bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hymenoptera venom allergy in children
Authors: Giovannini Mattia , Mori Francesca , Barni Simona , Saretta Francesca , Arasi Stefania , Castagnoli Riccardo , Liotti Lucia , Mastrorilli Carla , Pecoraro Luca , Caminiti Lucia , Sturm Gunter Johannes , Marseglia Gian Luigi , del Giudice Michele Miraglia , Novembre Elio 
Published: December 2024

AbstractFrom a taxonomic point of view, Hymenoptera are subclassified into families: Apidae, including honeybees (Apis mellifera) and bumblebees (Bombus), and Vespidae, which, in turn, are divided into the subfamilies of Vespinae (wasps, including hornets, vespules, dolichovespules) and Polistinae (paper wasp). Hypersensitivity to Hymenoptera venom can be linked to immunological (IgE-mediated or non-IgE-mediated) and non-immunological mechanisms. Reactions are classified into local reactions, large local reactions, systemic reactions, toxic reactions, and unusual reactions. In general, children sensitize less frequently and have less severe reactions than adults, probably due to less exposure to repeated stings and fewer comorbidities. There are risk factors for systemic reactions that should be discussed with patients and their parents as appropriate. A correct diagnosis of Hymenoptera venom allergy relies on a careful clinical history and the appropriate use of skin and in vitro tests. The in vitro tests include serum specific IgE toward venom extracts and toward allergenic molecules. In complex diagnoses, CAP-inhibition and the Basophil Activation Test can also be used. In the presence of a systemic reaction, the basal serum tryptase measurement should be performed to rule out mastocytosis. In case of allergic reactions to Hymenoptera stings, in the acute phase, according to the current guidelines, the treatment of signs and symptoms mainly includes the use of adrenaline as first-line treatment in case of anaphylaxis and antihistamines and corticosteroids as subsequent lines of treatment. Given the impossibility of avoiding a new sting with certainty, the treatment of choice in subjects with hypersensitivity to Hymenoptera venom who have experienced systemic reactions is based on venom immunotherapy (VIT), with the venom of the responsible stinging insect identified after an adequate allergological work-up. VIT is performed in a suitable environment and has proved to be safe and effective with various administration protocols, both accelerated and conventional. The prevention of Hymenoptera venom anaphylaxis in patients who have already developed a previous episode is crucial and must be supported by environmental protection interventions and early therapy. Places where one is more likely to encounter insects and risky behaviors should be avoided.
Inclusivity is child’s play: pilot study on usability, acceptability and user experience of a sensory-motor PC game for children with cerebral palsy (GiocAbile)
Authors: Consales Alessandra , Biffi Emilia , Nossa Roberta , Pittaccio Simone , Lazzari Fabio , Malosio Matteo , Lavit Nicora Matteo , Tauro Giovanni , Redaelli Davide Felice , Chaudhary Atul , Diella Eleonora , Valoriani Matteo , Fedeli Francesca , Picciolini Odoardo , Giannì Maria Lorella , Porro Matteo 
Published: December 2024

Abstract
Background
The use of video games in rehabilitation settings is gaining increasing popularity. However, the lack of commercial video games suitable for children with disabilities and the disappointing user experience of serious games limit their applicability. The aim of this study was to assess the usability, acceptability and user experience of GiocAbile, an active video game for children with cerebral palsy (CP).

Methods
This multicenter pilot observational study was conducted from May to September 2022 at the participating institutions, and enrolled school-aged children affected by CP. Enrolled children played GiocAbile in single-player mode for one hour. The gaming experience was evaluated through self-assessment questionnaires. Non-parametric correlation analysis was conducted to examine the influence of motor and cognitive abilities (GMFCS, MACS, ICF) on declared usability and acceptability.

Results
Nineteen children (9.01 ± 1.95 years, 63.1% male) with mild to severe CP were enrolled. The 100% of respondents expressed satisfaction and fulfillment associated with gameplay, with no reports of frustration or disappointment. The 83% would recommend the game to a friend. The controllers were generally deemed easy to use and maneuver, with very few reports of discomfort associated with their use. No correlations were found between usability/acceptability levels and measures of impairment (i.e., GMFCS, MACS, and ICF scales), while cognitive impairment positively correlated with satisfaction during gameplay.

Conclusions
GiocAbile is an accessible, user-friendly and enjoyable tool for children with CP, regardless of level of impairment. Based on existing literature, we hypothesize that GiocAbile may improve motivation, participation, and rehabilitation outcomes in children with CP, although further studies are needed to confirm our hypothesis.
Azadirachtin disrupts ecdysone signaling and alters sand fly immunity
Authors: Vieira Cecilia Stahl , Bisogno Sara , Salvemini Marco , Loza Telleria Erich , Volf Petr 
Published: December 2024

Abstract
Background
Leishmaniasis is a group of neglected vector-borne diseases transmitted by phlebotomine sand flies. Leishmania parasites must overcome various defenses in the sand fly midgut, including the insects’s immune response. Insect immunity is regulated by the ecdysone hormone, which binds to its nuclear receptor (EcR) and activates the transcription of genes involved in insect immunity. However, the role of ecdysone in sand fly immunity has never been studied. Phlebotomus perniciosus is a natural vector of Leishmania infantum; here, we manipulated its neuroendocrine system using azadirachtin (Aza), a natural compound known to affect ecdysone synthesis.

Methods
Phlebotomus perniciosus larvae and adult females were fed on food containing either Aza alone or Aza plus ecdysone, and the effects on mortality and ecdysis were evaluated. Genes related to ecdysone signaling and immunity were identified in P. perniciosus, and the expression of antimicrobial peptides (AMPs), EcR, the ecdysone-induced genes Eip74EF and Eip75B, and the transcription factor serpent were analyzed using quantitative polymerase chain reaction (PCR).

Results
Aza treatment inhibited molting of first-instar (L1) larvae to L2, with only 10% of larvae molting compared to 95% in the control group. Serpent and Eip74EF, attacin, defensin 1, and defensin 2 genes were downregulated by Aza treatment in larvae. Similarly, Aza-treated adult females also presented suppression of ecdysone signaling-related genes and the AMPs attacin and defensin 2. Notably, all gene repression caused by Aza was reversed by adding ecdysone concomitantly with Aza to the larval or female food, indicating that these genes are effective markers for ecdysone repression.

Conclusions
These results highlight the critical role of ecdysone in regulating the development and immunity of P. perniciosus, which potentially could interfere with Leishmania infection.

Graphical Abstract
Maximizing insights from longitudinal epigenetic age data: simulations, applications, and practical guidance
Authors: Großbach Anna , Suderman Matthew J. , Hüls Anke , Lussier Alexandre A. , Smith Andrew D. A. C. , Walton Esther , Dunn Erin C. , Simpkin Andrew J. 
Published: December 2024

Abstract
Background
Epigenetic age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk. Limited by available data, most studies investigating these relationships have been cross-sectional, using a single EA measurement. However, the recent growth in longitudinal DNAm studies has led to analyses of associations with EA over time. These studies differ in (1) their choice of model; (2) the primary outcome (EA vs. EAA); and (3) in their use of chronological age or age-independent time variables to account for the temporal dynamic. We evaluated the robustness of each approach using simulations and tested our results in two real-world examples, using biological sex and birthweight as predictors of longitudinal EA.

Results
Our simulations showed most accurate effect sizes in a linear mixed model or generalized estimating equation, using chronological age as the time variable. The use of EA versus EAA as an outcome did not strongly impact estimates. Applying the optimal model in real-world data uncovered advanced GrimAge in individuals assigned male at birth that decelerates over time.

Conclusion
Our results can serve as a guide for forthcoming longitudinal EA studies, aiding in methodological decisions that may determine whether an association is accurately estimated, overestimated, or potentially overlooked.
Whole genome sequence and LC-Mass for identifying antimicrobial metabolites of Bacillus licheniformis endophyte
Authors: Soliman Nourhan K. , Abbas Ahmad M. , El tayeb Wafaa N. , Alshahrani Mohammad Y. , Aboshanab Khaled M. 
Published: December 2024

AbstractAntimicrobial resistance (AMR) represents a critical public health issue that requiring immediate action. Wild halophytic plants can be the solution for the AMR crisis because they harbor unique endophytes capable of producing potent antimicrobial metabolites. This study aimed at identifying promising and antimicrobial metabolites produced by endophytic/epiphytic bacteria recovered from the wild Bassia scoparia plant. Standard methods were employed for the isolation of endophytes/epiphytes. Whole genome sequence (WGS) using Oxford Nanopore technology followed by antiSMASH analysis coupled with advanced LC-MS spectroscopic analysis were used for identification of the active antimicrobial metabolites. This study identified Bacillus licheniformis strain CCASU-B18 as a promising endophytic bacterium from the Bassia scoparia plant. In addition, the strain showed broad-spectrum antibacterial activity against three standard and five MDR clinical Gram-positive and Gram-negative isolates, and antifungal activity against the standard C. albicans strain. Six main antimicrobial metabolites—thermoactinoamide A, bacillibactins, lichenysins, lichenicidins, fengycin, and bacillomycin—were verified to exist by whole genome sequencing for identifying the respective conserved biosynthetic gene clusters in conjunction with LC/MS-MS analysis. The complete genomic DNA (4125835) and associated plasmid (205548 bp) of the promising endophytic isolate were sequenced, assembled, annotated, and submitted into the NCBI GenBank database under the accession codes, CP157373. In conclusion, Bacillus licheniformis strain CCASU-B18, a promising endophytic bacterium exhibiting broad-spectrum antimicrobial activities, was isolated. Future research is highly recommended to optimize the culture conditions that will be employed to enhance the production of respective antimicrobial metabolites, as well as testing these compounds against a broader range of MDR-resistant pathogens.
Impact of c-JUN deficiency on thalamus development in mice and human neural models
Authors: Shi Jiantao , Chen Qing , Lai Jianheng , Zhu Jieying , Zhang Ran , Mazid Md. Abdul , Li Dongwei , Su Huanxing , Qin Dajiang 
Published: December 2024

Abstract
Background
c-Jun is a key regulator of gene expression. Through the formation of homo- or heterodimers, c-JUN binds to DNA and regulates gene transcription. While c-Jun plays a crucial role in embryonic development, its impact on nervous system development in higher mammals, especially for some deep structures, for example, thalamus in diencephalon, remains unclear.

Methods
To investigate the influence of c-JUN on early nervous system development, c-Jun knockout (KO) mice and c-JUN KO H1 embryonic stem cells (ESCs)-derived neural progenitor cells (NPCs), cerebral organoids (COs), and thalamus organoids (ThOs) models were used. We detected the dysplasia via histological examination and immunofluorescence staining, omics analysis, and loss/gain of function analysis.

Results
At embryonic day 14.5, c-Jun knockout (KO) mice exhibited sparseness of fibers in the brain ventricular parenchyma and malformation of the thalamus in the diencephalon. The absence of c-JUN accelerated the induction of NPCs but impaired the extension of fibers in human neuronal cultures. COs lacking c-JUN displayed a robust PAX6+/NESTIN+ exterior layer but lacked a fibers-connected core. Moreover, the subcortex-like areas exhibited defective thalamus characteristics with transcription factor 7 like 2-positive cells. Notably, in guided ThOs, c-JUN KO led to inadequate thalamus patterning with sparse internal nerve fibers. Chromatin accessibility analysis confirmed a less accessible chromatin state in genes related to the thalamus. Overexpression of c-JUN rescued these defects. RNA-seq identified 18 significantly down-regulated genes including RSPO2, WNT8B, MXRA5, HSPG2 and PLAGL1 while 24 genes including MSX1, CYP1B1, LMX1B, NQO1 and COL2A1 were significantly up-regulated.

Conclusion
Our findings from in vivo and in vitro experiments indicate that c-JUN depletion impedes the extension of nerve fibers and renders the thalamus susceptible to dysplasia during early mouse embryonic development and human ThO patterning. Our work provides evidence for the first time that c-JUN is a key transcription regulator that play important roles in the thalamus/diencephalon development.
Minimum carbon dioxide is a key predictor of the respiratory health of pigs in climate-controlled housing systems
Authors: Lagua Eddiemar Baguio , Mun Hong-Seok , Ampode Keiven Mark Bigtasin , Park Hae-Rang , Sharifuzzaman Md , Hasan Md Kamrul , Kim Young-Hwa , Yang Chul-Ju 
Published: December 2024

Abstract
Background
Respiratory disease is an economically important disease in the swine industry. Housing air quality control is crucial for maintaining the respiratory health of pigs. However, maintaining air quality is a limitation of current housing systems. This study evaluated the growth and health parameters of pigs raised under different environmental conditions and identified key environmental variables that determine respiratory health. Eighty (Largewhite × Landrace) × Duroc crossed growing pigs (31.71 ± 0.53 kg) were equally distributed into two identical climate-controlled houses with distinct environmental conditions (CON = normal conditions and TRT = poor conditions). Two-sample tests were performed to compare the means of the groups, and a random forest algorithm was used to identify the importance scores of the environmental variables to respiratory health.

Results
Pigs in the TRT group were significantly exposed to high temperatures (28.44 vs 22.78 °C, p < 0.001), humidity (88.27 vs 61.86%, p < 0.001), CO2 (2,739.93 vs 847.91 ppm, p < 0.001), NH3 (20.53 vs 8.18 ppm, p < 0.001), and H2S (14.28 vs 6.70 ppm, p < 0.001). Chronic exposure to these factors significantly reduced daily feed intake (1.82 vs 2.32 kg, p = 0.002), resulting in a significant reduction in average daily gain (0.72 vs 0.92 kg, p = 0.026), increased oxidative stress index (3.24 vs 1.43, p = 0.001), reduced cortisol levels (2.23 vs 4.07 mmol/L, p = 0.034), and deteriorated respiratory health status (74.41 vs 97.55, p < 0.001). Furthermore, a random forest model identified Min CO2, Min NH3, and Avg CO2 as the best predictors of respiratory health, and CO2 was strongly correlated with NH3 and H2S concentrations.

Conclusions
These findings emphasize the critical importance of proper environmental management in pig farming and suggest that regular monitoring and control of either CO2 or NH3, facilitated by environmental sensors and integration into intelligent systems, can serve as an effective strategy for improving respiratory health management in pigs.
Real-World Treatment Patterns After Discontinuation of Venetoclax or BTKis in the Frontline Setting Among Older Adults With Chronic Lymphocytic Leukemia
Authors: Huntington Scott F. , Rhodes Joanna M. , Manzoor Beenish S. , Jawaid Dureshahwar , Puckett Justin T. , Emechebe Nnadozie , Ravelo Arliene , Kamal-Bahl Sachin , Marx Steven E. , Doshi Jalpa A. 
Published: December 2024

PURPOSE
Venetoclax and Bruton's tyrosine kinase inhibitors (BTKis) are key treatment options for patients with chronic lymphocytic leukemia (CLL) in the frontline setting. This study characterized postdiscontinuation treatment patterns and hospitalization of frontline venetoclax and BTKis in a national sample of older adults with CLL.

METHODS
We identified 1,770 Medicare beneficiaries 66 years and older with CLL initiating venetoclax with obinutuzumab (VEN-O, n = 193) or BTKi treatment (n = 1,577) in the frontline setting between June 01, 2019, and June 30, 2020. Discontinuation was defined as a consecutive 90-day gap in treatment at any point over an 18-month follow-up. BTKi patients were expected to receive treatment continuously; VEN-O patients were expected to complete 11 months of treatment (12 cycles × 28 days = 336 days). The rates of subsequent CLL treatment and all-cause/CLL-related hospitalization were assessed.

RESULTS
Over an 18-month follow-up, 102 (52.8%) VEN-O patients discontinued after completing the fixed-duration period; 597 (37.9%) BTKi and 57 (29.5%) VEN-O patients discontinued treatment prematurely. The median time to discontinuation was 11.9 months (VEN-O) and 4.0 months (BTKi patients), respectively. Few patients (n < 11) who discontinued VEN-O initiated another CLL treatment over a median postdiscontinuation follow-up period of 6.1 months. By contrast, 39.0% of discontinuers in the BTKi group had evidence of subsequent CLL treatment over a median 13.8-month postdiscontinuation follow-up period. Post-BTKi regimens included BCL-2 (35.6%), subsequent BTKi (31.8%), chemotherapy (14.6%), anti-CD20 monotherapy (9.9%), and other (8.2%). The rate of postdiscontinuation all-cause and CLL-related hospitalization per 100 patient-months was 2.0 and 1.5 for the VEN-O group and 3.3 and 2.9 for the BTKi group, respectively.

CONCLUSION
In this real-world study, early discontinuation was more common in patients initiating a BTKi in contrast to VEN-O. Patients who initiated a BTKi also had high rates of subsequent treatment and hospitalization.
Optimal ion shuttling for a noisy trap
Authors: Lu Xiao-Jing , Muga J. G. 
Published: December 2024

Abstract
We find continuous optimal trap trajectories to shuttle one ion with minimal excitation, when the trap spring constant is affected by white noise. The Euler-Lagrange method gives a lower bound for the dynamical (trajectory-dependent) energy sensitivity to the noise. Using a trigonometric ansatz for the state trajectories, the optimal trap trajectories are found for a given shuttling time and a fixed number of terms in the ansatz. The corresponding dynamical sensitivity tends to the lower bound as the number of terms increases. While the dynamical sensitivity increases by shortening the shuttling times, the static (trajectory-independent) one decreases, so we also find optimal shuttling times that minimize the global (static plus dynamical) sensitivity.
Effectiveness of Ventilation via an Endotracheal Tube in Pharynx Versus a Facemask in Patients With Potentially Difficult Airway: A Randomized, Crossover, and Blind Trial
Authors: Markham Travis , AlFarra Abraham S. , Tejani Mubeen , Tate Daniel J. , Barrera Jose E. , Paladugu Sreelekha , Saroukhani Sepideh , Jiang Yandong 
Published: December 2024

BACKGROUND:
The difficult airway is frequently encountered across many scenarios. The extreme form is a “cannot intubate and cannot oxygenate” scenario, which lacks a reliable rescue technique. Previous case reports or studies with small sample sizes indicate the feasibility and efficiency of an endotracheal tube in the pharynx (TTIP) to ventilate patients. We hypothesize that ventilation via TTIP is an effective rescue technique for failed mask ventilation.

METHOD:
One hundred forty-seven patients with potentially difficult airways were randomly assigned to the sequence (Tube first) of tube first ventilation via TTIP for 1 minute after induction, followed by via mask ventilation for 1 minute or in reverse sequence (Mask first). The ventilation was done with pressure control mode, a peak inspiratory airway pressure of 20 cmH2O, an inspiratory to expiratory time ratio of 1:2, and a respiratory rate of 10 breaths/min.

RESULTS:
A total of 136 patients underwent final analysis. The overall success rate (primary outcome) of ventilation via TTIP and mask, defined as the presence of expired carbon dioxide, was 93.4% (127/136) and 84.6% (115/136), respectively (P = .02). The success rate, 85.7% (6/7), of mask ventilation rescuing a failed TTIP ventilation and 100% (13/13) of TTIP rescuing a failed mask ventilation were comparable (P = .35).

CONCLUSIONS:
The success rates of TTIP and mask ventilation are comparable. Ventilation via TTIP could be an alternative rescue technique for managing a difficult airway.
Association Between Arterial Hyperoxia and Mortality in Pediatric and Adult Patients Undergoing Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis
Authors: Gu Wan-Jie , Shi Rui , Cen Yun , Ye Ying-Ying , Xie Xu-Dong , Yin Hai-Yan 
Published: December 2024

BACKGROUND:
In patients receiving extracorporeal membrane oxygenation (ECMO) support, the association between arterial hyperoxia and outcomes is unclear. We performed a systematic review and meta-analysis to determine the association between arterial Po
2 (Pao
2) and mortality in patients with ECMO.

METHODS:
The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42023467361). We systematically searched PubMed and Embase databases up to September 2023 for randomized trials or observational studies that investigated the association between Pao
2 and mortality in pediatric and adult patients receiving venovenous ECMO (VV-ECMO), venoarterial ECMO (VA-ECMO), and extracorporeal cardiopulmonary resuscitation (ECPR). The predefined outcome was 28-day mortality. We synthesized the data using a random-effects model, calculating odds ratios (OR) and corresponding 95% confidence intervals (CI).

RESULTS:
Thirteen cohort studies (17,766 participants) were included. All studies used categorical Pao
2 cutoff, with varying thresholds ranging from ≥100 mm Hg to ≥300 mm Hg. When compared with patients with normoxia, elevated Pao
2 levels at all studied thresholds were consistently associated with increased mortality (≥300 mm Hg: OR 1.56, 95% CI, 1.31–1.85, P < .01; ≥200 mm Hg: OR 1.43, 95% CI, 1.10–1.87, P < .01; ≥150 mm Hg: OR 1.51, 95% CI, 1.15–1.98, P < .01; and ≥100 mm Hg: OR 1.44, 95% CI, 1.03–2.02, P = .03). A sensitivity analysis focusing on studies reporting adjusted OR yielded similar results. We observed this association in both adult and pediatric populations.

CONCLUSIONS:
In critically ill patients on VV- or VA-ECMO, increased Pao
2 values were associated with increased 28-day mortality in ECMO patients. Our results should be interpreted with caution given observational nature of included studies. Further randomized trials are warranted to validate these results.