bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEVELOPMENT OF A METHOD FOR PRODUCING FAB/F(AB’)2 FRAGMENTS FROM A FULL-LENGTH MONOCLONAL ANTIBODY FOR BIOANALYTICAL ASSAYS
Authors: Zhang Hefeng , Zhu Lingling , Zou Emily , Liang Yu , Zou Linglong 
Published: July 2023

Abstract

Background
Monoclonal antibodies (mAb) comprise of two Fab fragments and one Fc fragment or one F(ab)’2 fragment and one Fc fragment. While a full-length mAb is frequently used as an assay reagent for bioanalysis, mAb fragments are required in certain cases. For example, to build a sandwich assay for detection of anti-drug antibodies (ADA) for therapeutic antibodies, Fab or F(ab)’2 fragment is used instead of a full-length mAb as capture reagent. This is because therapeutic antibodies, either humanized or fully human, are in many ways indistinguishable from the ADA generated in patients, especially in Fc fragment. When ADA detection methods utilizes anti-human Fc antibodies as the detection reagent, the full-length mAb drug will be directly bound by the detection reagent, causing interference. Preparation of a Fab or F(ab)’2 fragment is therefore needed.

Methods and results
We are developing a method for enzymatic digestion of therapeutic antibodies to generate monovalent Fab or bivalent F(ab’)2 fragments in this study. With such reagents becoming available, a sandwich ADA assay formats can be expanded to allow anti-human Fc antibodies as detection regents. To standardize the method, we explored various enzymatic conditions, including type of enzymes (i.e., pepsin, papain, and IdeS Protease), digestion-time (1, 2, 4, and 6 h), enzyme to antibody ratio (1:10, 1:20, and 1:40 w/w), IgG species and isotypes (human IgG1-κ, IgG1-λ, and IgG4-κ). The enzymatic hydrolysates were quantified by NanoDrop and purified by dialysis (10K MWCO) and Protein A/G/L magnetic bead methods. The effective recovery of truncated antibodies was &gt; 90%, as assessed by reduced/non-reduced SDS-PAGE and ELISA analysis. Digestion of human IgG1 and IgG4 with pepsin resulted into a complete cleavage into F(ab')2 fragments and degradation of Fc fragments. While IdeS Protease produced an equivalent quantity of F(ab’)2 and Fc fragments with a similar efficiency, removal of the intact Fc fragment was required as an additional step. If the Fab fragments were desired, papain could be used with yield being over 90%. We have subsequently utilized either Fab or F(ab’)2 as a capture reagent for ADA detection.

Conclusion
We have successfully developed the enzymatic digestion method to prepare Fab or F(ab’)2 fragments. The optimized conditions described here are broadly applicable to different IgG isotypes across many therapeutic antibodies.
ENGINEERING T CELLS TARGETING GPC2 FOR TREATING NEUROBLASTOMA
Authors: Quan Alex , Li Nan , Li Dan , Spetz Madeline , Zhang Hongbing , Liu Cheng , Ho Mitchell 
Published: July 2023

Abstract

Background and Significance
Neuroblastoma is a rare pediatric cancer that forms in immature nerve tissue of infants and accounts for 10 to 15 percent of cancer-related deaths in children. The five-year survival for high-risk neuroblastoma is 50% with current treatment practices being a combination of surgery, chemotherapy, and radiation. A more effective therapy is therefore needed to improve overall patient outcomes.

Methods
The CT3 mouse antibody that targets GPC2 was previously identified in the lab and has shown activity in the chimeric antigen receptor (CAR) T cell format against neuroblastoma. Humanization of the CT3 antibody was also done through CDR grafting in human germline sequences to prevent potential adverse immunogenic effects when treating patients. In the present study, the CT3 antibody and humanized CT3 (hCT3) antibody were engineered into T cells based on the engineered gamma/delta TCR scaffold (called AbTCR). The activities of the CT3 and hCT3 AbTCRs were tested in luciferase-based cell killing assays and xenograft mouse models.

Results
Humanized CT3 retains a comparable binding affinity for GPC2. The hCT3 CAR T cell showed its ability to regress tumor expression in mice. Furthermore, the mice treated with the CT3 AbTCR showed tumor regression while the mice treated with the hCT3 AbTCR became tumor free three weeks after treatment.

Conclusions
Overall, the hCT3 AbTCR T cells are very active when combating neuroblastoma tumors in mice. The efficacy at a low treatment dosage indicates that the GPC2 targeted hCT3 AbTCRs are a promising therapeutic for the treatment of neuroblastoma and other GPC2 positive cancers in patients.
ICARUS: flexible protein structural alignment based on Protein Units
Authors: Cretin Gabriel , Périn Charlotte , Zimmermann Nicolas , Galochkina Tatiana , Gelly Jean-Christophe 
Published: July 2023

Abstract

Motivation
Alignment of protein structures is a major problem in structural biology. The first approach commonly used is to consider proteins as rigid bodies. However, alignment of protein structures can be very complex due to conformational variability, or complex evolutionary relationships between proteins such as insertions, circular permutations or repetitions. In such cases, introducing flexibility becomes useful for two reasons: (i) it can help compare two protein chains which adopted two different conformational states, such as due to proteins/ligands interaction or post-translational modifications, and (ii) it aids in the identification of conserved regions in proteins that may have distant evolutionary relationships.

Results
We propose ICARUS, a new approach for flexible structural alignment based on identification of Protein Units, evolutionarily preserved structural descriptors of intermediate size, between secondary structures and domains. ICARUS significantly outperforms reference methods on a dataset of very difficult structural alignments.

Availability and implementation
Code is freely available online at https://github.com/DSIMB/ICARUS.
Molecular property prediction by semantic-invariant contrastive learning
Authors: Zhang Ziqiao , Xie Ailin , Guan Jihong , Zhou Shuigeng 
Published: July 2023

Abstract

Motivation
Contrastive learning has been widely used as pretext tasks for self-supervised pre-trained molecular representation learning models in AI-aided drug design and discovery. However, existing methods that generate molecular views by noise-adding operations for contrastive learning may face the semantic inconsistency problem, which leads to false positive pairs and consequently poor prediction performance.

Results
To address this problem, in this article, we first propose a semantic-invariant view generation method by properly breaking molecular graphs into fragment pairs. Then, we develop a Fragment-based Semantic-Invariant Contrastive Learning (FraSICL) model based on this view generation method for molecular property prediction. The FraSICL model consists of two branches to generate representations of views for contrastive learning, meanwhile a multi-view fusion and an auxiliary similarity loss are introduced to make better use of the information contained in different fragment-pair views. Extensive experiments on various benchmark datasets show that with the least number of pre-training samples, FraSICL can achieve state-of-the-art performance, compared with major existing counterpart models.

Availability and implementation
The code is publicly available at https://github.com/ZiqiaoZhang/FraSICL.
Efficacy of hydrodilatation in frozen shoulder: a systematic review and meta-analysis
Authors: Poku Daryl , Hassan Rifat , Migliorini Filippo , Maffulli Nicola 
Published: July 2023

AbstractIntroductionIt is unclear whether hydrodilatation is beneficial in the management of frozen shoulder compared with other common conservative management modalities. This systematic review evaluates the efficacy of hydrodilatation for the management of frozen shoulder.Sources of dataA systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An extensive search of PubMed, Embase, Scopus, Cochrane Central, Web of Science and CINAHL databases using multiple keyword combinations of ‘shoulder’, ‘rotator’, ‘adhesive capsulitis’, ‘hydrodilatat*’, ‘distension’ since inception of the databases to June 2023 was implemented.Areas of agreementHydrodilatation leads to at least transient more marked improvements in shoulder disability and passive external rotation compared with intra-articular corticosteroid injections.Areas of controversyHydrodilatation improves passive external rotation in the longer term. Moreover, hydrodilatation may be a preferable option over manipulation under anaesthesia, given its lower cost and better patient convenience.Growing pointsIntensive mobilization after hydrodilatation is a promising adjuvant treatment option for patients suffering from a frozen shoulder.Areas timely for developing researchAlthough current evidence suggests that hydrodilatation provides a transient improvement in disability in patients with frozen shoulder, its clinical relevance remains unclear. Further research is necessary to establish its role in the management of the condition.
Arsenic speciation in freshwater fish: challenges and research needs
Authors: Hoy Karen S , Davydiuk Tetiana , Chen Xiaojian , Lau Chester , Schofield Jordan R M , Lu Xiufen , Graydon Jennifer A , Mitchell Ruth , Reichert Megan , Le X Chris 
Published: July 2023

Abstract
Food and water are the main sources of human exposure to arsenic. It is important to determine arsenic species in food because the toxicities of arsenic vary greatly with its chemical speciation. Extensive research has focused on high concentrations of arsenic species in marine organisms. The concentrations of arsenic species in freshwater fish are much lower, and their determination presents analytical challenges. In this review, we summarize the current state of knowledge on arsenic speciation in freshwater fish and discuss challenges and research needs. Fish samples are typically homogenized, and arsenic species are extracted using water/methanol with the assistance of sonication and enzyme treatment. Arsenic species in the extracts are commonly separated using high-performance liquid chromatography (HPLC) and detected using inductively coupled plasma mass spectrometry (ICPMS). Electrospray ionization tandem mass spectrometry, used in combination with HPLC and ICPMS, provides complementary information for the identification and characterization of arsenic species. The methods and perspectives discussed in this review, covering sample preparation, chromatography separation, and mass spectrometry detection, are directed to arsenic speciation in freshwater fish and applicable to studies of other food items. Despite progress made in arsenic speciation analysis, a large fraction of the total arsenic in freshwater fish remains unidentified. It is challenging to identify and quantify arsenic species present in complex sample matrices at very low concentrations. Further research is needed to improve the extraction efficiency, chromatographic resolution, detection sensitivity, and characterization capability.
Understanding how whānau-centred initiatives can improve Māori health in Aotearoa New Zealand
Authors: Reweti Angelique 
Published: July 2023

Abstract
This article highlights the significance of prioritizing Indigenous voices and knowledge systems, using whānau-centred initiatives (a concept that encompasses the broader family and community) as a foundation for health promotion within an Indigenous context. Tū Kahikatea, a conceptual framework, is used to demonstrate the relationship between the values underpinning different whānau-centred initiatives and their corresponding outcomes. The framework highlights the capacity of whānau-centred initiatives to support whānau in attaining mana motuhake, which represents collective self-determination and the ability to exercise control over their own future. By doing so, these initiatives contribute to the improvement of whānau health outcomes. With recent changes to Aotearoa New Zealand’s health system, the findings underscore the benefits and potential of whānau-centred initiatives in enhancing whānau health outcomes, and advocate for continued strengths-based practices in Aotearoa New Zealand’s health system. By bridging the gap between academia and grassroots community action, the article demonstrates the potential of whānau-centred initiatives and contributes to a global call for integrating Indigenous viewpoints and practices into Westernized healthcare, in order to improve Indigenous health outcomes.
Variable exposure to multiple climate stressors across the California marine protected area network and policy implications
Authors: Hamilton S L , Kennedy E G , Zulian M , Hill T M , Gaylord B , Sanford E , Ricart A M , Ward M , Spalding A K , Kroeker K 
Published: July 2023

AbstractThe efficacy of marine protected areas (MPAs) may be reduced when climate change disrupts the ecosystems and human communities around which they are designed. The effects of ocean warming on MPA functioning have received attention but less is known about how multiple climatic stressors may influence MPAs efficacy. Using a novel dataset incorporating 8.8 million oceanographic observations, we assess exposure to potentially stressful temperatures, dissolved oxygen concentrations, and pH levels across the California MPA network. This dataset covers more than two-thirds of California’s 124 MPAs and multiple biogeographic domains. However, spatial-temporal and methodological patchiness constrains the extent to which systematic evaluation of exposure is possible across the network. Across a set of nine well-monitored MPAs, the most frequently observed combination of stressful conditions was hypoxic conditions (&lt;140 umol/kg) co-occurring with low pH (&lt;7.75). Conversely, MPAs exposed most frequently to anomalously warm conditions were less likely to experience hypoxia and low pH, although exposure to hypoxia varied throughout the 2014–2016 marine heatwaves. Finally, we found that the spatial patterns of exposure to hypoxia and low pH across the MPA network remained stable across years. This multiple stressor analysis both confirms and challenges prior hypotheses regarding MPA efficacy under global environmental change.
Decadal characteristics of small-scale fishing livelihoods in 13 Pacific Island Countries and Territories
Authors: Roscher M B , Eriksson H , Sharp M , Menaouer O , Andrew N 
Published: July 2023

AbstractSmall-scale fisheries are cornerstones of wealth, food, and tradition for people throughout the Pacific region. Yet, their governance is plagued by a lack of relevant data. Using data collected from household income and expenditure surveys carried out in 13 Pacific Island Countries and Territories over the last decade, we bring enhanced resolution to these fisheries by describing how households engage in small-scale fishing and accounting the income generated from these activities. We find most households do not actively participate in fishing, and most that do, fish only for subsistence. Over time, however, the rates at which households participate in fishing may be declining. Further, the total income generated through aquatic foods caught for subsistence is nearly double that of foods caught for sale, but on a per household basis fishing for commercial purposes is more lucrative. Differences point to important distinctions in how households engage with and generate income from commercial and subsistence fishing, including where activities are often conducted, and the types of aquatic foods targeted. These distinctions have implications for how livelihoods-focused policies and programmes can be developed to ensure aquatic food systems continue to support Pacific Island communities as the deadline for the Sustainable Development Goals approaches.
Pre-pregnancy and pregnancy disorders, pre-term birth and the risk of cerebral palsy: a population-based study
Authors: Razaz Neda , Cnattingius Sven , Lisonkova Sarka , Nematollahi Shahrzad , Oskoui Maryam , Joseph K S , Kramer Michael 
Published: July 2023

Abstract

Background
Cerebral palsy (CP) is the most common cause of childhood physical disability whose aetiology remains unclear in most cases. Maternal pre-existing and pregnancy complications are recognized risk factors of CP but the extent to which their effects are mediated by pre-term birth is unknown.

Methods
Population-based cohort study in Sweden including 2 055 378 singleton infants without congenital abnormalities, born between 1999 and 2019. Data on maternal and pregnancy characteristics and diagnoses of CP were obtained by individual record linkages of nationwide Swedish registries. Exposure was defined as maternal pre-pregnancy and pregnancy disorders. Inpatient and outpatient diagnoses were obtained for CP after 27 days of age. Adjusted rate ratios (aRRs) were calculated, along with 95% CIs.

Results
A total of 515 771 (25%) offspring were exposed to maternal pre-existing chronic disorders and 3472 children with CP were identified for a cumulative incidence of 1.7 per 1000 live births. After adjusting for potential confounders, maternal chronic cardiovascular or metabolic disorders, other chronic diseases, mental health disorders and early-pregnancy obesity were associated with 1.89-, 1.24-, 1.26- and 1.35-times higher risk (aRRs) of CP, respectively. Most notably, offspring exposed to maternal antepartum haemorrhage had a 6-fold elevated risk of CP (aRR 5.78, 95% CI, 5.00–6.68). Mediation analysis revealed that ∼50% of the effect of these associations was mediated by pre-term delivery; however, increased risks were also observed among term infants.

Conclusions
Exposure to pre-existing maternal chronic disorders and pregnancy-related complications increases the risk of CP in offspring. Although most infants with CP were born at term, pre-term delivery explained 50% of the overall effect of pre-pregnancy and pregnancy disorders on CP.
A Synthetic External Control Study Comparing the Clinical Efficacy of Wendan Decoction and 19 Antidepressants
Authors: Yang Yuting , Chen Rui , Li Caixia , Zheng Qingshan , Lv Yinghua , Li Lujin , Tan Hongsheng 
Published: July 2023

Abstract

Background
Wendan decoction (WDD) has been used as a treatment for depression in China since the Tang Dynasty. However, high-quality evidence for this is lacking. This study proposed a novel synthetic external control method to evaluate its clinical efficacy.

Methods
We searched public databases for clinical trials of WDD for major depression. The rate of change of the Hamilton Depression Scale score from baseline was used as an efficacy indicator, and a model-based meta-analysis was performed to analyze the clinical efficacy of WDD. To establish a reference standard for efficacy, the antidepressant efficacy distributions of a placebo and 19 antidepressants were virtually synthesized based on the same conditions as the clinical trial characteristics of WDD.

Results
This study included 5 clinical trials with 177 participants. WDD showed a slow onset, with a time to reach the maximum effect of 9.71 weeks. At 8 weeks, the rate of change in the Hamilton Depression Scale score from baseline was 66.4% (95% CI = 62.3%–70.3%) in the WDD group. The pure effect value of WDD, after deducting the placebo effect, was 26.9% (95%CI = 23.0%–30.9%), which was comparable with 5 types of antidepressants and significantly higher than the others.

Conclusion
The proposed external synthetic control method provides a solution to the bottleneck problem of clinical efficacy evaluation in real-world research on traditional Chinese medicine. WDD has high clinical development value for the treatment of depression, and large-scale randomized controlled trials are recommended to confirm its antidepressant effect.
Mammography Information Systems: A Survey of Breast Imaging Radiologist Satisfaction and Perspectives
Authors: Mullen Lisa A , Ambinder Emily B , Talati Nishi , Margolies Laurie R 
Published: July 2023

AbstractObjectiveTo assess use of mammography information systems (MISs) and explore features associated with breast imaging radiologist satisfaction.MethodsA 22-question survey regarding MISs was distributed electronically to the Society of Breast Imaging membership between February 16, 2022 and June 28, 2022. Differences in responses between respondents satisfied and dissatisfied with their MIS were analyzed using Pearson chi-squared test, Fisher exact test, and multivariate logistic regression.ResultsThe response rate was 11.4% (228/2007). Most respondents used a commercial MIS (195/228, 85.5%). Most used were Epic (47/228, 21%), MagView (47/228, 21%), and PenRad (37/228, 16%). Only 4.4% (10/228) reported that patient tracking was not integrated with results reporting. The majority (129/226, 57%) reported satisfaction with their MIS. Satisfaction correlated (P &lt; 0.05) with features such as picture archiving and communication system integration, structured reporting, access to physician outcomes metrics, and ability to query data. Less commonly reported features such as non-English language options and recognition of laterality and patient mismatch errors also correlated with satisfaction. Lack of these features correlated with dissatisfaction (P &lt; 0.05). Satisfaction also correlated with adequate training (P &lt; 0.001) and technology support (P &lt; 0.001). On multivariate analysis, longer time using the current MIS was independently associated with satisfaction.ConclusionMost respondents used a commercial MIS and were satisfied with their system. Satisfied users reported several helpful MIS features and adequate training and support. The survey results could help MIS companies when designing new products and inform radiologists and administrators when considering a new MIS.
A modified smell agent optimization for global optimization and industrial engineering design problems
Authors: Wang Shuang , Hussien Abdelazim G , Kumar Sumit , AlShourbaji Ibrahim , Hashim Fatma A 
Published: July 2023

Abstract
This paper introduces an Improved Smell Agent Optimization Algorithm (mSAO), a new and enhanced metaheuristic designed to tackle complex engineering optimization issues by overcoming the shortcomings of the recently introduced Smell Agent Optimization Algorithm. The proposed mSAO incorporates the jellyfish swarm active–passive mechanism and novel random operator in the elementary SAO. The objective of modification is to improve the global convergence speed, exploration–exploitation behaviour, and performance of SAO, as well as provide a problem-free method of global optimization. For numerical validation, the mSAO is examined using 29 IEEE benchmarks with varying degrees of dimensionality, and the findings are contrasted with those of its basic version and numerous renowned recently developed metaheuristics. To measure the viability of the mSAO algorithm for real-world applications, the algorithm was employed to solve to resolve eight challenges drawn from real-world scenarios including cantilever beam design, multi-product batch plant, industrial refrigeration system, pressure vessel design, speed reducer design, tension/compression spring, and three-bar truss problem. The computational analysis demonstrates the robustness of mSAO relatively in finding optimal solutions for mechanical, civil, and industrial design problems. Experimental results show that the suggested modifications lead to an improvement in solution quality by 10–20% of basic SAO while solving constraint benchmarks and engineering problems. Additionally, it contributes to avoiding local optimal stuck, and premature convergence limitations of SAO and simultaneously.