bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for lysosomal diseases in a selected pediatric population: the case of Gaucher disease and acid sphingomyelinase deficiency
Authors: Di Rocco Maja , Vici Carlo Dionisi , Burlina Alberto , Venturelli Francesco , Fiumara Agata , Fecarotta Simona , Donati Maria Alice , Spada Marco , Concolino Daniela , Pession Andrea 
Published: July 2023

Abstract
Background
GD and ASMD are lysosomal storage disorders that enter into differential diagnosis due to the possible overlap in their clinical manifestations. The availability of safe and effective enzymatic therapies has recently led many investigators to develop and validate new screening tools, such as algorithms, for the diagnosis of LSDs where the lack of disease awareness or failure to implement newborn screening results in a delayed diagnosis.

Results
the proposed algorithm allows for the clinical and biochemical differentiation between GD and ASMD. It is based on enzyme activity assessed on dried blood spots by multiplexed tandem mass spectrometry (MS/MS) coupled to specific biomarkers as second-tier analysis.

Conclusions
we believe that this method will provide a simple, convenient and sensitive tool for the screening of a selected population that can be used by pediatricians and other specialists (such as pediatric hematologists and pediatric hepatologists) often engaged in diagnosing these disorders.
Citrulline in the management of patients with urea cycle disorders
Authors: Imbard Apolline , Bouchereau Juliette , Arnoux Jean-Baptiste , Brassier Anaïs , Schiff Manuel , Bérat Claire-Marine , Pontoizeau Clément , Benoist Jean-François , Josse Constant , Montestruc François , de Lonlay Pascale 
Published: July 2023

Abstract
Background
Treatment recommendations for urea cycle disorders (UCDs) include supplementation with amino acids involved in the urea cycle (arginine and/or citrulline, depending on the enzyme deficiency), to maximize ammonia excretion through the urea cycle, but limited data are available regarding the use of citrulline. This study retrospectively reviewed clinical and biological data from patients with UCDs treated with citrulline and/or arginine at a reference center since 1990. The aim was to describe the prescription, impact, and safety of these therapies. Data collection included patient background, treatment details, changes in biochemical parameters (plasma ammonia and amino acids concentrations), decompensations, and patient outcomes.

Results
Overall, 79 patients (median age at diagnosis, 0.9 months) received citrulline and/or arginine in combination with a restricted protein diet, most with ornithine transcarbamylase (n = 57, 73%) or carbamoyl phosphate synthetase 1 (n = 15, 19%) deficiencies. Most patients also received ammonium scavengers. Median follow-up was 9.5 years and median exposure to first treatment with arginine + citrulline, citrulline monotherapy, or arginine monotherapy was 5.5, 2.5, or 0.3 years, respectively. During follow-up, arginine or citrulline was administered at least once (as monotherapy or in combination) in the same proportion of patients (86.1%); the overall median duration of exposure was 5.9 years for arginine + citrulline, 3.1 years for citrulline monotherapy, and 0.6 years for arginine monotherapy. The most common switch was from monotherapy to combination therapy (41 of 75 switches, 54.7%). During treatment, mean ammonia concentrations were 35.9 µmol/L with citrulline, 49.8 µmol/L with arginine, and 53.0 µmol/L with arginine + citrulline. Mean plasma arginine concentrations increased significantly from the beginning to the end of citrulline treatment periods (from 67.6 µmol/L to 84.9 µmol/L, P < 0.05). At last evaluation, mean height and weight for age were normal and most patients showed normal or adapted behavior (98.7%) and normal social life (79.0%). Two patients (2.5%) experienced three treatment-related gastrointestinal adverse reactions.

Conclusions
This study underlines the importance of citrulline supplementation, either alone or together with arginine, in the management of patients with UCDs. When a monotherapy is considered, citrulline would be the preferred option in terms of increasing plasma arginine concentrations.
Effects of miglustat therapy on neurological disorder and survival in early-infantile Niemann-Pick disease type C: a national French retrospective study
Authors: Freihuber Cécile , Dahmani-Rabehi Bahia , Brassier Anaïs , Broué Pierre , Cances Claude , Chabrol Brigitte , Eyer Didier , Labarthe François , Latour Philippe , Levade Thierry , Pichard Samia , Sevin Caroline , Vanier Marie T. , Héron Bénédicte 
Published: July 2023

AbstractBackgroundNiemann-Pick disease type C (NP-C) is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurodegeneration and premature death. While miglustat can stabilize neurological manifestations in later onset forms of NP-C, its efficacy in the early-infantile neurological form has not been demonstrated. In this observational retrospective study, we compared long-term neurodevelopmental outcome and survival between an untreated and a treated group of early infantile NP-C patients.MethodsData available on all NP-C patients with early infantile neurological onset diagnosed in France between 1990 and 2013 were compiled. Patients with incomplete data or who had died from a systemic perinatal, rapidly fatal form were excluded.ResultsTen patients were included in the treated group (year of birth: 2006–2012), and 16 patients in the untreated group [born 1987–2005 (n = 15), 2012 (n = 1)]. The median age at neurological onset was 9 months (5–18) in the treated group, and 12 months (3–18) in the untreated group (p = 0.22). Miglustat therapy was started at a median age of 24.5 months (9–29) and median duration was 30 months (11–56). Gastrointestinal adverse events were reported in 7/10 patients on miglustat. All patients developed loss of psychomotor acquisitions or additional neurological symptoms despite miglustat therapy. The ages of developmental milestones and neurological involvement did not significantly differ between the two groups. Four patients in the untreated group were lost to follow up. The 22 remaining patients had died by the end of the study and no patient survived beyond the age of 7.4 years. The median survival age was 4.42 years in the untreated group and 5.56 years in the treated group; the Kaplan–Meier survival curves were not significantly different (log-rank test: p = 0.11).ConclusionsMiglustat allowed no significant long-term neurodevelopmental improvement nor significant increase of survival in patients with early infantile NP-C.
The Vasopressin Loading for Refractory septic shock (VALOR) study: a prospective observational study
Authors: Nakamura Kensuke , Nakano Hidehiko , Ikechi Daisuke , Mochizuki Masaki , Takahashi Yuji , Koyama Yasuaki , Hashimoto Hideki , Abe Toshikazu , Hayakawa Mineji , Yamakawa Kazuma 
Published: July 2023

Abstract
Background
Vasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study.

Methods
Vasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 μg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events.

Results
Ninety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dtmax were higher in responders after loading. Median CAI changes were − 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%).

Conclusions
Vasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure.
Human platelet lysate stimulates neurotrophic properties of human adipose-derived stem cells better than Schwann cell-like cells
Authors: Brambilla Stefania , Guiotto Martino , Torretta Enrica , Armenia Ilaria , Moretti Matteo , Gelfi Cecilia , Palombella Silvia , di Summa Pietro G. 
Published: July 2023

Abstract
Background
Trauma-associated peripheral nerve injury is a widespread clinical problem causing sensory and motor disabilities. Schwann cells (SCs) contribute to nerve regeneration, mainly by secreting nerve growth factor (NGF) and brain-derived neurotrophic factor. In the last years, adipose-derived stem cells (ASCs) differentiated into SCs (SC-ASCs) were considered as promising cell therapy. However, the cell trans-differentiation process has not been effectively showed and presents several drawbacks, thus an alternative approach for increasing ASCs neurotrophic properties is highly demanded. In the context of human cell-based therapies, Good Manufacturing Practice directions indicate that FBS should be substituted with a xenogeneic-free supplement, such as Human Platelet Lysate (HPL). Previously, we demonstrated that neurotrophic properties of HPL-cultured ASCs were superior compared to undifferentiated FBS-cultured ASCs. Therefore, as following step, here we compared the neurotrophic properties of differentiated SC-like ASCs and HPL-cultured ASCs.

Methods
Both cell groups were investigated for gene expression level of neurotrophic factors, their receptors and neuronal markers. Moreover, the expression of nestin was quantitatively evaluated by flow cytometry. The commitment toward the SC phenotype was assessed with immunofluorescence pictures. Proteomics analysis was performed on both cells and their conditioned media to compare the differential protein profile. Finally, neurotrophic abilities of both groups were evaluated with a functional co-culture assay, assessing dorsal root ganglia survival and neurite outgrowth.

Results
HPL-cultured ASCs demonstrated higher gene expression of NGF and lower expression of S100B. Moreover, nestin was present in almost all HPL-cultured ASCs and only in one quarter of SC-ASCs. Immunofluorescence confirmed that S100B was not present in HPL-cultured ASCs. Proteomics analysis validated the higher expression of nestin and the increase in cytoskeletal and ECM proteins involved in neural regeneration processes. The co-culture assay highlighted that neurite outgrowth was higher in the presence of HPL-ASCs or their conditioned medium compared to SC-ASCs.

Conclusions
All together, our results show that HPL-ASCs were more neurotrophic than SC-ASCs. We highlighted that the HPL triggers an immature neuro-induction state of ASCs, while keeping their stem properties, paving the way for innovative therapies for nerve regeneration.

Graphical Abstract
DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion
Authors: Ren Dongyan , Luo Bin , Chen Peng , Yu Lulu , Xiong Mingtao , Fu Zhiqiang , Zhou Tian , Chen Wen-Bing , Fei Erkang 
Published: July 2023

Abstract
Background
Dendritic spines are the sites of excitatory synapses on pyramidal neurons, and their development is crucial for neural circuits and brain functions. The spine shape, size, or number alterations are associated with neurological disorders, including schizophrenia. DiGeorge syndrome critical region gene 2 (DGCR2) is one of the deleted genes within the 22q11.2 deletion syndrome (22q11DS), which is a high risk for developing schizophrenia. DGCR2 expression was reduced in schizophrenics. However, the pathophysiological mechanism of DGCR2 in schizophrenia or 22q11DS is still unclear.

Results
Here, we report that DGCR2 expression was increased during the neurodevelopmental period and enriched in the postsynaptic densities (PSDs). DGCR2-deficient hippocampal neurons formed fewer spines. In agreement, glutamatergic transmission and synaptic plasticity were decreased in the hippocampus of DGCR2-deficient mice. Further molecular studies showed that the extracellular domain (ECD) of DGCR2 is responsible for its transcellular interaction with cell adhesion molecule Neurexin1 (NRXN1) and spine development. Consequently, abnormal behaviors, like anxiety, were observed in DGCR2-deficient mice.

Conclusions
These observations indicate that DGCR2 is a novel cell adhesion molecule required for spine development and synaptic plasticity, and its deficiency induces abnormal behaviors in mice. This study provides a potential pathophysiological mechanism of DGCR2 in 22q11DS and related mental disorders.
Joint resource allocation and user association for multi-cell integrated sensing and communication systems
Authors: Zhang Jiahui , Fei Zesong , Wang Xinyi , Liu Peng , Huang Jingxuan , Zheng Zhong 
Published: July 2023

AbstractThe densification of the orthogonal frequency division multiplexing (OFDM) based fifth-generation communication systems, as well as the requirement of integrating sensing and communication functionalities, has promoted the development of integrated-sensing-and-communication (ISAC) dense cellular networks (DCNs). In the OFDM-based ISAC-DCN, multiple base stations simultaneously serve mobile users and sense targets based on the echo of downlink communication signals. In this paper, we establish the interference model in ISAC-DCN for sensing and communication. Focusing on the interference management of the ISAC-DCN, we investigate the multi-dimension resource allocation problem. In particular, we aim to maximize the network utility by jointly optimizing sub-band allocation, user association, and transmission power under the sensing signal-to-interference-plus-noise ratio constraint to be solved iteratively. The mixed-integer optimization problem is decoupled into three sub-problems. Specifically, a greedy genetic sub-band allocation scheme is proposed for sub-band allocation to reduce total interference. We employ the successive convex approximation technique to transform the transmission power control sub-problem and solve it via geometric programming. Simulation results illustrate the trade-off between sensing and communication performances, and show that the proposed algorithm significantly improves the network utility and achieves higher detection probability.
Variant rs17619600 in the gene encoding serotonin receptor 2B (HTR2B) increases the risk of gestational diabetes mellitus: a case–control study
Authors: Penno Juliana Regina Chamlian Zucare , Santos-Bezerra Daniele Pereira , Cavaleiro Ana Mercedes , da Silva Sousa Ana Maria , Zaccara Tatiana Assunção , da Costa Rafaela Alkmin , Francisco Rossana Pulcineli Vieira , Correa-Giannella Maria Lucia 
Published: July 2023

Abstract
Background
During pregnancy, the increase in maternal insulin resistance is compensated by hyperplasia and increased function of maternal pancreatic beta cells; the failure of this compensatory mechanism is associated with gestational diabetes mellitus (GDM). Serotonin participates in beta cell adaptation, acting downstream of the prolactin pathway; the blocking of serotonin receptor B (HTR2B) signaling in pregnant mice impaired beta cell expansion and caused glucose intolerance. Thus, given the importance of the serotoninergic system for the adaptation of beta cells to the increased insulin demand during pregnancy, we hypothesized that genetic variants (single nucleotide polymorphisms [SNPs]) in the gene encoding HTR2B could influence the risk of developing GDM.

Methods
This was a case–control study. Five SNPs (rs4973377, rs765458, rs10187149, rs10194776, and s17619600) in HTR2B were genotyped by real-time polymerase chain reaction in 453 women with GDM and in 443 pregnant women without GDM.

Results
Only the minor allele C of SNP rs17619600 conferred an increased risk for GDM in the codominant model (odds ratio [OR] 2.15; 95% confidence interval [CI] 1.53–3.09; P < 0.0001) and in the rare dominant model (OR 2.32; CI 1.61–3.37; P < 0.0001). No associations were found between the SNPs and insulin use, maternal weight gain, newborn weight, or the result of postpartum oral glucose tolerance test (OGTT). In the overall population, carriers of the XC genotype (rare dominant model) presented a higher area under the curve (AUC) of plasma glucose during the OGTT, performed for diagnostic purposes, compared with carriers of the TT genotype of rs17619600.

Conclusions
SNP rs17619600 in the HTR2B gene influences glucose homeostasis, probably affecting insulin release, and the presence of the minor allele C was associated with a higher risk of GDM.
Courier Dispatch in On-Demand Delivery
Authors: Chen Mingliu , Hu Ming 
Published: July 2023

We study a courier dispatching problem in an on-demand delivery system in which customers are sensitive to delay. Specifically, we evaluate the effect of temporal pooling by comparing systems using the dedicated strategy, with which only one order is delivered per trip, versus the pooling strategy, with which a batch of consecutive orders is delivered on each trip. We capture the courier delivery system’s spatial dimension by assuming that, following a Poisson process, demand arises at a uniformly generated point within a service region. With the same objective of revenue maximization, we find that the dispatching strategy depends critically on customers’ patience level, the size of the service region, and whether the firm can endogenize the demand. We obtain concise but informative results with a single courier and assuming that customers’ underlying arrival rate is large enough, meaning a crowded market, such as rush hour delivery. In particular, when the firm has a growth target and needs to achieve an exogenously given demand rate, using the pooling strategy is optimal if the service area is large enough to fully exploit the pooling efficiency in delivery. Otherwise, using the dedicated strategy is optimal. In contrast, if the firm can endogenize the demand rate by varying the delivery fee, using the dedicated strategy is optimal for a large service area. The reason is that it is optimal for the firm to sustain a relatively low demand rate by charging a high fee for a large service radius: within this large area, the pooling strategy leads to a long wait because it takes a long time for multiple orders to accumulate. Moreover, with an exogenous demand rate to meet, customers’ patience level has no impact on the dispatch strategy. However, when the demand rate can be endogenized, the dedicated strategy is preferable if customers are impatient. Furthermore, we extend our model to account for social welfare maximization, a hybrid contingent delivery policy, a general arrival rate that does not have to be large, a nonuniform distribution of orders in the service region, and multiple couriers. We also conduct numerical analysis and simulations to complement our main results and find that most insights in our base model still hold in these extensions and numerical studies. This paper was accepted by Jeannette Song, operations management. Funding: This work was supported by the Natural Sciences and Engineering Research Council of Canada [Grants RGPIN-2015-06757 and RGPIN-2021-04295]. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4858 .
“It feels like medically promoted disordered eating”: The psychosocial impact of gestational diabetes mellitus in the perinatal period
Authors: Benton Madeleine , Silverio Sergio A. , Ismail Khalida 
Published: July 2023

Background
The global prevalence of gestational diabetes mellitus (GDM) is increasing, and it can significantly impact women’s psychosocial outcomes in the perinatal period. The aim of this study was to explore the psychosocial impacts including experiences of support for women with GDM in the antenatal and postnatal period.

Methods
Semi-structured individual interviews were conducted with women (n = 33) living in the UK, who were either pregnant and recently diagnosed with GDM or had a previous GDM diagnosis within the past three years. Interviews were recorded, transcribed, and analysed using reflexive thematic analysis.

Findings
Analysis revealed six themes: 1. Diagnostic related frustration; 2. Impact on mental health; 3. The medicalisation of eating; 4. Losing agency to gain control; 5. Sourcing networks of support; 6. Current pregnancy; and future reproductive health. Each theme provides a unique insight into the experiences and psychological strain associated with GDM. From confusion and frustration at diagnosis, to the profound knock-on impact a diagnosis, associated lifestyle changes and medical appointments had on women’s mental health, and the perceived medicalisation of their eating behaviours and patterns.

Conclusion
Given the increasing prevalence of GDM and its wide-ranging psychosocial impacts, this study emphasises the need for healthcare professionals to consider the potential implications of GDM on women’s psychosocial outcome, and to consider alternative support options outside of the medical system, such as peer support.