, it was shown that HIF‐1α sufficiently induced astrocytic production of MIF. Mechanistically, HIF‐1α promoted MIF expression through interaction with MIF promoter. Inhibition of HIF‐1α activity using specific inhibitor markedly reduced the protein levels of MIF at lesion site following SCI, which in turn favored for the functional recovery.ConclusionSCI‐induced activation of HIF‐1α is able to promote MIF production from astrocytes. Our results have provided new clues for SCI‐induced production of DAMPs, which may be helpful for clinical treatment of neuroinflammation.
Fibroblast growth factor 21 ameliorates behavior deficits in Parkinson's disease mouse model via modulating gut microbiota and metabolic homeostasis
Authors: Yang Changwei , Wang Wuqiong , Deng Pengxi , Wang Xinyi , Zhu Lin , Zhao Liangcai , Li Chen , Gao Hongchang 
Published: June 2023

AbstractAimsThe effects of FGF21 on Parkinson's disease (PD) and its relationship with gut microbiota have not been elucidated. This study aimed to investigate whether FGF21 would attenuate behavioral impairment through microbiota–gut–brain metabolic axis in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) induced PD mice model.MethodsMale C57BL/6 mice were rendomized into 3 groups: vehicle (CON); MPTP 30 mg/kg/day i.p. injection (MPTP); FGF21 1.5 mg/kg/d i.p. injection plus MPTP 30 mg/kg/day i.p. injection (FGF21 + MPTP). The behavioral features, metabolimics profiling, and 16 s rRNA sequencing were performed after FGF21 treatment for 7 days.ResultsMPTP‐induced PD mice showed motor and cognitive deficits accompanied by gut microbiota dysbiosis and brain‐region‐specific metabolic abnormalities. FGF21 treatment dramatically attenuated motor and cognitive dysfunction in PD mice. FGF21 produced a region‐specific alteration in the metabolic profile in the brain in ways indicative of greater ability in neurotransmitter metabolism and choline production. In addition, FGF21 also re‐structured the gut microbiota profile and increased the relative abundance of Clostridiales, Ruminococcaceae, and Lachnospiraceae, thereby rescuing the PD‐induced metabolic disorders in the colon.ConclusionThese findings indicate that FGF21 could affect behavior and brain metabolic homeostasis in ways that promote a favorable colonic microbiota composition and through effects on the microbiota–gut–brain metabolic axis.
Effect of cryothermic and radiofrequency Cox‐Maze IV ablation on atrial size and function assessed by 2D and 3D echocardiography, a randomized trial. To freeze or to burn
Authors: Boano Gabriella , Vánky Farkas , Åström Aneq Meriam 
Published: June 2023

AbstractBackgroundAtrial linear scars in Cox‐Maze IV procedures are achieved using Cryothermy (Cryo) or radiofrequency (RF) techniques. The subsequent postoperative left atrial (LA) reverse remodelling is unclear. We used 2‐ and 3‐dimensional echocardiography (2‐3DE) to compare the impact of Cryo and RF procedures on LA size and function 1 year after Cox‐maze IV ablation concomitant with Mitral valve (MV) surgery.MethodsSeventy‐two patients with MV disease and AF were randomized to Cryo (n = 35) or RF (n = 37) ablation. Another 33 patients were enroled without ablation (NoMaze). All patients underwent an echocardiogram the day before and 1 year after surgery. The LA function was assessed on 2D strain by speckle tracking and 3DE.ResultsForty‐two ablated patients recovered sinus rhythm (SR) 1 year after surgery. They had comparable left and right systolic ventricular function, LA volume index (LAVI), and 2D reservoir strain before surgery. At follow‐up, the 3DE extracted reservoir and booster function were higher after RF (37 ± 10% vs. 26 ± 6%; p < 0.001) than Cryo ablation (18 ± 9 vs. 7 ± 4%; p < 0.001), while passive conduit function was comparable between groups (24 ± 11 vs. 20 ± 8%; p = 0.17). The extent of LAVI reduction depended on the duration of AF preoperatively.ConclusionsSR restoration after MV surgery and maze results in LA size reduction irrespective of the energy source used. Compared to RF, the extension of ablation area produced by Cryo implies a structural LA remodelling affecting LA systolic function.
Cerebrovascular and cardiovascular responses to the Valsalva manoeuvre during hyperthermia
Authors: Perry Blake G. , Korad Stephanie , Mündel Toby 
Published: June 2023

AbstractBackgroundDuring hyperthermia, the perturbations in mean arterial blood pressure (MAP) produced by the Valsalva manoeuvre (VM) are more severe. However, whether these more severe VM‐induced changes in MAP are translated to the cerebral circulation during hyperthermia is unclear.MethodsHealthy participants (n = 12, 1 female, mean ± SD: age 24 ± 3 years) completed a 30 mmHg (mouth pressure) VM for 15 s whilst supine during normothermia and mild hyperthermia. Hyperthermia was induced passively using a liquid conditioning garment with core temperature measured via ingested temperature sensor. Middle cerebral artery blood velocity (MCAv) and MAP were recorded continuously during and post‐VM. Tieck's autoregulatory index was calculated from the VM responses, with pulsatility index, an index of pulse velocity (pulse time) and mean MCAv (MCAvmean) also calculated.ResultsPassive heating significantly raised core temperature from baseline (37.9 ± 0.2 vs. 37.1 ± 0.1°C at rest, p < 0.01). MAP during phases I through III of the VM was lower during hyperthermia (interaction effect p < 0.01). Although an interaction effect was observed for MCAvmean (p = 0.02), post‐hoc differences indicated only phase IIa was lower during hyperthermia (55 ± 12 vs. 49.3 ± 8 cm s−1 for normothermia and hyperthermia, respectively, p = 0.03). Pulsatility index was increased 1‐min post‐VM in both conditions (0.71 ± 0.11 vs. 0.76 ± 0.11 for pre‐ and post‐VM during normothermia, respectively, p = 0.02, and 0.86 ± 0.11 vs. 0.99 ± 0.09 for hyperthermia p < 0.01), although for pulse time only main effects of time (p < 0.01), and condition (p < 0.01) were apparent.ConclusionThese data indicate that the cerebrovascular response to the VM is largely unchanged by mild hyperthermia.
Long‐term efficacy of antireflux mucosectomy in patients with refractory gastroesophageal reflux disease
Authors: Sumi Kazuya , Inoue Haruhiro , Ando Ryohei , Fujiyoshi Mary Raina Angeli , Fujiyoshi Yusuke , Tanabe Mayo , Shimamura Yuto , Onimaru Manabu 
Published: June 2023

ObjectivesMinimally invasive treatments have been applied for gastroesophageal reflux disease (GERD), but the long‐term results are controversial. Antireflux mucosectomy (ARMS) is a simple endoscopic procedure that does not require the insertion of a foreign body. We provide the first report on the long‐term results of ARMS.MethodsThis was a single‐center, single‐arm trial, prospective study of 88 patients with proton pump inhibitor (PPI)‐refractory GERD who underwent ARMS between June 2012 and June 2017. Primary outcomes were the rates of long‐term effectiveness and PPI discontinuation. Secondary outcomes were to compare patients' preoperative background characteristics, questionnaire, and multichannel intraluminal impedance and pH monitoring data to examine the predictive factors of ARMS. The clinical course was reviewed, including the need for additional treatment after ARMS.ResultsAntireflux mucosectomy produced a long‐term effect in 68.3% of the patients, and PPI could be discontinued in 42% of patients. There were significant differences in age, intensity of preoperative symptoms, and acid‐related indicators. Forty‐five percent (27/60) had reflux hypersensitivity and ARMS provided long‐term effectiveness in 81% of these patients. There was no significant difference in subjective symptom assessment between those with short‐term and long‐term efficacy. Additional treatment was administered in 23% (14/60) and scheduled at 1–2 years’ follow‐up.ConclusionsAntireflux mucosectomy showed long‐term efficacy, and many of the cases with short‐term effects were able to maintain them. In addition, ARMS is also effective in patients with reflux hypersensitivity, and provides a treatment option that bridges the gap between surgical and medical treatment.
Crosstalk between genetic variability of adiponectin and leptin, glucose‐insulin system and subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. The Verona Newly Diagnosed Type 2 Diabetes Study 14
Authors: Zusi Chiara , Csermely Alessandro , Rinaldi Elisabetta , Bertoldo Kezia , Bonetti Sara , Boselli Maria Linda , Travia Daniela , Bonora Enzo , Bonadonna Riccardo C. , Trombetta Maddalena 
Published: June 2023

AbstractAimTo evaluate the relationship of genetic variability of adiponectin (ADIPOQ), leptin (LEP) and leptin receptor (LEPR) genes with glucose‐insulin system and markers of subclinical atherosclerosis (ATS) in patients with newly diagnosed type 2 diabetes.Materials and methodsIn 794 subjects we performed: 1) euglycemic hyperinsulinemic clamp to assess insulin sensitivity; 2) mathematical modelling of a 5h‐OGTT to estimate β‐cell function; 3) resting ECG; 4) carotid artery and lower limb artery eco‐doppler sonography to identify ATS; 5) genotyping of tag‐SNPs within ADIPOQ, LEP and LEPR gene.ResultsRegression analyses showed: 1) adiponectin levels were negatively associated with BMI, waist‐to‐hip ratio and triglycerides and positively with HDL and insulin sensitivity (p‐all<0.03); 2) leptin levels were positively associated with BMI, HDL‐cholesterol and plasma triglycerides and negatively with insulin sensitivity (p‐all<0.001). Two SNPs (rs1501299 and rs2241767) within ADIPOQ gene were associated with circulating levels of adiponectin. The ADIPOQ‐GAACA haplotype was associated with plasma adiponectin (p=0.034; β=‐0.24), ECG abnormalities (p=0.012; OR=2.76), carotid ATS (p=0.025; OR=2.00) and peripheral limb artery ATS (p=0.032; OR=1.90). The LEP‐CTA haplotype showed an association with ischemic ECG abnormalities (p=0.017; OR=2.24). Finally, LEPR‐GAACGG was associated with circulating leptin (p=0.005; β=‐0.31) and worst β‐cell function (p=0.023; β=‐15.10). Omnibus haplotype analysis showed that ADIPOQ haplotypes were associated with levels of adiponectin and common carotid artery ATS, LEP with peripheral limb artery ATS, whereas LEPR haplotypes influenced circulating levels of leptin.ConclusionsResults of this study reinforce knowledge on adipokines’ role in regulating glucose metabolism; in particular highlighted the potential atherogenic role of leptin and the anti atherogenic role of adiponectin.
Serum uric acid lowering and effects of sodium‐glucose cotransporter‐2 inhibitors on gout: A meta‐analysis and meta‐regression of randomized controlled trials
Authors: Banerjee Mainak , Pal Rimesh , Maisnam Indira , Chowdhury Subhankar , Mukhopadhyay Satinath 
Published: June 2023

AbstractAimsTo pool the effects of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors on gout and to investigate the association of these effects with baseline serum uric acid (SUA), SUA lowering, and underlying conditions, such as type 2 diabetes mellitus (T2DM)/heart failure (HF).MethodsPubMed, Embase, Web of Science, Cochrane Library and clinical trial registry websites were searched for randomized controlled trials (RCTs) or post hoc analyses (≥1‐year duration; PROSPERO:CRD42023418525). The primary outcome was a composite of gouty arthritis/gout flares and commencement of anti‐gout drugs (SUA‐lowering drugs/colchicine). Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using a generic inverse‐variance method with a random‐effects model. Mixed‐effects model univariate meta‐regression analysis was performed.ResultsFive RCTs involving 29 776 patients (T2DM, n = 23 780) and 1052 gout‐related events were identified. Compared to placebo, SGLT2 inhibitor use was significantly associated with reduced risk of composite gout outcomes (HR 0.55, 95% CI 0.45‐0.67; I2 = 61%, P < 0.001). Treatment benefits did not differ between trials being conducted exclusively in baseline HF versus those conducted in patients with T2DM (P‐interaction = 0.37), but were greater with dapagliflozin 10 mg and canagliflozin 100/300 mg (P < 0.01 for subgroup differences). Sensitivity analysis excluding trials that evaluated the effects of empagliflozin 10/25 mg (HR 0.68, 95% CI 0.57‐0.81; I2 = 0%) accentuated the benefits of SGLT2 inhibitors with no between‐trial heterogeneity (HR 0.46, 95% CI 0.39‐0.55; I2 = 0%). Univariate meta‐regression found no impact of baseline SUA, SUA lowering on follow‐up, diuretic use, or other variables on their anti‐gout effects.ConclusionWe found that SGLT2 inhibitors significantly reduced the risk of gout in individuals with T2DM/HF. Lack of an association with SUA‐lowering effects suggests that metabolic and anti‐inflammatory effects of SGLT2 inhibitors may predominantly mediate their anti‐gout benefits.
Severe hypoglycaemia in adults presenting to a hospital emergency department: Clinical characteristics, comorbidities, and mortality outcomes
Authors: Song Soon H. , Frier Brian M. 
Published: June 2023

AbstractAimsTo determine the clinical characteristics, risk factors and mortality outcomes associated with severe hypoglycaemia (SH) treated at a hospital emergency department.Materials and MethodsAdult patients presenting with SH to the Northern General Hospital, Sheffield, UK over a 44‐month period were assessed for clinical characteristics, coexisting comorbidities and mortality outcomes, including cause of death, and analysed by age of diabetes onset, below and above age 40 years. Factors that predicted mortality were determined.ResultsA total of 619 episodes of SH occurred in 506 individuals. Most had type 1 (T1D; n = 172 [34.0%]) or type 2 diabetes (T2D; n = 216 [42.7%]), but several attendees did not have diabetes (non‐DM; n = 110 [21.7%]). Irrespective of age of diabetes onset, patients with T2D had more socioeconomic deprivation and comorbidities (P < 0.005). SH was uncommon in those with young‐onset T2D, who constituted 7.2% of all episodes in diabetes. Hospital admission was high (60%‐75%). The T2D cohort had the longest inpatient stay (median 5 days, vs. 2 and 3 days for the T1D and non‐DM cohorts, respectively). Survival after the index SH episode was lower and mortality was higher in the non‐DM (39.1%) and T2D (38.0%) cohorts than the T1D cohort (13.3%; all P < 0.05), with a median time to death of 13, 113 and 465 days, respectively. Most deaths (78%‐86%) were from non‐cardiovascular causes. Charlson index predicted mortality and poor survival in T1D and T2D (both P < 0.05).ConclusionsSevere hypoglycaemia requiring emergency hospital treatment is associated with non‐cardiovascular deaths and exerts a disproportionately greater impact on mortality in people with T2D and those without diabetes. Multimorbidity is an important risk factor for SH and increases mortality risk.
Democratic Citizenship Education in Digitized Societies: A Habermasian Approach
Authors: Culp Julian 
Published: June 2023

AbstractIn this article Julian Culp offers a new conceptualization of democratic citizenship education in light of the transformations of contemporary Western societies to which the use of digital technologies has contributed. His conceptualization adopts a deliberative understanding of democracy that provides a systemic perspective on society‐wide communicative arrangements and employs a nonideal, critical methodology that concentrates on overcoming democratic deficits. Based on this systemic, deliberative conception of democracy, Culp provides an analysis of the public sphere's normative deficits and argues that current political communication may be systemically distorted. Drawing on this analysis, he suggests that practices of democratic citizenship education in digitized societies must not concentrate narrowly on the effective and responsible use of digital technologies. Instead, these practices should also focus on the economic and cultural conditions that are co‐responsible for the structural problems of political communication as well as address the democratic deficits that are reflected in inadequate communicative arrangements.
Inclusive Universalism as a Normative Principle of Education
Authors: Stojanov Krassimir 
Published: June 2023

AbstractIn recent years we have seen a newfound engagement with Jürgen Habermas's work in philosophy of education, focusing on his conception of argumentative dialogue, or discourse, as the origin of both truth‐related epistemic judgments and justifications of moral norms that claim rightness rather than truth. In this article, Krassimir Stojanov first reconstructs the way in which Habermas determines the relation between truth and rightness, and he then shows that moral rightness functions as a “truth‐analogue” since moral norms, like true facts, transcend the actual and local practices of their justification. In the case of moral rightness, this transcendence occurs as an infinite process of inclusion of the perspectives and interests of all potentially concerned persons — also (and foremost) the perspectives and interests of those who are strange to each other in their respective values, worldviews, and interests. With this account of “truth‐analogue” moral rightness, Habermas conceptualizes a kind of processual and “difference‐sensible” universalism, which is very different from the substantialist universalism of some traditional conceptions of education, or Bildung. In the final section, Stojanov shows why including children in their otherness as children in the discursive process of production of moral knowledge, and thus treating them with a kind of epistemic respect, is a constitutive condition for that process. The demand for the discursive inclusion of children follows from the discourse ethics approach, but it requires an enlargement and some corrections of that approach.
Whole metagenome sequencing reveals host plant influences microbial community associated with larvae ofAnastrepha obliqua
Authors: Cárdenas‐Hernández Valentina , Velasco‐Cuervo Sandra , Toro‐Perea Nelson 
Published: June 2023

AbstractThe interactions between phytophagous insects and microorganisms allow the former to take advantage of plant tissue as a food resource, despite being nutritionally deficient and abundant in toxic metabolites. The West Indian fruit fly,Anastrepha obliqua(Macquart) (Diptera: Tephritidae), is a polyphagous species that feeds, as a larva, on the fruits of plants of various families. In Colombia, some of its hosts are red mombin (Spondias purpureaL.), mango (Mangifera indicaL.) (both Anacardiaceae), and star fruit (Averrhoa carambolaL.) (Oxalidaceae). We used whole metagenome sequencing (WMS) to characterize and compare the microbiota and microbiomes ofA. obliqualarvae when they fed on these three fruits. The microbiota constituted of bacteria, fungi, and, to a lesser extent, archaea, and the number of microorganisms in each of these groups varied among host plants. On mango, the main group was Firmicutes; on star fruit and red mombin, Proteobacteria. In addition, on red mombin, fungal groups were more represented than on the other two fruits. For four dominant microbial species,Acetobacter persiciIino et al.,Gluconobacter sphaericus(Ameyama) Malimas et al.,Tatumella ptyseosHollis et al., andWeissella confusa(Holzapfel & Kandler) Collins et al., the genomes were reconstructed. The annotation of these genomes allowed us to determine thatA. persici,G. sphaericus, andT. ptyseoscontain a large number of genes involved in amino acid metabolism pathways, whereasW. confusacontains many genes involved in carbohydrate metabolism pathways. These genes are important for the use of food resources, considering the poor nutritional composition of plant material. Our results form a starting point for understanding the contribution of microorganisms to the ability ofA. obliquato utilize its host plants, the evolutionary implications, and possible applications for the control of this pest insect.