bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bisimulation Learning
Authors: Abate Alessandro , Giacobbe Mirco , Schnitzer Yannik 
Published: July 2024

AbstractWe introduce a data-driven approach to computing finite bisimulations for state transition systems with very large, possibly infinite state space. Our novel technique computes stutter-insensitive bisimulations of deterministic systems, which we characterize as the problem of learning a state classifier together with a ranking function for each class. Our procedure learns a candidate state classifier and candidate ranking functions from a finite dataset of sample states; then, it checks whether these generalise to the entire state space using satisfiability modulo theory solving. Upon the affirmative answer, the procedure concludes that the classifier constitutes a valid stutter-insensitive bisimulation of the system. Upon a negative answer, the solver produces a counterexample state for which the classifier violates the claim, adds it to the dataset, and repeats learning and checking in a counterexample-guided inductive synthesis loop until a valid bisimulation is found. We demonstrate on a range of benchmarks from reactive verification and software model checking that our method yields faster verification results than alternative state-of-the-art tools in practice. Our method produces succinct abstractions that enable an effective verification of linear temporal logic without next operator, and are interpretable for system diagnostics.
Resummation of combined QCD-electroweak effects in Drell Yan lepton-pair production
Authors: Buonocore Luca , Rottoli Luca , Torrielli Paolo 
Published: July 2024

Abstract
We consider neutral- and charged-current Drell Yan lepton-pair production at hadron colliders, and include dominant classes of electroweak and mixed QCD-electroweak corrections to all orders in perturbation theory. The accurate description of these physical effects is vital for a precise determination of fundamental Standard Model parameters, such as the W-boson mass and the electroweak mixing angle, as well as for a solid assessment of the associated theoretical uncertainties. Our state-of-the-art resummation reaches next-to-leading-logarithmic accuracy in both the electroweak and the mixed QCD-electroweak perturbative expansions, including constant terms at first order beyond Born level in both couplings, i.e. at order α and αsα. These effects are incorporated on top of QCD predictions at next-to-next-to-next-to-leading-logarithmic accuracy, which include constant terms at third order in the strong coupling. Our results retain, for the first time at this accuracy, full dependence on the kinematics of the final-state leptons, thereby enabling a realistic comparison with experimental analyses at the differential level in presence of fiducial cuts. We present a phenomenological analysis of the impact of electroweak corrections in relevant observables at the LHC. We find visible shape distortions in resummation-dominated kinematical regions with respect to pure-QCD predictions, highlighting the importance of a complete description, not limited to QCD, for precision Drell Yan physics.
A path integral formula of quantum gravity emergent from entangled local structures
Authors: Liu Jinglong , Alexander Stephon , Marcianò Antonino , Pasechnik Roman 
Published: July 2024

Abstract
We couple to group field theory (GFT) a scalar field that encodes the entanglement between manifold sites. The scalar field provides a relational clock that enables the derivation of the Hamiltonian of the system from the GFT action. Inspecting the Hamiltonian, we show that a theory of emergent gravity arises, and that this can be recast according to the Ashtekar’s formulation of general relativity. The evolution of the GFT observables is regulated by the Shrödinger equation generated by the Hamiltonian. This is achieved by imposing a renormalization group (RG) flow that corresponds to a simplified Ricci flow. As a consequence of the quantization procedure, the Hamiltonian is recovered to be non-Hermitian, and can be related to the complex action formalism, in which the initial conditions and the related future evolution of the systems are dictated by the imaginary part of the action.
Seasonal patterns of hip fracture incidence and mortality rates across age groups of older adults in Israel
Authors: Yonai Yaniv , Masarwa Salim , Ben Natan Merav , Berkovich Yaron 
Published: July 2024

Abstract
Purpose
This study investigates the seasonal patterns of hip fracture occurrence and mortality rates in the elderly population of Israel.

Methods
In this retrospective study, we examined a random sample of 400 patients who underwent a hip fracture repair surgery at a 495-bed hospital in northern-central Israel during the years 2021–2022.

Results
Our findings reveal a heightened incidence of hip fractures during the spring (30.8%) in contrast to relatively consistent rates during other seasons (22-24.2%). Patients experiencing hip fractures in the spring were notably younger and had shorter hospital stays compared to those in other seasons. Furthermore, we identified seasonal variations in hip fracture incidence concerning gender, culture, and nationality. Over the 2-year follow-up period, 20% of patients had succumbed to mortality. The highest survival rate was associated with hip fractures sustained in the spring, while the lowest rates were observed in the autumn and winter.

Conclusion
While our study highlights significant seasonal variations in hip fracture occurrence and mortality rates among the elderly population in Israel, caution is warranted in interpreting the implications for post-fracture care and resource allocation. The observed heightened incidence of hip fractures during the spring, particularly among younger patients with shorter hospital stays, suggests the need for further investigation into potential risk factors and preventive measures specific to this season. Additionally, our identification of seasonal variations in hip fracture incidence across demographic factors underscores the importance of tailored interventions to address the diverse needs of different populations.
Structure-based humanization of a therapeutic antibody for multiple myeloma
Authors: Marino Stephen F. , Daumke Oliver 
Published: July 2024

Abstract
The optimal efficacy of xenogeneically generated proteins intended for application in humans requires that their own antigenicity be minimized. This necessary adaptation of antibodies to a humanized version poses challenges since modifications even distant from the binding sites can greatly influence antigen recognition and this is the primary feature that must be maintained during all modifications. Current strategies often rely on grafting and/or randomization/selection to arrive at a humanized variant retaining the binding properties of the original molecule. However, in terms of speed and efficiency, rationally directed approaches can be superior, provided the requisite structural information is available. We present here a humanization procedure based on the high-resolution X-ray structure of a chimaeric IgG against a marker for multiple myeloma. Based on in silico modelling of humanizing amino acid substitutions identified from sequence alignments, we devised a straightforward cloning procedure to rapidly evaluate the proposed sequence changes. Careful inspection of the structure allowed the identification of a potentially problematic amino acid change that indeed disrupted antigen binding. Subsequent optimization of the antigen binding loop sequences resulted in substantial recovery of binding affinity lost in the completely humanized antibody. X-ray structures of the humanized and optimized variants demonstrate that the antigen binding mode is preserved, with surprisingly few direct contacts to antibody atoms. These results underline the importance of structural information for the efficient optimization of protein therapeutics.

Key messages

Structure-based humanization of an IgG against BCMA, a marker for Multiple Myeloma.

Identification of problematic mutations and unexpected modification sites.

Structures of the modified IgG-antigen complexes verified predictions.

Provision of humanized high-affinity IgGs against BCMA for therapeutic applications.
Breeding and management of major resistance genes to stem canker/blackleg in Brassica crops
Authors: Vasquez-Teuber Paula , Rouxel Thierry , Mason Annaliese S. , Soyer Jessica L. 
Published: July 2024

AbstractBlackleg (also known as Phoma or stem canker) is a major, worldwide disease of Brassica crop species, notably B. napus (rapeseed, canola), caused by the ascomycete fungus Leptosphaeria maculans. The outbreak and severity of this disease depend on environmental conditions and management practices, as well as a complex interaction between the pathogen and its hosts. Genetic resistance is a major method to control the disease (and the only control method in some parts of the world, such as continental Europe), but efficient use of genetic resistance is faced with many difficulties: (i) the scarcity of germplasm/genetic resources available, (ii) the different history of use of resistance genes in different parts of the world and the different populations of the fungus the resistance genes are exposed to, (iii) the complexity of the interactions between the plant and the pathogen that expand beyond typical gene-for-gene interactions, (iv) the incredible evolutionary potential of the pathogen and the importance of knowing the molecular processes set up by the fungus to “breakdown’ resistances, so that we may design high-throughput diagnostic tools for population surveys, and (v) the different strategies and options to build up the best resistances and to manage them so that they are durable. In this paper, we aim to provide a comprehensive overview of these different points, stressing the differences between the different continents and the current prospects to generate new and durable resistances to blackleg disease.
Inpatient’s, therapist’s and staff’s expectations regarding treatment and their effects on placebo response in the psychiatric ward – results from an add-on oxytocin RCT
Authors: Nitzan Uri , Grossman-Girron A. , Sedoff O. , Maoz H. , Arad O. , Tilbor E. , Dror C. , Bitan D. Tzur 
Published: July 2024

Abstract
Objectives
Patient’s and therapist’s expectations are considered an important factor influencing placebo response in experimental and therapeutic settings. Nevertheless, the placebo effects of common neurological facilitators that promote treatment efficacy have not been explored. In the present study we examined the estimations of patients, therapists, and staff members, regarding their treatment type and assessed their influence on the facilitating effects of oxytocin.

Methods
Patients (N = 87) were randomized and double-blindly allocated to receive either oxytocin or placebo, twice daily for a period of four weeks, as part of a larger randomized, double-blind, placebo-controlled trial. Patient’s, therapist’s and staff’s expectations were assessed based on their estimation of treatment type (agent or placebo). Multilevel modeling and univariate and multivariate regression analysis were performed to assess the effects of patient’s, therapist’s, and staff’s estimations on treatment outcome beyond the effects of treatment type.

Results
Staff’s, therapist’s, and patient’s estimations were significantly associated with treatment outcomes. Nevertheless, only therapist’s and patient’s estimations significantly predicted improvement beyond actual administration, with therapist’s and patient’s estimations associated with improvement in trait anxiety (STAI-T, B=-1.80, p < .05, and B=-2.02, p < .05, respectively); therapist’s estimations were associated with improvement in general distress (OQ-45, B=-3.71, p < .05), and patient’s estimations were associated with symptom relief (HSCL-11, B=-0.13, p < .05). Overall, patient’s estimations had a higher relative contribution to treatment success, with standardized coefficients across scales ranging from − 0.06 to -0.26.

Conclusions
The neurobiological factors that promote treatment success are also influenced by patient’s and therapist’s expectations. Future studies should consider these effects when examining their impact in inpatient settings.
Cognitive reserve and executive functions in dual task gait performance in Parkinson’s disease
Authors: Fernández-Lago Helena , Bosch-Barceló Pere , Sánchez-Molina José Andrés , Ambrus Mira , Rio Dan , Fernández-Del-Olmo Miguel Ángel 
Published: July 2024

AbstractA higher level of education was correlated with less severe motor impairment in Parkinson’s Disease (PD). Nevertheless, there is limited evidence on the relationship between cognitive reserve and motor performance in complex situations in PD. To investigate the association between cognitive reserve and the dual-task gait effect in PD. Additionally, we examined the relationship between executive function, clinical and sociodemographic variables and, dual-task gait effects. We conducted a cross-sectional study with 44 PD participants. We evaluated dual-task effect on cadence, stride length, and gait velocity. Dual-task effects were correlated with neurophysiological factors, including cognitive reserve (Cognitive Reserve Index Questionnaire), overall cognitive performance of executive functions, a specific executive function domain (Trail Making Test), and the global cognitive status (Montreal Cognitive Assessment and Mini-Mental State Examination). Age, gender, and disease severity were considered as variables to be examined for correlation. We found that cognitive reserve did not influence gait performance under dual-task conditions in this sample. However, executive functions, age, and disease severity were associated with the dual-task effect on gait. The overall cognitive performance with respect to the Trail Making Test showed an inverse relationship in the dual-task gait effect on cadence. Our study’s findings have important implications for understanding the association between executive functions, age, and disease severity with the dual-task effect on gait in PD. Pre-life factors, such as education, occupation, and leisure activity, did not contribute to coping with complex gait situations in PD.
Painful sexual intercourse, quality of life and sexual function in patients with endometriosis: not just deep dyspareunia
Authors: Del Forno Simona , Raspollini Arianna , Doglioli Marisol , Andreotti Anna , Spagnolo Emanuela , Lenzi Jacopo , Borghese Giulia , Raimondo Diego , Arena Alessandro , Rodriguez Elena , Hernandez Alicia , Govoni Francesca , Seracchioli Renato 
Published: July 2024

Abstract
Purpose
To evaluate the prevalence of deep and superficial dyspareunia in women with diagnosis of endometriosis. Secondly, to assess the temporal relation between deep and superficial dyspareunia in women reporting both symptoms (concomitant dyspareunia) and the impact on quality of life (QoL) and sexual function.

Methods
This is a cross-sectional cohort study that included fertile women with diagnosis of endometriosis. Enrolled subjects reported pain symptoms including dyspareunia and its temporal onset and completed two one-time validated questionnaires regarding sexual function (Female Sexual Function Index) and QoL (International QoL Assessment SF-36).

Results
Among the 334 enrolled patients, 75.7% (95%) reported dyspareunia. Women were divided into four groups according to the presence and type of dyspareunia: isolated superficial dyspareunia (6.3%), isolated deep dyspareunia (26.0%), concomitant dyspareunia (43.4%) and no dyspareunia (24.3%). Women with concomitant dyspareunia reported higher NRS scores than women with isolated dyspareunia or no dyspareunia (P ≤ 0.001). The majority of women with concomitant dyspareunia (56.6%) reported that deep dyspareunia developed before superficial dyspareunia. Women with concomitant dyspareunia reported worse QoL and worse sexual function than women with isolated dyspareunia or without dyspareunia (P ≤ 0.001).

Conclusion
Dyspareunia is a common symptom in women with endometriosis, with many reporting concomitant deep and superficial dyspareunia. Concomitant dyspareunia can significantly impact sexual function and quality of life (QoL). Therefore, it is crucial to investigate dyspareunia thoroughly and differentiate between its types to tailor effective therapeutic strategies.
IKZF3 amplification predicts worse prognosis especially in intestinal-type gastric cancer
Authors: Cui Zhaomeng , Liang Huaiyu , Luo Rongkui , Huang Wen , Yuan Wei , Zhang Lei , Luan Lijuan , Su Jieakesu , Huang Jie , Xu Chen , Hou Yingyong 
Published: July 2024

Abstract
Purpose
IKAROS family zinc finger 3 (IKZF3) is an oncogene involved in different malignancies, particularly in the development and malignant progression of lymphocytes. However, IKZF3 amplification and clinical significance in gastric cancers (GCs) remain unexplored.

Methods
We examined IKZF3 amplification status in 404 GCs with HER2 amplification status using tissue microarray (TMA) and fluorescence in situ hybridization (FISH) assays.

Results
IKZF3 amplification was detected in 6.9% (28/404) of all GC patients, with higher rates in intestinal-type gastric cancer (IGC) (11.22%, 22/196) compared to other types (2.88%, 6/208). HER2 amplification was identified in 16.09% (65/404) of all GC patients, with higher rates in IGC (20.92%, 41/196) compared to other types (11.54%, 24/208). Co-amplification of IKZF3 and HER2 was detected in 8.16% (16/196) of IGC patients and in 2.40% (5/208) of other types. IKZF3 amplification showed significant correlation with IGC (P = 0.001) and HER2 amplification (P = 0.0001). IKZF3 amplification exhibited significantly worse disease-free survival (DFS) (P = 0.014) and overall survival (OS) (P = 0.018) in GC patients, particularly in IGC (DFS: P < 0.001; OS: P < 0.001), rather than other types. Cox regression analysis demonstrate IKZF3 amplification as an independent poor prognostic factor in all GCs (P = 0.006, P = 0.004 respectively) and in IGC patients, regardless of stages I-II or III-IV (P = 0.007, P = 0.004 respectively). On the other hand, HER2 amplification was significantly associated with worse DFS (P = 0.008) and OS (P = 0.01) in IGC patients, but not in all GCs and in multivariate analysis. Within the subset of patients with HER2 amplification, those also exhibiting IKZF3 amplification displayed potential poorer prognosis (P = 0.08, P = 0.11 respectively).

Conclusion
IKZF3 amplification was detected in minority of GC patients, especially in IGC, and was an independent indicator of poor prognosis. Our study, for the first time, found the prognostic value of IKZF3 was superior to HER2 for GC patients.
The use of peripheral CD3+γδ+Vδ2+ T lymphocyte cells in combination with the ALBI score to predict immunotherapy response in patients with advanced hepatocellular carcinoma: a retrospective study
Authors: Zhang Shuhan , Li Luyang , Liu Chengli , Pu Meng , Ma Yingbo , Zhang Tao , Chai Jiaqi , Li Haoming , Yang Jun , Chen Meishan , Kong Linghong , Xia Tian 
Published: July 2024

Abstract
Background
Currently, there is a lack of effective indicators for predicting the efficacy of immunotherapy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to investigate the expression and prognostic value of peripheral T lymphocyte subsets in advanced HCC.

Methods
Patients with advanced HCC who were treated with immune checkpoint inhibitors (ICIs) from December 2021 to December 2023 were included in the study. Flow cytometry was used to detect lymphocyte subsets before treatment. The patients were divided into disease control (DC) and nondisease control (nDC) groups based on treatment efficacy. Relationships between the clinical characteristics/peripheral T lymphocytes and immunotherapy efficacy were analyzed. The effectiveness of peripheral T lymphocyte subsets in predicting immunotherapy efficacy for patients with advanced HCC was analyzed using receiver operating characteristic (ROC) curves.

Results
A total of 40 eligible patients were included in this study. Non-DC was significantly associated with higher albumin-bilirubin (ALBI) scores. The percentages of γδ+Vδ2+PD1+ T cells and γδ+Vδ2+Tim3+ T cells were greater in the nDC group than in the DC group. Multivariable regression analysis revealed that the ALBI score and T lymphocytes expressing γδ+Vδ2+PD1+ and γδ+Vδ2+Tim3+ were founded to be independent influencing factors. The area under the ROC curve (AUC) values for these combinations was 0.944 (95% CI, 0.882 ~ 1.000).

Conclusions
The calculation of the ALBI score and determination of the percentages CD3+γδ+Vδ2+PD1+ T lymphocytes and CD3+γδ+Vδ2+Tim3+ T lymphocytes in the peripheral blood of patients with advanced HCC are helpful for predicting the patients’ responses to ICIs, helping to screen patients who may clinically benefit from immunotherapy.

Retrospectively registered
number: ChiCTR2400080409, date of registration: 2024-01-29.
MASCC/ISOO Clinical Practice Statement: Management of oral manifestations of chronic graft-versus-host-disease
Authors: Zadik Yehuda , Raber-Durlacher Judith E. , Epstein Joel B. , Majorana Alessandra , Laheij Alexa , Bardellini Elena , Blijlevens Nicole , Elad Sharon 
Published: July 2024

Abstract
Purpose
A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians, which concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of oral manifestations of chronic graft-versus-host-disease (cGVHD).

Methods
This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and table to generate a short manual about the best standard of care.

Results
The treatment goals in oral cGVHD are to relieve pain and xerostomia, improve oral function, prevent secondary infection, prevent deterioration of the dentition, and detect malignant transformation as early as possible. The prevention and treatment measures for oral mucosal lesions, hypofunction of the salivary glands, and sclerodermatous changes in the oral and perioral tissues are detailed, as well as the possible complications and side effects of these interventions.

Conclusions
Patients post allogeneic hematopoietic cell transplantations, with cGVHD manifest in the oral and perioral tissues, should be regularly monitored and treated as needed by an oral care practitioner. This CPS provides the clinician with practical tools for examining, preventing, and treating the various sequalae that may affect the oral cavity in these patients.
An audit of central venous catheter insertion and management practices in two French university hospitals
Authors: Khanafer Nagham , Gardes Sophie , De-Santis Nathalie , Liard Céline , Deschamps Florian , Verbist Pauline , Nancey Stephane , Cotte Eddy , Martin Olivier , Argaud Laurent , Lukaszewicz Anne Claire , Vanhems Philippe 
Published: July 2024

Abstract
Objective
To assess the compliance with French guidelines for the prevention of central venous catheter (CVC)-related infections in two university hospitals.

Methods
An observational audit was conducted in 7 wards using a digital tool.

Results
The prerequisite of hand hygiene (HH) were respected by 90% of health-care worker; 86% performed HH prior to equipment preparation and 59% repeated it prior to infusion. Wearing gloves when necessary and rinsing were respected in 46.7% and 75.6% of the observations.

Conclusion
Findings showed an acceptable level of adherence to recommended practices for CVC management. However, barriers of unrespect evidence-based recommendations need to be investigated in depth.