bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG fractal dimensions predict high-level behavioral responses in minimally conscious patients
Authors: Liuzzi Piergiuseppe , Hakiki Bahia , Draghi Francesca , Romoli Anna Maria , Burali Rachele , Scarpino Maenia , Cecchi Francesca , Grippo Antonello , Mannini Andrea 
Published: July 2023

Abstract

Objective. Brain-injured patients may enter a state of minimal or inconsistent awareness termed minimally conscious state (MCS). Such patient may (MCS+) or may not (MCS-) exhibit high-level behavioral responses, and the two groups retain two inherently different rehabilitative paths and expected outcomes. We hypothesized that brain complexity may be treated as a proxy of high-level cognition and thus could be used as a neural correlate of consciousness. Approach. In this prospective observational study, 68 MCS patients (MCS-: 30; women: 31) were included (median [IQR] age 69 [20]; time post-onset 83 [28]). At admission to intensive rehabilitation, 30 min resting-state closed-eyes recordings were performed together with consciousness diagnosis following international guidelines. The width of the multifractal singularity spectrum (MSS) was computed for each channel time series and entered nested cross-validated interpretable machine learning models targeting the differential diagnosis of MCS±. Main results. Frontal MSS widths (p < 0.05), as well as the ones deriving from the left centro-temporal network (C3: p = 0.018, T3: p = 0.017; T5: p = 0.003) were found to be significantly higher in the MCS+ cohort. The best performing solution was found to be the K-nearest neighbor model with an aggregated test accuracy of 75.5% (median [IQR] AuROC for 100 executions 0.88 [0.02]). Coherently, the electrodes with highest Shapley values were found to be Fz and Cz, with four out the first five ranked features belonging to the fronto-central network. Significance. MCS+ is a frequent condition associated with a notably better prognosis than the MCS-. High fractality in the left centro-temporal network results coherent with neurological networks involved in the language function, proper of MCS+ patients. Using EEG-based interpretable algorithm to complement differential diagnosis of consciousness may improve rehabilitation pathways and communications with caregivers.
Research on the application potential of solar energy in rural areas from the perspective of common prosperity
Authors: Liu Yixi , Hu Chun , Yu Anping 
Published: July 2023

Abstract
Under the policy background of common prosperity, the Hesheng Town and Yunling Township area of Yongjia County is selected as the research area. The development and application potential of solar energy resources are analyzed, aiming to contribute to wealth and income growth, based on three aspects: resource richness, stability and security, and sunshine time (including effective sunshine time). A comprehensive evaluation of regional microclimate simulation is conducted using the Digital Elevation Model (Abbreviated as DEM). ArcGIS is utilized to generate a potential map for solar energy resource development, which is further divided into five levels based on development potential. The results reveal that the eastern part of Yunling Township, Shiweiyan Community in Hesheng Town, the western and northeastern parts of Donggao Community in Hesheng Town, and the northern part of Xiyuan Community in Hesheng Town exhibit an extremely high abundance of solar energy resources. These areas have the potential for large-scale utilization and development. Moreover, the southwest and southeast regions of the central area of Hesheng Town, along with the northwest area of Xiyuan Community in Hesheng Town, possess a relatively high abundance of solar energy resources. These areas can be developed and utilized on a small-scale and seasonal basis.
Investigation of the dielectric properties and mechanical stability of lignocellulosic biomass based electrical insulation material for high voltage applications
Authors: Rajamanikandan T , Banumathi S , Karthikeyan B 
Published: July 2023

Abstract
The laminated insulation pressboards are used in electrical transformers and they are made from pure wood cellulose fibre. It is used in high-voltage transformers for electrical insulation due to its superior electrical and mechanical properties. Many researchers are searching for alternatives to wood raw materials to reduce deforestation. The banana is one of the lignocellulose-based raw materials; the banana fibre contains 48% cellulose. In this work, different frequencies and temperatures are used to investigate the electrical characteristics of epoxy resin composites reinforced with banana leaf fibres, including their dielectric constant, dissipation factor, and loss factor. At frequencies ranging from 1 to 10 kHz and temperatures ranging from 30 to 150 °C, the dielectric properties of several composites containing banana leaf fibre are studied. The composite’s dielectric properties gradually increased with temperature and decreased with frequency. Correspondingly, the mechanical tests involving a banana leaf fibre epoxy composite are conducted for tensile, bending, impact, and water absorption. The banana leaf fibre has been treated with a 5% sodium hydroxide (NaOH) solution to increase its dielectric and mechanical strength. According to this study, the mechanical strength of biocomposites containing up to 60% treated banana leaf fibre epoxy (TBLFE) composites is greater than that of pure epoxy. A thermogravimetric investigation of composites reinforced with banana fibres has revealed remarkable thermal stability up to 220 °C. In a composite made from chemically treated banana fibre pressboard, there is a good bond between the fibres and the matrix. The FESEM surface analysis shows that treated banana leaf fibril insulation boards have a better texture than composites that have not been treated. The testing results depict that banana leaf fibre is one of the good alternatives to wood cellulose for electrical insulation on pressboard for high-voltage applications.
A BIVALENT TIM-3/PD-1 BISPECIFIC ANTIBODY FOR THE TREATMENT OF PD-1 ANTIBODY RESISTANT OR REFRACTORY SOLID TUMORS
Authors: Luan Yan , Deng Hongyuan , Wang Fengpo , Wang Cuihui , Zhang Zhen , Liu Xun , Abuduwaili Kahaerjiang , Liu Jiajian 
Published: July 2023

Abstract

Background
Immune checkpoint inhibitors (ICI) PD-1/PD-L1 antibody are key drugs for the treatment of cancer. Bispecific antibody is one of the strategies aimed to meet the clinical needs for cancer patients who are resistant to or refractory from ICI treatment. TIM-3, one of the next generation of ICI targets, co-expressed on exhausted T cells with PD-1. It is also expressed by innate immune populations, including NK and DC. Dual blocking PD-1 and TIM-3 not only on T cells but also on DC, NK cells may achieve better clinical benefit for patients who are resistant to or refractory from ICI treatment.

Method
A bivalent TIM-3 and PD-1 bispecific antibody (Bis5) was developed, a series of in vitro and in vivo efficacy, preclinical pharmacokinetic and toxicity studies were conducted. A Phase I, multicenter, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of Bis5 in patients with advanced and/or metastatic solid tumors is ongoing in China.

Results
Bis5 showed affinity of 5-8 nM to both TIM-3 and PD-1, with better cell activity than TIM-3 and PD-1 mAb combination to activated T cell as well as NK and DC, over the other clinical stage reference BsAb. In huPD-1/TIM-3 double knock in mice-CT26 tumor model, Bis5 showed significant tumor inhibition activity and doubled the survival rate, while neither PD-1 mAb, TIM-3 mAb nor PD-1 and TIM-3 antibody combination showed activity. The highest non-severe toxicity dose (HNSTD) was 200mg/kg in monkeys. Nine cohorts (0.001-15 mg/kg) are planned to be enrolled sequentially in the dose escalation part in the Phase I study, as of April 2023, seven cohorts enrollment have completed. No dose limiting toxicity was observed, and the optimal effective dose was not reached. No TRAE higher than grade 2 was observed. The TRAE with ≥10% Incidence was anemia. SD &gt;4 or 2 months were shown in the suboptimal dose levels in NSCLC and CRC (0.3mg/kg, 1mg/kg). The Part 2 dose expansion will further characterize the safety profile and preliminary tumor response in several cohorts including NSCLC, CRC, ESCC etc.

Conclusion
Bis5 showed good preclinical efficacy and safety profile, its clinical performance is expected. Clinical trial information: NCT05357651.
ANTIBODY CO-FORMULATION TOOLBOX AND CAPABILITIES ESTABLISHED IN WUXI BIOLOGICS
Authors: Liu Anyuan , Weng Jingwen , Zhou Fangyuan , Wang Kewei , Wu Hongbing , Wang Shawn , Guo Jeremy 
Published: July 2023

Abstract

Introduction
Co-formulation containing two or more antibodies (mAbs) is deemed to hold distinct merits such as better treatment efficacy, higher efficiency and extended intellectual property right, attracting the demands from both patients and pharmaceutical companies. However, there are only limited numbers of approved drug products, partially due to the technical challenges in formulation development and analytical methods. Herein, we present WuXi Biologics efforts to accelerate the development of co-formulation drug products.

Methodology
We have established an antibody co-formulation specific toolbox with a dedicated team for co-formulation product development addressing the formulation and analytical challenges. Our co-formulation analytical expertise includes size exclusion-high performance liquid chromatography (SE-HPLC), caliper-sodium dodecyl sulfate reduced and non-reduced (Caliper-SDS-R & NR), imaged capillary isoelectric focusing (iCIEF), ion-exchange chromatography (IEC), reverse phase-liquid chromatography (RP-LC), hydrophobic interaction chromatography (HIC), Composition-Gradient Multi-Angle Light Scattering (CG-MALS), differential scanning calorimetry (DSC), enzyme-linked immunosorbent assay (ELISA) based and/or cell based potency, and peptide mapping with mass spectrometry etc.

Results
Remarkably, couple of antibodies co-formulation cases have completed successfully. Take one co-formulation case for instance, specifically, no substantial molecular interactions were observed between the two antibodies according to the results of differential light scattering (DLS) and CG-MALS. Besides, the main peaks of two mAbs were co-eluted in SE-HPLC and Caliper-SDS-NR, respectively. SE-HPLC and Caliper-SDS-NR methods were optimized to evaluate the purity of this co-formulation. As a result, the purity of these two mAbs in this co-formulation was comparable with its individual antibody respectively. Given the isoelectric point of two mAbs in this co-formulation differs by 1.0, iCIEF has been developed to separate the peaks of two mAbs completely. In another case, the isoelectric point of two mAbs differed by just 0.4, CEX has been developed. iCIEF and CEX method were optimized to evaluate the charge variants and determine the concentration ratio of these two mAbs in co-formulation product.
FULLY AI-DRIVEN HUMANOID VHH PHAGE LIBRARY
Authors: Zhao Yangyang , Niu Le , Pan Xuemin , Ye Xingda , Yu Quan , Zhu Yupeng , Chen Yile , Sun Zhiwu , Long Yunfei , Li Yi 
Published: July 2023

Abstract

Background & Significance
VHHs are small and stable fragments that have great potential as therapeutics due to their small size, stability, versatility, and potential for oral administration. The traditional source of VHHs is camelids, but humanization is usually needed for therapeutic development. A human VHH library is highly desirable for the generation of therapeutic VHHs, but natural human VH domains are usually unstable as standalone units. We developed a humanoid VHH library of AI-designed sequences that both resemble camelid VHHs in terms of stability and have such high human content that humanization is no longer needed.

Methods
In this study, we present a fully AI-driven approach for the de novo design of a VHH phage library. Firstly, public camelid data and nearly one million private human sequences were collected. Secondly, one autoregressive AI model was trained on human data and another AI model was trained on the mixed data of humans and camels. Thirdly, the CDR1, CDR2, CDR3 regions of VHH were all generated by the mentioned two AI models. Finally, an ultra large quantity (4E10) of VHH sequences generated by AI were utilized to build the Humanoid VHH phage library.

Results
In order to verify the effectiveness of our method, we randomly synthesized and expressed 26 VHH antibodies from our AI based library. At the same time, 3 human VH molecules reported in previous literature were included as positive controls. First of all, the success rate of expression is 96.1%, which is much higher than 72% of Progen and 66% of ESMdesign. Secondly, the average titer is 59.6mg/L, which is 1.5 times the average value of the positive control group. Thirdly, the hydrophobicity of 80% de novo sequences is comparable to the positive control group. Moreover, the immunogenicity of all AI sequences is less than the average value of the positive control group according to our proprietary algorithms. Finally, the diversity and naturalness of the Humanoid VHH phage library are also excellent.

Conclusions
In conclusion, we have developed a fully AI-driven solution that could stably and massively generate human-like VHH sequences satisfying multiple requirements (including high titer, low hydrophobicity, low immunogenicity and ultra high success rate of expression, high diversity, high naturalness) simultaneously. As VHH is a powerful therapeutic fragment, our approach has the potential to accelerate nanobody and bispecific antibody drug development.
YEAST SURFACE DISPLAY OF FULL-LENGTH IGG FOR ENGINEERING MONOCLONAL AND BISPECIFIC ANTIBODIES
Authors: Jiang Youwei 
Published: July 2023

Abstract
The single-chain variable fragment (scFv) and antigen-binding fragment (Fab) are widely used in yeast surface display for antibody engineering. However, these non-IgG antibody fragments are not always well-expressed or functional. We developed a novel approach to display full-length IgG on yeast surfaces for engineering monoclonal and bispecific antibodies.
The yeast surface display of full-length IgG was generated by transforming glycoengineered yeast P. pastoris with plasmids encoding for anchor protein, heavy chains, and light chains. IgG-displaying yeast cells were incubated with the fluorophore antigen and secondary detection antibody for FACS sorting. The displayed antibody with bound antigen and detection antibody was detected by FACS sorting based on both antibody affinity and display level. FACS sorting could eliminate the deviation caused by expression levels. The yeast surface display of IgG-like bispecific antibodies was also constructed, which exhibited specific binding of two distinct fluorophore antigens in flow-cytometry analysis. Thus, our yeast surface display of full-length IgG can be used to screen light chain libraries to isolate common light chains for bispecific antibodies.
To assess antigen-binding efficiency between different displaying formats, an antibody was respectively displayed as full-length IgG or Fab on the surface of yeast cells for flow-cytometry analysis. Cells displaying full-length IgG showed a higher level of fluorescence than those displaying Fab fragments, indicating that yeast surface display of full-length IgG is superior for high-throughput screening.
To test the specificity of the displayed antibody, we performed a demo experiment in which TNF-binding adalimumab-displaying cells were mixed with trastuzumab-displaying cells at a 1 to 1,000,000 ratio, mimicking the immune library. After three consecutive rounds of sorting, the yeast cells with high fluorescence were plated on a selective medium and the individual antibody clones were sequenced. All ten sequenced clones were confirmed to be adalimumab, demonstrating the maintenance of genotype-phenotype linkage for library screening in yeast surface display of full-length IgG.
A mutation library was also generated from the initial hit and displayed at the surface of yeast cells for the screening of higher affinity maturation antibodies by FACS. A pool of high-affinity binders was plated on a selective medium. Individual clones were analyzed by flow cytometry and sequenced to identify unique antibodies with higher affinity.
In summary, full-length IgG antibodies can be displayed on the yeast cell surface, mimicking their native forms in molecular structure and biophysical properties. The technique combines the high throughput of yeast display with mammalian-cell quality control. This novel approach can be used to engineer monoclonal and bispecific antibodies for high affinity and improved developability profiles.
Do executive functions differentiate Iranian children with attention-deficit/hyperactivity disorder with and without comorbid obesity?
Authors: Parhoon Kamal , Aita Stephen L , Mohammadi Azad , Roth Robert M 
Published: July 2023

Abstract

Objective
To compare multiple dimensions of executive function between children with attention-deficit/hyperactivity disorder (ADHD) with and without comorbid obesity.

Method
Participants were 90 Iranian children (ages 8–13, 50% female) who were equally dispersed across three study groups: typically developing (TD), ADHD with obesity (ADHD+O), and ADHD without obesity (ADHD-O). Study participants were administered a comprehensive battery of Iranian-adapted “cool” executive function tasks including Digit Span from the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V), Victoria Stroop Test (VST), Wisconsin Card Sorting Test (WCST), Tower of London, and dot-probe task (i.e., a task of attentional bias). Parents completed the Children’s Scale for Future Thinking Questionnaire, which assesses future-oriented cognition (e.g., saving, planning, episodic foresight, delay of gratification), aligning more with “hot” executive functions. Groups were compared using multivariate and post-hoc univariate general linear models.

Results
Significant group effects were observed for all executive function variables, broadly with the gradient pattern of TD &gt; ADHD-O &gt; ADHD+O. ADHD+O had poorer performances than ADHD-O for WISC-V Digit Span (d = −0.84), WCST Categories Completed (d = −0.55) and Perseverative Responses (d = 1.15), VST Interference Errors (d = 0.83) and Interference Time (d = 1.38), and Dot-Probe Task (d = 0.84). Relative to the ADHD-O group, ADHD+O had also poorer parent-reported Prospective Memory (d = −0.62), Episodic Foresight (d = −0.63), and Delay of Gratification (d = −0.54).

Conclusions
Children with ADHD-O have poorer executive functioning than those without obesity. We observed stronger effects for “cool” rather than “hot” domains of executive function, though this could be due to the former being performance-based and the latter parent-reported.
The Emerging Role of Injectable Weight Loss Medications in Plastic Surgery: A Systematic Review
Authors: Shridharani Sachin M , Kohan Joshua 
Published: July 2023

Abstract

Obesity is a multifactorial disease that represents a substantial global health concern. As of 2016, the World Health Organization (WHO) estimated that over 650 million adults were obese, and more than 1.9 billion were overweight. Surgical interventions or lifestyle changes are typically suggested to patients who experience comorbidities as a result of their weight; however, more recently, antidiabetic medications have been proposed, specifically sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs). This is the first systematic review to evaluate the safety, efficacy, and future role of SGLT-2 inhibitors and GLP-1RAs for weight loss in the world of aesthetic plastic surgery. Sixteen randomized controlled trials were identified that met the eligibility criteria for this systematic review and comprised data from 10,492 patients. All studies reported a decline in body weight following treatment with SGLT-2 inhibitors or GLP-1RAs, ranging from 1.5 to 5 kg. Although adverse events were reported in a large proportion of patients, primarily gastrointestinal manifestations, the literature reports that these were mild to moderate in severity and tended to subside following treatment adjustment. Future research is warranted to determine the ideal SGLT-2 inhibitor or GLP-1RA for weight loss management, and additional randomized controlled trials (RCTs) are needed to determine the efficacy and tolerability of potential combination therapies with SGLT-2 inhibitors and GLP-1RAs.

Level of Evidence: 3
quickBAM: a parallelized BAM file access API for high-throughput sequence analysis informatics
Authors: Pitman Anders , Huang Xiaomeng , Marth Gabor T , Qiao Yi 
Published: July 2023

Abstract

Motivation
In time-critical clinical settings, such as precision medicine, genomic data needs to be processed as fast as possible to arrive at data-informed treatment decisions in a timely fashion. While sequencing throughput has dramatically increased over the past decade, bioinformatics analysis throughput has not been able to keep up with the pace of computer hardware improvement, and consequently has now turned into the primary bottleneck. Modern computer hardware today is capable of much higher performance than current genomic informatics algorithms can typically utilize, therefore presenting opportunities for significant improvement of performance. Accessing the raw sequencing data from BAM files, e.g. is a necessary and time-consuming step in nearly all sequence analysis tools, however existing programming libraries for BAM access do not take full advantage of the parallel input/output capabilities of storage devices.

Results
In an effort to stimulate the development of a new generation of faster sequence analysis tools, we developed quickBAM, a software library to accelerate sequencing data access by exploiting the parallelism in commodity storage hardware currently widely available. We demonstrate that analysis software ported to quickBAM consistently outperforms their current versions, in some cases finishing an analysis in under 3 min while the original version took 1.5 h, using the same storage solution.

Availability and implementation
Open source and freely available at https://gitlab.com/yiq/quickbam/, we envision that quickBAM will enable a new generation of high-performance informatics tools, either directly boosting their performance if they are currently data-access bottlenecked, or allow data-access to keep up with further optimizations in algorithms and compute techniques.