bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different approaches in management of neonatal unconjugated hyperbilirubinemia: a review article
Authors: Fouly Amira A. , Bendas Ehab R. , Farid Yasmin A. , Sabry Sarah , Abou El Fadl Dina K. 
Published: November 2024

Abstract
Background
Neonatal hyperbilirubinemia is a prevalent condition that affects newborns, characterized by elevated serum bilirubin levels. The accumulation of bilirubin can cause neurotoxicity, resulting in various complications, and in severe cases, even mortality. The underlying pathophysiology of this condition primarily involves an inconsistency between the synthesis and excretion of bilirubin. Despite the short- and long-term side effects of phototherapy, it is considered a core treatment of neonatal hyperbilirubinemia. Exchange transfusion is considered a last resort in cases where phototherapy fails. Several studies have investigated the use of various agents either to replace phototherapy or to be added as adjuvants to reduce the time required for phototherapy and hence minimize the adverse effects. Some of these studies have demonstrated positive outcomes, indicating their effectiveness, while others have failed to yield any significant differences in treatment duration.

Main text
The present review summarized the etiology of neonatal hyperbilirubinemia. It was demonstrated that neonatal hyperbilirubinemia has mainly two types: Conjugated and unconjugated hyperbilirubinemia. Treatment options for neonatal hyperbilirubinemia were discussed with phototherapy as the most prevalent and successful option followed by exchange transfusion. Side effects of phototherapy were also discussed together with the different approaches introduced to clinical practice to minimize these side effects.

Conclusion
Phototherapy is the most successful treatment of neonatal hyperbilirubinemia, although its side effects are of great concern. Studies introducing adjuvants such as zinc sulfate and ursodeoxycholic acid have demonstrated promising results in reducing the duration of phototherapy and minimizing the side effects. However, these results are inconclusive, and further research is required to validate the safety and efficacy of these adjuvants.
A Novel Y-Shaped Pegylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency
Authors: Liang Yan , Wei Haiyan , Yang Fan , Zhang Hua , Chen Linqi , Yao Hui , Luo Xiaoming , Cheng Xinran , Yang Yu , Lian Qun , Du Hongwei , Li Tang , Li Pin , Zhang Gaixiu , Song Fuying , Liang Liyang , Liu Deyun , Zhu Shunye , Gong Haihong , Gong Chunxiu , Cheng Xiangao , Xu Zhuangjian , Ma Yaping , Su Zhe , Zhou Weidong , He Ruoyi , Yin Yalin , Sun Li , Luo Xiaoping 
Published: November 2024

Abstract

Context
Pegpesen is a novel Y-shape pegylated recombinant human growth hormone (rhGH) for once-weekly treatment of children with growth hormone deficiency (GHD).

Objective
This work aimed to evaluate the efficacy and safety of Pegpesen in children with GHD vs daily rhGH.

Methods
A multicenter, randomized, controlled phase 3 clinical trial was conducted at 23 centers in China with a duration of 52 weeks’ treatment. There were 391 pediatric participants diagnosed with GHD. Participants were randomly assigned 2:1 to a weekly Pegpesen group (140 μg/kg/week) or a daily rhGH group (245 μg/kg/week) for 52 weeks. The primary end point was the growth velocity (GV) at 52 weeks, and the secondary end points mainly involved changes from baseline in height SD scores for chronological age and bone age (ΔHt SDS CA and ΔHt SDS BA).

Results
At 52 weeks, the least squares mean (LS means) of GV was 9.910 cm/year in the Pegpesen group and 10.037 cm/year in the daily rhGH group. The LS means difference between groups was −0.127 (95% CI, −0.4868 to 0.2332), confirming that weekly Pegpesen is noninferior to daily rhGH. The LS means of ΔHt SDS CA, ΔHt SDS BA, were similar across both groups (all P &gt; .05). Safety profiles and adherence were comparable.

Conclusion
Pegpesen was noninferior to daily rhGH, with similar safety, lower dosage requirements, thus presenting a new therapeutic option for children with GHD.
Characterization of a Novel Variant in the NR3C1 Gene: Differentiating Glucocorticoid Resistance From Cushing Syndrome
Authors: Laulhé Margaux , Yacobi Bach Michal , Perrot Julie , Gershinsky Michal , Fagart Jérôme , Shefer Gabi , Amazit Larbi , Kamenický Peter , Viengchareun Say , Martinerie Laetitia , Greenman Yona 
Published: November 2024

Abstract

Context
Primary generalized glucocorticoid resistance syndrome (GGRS) is a rare endocrine disease caused by loss-of-function variants of the NR3C1 gene encoding the glucocorticoid receptor (GR).

Objective
We describe a novel heterozygous missense variant (NM_000176.3, c.1330T&gt;G, p.Phe444Val) within the DNA-binding domain.

Clinical Case
Elevated urinary free cortisol levels were detected in a 59-year-old male patient before bariatric surgery (body mass index 39.9 kg/m2). Early-onset hypertension was well controlled. The low-dose dexamethasone suppression test was pathologic, but ACTH and midnight salivary cortisol levels were normal. The patient was initially referred to transsphenoidal surgery for a presumed diagnosis of Cushing disease. He presented to our department at the age of 68, when the clinical diagnosis of GGRS was established.

Methods
Functional characterization of the variant was performed ex vivo through transient transfection assays in HEK 293T cells to assess transcriptional activity and nuclear translocation.

Results
The variant showed a lack of transcriptional activity (GRWT: 91.5 [80.5; 101.2] vs GRF444V: 1.0 [1.0; 1.0]) despite efficient nuclear translocation in response to dexamethasone, suggesting a DNA binding defect of the variant. These results are discussed in the light of previously reported GGRS cases.

Conclusion
We have described a novel heterozygous mutation of the NR3C1 gene associated with primary GGRS. This case highlights the importance of raising awareness of clinical and laboratory features of this rare disorder, to enable early diagnosis and avoid unnecessary and potentially dangerous diagnostic and therapeutic procedures.
Role of the GH-IGF Axis in Statural Growth and Harmonious Body Proportionality: In Search of Vitruvian Man?
Authors: Guevara-Aguirre Jaime , Bright George M , Guevara Alexandra , Tite Maria , Saavedra Jannette , Teran Enrique , Rosenfeld Ron G 
Published: November 2024

Abstract

Context
Body proportions are the objective parameters of harmonious growth and reflect the interplay of genetic, environmental, metabolic, and hormonal actions. Mutations in the growth hormone receptor gene (GHR) result in severe growth failure. The study of individuals affected with these mutations can inform us about the role of growth peptides in harmonious, proportional growth.

Objective
The aim of this study was to critically assess the role of the growth hormone–insulin-like growth factor (GH-IGF) axis in statural growth and in particular body proportionality.

Methods
In this epidemiological, noninterventional study, we compared the anthropometric measurements and body proportions of an Ecuadorian cohort of adults with GH insensitivity (GHI) due to a homozygous mutation at codon 180/exon 6 of GHR, to their carrier and noncarrier relatives, and to noncarrier unrelated controls. We also investigated the relations between serum IGF-I concentrations and auxological determinations.

Results
In this cohort of 201 adults, sex-specific distributions of height (Ht), lower segment, upper segment, arm span, head circumference (HC), and hand and foot length were lower in the GHI individuals than in the other groups. The GHI individuals had the lowest lower segment/Ht, the highest upper segment/Ht, the lowest arm span/Ht and the highest HC/Ht ratio. Hand and foot length/Ht ratios were not uniformly affected. Serum IGF-I concentrations displayed a positive logarithmic correlation with all body measurements but were negatively correlated with the HC/Ht ratio.

Conclusion
These findings indicate that individuals homozygous for the GHR mutation have disharmonious body proportions due to abnormal GH/IGF-I action on the growth of the long bones. Contrary to common assumptions, disruption of the GH-IGF axis results in disproportionality and disharmonious growth.
Evaluation of Sleep Health in Children With Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
Authors: Golob Laura , Mercado-Munoz Yesica , Liu Wenxi , Singh Anvita , Hodges James S , Siegel Lianne , Morero Helena , Gao Zan , Tipp Angela , Simon Stacey L , Sarafoglou Kyriakie 
Published: November 2024

Abstract

Context
Literature on sleep health in children with congenital adrenal hyperplasia (CAH) is sparse despite the important role the hypothalamic-pituitary-adrenal axis plays in sleep onset, duration, and awakenings after sleep onset.

Objective
To evaluate sleep health in children and adolescents with CAH as measured by wrist actigraphy and validated sleep questionnaires.

Methods
Cross-sectional study at our multidisciplinary CAH clinic. Participants aged 3 to 18 years with classic CAH wore an ActiGraph GT3X+ accelerometer for 1 week. Children and parents completed sleep questionnaires, and the results were compared to published samples from the community and children with sleep disorders (clinical). Actigraphy sleep health measures were compared to consensus sleep duration recommendations and normative data in healthy children.

Results
Forty-four participants (23 male) with CAH completed the study. Actigraphy found sleep duration in children with CAH was less than recommended guidelines with significantly worse sleep efficiency and increased wake after sleep onset (P &lt; .05) compared to healthy children. After sleep onset, the average number of awakenings increased from 1.67 per hour during the first 2 hours after the evening hydrocortisone dose to 3.12 per hour 4 to 7 hours after the dose, corresponding with washout of the evening hydrocortisone dose. Parents of 3- to 10-year-olds reported significantly worse sleep onset delay and decreased sleep duration than both the community and clinical samples, and significantly more night awakenings than the community sample.

Conclusion
Our findings suggest that sleep health is impaired in children with CAH and is an important consideration for both clinical practice and future research.
Severe, Symptomatic Hypercalcemia Secondary to PTH-secreting Pancreatoblastoma
Authors: Gandhi Anand D , McCallum James D , Fisher Jonathan S 
Published: November 2024

Abstract
Hypercalcemia may be induced by a variety of etiologies, most commonly primary hyperparathyroidism. Although primary hyperparathyroidism represents a relatively common endocrinological disorder, ectopic PTH secretion is a rare entity that is less well described in literature. We describe the first case to our knowledge of severe, symptomatic hypercalcemia found to be secondary to a PTH-secreting pancreatoblastoma. The patient initially presented with fatigue and progressive upper extremity intermittent muscular twitching. He was found to have biochemical evidence of primary hyperparathyroidism. A computed tomography scan of the neck and a sestamibi nuclear scan failed to definitively demonstrate a parathyroid adenoma or hyperplasia and bilateral surgical parathyroid exploration was unrevealing for any pathology. Abdominal imaging via computed tomography was obtained for evaluation of progressive postoperative epigastric pain, and the patient was found to have a retroperitoneal mass that, after biopsy, was diagnostic for a pancreatoblastoma. This mass was resected resulting in a fall in intraoperative PTH values and subsequent postoperative hypocalcemia secondary to hungry bone syndrome. Upon follow-up, the patient's parathyroid function recovered and doses of supplemental calcium and vitamin D could be tapered. Ectopic PTH-secreting masses represent a rare entity but should be considered in individuals with unclear etiology of recalcitrant primary hyperparathyroidism.
Disparities in Diabetes Technology Uptake in Youth and Young Adults With Type 1 Diabetes: A Global Perspective
Authors: Conway Rebecca Baqiyyah , Snell-Bergeon Janet , Honda-Kohmo Kyoko , Peddi Anil Kumar , Isa Salbiah Binti , Sulong Shakira , Sibomana Laurien , Gerard Gonzalez Andrea , Song Jooyoun , Lomax Kate Elizabeth , Lo Ching-Nien , Kim Wondong , Haynes Aveni , de Bock Martin , Burckhardt Marie-Anne , Schwab Savannah , Hong Kwanho 
Published: November 2024

Abstract
Globally, nearly 9 million people are living with type 1 diabetes (T1D). Although the incidence of T1D is not affected by socioeconomic status, the development of complications and limited access to modern therapy is overrepresented in vulnerable populations. Diabetes technology, specifically continuous glucose monitoring and automated insulin delivery systems, are considered the gold standard for management of T1D, yet access to these technologies varies widely across countries and regions, and varies widely even within high-income countries. This review focuses on disparities in diabetes technology use among adolescents and young adults with T1D, barriers to access and use, and summarizes common themes emerging across countries and regions. We conducted a survey among medical technology manufacturers and physicians in various countries across diverse geographical regions and performed extensive literature searches. Across all countries and regions, economic barriers stand out as the largest and most common barriers, either preventing market penetrance of technology into a country or limiting its access to the individual with diabetes due to high out of pocket costs. Other common barriers include structural or accessibility barriers, such as stringent eligibility requirements by insurance providers, regardless of whether the insurance was private or government-based, and provider/individual level barriers. Based on the evidence presented, we suggest the need for a joint effort involving governments, private health insurers, technology manufacturers, and healthcare providers to address the global disparities of diabetic technology utilization and ensure equitable access for all individuals living with T1D worldwide.
Early-life challenge enhances cortisol regulation in zebrafish larvae
Authors: Castillo-Ramírez Luis A. , Herget Ulrich , Ryu Soojin , De Marco Rodrigo J. 
Published: November 2024

ABSTRACT
The hypothalamic-pituitary-adrenal (HPA) axis in mammals and the hypothalamic-pituitary-interrenal (HPI) axis in fish are open systems that adapt to the environment during development. Little is known about how this adaptation begins and regulates early stress responses. We used larval zebrafish to examine the impact of prolonged forced swimming at 5 days post-fertilization (dpf), termed early-life challenge (ELC), on cortisol responses, neuropeptide expression in the nucleus preopticus (NPO), and gene transcript levels. At 6 dpf, ELC-exposed larvae showed normal baseline cortisol but reduced reactivity to an initial stressor. Conversely, they showed increased reactivity to a second stressor within the 30-min refractory period, when cortisol responses are typically suppressed. ELC larvae had fewer corticotropin-releasing hormone (crh), arginine vasopressin (avp), and oxytocin (oxt)-positive cells in the NPO, with reduced crh and avp co-expression. Gene expression analysis revealed upregulation of genes related to cortisol metabolism (hsd11b2, cyp11c1), steroidogenesis (star), and stress modulation (crh, avp, oxt). These results suggest that early environmental challenge initiates adaptive plasticity in the HPI axis, tuning cortisol regulation to balance responsiveness and protection during repeated stress. Future studies should explore the broader physiological effects of prolonged forced swimming and its long-term impact on cortisol regulation and stress-related circuits.
Exact Solution of the Vehicle Routing Problem with Drones
Authors: Schmidt Jeanette , Tilk Christian , Irnich Stefan 
Published: November 2024

The vehicle routing problem with drones (VRP-D) that we consider is an extension of the capacitated vehicle routing problem in which the fleet consists of trucks equipped with one drone each. A truck and its drone can either move together or separately. A truck can release its drone at the depot or at a customer location and must pick it up later at another customer or the depot location. In this way, both trucks and drones deliver goods to customers working together as synchronized working units. A feasible route has to satisfy the capacity constraints of both the truck and the drone. A feasible solution to the VRP-D is a set of feasible routes such that each customer is served exactly once by either a truck or a drone. We investigate two standard objectives considered in the literature, that is, the minimization of the total routing cost and the sum of the routes’ durations. To solve the VRP-D exactly, we develop a branch-price-and-cut (BPC) algorithm. In particular, we present a new forward and implicit bidirectional labeling algorithm defined over an artificial network to solve the column-generation subproblems. The new bidirectional labeling algorithm substantially accelerates the solution process compared with its monodirectional counterpart. The time needed to solve the pricing problems is reduced by 55% on average when minimizing routing costs and by 30% when minimizing the sum of the routes’ durations. In further computational experiments, we analyze algorithmic components of the BPC algorithm, compare the cost and duration objectives, and highlight the impact of the drones’ speed on the structure of VRP-D solutions. For the routing-cost minimization objective, our BPC algorithm is able to solve several VRP-D instances with 50 vertices to proven optimality within one hour of computation time. The same instances with duration minimization are more difficult, and the BPC algorithm provides only heuristic solutions with an average gap not exceeding 3%. Funding: This work was supported by Deutsche Forschungsgemeinschaft [Project 418727865, Grant IR 122/10-1]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/trsc.2024.0544 .
Governance globaler Prozess- und ERP-Harmonisierung in dezentralen Unternehmen
Authors: Winter Robert , Scholz Thilo 
Published: November 2024

Zusammenfassung
Transformationsprogramme auf Unternehmensebene zielen darauf ab, sowohl lokale wie auch globale Veränderungsvorteile zu erzielen. Obwohl die Balance zwischen lokaler Differenzierung und globaler Konsistenz als Schlüsselfaktor für den Transformationserfolg anerkannt wird, wird das Verständnis für und der Umgang mit Spannungen im bestehenden Governance-Wissen und in der Praxis wenig behandelt. Neuere Forschungsbeiträge verwenden „Tension Theory“ und Erkenntnisse aus der vergleichenden Untersuchung von Transformationsprogrammen in der Praxis, um Gestaltungsprinzipien für eine spannungsbewusste Programm-Governance vorzuschlagen. Die vorliegende Studie berichtet, wie dieser Vorschlag in einem globalen Transformationsprogramm eines grossen internationalen Infrastrukturanbieters angepasst und weiterentwickelt wird. In der ersten Phase des Programms wird die Prozesslandschaft des Service-Produktionsmanagements über 22 global verteilte Landesgesellschaften hinweg harmonisiert, um die Grundlage für eine globale, konzernweite ERP-Harmonisierung zu schaffen. Zu den Erkenntnissen dieser Studie gehören Unterschiede in der Anwendbarkeit der vorgeschlagenen Gestaltungsprinzipien sowie der Vorschlag zusätzlicher Differenzierungen für die systematische Etablierung einer Governance für grosse Programme in heterogenen Umgebungen mit erheblicher lokaler Autonomie. Über fallbezogene Erkenntnisse hinaus zielt die Studie auch darauf ab, die Kontextualisierung generischer Gestaltungsprinzipien besser zu verstehen und die Notwendigkeit einer situativen Unterstützung der Governance von Transformationsprogrammen zu unterstreichen.
Exercise stress echocardiography shows impaired left ventricular function after hospitalization with COVID‐19 without overt myocarditis: A pilot study
Authors: Goldstein Robert E. , Hulten Edward A. , Arnold Thomas B. , Thomas Victoria M. , Heroy Andrew , Walker Erika N. , Fox Keiko , Lee Hyun , Libbus Joya , Markos Bethelhem , Hood Maureen N. , Harrell Travis E. , Haigney Mark C. 
Published: November 2024

AbstractUsual clinical testing rarely reveals cardiac abnormalities persisting after hospitalization for COVID. Such testing may overlook residual changes causing increased adverse cardiac events post‐discharge. To clarify status post‐hospitalization, we related exercise stress echocardiography (ESE) in 15 recovering patients (RP) age 30–63 without myocarditis to matching published data from healthy subjects (HS). RP exercise, average duration 8.2 ± 2.2 SD, was halted by dyspnea or fatigue. RP baselines matched HS except for higher heart rate. At peak stress, RP had significantly lower mean left ventricular (LV) ejection fraction (67% ± 7 vs. 73% ± 5, p < 0.0017) and higher peak early mitral inflow velocity/early mitral annular velocity (E/e’, 9.1 ± 2.5 vs. 6.6 ± 2.5, p < 0.006) compared with HS performing equal exercise (8.5 ± 2.6 min). Thus, when stressed, patients without known cardiac impairment showed diminished systolic contractile function and diastolic LV compliance vs. HS. RP peak heart rate was significantly higher (172 ± 18 vs. 153 ± 20); peak systolic blood pressure trended higher (192 ± 31 vs. 178 ± 19). Pulmonary artery systolic pressures among RP remained normal. ESE uniquely identified residual abnormality in cardiac contractile function not evident unstressed, exposing previously unrecognized residual influence of COVID‐19. This may reflect autonomic dysfunction, microvascular disease, or diffuse interstitial changes; these results may have implications for clinical management and later prognosis.
Lotmanian referentiality and (cultural) semantics
Authors: Rodríguez Higuera Claudio J. 
Published: November 2024

Abstract
Lotmanian semiotics comprises a complex and wide-encompassing system for understanding meaning-making in culture and cultural dynamics more generally. Its complexity is compounded by Lotman’s historically and artistically minded orientation. In this paper we propose a brief rereading of a particular aspect of Lotmanian theory – what we will term Lotmanian semantics – based on an interpretation of modeling systems theory that, by our account, retains the form of the original by appealing to the notion of language employed by Lotman and deployed as propositional thought qua language. We revisit Sebeok’s critique of modeling systems theory and find it unnecessary for the interpretation that we make of Lotman’s semiotics, and we then propose a two-level interpretation of the theory that allows us to describe both perceptual and cultural phenomena as different semantic kinds.