bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel, Heterozygous, de novo Splicing Variant Affecting the Intracellular Domain of the Growth Hormone Receptor, and Causing a Mild Short Stature
Authors: Giannakopoulos Aristeidis , Papanastasiou Anastasios D. , Zarkadis Ioannis K. , Andrew Shayne F. , Rosenfeld Ron G. , Efthymiadou Alexandra , Chrysis Dionisios , Hwa Vivian
Published: October 2023

Introduction: Although the majority of growth hormone insensitivity syndrome (GHIS) cases are classical, the spectrum of clinical phenotypes has expanded to include “atypical” GHIS subjects with milder phenotypes due to very rare heterozygous growth hormone receptor (GHR) mutations with dominant negative effects. Case Presentation: A 13-year-old pubertal boy presented with short stature (−1.7 SDS) and delayed bone age (11.5 years). His serum IGF-1 was low (16 ng/mL; reference range: 179–540). IGFBP-3 (1.3 mg/L; 3.1–9.5) and ALS (565 mU/mL; 1,500–3,500) were also low. GH stimulation test was normal, and GHBP was markedly elevated (6,300 pmol/L; 240–3,000). Additionally, the boy had insulin resistance and liver steatosis. His final height reached −1.8 SDS, which was 3.0 SDS below his mid-parental height. GHR gene from genomic DNA and established primary fibroblast culture was analyzed and a synonymous heterozygous GHR: c.945G>A variant, in the last nucleotide of exon 9 (encoding intracellular domain of GHR) was identified. In vitro analysis of the GHR cDNA demonstrated a splicing defect, leading to the heterozygous excision of exon 9. The final predicted product was a truncated GHR protein which explained the elevated GHBP levels. Conclusion: We describe the first synonymous heterozygous GHR splicing variant in the exon 9-encoding part of the intracellular domain of GHR identified in a patient with mild short stature, thus supporting the continuum of genotype-phenotype of GHIS.
Isolated Femoral or Tibial Component Revision in Total Knee Arthroplasty: A Systematic Review
Authors: Maestri Marco , Castagnini Francesco , Giardina Federico , Tella Giuseppe , Tassinari Enrico , Traina Francesco
Published: October 2023

Objective: The purpose of this systematic review was to assess clinical and radiographic outcomes, complication rates, rates and reasons of re-revision of isolated femoral or tibial component revisions, comparing them with total knee revisions. Methods: A review of the published literature was performed using MEDLINE, Embase, and Cochrane libraries. The terms “isolate” and “revision” and “knee arthroplasty” or “knee replacement” were together used as MeSH terms. Partial knee replacement, non-English literature, case reports, and papers published before 2000 were excluded. Results: Out of 911 papers, six papers met the inclusion criteria. Mean MINORS scores achieved quite low values (13.33 and 13.67). No study encompassed revisions for septic loosening or infection. Total revisions performed for instability and wear achieved better clinical outcomes: in the other cases, partial and total revisions showed no differences in clinical outcomes. Both the cohorts showed similar radiographic features. Lesser bleeding and shorter operative times were observed in partial revisions compared to total revisions. The re-revision rates were similar in most of comparative studies: only one study noticed a significant difference in the failure rate between partial (25% at 3 years) and full (7% at 3.5 years) revisions. Conclusions: The poor quality of the studies precluded sound conclusions. Isolated tibial or femoral component revision is an option when the other component is well fixed and positioned and in absence of chronic periprosthetic infection; nevertheless, it should be carefully evaluated when the reasons for revision are wear or instability.
Changes in Network Size, Quality, and Composition among Informal Caregivers in Different Welfare Clusters: Longitudinal Analyses Based on a Pan-European Survey (SHARE)
Authors: Zwar Larissa , König Hans-Helmut , Hajek André
Published: October 2023

Introduction: This study analyzed the association between transitions into informal caregiving, inside and outside their own household, and changes in network size, quality, and composition among older adults (≥50 years) in four different welfare systems in Europe. Methods: Data from waves 4, 6, and 8 of the Survey of Health, Ageing and Retirement in Europe was used and included up to 110,823 participants (aged ≥50 years) from 12 countries. Participants were asked about informal caregiving inside and outside the household and their network size, quality (emotional closeness, contact frequency), and composition (family, friends, men, women). Adjusted linear and Poisson fixed effects regression analyses were conducted. Results: Participants transitioning into any caregiving (inside or outside the household) had a larger network. More women and family members were found among all those transitioning into caregiving, but only outside caregiving was associated with more men and friends in the network. Transitioning into caregiving outside was associated with reduced network closeness and contact. Changes among caregivers outside were similar in all welfare states but were more pronounced among caregivers inside the household of Eastern Europe. Conclusion: Different patterns of changes in network size, quality, and composition were found among adults transitioning into caregiving inside and outside the household. All parameters changed among caregivers outside the household. However, the welfare system played a key role in the network changes among inside household caregivers. Thus, the micro as well as the macro context of caregiving is important for the support network of informal caregivers.
Effects of Transcranial Direct Current Stimulation on Graph Naming Function and Brain Connectivity in Postinfarction Aphasia Patients: An fMRI Study
Authors: Song Yancheng , Liu Fenghai , Kang Liqing , Xue Cheng , Wang Xiaoxuan , Yang Yanlong , Sun Min , Zhao Meng , Lu Shan
Published: October 2023

Introduction: The study aimed to investigate the mechanisms of impairment and recovery in graph naming functions among patients with aphasia due to cerebral infarction. Specifically, the study compared immediate effects of transcranial direct current stimulation (tDCS) treatment in patients at different stages postinfarction: the acute phase (AP) and the recovery period (RP). Methods: Twenty-eight patients were selected, consisting of 16 in the AP and 12 in the RP, along with 18 healthy controls. Both patient groups underwent 2 weeks of tDCS treatment. Posttreatment changes in functional connectivity (FC) within language-related brain regions, as well as in graph naming abilities, were assessed in both patient groups. Results: Both AP and RP groups exhibited significant improvements in graph naming ability following tDCS treatment. Compared to healthy controls, patients showed decreased FC in multiple brain regions of both hemispheres, particularly in the dominant hemisphere. Posttreatment assessments revealed significant increases in FC within the bilateral frontotemporal lobes for both AP and RP groups, and within the bilateral temporo-occipital regions for the AP group. Moreover, the RP group demonstrated decreased FC in the left temporal lobe posttreatment, which had shown increased FC pre-treatment. Conclusions: This study suggests that tDCS can effectively enhance graph naming functions in patients with postinfarction aphasia. The therapeutic effects appear to be mediated by enhancing FC within bilateral frontotemporal lobes.
A Short-Time Real-World Study of Two Perfluoropropane Tamponade Methods in Pars Plana Vitrectomy for Retinal Detachment
Authors: Tan Shumei , Wu Sefei , Miao Jinhong , Han Jing , Jin Wei , Li Dan , Cui Shuang , Wan Xiaohui , Zhang Li , Yao Ting , Zhang Chun , Wang Changguan , Hu Jinping
Published: October 2023

Introduction: This real-world study evaluated the efficacy, safety, and operative parameters of two perfluoropropane (C3F8) tamponade methods combined with pars plana vitrectomy (PPV) for retinal detachment (RD). Methods: A retrospective study of 132 patients (132 eyes) with RD (pure C3F8 in 38 eyes, mixed C3F8 in 94 eyes). All eyes underwent PPV with C3F8 tamponade and were followed up for at least 3 months. Retinal reattachment rate, time of gas configuration and injection, C3F8 dosage, intraocular pressure (IOP), best corrected visual acuity, postoperative ocular inflammation, and patients’ complaints were evaluated. Results: The single-surgery retinal reattachment rates of the pure C3F8 group and mixed C3F8 group were 97.4% and 96.8%, respectively, with no significant difference (p = 1.00). The final retinal reattachment rates of the two groups were 100% and 97.2%, respectively, with no significant difference (p = 1.00). The gas configuration time, gas injection time, and C3F8 dosage were significantly less in the pure C3F8 group (all p < 0.001). Time, but not group, was the influencing factor of postoperative IOP changes in the two groups (p < 0.001, p = 0.547, respectively). Compared with the baseline, the IOP estimates of the pure C3F8 group showed a significant increase immediately after surgery (p < 0.001), and the mixed C3F8 group showed a significant increase immediately and 1–2 days after surgery (all p < 0.05). There was no statistical difference in ocular inflammation (p = 0.339) and patients’ complaints of discomfort (p = 0.175) between the two groups. Conclusion: Both the two methods of C3F8 tamponade combined with PPV in RD patients showed good efficacy and safety, but the clinical operation of pure C3F8 tamponade was more convenient and eco-friendly.
Mycosis Fungoides in Solid-Organ Transplant Recipients: A Multicenter Retrospective Cohort Study
Authors: Amitay-Laish Iris , Didkovsky Elena , Davidovici Batya , Friedland Rivka , Ben Amitai Dan , Landov Hagai , Greenberger Shoshana , Ollech Ayelet , Prag Naveh Hadas , Hodak Emmilia , Barzilai Aviv
Published: October 2023

Background: Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics. Objective: The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy. Methods: A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022. Results: Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5–22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA – 4, IB – 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1–8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB – 4, III – 1). Conclusions: MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.
NSCLC: Unabhängige prädiktive Marker für Langzeitansprechen auf kombinierte Immuntherapie identifizieren
Authors: Möller Miriam , Schütte Wolfgang
Published: October 2023

Introduction: Combination immunotherapy is widely used in clinical practice as the first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, predictive factors associated with long-term response to combination immunotherapy have not been well investigated. Herein, we compared the clinical findings, including systemic inflammatory nutritional biomarkers, between responders and nonresponders to combination immunotherapy. In addition, we investigated the predictive factors associated with long-term response to combination immunotherapy. Methods: This study included a total of 112 previously untreated advanced NSCLC patients who received combination immunotherapy at eight institutions in Nagano prefecture between December 2018 and April 2021. The responders were defined as those who achieved progression-free survival for 9 months or longer with combined immunotherapy. We evaluated predictive factors associated with long-term response, and the favorable prognostic predictors associated with overall survival (OS) using statistical analyses. Results: The responder and nonresponder groups included 54 and 58 patients, respectively. Compared with the nonresponder group, the responder group had significantly younger age (p = 0.046), higher prognostic nutritional index (44.8 vs. 40.7, p = 0.010), lower C-reactive protein/albumin ratio (CAR) (0.17 vs. 0.67, p = 0.001), and a higher rate of complete plus partial response (83.3% vs. 34.5%, p < 0.001). The area under the curve and optimal cut-off value for CAR were 0.691 and 0.215, respectively. The CAR and best objective response were identified as independent favorable prognostic predictors associated with OS in the multivariate analyses.
Occurrence of Corneal Staining after Cataract Surgery with and without Chitosan-N-Acetylcysteine Eye Drops
Authors: Palkovits Stefan , Schlatter Andreas , Ruiss Manuel , Georgiev Stefan , Zeilinger Johannes , Pilwachs Caroline , Findl Oliver
Published: October 2023

Introduction: The objective of this study was to evaluate the prevalence of ocular surface damage assessed by corneal staining scores right after cataract surgery and whether it can be prevented using chitosan-N-acetylcysteine (C-NAC) eye drops. Methods: We included patients scheduled for routine cataract surgery. Each patient was randomly assigned to one of three groups. Patients in group 1 underwent routine cataract surgery with no additional eye drops. In group 2, patients received C-NAC eye drops after cataract surgery, and in group 3, C-NAC was applied both before and after surgery. Both groups continued the treatment once daily for 4 days. Ocular surface alteration was assessed using the National Eye Institute (NEI) score, and the visual analog scale (VAS) was used to evaluate subjective complaints. Results: Thirty-six patients were included in the final analyses. One hour after cataract surgery, a statistically significant increase in corneal fluorescein staining was observed in all groups, which decreased again after 1 week. There was no significant difference between the groups 1 h after cataract surgery, though a tendency toward lower NEI scores was observed during this time point in group 3. Discussion: Cataract surgery induced ocular surface staining and subjective complaints after 1 h. However, the increase in VAS score was small and probably not clinically relevant. The application of perioperative C-NAC eye drops did reduce the rate of corneal staining after cataract surgery in a clinically relevant manner.
A Comparison of Adult and Juvenile Behcet Patients and a Look at Clinical Trends: Retrospective Data from a Turkish Follow-Up Cohort Study
Authors: Boyvat Ayse , Oktem Ayse , Kalay Yildizhan Incilay , Ates Askın , Yalcindag Nilufer , Koksoy Cuneyt , Yucesan Canan
Published: October 2023

Background: Previous reports indicate that juvenile Behçet’s disease (BD) may have a different course than adult BD. However, as a direct comparison with adult Behçet patients has only been made in a limited number of studies, the issue is still controversial. Objectives: The primary aim of our study was to compare clinical manifestations in a large cohort of juvenile and adult Behçet patients registered in a single centre. The secondary aim of our study was to compare the data of newly diagnosed patients registered between 1998 and 2020 with the data of those registered between 1976 and 1997. Methods: Data were collected retrospectively from medical records of patients registered between 1998 and 2020. Juvenile BD was defined as fulfilment of International Criteria for Behçet’s Disease at or before 16 years of age. Results: A similar course of disease was noted in juvenile and adult Behçet patients with no significant difference in the frequency of mucocutaneous findings, major organ involvement, and positivity of the pathergy test. A comparison of the periods, 1976–1997 and 1998–2020, revealed no significant difference in the prevalence of mucocutaneous lesions and major organ involvement. Conclusions: Our results indicate that juvenile and adult Behçet patients have a similar course with a similar frequency of clinical manifestations. Contrary to reports suggesting an overall tendency to milder disease over time, no decrease in the risk of major organ involvements was observed. A significant trend towards a decline in pathergy test positivity was noted.
Omalizumab Transitions in Severe Asthma: Factors Influencing Switching Decisions and Timing for Optimal Response
Authors: Al-Ahmad Mona , Ali Asmaa , Maher Ahmed
Published: October 2023

Objective: The objective of this study was to assess the effectiveness of switching from omalizumab to another biologic therapy for patients with severe asthma and evaluate factors that influenced the decision to switch and determined the optimal time for a good biologic response. Subjects and Methods: A retrospective study of severe asthma patients was conducted at Al-Rashed Allergy Center, a tertiary center in Kuwait. After meeting the eligibility criteria, patients were divided into two comparative groups: those continuing with omalizumab and those who started with omalizumab but switched to another biologic. Results: One hundred sixteen patients with severe asthma were recruited, and only 33 had access to multiple biological treatments. Approximately 22.4% switched from omalizumab. Male patients with a history of ischemic heart disease, chronic rhinosinusitis, and nasal polyps were more likely to switch if they had higher levels of eosinophils in the sputum. This study showed that every 1% increase in sputum eosinophils doubled the likelihood of a switch. Patients with access to alternative biological options had a much shorter mean duration of omalizumab therapy before switching compared to those with only affordable omalizumab: 4.9 ± 1.5 years versus 8.9 ± 1.3 years (p < 0.001). The optimal time to predict the likelihood of a good response was less than 5.5 years, with an area under the curve of 0.91 and p = 0.003. This cutoff point provided a sensitivity and specificity of approximately 89% and 100%, respectively. Conclusion: An early transition from omalizumab, specifically within the first 5 years of treatment, in patients with severe asthma and higher sputum eosinophils may enhance the likelihood of a good response if other biological therapies were available.
Explaining Variation in Individual Aging, Its Sources, and Consequences: A Comprehensive Conceptual Model of Human Aging
Authors: Rothermund Klaus , Englert Christoph , Gerstorf Denis
Published: October 2023

We define aging as a characteristic deterioration in one (or more) observable attributes of an organism that typically occurs during later life. With this narrow functional definition, we gain the freedom to separate aging from other processes of age-related change (e.g., maturation, growth, illness, terminal decline). We introduce a structural model that distinguishes between (1) the phenomenon of aging, (2) the subjective experience of aging, (3) sources of aging, and (4) consequences of aging. A core focus of the model is on the role of buffering mechanisms of biological repair and personal adaptation that regulate the relations between sources of aging, aging proper, and its consequences. The quality and level of functioning of these buffering mechanisms also varies across the life span, which directly affects the sources of aging, resulting in either resilience against or accelerated aging, and thus can be considered to be a major source of the variation in aging processes among different individuals. External factors comprising attributes of the physical environment and sociocultural characteristics are considered as contexts in which aging occurs. These contextual factors are assumed to feed into the various components of the model. Our model provides an interdisciplinary account of human aging, its sources and consequences, and also its subjective experience, by integrating biological, psychological, lifestyle, and sociocultural factors, and by specifying their interrelations and interactions. The model provides a comprehensive understanding of individual human aging, its underlying processes, and modulating factors. It allows for the derivation of empirically testable hypotheses, and it helps practitioners to identify elements that lend themselves to targeted intervention efforts aimed at increasing the resilience of individuals against aging and buffering its negative consequences.
ILD: Wann brauchen wir die chirurgische Lungenbiopsie in der Diagnostik?
Authors: Wagner Manfred
Published: October 2023

Background: The diagnostic accuracy and safety of transbronchial lung cryobiopsy (TBLC) via a flexible bronchoscope under sedation compared with that of surgical lung biopsy (SLB) in the same patients is unknown. Methods: Retrospectively the data of fifty-two patients with interstitial lung diseases (median age: 63.5 years; 21 auto-antibody positive) who underwent TBLC followed by SLB (median time from TBLC to SLB: 57 days) was collected. The samples from TBLC and SLB were randomly labelled to mask the relationship between the two samples. Diagnosis was made independently by pathologists, radiologists, and pulmonary physicians in a stepwise manner, and a final diagnosis was made at multidisciplinary discussion (MDD). In each diagnostic step the specific diagnosis, the diagnostic confidence level, idiopathic pulmonary fibrosis (IPF) diagnostic guideline criteria, and treatment strategy were recorded. Results: Without clinical and radiological information, the agreement between the histological diagnoses by TBLC and SLB was 42.3% (kappa [κ] = 0.23, 95% confidence interval [CI]: 0.08–0.39). However, the agreement between the TBLC-MDD and SLB-MDD diagnoses and IPF/non-IPF diagnosis using the two biopsy methods was 65.4% (κ = 0.57, 95% CI: 0.42–0.73) and 90.4% (47/52), respectively. Out of 38 (73.1%) cases diagnosed with high or definite confidence at TBLC-MDD, 29 had concordant SLB-MDD diagnoses (agreement: 76.3%, κ = 0.71, 95% CI: 0.55–0.87), and the agreement for IPF/non-IPF diagnoses was 97.4% (37/38). By adding the pathological diagnosis, the inter-observer agreement of clinical diagnosis improved from κ = 0.22 to κ = 0.42 for TBLC and from κ = 0.27 to κ = 0.38 for SLB, and the prevalence of high or definite diagnostic confidence improved from 23.0% to 73.0% and from 17.3% to 73.0%, respectively. Of all 383 TBLC performed during the same period, pneumothorax occurred in 5.0% of cases, and no severe bleeding, acute exacerbation of interstitial lung disease, or fatal event was observed.
Chronische noduläre Prurigo: Update zu Pathogenese und Management
Authors: Wong Lai-San , Yen Yu-Ta
Published: October 2023

Die chronische noduläre Prurigo (CNPG) ist eine chronische, rezidivierende Juckreizkrankheit, die die Lebensqualität beeinträchtigt. Sie kann durch eine Vielzahl von Ursachen ausgelöst werden, darunter atopische Dermatitis, Diabetes und chronische Nierenerkrankungen. Die Mechanismen der CNPG sind komplex und beinhalten das Zusammenspiel von Haut-, Immun- und Nervensystem. Verschiedene Immunzellen, darunter Eosinophile, Neutrophile, T-Zellen, Makrophagen und Mastzellen, haben die Haut der CNPG-Läsionen infiltriert, was zur Freisetzung inflammatorischer Zytokine und Pruritogene geführt hat. Darüber hinaus verursacht die Interaktion zwischen Immunzellen und peripheren sensorischen Nervenfasern, die durch Neurotransmitter aktiviert wurden, eine Neuroinflammation in der Haut und einen anhaltenden Juckreiz. Dieser Teufelskreis von Juckreiz und Kratzen führt zu einer Verschlimmerung der Erkrankung. Die CNPG ist mit herkömmlichen Therapien schwer zu behandeln. Kürzlich wurden große Fortschritte in der Pathophysiologie sowohl der Entzündung als auch der Pruritustransmission bei CNPG gemacht. In dieser Übersichtsarbeit fassen wir die aktuellen Mechanismen und neuen Therapien für CNPG zusammen.
Predictors of New Onset Atrial Fibrillation Burden in the Critically Ill
Authors: Lancini Daniel , Sun Jennifer , Mylonas Georgia , Boots Robert , Atherton John , Prasad Sandhir , Martin Paul
Published: October 2023

Introduction: Atrial fibrillation (AF) is common in the intensive care unit (ICU) setting and has been associated with adverse outcomes. In this context, there is increasing research interest in AF burden as a predictor of subsequent adverse events. However, the pathophysiology and drivers of AF burden in the ICU are poorly understood. This study sought to evaluate the predictors of AF burden in critical illness-associated new-onset AF (CI-NOAF). Methods: Out of 7,030 admissions in a tertiary general ICU between December 2015 and September 2018, 309 patients developed CI-NOAF. AF burden was defined as the percentage of monitored time in AF, as extracted from hourly interpretations of continuous ECG monitoring. Low and high AF burden groups were defined relative to the median AF burden. Clinical, laboratory, and echocardiographic parameters were extracted, and multivariable modelling with binary logistic regression was performed to evaluate for independent associations with AF burden. Results: The median AF burden was 7.0%. Factors associated with increased AF burden were age, dyslipidaemia, chronic kidney disease, increased creatinine, CHA2DS2-VASc score, ICU admission diagnosis category, amiodarone administration, and left atrial area (LAA). Factors associated with lower AF burden were previous alcohol excess, burden of ventilation, the use of inotropes/vasopressors, and beta blockers. On multivariate analysis, increased LAA, chronic kidney disease, and amiodarone use were independently associated with increased AF burden, whereas beta blocker use was associated with lower AF burden. Conclusion: Left atrial size and chronic cardiovascular comorbidities appear to be the primary drivers of CI-NOAF burden, whereas factors related to acute illness and critical care intervention paradoxically did not appear to be a substantial driver of arrhythmia burden. Further research is needed regarding drivers of AF and the efficacy of rhythm control intervention in this unique setting.
Pregnancy Outcomes in Females with Eosinophilic Esophagitis: A Nationwide Population-Based Study
Authors: Röjler Lovisa , Uchida Amiko M. , Garber John J. , Stephansson Olof , Söderling Jonas , Roelstraete Bjorn , Ludvigsson Jonas F.
Published: October 2023

Introduction: Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. It has a peak incidence in the 2nd and 3rd decades of life. Despite this, little is known about pregnancy outcomes in patients with EoE. Methods: Using a validated histopathologic and nationwide population-based cohort for the diagnosis of EoE, we examined maternal and fetal outcomes, with preterm birth as the primary outcome, in females with EoE compared to matched controls. Odds ratios (ORs) were calculated using logistic regression. Results: Between 1992 and 2016, we identified 19 females with EoE who gave birth to 23 children (reference births: n = 115). There was 1 (4.3%) preterm birth in the EoE cohort versus 8 (7.0%) in the reference cohort (OR = 0.60; 95% CI = 0.07–5.14). Secondary fetal outcomes included stillbirth, neonatal death, small for gestational age, low birth weight (LBW), and low Apgar score. Of these, LBW (<2,500 g) in patients with EoE compared to controls correlated to an OR of 12.42 (95% CI = 1.26–122.42); however, this finding was based on very low numbers. The remaining fetal outcomes were not significantly different between females with EoE and controls. Secondary pregnancy and maternal outcomes including induction of labor, instrumental delivery, gestational diabetes, or pre-eclampsia were not significantly different between patients with EoE and controls. Discussion/Conclusion: Overall in this nationwide cohort study, we did not find increased association of preterm birth in patients with EoE.
Lifestyle Factors and Silent Inflammatory Bowel Disease
Authors: Coates Matthew D. , Dalessio Shannon , Stuart August , Walter Vonn , Tinsley Andrew , Clarke Kofi , Williams Emmanuelle D.
Published: October 2023

Introduction: Hypoalgesic or silent inflammatory bowel disease (IBD) is a poorly understood condition that has been associated with poor clinical outcomes. There is evidence that lifestyle factors, including diet, exercise, and substance use can influence inflammatory activity and symptoms in IBD. It is unclear, though, whether these issues impact pain experience in IBD. We performed this study to evaluate the potential relationship between several key lifestyle factors and silent IBD. Methods: We performed a retrospective analysis using an IBD natural history registry based in a single tertiary care referral center. We compared demographic and clinical features in 2 patient cohorts defined using data from simultaneous pain surveys and ileocolonoscopy: (a) active IBD without pain (silent IBD) and (b) active IBD with pain. We also evaluated the relative incidence of characteristics related to diet, exercise, sexual activity, and substance abuse. Results: One hundred and eighty IBD patients had active disease and 69 (38.3%) exhibited silent IBD. Silent IBD patients exhibited incidences of disease type, location, and severity as pain-perceiving IBD patients. Silent IBD patients were more likely to be male and less likely to exhibit anxiety and/or depression or to use cannabis, analgesic medication, or corticosteroids. There were no significant differences in dietary, exercise-related, or sexual activities between silent and pain-perceiving IBD patients. Conclusions: Silent IBD was associated with reduced incidence of substance and analgesic medication use. No relationships were found between silent IBD and diet, exercise, or sexual activity, though specific elements of each require further dedicated study.
Genetic/Epigenetic Alteration and Tumor Immune Microenvironment in Intrahepatic Cholangiocarcinoma: Transforming the Immune Microenvironment with Molecular-Targeted Agents
Authors: Nishida Naoshi , Kudo Masatoshi
Published: October 2023

Background: Intrahepatic cholangiocarcinoma (iCCA) is often diagnosed at an advanced stage, leading to limited treatment options and a poor prognosis. So far, standard systemic therapy for advanced iCCA has been a combination of gemcitabine and cisplatin. However, recent advancements in the understanding of the molecular characteristics of iCCA have opened new possibilities for molecular-targeted therapies and immunotherapy. Summary: Reportedly, 9–36% of iCCA cases have an inflamed tumor immune microenvironment (TME) based on the immune gene expression signature, which is characterized by the presence of immune cells involved in anti-tumor immune responses. The majority of iCCA cases have a non-inflamed TME with a lack of effector T cells, rendering immune checkpoint inhibitors (ICIs) ineffective in these cases. Interestingly, alterations in the fibroblast growth factor receptor (FGFR2) gene and IDH1/2 gene mutations are often observed in the non-inflamed TME in iCCA. Several mechanisms have been reported for the role of driver mutations on the establishment of TME unique for iCCA. For example, IDH1/2 mutations, which cause an increase in DNA methylation, are associated with the downregulation and hypermethylation of antigen processing and presentation machinery, which may contribute to the establishment of a non-inflamed TME. Therefore, inhibitors targeting IDH1/2 may restore the DNA methylation and expression status of molecules involved in antigen presentation, potentially improving the efficacy of ICIs. FGFR inhibitors may also have the potential to modulate immunosuppressive TME by inhibitingthe suppressor of cytokine signaling 1 and activating the interferon-γ signaling as a consequence of inhibition of the FGFR signal. From this perspective, understanding the molecular characteristics of iCCA, including the TME and driver mutations, is essential for the effective application of ICIs and molecular-targeted therapies. Key Messages: Combination approaches that target both the tumor and immune system hold promise for improving the outcomes of patients with iCCA. Further research and clinical trials are needed to validate these approaches and optimize the treatment strategies for iCCA.
Endotoxin-Induced Physiological and Psychological Sickness Responses in Healthy Humans: Insights into the Post-Acute Phase
Authors: Engler Harald , Brinkhoff Alexandra , Wilde Benjamin , Kribben Andreas , Rohn Hana , Witzke Oliver , Schedlowski Manfred , Benson Sven
Published: October 2023

Introduction: Experimental endotoxemia is a translational model of systemic inflammation that has contributed significantly to our current understanding of sickness behavior and inflammation-associated depression. Previous studies using this model revealed a strong association between cytokine levels, endocrine changes, and psychological sickness symptoms during the acute phase of inflammation. The objective of this randomized, double-blind, placebo-controlled crossover study was to gain insight into potential post-acute physiological and psychological consequences of endotoxin administration that may either persist or newly emerge between 24 and 72 h after injection. The main focus was on associations between serum levels of C-reactive protein (CRP) and affective symptoms as well as alterations in diurnal cortisol profile, the two key features of inflammation-associated depression. Methods: Healthy male volunteers (N = 18) received an injection of either endotoxin (0.8 ng/kg) or placebo on two separate but otherwise identical study days, 7 days apart. Blood and saliva samples were collected during acute and post-acute phases after injection to measure blood inflammatory markers (interleukin [IL]-6, IL-1 receptor antagonist [ra], CRP) and salivary cortisol levels. In addition, participants completed a comprehensive battery of questionnaires to assess physical and psychological sickness symptoms. Results: Endotoxin treatment induced a short-time rise in plasma IL-6 and a longer increase in IL-1ra. The increase in serum CRP was delayed compared to cytokines, peaking at 24 h and gradually decreasing until 72 h after injection. The inflammatory response was accompanied by bodily and psychological sickness symptoms which occurred only in the acute phase, whereas none of the symptoms persisted or recurred in the post-acute phase. Salivary cortisol levels were significantly increased during the acute phase and exhibited pronounced circadian changes. However, no significant differences in diurnal cortisol profiles were observed between placebo and endotoxin conditions on the days after treatment. Conclusion: Our findings suggest that CRP, which is elevated in patients with inflammation-associated depression, does not appear to be responsible for depressive symptomatology. Moreover, a single inflammatory episode is not sufficient to alter diurnal cortisol profiles, as observed in inflammation-associated depression. In addition, the absence of persistent lipopolysaccharide-induced psychological and physiological changes beyond the acute phase further supports the safety of endotoxin administration in humans.
Comparison of Outcomes between a Basket Catheter and a Balloon Catheter for Endoscopic Common Bile Duct Stone Removal
Authors: Saito Hirokazu , Iwasaki Hajime , Itoshima Hisashi , Kadono Yoshihiro , Shono Takashi , Kamikawa Kentaro , Urata Atsushi , Nasu Jiro , Uehara Masayoshi , Matsushita Ikuo , Kakuma Tatsuyuki , Hashigo Shunpei , Tada Shuji
Published: October 2023

Introduction: Evidence for the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) between a basket catheter and a balloon catheter for endoscopic common bile duct stone (CBDS) removal is lacking. This study aimed to compare ERCP outcomes using a basket catheter and a balloon catheter for endoscopic CBDS removal. Methods: This multicenter retrospective study included 904 consecutive patients with native papilla who underwent endoscopic stone removal for CBDS ≤10 mm using a basket catheter and/or a balloon catheter at three institutions in Japan. ERCP outcomes between the basket and balloon groups were compared using inverse probability of treatment weighting (IPTW) method. Results: ERCP-related adverse events occurred in 6.5% (29/449) and 7.7% (35/455) of patients in the basket and balloon groups, respectively (IPTW-adjusted p = 0.52). The incidences of post-ERCP pancreatitis, cholangitis, and perforation were similar in the basket and balloon groups (3.8% vs. 2.9%, 1.3% vs. 0.9%, and 0.7% vs. 0.7%, respectively). However, bleeding incidences were significantly higher in the balloon group than in the basket group (3.3% vs. 0.7%, IPTW-adjusted p = 0.012). Successful complete stone removal at one ERCP session using a single catheter was achieved in 17.8% (80/449) in the basket group and in 81.3% (370/455) in the balloon group (IPTW-adjusted p < 0.001). Discussion: A balloon catheter is more likely to complete stone extraction for CBDS ≤10 mm with a single catheter at one endoscopic stone removal session. However, the risk for post-ERCP bleeding is higher in the balloon group than in the basket group.
Clopidogrel-Related High Residual Platelet Reactivity Associated with Estimated Glomerular Filtration Rate in Patients with Acute Ischemic Stroke
Authors: Zhang Yongkang , Zong Yuan , Liu Jiarui , Yin Kangli , Wang Yuzhen , Bian Yuefeng , Huang Yichen , Liu Wei , Cao Yemin
Published: October 2023

Introduction: There are few studies on the relationship between the occurrence of clopidogrel-related high residual platelet reactivity (HRPR) and estimated glomerular filtration rate (eGFR) at admission in patients with ischemic stroke. The aim of this study was to investigate the possible relationship between the two. Methods: Patients who were hospitalized and diagnosed with acute ischemic stroke were recruited from July 1, 2017, to June 30, 2018, at Shanghai TCM-Integrated Hospital. Renal function was measured within 24 h of enrollment and eGFR was calculated. Patients were tested for platelet reactivity using the VerifyNow system after 7 days of antiplatelet therapy with clopidogrel 75 mg/d alone, and patients with P2Y12 reaction unit values ≥230 were diagnosed with HRPR. The association between HRPR and eGFR was analyzed. Results: A total of 274 patients were enrolled in the study, of whom 91 (33.21%) had HRPR. Multivariate logistic regression analysis suggested that an increased risk of HRPR was independently associated with female sex and reduced eGFR (female sex: OR = 2.24, 95% CI: 1.26–3.99, p = 0.006; mild chronic kidney disease [CKD]: OR = 2.95, 95% CI: 1.47–5.93, p = 0.002; moderate CKD: OR = 3.07, 95% CI: 1.08–8.75, p = 0.04). Conclusion: Decreased eGFR is an independent risk factor for the occurrence of HRPR in patients with ischemic stroke.
Management and Morbidity of Major Pelvic Hemorrhage in Complex Abdominopelvic Surgery
Authors: Aytac Erman , Sökmen Selman , Öztürk Ersin , Rencüzoğulları Ahmet , Sungurtekin Uğur , Akyol Cihangir , Demirbaş Sezai , Leventoğlu Sezai , Karakayalı Feza , Korkut Mustafa Ali , Öncel Mustafa , Gülcü Barış , Canda Aras Emre , Eray İsmail Cem , Özgen Utku , Ersöz Şiyar , Özer Tahir , Özerhan İsmail Hakkı , Bozbıyık Osman , Haksal Mustafa , Oral Berke Mustafa
Published: October 2023

Introduction: Hemorrhage is a challenging complication of pelvic surgery. This study aimed to analyze the causes, management, and factors associated with morbidity in patients experiencing major pelvic hemorrhage during complex abdominopelvic surgery. Methods: Patients who had major intraoperative pelvic hemorrhage during complex abdominopelvic surgery at 11 tertiary referral centers between 1997 and 2017 were included. Patient characteristics, management strategies to control bleeding, short- and long-term postoperative outcomes were evaluated retrospectively. Results: There were 120 patients with a mean age of 56.6 ± 2.4 years and a mean BMI of 28.3 ± 1 kg/m2. While 104 (95%) of the patients were operated for malignancy, 16 (5%) of the patients had surgery for a benign disease. The most common bleeding site was the presacral venous plexus 90 (75%). Major pelvic hemorrhage was managed simultaneously in 114 (95%) patients. Electrocauterization 27 (23%), pelvic packing 26 (22%), suturing 7 (6%), thumbtacks application 7 (6%), muscle welding 4 (4%), use of energy devices 2 (2%), and topical hemostatic agents 2 (2%) were the management tools. Combined techniques were used in 43 (36%) patients. Short-term morbidity and mortality rates were 48 (40%) and 2 (2%), respectively. High preoperative CRP levels (p = 0.04), history of preoperative radiotherapy (p = 0.04), longer bleeding time (p = 0.006), and increased blood transfusion (p = 0.005) were the factors associated with postoperative morbidity. Conclusion: Postoperative morbidity related to major pelvic hemorrhage can be reduced by optimizing the risk factors. Prehabilitation prior to surgery to moderate inflammatory status and prompt action with proper technique to control major pelvic hemorrhage can prevent excessive blood loss in complex abdominopelvic surgery.
Thermal consequences of sintering the borosilicate matrix blue-green color release properties
Authors: Tung Ha Thanh , Nguyen Thi Dieu An
Published: October 2023

Color transformation glass ceramics were produced of borosilicate matrix co-doped (SrBaSm)Si2O2N2:(Eu3+Ce3+) blue–green (B-G) (abbreviated as (SBS)SON:(EuCe) B-G) phosphors using a two-step co-sintering technique. The shift in illumination characteristics and drift of chromaticity coordinates (CIE) of (SBS)SON:(EuCe) (B-G) phosphors and hue transformation glass ceramics were investigated over a 600–800 ºC sintering thermal range. With rising sintering heat, the illuminated strength and inner quantum yield (QY) of (abbreviated as B-G) phosphors and glass ceramics reduced. Once the sintering heat was raised above 750 ºC, the phosphors and hue transformation glass ceramics showed nearly no high point among their luminescence photoluminescence (PL) and photoluminescence excitation (PLE) bands of color. B-G phosphors have low heating steadiness at more elevated temperatures, according to the findings. The glass matrix destructed the phosphors lattice layout and the Ce3+ in the phosphors was oxidized to Ce4+, resulting in a reduction in the luminous characteristics of the color transformation glass ceramics.
Growth predictions of lettuce in hydroponic farm using autoregressive integrated moving average model
Authors: Asy'ari Muhammad Zacky , Chrysdi Aten Julius Felix , Prasetyo Dimas
Published: October 2023

Hydroponic farming techniques can grow plants faster when intensive monitoring is carried out. However, sometimes proper monitoring does not occur, which causes some plants not to grow as expected. This research uses a sensor to measure a parameter that affects the growth of the hydroponic plants and uses a camera to take pictures periodically to measure daily growth. The research presented in this article is to build a model and forecasting plant growth in hydroponics farming using a time series approach. This paper demonstrated that the historical data on lettuce growth could be used to predict future plant size. The autoregressive integrated moving average (ARIMA) model was used and analyzed according to the six performance criteria: mean absolute error (MAE), root mean squared error (RMSE), mean absolute percentage error (MAPE), Akaike information criterion (AIC), and Bayesian information criterion (BIC). To find the best model, different autoregressive (p) and moving average (q) parameters were examined. We find that the appropriate statistical model for lettuce growth is ARIMA (2, 2, 1) which has the lowest AIC, BIC, and MAPE with values of 76.67, 79.02, and 0.04, respectively, to forecast the plant size for the next three days.
Security analysis of encrypted audio based on elliptic curve and hybrid chaotic maps within GFDM modulator in 5G networks
Authors: Mohammed Ameen Mohammed Jabbar , S. Hreshee Saad
Published: October 2023

Wireless communications face significant security challenges, so there is an ongoing necessity to develop an appropriate security strategy to protect data from eavesdroppers using cryptography based on chaos theory. Generalized frequency division multiplexing (GFDM) is a modern multicarrier waveform adaptable to 5G requirements, but its security issues have not been considered. Therefore, this paper proposed an efficient security technique within the GFDM modulator to protect the audio transmission against eavesdropping in 5G networks. The proposed GFDM is achieved by separating the subsymbols for the subcarrier into real and imaginary parts and combining them using a mixture of elliptic curve-linear congruential generator sequence (EC-LCG) with Ikeda and Tent maps, respectively. After that, the subsymbols of each subcarrier are permuted independently using the Duffing map. The effectiveness of the proposed approach to resist attacks was tested, and findings that were achieved are histogram, signal to noise ratio (SNR=-27.8068), spectral segment SNR (SSSNR=-34.9912), peak SNR (PSNR=0.9142), frequency weighted log spectral distance (dFWLOG=37.498), cepstral distance (dCD=9.0176), mean square error (MSE=0.82097), keyspace, and speed. These results show that the proposed model provides a high-security level, high speed in the encryption/decryption, large keyspace, and high sensitivity to the initial conditions.
Robust attribute selection to improve the Parkinson's disease classification: a hybrid approach
Authors: Al-Mashanji Ameer K. , Alhasnawy Laith Hamid , Hamza Aseel Hamoud
Published: October 2023

Parkinson’s disease (PD) is known to be a neurodegenerative syndrome that progresses chronically. As a result of the damage or death of brain neurons that generate dopamine patients tend to face difficulty when performing simple everyday tasks like walking, writing, or speaking. The main contribution of this work presents a hybrid method for improving predicting PD. This methodology has been obtained by means of testing a number of different combinations of classification algorithms and approaches for selecting attributes. A total of three attributes selection methods (correlation, information gain, and variance threshold) and three classifiers (decision trees (DT), naive bayes (NB), and support vector machine (SVM)) have been adopted. The speech data set provided by University of California-Irvine (UCI) machine learning (ML) repository is adopted to analyze the performance of different combinations. The combination of information gain and DT classifier achieved the best performance rather than other combination methods, reaching a classification accuracy of (97.43%). Finally, an additional comparison of the performance analysis with the results of previous studies was made and it was found that the proposed methodology proved to outperform the results of other studies conducted in this field.