bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-domain antibodies against SARS-CoV-2 RBD from a two-stage phage screening of universal and focused synthetic libraries
Authors: Chen Fangfang , Liu Zhihong , Kang Wei , Jiang Fan , Yang Xixiao , Yin Feng , Zhou Ziyuan , Li Zigang 
Published: February 2024

AbstractBackgroundCoronavirus disease 2019 (COVID-19) is an evolving global pandemic, and nanobodies, as well as other single-domain antibodies (sdAbs), have been recognized as a potential diagnostic and therapeutic tool for infectious diseases. High-throughput screening techniques such as phage display have been developed as an alternative to in vivo immunization for the discovery of antibody-like target-specific binders.MethodsWe designed and constructed a highly diverse synthetic phage library sdAb-U (single-domain Antibody - Universal library ) based on a human framework. The SARS-CoV-2 receptor-binding domain (RBD) was expressed and purified. The universal library sdAb-U was panned against the RBD protein target for two rounds, followed by monoclonal phage ELISA (enzyme-linked immunosorbent assay) to identify RBD-specific binders (the first stage). High-affinity binders were sequenced and the obtained CDR1 and CDR2 sequences were combined with fully randomized CDR3 to construct a targeted (focused) phage library sdAb-RBD, for subsequent second-stage phage panning (also two rounds) and screening. Then, sequences with high single-to-background ratios in phage ELISA were selected for expression. The binding affinities of sdAbs to RBD were measured by an ELISA-based method. In addition, we conducted competition ELISA (using ACE2 ectodomain S19-D615) and SARS-CoV-2 pseudovirus neutralization assays for the high-affinity RBD-binding sdAb39.ResultsSignificant enrichments were observed in both the first-stage (universal library) and the second-stage (focused library) phage panning. Five RBD-specific binders were identified in the first stage with high ELISA signal-to-background ratios. In the second stage, we observed a much higher possibility of finding RBD-specific clones in phage ELISA. Among 45 selected RBD-positive sequences, we found eight sdAbs can be well expressed, and five of them show high-affinity to RBD (EC50 < 100nM). We finally found that sdAb39 (EC50 ~ 4nM) can compete with ACE2 for binding to RBD.ConclusionOverall, this two-stage strategy of synthetic phage display libraries enables rapid selection of SARS-CoV-2 RBD sdAb with potential therapeutic activity, and this two-stage strategy can potentially be used for rapid discovery of sdAbs against other targets.
Fostering the social and physical challenges of female recreational or professional athletes in pregnancy and postpartum
Authors: Santos-Rocha Rita , Szumilewicz Anna 
Published: February 2024

AbstractCombining pregnancy and parenthood with sporting activities or a professional athletic career can be challenging. The objective of this Collection is to gain a deeper understanding of the effects of pregnancy and postpartum on female athletes, both recreational and professional, in order to improve their health and fitness outcomes and support their continued success in sports.
Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur)
Authors: Hitchcock Kathryn E. , Miller Eric D. , Shi Qian , Dixon Jesse G. , Gholami Sepideh , White Sarah B. , Wu Christina , Goulet Christopher C. , George Manju , Jee Kyung-Wook , Wright Chadwick L. , Yaeger Rona , Shergill Ardaman , Hong Theodore S. , George Thomas J. , O’Reilly Eileen M. , Meyerhardt Jeffrey A. , Romesser Paul B. 
Published: February 2024

Abstract
Background
For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed.

Methods
The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16–26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility.

Discussion
The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.

Trial registration
ClinicalTrials.gov: NCT05673148, registered December 21, 2022.
Correlation between choroidal vascularity and retrobulbar ocular blood flow changes and thyroid-associated ophthalmopathy activity: a cross-sectional study
Authors: Sun Xinghong , Su Mengru , Zhang Xiaowen , Shen Haiyun , Xie Zhenggao , Kong Wentao , Zhu Dandan 
Published: February 2024

Abstract
Objective
To evaluate the alterations in retrobulbar color Doppler imaging (CDI) parameters and retinal/choroidal optical coherence tomography angiography (OCTA) parameters and their association with the clinical activity and severity in thyroid-associated orbitopathy (TAO) patients.

Methods
In this study, the retrobulbar flow parameters including resistance index (RI), Pulsatile Index(PI), peak systolic velocity (PSV) and end diastolic velocity (EDV) in posterior ciliary artery (PCA), central retinal artery (CRA) and ophthalmic artery (OA) were determined by CDI. Moreover, the retina and choroidal vascularity including the superficial vessel density (SVD), deep vessel density (DVD), choroidal thickness (ChT) and choroidal vascularity, including total choroidal area (TCA), luminal area (LA), stromal area (SA) and Choroidal Vascularity Index (CVI), were determined by OCTA. All patients grouped as active TAO and inactive TAO based on Clinical activity score (CAS). We picked the severe eye among the subjects and compared all parameters between two groups. We analyzed the correlations among those parameters.

Results
There was a significant difference in CAS score, proptosis value, ChT, LA, CVI between patients with active TAO and inactive TAO. In the active group, PSV and EDV of PCA were significantly higher than the inactive group. On logistic regression analysis, CAS was closely associated with PSV-PCA. On multiple linear regression, proptosis value was closely associated with ChT, LA, SA and CVI.

Conclusion
Choroidal vascularization and retrobulbar blood flow were concurrently higher in active TAO patients and several variables in choroid circulation was closely related to TAO clinical features.
The puppet interview to measure illness perceptions in paediatric oncology: development and psychometric properties in acute treatment and follow-up care
Authors: Herzog Kristina , Schepper Florian , Herrmann Jessy , Martini Julia 
Published: February 2024

Abstract
Background
Illness perceptions comprise assumptions about symptoms, timeline, consequences, controllability, and emotional responses to an illness. Recent evidence shows that illness perceptions are associated with coping and well-being. So far, assessment in paediatric care was based on parental report only, since no instrument for the direct assessment of young children was available. We aim to describe the development (incl. indication and contraindication) of an innovative puppet interview to assess illness perceptions in children with cancer from the age of four years. Moreover, we investigate longitudinal trajectories and examine psychometric properties.

Methods
The puppet interview was developed based on the Illness-Perception-Questionnaire-Revised and the Berkeley-Puppet-Interview. Longitudinal trajectories and psychometric properties were examined in a sample of patient-parent dyads (N = 75) in a prospective longitudinal study in acute treatment with a 1-year follow-up (study 1: nT1 = 41, nT2 = 27) and in a cross-sectional study in follow-up care (study 2, n = 34).

Results
The puppet interview is comprehensible and well-received by children in acute treatment and follow-up care. There were significant differences in perceptions of a chronic timeline (U = 301.00, p = .008), consequences (U = 251.00, p = .008), and emotional representations (U = 244.50, p = .020) between children in acute treatment and children in follow-up care. Over the course of one year, children in acute treatment perceived more symptoms as part of their illness (MT1 = 3.6, SDT1 = 2.9, MT2 = 4.5, SDT2 = 3.1, n = 27, Z = -2.603, p = .009). We found expected intercorrelations between illness perception dimensions, e.g. between perception of consequences and emotional representations (rτ = .27, p = .033), and between perception of a chronic timeline and consequences (rτ = .38, p = .001). Moreover, we found confirming results regarding construct validity, as child’s perceptions of symptoms correlated with their self-rated HRQoL (rτ = -.32, padj. = .014). Also parent-rated subscale on illness-specific aspects of child’s HRQoL correlated with child’s perception of symptoms (rτ = -.26, padj. = .016), cyclicity (rτ = -.28, padj. = .016), and consequences (rτ = -.34, padj. = .014). Acceptable internal consistency was shown for the dimensions timeline-acute/chronic and personal control.

Conclusions
Parental report can now be complemented by a self-report of illness perceptions in children aged four years and older. This will allow for the further adaptation of medical and psychosocial care during and after acute cancer treatment.

Trial registration
The study has been pre-registered at the German Clinical Trials Register (registered 30/06/2020; DRK-S00022034) and at the Open Science Foundation (https://osf.io/7xr6z).
Towards an intelligent malaria outbreak warning model based intelligent malaria outbreak warning in the northern part of Benin, West Africa
Authors: Gbaguidi Gouvidé Jean , Topanou Nikita , Filho Walter Leal , Ketoh Guillaume K. 
Published: February 2024

Abstract
Background
Malaria is one of the major vector-borne diseases most sensitive to climatic change in West Africa. The prevention and reduction of malaria are very difficult in Benin due to poverty, economic insatiability and the non control of environmental determinants. This study aims to develop an intelligent outbreak malaria early warning model driven by monthly time series climatic variables in the northern part of Benin.

Methods
Climate data from nine rain gauge stations and malaria incidence data from 2009 to 2021 were extracted from the National Meteorological Agency (METEO) and the Ministry of Health of Benin, respectively. Projected relative humidity and temperature were obtained from the coordinated regional downscaling experiment (CORDEX) simulations of the Rossby Centre Regional Atmospheric regional climate model (RCA4).
A structural equation model was employed to determine the effects of climatic variables on malaria incidence. We developed an intelligent malaria early warning model to predict the prevalence of malaria using machine learning by applying three machine learning algorithms, including linear regression (LiR), support vector machine (SVM), and negative binomial regression (NBiR).

Results
Two ecological factors such as factor 1 (related to average mean relative humidity, average maximum relative humidity, and average maximal temperature) and factor 2 (related to average minimal temperature) affect the incidence of malaria. Support vector machine regression is the best-performing algorithm, predicting 82% of malaria incidence in the northern part of Benin.
The projection reveals an increase in malaria incidence under RCP4.5 and RCP8.5 over the studied period.

Conclusion
These results reveal that the northern part of Benin is at high risk of malaria, and specific malaria control programs are urged to reduce the risk of malaria.
Marginal adaptation of bulk-fill resin composites with different viscosities in class II restorations: a micro-CT evaluation
Authors: Baltacioğlu İsmail Hakkı , Demirel Gülbike , Öztürk Burcu , Aydin Fulya , Orhan Kaan 
Published: February 2024

Abstract
Background
The purpose of this study is to evaluate the marginal adaptation of bulk-fill resin composites with different viscosities (paste-like and flowable) in Class II restorations using micro-CT imaging.

Methods
Forty extracted human molars were used. Mesial and distal Class II box cavities (approximately 3 mm x 3 mm x 4 mm) were prepared for each tooth, with cavity floors located 1 mm below the enamel-cementum junction. Following adhesive application, teeth were restored using eight different groups: Group XB: X-tra Base Bulk-fill Flowable (VOCO), Group XF: X-tra Fill Bulk-fill (VOCO), Group FB: Filtek Bulk-fill Posterior (3 M ESPE), Group FF: Filtek Bulk-fill Flowable (3 M ESPE), Group BB: Beautifil-Bulk (SHOFU), Group BF: Beautifil-Bulk Flowable (SHOFU), and Group CO: “as a control group”, Clearfil Majesty Posterior (KURARAY) and Group CF: “as a control group”, Clearfil Majesty Flow + Clearfil Majesty Posterior (KURARAY). The restored teeth underwent an aging protocol involving 1000 cycles in a water bath fluctuating between 5 ± 1.0 °C and 55 ± 1.0 °C. Post-aging, teeth were immersed in 50% silver nitrate solution for 24 h and then in a film developer solution for 8 h. Microleakage analysis was performed using micro-CT, evaluated with 3D Slicer software. A two-way ANOVA was employed for statistical analysis.

Results
Two-way ANOVA results indicated significant effects of both viscosity (p < 0.0001) and composite type (p < 0.0001) on marginal adaptation. Viscosity analysis (comparing flowable and paste-like) revealed no significant differences in the FB-FF, XB-XF and BB-BF groups but significant differences in the and CO-CF group, with flowable type exhibiting less microleakage than paste-like type.

Conclusions
The study suggests that while the viscosity of bulk-fill composites did not significantly affect marginal adaptation, the brand of bulk-fill composite did influence it.
Effect of clear aligner type on maxillary full-arch intrusion: 3D analysis using finite element method
Authors: Geramy Allahyar , Safari Fatemeh 
Published: February 2024

Abstract
Background
Vertical maxillary excess (VME) is one of the most common reasons for seeking orthodontic treatment. Total intrusion with aligners is a promising alternative to surgery in some cases. Considering the elastic deformation of aligners, this study aimed to evaluate the possible desirable and undesirable teeth displacements during full maxillary arch intrusion using clear aligners and temporary anchorage devices (TADs).

Methods
The maxillary arch and clear aligners were modeled in SolidWorks. Four aligner brands including Leon, Duran, Duran Plus, and Essix Plus were selected based on their material properties. Anterior and posterior intrusion forces of 80 and 300 g were applied from attachments between the canines and first premolars and between the first and second molars, respectively. Vertical and anteroposterior tooth displacements were determined.

Results
The greatest intrusion was recorded at the buccal of the second molar, followed by the first molar. The lowest value was measured at the palatal of the molars with all aligners except Duran, which indicated minimal intrusion in the central incisor. All teeth were mesially displaced at the incisal/occlusal except incisors that moved distally. All apices showed distal movement.

Conclusions
Total intrusion using clear aligners may be accompanied by other tooth movements, including buccal tipping and mesial-in rotation of the molars, retrusion of incisors, and mesial movement of other teeth.
Development of a predictive machine learning model for pathogen profiles in patients with secondary immunodeficiency
Authors: Liu Qianning , Chen Yifan , Xie Peng , Luo Ying , Wang Buxuan , Meng Yuanxi , Zhong Jiaqian , Mei Jiaqi , Zou Wei 
Published: February 2024

Abstract
Background
Secondary immunodeficiency can arise from various clinical conditions that include HIV infection, chronic diseases, malignancy and long-term use of immunosuppressives, which makes the suffering patients susceptible to all types of pathogenic infections. Other than HIV infection, the possible pathogen profiles in other aetiology-induced secondary immunodeficiency are largely unknown.

Methods
Medical records of the patients with secondary immunodeficiency caused by various aetiologies were collected from the First Affiliated Hospital of Nanchang University, China. Based on these records, models were developed with the machine learning method to predict the potential infectious pathogens that may inflict the patients with secondary immunodeficiency caused by various disease conditions other than HIV infection.

Results
Several metrics were used to evaluate the models’ performance. A consistent conclusion can be drawn from all the metrics that Gradient Boosting Machine had the best performance with the highest accuracy at 91.01%, exceeding other models by 13.48, 7.14, and 4.49% respectively.

Conclusions
The models developed in our study enable the prediction of potential infectious pathogens that may affect the patients with secondary immunodeficiency caused by various aetiologies except for HIV infection, which will help clinicians make a timely decision on antibiotic use before microorganism culture results return.
Barriers and facilitators associated with the upscaling of the Transmural Trauma Care Model: a qualitative study
Authors: Ratter Julia , Wiertsema Suzanne , Ettahiri Ilham , Mulder Robin , Grootjes Anne , Kee Julia , Donker Marianne , Geleijn Edwin , de Groot Vincent , Ostelo Raymond W. J. G. , Bloemers Frank W. , van Dongen Johanna M. 
Published: February 2024

Abstract
Background
To assess the barriers and facilitators associated with upscaling the Transmural Trauma Care Model (TTCM), a multidisciplinary and patient‐centred transmural rehabilitation care model.

Methods
Semi-structured interviews were conducted with eight trauma surgeons, eight hospital-based physiotherapists, eight trauma patients, and eight primary care physiotherapists who were part of a trauma rehabilitation network. Audio recordings of the interviews were made and transcribed verbatim. Data were analysed using a framework method based on the “constellation approach”. Identified barriers and facilitators were grouped into categories related to structure, culture, and practice.

Results
Various barriers and facilitators to upscaling were identified. Under structure, barriers and facilitators belonged to one of five themes: “financial structure”, “communication structure”, “physical structures and resources”, “rules and regulations”, and “organisation of the network”. Under culture, the five themes were “commitment”, “job satisfaction”, “acting as a team”, “quality and efficiency of care”, and “patients’ experience”. Under practice, the two themes were “practical issues at the outpatient clinic” and “knowledge gained”.

Conclusion
The success of upscaling the TTCM differed across hospitals and settings. The most important prerequisites for successfully upscaling the TTCM were adequate financial support and presence of “key actors” within an organisation who felt a sense of urgency for change and/or expected the intervention to increase their job satisfaction.

Trial registration
NL8163 The Netherlands National Trial Register, date of registration 16-11-2019.
Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review
Authors: Ghasemi Mohammad-Reza , Tehrani Fateh Sahand , Moeinafshar Aysan , Sadeghi Hossein , Karimzadeh Parvaneh , Mirfakhraie Reza , Rezaei Mitra , Hashemi-Gorji Farzad , Rezvani Kashani Morteza , Fazeli Bavandpour Fatemehsadat , Bagheri Saman , Moghimi Parinaz , Rostami Masoumeh , Madannejad Rasoul , Roudgari Hassan , Miryounesi Mohammad 
Published: February 2024

Abstract
Background
Pontocerebellar hypoplasia is an umbrella term describing a heterogeneous group of prenatal neurodegenerative disorders mostly affecting the pons and cerebellum, with 17 types associated with 25 genes. However, some types of PCH lack sufficient information, which highlights the importance of investigating and introducing more cases to further elucidate the clinical, radiological, and biochemical features of these disorders. The aim of this study is to provide an in-depth review of PCH and to identify disease genes and their inheritance patterns in 12 distinct Iranian families with clinically confirmed PCH.

Methods
Cases included in this study were selected based on their phenotypic and genetic information available at the Center for Comprehensive Genetic Services. Whole-exome sequencing (WES) was used to discover the underlying genetic etiology of participants' problems, and Sanger sequencing was utilized to confirm any suspected alterations. We also conducted a comprehensive molecular literature review to outline the genetic features of the various subtypes of PCH.

Results
This study classified and described the underlying etiology of PCH into three categories based on the genes involved. Twelve patients also were included, eleven of whom were from consanguineous parents. Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features. Strabismus and elevation in lactate levels in MR spectroscopy were novel phenotypes for the first time in PCH types 7 and 9.

Conclusions
This study merges previously documented phenotypes and genotypes with unique novel ones. Due to the diversity in PCH, we provided guidance for detecting and diagnosing these heterogeneous groups of disorders. Moreover, since certain critical conditions, such as spinal muscular atrophy, can be a differential diagnosis, providing cases with novel variations and clinical findings could further expand the genetic and clinical spectrum of these diseases and help in better diagnosis. Therefore, six novel genetic variants and novel clinical and paraclinical findings have been reported for the first time. Further studies are needed to elucidate the underlying mechanisms and potential therapeutic targets for PCH.