bluuebunny/crossref_metadata_2025 huggingface dataset:
A two‐component model of hair cortisol concentration in fibromyalgia: Independent effects of pain chronicity and severity
Authors: Reyes del Paso G. A. , Garcia‐Hernandez A. , Contreras‐Merino A. M. , Galvez‐Sánchez C. M. , de la Coba P. , Montoro C. I. , Davydov D. M.
Published: December 2023

Background

Fibromyalgia (FM) is a chronic pain disorder of unknown aetiopathogenesis, in which the role of activity of the hypothalamic–pituitary–adrenal (HPA) axis is not clearly established.

Methods

This study analysed the modulatory effects of disease chronicity and severity on cortisol levels. Hair cortisol concentrations (HCC) and clinical evaluation data (pain severity, impact of FM on daily activities, depression, anxiety, fatigue and insomnia) were collected from 47 female patients with FM and 36 healthy women (HW).

Results

The results showed that disease chronicity, with a negative effect, and symptom severity, with a positive effect, were independent predictors of HCC. Patients with a shorter disease duration had higher HCC than patients with a longer disease duration and healthy participants. Furthermore, patients with greater symptom severity had higher HCC than those patients with lower clinical severity and healthy participants. While disease chronicity in FM was associated with a decrease in HCC, clinical severity increased HCC.

Conclusions

These results support the existence of a dysfunction in the regulation of the HPA axis in FM and its possible contribution to chronic pain development.

Significance

This is the first study to assess hair cortisol concentrations in a specific sample of patients with fibromyalgia (FM). This method is especially useful for the assessment of long‐term regular cortisol excretion. Results showed a two‐component model for explaining cortisol levels: disease chronicity, with a negative effect, and symptom severity, with a positive effect. This suggests that severe pain/stress evokes higher cortisol levels at earlier stages of FM, while in the longer term a decrease in cortisol levels was observed.
EPPTA: Efficient partially observable reinforcement learning agent for penetration testing applications
Authors: Li Zegang , Zhang Qian , Yang Guangwen
Published: December 2023

In recent years, penetration testing (pen‐testing) has emerged as a crucial process for evaluating the security level of network infrastructures by simulating real‐world cyber‐attacks. Automating pen‐testing through reinforcement learning (RL) facilitates more frequent assessments, minimizes human effort, and enhances scalability. However, real‐world pen‐testing tasks often involve incomplete knowledge of the target network system. Effectively managing the intrinsic uncertainties via partially observable Markov decision processes (POMDPs) constitutes a persistent challenge within the realm of pen‐testing. Furthermore, RL agents are compelled to formulate intricate strategies to contend with the challenges posed by partially observable environments, thereby engendering augmented computational and temporal expenditures. To address these issues, this study introduces EPPTA (efficient POMDP‐driven penetration testing agent), an agent built on an asynchronous RL framework, designed for conducting pen‐testing tasks within partially observable environments. We incorporate an implicit belief module in EPPTA, grounded on the belief update formula of the traditional POMDP model, which represents the agent's probabilistic estimation of the current environment state. Furthermore, by integrating the algorithm with the high‐performance RL framework, sample factory, EPPTA significantly reduces convergence time compared to existing pen‐testing methods, resulting in an approximately 20‐fold acceleration. Empirical results across various pen‐testing scenarios validate EPPTA's superior task reward performance and enhanced scalability, providing substantial support for efficient and advanced evaluation of network infrastructure security.
Experimental Investigation of Energy and Exergy Assessment of Vapor Compression Refrigeration Unit Enhanced via Encapsulated Phase Change Material
Authors: Ismail Mohamed , Hassan Hamdy
Published: December 2023

Energy and exergy performance of simple vapor compression refrigeration unit is investigated experimentally with and without coupling heat exchanger of phase change material before the condenser. The hot outside air is cooled before entering the condenser throughout the day by flowing over the cooled phase change material structure that previously solidified during nighttime. Phase change material SP24 is employed because its melting/freezing range is suitable for most selected countries' climates. An experimental set‐up of an air‐phase change material heat exchanger coupled with the unit is constructed to examine its performance, including pressure–enthalpy curve, coefficient of performance, exergy performance, and power consumption including inflow air temperatures and flow rates impacts. Results affirm that the coefficient of performance, cooling capacity, power usage, and exergy destruction are improved by using phase change material. Compared to the unmodified unit, the maximum percentage of saved power and exergy destruction enhancement for the modified refrigeration unit with phase change material is about 8.8% and 10%, respectively. The maximum coefficient of performance and exergy efficiency rise is about 15.1% and 14.2%, respectively. Increasing the temperature differential across the phase change material heat exchanger, either by increasing inlet temperature or decreasing airflow, enhances the refrigeration unit power saving.
Storage stability and shelf‐life of soymilk obtained via repeated boiling and filtering: A predictive model
Authors: Fan Liu , Duan Yitong , Huang Zhanrui , Zhao Dan , Zhao Liangzhong , He Wanying , Zhang Xuejiao , Li Ming , Lin Yingyi , Chen Yu
Published: December 2023

This study investigated the effects of different processing methods on the quality and nutrition of soymilk, as well as the changes in storage stability (centrifugal sedimentation rate (CSR), viscosity, and particle size) and shelf‐life of soymilk at different storage temperatures (25°C, 35°C, 45°C, and 55°C). Results showed that soymilk processed via the repeated boiling‐to‐filtering method (RBFM) exhibited the highest protein content (3.89 g/100 g), carbohydrate content (1.27 g/100 g), and stability coefficient (0.950). The CSR and particle size of RBFM soymilk increased gradually during storage at different temperatures, while the viscosity and sensory score decreased. The correlation between the CSR and the sensory score of RBFM soymilk was the highest (R2 = .9868). The CSR was selected as the key indicator to predict the shelf‐life of RBFM soymilk. The average residual variation in RBFM soymilk shelf‐life based on the predictive model was 10.78%, indicating the strong accuracy of the model for predicting the shelf‐life of RBFM soymilk stored at temperatures ranging from 25–45°C. This study provides a theoretical basis and technological support for the development, transportation, and storage of soymilk and soymilk beverage products.
KMT2 (MLL) family of methyltransferases in head and neck squamous cell carcinoma: A systematic review
Authors: da Silva Santos Marcos Ezequiel , de Carvalho Abreu Anna Karolina , Martins da Silva Fábio Willian , Barros Ferreira Elaine , Diniz dos Reis Paula Elaine , do Amaral Rabello Ramos Doralina
Published: December 2023

Background

The involvement of the KMT2 methyltransferase family in the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains elusive.

Method

This study adhered to the PRISMA guidelines, employing a search strategy in the LIVIVO, PubMed, Scopus, Embase, Web of Science, and Google Scholar databases. The methodological quality of the studies was assessed by the Joanna Briggs Institute.

Results

A total of 33 studies involving 4294 individuals with HNSCC were included in this review. The most important alteration was the high mutational frequency in the KMT2C and KMT2D genes, with reported co‐occurrence. The expression of the KMT2D gene exhibited considerable heterogeneity across the studies, while limited data was available for the remaining genes.

Conclusions

KMT2C and KMT2D genes seem to have tumor suppressor activities, with involvement of cell cycle inhibitors, regulating different pathways that can lead to tumor progression, disease aggressiveness, and DNA damage accumulation.
Emerging advances in fluorescence imaging and phototherapy of arthritis
Authors: Wang Xiaoxuan , Dai Jingying , Shao Cong , Goto Takashi , Dai Honglian
Published: December 2023

Arthritis is a chronic disease whose etiology is difficult to pinpoint, and the difficulty of arthritis detection and subsequent treatment causes enormous distress to patients. In recent years, thanks to advances in medicine and detection, a variety of treatment modalities for arthritis have emerged. The combination of emerging detection technologies with different anti‐inflammatory medications and even advances in surgical techniques have all played a positive role in the treatment of arthritis. In the present work, we have collected relevant literature on fluorescence (FL) imaging and phototherapy of arthritis in recent years, intending to reveal the advantages and potential application value of FL imaging and phototherapy for researchers. Meanwhile, due to the shortcomings of FL imaging and phototherapy in the diagnosis and treatment of arthritis, we advocate overcoming these difficulties in future research.
Deep learning approach for brain tumor classification using metaheuristic optimization with gene expression data
Authors: Joshi Amol Avinash , Aziz Rabia Musheer
Published: December 2023

This study addresses the critical challenge of accurately classifying brain tumors using artificial intelligence. Early detection is crucial, as untreated tumors can be fatal. Despite advances in AI, accurately classifying tumors remains a challenging task. To address this challenge, we propose a novel optimization approach called PSCS combined with deep learning for brain tumor classification. PSCS optimizes the classification process by improving Particle Swarm Optimization (PSO) exploitation using Cuckoo search (CS) algorithm. Next, classified gene expression data of brain tumor using Deep Learning (DL) to identify different groups or classes related to a particular tumor along with the PSCS optimization technique. The proposed optimization technique with DL achieves much better classification accuracy than other existing DL and Machine learning models with the different evaluation matrices such as Recall, Precision, F1‐Score, and confusion matrix. This research contributes to AI‐driven brain tumor diagnosis and classification, offering a promising solution for improved patient outcomes.
In ovo o,p′‐DDT exposure induces malformation of reproductive organs and alters the expression of genes controlling sexual differentiation in Japanese quail embryo
Authors: Win‐Shwe Tin‐Tin , Abe Natsuko , Sakiyama Akari , Suzuki Maho , Sano Kazuhiro , Kawashima Takaharu , Tsukahara Shinji
Published: December 2023

In ovo exposure to o,p′‐dichloro‐diphenyl‐trichloroethane (o,p′‐DDT) impairs reproduction by inducing malformation of the reproductive organs in birds, although the mechanism remains unclear. Here, we examined the effects of o,p′‐DDT on the development of the reproductive organs, the expression of genes controlling sexual differentiation, and the plasma concentrations of testosterone and estradiol in Japanese quail embryos. o,p′‐DDT‐containing sesame oil was injected into the yolk sac on Embryonic Day (E) 3 at a dose of 500, 2,000, or 8,000 μg per egg. On E15, the reproductive organs were observed; the gonads and Müllerian ducts (MDs) were sampled to measure the mRNA of steroidogenic enzymes, sex steroid receptors, anti‐Müllerian hormone (AMH), and AMH receptor 2 (AMHR2); blood samples were collected to assay plasma testosterone and estradiol levels; and the gonads were used for histological analysis. o,p′‐DDT dose‐dependently increased the prevalence of hypertrophic MDs in females and residual MDs in males. In female MDs, o,p′‐DDT dose‐dependently decreased estrogen receptor (ER) α, ERβ, and AMHR2 mRNA expression. o,p′‐DDT dose‐dependently induced left‐biased asymmetry of testis size, and ovary‐like tissue was found in the left testis after exposure to 8,000 μg per egg o,p′‐DDT, although asymmetric gene expression did not occur. o,p′‐DDT did not affect ovarian tissue but did decrease 17α‐hydroxylase/C17‐20 lyase mRNA expression and dose‐dependently increased ERβ mRNA expression. o,p′‐DDT decreased plasma testosterone concentrations in females. These findings suggest that o,p′‐DDT induces hypertrophy of the MDs and ovarian tissue formation in the left testis. Abnormal MD development may be linked to altered gene expression for sensing estrogens and AMH signals.
Biochemical characterization on muscle tissue of a novel biallelic ACO2 mutation in an infant with progressive encephalopathy
Authors: Ricci Federica Silvia , Stanga Serena , Mezzanotte Mariarosa , Marinaccio Cristina , D'Alessandro Rossella , Somà Alessandra , Sottemano Stefano , Conio Alessandra , Morana Giovanni , Spada Marco , Boido Marina , Mongini Tiziana E.
Published: December 2023

The ACO2 gene encodes the mitochondrial protein aconitate hydratase, which is responsible for catalyzing the interconversion of citrate into isocitrate in the tricarboxylic acid (TCA) cycle. Mitochondrial aconitase is expressed ubiquitously, and deficiencies in TCA‐cycle enzymes have been reported to cause various neurodegenerative diseases due to disruption of cellular energy metabolism and development of oxidative stress. We investigated a severe early infantile‐onset neurometabolic syndrome due to a homozygous novel variant in exon 13 of the ACO2 gene. The in vitro pathogenicity of this variant of unknown significance was demonstrated by the loss of both protein expression and its enzymatic activity on muscle tissue sample taken from the patient. The patient presented with progressive encephalopathy soon after birth, characterized by hypotonia, progressive severe muscle atrophy, and respiratory failure. Serial brain magnetic resonance imaging showed progressive abnormalities compatible with a metabolic disorder, possibly mitochondrial. Muscle biopsy disclosed moderate myopathic alterations and features consistent with a mitochondriopathy albeit nonspecific. The course was characterized by progressive worsening of the clinical and neurological picture, and the patient died at 5 months of age. This study provides the first report on the validation in muscle from human subjects regarding in vitro analysis for mitochondrial aconitase activity. To our knowledge, no prior reports have demonstrated a correlation of phenotypic and diagnostic characteristics with in vitro muscle enzymatic activity of mitochondrial aconitase in humans. In conclusion, this case further expands the genetic spectrum of ACO2 variants and defines a complex case of severe neonatal neurometabolic disorder.
Sexual dimorphism in the proventriculus of the buff‐tailed bumblebee Bombus terrestris (L. 1758) (Hymenoptera: Apidae)
Authors: Hüftlein Frederic , Ritschar Sven , Laforsch Christian
Published: December 2023

Research on eusocial bee species like Bombus terrestris is primarily focused on the worker caste, which is why their morphology and anatomy are already well described. This includes the alimentary tract, which is adapted for feeding on nectar and pollen. Located at the transition between crop and ventriculus is a highly specialised compartment, the proventriculus. In female workers of B. terrestris, the proventriculus is surrounded by muscles and consists of four anterior lips. A detailed description, however, is only provided for B. terrestis worker bees while studies on the proventriculus of the male reproductive caste are absent. Here, we provide a detailed analysis of the differences between the proventriculus of the B. terrestris males and females through morphometrics, histology and scanning electron microscopy imaging, and unravel a distinct sexual dimorphism. The male proventriculus is wider resulting in a greater volume than the female proventriculus. Histological analysis revealed 4 distinctive chambers of the male proventriculus, which are completely covered with hairs on the inside. In contrast, those chambers in the proventriculus of female B. terrestris, are only rudimentarily present forming only small pouches with hairs in the junctions between the proventricular folds inside the proventriculus. The morphological differences in the proventriculus may be based on different modi vivendi, as males do not return to the colony and fly longer distances. This and the synthesis of sperm and mating plug might require higher energy reserves, leading to the necessity of higher food storage capacities.
Emerging concerns of atypical hand foot and mouth disease caused by recombinant Coxsackievirus A6 variants in Henan, China
Authors: Chen Shouhang , Chen Yu , Ji Wangquan , Wang Fang , Zhang Xiaolong , Jin Yuefei , Liu Yufeng
Published: December 2023

An increasing number of studies have reported that atypical hand, foot, and mouth disease (HFMD) is becoming a new concern for children's health. At present, there is no official definition for atypical HFMD, but some studies have defined that it occurs at anatomic sites not listed in the definition of HFMD issued by the World Health Organization. Several pathogens have been reported to cause atypical HFMD, such as Coxsackievirus (CV)A6. As one of the most prevalent enteroviruses in the world, CVA6 seems to affect a wider range of children and causes more severe and prolonged illness than other enteroviruses. The early lesions of atypical HFMD are very similar to the clinical presentations of other diseases, such as eczema, which poses a challenge for clinicians aiming to identify and diagnose HFMD in a timely manner. Here, we report on six atypical HFMD patients caused by recombinant CVA6 variants, and the atypical manifestations include eczema coxsackium, large herpes, rice‐like red papules and herpes, purpuric rash, and onychomadesis, as well as and large red herpes on scalp, perianal, testicles, shoulders and neck, and other atypical eruption sites, hoping to draw the attention of other pediatricians. This study will provide scientific guidance for timely diagnosis of HFMD to prevent serious complications.
The prevalence of mpox and its association with sexual behavior among Chinese men who have sex with men in early August 2023
Authors: Du Min , Zheng Min , Liu Jue , Yang Guanghong , Yao Yongming , Qian Xiaohan , Yuan Zhi , Ma Lin , Tao Rui , Zhu Zhilin , Zhou Feng , Dai Siqi , Yang Jie , Liu Min
Published: December 2023

Study investigating mpox infection and its association with sexual behavior among men who have sex with men (MSM) in China was lacking. This observational survey aimed to provide evidence on detail characteristics of mpox cases and sexual behavior, then analyze their relationship among MSM in China to help formulate prevention and control policies. An anonymous cross‐sectional study was conducted in 27 MSM social organizations across 21 provinces, municipalities, and autonomous regions from July 31 to August 4, 2023. A safe sexual behavior index was constructed based on three risky sexual behaviors in the last month, including condomless anal intercourse, commercial sex and group sex. High safe sexual behavior indicated that the participant engaged in none of the three, and low safe sexual behavior indicated that they engaged in all three behaviors; otherwise, moderate safe sexual behavior was indicated. Among 7538 MSM, the prevalence of mpox was 0.73% (55/7538). The proportion of high safe sexual behavior was 79.64% (6003/7538). The crude prevalence of mpox was lower in the high safe sexual behavior group (0.35%, 21/6003), compared with the low (12.12%, 8/66) and moderate safe (1.78%, 26/1469) sexual behavior group. In the multivariable‐adjusted analysis, after adjusting for all covariates, compared with low safe sexual behavior group, moderate safe sexual behavior group (aOR = 0.21; 95% CI = 0.08, 0.54) and high safe sexual behavior group (aOR = 0.04; 95% CI = 0.02, 0.12) both had lower risk of mpox. Of three sexual behaviors, MSM who reported no commercial sex had the lowest risk of mpox (aOR = 0.23; 95% CI = 0.13, 0.41), compared with those who reported commercial sex in the last month. The other two safe sexual behaviors both were associated with lower risk of mpox (no group sex vs. group sex: aOR = 0.15; 95% CI = 0.08, 0.28; no condomless anal intercourse vs. condomless anal intercourse: aOR = 0.23; 95% CI = 0.13, 0.41). The prevalence of mpox virus infection was nearly 1% among MSM in China. Strengthening mpox surveillance, emphasizing safe sexual behavior in health education are essential for the control of mpox among MSM in China.
Fatigue in pediatric inflammatory bowel diseases: A systematic review and a single center experience
Authors: Turner Shira T. , Focht Gili , Orlanski‐Meyer Esther , Lev‐Tzion Raffi , Ledder Oren , Yogev Dotan , Assa Amit , Shaoul Ron , Crowely Eileen , Otley Anthony , Griffiths Anne M. , Turner Dan
Published: December 2023

Objectives

We aimed to review the literature on fatigue in pediatric inflammatory bowel diseases (PIBD), to explore how it is measured, and approximate its rate in an inception pediatric cohort.

Methods

Studies on fatigue were systematically reviewed and selected by two authors. Next, we retrieved the two fatigue‐related questions of the IMPACT‐III questionnaire at 4 and 12 months after diagnosis from a prospectively maintained cohort of PIBD patients, each scoring 0‐100 (lower scores imply more fatigue), and 44 healthy controls.

Results

The systematic review identified 14 studies reporting fatigue in children, of which nine had fatigue as the primary outcome and only two provided rates of fatigue. No standalone index was identified for measuring fatigue specifically for PIBD. Of 80 children included in the inception cohort, 62 (78%) scored an average of ≤75 on the two IMPACT‐III questions (approximating at least mild fatigue), 26 (33%) scored ≤50 (at least moderate fatigue) and nine (11%) scored ≤25 (severe fatigue). In comparison, only four (9%) healthy children scored at least moderate fatigue (p = 0.007). Fatigue rates at 12 months were only slightly and nonsignificantly lower. Fatigue of any severity was reported in 92% children with active disease versus 63% of those in clinical remission (p = 0.01).

Conclusion

Literature reporting on fatigue in PIBD is scarce, and no PIBD‐specific tool is available to measure fatigue. In our cohort, fatigue‐related questions were frequently scored low in children with IBD, mainly among children with active disease but also during clinical remission.
Intraperitoneal insufflation of carbon dioxide rescues intestinal damage in an experimental murine model of colitis
Authors: Haffreingue Aurore , Tourneur‐Marsille Julien , Montalva Louise , Berrebi Dominique , Ogier‐Denis Éric , Bonnard Arnaud
Published: December 2023

Objectives

Necrotizing enterocolitis (NEC) is a severe neonatal surgical condition, associated with a prolonged pro‐inflammatory state, leading to high mortality and morbidity rates. Carbon dioxide (CO2) insufflation during laparoscopy may have an anti‐inflammatory effect. We aimed to evaluate the effects of CO2‐insufflation on experimental colitis.

Methods

Acute colitis was induced in 6‐week‐old Balb/c mice by the administration of 2%‐dextran sulfate‐sodium (DSS) during 7 days (n = 45). On Day 4, two groups received intraperitoneal insufflation (duration: 30 mn, pressure: 5 mmHg) of CO2 (“DSS+CO2”) or air (“DSS+air”). A group received no insufflation (“DSS”). Groups were compared for clinical severity using the disease activity index (DAI—body weight loss, stool consistency, and bleeding), histological severity (histopathological activity index, colon length, and ulcerations), colonic mucosecretion, and inflammation.

Results

DAI was significantly decreased in DSS+CO2 group, compared to DSS (p < 0.0001) or DSS+air (p < 0.0001) groups. Colon length was increased in DSS+CO2 treated mice compared to DSS (p = 0.0002). The histopathological activity index was lower in DSS+CO2 (vs. DSS, p = 0.0059/vs. DSS+air, p = 0.0389), with decreased ulcerations (3.77 vs. 10.7, p = 0.0306), and persistent mucosecretion with increased mucin‐secreting cells.

Conclusions

CO2‐insufflation attenuates DSS‐induced colitis and improves both clinical and histological scores. Laparoscopy with CO2 insufflation represents a therapeutic anti‐inflammatory strategy for NEC.
Health‐related quality of life in children with coeliac disease and in their families: A long‐term follow‐up study
Authors: Crocco Marco , Malerba Federica , Calvi Angela , Zampatti Noemi , Gandullia Paolo , Madeo Annalisa , Tappino Barbara , Proietti Stefania , Bonassi Stefano
Published: December 2023

Objectives

The aim of the study was to assess long‐term health‐related quality of life (HRQoL) in children and adolescents with coeliac disease (CD), and their parents.

Methods

We re‐evaluated prospectively the HRQoL and clinical characteristics of 80 families, assessed 5 years earlier, using a disease‐specific questionnaire, the CD Dutch Questionnaire (CDDUX), and a generic questionnaire, the Paediatric Quality of Life Inventory (PedsQL).

Results

After a 10‐year follow‐up, there was no significant change in the total CDDUX and PedsQL scores in children and their parents when compared to the evaluation conducted 5 years earlier. The total CDDUX score reflected a neutral QoL, while for the generic PedsQL was good‐very good. The only significant decrease after 5 years was the PedsQL subdomain Emotional functioning. Patients who admitted voluntarily eating gluten reported lower score in CDDUX Diet. Lower scores in subdomain “Physical functioning” (PedsQL) were reported in patients with positivity of TTG or associated diseases.

Conclusions

The CDDUX score indicated a consistently stable and neutral QoL perception among coeliac patients and caregivers, even after 10‐year postdiagnosis, suggesting minimal fluctuations in the impact of CD on disease‐specific health domains over time. Furthermore, the consistently good PedsQL score could be a reflection of the resilience of coeliac families in coping with this chronic condition. Gluten‐free diet compliance was confirmed to be determinant of HRQoL in the long term. The study confirms the importance of extending surveillance on these patients, possibly using different questionnaires, to assess QoL from different perspectives.
Intestinal dysbiosis and inflammation in children with repaired esophageal atresia
Authors: Traini Isabelle , Chan Sin Y. , Menzies Jessica , Hughes Jennifer , Coffey Michael J. , McKay Isabelle R. , Ooi Chee Y. , Leach Steven T. , Krishnan Usha
Published: December 2023

Objectives

This study aims to compare the intestinal microbiota and intestinal inflammation of children with esophageal atresia (EA) to matched healthy controls, and to investigate the relationship between these factors and clinical outcomes.

Methods

A cross‐sectional study of 35 children with EA and 35 matched healthy controls (HC) from a single tertiary pediatric hospital in Australia was conducted. Demographic and dietary data were collected using surveys. Stool samples were analyzed using 16S rRNA sequencing, and fecal calprotectin measurements were used to measure intestinal inflammation. Comparisons were made between the groups, and correlations between the microbiota and clinical factors were investigated in the EA cohort.

Results

Compared to HC, children with EA had similar alpha diversity, but beta diversity analysis revealed clustering of EA and HC cohorts. Children with EA had a significantly higher relative abundance of the order Lactobacillales, and a lower abundance of the genus uncultured Bacteroidales S24‐7. Fecal calprotectin was significantly higher in children with EA compared to HC. In the EA cohort, children taking proton pump inhibitors (PPI's) had lower alpha diversity and higher calprotectin levels compared to those not taking PPI's. There was a negative correlation between calprotectin and length/height‐for‐age z scores, and children with higher calprotectin levels had a greater burden of gastrointestinal symptoms.

Conclusions

Children with EA have an altered intestinal microbiota compared to HC, which is likely related to PPI use, and may be impacting on growth and quality of life. It is important to rationalize PPI use in this cohort.
The contributions of clinical disease activity, functional disability, and illness intrusiveness to depressive symptoms in pediatric inflammatory bowel disease
Authors: Edwards Clayton S. , Baudino Marissa N. , Roberts Caroline M. , Basile Nathan L. , Dattilo Taylor M. , Gamwell Kaitlyn L. , Jacobs Noel J. , Edwards Desti S. , Tung Jeanne , Parker Colton V. , Chaney John M.
Published: December 2023

Background

Clinical disease activity associated with inflammatory bowel disease (IBD) can place physical limitations on youths' activities of daily living. In turn, functional limitations potentially contribute to youths' heightened experience of IBD‐induced intrusions on a wide range of routine and valued activities (i.e., illness intrusiveness), which can increase their risk for depressive symptoms. The present study examined the contributions of clinical disease activity, functional disability, and illness intrusiveness to depressive symptoms in youth with IBD.

Methods

Youth (N = 180) completed the Functional Disability Inventory (FDI), Illness Intrusiveness Scale‐Child (IIS‐C), and Children's Depression Inventory‐2 (CDI‐2). Physicians completed the Physicians Global Assessment of disease activity (PGA).

Results

Results revealed a mediating effect for functional disability in the association between disease activity and depressive symptoms (PGA → FDI → CDI‐2); illness intrusiveness mediated the association between functional disability and depressive symptoms (i.e., FDI → IIS‐C → CDI‐2). Serial mediation revealed that clinical disease activity conferred an indirect effect on youth depressive symptoms through the sequential effects of functional disability and illness intrusiveness (i.e., PGA → FDI → IIS‐C → CDI‐2).

Conclusions

Taken together, these findings indicate that youth who encounter more physical limitations as a function of clinical disease activity are more likely to experience an amplified sense of IBD‐related intrusions on their ability to participate in meaningful activities. In turn, heightened illness intrusiveness increases the likelihood of depressive symptoms. Clinical interventions that help youth maintain adequate functional ability in the face of IBD disease activity and encourage involvement in positively valued activities could decrease the negative impact of IBD on youths' emotional adjustment.
Clinical presentation and outcomes of Helicobacter heilmannii gastritis in children in the New England region of the United States
Authors: Chang Denis , Gluchowski Nina L. , Abu Alfa Amer K. , Goldsmith Jeffrey D. , Redston Mark , Bonilla Silvana
Published: December 2023

Objective

To describe the clinical, endoscopic, histologic, and treatment outcomes of Helicobacter heilmannii (H. heilmannii) associated gastritis in children in the New England region of the United States.

Methods

Retrospective study of children (1–18 years) with H. heilmannii identified on gastric mucosal biopsies from two pediatric centers over a 21‐year period, January 2000–December 2021. Cases were identified by querying pathology databases at each institution. Demographic and clinical data were obtained from the medical record. Endoscopic and histologic findings were extracted from endoscopy and pathology reports, respectively.

Results

Thirty‐eight children were diagnosed with H. heilmannii‐associated gastritis during the study period. The mean age at diagnosis was 10.1 ± 5.3 years, and 25/38 (66%) cases were male. Abdominal pain (32%) and nausea with or without vomiting (26%) were the most common symptoms. Thirty‐two children (84%) had endoscopic findings including gastric nodularity (55%) and erythema (26%). All children had histologic signs of chronic gastritis, including those with normal endoscopic exams. Antibiotic regimens used for treating Helicobacter pylori were frequently prescribed. Of the 17 children who underwent a follow‐up endoscopy (range 2–68 months), 15 (88%) did not have H. heilmannii identified on gastric biopsies.

Conclusion

H. heilmannii was an infrequent but potential cause of epigastric abdominal pain and nausea in our cohort of New England children. While morphologically distinct from H. pylori, the bacteria can result in similar endoscopic and histologic findings of nodularity and chronic gastritis, respectively. The rate of eradication, as assessed by histology following treatment with H. pylori therapies, was below the 90% recommended goal for antimicrobial therapies.
Can vulvar edema be the presenting sign of Crohn's disease? A case series
Authors: Rios Melendez Sandra , Majluta Aldo , Medina Annette , Restrepo Ricardo , Felipez Lina M.
Published: December 2023

Vulvar involvement as an extraintestinal manifestation of Crohn's disease (CD) is a challenging diagnosis considering that vaginal findings may precede gastrointestinal symptoms. The aim of this study is to describe the clinical presentation, radiological findings, and treatment of vulvar Crohn's disease (VCD). We reviewed the time from initial presentation to diagnosis, presenting symptoms, radiological findings, gastrointestinal Crohn's disease Paris classification, and treatment response of five female pediatric patients. All the patients had radiological findings of vulvar inflammation on magnetic resonance imaging. Vaginal symptoms preceded gastrointestinal disease in two of the patients, which correlated with a delay in diagnosis. All patients had active disease on colonoscopy, with three of them having significant colorectal inflammation. Four of the patients were treated with infliximab, while one patient received ustekinumab with a resolution of their symptoms. In conclusion, VCD can precede gastrointestinal symptoms and is easily miss‐diagnosed, leading to a delayed Crohn's disease diagnosis and treatment.
Music therapy and weight gain in preterm infants: Secondary analysis of the randomized controlled LongSTEP trial
Authors: Bauer‐Rusek Sofia , Shalit Shachar , Yakobson Dana , Levkovitz Orly , Ghetti Claire , Gold Christian , Stordal Andreas Størksen , Arnon Shmuel
Published: December 2023

Objectives

This study assessed the association between MT and weight gain among preterm infants hospitalized in Neonatal Intensive Care Units.

Methods

Data collected during the international, randomized, Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and their Caregivers (LongSTEP) study were compared between the MT group and the standard care (SC) group. Weights were recorded at birth, enrollment, and discharge. Weight percentiles, Z‐scores, weight gain velocity, and extrauterine growth restriction (EUGR) were calculated.

Results

Among 201 preterm infants included, no significant differences in weight parameters (weight, weight percentiles, weight Z‐scores; all p ≥ 0.23) were found between the MT group (n = 104) and the SC (n = 97) group at birth, enrollment, or discharge. No statistical differences in EUGR represented by change in Z‐scores from birth to discharge were recorded between MT and SC (0.8 vs. 0.7). Among perinatal parameters, younger gestational age (p = 0.005) and male sex (p = 0.012) were associated with increased risk of EUGR at discharge. Antenatal steroid treatment, systemic infection, bronchopulmonary dysplasia, neurological morbidities, retinopathy of prematurity, necrotizing enterocolitis, parental factors (amount of skin‐to‐skin care, bonding, anxiety, and depression questionnaire scores), and type of enteral nutrition did not significantly influence weight gain parameters (all p > 0.05).

Conclusions

In the LongSTEP study, MT for preterm infants and families was not associated with better weight parameters compared to the SC group. The degree of prematurity remains the main risk factor for unfavorable weight parameters.
Food protein‐induced allergic proctocolitis in infants is associated with low serum levels of macrophage inflammatory protein‐3a
Authors: Koksal Burcu Tahire , Barıs Zeren , Sencelikel Tugce , Ozcay Figen , Ozbek Ozlem Yılmaz
Published: December 2023

Background

Food protein‐induced allergic proctocolitis (FPIAP) is a nonimmunoglobulin (IgE)‐mediated food hypersensitivity and the exact mechanisms that cause FPIAP are unknown. Chemokines play crucial roles in the development of allergic diseases.

Objective

To examine serum levels of a group of chemokines in infants with FPIAP.

Methods

In 67 infants with FPIAP and 65 healthy infants, we measured serum levels of mucosa‐associated epithelial chemokine (MEC/CCL28), thymus‐expressed chemokine (TECK/CCL25), CX3CL1 and macrophage inflammatory protein (MIP)‐3a/CCL20.

Results

Infants with FPIAP had a lower median value of MIP3a/CCL20 than healthy infants [0.7 (0–222) vs. 4 (0–249) pg/mL, respectively] (p < 0.001). Infants with MIP3a/CCL20 levels ≤0.95 pg/mL have 13.93 times more risk of developing FPIAP than infants with MIP3a/CCL20 levels >0.95 pg/mL. Serum MEC/CCL28, TECK/CCL25, and CX3CL1 levels were similar between the infants with FPIAP and the control group.

Conclusion

MIP3a/CCL20 serum levels were reduced in infants with FPIAP compared with healthy controls. Whether this finding has a role in pathogenesis remains to be determined.
Evaluation of acute terminal ileitis in children before and during the COVID‐19 pandemic
Authors: Koyuncu Hilal , Bükülmez Ayşegül , Güngör Ayşe , Sarıkaya Yasin
Published: December 2023

Objectives

The aim of this study was to examine the clinical features of acute terminal ileitis in children and evaluate its rate before and during the COVID‐19 pandemic.

Methods

This retrospective study was performed in our pediatric emergency department between 2018 and 2022. The records of 5363 patients who required abdominal imaging due to acute abdomen were analyzed, and 143 patients with terminal ileitis were included. The rate and etiological causes were compared during and before the COVID‐19 pandemic.

Results

The rate of acute terminal ileitis has increased over the years. The fastest increase was in 2021, when the COVID‐19 pandemic was experienced. While 59 (41.2%) patients showed acute nonspecific ileitis, the most common etiologic cause that could be identified was acute gastroenteritis. It was determined that multisystem inflammatory syndrome in children was among the causes of ileitis after the COVID‐19 pandemic and was one of the top three causes.

Conclusions

Acute terminal ileitis, which has many etiologies, is one of the rare radiological findings in acute abdominal pain. Examination and laboratory findings are not specific. Guidelines are needed for the investigation of the underlying etiology of acute terminal ileitis in children. The incidence of acute terminal ileitis is increasing, and the increase has been found to be faster after the COVID‐19 pandemic.
Factors associated with D‐lactic acidosis in pediatric intestinal failure: A case‐control study
Authors: Nes Emily , Knell Jamie , Keefe Gregory , Culbreath Katherine , Han Sam M. , McGivney Megan , Staffa Steven J. , Modi Biren P. , Carey Alexandra N. , Jaksic Tom , Duggan Christopher P.
Published: December 2023

Background

D‐lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D‐lactate which can lead to metabolic acidosis and neurologic symptoms.

Methods

A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D‐lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L.

Results

Of forty‐six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007).

Conclusion

DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.
Midodrine reduces new‐onset acute kidney injury and hyponatremia in children with cirrhosis and ascites awaiting liver transplantation: Results from an open‐label RCT
Authors: Ashritha A. , Lal Bikrant B. , Khanna Rajeev , Sood Vikrant , Sood Arun K. , Alam Seema
Published: December 2023

Objectives

Midodrine, an oral α‐1‐adrenergic receptor agonist, counters arterial hypovolemia and reduces complications in adult patients with cirrhosis. This randomized controlled trial (RCT) aimed to assess the efficacy and safety of midodrine in preventing complications and improving survival in children with cirrhosis and ascites who are awaiting liver transplantation (LT).

Methods

This open‐label RCT conducted from January 2022 to May 2023 included children under 18 years with cirrhosis and ascites. Patients were randomized to receive either midodrine plus standard medical therapies (SMTs) or SMT alone. The primary outcome measure was the incidence of cirrhosis‐related complications within 6 months.

Results

Thirty‐five subjects were enrolled and randomized. Patients in the midodrine arm had a lower incidence of new‐onset acute kidney injury (AKI) compared with the SMT arm (11.1% vs. 41.2%). Patients in the midodrine arm showed a decline in serum creatinine and improvement in glomerular filtration rate, whereas no changes were observed in the SMT arm. There was a lower incidence of new‐onset hyponatremia in the midodrine arm (20% vs. 56%). Midodrine led to reduction in plasma rennin activity (PRA) and improvement in systemic hemodynamics. There was no difference in the rate of resolution of ascites, recurrence of ascites, requirement of therapeutic paracentesis, cumulative albumin infusion requirement, episodes of spontaneous bacterial peritonitis, and hepatic encephalopathy between the two arms.

Conclusion

Midodrine, when added to SMT, was effective in reducing the incidence of new‐onset AKI and hyponatremia in pediatric cirrhotics awaiting LT. It also improved systemic hemodynamics and showed a trend towards reducing PRA.
Genotypes predisposing for celiac disease and autoimmune diabetes and risk of infections in early childhood
Authors: Størdal Ketil , Tapia German , Lund‐Blix Nicolai A. , Stene Lars C.
Published: December 2023

Objectives

Infections in early childhood have been associated with risk of celiac disease (CD) and type 1 diabetes (T1D). We investigated whether this is driven by susceptibility genes for autoimmune disease by comparing infection frequency by genetic susceptibility variants for CD or T1D.

Methods

We genotyped 373 controls and 384 children who developed CD or T1D in the population‐based Norwegian Mother, Father and Child Cohort study (MoBa) study for human leukocyte antigen (HLA)‐DQ, FUT2, SH2B3, and PTPN22, and calculated a weighted non‐HLA genetic risk score (GRS) for CD and T1D based on over 40 SNPs. Parents reported infections in questionnaires when children were 6 and 18 months old. We used negative binomial regression to estimate incidence rate ratio (IRR) for infections by genotype.

Results

HLA genotypes for CD and T1D or non‐HLA GRS for T1D were not associated with infections. The non‐HLA GRS for CD was associated with a nonsignificantly lower frequency of infections (aIRR: 0.95, 95% CI: 0.87−1.03 per weighted allele score), and significantly so when restricting to healthy controls (aIRR: 0.89, 0.81−0.99). Participants homozygous for rs601338(A;A) at FUT2, often referred to as nonsecretors, had a nonsignificantly lower risk of infections (aIRR: 0.91, 95% CI: 0.83−1.01). SH2B3 and PTPN22 genotypes were not associated with infections. The association between infections and risk of CD (OR: 1.15 per five infections) was strengthened after adjustment for HLA genotype and non‐HLA GRS (OR: 1.24).

Conclusions

HLA variants and non‐HLA GRS conferring susceptibility for CD were not associated with increased risk of infections in early childhood and is unlikely to drive the observed association between infections and risk of CD or T1D in many studies.
Rheology of novel photosensitive viscoelastic trimeric cationic surfactant/trans‐ortho‐methoxycinnamic acid micellar solutions
Authors: He Jinlan , Han Xiaoyang , Fang Bo , Wu Huinan , Xu Wenting , Xin Hui , Yu Luyao , Li Kejing
Published: December 2023

Photosensitive micellar solutions of mixed surfactants and photosensitive additives have gained much interest. However, there are no reports on photosensitive micellar solutions containing trimeric cationic surfactant. In the study, novel photosensitive viscoelastic micellar solutions consisting of trimeric cationic surfactant (TEC) and trans‐ortho‐methoxycinnamic acid (trans‐OMCA) were investigated. This study utilized rheology, UV–vis spectroscopy, and cryo‐TEM to investigate the photo‐responsive behavior and mechanism of the TEC/trans‐OMCA micellar solutions. Rheological studies revealed that the concentration of TEC and trans‐OMCA, as well as temperature, significantly affected the viscoelastic properties of the micellar solutions. Furthermore, the Carreau and Maxwell models might be used to characterize the flow curves and viscoelasticity of the micellar solutions, respectively. Notably, TEC/trans‐OMCA micellar solutions exhibited excellent light‐induced thinning characteristic, with the optimal performance at a mass ratio of φ = 0.5. After UV irradiation, the zero‐shear viscosity of TEC/trans‐OMCA (0.6/0.3 wt%) micellar solution was reduced by 352 times, while the viscoelasticity and the area of hysteresis loops were significantly reduced. This drastic change in the rheological characteristics of the micellar solutions could be attributed to the photoisomerization of trans‐OMCA and the resulting changes in the internal microstructure of the solutions. Moreover, the viscosity of the micellar solutions diminished as the temperature increased, with the remaining viscosity of the TEC/trans‐OMCA (1.0/0.5 wt%) micellar solution at 36.4 mPa s at 95°C. This study expands on the potential utilization of oligomeric surfactants in the construction of photorheological viscoelastic fluids.