bluuebunny/crossref_metadata_2025 huggingface dataset:
Tau here, tau there, tau almost everywhere: Clarifying the distribution of tau in the adult CNS
Authors: Kanaan Nicholas M.
Published: December 2023

The microtubule‐associated protein tau has gained significant attention over the last several decades primarily due to its apparent role in the pathogenesis of several diseases, most notably Alzheimer's disease. While the field has focused largely on tau's potential contributions to disease mechanisms, comparably less work has focused on normal tau physiology. Moreover, as the field has grown, some misconceptions and dogmas regarding normal tau physiology have become engrained in the traditional narrative. Here, one of the most common misconceptions regarding tau, namely its normal cellular/subcellular distribution in the CNS, is discussed. The literature describing the presence of tau in neuronal somata, dendrites, axons and synapses, as well as in glial cells is described. The origins for the erroneous description of tau as an “axon‐specific,” “axon‐enriched” and/or “neuron‐specific” protein are discussed as well. The goal of this work is to help address these specific dogmatic misconceptions and provide a concise description of tau's normal cellular/subcellular localization in the adult CNS. This information can help refine our collective understanding of‐ and hypotheses about tau biology and pathobiology.
Sustainable production of triazoles from lignin major motifs
Authors: Zhu Wenqing , Shi Yue , Lu Jinfei , Han Fengan , Luo Wenhao , Xu Dezhu , Guo Tenglong , Huang Genping , Kühn Fritz E. , Zhang Bo , Zhang Tao
Published: December 2023

An efficiently catalyzed synthesis of pharmaceutically relevant 1,2,3‐trazoles from renewable resources is highly desirable. However, due to incompatible catalysis conditions, this endeavor remained challenging so far. Herein, a practical access protocol to 1,2,3‐triazoles, starting from lignin phenolic β‐O‐4 with γ‐OH group utilizing a vanadium‐based catalyst is presented. A broad substrate scope reaching up to 97 % yield of 1,2,3‐triazoles are obtained. The reaction pathway includes selective cleavage of double C−O bonds, cycloaddition, and dehydrogenation. Mechanistic studies and density‐functional theory (DFT) calculations suggest that the V‐based complex acts as a bifunctional catalyst for both selective C−O bonds cleavage and dehydrogenation. This synthetic pathway has been applied for the synthesis of pharmacological and biological active carbohydrate derivatives starting from biomass components as feedstock, enabling a potential sustainable route to triazolyl carbohydrate derivatives, which paves the way for lignin‐based heterocyclic aromatics in the pharmaceutical applications.
Beyond Small Molecular Cations: Elucidating the Alkaline Stability of Cationic Moieties at the Membrane Scale
Authors: Ling Qianjun , Wang Chenxi , Wang Tao , Yang Shanzhong , Li Xueliang , Wei Haibing , Ding Yunsheng
Published: December 2023

A major hindrance in the commercialization of alkaline polyelectrolyte‐based electrochemical energy conversion devices is the development of durable anion exchange membranes (AEMs). Despite many alkali‐stable cations that have been explored, the stability of these cationic moieties at the membrane scale is in the blind. Herein, we present a molecularly designed polyaromatic AEM with cationic moieties in an alternating manner to unbiasedly compare the alkaline stability of piperidinium and ammonium groups at the membrane state. Using nuclear magnetic resonance spectroscopy, we demonstrate that the pentyltrimethyl group is about 2‐fold more stable than piperidinium within a polyaromatic scaffold, either in ex‐situ alkaline soaking or in‐situ cell operation. This finding challenges the judgment extrapolated from the stability trend of cations, that is, the piperidinium‐functionalized AEM is more alkali‐stable than the counterparts based on quaternary ammoniums. Moreover, the deterioration mechanism of piperidinium moiety after being embedded in polyaromatic backbone is rationalized by density functional theory.
Generation of a Dcx‐CreERT2 knock‐in mouse for genetic manipulation of newborn neurons
Authors: Perez Gabriella A. , Park Kyung‐Won , Lanza Denise , Cicardo Jenna , Uddin M. Danish , Jankowsky Joanna L.
Published: December 2023

A wide variety of CreERT2 driver lines are available for genetic manipulation of adult‐born neurons in the mouse brain. These tools have been instrumental in studying fate potential, migration, circuit integration, and morphology of the stem cells supporting lifelong neurogenesis. Despite a wealth of tools, genetic manipulation of adult‐born neurons for circuit and behavioral studies has been limited by poor specificity of many driver lines targeting early progenitor cells and by the inaccessibility of lines selective for later stages of neuronal maturation. We sought to address these limitations by creating a new CreERT2 driver line targeted to the endogenous mouse doublecortin locus as a marker of fate‐specified neuroblasts and immature neurons. Our new model places a T2A‐CreERT2 cassette immediately downstream of the Dcx coding sequence on the X chromosome, allowing expression of both Dcx and CreERT2 proteins in the endogenous spatiotemporal pattern for this gene. We demonstrate that the new mouse line drives expression of a Cre‐dependent reporter throughout the brain in neonatal mice and in known neurogenic niches of adult animals. The line has been deposited with the Jackson Laboratory and should provide an accessible tool for studies targeting fate‐restricted neuronal precursors.
Copper‐Catalyzed Directed Diamination of Terminal Olefins with Diaziridinone
Authors: Li Junhua , Yang Yan , Shi Yian
Published: December 2023

This work describes a copper‐catalyzed 8‐aminoquinoline‐assisted diamination of terminal olefins with di‐t‐butyldiaziridinone as nitrogen source, providing a variety of 2‐(2‐oxoimidazolidin‐4‐yl)‐N‐(quinolin‐8‐yl)acetamides in moderate to good yields.
Energy, Exergy, Economic and Exergoeconomic Analyses of Chemical Looping Combustion Plant Using Waste Bark for District Heat and Power Generation with Negative Emissions
Authors: Surywanshi Gajanan Dattarao , Leion Henrik , Soleimanisalim Amir H.
Published: December 2023

The greenhouse gas emissions from the boiler of pulp and paper industries can be minimized by adapting chemical looping combustion (CLC) technology. This work aims to analyze the energy, exergy, economic, and exergoeconomic performance of an industrial scale CLC plant for district heat and electricity generation using waste bark from the paper and pulp industry. The CLC plant with one natural ore and one industrial waste oxygen carrier (OC) is modeled using Aspen Plus. The performance of the CLC plant has been compared to Örtofta combined heat and power plant without CO2 capture and with post‐combustion CO2 capture as the reference cases. Results showed that the CLC‐based power plant is energetically, exegetically, and economically efficient compared to the reference cases. The circulating fluidized bed boiler unit contributes the highest exergy destruction (about 50–80%). Among the CO2 capture plants, the CLC plant with ilmenite has the lowest levelized cost of district heat (4.58 € GJ−1), and a payback period (9.69 years) followed by the CLC plant with LD slag (5.91 € GJ−1 and 11.84 years), and the plant with PCC (6.94 € GJ−1 and 13.58 years). The exergoeconomic analysis reveals that the CLC reactors have the highest cost reduction potential, followed by the steam turbine.
Economical and eco‐friendly adsorbent derived from “Halodule uninervis” for effective removal of N‐nitrosodiphenylamine from wastewater: Equilibrium, reusability, and mechanism studies
Authors: Gijjapu Durga Rao , Nazal Mazen K. , Abuzaid Nabeel
Published: December 2023

N‐nitrosodiphenylamine (NDPhA) is soluble in water and highly toxic. Exposure to NDPhA even at low concentrations for a long period can cause several health effects. Hence the removal of NDPhA from aqueous samples using a widely abundant and economical adsorbent is highly challenging. In this study, a highly efficient, eco‐friendly, and low‐cost adsorbent was derived from the dead leaves of Halodule uninervis seagrass (SG) without any chemical modifications. The derived adsorbent was characterized and investigated for the removal of NDPhA from aqueous solutions. The effects of solution pH, contact time, adsorbent dosage, and adsorbate concentration were studied and optimized. The SG adsorbent showed a significant removal efficiency of 83% for NDPhA from wastewater solution using 1 g L−1 adsorbent. The maximum adsorption capacity for SG was found to be 64.84 mg g−1 at neutral pH and room temperature. The adsorption isotherm results fitted with the Langmuir model and followed pseudo‐second‐order kinetics. From the thermodynamic parameters, it has been found that the adsorption of NDPhA onto SG adsorbent is favorable, endothermic, and the chemical adsorption mechanism is predominant. This study indicated that SG adsorbent is reusable and can be easily regenerated and reused at least three times with a slight decrease in its removal efficiency.
Clinical characteristics and diagnoses of 1213 children referred to a first seizure clinic
Authors: Slinger Geertruida , Noorlag Lotte , van Diessen Eric , Otte Willem M. , Zijlmans Maeike , Jansen Floor E. , Braun Kees P. J.
Published: December 2023

Objective

New‐onset seizure‐like events (SLEs) are common in children, but differentiating between epilepsy and its mimics is challenging. This study provides an overview of the clinical characteristics, diagnoses, and corresponding etiologies of children evaluated at a first seizure clinic (FSC), which will be helpful for all physicians involved in the care of children with SLEs.

Methods

We included 1213 children who were referred to the FSC of a Dutch tertiary children's hospital over a 13‐year period and described their clinical characteristics, first routine EEG recording results, and the distribution and specification of their eventual epilepsy and non‐epilepsy diagnoses. The time interval to correct diagnosis and the diagnostic accuracy of the FSC were evaluated.

Results

“Epilepsy” was eventually diagnosed in 407 children (33.5%), “no epilepsy” in 737 (60.8%), and the diagnosis remained “unclear” in 69 (5.7%). Epileptiform abnormalities were seen in 60.9% of the EEG recordings in the “epilepsy” group, and in 5.7% and 11.6% of the “no epilepsy” and “unclear” group, respectively. Of all children with final “epilepsy” and “no epilepsy” diagnoses, 68.6% already received their diagnosis at FSC consultation, and 2.9% of the children were initially misdiagnosed. The mean time to final diagnosis was 2.0 months, and 91.3% of all children received their final diagnosis within 12 months after the FSC consultation.

Significance

We describe the largest pediatric FSC cohort to date, which can serve as a clinical frame of reference. The experience and expertise built at FSCs will improve and accelerate diagnosis in children with SLEs.

Plain language summary

Many children experience events that resemble but not necessarily are seizures. Distinguishing between seizures and seizure mimics is important but challenging. Specialized first‐seizure clinics can help with this. Here, we report data from 1213 children who were referred to the first seizure clinic of a Dutch children's hospital. One‐third of them were diagnosed with epilepsy. In 68.8% of all children—with and without epilepsy—the diagnosis was made during the first consultation. Less than 3% were misdiagnosed. This study may help physicians in what to expect regarding the diagnoses in children who present with events that resemble seizures.
Mangrove forest drag and bed stabilisation effects on intertidal flat morphology
Authors: Gijsman Rik , Horstman Erik M. , Swales Andrew , MacDonald Iain T. , Bouma Tjeerd J. , van der Wal Daphne , Wijnberg Kathelijne M.
Published: December 2023

Mangrove trees influence their physical environment by exerting drag on tidal flows and waves while also stabilising the sediment bed of intertidal flats. These processes influence sediment accretion, the mangrove habitat and their resilience to sea level rise. However, little is known about the magnitude and spatial extent of the effects of mangrove forests on sediment transport and the morphology of the intertidal flat. We use manipulated simulations with an extended process‐based numerical model, to study the influence of mangrove forests on intertidal flat morphology on a yearly timescale. The model includes the influence of mangrove trees on tidal flows, waves and sediment dynamics. The model is calibrated and validated with a comprehensive set of measurement data including hydrodynamics, sediment transport and morphological processes from an expanding mangrove forest in the sediment‐rich Firth of Thames estuary in Aotearoa New Zealand.

Sediment accretion on the upper intertidal flat is predominantly influenced by the characteristic morphology of the established mangrove forest, with increased bed stability at higher mudflat elevations related to prolonged aerial exposure and drying of the bed. Our results show that, in comparison to the situation without mangroves, sediment accretion increases in the most seaward fringe area of the forest. The unvegetated intertidal flat fronting the mangrove forest captures less sediment compared to the situation without mangroves. The mangrove forest drag triggers the development of a steeper, convex‐up‐shaped, upper intertidal flat profile, especially during periods with higher water levels and waves. These effects are expected to influence the development and storm‐recovery of natural and restored mangrove forests and may contribute to the resilience and persistence of mangrove‐vegetated intertidal flats for coastal flood risk reduction.
Brain tumor grade classification using multi‐step pre‐training
Authors: Mehmood Yasar , Bajwa Usama Ijaz , Anwar Muhammad Waqas
Published: December 2023

Medical images offer a non‐invasive method to diagnose different diseases, but using them manually produces unreliable results. Modern deep learning architectures and techniques are computed and data‐intensive, making them difficult to use for relatively smaller datasets of medical images. Transfer learning has been used as a remedy for the problem mentioned above. However, the domain difference between the datasets used for pre‐training (e.g., ImageNet) and the target datasets, like medical images, negatively impacts the transfer learning results. Recently, many researchers have used additional pre‐training called domain‐adaptive pre‐training (DAPT) using the data from the target domain (e.g., medical images) before using the model on the target tasks to achieve superior performance. This study proposes a variant of DAPT by performing it on a subset of the architecture. It has achieved state‐of‐the‐art performance for brain tumor grading on the BraTS 2019 while being computationally efficient.
A self‐powered biosensor based on triboelectric nanogenerator for dual‐specificity bacterial detection
Authors: Lu Wei , Wang Xiaoqiang , Wang Congyu , Gong Ke , Li Jiawei , Li Xue , Wang Peng
Published: December 2023

Pathogenic and corrosive bacteria pose a significant risk to human health or economic well‐being. The specific, sensitive, and on‐site detection of these bacteria is thus of paramount significance but remains challenging. Taking inspiration from immunoassays with primary and secondary antibodies, we describe here a rational design of microbial sensor (MS) under a dual‐specificity recognition strategy using Pseudomonas aeruginosa (P. aeruginosa) as the detection model. In the MS, engineered aptamers are served as the primary recognition element, while polydopamine‐N‐acetyl‐D‐galactosamine (PDA‐Gal NAc) nanoparticles are employed as the secondary recognition element, which will also generate and amplify changes in the output voltage signal. To achieve self‐powering capability, the MS is constructed based on a triboelectric nanogenerator (TENG) with the specific aptamers immobilized on the TENG electrode surface. The as‐prepared MS‐TENG system exhibits good stability in output performance under external forces, and high specificity toward P. aeruginosa, with no cross‐reactivity observed. A linear relationship (R2 = 0.995) between the output voltage and P. aeruginosa concentration is established, with a limit of detection estimated at around 8.7 × 103 CFU mL−1. The utilization of PDA‐Gal NAc nanoparticles is found to play an important role in enhancing the specific and reliability of detection, and the underlying mechanisms are further clarified by computational simulations. In addition, the MS‐TENG integrates a wireless communication module, enabling real‐time monitoring of bacterial concentration on mobile devices. This work introduces a pioneering approach to designing self‐powered smart microbial sensors with high specificity, using a double recognition strategy applicable to various bacteria beyond P. aeruginosa.

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Eluding easy definitions: A review of Literary Knowing and the Making of English Teachers—The Role of Literature in Shaping English Teachers' Professional Knowledge and Identities
Authors: Davis Roberts Megan
Published: December 2023

Literary Knowing and the Making of English Teachers offers a thorough exploration of the relationship between literature, knowledge, and the professional identities of English teachers. The book engages fundamental questions about knowledge in the English classroom and presents a 3‐year longitudinal study involving 24 early‐career English teachers in Australia. Through interviews and a national survey, the authors provide a multivocal exploration of teachers' perceptions of literary knowledge, curriculum design, and their roles in mediating the relationship between students and texts. This thought‐provoking work highlights literature's formative role in shaping teachers' professional practices and identities while inviting readers to reflect on the broader debates surrounding literature's place in the English Language Arts classroom.
Evaluation of human herpesvirus‐8 viremia and antibody positivity in patients with HIV infection with human herpesvirus‐8‐related diseases
Authors: Watanabe Dai , Iida Shun , Hirota Kazuyuki , Ueji Takashi , Matsumura Takuro , Nishida Yasuharu , Uehira Tomoko , Katano Harutaka , Shirasaka Takuma
Published: December 2023

Human herpesvirus‐8 (HHV‐8) viremia is associated with refractory conditions in patients infected with HIV‐1. Therefore, we evaluated the factors related to plasma HHV‐8‐DNA. Participants included patients infected with HIV‐1 who visited our hospital. Plasma HHV‐8‐DNA levels were measured using real‐time polymerase chain reaction, and anti‐HHV‐8 antibodies were assessed through enzyme immunoassays using multiple antigens (K8.1, ORF59, ORF65, and LANA). Factors related to plasma HHV‐8‐DNA were examined using Fisher's exact test or Mann–Whitney U test. The study involved 36 patients infected with HIV‐1, of whom 19 were histologically diagnosed with Kaposi's sarcoma (KS), two had multicentric Castleman's disease (MCD), and 15 did not exhibit HHV‐8‐related disease. Before the introduction of antiretroviral therapy (ART), plasma HHV‐8‐DNA was detected in 44% (7/16) of patients with KS and in 9% (1/11) of patients without HHV‐8‐related disease. Among patients with KS, elevated plasma HHV‐8‐DNA levels (≥0.05 copies/µL) correlated with the presence of CDC category C diseases other than KS (p = 0.0337), anti‐HHV‐8 antibody negativity (p = 0.0337), anemia (p = 0.0474), and thrombocytopenia (p = 0.0146). Following ART initiation, the percentage of patients positive for plasma HHV‐8‐DNA decreased from 44% (7/16) to 6% (1/17), and the percentage of patients positive for anti‐HHV‐8 antibodies increased from 44% (7/16) to 88% (15/17). Finally, plasma HHV‐8‐DNA positivity and anti‐HHV‐8 antibody negativity were observed in two patients with MCD. Our findings suggest that insufficient production of anti‐HHV‐8 antibodies was associated with HHV‐8 viremia, and that anti‐HHV‐8 antibody production was recovered with ART; thus, indicating the possibility of involvement of humoral immunity in suppressing HHV‐8 viremia.
Systematic observation‐based diagnosis of atrioventricular nodal reentrant tachycardia with a bystander concealed nodoventricular pathway
Authors: Nagashima Koichi , Maruyama Mitsunori , Kaneko Yoshiaki , Sakai Satoshi , Sekihara Takayuki , Kawaji Tetsuma , Iwakawa Hidehiro , Egami Yasuyuki , Ota Chisato , Nagase Satoshi , Yagi Tetsuo , Suzuki Keisuke , Fukaya Hidehira , Nakamura Hironori , Mori Hitoshi , Ueda Akiko , Soejima Kyoko , Watanabe Ryuta , Wakamatsu Yuji , Hirata Shu , Hirata Moyuru , Okumura Yasuo
Published: December 2023

Background

This study aimed to establish a systematic method for diagnosing atrioventricular nodal reentrant tachycardia (AVNRT) with a bystander concealed nodoventricular pathway (cNVP).

Methods

We analyzed 13 cases of AVNRT with a bystander cNVP, 11 connected to the slow pathway (cNVP‐SP) and two to the fast pathway (cNVP‐FP), along with two cases of cNVP‐related orthodromic reciprocating tachycardia (ORT).

Results

The diagnostic process was summarized in three steps. Step 1 was identification of the presence of an accessory pathway by resetting the tachycardia with delay (n = 9) and termination without atrial capture (n = 4) immediately after delivery of a His‐refractory premature ventricular contraction (PVC). Step 2 was exclusion of ORT by atrio‐His block during the tachycardia (n = 4), disappearance of the reset phenomenon after the early PVC (n = 7), or dissociation of His from the tachycardia during ventricular overdrive pacing (n = 1). Moreover, tachycardia reset/termination without the atrial capture (n = 2/2) 1 cycle after the His‐refractory PVC was specifically diagnostic. Exceptionally, the disappearance of the reset phenomenon was also observed in the two cNVP‐ORTs. Step 3 was verification of the AVN as the cNVP insertion site, evidenced by an atrial reset/block preceding the His reset/block in fast–slow AVNRT with a cNVP‐SP and slow–fast AVNRT with a cNVP‐FP or His reset preceding the atrial reset in slow–fast AVNRT with a cNVP‐SP.

Conclusion

AVNRT with a bystander cNVP can be diagnosed in the three steps with few exceptions. Notably, tachycardia reset/termination without atrial capture one cycle after delivery of a His‐refractory PVC is specifically diagnostic.
The 2023 Orthopaedic Research Society's International Consensus Meeting on musculoskeletal infection: Summary from the host immunity section
Authors: Schwarz Edward M. , Archer Nathan K. , Atkins Gerald J. , Bentley Karen L. de Mesy , Botros Mina , Cassat James E. , Chisari Emanuele , Coraça‐Huber Débora C. , Daiss John L. , Gill Steven R. , Goodman Stuart B. , Harro Janette , Hernandez Christopher J. , Ivashkiv Lionel B. , Kates Stephen L. , Marques Cláudia N. H. , Masters Elysia A. , Muthukrishnan Gowrishankar , Owen John R. , Raafat Dina , Saito Motoo , Veis Deborah J. , Xie Chao
Published: December 2023

Musculoskeletal infections (MSKI), which are a major problem in orthopedics, occur when the pathogen eludes or overwhelms the host immune system. While effective vaccines and immunotherapies to prevent and treat MSKI should be possible, fundamental knowledge gaps in our understanding of protective, nonprotective, and pathogenic host immunity are prohibitive. We also lack critical knowledge of how host immunity is affected by the microbiome, implants, prior infection, nutrition, antibiotics, and concomitant therapies, autoimmunity, and other comorbidities. To define our current knowledge of these critical topics, a Host Immunity Section of the 2023 Orthopaedic Research Society MSKI International Consensus Meeting (ICM) proposed 78 questions. Systematic reviews were performed on 15 of these questions, upon which recommendations with level of evidence were voted on by the 72 ICM delegates, and another 12 questions were voted on with a recommendation of “Unknown” without systematic reviews. Two questions were transferred to another ICM Section, and the other 45 were tabled for future consideration due to limitations of available human resources. Here we report the results of the voting with internet access to the questions, recommendations, and rationale from the systematic reviews. Eighteen questions received a consensus vote of ≥90%, while nine recommendations failed to achieve this threshold. Commentary on why consensus was not achieved on these questions and potential ways forward are provided to stimulate specific funding mechanisms and research on these critical MSKI host defense questions.
Alanine aminotransferase cutoffs for the pediatric fatty liver disease: Major impact of the reference population
Authors: Aitokari Linnea , Lahti Siiri , Kivelä Laura , Riekki Hanna , Hiltunen Pauliina , Vuorela Nina , Viitasalo Anna , Soininen Sonja , Huhtala Heini , Lakka Timo , Kurppa Kalle
Published: December 2023

Objectives and Study

The often‐recommended alanine aminotransferase (ALT) cutoffs (girls 21 U/l, boys 25 U/l) are based on a NHANES cohort. A novel concept of metabolic dysfunction associated steatotic liver disease (MASLD) emphasizes the role of ALT. We tested the prevalence of increased ALT and MASLD in children with overweight or obesity applying population‐based and NHANES‐based cut‐offs.

Methods

Six‐ to seventeen‐year‐old children underwent data collection in a prospective Physical Activity and Nutrition in Children (PANIC) study. ALT 95th percentiles were calculated from 1167 separate measurements considering various confounders. Test cohort comprised 1044 children with overweight/obesity.

Results

ALT values increased at puberty onset (p = 0.031) and correlated negatively with age in girls (r = −0.222, p < 0.001). Particularly overall and central obesity increased ALT, whereas underweight or metabolic abnormalities had smaller effect. After applying the tested exclusions, the age‐related ALT 95th percentiles were 24–29 U/l for girls and 29–32 U/l for boys. In 6–8‐year‐old children with overweight/obesity, the prevalence of increased ALT and MASLD were 21.6% and 2.4% with age‐specific PANIC cutoffs. In older children, when NHANES‐based cutoffs were used, there was a trend for higher prevalence of increased ALT and MASLD in all age groups for both sexes, reaching significance for increased ALT in 12–16‐year‐old boys (NHANES 63.5%, 95% confidence interval [CI]: 56.4%–70.0% vs. PANIC 47.1%, 95% CI [40.1%–54.2%]) and 9–11‐year‐old girls (60.0% [49.4%–69.8%] vs. 31.8% [22.8%–42.3%]), respectively. Increased ALT/MASLD were more common in boys than in girls, and in boys these increased with age, whereas in girls these peaked at age 9–12 years.

Conclusion

A reference population impacts on the prevalence of increased ALT and MASLD. Considering this help optimizing screening while avoiding unnecessary investigations and surveillance. The prospective part of this study is registered in clinicaltrials.gov; identifier NCT01803776.
Update on the diagnosis and management of neonatal intrahepatic cholestasis caused by citrin deficiency: Expert review on behalf of the Asian Pan‐Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition
Authors: Inui Ayano , Ko Jae Sung , Chongsrisawat Voranush , Sibal Anupam , Hardikar Winita , Chang Mei‐Hwei , Treepongkaruna Suporn , Arai Katsuhiro , Kim Kyung Mo , Chen Huey‐Ling
Published: December 2023

Citrin deficiency is an autosomal recessive metabolic liver disease caused by mutations in the SLC25A13 gene. The disease typically presents with cholestasis, elevated liver enzymes, hyperammonemia, hypercitrullinemia, and fatty liver in young infants, resulting in a phenotype known as “neonatal intrahepatic cholestasis caused by citrin deficiency” (NICCD). The diagnosis relies on clinical manifestation, biochemical evidence of hypercitrullinemia, and identifying mutations in the SLC25A13 gene. Several common mutations have been found in patients of East Asian background. The mainstay treatment is nutritional therapy in early infancy utilizing a lactose‐free and medium‐chain triglyceride formula. This approach leads to the majority of patients recovering liver function by 1 year of age. Some patients may remain asymptomatic or undiagnosed, but a small proportion of cases can progress to cirrhosis and liver failure, necessitating liver transplantation. Recently, advancements in newborn screening methods have improved the age of diagnosis. Early diagnosis and timely management improve patient outcomes. Further studies are needed to elucidate the long‐term follow‐up of NICCD patients into adolescence and adulthood.
Clinical relevance of inflammation on rectal biopsy for Hirschsprung disease: An outcomes analysis
Authors: Lotakis Dimitra M. , Rubalcava Nathan S. , Lopyan Natalie M. , Heider Amer , Rabah Raja , Elizabeth Speck K. , Jarboe Marcus D. , Ehrlich Peter F. , Ralls Matthew W.
Published: December 2023

Objectives

Inflammation on diagnostic rectal biopsy for children with suspected Hirschsprung disease (HSCR) is reported on pathology, and its significance is unknown. We describe the management and outcomes of a cohort with inflammation on rectal biopsy compared to those without. Specifically, to address the hypothesis that inflammation on diagnostic biopsy is associated with increased complication rates irrespective of intervention type and timing.

Methods

A single institution retrospective review of children with HSCR who underwent biopsy and endorectal pull‐through (ERPT) from 2010 to 2020 was performed. The primary outcome was overall complications at 30‐days following ERPT. Secondary outcomes included timing and type of operative intervention as well as postoperative enterocolitis diagnosed within 6‐months of ERPT.

Results

Forty‐nine children were identified; inflammation was present on diagnostic biopsy for 17 children. Those with inflammation were more likely to have clinical evidence of enterocolitis at the time of biopsy (p = 0.001) and were more likely to undergo leveling colostomy before ERPT (p = 0.01). Children with inflammation had a higher anastomotic leak rate (p = 0.04). Subgroup analysis of patients with inflammation undergoing primary ERPT versus leveling colostomy demonstrated no significant difference in outcomes following definitive ERPT.

Conclusions

Our study suggests inflammation on diagnostic rectal biopsy for HSCR is associated with increased anastomotic leak rates. While additional prospective studies are indicated, attention to methods of mitigating inflammation and confirming its resolution before definitive pull‐through may be of benefit for improving clinical outcomes in patients found with inflammation on diagnostic rectal biopsy.
Brain imaging abnormalities in children with dysphagia with aspiration: A retrospective study
Authors: Patel Bhumi , Muston Heather , Pitman Ryan T.
Published: December 2023

Objective

Head imaging is often performed in children with persistent dysphagia with aspiration to evaluate for Chiari malformations that may be associated with dysphagia. Unfortunately, the frequency of Chiari malformations or other head imaging abnormalities in children who aspirate is unknown. The goal of this study is to determine the frequency of head imaging abnormalities in children with evidence of aspiration or penetration on video fluoroscopic swallow study (VFSS).

Setting

Tertiary Children's Hospital.

Methods

We performed retrospective analysis of children with a diagnosis of aspiration evaluated at our center from January 2010 through April 2021. In this study, we included children with VFSS confirmed aspiration or penetration, brain magnetic resonance imaging (MRI) performed at our center, and without known genetic, congenital craniofacial, or neurologic abnormalities.

Results

Of the 977 patients evaluated in our system during that time with a diagnosis of aspiration, 185 children met the inclusion criteria. Eight children were diagnosed with Chiari malformations (4.3%) and 94 head MRIs were abnormal (51.4%). There was no difference in VFSS findings (frequency of aspiration, penetration, penetration‐aspiration score, or recommended thickness of liquid) in children with a Chiari malformation versus other abnormalities or normal brain imaging. The majority of other non‐Chiari brain imaging abnormalities were nonspecific. There was no difference in VFSS findings in children with abnormal MRI findings versus normal MRI.

Conclusions

Brain imaging abnormalities are common in children who aspirate. Intervenable lesions are rare. Further studies are required to determine patients that will most likely benefit from brain imaging.
Trajectory of body mass index and obesity in children with Crohn's disease compared to healthy children
Authors: Mitchel Elana B. , Huang Jing , Zemel Babette , Baldassano Robert , Albenberg Lindsey , Denburg Michelle
Published: December 2023

Background

There is increasing recognition that children with Crohn's Disease (CD) can develop obesity.

Methods

Using the RISK Study, an inception cohort of pediatric CD participants, and Bone Mineral Density in Childhood Study (BMDCS), a longitudinal cohort of healthy children, multivariable linear mixed effects, generalized linear mixed effects, and logistic regression models were used to evaluate factors associated with change in body mass index z‐score (BMIZ), obesity, and excessive weight gain, respectively.

Results

1029 CD participants (625 exposed to antitumor necrosis factor (anti‐TNF) therapy) and 1880 healthy children were included. Change in BMIZ was higher in CD exposed to anti‐TNF as compared to CD unexposed to anti‐TNF and the healthy reference group. Sex, age, baseline BMIZ, C‐reactive protein, anti‐TNF, and steroids were associated with changes in BMIZ in CD. CD exposed (odds ratio [OR] 4.81, confidence interval [CI] 4.00–5.78) and unexposed (OR 3.14, CI 2.62–3.76) had a greater likelihood of becoming obese versus the healthy reference group. While the prevalence of obesity was higher at baseline in the healthy reference group (21.3%) versus CD participants (8.5% exposed vs. 11.1% unexposed), rates of obesity were similar by the end of follow‐up (21.4% healthy vs. 20.3% exposed vs. 22.5% unexposed). Anti‐TNF therapy was an independent risk factor for the development of obesity and excessive weight gain in CD participants.

Conclusions

Patients with CD have dynamic changes in BMIZ over time, and while for most, this is restorative, for some, this can lead to obesity and excessive weight gain. It is important to understand the factors that may lead to these changes, including anti‐TNF therapy. Counseling of patients and early lifestyle intervention may be necessary.
Identifying risk factors of anti‐TNF induced skin lesions and other adverse events in paediatric patients with inflammatory bowel disease
Authors: van Hoeve Karen , Thomas Debby , Hillary Tom , Hoffman Ilse , Dreesen Erwin
Published: December 2023

Objectives

While higher infliximab (IFX) trough concentrations (TCs) are associated with better outcomes in patients with inflammatory bowel disease (IBD), they could pose a risk for adverse events (AEs), including IFX‐induced skin lesions. Therefore, we studied correlations between IFX TCs and occurrence of AEs in paediatric IBD patients.

Methods

In this single‐centre study, all children with Crohn's disease (CD) and ulcerative colitis (UC) receiving IFX maintenance therapy who underwent proactive drug monitoring between March 2015 and August 2022 were included. IFX doses/intervals/TCs and patient characteristics were systematically registered, as well as AEs and skin lesions appearance.

Results

A total of 109 patients (72 CD and 37 UC) contributed 2913 IFX TCs. During a median follow‐up of 3.0 [1.5–4.5] years, we observed 684 AEs in 101 patients and 49 skin lesions in 35 patients. There was no significant difference (p = .467) in median TCs between patients with and without skin lesions. However, higher median IFX doses were associated with an increased hazard rate of skin lesions [HR 1.084 (1.024–1.148), p = .005], in addition to female sex [2.210 (1.187–5.310), p = .016] and diagnosis of CD [1.695 (1.241–1.877), p = .011]. Considering IFX therapeutic TC cut‐offs of 5.0 and 9.0 µg/mL, there was no significant difference in AE rate (p = .749 and p = .833, respectively). Also, no significant association between IFX doses and AE rate (p = .159).

Conclusions

Increasing the IFX dose to achieve therapeutic TCs may not increase the overall risk of AEs in paediatric IBD patients. However, concerns arise regarding the risk of skin lesions, especially in female CD patients.
Budd‐Chiari syndrome in children: Radiological intervention and role of shear wave elastography in monitoring response
Authors: Samanta Arghya , Srivastava Anshu , Yadav Rajnikant , Kapoor Aditya , Ghosh Anindya , Mishra Prabhakar , Sen Sarma Moinak , Poddar Ujjal
Published: December 2023

Objectives

Radiological intervention (RI) is the preferred treatment in children with Budd‐Chiari syndrome (BCS). We studied the comparative long‐term outcome of BCS children, with and without RI and utility of liver and splenic stiffness measurement (LSM, SSM) by 2‐dimensional shear wave elastography (2D‐SWE) in assessing response.

Methods

Sixty children (40 boys, median age 10.5 [6.5–15.25] years) with BCS (29 newly diagnosed, 31 follow‐up) were evaluated. LSM and SSM by 2D‐SWE and vascular patency were monitored pre‐ and postprocedure (≥ 6 months postprocedure) in those undergoing RI. Medical therapy without anticoagulation and monitoring was done in subjects without RI. The RI and no‐RI groups were compared.

Results

Ascites (54,90%), hepatomegaly (56,93%) and prominent abdominal‐veins (42,70%), were the commonest features. The majority (46,78%) had isolated hepatic vein block. 44 (73%) cases underwent RI, while 16 (27%) were managed conservatively. Both groups were similar at baseline. Post‐RI subjects showed significant improvement in clinical findings, liver functions and portal hypertension. LSM [33 (32–34.5) to 19.2 (18–20.67) kPa] and SSM [54.5 (52.3–57.6) to 28.9 (27.6–30.25) kPa] showed a significant decline from baseline value over a follow‐up of 12 (6–13) months. Gradual reduction occurred in the LSM and SSM over 1–5 years, with near‐normal LSM [10.2 (9.2–11.5) kPa] and SSM [22.3 (20.5–24.3) kPa] values in patients (n‐16) with > 5 years follow‐up. Patients without RI showed worsening in LSM and SSM. Hepatopulmonary syndrome and hepatocellular carcinoma developed in 4 (8%) and 1 (1.7%) cases respectively.

Conclusion

RI leads to clinical recovery and reduction with near normalization of LSM and SSM over long‐term follow‐up in children with BCS. 2D‐SWE is a promising tool to monitor outcomes.
Comprehensive analyses of neurodevelopmental outcomes and quality of life of children with biliary atresia
Authors: Satomura Yoshinori , Tachibana Makiko , Yasuda Kie , Yamano Yuki , Inoue Taisuke , Fukui Miho , Onuma Shinsuke , Fukuoka Tomoya , Kimura Takeshi , Ueno Takehisa , Tachibana Masaya , Ozono Keiichi , Bessho Kazuhiko
Published: December 2023

Objectives

To holistically evaluate neurodevelopmental outcomes and quality of life (QOL) of Japanese patients with biliary atresia (BA) and to investigate the factors associated with the outcomes.

Methods

This study enrolled patients with BA aged 5–18 years who visited Osaka University Hospital in 2021. Neurodevelopmental assessments were performed to evaluate intellectual ability, cognitive functions and adaptive skill levels. Furthermore, emotional and behavioral issues, characteristics of attention deficit hyperactivity disorder, and QOL were concomitantly assessed in the same cohort. Biochemical and social factors associated with the results were examined.

Results

Fifty‐three patients, with a median age of 11.2 years were included in the analyses. Patients with BA had a significantly lower Full‐Scale Intelligence Quotient or developmental quotient (FSIQ/DQ) score and Vineland Adaptive Behavior Scale (VABS) composite score than the general Japanese population. Household education level and short stature were associated with low and borderline FSIQ/DQ and VABS composite scores, respectively. Among patients with low and borderline FSIQ/DQ scores, those with average or high VABS composite scores received significantly less neuroeducational care than those with low and borderline VABS composite scores. Despite the low FSIQ/DQ and VABS composite scores, the total QOL scores were higher than those of the general population.

Conclusion

Patients with BA had intellectual and behavioral impairments. Notably, patients with intellectual impairments are overlooked and not followed up, especially if adaptive skills are maintained.
Faster discharge with lactated ringers than normal saline in first 72 h of acute pancreatitis: A multicenter randomized trial
Authors: Farrell Peter R. , DesPain Angelica W. , Farmer Peter , Farrell Leslie M. , Greenfield Bryan , Rogers Michael E. , Hornung Lindsey , Kim Esther , Pearman Ryan , Neway Beemnet , Thompson Tyler , Heubi James E. , Sehgal Sona , Ammoury Rana , Abu‐El‐Haija Maisam
Published: December 2023

Objectives

Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS.

Study Design

A multisite randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 h. Primary outcomes were serial C‐reactive protein (CRP) values. Secondary outcomes included other lab values, time to feeds, length of stay (LOS), systemic inflammatory response syndrome (SIRS) development, and progression to severe AP (SAP).

Results

We studied 76 patients (38 LR, 38 NS). CRP at 24 and 48 h were not significantly different between LR or NS group. Additionally, there were no differences in trends of BUN, amylase, lipase, SIRS status, or SAP development between the LR and NS group at 24 and 48 h. A higher proportion of LR patients (32%, 12/38) were discharged before 48 h compared to NS (13%, 5/38). The LR group had a significantly higher rate of discharge within the first 72 h compared to the NS group (p = 0.02).

Conclusion

The use of LR was associated with a faster rate of discharge during the intervention period and in the first 72 h, but no other differences compared to NS. This reduction in length of hospitalization has significant implications for patients and healthcare costs.
Effect of oropharyngeal colostrum therapy on neonatal sepsis in preterm neonates: A systematic review and meta‐analysis
Authors: Anne Rajendra Prasad , Kumar Jogender , Kumar Praveen , Meena Jitendra
Published: December 2023

Various studies have shown that oropharyngeal colostrum application (OPCA) is beneficial to preterm neonates. We performed a systematic review and meta‐analysis to assess whether OPCA reduces the incidence of culture‐proven neonatal sepsis in preterm neonates. Randomized controlled trials comparing OPCA with placebo or standard care in preterm neonates were included. Medline, Embase, Web of Science, Cumulated Index to Nursing and Allied Health Literature, Scopus, and CENTRAL were searched for studies published up to June 15, 2023. We used the Cochrane Risk of Bias tool, version 2, for risk of bias assessment, the random‐effects model (RevMan 5.4) for meta‐analysis, and Gradepro software for assessing the certainty of evidence. Twenty‐one studies involving 2393 participants were included in this meta‐analysis. Four studies had a low risk of bias, whereas seven had a high risk. Oropharyngeal colostrum significantly reduced the incidence of culture‐proven sepsis (18 studies, 1990 neonates, risk ratio [RR]: 0.78, 95% confidence interval [95% CI]: 0.65, 0.94), mortality (18 studies, 2117 neonates, RR: 0.73, 95% CI: 0.59, 0.90), necrotizing enterocolitis (NEC) (17 studies, 1692 neonates, RR: 0.59, 95% CI: 0.43, 0.82), feeding intolerance episodes (four studies, 445 neonates, RR: 0.59, 95% CI: 0.38, 0.92), and the time to full enteral feeding (19 studies, 2142 neonates, mean difference: −2 to 21 days, 95% CI: −3.44, −0.99 days). There was no reduction in intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, ventilator‐associated pneumonia, neurodevelopmental abnormalities, hospital stay duration, time to full oral feeding, weight at discharge, pneumonia, and duration of antibiotic therapy. The certainty of the evidence was high for the outcomes of culture‐positive sepsis and mortality, moderate for NEC, low for time to full enteral feeding, and very low for feeding intolerance. OPCA reduces culture‐positive sepsis and mortality (high certainty), NEC (moderate certainty), and time to full enteral feeding (low certainty) in preterm neonates. However, scarcity of data from extremely premature infants limits the generalizability of these results to this population.
Microbial biosurfactant based nanoemulsions and their applications: A review
Authors: Yoosuf Subi , Nambiar Prajith
Published: December 2023

Nanoemulsions exhibit a wide range of practical applications owing to their smaller particle size, stability, and enhanced bioavailability. Conventional surfactants widely used in nanoemulsion formulations namely, polysorbate 80, macrogolglycerol ricinoleate, and 4‐octylphenol polyethoxylate have been associated with anaphylactoid responses, alterations in normal flora, cytotoxicity and tissue damage. The use of less toxic, environment‐friendly microbial biosurfactants in the formulation of nanoemulsions have been demonstrated to manifest stability, slow drug release, enhanced skin permeability, and bioactivity. The type and composition of mixed microbial biosurfactants used in nanoemulsions can decrease the droplet size and synergistically increase the stability. Moreover, a lower concentration of drug‐loaded surfactin‐based nanoemulsion synergistically inhibited the proliferation of cancer cells by 50% (IC50). The scope of the current review is to focus on the prospect of substituting conventional surfactants with biosurfactants obtained from microbial origin for nanoemulsion formulations. It also aims to draw attention to the paucity of research in the combinatorial study of biosurfactants and functional drugs used in nanoemulsions. The review emphasizes the bioactivity of microbial biosurfactant‐based nanoemulsions and their applications in diverse sectors. The differences in emulsion stability and size of microbial biosurfactant and conventional surfactant‐based nanoemulsions have been highlighted. The study intends to promote comparative research between nanoemulsions prepared using conventional surfactants and microbial biosurfactants.
Angiosarcoma of the scalp successfully treated with Nivolumab—A case report
Authors: Coltoiu Casandra A. , Piroth Marie , Bonnelye Julia , Zimmermann Ute , Quereux Gaëlle
Published: December 2023

Angiosarcomas are rare, aggressive tumours with a propensity for the head and neck region. Surgery is the mainstay of treatment of localised angiosarcoma, but in unresectable or metastatic disease, the treatment is much more challenging. Traditionally, chemotherapy (Paclitaxel in particular) has been the treatment of choice. Evidence from case reports and small trials shows that PD1 inhibitors have activity against angiosarcomas, despite the lack of a large clinical trial data demonstrating definitive efficacy. The present case exemplifies the susceptibility of this malignancy to anti‐PD1 agents. We report a 77‐year‐old male patient with an advanced, multifocal angiosarcoma of the frontotemporal and malar region. The patient was pretreated using the association of Propranolol and Endoxan and then Paclitaxel. Because of the lack of efficacy, the patient was started on Nivolumab as the third line of therapy. After five cycles of immunotherapy, an excellent response was achieved, with complete remission of the cutaneous lesions as well as a partial remission of the hepatic nodules. The duration of response is currently 14 months, the patient being still alive at the present time. This case suggests that immune checkpoint inhibitors may represent a viable therapeutic option that needs further exploration for the treatment of locally advanced, unresectable or metastatic cases of cutaneous angiosarcoma.