bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Clinical Outcomes With Early Anti-Tumour Necrosis Factor Alpha Therapy in Children With Newly Diagnosed Crohn’s Disease: Real-world Data from the International Prospective PIBD-SETQuality Inception Cohort Study
Authors: Klomberg Renz C W , van der Wal Hella C , Aardoom Martine A , Kemos Polychronis , Rizopoulos Dimitris , Ruemmele Frank M , Charrout Mohammed , Escher Hankje C , Croft Nicholas M , de Ridder Lissy ,   PIBD-SETQuality collaborative group, Milovanovich Ivan D , Ashton James J , Henderson Paul , Ledder Oren , de Meij Tim G J , Hansen Richard , Hummel Thalia Z , Arai Katsuhiro , Rodrigues Astor , Cameron Fiona , Koletzko Sibylle , Muhammed Rafeeq , Nedelkopoulou Natalia 
Published: November 2023

Abstract

Background and Aims
Treatment guidelines for paediatric Crohn’s disease [CD] suggest early use of anti-tumour necrosis factor alpha [anti-TNFα] in high-risk individuals. The aim is to evaluate the effect of early anti-TNF in a real-world cohort.

Methods
Children with newly diagnosed CD were prospectively recruited at 28 participating sites of the international observational PIBD-SETQuality study. Outcomes were compared at 3 months, 1 and 2 years between patients receiving early anti-TNF [&lt;90 days after diagnosis] and those not receiving early anti-TNF. Outcomes included sustained steroid-free remission [SSFR] without treatment intensification [specified as SSFR*] and sustained steroid-free mild/inactive disease without treatment intensification [specified as SSFMI*]. Penalised logistic regression model-based standardisation was applied to estimate the relative risks [RR] of early therapy on outcomes. RRs were estimated for high-risk and low-risk patients, based on presence of predictors of poor outcome [POPOs] and disease activity at diagnosis.

Results
In total, 331 children (median age 13.9 years [IQR 12.2–15.3]) were enrolled, with 135 [41%] receiving early anti-TNF. At 1 year, patients on early anti-TNF had higher rates of SSFR* [30% vs 14%, p &lt;0.001] and SSFMI* [69% vs 33%, p &lt;0.001], with RRs of 2.95 [95% CI 1.63-5.36] and 4.67 [95% CI 2.46-8.87], respectively. At 1 year, the RRs for SSFMI* were higher, and statistically significant in high-risk patients, i.e. those with moderate/severe disease compared with mild/inactive disease at diagnosis (5.50 [95% CI 2.51-12.05] vs 2.91 [95% CI 0.92-9.11]), and those with any POPO compared with no POPO (5.05 [95% CI 2.45-10.43] vs 3.41 [95% CI 0.54-21.7]).

Conclusion
In this cohort of children with newly-diagnosed CD, early anti-TNF demonstrated superior effectiveness in high-risk patients.
The Role of Platelets and von Willebrand Factor in the Procoagulant Phenotype of Inflammatory Bowel Disease
Authors: Schellenberg Célia , Lagrange Jérémy , Ahmed Muhammad Usman , Arnone Djésia , Campoli Philippe , Louis Huguette , Touly Nina , Caron Bénédicte , Plénat François , Perrin Julien , Lenting Peter J , Regnault Véronique , Lacolley Patrick , Denis Cécile V , Peyrin-Biroulet Laurent 
Published: November 2023

Abstract

Aims
Although the risk of thrombosis is well documented for inflammatory bowel disease [IBD] patients, the underlying pathological mechanism seems to be different from other thrombotic conditions. Determining the factors responsible for the increased risk of thrombosis in IBD would help to improve the management of this frequent complication.

Methods
We studied the interplay between platelets, coagulation, and von Willebrand factor [VWF] in 193 IBD patients and in experimental models [acute and chronic] of colitis in wild-type and VWF-deficient mice.

Results
We found a platelet-dependent increase in thrombin generation in IBD patients and in our mouse model of colitis. Agglutinated platelets were present in the blood of patients and mice. Interestingly, we observed not only a significant increase in total VWF antigen, but we were also able to detect the presence of active VWF [VWF in its platelet-binding conformation; 3.2 ± 2.7 μg/mL] in the plasma of 30% of all IBD patients. In healthy controls, active VWF levels were &lt;0.3 μg/mL. This led us to further explore experimental colitis in VWF-deficient mice and we observed that these mice were protected against the procoagulant state triggered by the colitis. Unexpectedly, these mice also showed a significant worsening of colitis severity in both acute and chronic models.

Conclusion
Platelets and VWF [including its active form] appear to be central players in the procoagulant phenotype in IBD. We observed that the role of VWF in haemostasis differs from its role in colonic tissue healing, potentially opening new therapeutic avenues for a life-threatening complication in IBD patients.
Successful permanent pacemaker explantation after diagnosis and treatment of Lyme carditis complete heart block: a case report
Authors: Messner Christopher R , Amara Richard S 
Published: November 2023

Abstract

Background
Lyme carditis (LC) complete heart block (CHB) is typically treated with i.v. antibiotics without requiring permanent pacing. In patients with high degree atrioventricular (AV) block, suspicious index in Lyme carditis (SILC) scoring is highly sensitive for diagnosing LC.

Case summary
We present a case of CHB where a permanent pacemaker (PPM) was implanted prior to LC diagnosis. Suspicious index in Lyme carditis score was 2 at the time of exam, indicating a low risk for LC. However, per further discussion at follow-up, his score was retroactively increased to an intermediate risk of 4 and Lyme titres returned positive. An outpatient oral antibiotic regimen was given, and 2 months later, the patient had &lt;0.1% V-pacing on interrogation with a subsequent unremarkable event monitor. The pacemaker was removed after considerations ensuring full conduction recovery. The patient is doing well at follow-up &gt; 1 year.

Discussion
Lyme carditis spontaneous resolution of CHB is common. Once safe extraction parameters have been established, it is appropriate to engage patients without ongoing pacer requirements about explantation of their PPM. For CHB patients without clear aetiology, SILC scoring may be a predictive measure to help prevent unnecessary PPM placement in the future.
Cardiac arrest in seronegative idiopathic inflammatory myopathy: a case report
Authors: Srivatsav Varun , Khan Ambreen , Wardell Stephan 
Published: November 2023

Abstract

Background
Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases that are characterized by muscle injury. These disorders can cause cardiomyopathy and heart failure, myocarditis, and arrhythmias. However, only a few cases of cardiac arrest as a result of IIMs have been previously reported.

Case summary
A 46-year-old male presented with an out-of-hospital ventricular fibrillation cardiac arrest. A diagnosis of IIM had been made through a muscle biopsy performed 2 years before presentation. The patient had a positive anti-nuclear antibody but negative myositis-specific antibodies. His initial symptoms of IIM were mild and consisted of myalgias. His only cardiac symptoms were minor palpitations that occurred 3 years prior to the cardiac arrest, with a negative Holter monitor test result at that time. His cardiac catheterization was normal. He was suspected to have myocarditis, and a rheumatologist was consulted, following which the patient was initiated on intravenous immunoglobulin (IVIG). Cardiac magnetic resonance imaging demonstrated evidence of chronic myocarditis and an ejection fraction of 44%. He was initiated on goal-directed medical therapy for heart failure. A VVI implantable cardioverter defibrillator was implanted for secondary prevention. He was discharged and prescribed additional immunosuppression including further IVIG infusions, prednisone taper and rituximab infusions.

Discussion
Our case demonstrates that cardiac arrest in IIM is not only plausible, but can be the first major cardiac manifestation of the disease. When a diagnosis of IIM is made, patients require a thorough assessment of cardiac symptomatology and a low threshold for additional cardiac investigations.
The Limitations of Activity-Based Instruction to Improve the Productivity of Schooling
Authors: de Barros Andreas , Fajardo-Gonzalez Johanna , Glewwe Paul , Sankar Ashwini 
Published: November 2023

Abstract
There is substantial emphasis on improving classroom practices, primarily through activity-based instruction, to increase the productivity of schooling. We study a large programme that seeks to promote mathematics learning in government primary schools in India. Through a cluster-randomised trial we find that the programme increased activity-based instruction, but yielded only muted impacts on learning. We provide a potential explanation: school value-added models suggest a negative relationship between activity-based instruction and test score gains. Our findings are robust to adding a community-engagement component to the intervention. These results highlight the limitations of activity-based instruction programmes for increasing school productivity.
Prognostic outcomes and recurrence patterns in resected stage I lung adenocarcinoma harbouring atypical epidermal growth factor receptor mutations
Authors: Chen Tao , Wen Jialiang , Li Yingze , Deng Jiajun , Zhong Yifan , Hou Likun , She Yunlang , Xie Dong , Chen Chang 
Published: November 2023

Abstract

OBJECTIVES
Limited data exist on the characteristics of atypical epidermal growth factor receptor (EGFR) mutations in early-stage lung cancer. Our goal was to elucidate the associations with outcomes and recurrence patterns in resected stage I lung adenocarcinoma harbouring atypical EGFR mutations.

METHODS
Eligible patients between 2014 and 2019 were retrospectively identified and grouped into exon20 insertion mutations and major atypical mutations, which included G719X, L861Q and S768I. Disease-free survival (DFS) was evaluated in the entire cohort and stratified by radiologic characteristics. Recurrence patterns were investigated and compared between groups. A competing risk model was used to estimate the cumulative incidence of recurrence.

RESULTS
A total of 710 patients were finally included. Among them, 289 (40.7%) patients had exon 20 insertion mutations and 421 (59.3%) patients had major atypical mutations. There was no significant difference regarding DFS (P = 0.142) between groups in the entire cohort. The interaction between mutation subtype and the presence of ground-glass opacities was significant (hazard ratio 2.00, 95% confidence interval 1.59–2.51, P &lt; 0.001), indicating DFS between exon 20 insertion mutations and major atypical mutations may be different among subsolid and solid tumours. Survival analysis consistently revealed no significant difference in subsolid tumours (P = 0.680), but favourable DFS of exon 20 insertion mutations in solid tumours (P = 0.037). Furthermore, patients with exon 20 insertion mutations had a lower risk of developing bone metastases did those with radiologic solid tumours (Gray’s test, P = 0.012).

CONCLUSIONS
Exon 20 insertion mutations were correlated with favourable DFS and lower incidence of bone metastases in radiologic solid lung adenocarcinomas harbouring atypical EGFR mutations.
Predisposing factors for adrenal crisis in chronic adrenal insufficiency: a case–control study
Authors: Chifu Irina , Burger-Stritt Stephanie , Schrader Anna , Herterich Sabine , Freytag Janik , Kurlbaum Max , Vogg Nora , Werner Johanna , Quinkler Marcus , Hahner Stefanie 
Published: November 2023

Abstract

Objective
This study aims to identify susceptibility markers for adrenal crises (AC) in educated patients with chronic adrenal insufficiency (AI).

Design
A case–control study involving 66 patients with AI analyzing the impact of glucocorticoid and mineralocorticoid exposure, adrenomedullary function, inflammatory parameters, and educational status on AC frequency. Patients were categorized into low (n = 32) and high (n = 34) AC frequency groups based on AC occurrence (below or 2 times above the average of the reported AC frequency of 8.3 AC/100 patient-years in a previous prospective study).

Methods
Parameters, including cortisol plasma profile and urinary steroid excretion after administration of the morning glucocorticoid dose, 24-h urinary steroid profiling, salivary cortisol profiling, and hair cortisol, estimated cortisol exposure. Polymorphisms (single nucleotide polymorphism [SNP]) of the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) associated with individual steroid sensitivity were assessed together with SNPs for 11β-hydroxysteroid dehydrogenase 1 (HSD11B1) and 11β-hydroxysteroid dehydrogenase 2 (HSD11B2). Mineralocorticoid replacement was evaluated by serum and urinary electrolytes and osmolality, plasma–renin concentration, and ambulatory blood pressure levels. We additionally measured plasma and urinary catecholamines, serum levels of IL6 and hsCRP, and SNPs of IL6 and TNF-alpha. Patient knowledge of AC prevention was assessed by questionnaires.

Results
Frequent AC patients had higher daily glucocorticoid doses and hair cortisol levels, with no significant differences in other parameters investigated. AC frequency is inversely correlated with the frequency of self-reported adjustments of the glucocorticoid replacement.

Conclusion
Higher glucocorticoid dosages in high-risk patients, despite unaffected cortisol metabolism, may be linked to decreased cortisol sensitivity or impaired glucocorticoid absorption. Proactive dose adjustments show a protective effect against AC, regardless of biological vulnerability.
Changes in the swallowing pattern and tongue posture during the transition from deciduous to mixed dentition—a longitudinal ultrasonography study
Authors: Ovsenik Rok , Marolt Mušič Maja , Primožič Jasmina 
Published: November 2023

Summary

Background
Given the importance that swallowing pattern and tongue posture might have in the aetiology of malocclusion, it appears important to be aware of the physiological changes of tongue function and its posture.

Objectives
The study aimed to assess changes of the swallowing pattern and tongue posture during the transition from the deciduous to mixed dentition and the association between them.

Materials and Methods
The study included 57 subjects aged 5.87 ± 0.5 with normal occlusion, orofacial functions, no history of trauma, or orthodontic treatment. Ultrasonography was used for the assessment of tongue posture and swallowing pattern, where the spontaneous act of swallowing was recorded. To evaluate the possible effect of incisors’ eruption, the swallowing pattern and tongue posture ultrasonograms were compared at the deciduous (DD), early mixed (EMD), and intermediate mixed (IMD) timepoints.

Results
A significant association between the swallowing pattern and tongue posture at the DD and IMD timepoint was found. Moreover, the visceral swallowing pattern decreases with age (odds ratio [OR] = 0.777), as well as with a prolonged phase IIa (OR = 0.071), while it increases when the tongue is postured on the mouth floor (OR = 5.020).

Limitations
The young age of the investigated subjects, direct contact of the probe, and the determination of the rest phase of the tongue were considered limitations.

Conclusions
No statistically significant changes in swallowing pattern and tongue posture occurred during the transition period; however, a significant association between the swallowing pattern and tongue posture among subjects with normal occlusion, regardless of the dentition phase was detected.
Natural unemployment and activity rates in Italy: flow-based determinants and implications for price dynamics
Authors: D’Amuri Francesco , De Philippis Marta , Guglielminetti Elisa , Lo Bello Salvatore 
Published: November 2023

Abstract
Despite the magnitude and cyclicality of transitions into and out of the labour force, the literature generally considers unemployment as a sufficient statistic of labour market slack. We question this view by jointly estimating natural unemployment and participation rates through a Phillips curve informed by structural labour market flows. Focusing on Italy, a country where flows into and out of the labour force are particularly large, we find that the participation margin accounts for a significant share of total slack and explains one-third of the missing inflation that followed the 2011 Sovereign Debt Crisis. Exploiting a reform that sharply and unexpectedly increased the statutory retirement age and expanded labour supply without directly affecting unemployment, we confirm that neglecting the participation gap biases inflation forecasts.
Long-term performance of single-connector (DF4) implantable defibrillator leads
Authors: Ibrahim Rand , Al-Gibbawi Mounir , Mekary Wissam , Bhatia Neal Kumar , Kiani Soroosh , Westerman Stacy B , Shah Anand D , Lloyd Michael S , Leal Miguel , De Lurgio David B , Patel Anshul M , Tompkins Christine , Leon Angel R , Merchant Faisal M , El-Chami Mikhael F 
Published: November 2023

Abstract

Aims
Single-connector (DF4) defibrillator leads have become the predominantly implanted transvenous implantable cardioverter-defibrillator lead. However, data on their long-term performance are derived predominantly from manufacturer product performance reports.

Methods and results
We reviewed medical records in 5289 patients with DF4 leads between 2011 and 2023 to determine the frequency of lead-related abnormalities. We defined malfunction as any single or combination of electrical abnormalities requiring revision including a sudden increase (≥2×) in stimulation threshold, a discrete jump in high-voltage impedance, or sensing of non-physiologic intervals or noise. We documented time to failure, predictors of failure, and management strategies. Mean follow-up after implant was 4.15 ± 3.6 years (median = 3.63), with 37% of leads followed for &gt;5 years. A total of 80 (1.5%) leads demonstrated electrical abnormalities requiring revision with an average time to failure of 4 ± 2.8 years (median = 3.5). Of the leads that malfunctioned, 62/80 (78%) were extracted and replaced with a new lead and in the other 18 cases, malfunctioned DF4 leads were abandoned, and a new lead implanted. In multivariable models, younger age at implant (OR 1.03 per year; P &lt; 0.001) and the presence of Abbott/St. Jude leads increased the risk of malfunction.

Conclusion
DF4 defibrillator leads demonstrate excellent longevity with &gt;98.3% of leads followed for at least 5 years still functioning normally. Younger age at implant and lead manufacturer are associated with an increased risk of DF4 lead malfunction. The differences in lead survival between manufacturers require further investigation.
Complex repolarization dynamics in ex vivo human ventricles are independent of the restitution properties
Authors: Iravanian Shahriar , Uzelac Ilija , Shah Anand D , Toye Mikael J , Lloyd Michael S , Burke Michael A , Daneshmand Mani A , Attia Tamer S , Vega John David , El-Chami Mikhael F , Merchant Faisal M , Cherry Elizabeth M , Bhatia Neal K , Fenton Flavio H 
Published: November 2023

Abstract

Aims
The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts.

Methods and results
We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel.

Conclusion
We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.
Relationship between health-related determinants and adherence to breast and colorectal cancer screening: a population-based study in Flanders, Belgium
Authors: Ferrari Allegra , Tran Thuy Ngan , Hoeck Sarah , Peeters Marc , Goossens Mathijs , Van Hal Guido 
Published: November 2023

AbstractBackgroundDespite the recognized benefits of structured cancer screening, tests outside organized screening programs are common. Comprehensive reports on outside program screening in Europe are lacking, but the Flemish breast cancer (BC) and colorectal cancer (CRC) screening programs monitor data on non-organized tests prescribed by GPs and specialists.MethodsUsing data at aggregated level, logistic regression was used to examine the relationship between health care utilization and screening coverage in 308 Flemish municipalities during 2015–18.ResultsWith regards to BC, municipalities with higher rates of gynecologists’ visits had lower odds of coverage inside (−8%) and higher odds of coverage outside (+17%) the program. By contrast, municipalities with higher rates of GP visits, had higher odds of coverage inside (+6%) and lower odds of coverage outside (−7%) the program. As for CRC, municipalities with higher rates of visits gastroenterologists’ visits had lower odds of coverage inside (−3%). Instead, municipalities with higher rates of GP visits, had higher odds of coverage both inside (+2%) and outside (+5%) the program. Municipalities with higher percentages of people with chronic conditions had higher odds of coverage within both the BC and CRC programs (+5% and +3%), and lower odds of outside screening (−7% and −6%). Municipalities with higher percentages of people 65+ with dementia and with mood disorders had, respectively, higher odds (+13% and +5%) and lower odds (−3% and −4%) of coverage inside both the BC and CRC programs.ConclusionOur findings underscore the impact of healthcare utilization on cancer screening coverage at the municipal level in Flanders.