bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal Insights into Glioma Oncostream Dynamics: Unraveling Formation, Stability, and Disassembly Pathways
Authors: Faisal Syed M. , Clewner Jarred E. , Stack Brooklyn , Varela Maria L. , Comba Andrea , Abbud Grace , Motsch Sebastien , Castro Maria G. , Lowenstein Pedro R.
Published: February 2024

Glioblastoma (GBM) remains a challenge in Neuro‐oncology, with a poor prognosis showing only a 5% survival rate beyond two years. This is primarily due to its aggressiveness and intra‐tumoral heterogeneity, which limits complete surgical resection and reduces the efficacy of existing treatments. The existence of oncostreams—neuropathological structures comprising aligned spindle‐like cells from both tumor and non‐tumor origins‐ is discovered earlier. Oncostreams are closely linked to glioma aggressiveness and facilitate the spread into adjacent healthy brain tissue. A unique molecular signature intrinsic to oncostreams, with overexpression of key genes (i.e., COL1A1, ACTA2) that drive the tumor's mesenchymal transition and malignancy is also identified. Pre‐clinical studies on genetically engineered mouse models demonstrated that COL1A1 inhibition disrupts oncostreams, modifies TME, reduces mesenchymal gene expression, and extends survival. An in vitro model using GFP+ NPA cells to investigate how various treatments affect oncostream dynamics is developed. Analysis showed that factors such as cell density, morphology, neurotransmitter agonists, calcium chelators, and cytoskeleton‐targeting drugs influence oncostream formation. This data illuminate the patterns of glioma migration and suggest anti‐invasion strategies that can improve GBM patient outcomes when combined with traditional therapies. This work highlights the potential of targeting oncostreams to control glioma invasion and enhance treatment efficacy.
Preparation of Distant Quantum Entanglement and One‐way Quantum Steering in Hybrid Cavity‐Magnonics‐and‐Cavity‐Optomechanical Systems
Authors: Wan Qin‐Min , Lin Yue‐Han , Lin Ya‐Qin , Cong Long‐Jiang , Yang Rong‐Can , Liu Hong‐Yu
Published: February 2024

A hybrid system that combines cavity magnonics and cavity optomechanics is proposed to facilitate the generation of long‐distance entanglement and enable one‐way steering between magnons and phonons. This configuration involves two directly coupled cavities, with one interacting with magnons and the other coupling with a mechanical oscillator (i.e., phonons). By driving the microwave cavity with a weak squeezed vacuum field generated by a flux‐driven Josephson parametric amplifier, entanglement and one‐way steering can be further enhanced. Moreover, the results demonstrate that magnon–phonon entanglement and one‐way quantum steering exhibit robustness against temperature variations, which has significant implications for quantum information processing and storage.
Advanced Functionalized Nanoclusters (Cu, Ag, and Au) as Effective Catalyst for Organic Transformation Reactions
Authors: Kumar Parveen , Nemiwal Meena
Published: February 2024

A considerable amount of research has been carried out in recent years on synthesizing metal nanoclusters (NCs), which have wide applications in the field of optical materials with non‐linear properties, bio‐sensing, and catalysis. Aside from being structurally accurate, the atomically precise NCs possess well‐defined compositions due to significant tailoring, both at the surface and the core, for certain functionalities. To illustrate the importance of atomically precise metal NCs for catalytic processes, this review emphasizes 1) the recent work on Cu, Ag, and Au NCs with their synthesis, 2) the parameters affecting the activity and selectivity of NCs catalysis, and 3) the discussion on the catalytic potential of these metal NCs. Additionally, metal NCs will facilitate the design of extremely active and selective catalysts for significant reactions by elucidating catalytic mechanisms at the atomic and molecular levels. Future advancements in the science of catalysis are expected to come from the potential to design NCs catalysts at the atomic level.
Modellbasierte Entwicklung und Umsetzung der digitalen Bauwerksakte
Authors: Hindersmann Iris , Haferkamp David , Probst Rebecca , Krenz Lisa‐Marie , Nieborowski Sonja , Bednorz Jennifer
Published: February 2024

Der Einsatz von BIM im Brückenbau ist aktuell noch überwiegend auf die Phasen Planen und Bauen beschränkt, aber insbesondere für den Betrieb von Bauwerken kann BIM einen großen Mehrwert erzielen. Grundlage für die Anwendung der BIM‐Methode in der Lebenszyklusphase Betrieb ist die Überleitung der relevanten Informationen aus den Lebenszyklusphasen Planen und Bauen in die Lebenszyklusphase Betrieb. Die Erstellung einer modellbasierten digitalen Bauwerksakte während der Leistungsphase 8 ermöglicht die digitale Übergabe und Weiterverwendung der relevanten Informationen für den Betrieb. Der Beitrag ordnet die Erstellung und Nutzung modellbasierter digitaler Bauwerksakten sowohl in den wissenschaftlichen Kontext als auch in die aktuelle Arbeitsmethode mit analoger Schlussrechnungs‐ und Bauwerksakte ein. Darüber hinaus beinhaltet er die praktische Umsetzung an einem konkreten Projekt. Weiterhin wird der Bezug zu den standardisierten Anwendungsfällen 190 „Projekt‐ und Bauwerksdokumentation“ und 200 „Nutzung für Betrieb und Erhaltung“ dargestellt. Die Umsetzung der modellbasierten digitalen Bauwerksakte wird am Beispiel des Autobahndreiecks Köln‐Heumar demonstriert. Hierbei wird auf die Ziele und Grundlagen, welche mit dem Einsatz von BIM verbunden sind, die Projektentwicklung und die Hintergründe eingangen. Die Umsetzung und Übergabe der modellbasierten digitalen Bauwerksakte wird für das Praxisbeispiel umfangreich beschrieben.
Sub‐1 nm Nanomaterials Applied in Energy Storage
Authors: Yuan Guobao , Liu Junli , Zhang Yu
Published: February 2024

Sub‐1 nm nanomaterials (SNMs) present rapid electrons/ions transport and unique polymer‐analogue properties due to their ultrahigh specific surface area and nearly 100 % surface atomic exposure, which are very promising in the application of energy storage devices. However, there still lack of relative review about the SNMs applied in energy storage until now. This review focuses on the structural advantages of SNMs and their synthesis methods, and then discusses latest advances of employing SNMs for advanced battery systems. The superior functions of SNMs are emphasized for designing every single component in batteries, including electrode materials, separators and electrolytes, greatly improving the performance of batteries. Finally, the current challenges and future research directions of SNMs are proposed, aiming to provide a new insight into the design and manufacture of SNMs for the further development of high‐performance energy storage devices.
Peak occipital alpha frequency mediates the relationship between sporting expertise and multiple object tracking performance
Authors: Mackenzie Andrew K. , Baker Joshua , Daly Rosie C. , Howard Christina J.
Published: February 2024

Background

Multiple object tracking (MOT) is often used as a lab‐based paradigm for investigating goal‐driven attention as an indicator for “real‐world” attention in tasks such as sport. When exploring MOT performance in the context of sporting expertise, we typically observe that individuals with sporting expertise outperform non‐sporting individuals. There are a number of general explanations for performance differences such as cognitive transfer effects; however, the potential neurophysiological mechanisms explaining the relationship between sporting expertise and performance differences in MOT are not clear. Based on the role occipital alpha (posterior oscillations usually around 8–12 Hz) has been shown to have in visuospatial attention, the aim of this study was to examine whether individual differences in occipital peak alpha frequency (PAF) mediate the relationship between sporting expertise and performance in two object tracking tasks: a standard MOT task and a visuomotor‐controlled object tracking task (multiple object avoidance [MOA]).

Method

Using electroencephalography (EEG), participants, who either played sport competitively or did not, had their posterior PAF measured at rest (eyes closed) across a 2‐min window. They completed the two tasks separately from the resting EEG measures.

Results

Those who engaged in sport performed better in the MOT and MOA tasks and had higher PAF. Higher PAF predicted superior MOT performance. The mediation analysis revealed that sporting individuals had significantly higher PAF, and this was in turn related to superior MOT performance.

Conclusions

It is suggested that PAF is a possible neurophysiological mediating mechanism as to why sporting individuals have superior MOT performance. There was no evidence that PAF mediated the relationship between sporting expertise and visuomotor MOA performance. Explanations and implications are discussed, and unanswered questions are proposed.
Development of an Enzyme Cascade System for the Synthesis of Enantiomerically Pure D‐Amino Acids Utilizing Ancestral L‐Amino Acid Oxidase
Authors: Araseki Hayato , Sugishima Narumi , Chisuga Taichi , Nakano Shogo
Published: February 2024

Enantiomerically pure D‐amino acids hold significant potential as precursors for synthesizing various fine chemicals, including peptide‐based drugs and other pharmaceuticals. This study focuses on establishing an enzymatic cascade system capable of converting various L‐amino acids into their D‐isomers. The system integrates four enzymes: ancestral L‐amino acid oxidase (AncLAAO‐N4), D‐amino acid dehydrogenase (DAADH), D‐glucose dehydrogenase (GDH), and catalase. AncLAAO‐N4 initiates the process by converting L‐amino acids to corresponding keto acids, which are then stereo‐selectively aminated to D‐amino acids by DAADH using NADPH and NH4Cl. Concurrently, any generated H2O2 is decomposed into O2 and H2O by catalase, while GDH regenerates NADPH from D‐glucose. Optimization of reaction conditions and substrate concentrations enabled the successful synthesis of five D‐amino acids, including a D‐Phe derivative, three D‐Trp derivatives, and D‐phenylglycine, all with high enantiopurity (>99 % ee) at a preparative scale (>100 mg). This system demonstrates a versatile approach for producing a diverse array of D‐amino acids.
Investigating Recurrent Matere Bonds in Pertechnetate Compounds
Authors: Grödler Dennis , Burguera Sergi , Frontera Antonio , Strub Erik
Published: February 2024

In this manuscript we evaluate the X‐ray structure of five new pertechnetate derivatives of general formula [M(H2O)4(TcO4)2], M=Mg, Co, Ni, Cu, Zn (compounds 1–5) and one perrhenate compound Zn(H2O)4(ReO4)2 (6). In these complexes the metal center exhibits an octahedral coordination with the pertechnetate units as axial ligands. All compounds exhibit the formation of directional Tc⋅⋅⋅O Matere bonds (MaBs) that propagate the [M(H2O)4(TcO4)2], into 1D supramolecular polymers in the solid state. Such 1D polymers are linked, generating 2D layers, by combining additional MaBs and hydrogen bonds (HBs). Such concurrent motifs have been analyzed theoretically, suggesting the noncovalent σ‐hole nature of the MaBs. The interaction energies range from weak (~ −2 kcal/mol) for the MaBs to strong (~ −30 kcal/mol) for the MaB+HB assemblies, where HB dominates. In case of M=Zn, the corresponding perrhenate Zn(H2O)4(ReO4)2 complex, has been also synthesized for comparison purposes, resulting in the formation of an isostructural X‐ray structure, corroborating the structure‐directing role of Matere bonds.
Targeting of G‐quadruplex DNA with 99mTc(I)/Re(I) Tricarbonyl Complexes Carrying Pyridostatin Derivatives
Authors: Palma Elisa , Içhedef Cigdem , Fernandes Célia , Belchior Ana , Raposinho Paula , Gano Lurdes , Miranda André , Moreira David , Lourenço Pedro , Cruz Carla , Pires Ana Salomé , Botelho Maria Filomena , Paulo António
Published: February 2024

The main goal of this work was to elucidate the potential relevance of (radio)metal chelates of 99mTc and Re targeting G‐quadruplex structures for the design of new tools for cancer theranostics. 99mTc provides the complexes with the ability to perform single‐photon‐emission computed tomography imaging studies, while the Re complexes should act as anticancer agents upon interaction with specific G4 DNA or RNA structures present in tumor tissues. Towards this goal, we have developed isostructural 99mTc(I) and Re(I) tricarbonyl complexes anchored by a pyrazolyl‐diamine (Pz) chelator carrying a pendant pyridostatin (PDS) fragment as the G4‐binding motif. The interaction of the PDF‐Pz‐Re (8) complex with different G4‐forming oligonucleotides was studied by circular dichroism, fluorescence spectroscopy and FRET‐melting assays. The results showed that the Re complex retained the ability to bind and stabilize G4‐structures from different DNA or RNA sequences, namely those present on the SRC proto‐oncogene and telomeric RNA (TERRA sequence). PDF‐Pz‐Re (8) showed low to moderate cytotoxicity in PC3 and MCF‐7 cancer cell lines, as typically observed for G4‐binders. Biodistribution studies of the congener PDF‐Pz‐99mTc (12) in normal mice showed that the complex undergoes a fast blood clearance with a predominant hepatobiliary excretion, pointing also for a high in vitro stability.
Critical perspective on the elimination of emerging contaminants from industrial wastewater via microbial electrochemical technologies
Authors: Sikarwar Divyanshu , Bashir Yasser , Sharma Neha , Rasheed Almeenu , Das Sovik
Published: February 2024

Industrial water pollution originating from various industries like textile, dairy, oil, and petrochemical industries, etc. is a huge concern globally and has led to devastating effects on the environment due to the release of refractory emerging contaminants (ECs). These ECs of concern have attracted wide devotion from the scientific community due to their recalcitrant nature and disastrous effects on plants, aquatic life forms, and humans. In this regard, conventional wastewater treatment technologies such as coagulation, flocculation, membrane technologies, electrocoagulation, and other biological technologies like sequencing batch reactor, anaerobic up‐flow sludge blanket reactor, etc., are inefficient in removing ECs from the industrial effluent, while conventional advanced oxidation processes incur high cost due to the extensive requirement of energy for the degradation of ECs. To overcome this issue, microbial electrochemical technologies (METs) can be employed. For instance, METs have shown promising results in the degradation of various ECs, such as microbial fuel cells, which have shown nearly 92% to 98% removal of sulfamethoxazole with simultaneous power recovery. Alizarin yellow R, nitrobenzene, and Congo red were degraded by microbial electrolysis cells with removal efficiency in the range of 88% to 98%, demonstrating their superiority in the elimination of trace contaminants. Similarly, almost 100% mineralization of pyraclostrobin was noticed for the bio‐electro‐Fenton process, showing the elevated potential of these neoteric technologies for the remediation of recalcitrant pollutants. Thus, the current review article aims to critically analyze the intervention of METs for the elimination of ECs from industrial wastewater.
Assessment of circulating apoE4 levels from dried blood spot samples in a large survey setting
Authors: Borbye‐Lorenzen Nis , Deza‐Lougovski Yacila I. , Holmgaard Solveig , Weiss Luzia M. , Bækvad‐Hansen Marie , Skogstrand Kristin , Rieckmann Anna , Börsch‐Supan Axel , Börsch‐Supan Martina
Published: February 2024

INTRODUCTION

The apolipoprotein E (APOE) ε4 allele is associated with high risk for Alzheimer's disease. It is unclear whether individual levels of the circulating apoE4 protein in ε4 carriers confer additional risk. Measuring apoE4 protein levels from dried blood spots (DBS) has the potential to provide information on genetic status as well as circulating levels and to include these measures in large survey settings.

METHODS

We developed a multiplex immunoassay to detect apoE4 protein levels in DBS from 15,974 participants, aged 50+ from Wave 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE).

RESULTS

The apoE4 protein signal was presented in two separable distributions. One distribution corresponded to carriers of at least one copy of the ε4 allele. Fieldwork cofounders affected protein levels but did not explain individual differences.

DISCUSSION

Future research should investigate how genotype and apoE4 level interact with lifestyle and other variables to impact cognitive aging.
Food quality shapes gradual phenotypic plasticity in ectotherms facing temperature variability
Authors: Van Baelen Marine , Bec Alexandre , Sperfeld Erik , Frizot Nathan , Koussoroplis Apostolos‐Manuel
Published: February 2024

Organisms exhibit reversible physiological adjustments as a response to rapidly changing environments. Yet such plasticity of the phenotype is gradual and may lag behind environmental fluctuations, thereby affecting long‐term average performance of the organisms. By supplying energy and essential compounds for optimal tissue building, food determines the range of possible phenotypic changes and potentially the rate at which they occur. Here, we assess how differences in the dietary supply of essential lipids modulate the phenotypic plasticity of an ectotherm facing thermal fluctuations. We use three phytoplankton strains to create a gradient of polyunsaturated fatty acid and sterol supply for Daphnia magna under constant and fluctuating temperatures. We used three different fluctuation periodicities to unravel the temporal dynamics of gradual plasticity and its long‐term consequences for D. magna performance measured as juvenile somatic growth rate. In agreement with gradual plasticity theory, we show that in D. magna, fluctuation periodicity determines the differential between observed growth rates and those expected from constant conditions. Most importantly, we show that diet modulates both the size and the direction of the growth rate differential. Overall, we demonstrate that the nutritional context is essential for predicting ectotherm consumers' performance in fluctuating thermal environments.
Improving liposolubility and lipid antioxidant activity of mangiferin through esterification by lipase
Authors: Yu Xin , Yang Xinyi , Qian Junqing , Guo Hui
Published: February 2024

Mangiferin is one of the main bioactive ingredients in leaves of Mangifera indica. But the poor liposolubility and low bioavailability restrict its application. This study aimed to esterify mangiferin with lipase to improve its lipophilicity, and evaluate its antioxidant activity and hypoglycemic properties. Four fatty acids (palmitic acid, lauric acid, stearic acid, oleic acid) were selected for enzymatic esterification with mangiferin by single‐factor experiments. Under the following optimum reaction conditions of tetrahydrofuran (THF):tert‐amyl alcohol (2:1) was used as solvent, water activity was 0.31, TLIM lipase was 45 mg mL–1, The ratio of mangiferin to fatty acid was 1:50, and the substrates were pretreated by ultrasonic for 0.5 h, then reacted at 55°C for 21 h, the resulting conversion rates of mangiferin‐esterified derivatives exceeded 70.0%.

Lipophilicity, antioxidant, and PTP1B inhibitory activity of mangiferin‐esterified derivatives were determined. The results demonstrated that compared with mangiferin, the ability to scavenge DPPH radicals decreased by about 9%, but the lipophilicity was increased by 10–30 times, and the lipid antioxidant capacity was also improved significantly. Moreover, the inhibitory activity of protein tyrosine phosphatase 1B (PTP1B) exhibited minimal alteration. This indicates that esterification can not only improve the lipophilicity of mangiferin, but also improve its lipid antioxidant capacity.

Practical Applications: In the study, a series of mangiferin‐esterified derivatives were synthesized and their lipophilicity, antioxidant properties, and PTP1B inhibitory activity were determined. The results indicated that, compared with the untreated mangiferin, the mangiferin‐esterified derivatives exhibited superior lipid antioxidant and hypoglycemic activities. Furthermore, the enzymatic esterification method employed in this study offered greater economic and environmental advantages when compared to chemical catalysis. Therefore, the preparation of mangiferin derivatives through enzymatic esterification were deemed feasible with potential application value for enhancing lipid antioxidant capacity in high‐fat foods.
Educational needs and career development of young epileptologists in Italy
Authors: Spagnoli Carlotta , Duca Maddalena , Pelliccia Veronica , Lanzone Jacopo , Masnada Silvia , Chiarello Daniela , Barco Tommaso Lo , Dono Fedele , Nucera Bruna
Published: February 2024

Objective

The Education and Career Task Force of the Young Epilepsy Section‐Italy focuses on educational and career development needs of young Italian epileptologists. Two surveys were developed (pre‐ and post COVID‐19 pandemic) in order to identify the needs of members of the Lega Italiana Contro l'Epilessia under 40 years of age.

Methods

The first was distributed during the 42nd National Congress (Rome, June 5–7, 2019); the second during the 45th National Congress (Padova, June 8–10, 2022) and subsequently by e‐mail until July 9, 2022. Data from the 2019 survey were analyzed descriptively. Data from the 2022 survey were further analyzed with Pearson's chi‐square test to establish if gender, field of clinical practice, and professional role were associated with different needs.

Results

Sixty surveys were completed in 2019 and 69 in 2022. Attendance to courses and congresses as the preferred way to keep medical knowledge updated reduced between 2019 and 2022. The reason was different between trainees (mostly elevated costs) and early‐career consultants (mostly organizational issues) (p = 0.005). The main needs for improvement also diverged: trainees indicated differential diagnosis and diagnostic approach to the first seizure while consultants indicated diagnostic approach to genetic epilepsies (p = 0.004); in the genetic field, priority needs were selection of genetic investigations for trainees versus genotype–phenotype correlations for consultants (p = 0.022). The field of practice (pediatric vs. adult) also impacted on the main needs for improvement that is, acquisition of expertise in neuroradiology and drug therapy for pediatric versus genetics for adult neurology trainees or consultants (p = 0.018); in the clinical area, differential diagnosis and approach to the first seizure versus status epilepticus (p = 0.027); in the genetic field, precision medicine versus genotype–phenotype correlations (p = 0.034). No differences were found based on gender.

Significance

The surveys identified different needs based on professional role and discipline.

Plain Language Summary

The Education and Career Task Force of the Young Epilepsy Section‐Italy (YES‐I) launched two surveys among young Italian epileptologists. Our research shows that the educational and professional needs of young Italian epileptologists vary based on their job role and field of practice, but not on gender. Their preference for on‐site congresses and courses reduced after the pandemic, and the main reason is linked to financial constraints for trainees and to organizational issues for consultants. The main expectation toward YES‐I is to receive support for education and career development. Thus, we collected useful suggestions on how to organize our future YES‐I activities.
Reproductive late effects and testosterone replacement therapy in male childhood cancer survivors: A population‐based study (the Fex‐Can study)
Authors: Haavisto Anu , Lampic Claudia , Wettergren Lena , Lähteenmäki Päivi M. , Jahnukainen Kirsi
Published: February 2024

Childhood cancer survivors are at risk of various endocrine late effects affecting their quality of life. The aim of this study was to assess the prevalence and predictors of endocrine and reproductive outcomes in young adult survivors. A secondary aim was to assess possible associations between testosterone replacement therapy (TRT) and other endocrine, cardiovascular and psychosocial late effects. This nationwide study comprised 1212 male childhood cancer survivors aged 19–40 years, identified through the National Quality Registry for Childhood Cancer in Sweden. Median age at diagnosis during 1981–2017 was 7 (range 0–17) and at study 29 (19–40) years. The study combined self‐report survey data with cancer treatment data from the national registry. Hormone‐induced puberty was self‐reported by 3.8% of the survivors and ongoing TRT by 6.0%. In separate logistic regression analyses, these treatments were associated with hematopoietic stem cell transplantation and cranial radiotherapy. Hormone‐induced puberty was additionally associated with younger age at diagnosis. Men with TRT had a higher prevalence of other endocrine deficiencies, cholesterol medication, depressive symptoms and fatigue as well as a lower probability of living with a partner, having a biological child or current occupation. In the total male cohort, 28.2% reported having a biological child. Reassuring reproductive outcomes after less intensive therapies and low frequency of TRT were observed in young adult male childhood cancer survivors treated in the most recent treatment era. However, men with TRT suffered from several other endocrine, cardiovascular and psychosocial late effects, indicating a need for long‐term monitoring of this high‐risk group.
Iron Deficiency and Intestinal Malabsorption in HIV Disease
Authors: Castaldo Annunziata , Tarallo Luigi , Palomba Elvia , Albano Fabio , Russo Stefania , Zuin Giovanna , Buffardi Floriana , Guarino Alfredo
Published: February 2024

Children with human immunodeficiency virus (HIV) infection have a higher prevalence of intestinal malabsorption. Anemia is also a common feature in these children. The aims of this work were (a) to establish the prevalence of iron deficiency in HIV‐infected children, (b) to test the hypothesis that iron deficiency is related to intestinal malabsorption, (c) to see whether it may contribute to anemia, and (d) to evaluate the sensitivity of oral iron load in the investigation of intestinal function. To accomplish these goals, 71 HIV‐infected symptomatic children were enrolled. Iron serum values were determined before and after oral load with ferrous sulfate. The correlation between basal and post‐load iron levels was evaluated by linear regression. Xylose level after oral load, fecal fat, and fecal alpha1‐antitrypsin concentration were also determined. Iron deficiency was detected in 48% of patients, and it was significantly associated with intestinal iron malabsorption. Sugar malabsorption, steatorrhea, and fecal protein loss were detected in 26,36, and 17% of patients, respectively. Low hemoglobin levels were detected in 66% of patients. The majority of children with iron deficiency also had anemia. Preliminary data showed that oral iron administration was sufficient for raising hemoglobin in children with normal iron absorption, whereas parenteral administration was required in those with iron malabsorption. We conclude that (a) iron deficiency is a major feature of pediatric HIV infection, (b) it is related to intestinal malabsorption, and (c) it contributes to anemia. Finally, oral iron load is a sensitive test for investigating intestinal function.
Gastrointestinal pH, Motility/Transit and Permeability in Cystic Fibrosis
Authors: Gregory P. C.
Published: February 2024

I reviewed the literature (1966‐1994) concerning gastrointestinal (GI) pH, motility/transit, and permeability in cystic fibrosis (CF). Most studies reported were performed with very small numbers of patients, but even when considered together the published data do not confirm some generally expressed views on these topics. The only clear findings were a high incidence of gastroesophageal reflux in CF; pre‐ and postprandial duodenal pH is 1‐2 U lower in patients with CF than in healthy controls; and small intestinal paracellular permeability is 4‐10 times greater than normal in CF. Some patients showed abnormalities of lower esophageal sphincter pressure and of esophageal motility, but apart from one case study other disturbances of GI motility have not been reported. The results of hydrogen breath tests strongly suggest that oro‐cecal transit is slowed in CF, but these results must be confirmed by an alternative test. Measurements of colonic transit and colonic permeability have not been reported. The few studies of gastric emptying reported are controversial. Whether GI pH, apart from duodenal pH, is normal in CF or whether a subset of patients has exceptionally acid intestinal contents requiring specialized pancreatic enzyme supplementation to normalize digestion is not clear. Finally, I briefly discuss the findings in relation to their possible impact on the pathogenesis of fibrosing colonopathy.
Increased Prevalence of Diabetes‐Related Autoantibodies in Celiac Disease
Authors: Rapoport M. J. , Bistritzer T. , Vardi O. , Broide E. , Azizi A. , Vardi P.
Published: February 2024

Forty‐four nondiabetic patients with celiac disease (CD) were examined for the presence of insulin‐dependent diabetes mellitus (IDDM)‐related autoantibodies. Islet cell antibodies (ICA) were detected in 2 of 44 (4.5%). None of the 200 age‐ and sex‐matched healthy controls was ICA positive (p < 0.05). Competitive anti‐insulin antibodies (CIAA) were detected in 1 of 44 (2.5%) patients. First‐phase insulin reserve (FPIR), stimulated insulin reserve (SIR), and glycosylated hemoglobin (GHB) levels were normal in the autoantibody‐positive patients. Our data suggest that, like first‐degree relatives of IDDM patients, CD patients are characterized by an increased prevalence of diabetes‐related autoantibodies. Further follow‐up is needed to determine whether the presence of these autoantibodies in nondiabetic CD patients predicts future IDDM.
Dietary Management of Acute Diarrhoea in Children: Effect of Fermented and Amylase‐Digested Weaning Foods on Intestinal Permeability
Authors: Willumsen Juana F. , Darling Jonathan C. , Kitundu Jesse A. , Kingamkono Rose R. , Msengi Abel E. , Mduma Benedicta , Sullivan Keith R. , Tomkins Andrew M.
Published: February 2024

Background:

There is a strong relationship between diarrhoea, malnutrition, and intestinal integrity. To investigate the effect of different dietary treatment on intestinal permeability during acute diarrhoea, 87 Tanzanian children aged 6‐25 months were recruited to this study when admitted to hospital.

Methods:

Children with acute diarrhoea were rehydrated and then randomly assigned to one of three dietary treatment groups: a conventional low‐energy density porridge, a high‐energy density amylase digested porridge (AMD), or a high‐energy density amylase digested and then fermented porridge (FAD). Lactulose/mannitol permeability tests were performed on admission, at 3 days, and at follow‐up 2 and 4 weeks after discharge. The lactulose/mannitol (L/M) ratios were compared between dietary treatment groups and to a group of age‐matched, healthy control subjects.

Results:

Children with diarrhoea had higher L/M ratios (geometric mean 0.85, 95% CI 0.68‐1.05) compared with control subjects (0.14, 0.12‐0.17) on admission. There was a significant difference in the change in L/M ratio between admission and 3 days between dietary treatment groups in favour of the FAD group (p < 0.05).

Conclusions:

Dietary treatment and intestinal damage at admission explain 13.5% of the variation in L/M ratio, but when age at admission and age at weaning are included as covariants, 21.9% is explained. FAD porridge seems to be more effective in the treatment of intestinal permeability than AMD or conventional porridge. Urinary lactose concentrations in spot urine samples taken prior to the permeability test were also measured. There was a significant correlation with the L/M ratio (correlation coefficient = 0.62, p < 0.001).
Hepatocellular Adenomas in Glycogen Storage Disease Type I and III: A Series of 43 Patients and Review of the Literature
Authors: Labrune Philippe , Trioche Pascale , Duvaltier Isabelle , Chevalier Paquita , Odièvre Michel
Published: February 2024

Background:

Hepatocellular adenomas may develop in patients with glycogen storage disease types I and III, and the malignant degeneration of adenomas in hepatocellular carcinoma has been reported in ten cases. The aim of this work was to study the characteristics of hepatic adenomas in a large series of 43 patients with glycogen storage disease types I and III and to determine the optimal means of follow‐up.

Methods:

The charts of 43 patients with glycogen storage disease type I and III were studied. In all these patients, abdominal ultrasonography and the determination of serum α‐fetoprotein had been performed yearly and serum concentrations of several proteins were determined once.

Results:

51.8% of patients with type I and 25% of patients with type III glycogen storage disease had hepatic adenomas at the time of the study. The male to female ratio was 2 to 1 in type I, and no female had adenomas in type III. No evidence of malignant transformation was observed during the follow‐up period. Serum concentrations of several proteins were significantly higher in patients with hepatic adenomas than in patients without such lesions.

Conclusions:

In patients with glycogen storage disease type I and III, the determination of α‐fetoprotein serum concentration has to be combined with yearly hepatic ultrasound examinations. Other investigations such as CT scan should be considered when the size of any adenoma increases. The malignant transformation of hepatocellular adenoma into hepatocellular carcinoma remains a rare event.
Nutritional Factors and Helicobacter pylori Infection in Colombian Children
Authors: Goodman Karen J. , Correa Pelayo , Tenganá Aux Heraldo J. , DeLany James P. , Collazos Tito
Published: February 2024

Background:

Helicobacter pylori infection occurs most frequently in impoverished populations; however, little is known about specific determinants of susceptibility. This report describes the relationship between H. pylori infection and nutritional indicators among children from a rural village in the Colombian Andes, where a prevalence of 69% was observed in children from 2 to 9 years old.

Methods:

In a cross‐sectional study of 684 children, comprising 92% of the 2‐ to 9‐year‐old population of Aldana, Colombia, information was obtained on dietary factors by questionnaire, height and weight by direct measurement, and H. pylori status using the carbon‐13 urea breath test. Multivariate logistic regression was used to estimate relative risks for nutritional indicators.

Results:

The infection was least frequent among children who ate several servings of fruits and vegetables daily, drank two or more cups of milk daily, and were in the upper quintile of height for their age. The odds of infection increased 19‐fold (95% confidence interval, 4.0‐91.9) among children who consumed less than two daily servings of fruits and vegetables compared with the modal intake of three to five daily servings. Children whose daily vitamin C intake from fruits and vegetables was less than 40 mg had greatly increased odds of infection (odds ratio, 7.2; 95% confidence interval, 1.5‐34.1) compared to the modal intake of 80‐119 mg; for beta‐carotene, the odds ratio was 3.1 (95% confidence interval, 1.2‐7.9) for intakes of less than 300 IU per day, compared with the modal daily intake of 900 IU or more.

Conclusions:

The results of this population‐based study suggest that nutritional factors may play a role in determining susceptibility to H. pylori infection.
Measurement of the Rate of Entry of Intact Colon‐Derived Lactose into the Circulation: A Model for Assessing Gut Uptake of Molecules Not Endogenously Synthesized
Authors: Kien C. Lawrence , Murray Robert D. , Ailabouni Anton H. , Habash Diane L. , Powers Priscilla A.
Published: February 2024

Background:

Results of in vitro studies have documented colonic absorption of lactose in the newborn. A stable isotope model was developed for assessing the entry rate of intact lactose into the portal circulation in newborn piglets.

Methods:

In experiment 1, unlabeled and [D‐1‐13‐C]‐lactose were infused into two separate mesenteric veins, and in experiment 2, labeled lactose was infused into a mesenteric vein and unlabeled lactose was infused into the colon. The 13C‐enrichment of plasma lactose was assessed by high performance liquid chromatography gas chromatography combined with mass spectrometry.

Results:

The isotopic estimate of the mesenteric venous infusion rate of lactose was 91% of the theoretical. In the second experiment 13% of the unlabeled lactose infused into the colon reached the portal circulation.

Conclusions:

The current study provides the first, direct, in vivo confirmation of colon absorption of intact lactose. The tracer model could be used to evaluate intestinal or colonic absorption of other organic compounds not endogenously synthesized, including vitamins or drugs.
Vomiting and Gastroesophageal Motor Activity in Children with Disorders of the Central Nervous System
Authors: Ravelli Alberto M. , Milla Peter J.
Published: February 2024

Background:

Vomiting is common in children with disorders of the central nervous system(CNS) and is usually ascribed to gastroesophageal reflux (GER). However, recent acquisitions on the pathophysiology of vomiting suggest that the dysmotility of the foregut may be more widespread.

Methods:

Fifty‐five children with CNS disorders, 50 of whom suffered from retching and/or vomiting (18 following fundoplication) were studied. We assessed GER by 24 hour pH monitoring and endoscopy, gastric electrical activity by electrogastrography, and gastric half‐emptying time (T½) of a milk meal be electrical impedance tomography.

Results:

Of the 50 vomiting patients, 29 had GER (reflux index of 5.7%‐87.4%; controls: <5%), and 31 had gastric dysrhythmias (12 tachyarrhythmia at 5.5‐11.2 cpm, 4 bradyarrhythmia at 1.7‐1.9 cpm, 15 unstable electrical activity; controls: 2.2‐4.0 cpm). Sixteen patients had GER and gastric dysrhythmias. Eleven of 18 patients with fundoplication had gastric dysrhythmias. Gastric T½ was delayed in 12 of 13 patients with gastric dysrhythmia (6 with GER), versus 2 of 5 with GER alone. No abnormalities were detected in the 5 patients who did not suffer from vomiting.

Conclusions:

Children with CNS disorders who vomit have abnormal gastric motility as often as GER. Following fundoplication, many patients continue to have symptoms possibly related to gastric dysrhythmias, the effects of which may be unmasked by fundoplication. Foregut dysmotility may be related to abnormal modulation of the enteric nervous system by the CNS or to involvement of the enteric nervous system by the same process affecting the brain.
Pudendal Nerve Function in Normal and Encopretic Children
Authors: Sentovich Stephen M. , Kaufman Stuart S. , Cali Rebecca L. , Falk Peter M. , Blatchford Garnet J. , Antonson Dean L. , Thorson Alan G. , Christensen Mark A.
Published: February 2024

Background:

Abnormal pudendal nerve function contributes to fecal retention and incontinence in adults. To determine the role of pudendal neuropathy in childhood, we prospectively evaluated pudendal nerve function in normal and encopretic children.

Methods:

We studied pudendal nerve terminal motor latency in 23 encopretic children and in an equal number of similarly aged, normal children. Anal manometry and electromyography were also obtained in all children.

Results:

Pudendal nerve latency in the encopretic children equaled 1.58 ± 0.33 msec, which was the same as that in control children. Of the 75 pudendal nerves tested, latency was prolonged in only one encopretic child. In contrast, anal electromyography demonstrated nonrelaxation of the external anal sphincter in 75% of the encopretic children but in only 13% of the normal children (p < 0.001). Anorectal manometry demonstrated, on average, lower anal sphincter pressures at rest and with squeezing in the encopretic children (p < 0.01), but only 17% had sphincter pressures more than two standard deviations below normal.

Conclusions:

Other than poor relaxation response of the external anal sphincter during evacuation, these data reveal a paucity of functionally important abnormalities in encopretic children. In particular, we find no evidence that abnormal pudendal nerve function is important in the etiology or pathogenesis of encopresis in children.
Pancreatic Enzyme Supplementation in Cystic Fibrosis Patients Before and After Fibrosing Colonopathy
Authors: Stevens John C. , Maguiness Karen M. , Hollingsworth Judy , Heilman Douglas K. , Chong Sonny K. F.
Published: February 2024

Background:

In 1994 we cared for nine cystic fibrosis patients with fibrosing colonopathy. To evaluate the relationship between fibrosing colonopathy and supplemental pancreatic enzymes we reviewed our dosing of enzymes prior to fibrosing colonopathy development and then evaluated the subsequent effect of drastically reducing pancreatic enzyme dose.

Methods:

We retrospectively reviewed pancreatic enzyme dosing for 267 cystic fibrosis patients with pancreatic insufficiency. The supplemental enzyme history of nine patients with fibrosing colonopathy was contrasted with the history of 258 nonaffected patients. The pancreatic enzyme doses of 75 patients taking at least 6,000 U lipase/kg/meal were systematically reduced to approximately 2,000 lipase units/kg/meal. We evaluated the effect of this dose reduction on change in height and weight z scores one year after achievement of stable enzyme dose.

Results:

In the year prior to diagnosis patients with fibrosing colonopathy took a significantly larger pancreatic enzyme dose, whether assessed by highest dose or cumulative dose, than did nonaffected patients. Similar results were observed after controlling for sex and age. All 75 patients on at least 6,000 U lipase/kg/meal were able to tolerate a significant reduction in dose while achieving clinically acceptable nutrient absorption, with no change over one year in height and weight z scores.

Conclusions:

Our data demonstrate a strong relationship between very high doses of pancreatic enzyme supplementation and formation of fibrosing colonopathy. These very high doses do not appear to be needed for adequate nutrient absorption and growth.
Reducing Parenteral Requirement in Children with Short Bowel Syndrome: Impact of an Amino Acid‐Based Complete Infant Formula
Authors: Bines Julie , Francis Dorothy , Hill David
Published: February 2024

Background:

The aim of this study was to assess the impact of an amino acid‐based complete infant formula on enteral feeding tolerance and parenteral nutrition requirement in children with severe short bowel syndrome.

Methods:

Four children (23 months‐4.75 years) with short bowel syndrome who required long‐term parenteral nutrition due to persistent feeding intolerance while receiving an extensively hydrolyzed formula were assessed before and after the commencement of an amino acid‐based complete infant formula for a mean follow‐up period of 48 months (range 39‐51 months). Assessment included clinical monitoring of feeding tolerance and nutritional status, biochemistry, stool analysis, skin‐prick testing to common food antigens, esophagogastroduodenoscopy and colonoscopy or jejunoscopy with biopsies, and measurement of disaccharidase levels and intestinal permeability.

Results:

All patients ceased parenteral nutrition within 15 months as a result of decreased stool output and resolution of vomiting. Patients had a reduction in hospitalization (mean: 198 versus 98 days/patient/year), episodes of proven(mean: 4.3 versus 3.3/patient/year) and suspected (mean: 6.5 versus 4.0/patient/year) bacterial sepsis and central line insertions (mean: 2.5 versus 1.5/patient/year). Intestinal permeability to lactulose fell markedly(mean: 69% versus 2.7%). Disaccharidase levels increased in all three patients undergoing repeat studies.

Conclusions:

An amino acid‐based complete infant formula improved feeding tolerance and eliminated the need for parenteral nutrition in four children with short bowel syndrome who had previously required long‐term parenteral nutrition. The clinical improvement was mirrored by improvement in measurements of intestinal function.
Vitamins A and E Serum Levels in Children and Young Adults with Inflammatory Bowel Disease: Effect of Disease Activity
Authors: Bousvaros Athos , Zurakowski David , Duggan Christopher , Law Terry , Rifai Nader , Goldberg Nancy E. , Leichtner Alan M.
Published: February 2024

Background:

Hypovitaminosis and fat‐soluble vitamin deficiency have been reported in adults with inflammatory bowel disease (IBD). A prospective study was undertaken to determine the prevalence of low serum levels of vitamins A and E in children and young adults with IBD.

Methods:

Clinical information and serum for vitamin levels was gathered prospectively from 61 patients with Crohn's disease, 36 patients with ulcerative colitis, and 23 control subjects. Disease activity and disease location were determined for IBD patients. Serum retinol and alpha‐tocopherol levels were determined by high‐performance liquid chromatography.

Results:

The prevalence of hypovitaminosis A (defined as serum vitamin A <20μg/dl) or hypovitaminosis E (defined as serum vitamin E <5 mg/l) was 16% in the pediatric IBD population studied. Low vitamin A levels were more common than low vitamin E levels. Serum retinol levels correlated significantly with alpha‐tocopherol levels. Hypovitaminosis was significantly more prevalent in the Crohn's disease patients who had active disease, an erythrocyte sedimentation rate of more than 25 mm/hour, or a serum albumin level less than 3 mg/dl.

Conclusions:

Children and young adults with active IBD frequently have low serum levels of vitamin A or vitamin E. The severity of disease activity is a better predictor of risk for hypovitaminosis than is nutritional status. Further work is necessary to determine whether the hypovitaminosis seen in children with IBD reflects true deficiency.
Gastric Lipase and Pepsin Activities in the Developing Ferret: Nonparallel Development of the Two Gastric Digestive Enzymes
Authors: Hamosh Margit , Henderson Theresa R. , Hamosh Paul
Published: February 2024

Background:

Gastric lipase has an important compensatory function in neonatal fat digestion. The activity level of pepsin and its role in protein digestion is less well understood. We have, therefore, studied the ontogeny of lipase and pepsin in the ferret, a species with a neonatal fat digestion pattern similar to that of humans.

Methods:

Gastric lipase and pepsin activities were quantified from the late fetal period throughout lactation, and were compared with those of the adult.

Results:

The data show earlier ontogeny and much more rapid rise of lipase activity than of pepsin. Lipase activity was present during the last week of fetal development, whereas pepsin was detected only postnatally. Lipase activity was 72.8% ± 14.2% and 153% ± 9.95% and pepsin activity was 11.6%± 1.3% and 30.1% ± 1.3% of the adult level at 2 and 4 wk of age, respectively.

Conclusions:

We conclude that lipase activity develops early and exceeds adult activity during the suckling period, when fat intake is very high. The low pepsin activity and high postprandial pH probably limit gastric proteolysis, thereby contributing to the structural and functional stability of milk proteins, many with protective or bioactive function in the gastrointestinal tract of the newborn.