bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landscape of Invasive Fusariosis in Pediatric Cancer Patients: Results of a Multicenter Observational Study From Latin America
Authors: Carlesse Fabianne , Paixão de Sousa da Silva Adriana Maria , Sztajnbok Jaques , Litivinov Nadia , Peron Karina , Otsuka Marcelo , Volpe Arnoni Mariana , Schirmer Marcelo , de Oliveira Costa Patricia , Munhoz Cavalcanti de Albuquerque Ana Lucia , Morales Hugo , Lopez-Medina Eduardo , A. Portilla Carlos , Valenzuela Romina , Motta Fabrizio , Motta Fabio Araújo , de Almeida Junior João Nobrega , Santolaya Maria Elena , Lopes Colombo Arnaldo 
Published: May 2024

Abstract
Invasive fusariosis (IF) is a life-threatening opportunistic infection that affects vulnerable hosts. We conducted a multicenter and multinational retrospective study to characterize the natural history and clinical management of IF in pediatric cancer patients. We selected patients &lt;18 years old who were sequentially hospitalized in 10 Latin American medical centers with a diagnosis of IF between 2002 and 2021. Data were collected using an electronic case report form complemented by a dictionary of terms. We assessed mortality rates at 30, 60, and 90 days. We collected data from 60 episodes of IF (median age, 9.8 years) that were mostly documented in patients with hematologic cancer (70%). Other risk conditions found were lymphopenia (80%), neutropenia (76.7%), and corticosteroid exposure (63.3%). IF was disseminated in 55.6% of patients. Skin lesions was present in 58.3% of our patients, followed by pulmonary involvement in 55%, sinusitis in 21.7%, bone/joint involvement in 6.7% and 1 case each of endocarditis and brain abscess. Positive blood and skin biopsy cultures were detected in 60% and 48.3% of cases, respectively. Fusarium solani complex was the most commonly identified agent (66.6%). The majority of patients received monotherapy within the first 72 hours (71.6%), either with voriconazole or amphotericin B formulation. The mortality rates at 30, 60, and 90 days were 35%, 41.6%, and 45%, respectively. An important factor affecting mortality rates appears to be disseminated disease. The high percentage of patients with fungal involvement in multiple organs and systems highlights the need for extensive workup for additional sites of infection in severely immunocompromised children.
Bona Fide Plant Steroid Receptors are Innovated in Seed Plants and Angiosperms through Successive Whole-Genome Duplication Events
Authors: Liu Jing , Wei Qiang , Zhao Zhen , Qiang Fanqi , Li Guishuang , Wu Guang 
Published: May 2024

Abstract
Whole-genome duplication (WGD) events are widespread in plants and animals, thus their long-term evolutionary contribution has long been speculated, yet a specific contribution is difficult to verify. Here, we show that ɛ-WGD and ζ-WGD contribute to the origin and evolution of bona fide brassinosteroid (BR) signaling through the innovation of active BR biosynthetic enzymes and active BR receptors from their respective ancestors. We found that BR receptors BRI1 (BR INSENSITIVE 1) and BRL1/3 (BRI1-LIKES 1/3) derived by ɛ-WGD and ζ-WGD, which occurred in the common ancestor of angiosperms and seed plants, respectively, while orphan BR receptor BRL2 first appeared in stomatophytes. Additionally, CYP85A enzymes synthesizing the bioactive BRs derived from a common ancestor of seed plants, while its sister enzymes CYP90 synthesizing BR precursors presented in all land plants, implying possible ligand–receptor coevolution. Consistently, the island domains (IDs) responsible for BR perception in BR receptors were most divergent among different receptor branches, supporting ligand-driven evolution. As a result, BRI1 was the most diversified BR receptor in angiosperms. Importantly, relative to the BR biosynthetic DET2 gene presented in all land plants, BRL2, BRL1/3 and BRI1 had high expression in vascular plants ferns, gymnosperms and angiosperms, respectively. Notably, BRI1 is the most diversified BR receptor with the most abundant expression in angiosperms, suggesting potential positive selection. Therefore, WGDs initiate a neofunctionalization process diverged by ligand-perception and transcriptional expression, which might optimize both BR biosynthetic enzymes and BR receptors, likely contributing to the evolution of land plants, especially seed plants and angiosperms.
Fluid dynamics and leukocyte transit in the lymphatic system
Authors: Li Huabing , Zhang Jingjing , Padera Timothy P , Baish James W , Munn Lance L 
Published: May 2024

Abstract
The lymphatic system plays a vital role in maintaining fluid balance in living tissue and serves as a pathway for the transport of antigen, immune cells, and metastatic cancer cells. In this study, we investigate how the movement of cells through a contracting lymphatic vessel differs from steady flow, using a lattice Boltzmann-based computational model. Our model consists of cells carried by flow in a 2D vessel with regularly spaced, bi-leaflet valves that ensure net downstream flow as the vessel walls contract autonomously in response to calcium and nitric oxide levels regulated by stretch and shear stress levels. The orientation of the vessel with respect to gravity, which may oppose or assist fluid flow, significantly modulates cellular motion due to its effect on the contraction dynamics of the vessel, even when the cells themselves are neutrally buoyant. Additionally, our model shows that cells are carried along with the flow, but when the vessel is actively contracting, they move faster than the average fluid velocity. We also find that the fluid forces cause significant deformation of the compliant cells, especially in the vicinity of the valves. Our study highlights the importance of considering the complex, transient flows near the valves in understanding cellular motion in lymphatic vessels.
SMAD2/3-SMYD2 and developmental transcription factors cooperate with cell-cycle inhibitors to guide tissue formation
Authors: Militi Stefania , Nibhani Reshma , Pook Martin , Pauklin Siim 
Published: May 2024

Abstract
Tissue formation and organ homeostasis are achieved by precise coordination of proliferation and differentiation of stem cells and progenitors. While deregulation of these processes can result in degenerative disease or cancer, their molecular interplays remain unclear. Here we show that the switch of human pluripotent stem cell (hPSC) self-renewal to differentiation is associated with the induction of distinct cyclin-dependent kinase inhibitors (CDKIs). In hPSCs, Activin/Nodal/TGFβ signaling maintains CDKIs in a poised state via SMAD2/3-NANOG-OCT4-EZH2-SNON transcriptional complex. Upon gradual differentiation, CDKIs are induced by successive transcriptional complexes between SMAD2/3-SMYD2 and developmental regulators such as EOMES, thereby lengthening the G1 phase. This, in turn, induces SMAD2/3 transcriptional activity by blocking its linker phosphorylation. Such SMAD2/3-CDKI positive feedback loops drive the exit from pluripotency and stepwise cell-fate specification that could be harnessed for producing cells for therapeutic applications. Our study uncovers fundamental mechanisms of how cell-fate specification is interconnected to cell-cycle dynamics and provides insight into autonomous circuitries governing tissue self-formation.
Yet Another Lattice Formulation of 2D U(1) Chiral Gauge Theory via Bosonization
Authors: Morikawa Okuto , Onoda Soma , Suzuki Hiroshi 
Published: May 2024

Abstract
Recently, lattice formulations of Abelian chiral gauge theory in two dimensions have been devised on the basis of the Abelian bosonization. A salient feature of these 2D lattice formulations is that the gauge invariance is exactly preserved for anomaly-free theories and thus is completely free from the question of the gauge mode decoupling. In the present paper, we propose yet another lattice formulation sharing this desired property. A particularly unique point in our formulation is that the vertex operator of the dual scalar field, which carries the vector charge of the fermion and the “magnetic charge” in the bosonization, is represented by a “hole” excised from the lattice; this is the excision method formulated recently by Abe et al. in a somewhat different context.
Rising Security and Religious Decline: Refining and Extending Insecurity Theory
Authors: Molteni Francesco 
Published: May 2024

Abstract
Explaining the reasons—while not the causes—behind religious decline is a central issue for sociologists interested in secularization processes. Many theoretical perspectives have been proposed over the last decades, and this article focuses on one of them. In particular, it refers to the so-called insecurity theory, formalized by Norris and Inglehart (2011), which reads processes of religious decline in light of the increased security coming with modernization. It summarizes the empirical evidence proposed so far by distinguishing between individual and contextual insecurity and static and longitudinal approaches. Moreover, it underlines the difference between economic and existential insecurity as well as the leading role of socialization processes. From this basis, it provides a summary of the main potential weaknesses of the theory and the main criticisms leveled against it, in order to expand its theoretical relevance and clarify what insecurity theory can, and cannot, tell us about secularization processes.
Testosterone replacement therapy in patients with cachexia: a contemporary review of the literature
Authors: Tabei Seyed Sajjad , Kataria Rhea , Hou Sean , Singh Armaan , Al Hameedi Hasan , Hasan Doaa , Hsieh Mike , Raheem Omer A 
Published: May 2024

AbstractIntroductionPatients with long-term chronic illnesses frequently present with hypogonadism, which is primarily managed through exogenous testosterone. These same patients also experience a high degree of cachexia, a loss of skeletal muscle and adipose tissue.ObjectiveTo perform a contemporary review of the literature to assess the effectiveness of testosterone replacement therapy (TRT) for managing chronic disease–associated cachexia.MethodsWe performed a PubMed literature search using MeSH terms to identify studies from 2000 to 2022 on TRT and the following cachexia-related chronic medical diseases: cancer, COPD, HIV/AIDS, and liver cirrhosis.ResultsFrom the literature, 11 primary studies and 1 meta-analysis were selected. Among these studies, 3 evaluated TRT on cancer-associated cachexia, 3 on chronic obstructive pulmonary disease, 4 on HIV and AIDS, and 2 on liver cirrhosis. TRT showed mixed results favoring clinical improvement on each disease.ConclusionsCachexia is commonly observed in chronic disease states. Its occurrence with hypogonadism, alongside the shared symptoms of these 2 conditions, points toward the management of cachexia through the administration of exogenous testosterone. Robust data in the literature support the use of testosterone in increasing lean body mass, improving energy levels, and enhancing the quality of life for patients with chronic disease. However, the data are variable, and further studies are warranted on the long-term efficacy of TRT in patients with cachexia.
Initial leadership concerns and availability of tobacco cessation services moderate changes in employee-reported concerns about tobacco-free workplace policy implementation over time
Authors: Siddiqi Ammar D , Carter Brian J , Chen Tzuan A , Martinez Leal Isabel , Britton Maggie , Correa-Fernández Virmarie , Rogova Anastasia , Kyburz Bryce , Williams Teresa , Reitzel Lorraine R 
Published: May 2024

Abstract
Tobacco-free workplace policies (TFWPs) are underused evidence-based interventions that reduce the elevated use of tobacco among substance use treatment center (SUTC) employees and patients. SUTC employees’ anticipated concerns about stakeholder pushback are barriers to TFWP adoption. Examination of discrepancies between anticipated and actualized employee-reported TFWP concerns arising from coworkers, patients, and community members in the context of leadership concerns and tobacco cessation care availability for employees may inform strategies to increase TFWP uptake. This study analyzed changes in employee-reported TFWP concerns from before to after a comprehensive tobacco-free workplace intervention that included TFWP implementation, using Chi-square/Fisher’s exact tests. Preimplementation leadership policy concerns and tobacco cessation care availability were examined as moderators in generalized linear mixed models. Overall, 452 employees and 13 leaders provided data from 13 SUTCs collectively serving &gt;82 000 patients annually. Results revealed significant decreases over time in employee-reported concerns about TFWP resistance from coworkers. Moderation analyses indicated that employee-anticipated concerns from coworkers and patients, respectively, were less likely to be actualized in SUTCs where leadership endorsed preimplementation TFWP concerns, whereas employee-reported patient concerns rose over time in SUTCs where leadership had no initial implementation concerns. Additionally, employee-anticipated concerns from coworkers were overestimated in SUTCs that did not offer tobacco cessation care to employees. Results supporting the nonactualization of anticipated employee concerns following TFWP implementation can be used to engage other SUTCs for TFWP adoption. Furthermore, moderation effects may suggest that center characteristics translate to greater attention to rollout, ultimately enhancing TFWP stakeholder acceptance.
The paradox of Picroside II: As a natural antioxidant, but may instead futher aggravate liver injury by exacerbating mitochondrial oxidative stress
Authors: Yifan Xu , Jingfeng Huang , Huichuan Zhuang , Junqian Lin , Zhenzhou Jiang , Lixin Sun , Xin Huang , Luyong Zhang , Tao Wang 
Published: May 2024

Abstract

Background
Picroside II (PII), an iridoid glycoside extracted from the rhizomes and stems of the genus Picroside, exhibits pronounced hepatoprotective properties. Pre-administration of PII protects against acute liver injury caused by D-galactosamine (D-Gal), carbon tetrachloride (CCl4), and acetaminophen (APAP). This study aimed to elucidate the ramifications of PII administration subsequent to the initiation of acute hepatic injury.

Methods
Exploring the role of PII treatment in APAP-treated cell and rat models and in D-Gal and CCl4-treated rat models.

Results
In rats, APAP treatment increased serum aspartate transaminase, alanine transaminase, and alkaline phosphatase levels and decreased glutathione activity and the fluidity of the liver mitochondrial membrane. In L-02 cells, APAP exposure resulted in a decrement in membrane potential, an augmentation in the liberation of reactive oxygen species, and an acceleration of apoptotic processes. Moreover, PII pre-administration protected against D-Gal-induced acute hepatic injury and CCl4-induced chronic hepatic injury in rodent models, whereas PII administration post-injury aggravated CCl4-induced chronic hepatic injury.

Conclusions
Our results suggest that the effects of PII depend on the hepatic physiological or pathological state at the time of intervention. While PII possesses the potential to avert drug-induced acute hepatic injury through the mitigation of oxidative stress, its administration post-injury may exacerbate the hepatic damage, underscoring the critical importance of timing in therapeutic interventions.
Police Contact, Non-Suicidal Self-Injury, and Suicidal Ideation
Authors: Jackson Dylan B. , Testa Alexander , Fix Rebecca L. , Semenza Daniel C. , Nagata Jason M. , Ganson Kyle T. 
Published: May 2024

Background and Objectives:
The purpose of this research is to investigate associations between police contact, non-suicidal self-injury (NSSI), and suicidal ideation (SI) among a national sample of Canadian adolescents and young adults (ages 16-30).

Methods:
Data used in this study were obtained from the Canadian Study of Adolescent Health Behaviors (N = 940), a national survey of Canadians ages 16-30.

Results:
Police contact was associated with higher odds of NSSI (OR = 1.98, 95% CI = 1.37, 2.86). Those who reported police contact with intrusion (OR = 2.39, 95% CI = 1.49, 3.38) and police contact with harassment (OR = 3.98, 95% CI = 2.30, 6.88) had higher odds of NSSI relative to respondents with no contact. Finally, any police contact was associated with higher odds of SI (OR = 1.56, 95% CI = 1.04, 2.34) and respondents experiencing police stops with harassment had higher odds of SI compared to those who had never been stopped (OR = 2.48, 95% CI = 1.45, 4.24).

Conclusions:
Distressing police contact heightens the risk of NSSI and SI among young people. Rigorous evaluation of trauma-informed, developmentally appropriate strategies for identifying and intervening on NSSI and SI following adverse police encounters should be prioritized.
Pharmacokinetic Variability of Rufinamide and Stiripentol in Children With Refractory Epilepsy: A Retrospective Study of Therapeutic Drug Monitoring From the National Epilepsy Centers in Denmark and Norway
Authors: Heger Katrine , Burns Margrete Larsen , Nikanorova Marina , Johannessen Svein I. , Johannessen Landmark Cecilie 
Published: May 2024

Background:
Rufinamide and stiripentol, orphan drugs used in Lennox–Gastaut and Dravet syndromes, respectively, are antiseizure medications (ASMs), often administered to children; however, pharmacokinetic studies are lacking. The authors compared the pharmacokinetic variability of these drugs with respect to the dose, serum concentrations, comedication, age, and duration of treatment.

Methods:
Children and adolescents (<18 years) whose serum concentrations were measured were retrospectively identified from the therapeutic drug monitoring (TDM) databases at 2 national epilepsy centers in Norway and Denmark (2012–2021).

Results:
Data from 165 patients (56% boys/44% girls) treated with rufinamide and 52 patients (50% boys/50% girls) treated with stiripentol were included. For rufinamide, the median age was 10 (range 2–17) years, dose 23 (3–73) mg/d, and serum concentration 34 (3–227) µmol/L [8.1 mg/L (0.71–54.0 mg/L)]. For stiripentol, the median age was 8.5 (range 1–17) years, dose 37 (18–76) mg/d, and serum concentration 33 (4–113) µmol/L [7.7 mg/L (0.93–26.3 mg/L)]. The concomitant use of 1–9 other ASMs during the data collection was noted. Pharmacokinetic variability, calculated as the concentration/(dose/kg) ratio, ranged from 0.26 to 11.31 (µmol/L)/(mg/kg) for rufinamide and 0.17–1.52 (µmol/L)/(mg/kg) for stiripentol. The intraindividual coefficients of variation ranged widely, from 5% to 110% for rufinamide and 11%–117% for stiripentol. The treatment period was at least 5 years in 50% of patients. No statistically significant effects of age, sex, or ASM comedication were observed, possibly due to the small sample size and heterogeneous groups with variable seizure situations, comorbidities, and changes in comedication and physiology.

Conclusions:
This study demonstrates considerable pharmacokinetic variability in and between patients for both drugs and similar use in terms of age, burden of comedication and retention rates. TDM may be useful in the clinical setting to monitor and optimize treatment in this vulnerable patient group.
Management of the Drug–Drug Interactions Between Valproic Acid and Dolutegravir—A Case Study
Authors: Cattaneo Dario , Giacomelli Andrea , Calvagna Nunziata , Bonini Igor , Ridolfo Anna Lisa , Gervasoni Cristina 
Published: May 2024

Objective:
Preliminary evidence shows that concomitant administration of valproic acid can reduce the exposure to dolutegravir with limited clinical impacts. Here, we describe a male living with HIV who experienced a drastic reduction in dolutegravir trough concentrations a few weeks after starting valproic acid treatment as identified by therapeutic drug monitoring. Concomitantly, pharmacists recommended a supplementation of magnesium to improve insomnia.

Case report:
A 62-year-old man with HIV on antiretroviral therapy with dolutegravir and lamivudine recently added valproic acid to clonazepam and sertraline to treat severe sleep disturbances. An 84% reduction in dolutegravir trough concentrations was observed compared with the previous outpatient visit (418 versus 2714 ng/mL), with values close to the minimum effective drug concentration (300 ng/mL). Considering this, we strongly discourage the use of magnesium.

Conclusions:
We are confident that our findings can contribute to a better understanding of the clinical problems that infectious disease physicians encounter in their daily management of people with HIV and how therapeutic drug monitoring may add value in this context. This case also highlights the importance of multidisciplinary services for the optimal management of polypharmacy in people with HIV.
Impact of Insurance Type on Access to Pediatric Surgical Care
Authors: Watson Rachel R. , Niedziela Cassi J. , Nuzzi Laura C. , Netson Rebecca A. , McNamara Catherine T. , Ayannusi Anuoluwa E. , Flanagan Sarah , Massey Gabrielle G. , Labow Brian I. 
Published: May 2024

Background:
This study aimed to measure the impact of insurance type on access to pediatric surgical care, clinical and surgical scheduling decisions, provider-driven cancelations, and missed care opportunities (MCOs). We hypothesize that patients with public health insurance experience longer scheduling delays and more frequently canceled surgical appointments compared with patients with private health insurance.

Methods:
This retrospective study reviewed the demographics and clinical characteristics of patients who underwent a surgical procedure within the plastic and oral surgery department at our institution in 2019. Propensity score matching and linear regressions were used to estimate the effect of insurance type on hospital scheduling and patient access outcomes while controlling for procedure type and sex.

Results:
A total of 457 patients were included in the demographic and clinical characteristics analyses; 354 were included in propensity score matching analyses. No significant differences in the number of days between scheduling and occurrence of initial consultation or number of clinic cancelations were observed between insurance groups (P > 0.05). However, patients with public insurance had a 7.4 times higher hospital MCO rate (95% CI [5.2–9.7]; P < 0.001) and 4.7 times the number of clinic MCOs (P = 0.007).

Conclusions:
No significant differences were found between insurance groups in timely access to surgical treatment or cancelations. Patients with public insurance had more MCOs than patients with private insurance. Future research should investigate how to remove barriers that impact access to care for marginalized patients.