bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activating A1 adenosine receptor signaling boosts early pulmonary neutrophil recruitment in aged mice in response to Streptococcus pneumoniae infection
Authors: Simmons Shaunna R. , Herring Sydney E. , Tchalla Essi Y.I , Lenhard Alexsandra P. , Bhalla Manmeet , Bou Ghanem Elsa N. 
Published: June 2024

Abstract
Background
Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia in older adults. Successful control of pneumococci requires robust pulmonary neutrophil influx early in infection. However, aging is associated with aberrant neutrophil recruitment and the mechanisms behind that are not understood. Here we explored how neutrophil recruitment following pneumococcal infection changes with age and the host pathways regulating this.

Results
Following pneumococcal infection there was a significant delay in early neutrophil recruitment to the lungs of aged mice. Neutrophils from aged mice showed defects in trans-endothelial migration in vitro compared to young controls. To understand the pathways involved, we examined immune modulatory extracellular adenosine (EAD) signaling, that is activated upon cellular damage. Signaling through the lower affinity A2A and A2B adenosine receptors had no effect on neutrophil recruitment to infected lungs. In contrast, inhibition of the high affinity A1 receptor in young mice blunted neutrophil recruitment to the lungs following infection. A1 receptor inhibition decreased expression of CXCR2 on circulating neutrophils, which is required for trans-endothelial migration. Indeed, A1 receptor signaling on neutrophils was required for their ability to migrate across endothelial cells in response to infection. Aging was not associated with defects in EAD production or receptor expression on neutrophils. However, agonism of A1 receptor in aged mice rescued the early defect in neutrophil migration to the lungs and improved control of bacterial burden.

Conclusions
This study suggests age-driven defects in EAD damage signaling can be targeted to rescue the delay in pulmonary neutrophil migration in response to bacterial pneumonia.
Evaluating the impact of virtual reality game training on upper limb motor performance in children and adolescents with developmental coordination disorder: a scoping review using the ICF framework
Authors: Alharbi Mohammed , Du Haoyang , Harris David , Wood Greg , Dodd Helen , Buckingham Gavin 
Published: June 2024

Abstract
Objective
This scoping review aims to explore published literature testing Virtual Reality (VR) interventions for improving upper limb motor performance in children and adolescents with Developmental Coordination Disorder (DCD). Our primary focus was on the types of VR systems used and the measurement tools employed within the International Classification of Functioning, Disability and Health Children and Youth Version (ICF-CY) domains in these studies.

Methods
A comprehensive search of six electronic databases up to 11th January 2024 was conducted using predefined terms. Inclusion and exclusion criteria were applied to determine study eligibility, with two authors independently assessing titles, abstracts, and full-text articles.

Results
Out of 788 potential studies, 14 met the eligibility criteria. Studies predominantly utilized non-immersive VR (nVR) systems, for example, commercial platforms such as Nintendo Wii. Most interventions targeted general motor coordination or balance, with only four studies specifically focusing on upper limb motor performance. The Movement Assessment Battery for Children-2 was the predominant assessment tool. However, the use of game scores and trial durations raised concerns about the accuracy of assessments. The majority of studies reported no significant improvement in upper limb motor performance following VR interventions, though some noted improvements in specific tasks or overall outcomes.

Conclusion
The findings suggest that, while nVR interventions are being explored for paediatric motor rehabilitation, their impact on enhancing upper limb motor performance in children with DCD is unclear. The variability in intervention designs, outcome measures, and the predominant focus on general motor skills rather than specific upper limb improvements highlight the need for more targeted research in this area.

Impact
This review underscores the importance of developing precise and clinically relevant measurement tools in a broader range of VR technologies to optimize the use of VR in therapy for children with DCD. Future research should aim for more rigorous study designs and emerging immersive technologies to maximize therapeutic benefits.
A survey of breastfeeding among women with previous surgery for benign breast disease: a descriptive exploratory study
Authors: Mao Siying , He Jiafa , Huang Lezhen , Sun Yang , Dai Yan , Guo Qianqian , Qiu Chang , Song Xue , Lin Xiaojie , Chen Shengying , Ye Lingling , Xu Rui 
Published: June 2024

Abstract
Background
Surgery is the primary treatment for benign breast disease and causes some disruption to the normal physiology of the breast, even when this disruption is localised, it remains unclear whether it affects women’s ability to breastfeed. There are only a few studies describing the experience of breastfeeding in women who have undergone benign breast disease (BBD) surgery.

Methods
We retrospectively analysed data from patients aged 20–40 years in Guangdong, China, who underwent breast lumpectomy for BBD in our department between 01 January 2013 and 30 June 2019, with a follow-up date of 01 February 2022. Patients were included who had a history of childbirth between the time of surgery and the follow-up date. By collecting general information about this group of patients and information about breastfeeding after surgery, we described the breastfeeding outcomes of women of a fertile age who had previously undergone surgery for benign breast disease.

Results
With a median follow-up of 5.9 years, a total of 333 patients met the inclusion criteria. From the breastfeeding data of the first child born postoperatively, the mean duration of ‘exclusive breastfeeding’ was 5.1 months, and the mean duration of ‘any breastfeeding’ was 8.8 months. The rate of ‘ever breastfeeding’ is 91.0%, which is lower than the national average of 93.7%, while the exclusive breastfeeding rate at six months was 40.8%, was higher than the 29.2% national average. The any breastfeeding rate at 12 months was 30.0%, which was well below the 66.5% national average. The common reason for early breastfeeding cessation was insufficient breast milk. A total of 29.0% of patients who had ever breastfed after surgery voluntarily reduced the frequency and duration of breastfeeding on the operated breast because of the surgery.

Conclusions
There are some impacts of BBD surgery on breastfeeding and some may be psychological. Institutions should provide more facilities for mothers who have undergone breast surgery to help them breastfeed, such as conducting community education on breastfeeding after breast surgery, training professional postoperative lactation consultants in hospitals, and extending maternity leave. Families should encourage mothers to breastfeed with both breasts instead of only the non-operated breast.
Novel homozygous frameshift insertion variant in the last exon of the EDARADD causing hypohidrotic ectodermal dysplasia in two siblings: case report and review of the literature
Authors: Kablan Ahmet , Tasdelen Elifcan 
Published: June 2024

Abstract
Background
Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that results in the abnormal development of structures derived from ectodermal tissue. This rare condition predominantly affects the hair, nails, eccrine glands, and teeth. While HED can be caused by various genes, the EDA, EDAR, EDARADD, and WNT10A genes account for approximately 90% of cases. Notably, HED forms associated with variants in the EDA, EDAR, or EDARADD genes may exhibit similar phenotypes due to defects in a common signaling pathway. Proper interaction among the products of these genes is crucial for the activation of the nuclear factor (NF-κB) signaling pathway, which subsequently regulates the transcription of targeted genes. The EDARADD gene, in particular, harbors one of the rarest reported variants associated with HED.

Case presentation
Five-and two-years-old brothers born into consanguineous parents were examined at our outpatient medical genetics clinic at Sanliurfa Training and Research Hospital, Turkey. Both displayed the same classical phenotypic features of HED. The elder had a very sparse dark and brittle hair, sparse eyebrows and eyelashes, conical upper and lower premolar teeth with hypodontia, widely spaced teeth, very dry skin, mildly prominent forehead, and periorbital wrinkles. The younger one showed the same, but less severe, clinical features. After thorough examination and patient history evaluation, targeted next-generation sequencing analysis yielded the novel homozygous insertion variant c.322_323insCGGGC p.(Arg108ProfsTer7) in EDARADD. The mutation has not been reported to date in the literature.

Conclusions
In this report, we present two siblings exhibiting classical HED symptoms and a novel insertion variant of the EDARADD gene, which leads to a frameshift introducing a stop codon. Both brothers inherited such mutation from their parents, who were heterozygous carriers of the same variant. The present study may shed light about the pathogenic mechanisms underlying HED, and expand the spectrum of EDARADD gene variants associated with this condition.
Effectiveness of janus kinase inhibitors in relapsing giant cell arteritis in real-world clinical practice and review of the literature
Authors: Loricera Javier , Tofade Toluwalase , Prieto-Peña Diana , Romero-Yuste Susana , de Miguel Eugenio , Riveros-Frutos Anne , Ferraz-Amaro Iván , Labrador Eztizen , Maiz Olga , Becerra Elena , Narváez Javier , Galíndez-Agirregoikoa Eva , González-Fernández Ismael , Urruticoechea-Arana Ana , Ramos-Calvo Ángel , López-Gutiérrez Fernando , Castañeda Santos , Unizony Sebastian , Blanco Ricardo 
Published: June 2024

Abstract
Background
A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature.

Methods
Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted.

Results
Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them.

Conclusions
This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202).
Immunosuppression at ICU admission is not associated with a higher incidence of ICU-acquired bacterial bloodstream infections: the COCONUT study
Authors: Zebian Ghadi , Kreitmann Louis , Houard Marion , Piantoni Antoine , Piga Gaetan , Ruffier des Aimes Sarah , Holik Bérénice , Wallet Frédéric , Labreuche Julien , Nseir Saad 
Published: June 2024

Abstract
Background
Immunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated.

Methods
Retrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups.

Results
A total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre‐specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes.

Conclusion
The 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission.
On steady state of viscous compressible heat conducting full magnetohydrodynamic equations
Authors: Azouz Mohamed , Benabidallah Rachid , Ebobisse François 
Published: June 2024

AbstractThis paper is concerned with the study of equations of viscous compressible and heat-conducting full magnetohydrodynamic (MHD) steady flows in a horizontal layer under the gravitational force and a large temperature gradient across the layer. We assume as boundary conditions, periodic conditions in the horizontal directions, while in the vertical directions, slip-boundary is assumed for the velocity, vertical conditions for the magnetic field, and fixed temperature or fixed heat flux are prescribed for the temperature. The existence of stationary solution in a small neighborhood of a stationary profile close to hydrostatic state is obtained in Sobolev spaces as a fixed point of some nonlinear operator.
A color prediction model for mending materials of the Yuquan Iron Pagoda in China based on machine learning
Authors: Liu Xuegang , Liu Yuhang , Wang Ke , Zhang Yang , Lei Yang , An Hai , Wang Mingqiang , Chen Yuqiu 
Published: June 2024

Abstract
During the restoration of iron cultural relics, the removal of rust from these artifacts is necessary. However, this rust removal process may lead to inconsistent local color on the iron relics. To address this, mending materials are applied to treat the surface, ensuring consistent local color. In the surface treatment of iron cultural relics, a significant challenge lies in modulating the color of these mending materials. The corrosion products of Yuquan Iron Pagoda are mainly Fe3O4, γ-FeO(OH), α-FeO(OH) and α-Fe2O3, with contents of 13.1, 16.1, 40.2 and 30.6%, respectively. Due to their structural stability and suitable color characteristics, Fe3O4 and α-Fe2O3 are selected as the primary raw materials for the repair material. This study employs machine learning methods to predict the color of mending materials corresponding to varying contents of α-Fe2O3, Fe3O4, and epoxy resin. The Artificial Neural Network (ANN), eXtreme Gradient Boosting (XGBoost), and Light Gradient Boost Machine (LightGBM) algorithms are utilized to develop the model, and the predictive performance of these three algorithms is compared. XGBoost exhibits the best prediction performance, achieving a square correlation coefficient (R2) of 0.94238 and a mean absolute error (MAE) of 0.68485. Additionally, the SHapley Additive exPlanations (SHAP) method is employed to analyze the most crucial raw material affecting the color of mending materials, which is identified as Fe3O4. The study illustrates the specific process of employing this model by applying it to the surface treatment of the Yuquan Iron Pagoda, demonstrating the practicality of the model. This model can be applied to assist in the surface treatment of other iron cultural relics.
Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator’s choice of therapy for KRAS G12C-mutated metastatic colorectal cancer (mCRC).
Authors: Fakih Marwan , Salvatore Lisa , Esaki Taito , Modest Dominik Paul , Páez Lopez-Bravo David , Taieb Julien , Karamouzis Michalis , Ruiz-Garcia Erika , Kim Tae Won , Kuboki Yasutoshi , Meriggi Fausto Angelo , Cunningham David , Yeh Kun-Huei , Chan Emily , Chao Joseph , Tran Qui , Cremolini Chiara , Pietrantonio Filippo 
Published: June 2024

LBA3510 Background: In CodeBreaK 300 (NCT05198934), soto+pani was superior to investigator’s choice at the primary analysis of progression-free survival (PFS) in patients (pts) with chemorefractory KRAS G12C-mutated mCRC (Fakih et al. NEJM. 2023). OS data were immature at the PFS analysis. We now report the final OS analysis of CodeBreaK 300. Methods: Study procedures and eligibility criteria were previously reported. The PFS primary endpoint was tested at primary analysis. Key secondary endpoints included OS and objective response. Though the study sample size was not powered for OS, OS hypothesis testing using stratified log-rank test was planned when 50% of pts had observed events per protocol. Stratified Cox hazard ratio (HR) and Kaplan-Meier median estimates are provided. Results: In total, 160 pts were randomly assigned 1:1:1 to soto960+pani (n=53), soto240+pani (n=53), or investigator’s choice of trifluridine/tipiracil, or regorafenib (investigator’s choice; n=54). As of Dec 18, 2023, with a median follow-up of 13.6 months, 82 deaths had occurred with 24, 28, and 30 deaths in the soto960+pani, soto240+pani, and investigator’s choice arms, respectively. Median OS (95% CI) was not reached for soto960+pani, 11.9 months (7.5, NE) for soto240+pani, and 10.3 months (7.0, NE) for investigator’s choice. Hazard ratio (95% CI) was 0.70 (0.41, 1.18) for soto960+pani compared to investigator’s choice and 0.83 (0.49, 1.39) for soto240+pani compared to investigator’s choice. Updated ORR, DOR, and DCR are included in Table. No new safety signals were observed. Conclusions: While CodeBreaK 300 was not powered to detect a statistically significant difference in OS, the study showed a trend toward improved OS for patients randomized to soto960+pani. Together with PFS and response rates, these results support the use of soto960+pani as a potential SOC for pts with chemorefractory KRAS G12C-mutated mCRC. Acknowledgements: The authors thank the patients, investigators, and study staff who contributed to this study; The study was sponsored and funded by Amgen Inc.; Medical writing support was provided by Shubha Dastidar, PhD (CACTUS) and Christopher Nosala, PhD (Amgen Inc.). Clinical trial information: NCT05198934 . [Table: see text]
Phase III randomized trial evaluating tilsotolimod in combination with ipilimumab versus ipilimumab alone in patients with advanced refractory melanoma (ILLUMINATE 301).
Authors: Diab Adi , Ascierto Paolo Antonio , Abdel-Wahab Reham , Maio Michele , Negrier Sylvie , Mortier Laurent , Dalle Stéphane , Krajsova Ivana , de la Cruz Luis , Leccia Marie Thérèse , Guida Michele , Lebbe Celeste , Grob Jean-Jacques , Butler Marcus O. , In Gino Kim , Chunduru Srinivas , Rahimian Shah , Robert Caroline 
Published: June 2024

LBA9516 Background: There are limited treatment options for advanced melanoma that has progressed during or after immune checkpoint inhibitor therapy. Intratumoral (IT) immunotherapy may improve tumor-specific immune activation by promoting local tumor antigen presentation while avoiding systemic toxicities. The Phase 3 ILLUMINATE-301 study (NCT03445533) evaluated tilsotolimod, a toll-like receptor 9 agonist, with or without ipilimumab in patients with anti-programmed death-1 (PD-1)-advanced refractory melanoma. Methods: Patients with unresectable Stage III–IV melanoma that progressed during or after anti-PD-1 therapy were randomized 1:1 to receive 24 weeks of tilsotolimod plus ipilimumab or 10 weeks of ipilimumab alone. Nine IT injections of tilsotolimod were administered to a single designated lesion over 24 weeks. Intravenous ipilimumab 3 mg/kg was administered every 3 weeks from Week 2 in the tilsotolimod arm and Week 1 in the ipilimumab arm. The primary endpoint was efficacy measured using objective response rate (ORR; independent review) and overall survival (OS). Results: A total of481 patients received tilsotolimod plus ipilimumab (n = 238) or ipilimumab alone (n = 243). ORRs were 8.8% in the tilsotolimod arm and 8.6% in the ipilimumab arm, with disease control rates of 34.5% and 27.2%, respectively. Median OS was 11.6 months in the tilsotolimod arm and 10.0 months in the ipilimumab arm (hazard ratio (HR) 0.96 [95% confidence interval (CI) 0.77–1.19]; P = 0.7). Grade ≥3 treatment-emergent adverse events occurred in 61.1% and 55.5% of patients in the tilsotolimod and ipilimumab arms, respectively. Conclusion: Adding tilsotolimod to ipilimumab did not improve response or OS in patients with PD-1 refractory advanced melanoma. However, the results represent the largest prospective dataset reported to date on using ipilimumab in this setting and are a valuable addition to the knowledge base. Clinical trial information: NCT03445533 .
Model-based machine learning of critical brain dynamics
Authors: Bocaccio Hernán , Tagliazucchi Enzo 
Published: June 2024

Abstract
Criticality can be exactly demonstrated in certain models of brain activity, yet it remains challenging to identify in empirical data. We trained a fully connected deep neural network to learn the phases of an excitable model unfolding on the anatomical connectome of human brain. This network was then applied to brain-wide fMRI data acquired during the descent from wakefulness to deep sleep. We report high correlation between the predicted proximity to the critical point and the exponents of cluster size distributions, indicative of subcritical dynamics. This result demonstrates that conceptual models can be leveraged to identify the dynamical regime of real neural systems.