Monoclonal antibodies are attractive therapeutic agents in a wide range of human disorders that bind specifically to their target through their complementary-determining regions (CDRs). Small proteins with structurally preserved CDRs are promising alternatives to antibodies. In this study, we presented new antibody mimetics against colorectal cancer marker epidermal growth factor receptor (EGFR) created by CDRs grafting technique. Ten potential graft acceptor sites that efficiently immobilise the grafted CDR loops were selected from three small protein scaffolds by computational identification. The three most involved CDR loops in antibody-receptor interactions extracted from panitumumab monoclonal antibody against domain III of EGFR (EGFR DIII) crystal structure were then grafted to the selected scaffolds through the loop randomization technique. The combination of three CDR loops and 10 grafting sites revealed that three of the 36 combinations showed specific binding to EGFR DIII by binding energy calculation. Thus, the present strategy and selected small protein scaffolds are promising in designing new binders against EGFR with high binding energy.

Objective: Learning the critical elements that should be included in a comprehensive measure reflecting the key concepts underlying asthma self-management for adolescents is important to ensure the transfer of optimal care to adolescents. This review identifies and evaluates adolescent self-reported measures for asthma management in experimental and quasi-experimental studies. Data Sources: Eighteen studies were identified using CINAHL, Nursing Allied Health Prevention, Medline, ProQuest, and PubMed databases. Search terms were based on the National Library of Medical subject headings (MeSH terms) and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Study Selections: Studies included were peer-reviewed and published in English between 2010-2022. Experimental and quasi-experimental studies that used asthma measures for children and adolescents between 10 and 19 years old were considered to identify high-quality, validated measures. Results: In total, 18 studies were included, comprised of 14 experimental and four quasi-experimental. This review revealed six major concepts: quality of life, disease control, self-efficacy, knowledge, attitudes, and asthma self-management. The review found an apparent heterogeneity of measures and a deficiency of comprehensive measurements focused on actual ASM behaviors. Conclusion: A comprehensive measure was not uncovered; therefore, the development of a reliable and valid comprehensive asthma measure is necessary to assess adolescents’ asthma self-management abilities and to evaluate the essential components of educational interventions. In terms of assessment and evaluation, research studies and clinical practices would greatly benefit from a standardized measure that encompasses the identified major concepts.

Background: Subcutaneous immunotherapy is an effective and safe treatment for allergic asthma. However, there have been very few studies about comparison of single mite vs double mite subcutaneous immunotherapy. In this study, we aimed to evaluate the difference in clinical efficacy and safety of subcutaneous immunotherapy with dust mite allergen vaccines in children with allergic asthma. Methods: This study is a retrospective and single-center study performed from Jan 2019 to Jun 2022. A total of 124 children who were grouped into single mite preparation group and double mite preparation group. The efficacy scores, changes in pulmonary function and the occurrence of adverse effects were compared between the 2 groups before and after treatment. Results: The efficacy scores were significantly decreased in all children with SCIT after 6 months treatment, and the quality of life significantly improved compared with those before treatment (P< 0.01). After 2 years of treatment, double mite preparation were statistically significant improved in PEF, FEV1, and FVC(P<0.05); single mite preparation were better for CS, VAS improvement(P<0.05); single mite preparation has higher rate of local and systemic adverse reactions(P < 0.05). Conclusion: Both preparations can achieve significant efficacy and safety in children with allergic asthma. The short-term improvement of asthma symptoms was more significant with the double mite preparation, but the single mite preparation was more effective as the treatment course was extended. Single mite preparation was more effective in improving the symptoms of rhinitis. Double mite preparation had a better safety and was better for lung function improvement.

Identifying sex-linked markers in genomic datasets is important, because their analyses can reveal sex-specific biology, and their presence in supposedly neutral autosomal datasets can result in incorrect estimates of genetic diversity, population structure and parentage. But detecting sex-linked loci can be challenging, and available scripts neglect some categories of sex-linked variation. Here, we present new R functions to (1) identify and separate sex-linked loci in ZW and XY sex determination systems and (2) infer the genetic sex of individuals based on these loci. Two additional functions are presented, to (3) remove loci with artefactually high heterozygosity, and (4) produce input files for parentage analysis. We test these functions on genomic data for two sexually-monomorphic bird species, including one with a neo-sex chromosome system, by comparing biological inferences made before and after removing sex-linked loci using our function. We found that standard filters, such as low read depth and call rate, failed to remove up to 28.7% of sex-linked loci. This led to (i) overestimation of population FIS by ≤ 9%, and the number of private alleles by ≤ 8%; (ii) wrongly inferring significant sex-differences in heterozygosity, (iii) obscuring genetic population structure, and (iv) inferring ~11% fewer correct parentages. We discuss how failure to remove sex-linked markers can lead to incorrect biological inferences (e.g., sex-biased dispersal and cryptic population structure) and misleading management recommendations. For reduced-representation datasets with at least 15 known-sex individuals of each sex, our functions offer convenient, easy-to-use resources to avoid this, and to sex the remaining individuals.

The giant river prawn Macrobrachium rosenbergii is an important aquaculture prawn, showing sexual dimorphism in growth, with males growing much faster than females. However, the mechanisms controlling these complex traits are not yet well understood. The nervous system plays an important role in regulating life functions. This study aimed to obtain and characterize the full-length transcriptomes of brain and ganglion in female and male prawns by PacBio RNA sequencing. Based on the result of PacBio sequencing, transcript’s functional annotation, transcript factors, and simple sequence repeat analysis, long non-coding RNAs (LncRNAs) and transposable element predictions were accomplished. Total 159.1-Gb subreads were obtained and average length was 2,175 bp, with 93.2% completeness. After clustering and polishing, 84,627 high quality unigene sequences were produced and annotated by functional databases. 6,367 transcript factors and 6,287 LncRNAs were predicted. Illumina sequencing of brains and ganglia extracted from female and male prawns was carried out. A significant number of differentially expressed genes (DEGs) were found and confirmed by qRT-PCR analysis. Of the related 435 genes in protein processing pathways in the endoplasmic reticula, compared to females, 42 DEGs were detected, and 21/26 DEGs with up-regulated expression in male prawn brain/ganglion. DEGs in this pathway are likely to be regulated by multiple LncRNAs in polypeptide folding and misfolded protein degradation in the different organs and sexes of the prawn. Our study lays a foundation for understanding the growth dimorphism controlled by nervous system, and is a valuable resource for sex-controlled breeding of prawns in the future.

Although plastid genome (plastome) structure is highly conserved across most seed plants, investigations during the past two decades have revealed several disparately related lineages that have experienced substantial rearrangements. Most plastomes have two inverted repeat regions and two single-copy regions with few dispersed repeats. However, the plastomes of some taxa do harbor long repeat sequences (>300 bp). These long repeats make it difficult to assemble complete plastomes using short read data, leading to misassemblies and consensus sequences that have spurious rearrangements. Long read sequencing can potentially overcome these challenges. However, there is no consensus as to the most effective method for accurately assembling plastomes using long read data. Here, we generated a pipeline, plastid Genome Assembly Using Long-read data (ptGAUL) to address the problem of assembling of plastomes using long read data from Oxford Nanopore Technologies (ONT) or Pacific Biosciences (Pacbio) platforms. We demonstrated the efficacy of the ptGAUL pipeline using 16 published long read datasets. We showed that ptGAUL produces accurate and unbiased assemblies. Additionally, we applied ptGAUL to assemble four Juncus (Juncaceae) plastomes using ONT long reads. Our results revealed many long repeats and rearrangements in Juncus plastomes compared with basal lineages of Poales.

Objective: We compared prenatal care utilization, preterm birth, and low birth weight neonates among women 35 years and older compared to women 20-34 years old in Mexico, 2008-2019. Methods: We used birth certificate data and conducted a historical cohort study of all singleton live births in Mexico from 2008-2019. Study outcomes were inadequate prenatal care (timing of initiation of care and number of visits), preterm birth, and low birth weight. We compared outcomes among women 35-39, 40-44, and 45-49 with births to women 20-34. We used logistic regression to account for individual and contextual confounders. Results: We included a total of N=19,526,922 births; 11.9% (n=2,325,725) were to women 35 and older. Compared to women aged 20 to 34, the oldest (45-49 years old) were more likely to reside in poorer communities, have less education, and be uninsured. The odds of inadequate prenatal care (aOR 1.12 95% CI 1.09-1.15 p<0.01), preterm birth (aOR 2.05 95% CI 1.97-2.13 p<0.01), and low birth weight (2.03 95% CI 1.95-2.12 p<0.01) were highest for women 45-49, compared to women 20-34. Patterns were similar among women 35-39 and 40-44 with the exception of lower odds of inadequate prenatal care (aOR 0.77 95% CI 0.76-0.77 p<0.01) for 35-39 compared to women 20-34. Conclusion: Women who deliver at 35 years old and over are a heterogeneous group in Mexico. Being 35 years old and older is associated with increases in preterm birth and low birth weight neonates. Women who give birth between 45-49 may be especially vulnerable.

The present work proposes a coordinated power distribution control of wind-energy fed self-excited induction generator (SEIG) based low-voltage direct current (LVDC) autonomous microgrid. The battery and supercapacitor (SC) hybrid energy storage system (HESS) is interfaced with the common 48 V LVDC bus using a parallel-active configuration through two bidirectional converters. The prime idea of hybridization is to limit the instantaneous peak current demand and also to alleviate the charge/discharge stress during transients, thus reducing the size of the battery. The developed autonomous LVDC system with the supervisory power distribution control scheme (PDCS) is experimentally validated for different operating modes. The comparative experimental result analysis substantiates the efficacy of the proposed PDCS along with seamless transition between various modes.

The unceasing efforts to design an optimal controller for automatic generation control (AGC) in power systems motivate the design of a novel Two-Degree-of-Freedom-Combined Fractional Order PID (2-DOF-Combined FOPID) controller. Two-area interconnected power systems comprised of reheated thermal and hydro units with boiler dynamics, generator rate constraints and dead zone non-linearity in each area are tested using the designed controller. The performance of the proposed controller is studied with the conventional PID controller, the classical Two-Degree-of-Freedom PID (2-DOF-PID) controller, and the Two Degree-of-Freedom Fractional Order PID controller (2DOF FOPID). The elemental intension of designing supplementary controllers is to diminish the area of control error (ACE). The Crow search algorithm (CSA) is chosen to determine the optimal values of controller gain parameters in order to curtail the figure of demerit. The dynamic behavior of the system is investigated pertaining to a 0.01 p.u. load disturbance in area 1. The performance of the designed controller is explored using wind integration and an CSA optimized small hydro power plant. Investigations reveal that the transient response is superior using the 2-DOF-Combined FOPID concerning the stability indices viz. overshoot (Osh), undershoot (Ush), and settling time response of the power system.

Purpose: To evaluate the feasibility of a drug utilization study (DUS) investigating real-world use of Saxenda ® and Victoza ® in Europe. Economic and time constraints may incite researchers to avoid formalized pilot studies. Here, we report results of a pilot study which rectified the ensuing DUS protocol, thus ascertaining fit-for-purpose data availability and quality, and supporting regulatory decision making. Methods: A retrospective multicenter medical chart review in Germany and Italy, 6 months after Saxenda ® (liraglutide 3.0 mg, a once-daily human glucagon-like peptide-1 analog for weight management) launch, ahead of a full DUS. Collected data included: site characteristics, patient demographics, medical history, drug utilization (e.g., brand, dose, indication, weight-related comorbidities). Target study population: 100 initiators (25 Saxenda ® and 25 Victoza ® initiators in both Germany and Italy). Informed consent was obtained before medical-chart data extraction. Results: Overall, 218 sites were contacted. Fifteen sites (nine in Italy; six in Germany) enrolled initiators. There were 39 Saxenda ® initiators (33 in Italy; six in Germany) and 52 Victoza ® initiators (31 in Italy; 21 in Germany). Data were available for all Saxenda ® initiators and all Victoza ® initiators in Italy, and for 12 of 21 Victoza ® initiators in Germany. In nine of the 12 initiators, only target dose was recorded, with no current dose provided. Conclusions: The pilot study indicated a poor enrollment feasibility of Saxenda ® initiators in Germany and an unfit-for-purpose dose-related data quality. Based on these findings, refinements were implemented to the ensuing DUS protocol, thus ensuring robust real-world data to support regulatory decision making.

A document by George Crossley. Click on the document to view its contents.

Adaptive phenotypes are shaped by a combination of genetic and environmental forces, and while the literature is rich with studies focusing on either genetics or environment contributions, those that consider both are rare. Here we utilize the cichlid oral jaw apparatus to fill this knowledge-gap. First, we employed RNA-seq in bony and ligamentous tissues important for jaw opening to identify differentially expressed genes between species and across foraging environments. Our foraging treatments were designed to force animals to employ either suction or biting/scraping, which broadly mimic pelagic or benthic modes of feeding. We found a large number of differentially expressed genes between species, and while we identified relatively few differences between environments, species differences were far more pronounced when reared in the pelagic versus benthic environment. Further, these data carried the signature of genetic assimilation, and implicated cell cycle regulation in shaping the jaw across species and environments. Next, we repeated the foraging experiment and performed ATAC-seq procedures on nuclei harvested from the same tissues. Cross-referencing results from both analyses revealed subsets of genes that were both differentially expressed and differentially accessible in either the pelagic (n=15) or the benthic environment (n=11), as well as loci where differences were robust to foraging environment (n=13). All in all, these data provide novel insights into the epigenetic, genetic, and cellular bases of species- and environment-specific bone shapes, as well as the evolution of phenotypic plasticity in this iconic model system.

Key PointsPrevious studies have linked recurrent or persistent BPPV to age, anxiety or/and depression and medical comorbidityFactors such as the socioeconomical status have not been assessed.In our retrospective powered cohort we showed that there is a positive correlation between recurrent or persistent BPPV and ageWe found no correlation with the presence of underlying anxiety/depression and recurrent or persistent BPPV and age.While one would have expected that the socioeconomical and educational status would have had an impact on recurrent/persistent BPPV, using the Scottish Index of Multiple Deprivation, we did not identify such link.

Recently, enormous culture profiles and datasets from biomanufacturing processes to produce recombinant therapeutic proteins (RTP) such as monoclonal antibodies (mAbs) could be generated by virtue of the advancement in process analytical techniques and artificial intelligence (AI). Thus, now it is highly necessary to develop AI-based data-driven models (DDMs) and exploit them accordingly in order to further enhance operational efficiency and accelerate reliable product supply. Since bioprocess is a complex and dynamic system, DDMs are practical and particularly useful to describe the intrinsic relationship among biological and process parameters and cell culture conditions by capturing inherent patterns and to produce high-quality RTP under consistent operations as well as to decrease cost and time by predicting incipient or abrupt faults during the cell cultures. In this work, we provide the practical guideline for choosing the best DDM on given mAb-producing Chinese hamster ovary (CHO) cell culture data sets, enabling us to forecast culture performance such as VCD, and mAb titer as well as glucose, lactate and ammonia concentrations in real time manner. Via the case study with 32 fed-batch data sets of CHO cell cultures, we suggested best combination of model elements including AI algorithms and multi-step ahead forecasting strategies, for good prediction in terms of the computational load as well as the model accuracy and reliability, which is applicable to implementation of interactive data-driven model within bioprocess digital twins. We believe this systematic study can help bioprocess engineers to start developing predictive DDMs with their own data and learn how their cell cultures behave in near future, thereby making proactive decision possible.

Do we need more studies?Max M. van Noesel, MD, PhD, MSc1,2*Department of Solid Tumors, Princess Máxima Center for Pediatric Oncology, Utrecht, the NetherlandsDivision Imaging & Oncology, University Medical Center Utrecht, Utrecht, the Netherlands*Correspondance to: M.M van Noesel, MD, PhD, MSc, Department of Solid Tumors, Princess Máxima Center, Heidelberglaan 25, 3584 CS Utrechtc, Telephone: +31-6 5000 6581, Email: m.m.vannoesel@prinsesmaximacentrum.nl Text word count: 968 Abstract: - Short running title: Highlight PBC-22-1061 Tables: - Figures: - Abbreviations: -

CZTS material is seen as a very potential replacement for toxic CIGS, and CIS material as a thin-film solar cell absorber layer. Because of its extraordinary light absorption capacity and generation of electron-hole pairs, CZTS has been implemented as a thin-film solar cell. Research is going on over the last decade on increasing the efficiency of the CZTS solar cell. Different structural and material properties have been experimentally altered to achieve higher efficiency. But even after several attempts the single junction CZTS solar cell has not achieved an efficiency of more than 13%. In this article, a detailed review is done of the developments that have taken place and the future scope of the CZTS thin-film solar cell (TFSC). From its evolution, materials preparation, fabrication process, TFSC design, and defects in CZTS to its implementation as a solar cell are discussed in this manuscript.

A document by M. Teresa Higuera-Toledano. Click on the document to view its contents.

System development is frequent nowadays, and maintaining an ideal degree of security and trustworthiness remains challenging. However, research shows that software developers usually lack the knowledge and skills required to design safe software systems. Such expertise ensures that, in addition to adhering to the safe software development lifecycle, the relevant security parameters are fulfilled. Engineers and developers are always concerned with monitoring, tracking, and implementing critical product requirements. However, as technology evolves, digitization brings several opportunities for more sustainable system engineering and administration. With the aid of digital twins, a dynamic digital representation of a physical system is updated and maintained to build a more detailed virtual replica of the system. For better administration and faster processing, we believe digital twins to be a superior approach to examine the enhanced output and specified structure of safe software systems and their implementation. This article discusses a methodology for designing and monitoring safe software with the use of digital twins. It also describes how it works and how it may be used to make software systems more secure.

Objective To determine the clinical characteristics and treatment outcomes of women with recurrent uterine leiomyosarcoma (uLMS). Methods We conducted a retrospective cohort study to evaluate the clinical characteristics and survival of women with recurrent uLMS and identify prognostic factors. Results Overall, 71 patients with first recurrence of uLMS were included in our study. 19 patients (26.8%) received systematic therapy and 52 patients (73.2%) received secondary cytoreductive surgery (SCS). In SCS subgroup (n=52), a complete resection with no residual disease was reported in 47 patients (90.4%). 38.5% (20/52) patients received non-genital organ surgeries. 10 (19.2%) patients had received thoracic surgery because of lung-only recurrences. Bowel, bladder surgery was performed in 8 (15.4%), 3 (5.8%) patients, respectively. 1 (1.9%) patient had received liver surgery. The median follow-up duration was 38.7 months (range: 2.7-317.6 months). 41 (57.7%) patients died during follow-up. 5-year OS for the entire cohort was 52.9%. Patients experienced first recurrence after initial diagnoses within 12 months (n=24) had a worse 5-year OS than those after 12 months (n=47) (17.0% vs 69.1%, P<0.001). 5-year OS for the SCS and non-SCS subgroup was 62.0% and 28.0%, respectively (P<0.001). Multivariate analysis showed time to fist recurrence within 12 months (HR=4.60, 95% CI: 1.49-14.4, P = 0.008) was an independent predictor of decreased 5-year OS in SCS subgroup. Conclusion SCS is an important treatment choice for recurrent uLMS and seems to have benefited patients. Time to fist recurrence within 12 months is an independent predictor of decreased 5-year OS in SCS subgroup.

3D segmentation has been a hot spot in numerical geometry processing. But the accuracy of the segmentation methods can be easily affected by the types of models because their sensitivity to different models is uneven. To address this problem, we propose a semi-automatic 3D mesh segmentation algorithm based on harmonic field. Firstly, our algorithm utilizes the strokes of users as constraints on the harmonic field of the mesh surface. Secondly, a smooth harmonic field based on Laplacian operator and Poisson equation is introduced. Through the generated harmonic field, the correct weights are selected to further fit the geometric characteristics of the grid. Afterwards, we find a set of most suitable isolines on the harmonic field as the segmentation path. Finally, a mesh density enhancement method is designed, which optimizes sub-graphs after segmentation. Experimental results demonstrate that the effectiveness of our proposed algorithm. Moreover, the semi-automatic 3D mesh segmentation algorithm can better understand the intention of users.

The design and fabrication of flexible, porous, conductive electrodes with customizable functions become the prime challenge in the development of new-generation wearable electronics, especially for rechargeable batteries. Here, NiCo bi-alloy particulate catalysts loaded self-supporting carbon foam framework (NiCo@SCF) as a flexible electrode has been fabricated through one facile adsorption-pyrolysis method using a commercial melamine foam. Compared with the electrode with Pt/C and Ir/C benchmark catalysts, the NiCo@SCF electrode exhibited superior bifunctional electrocatalytic performance in alkaline media with a half-wave potential of 0.906V for oxygen reduction reaction, an overpotential of 286 mV at j=10 mA cm−2 for oxygen evolution reaction, and stable bifunctional performance with a small degradation after 20,000 voltammetric cycles. The as-assembled aqueous zinc-air battery (ZAB) with NiCo@SCF as a self-supporting air cathode demonstrated a high peak power density of 178.6 mW cm-2 at a current density of 10 mA cm−2 and a stable voltage gap of 0.94V a 540 h charge-discharge operation. Remarkably, the as-assembled flexible solid-state ZAB with self-supporting NiCo@SCF as air cathode presented an engaging peak power density of 80.1 mW cm-2 and excellent durability of 95 h undisrupted operation, showing promise for the design of wearable ZAB.

Rationale: Patients with congenital central hypoventilation syndrome (CCHS) require long-term ventilation to ensure gas exchange and to prevent deleterious consequences for neurocognitive development. Two ventilation modes may be used for these patients depending on their tolerance, one invasive by tracheostomy and the other noninvasive (NIV). For patients who have undergone a tracheostomy, transition to NIV is possible when they meet predefined criteria. Identifying the conditions favorable for weaning from a tracheostomy it critical for the success of the process. Objective: The aim of the study was to share our experience of decannulation in a reference center; we hereby describe the modality of ventilation and its effect on nocturnal gas exchange before and after tracheostomy removal. Methods: Retrospective observational study at Robert Debré Hospital over the past 10 years. The modalities of decannulation and transcutaneous carbon dioxide recordings or polysomnographies before and after decannulation were collected. Results: Sixteen patients underwent decannulation following a specific procedure for transition from invasive to NIV. All decannulations were successful. The median age at decannulation was 12.6 [9.7; 15.0] years. Nocturnal gas exchange was not significantly different before and after decannulation, while expiratory positive airway pressure and inspiratory time increased significantly. An oronasal interface was chosen in two out of three patients. The mean duration of hospital stay for decannulation was 4.0 [3.0; 6.0] days. Conclusion: Our study underlines that decannulation and transition to NIV are achievable in CCHS children using a well-defined procedure. Patient preparation is crucial to the success of the process.

This paper presents an impedance differential protection scheme for a double-circuit transmission line. Current and voltage measurements at both line ends enable the formulation of a differential impedance that serves as an effective protection standard for transmission lines. The proposed method takes into consideration the effects of the line's shunt capacitance since it is based on the distributed parameter line model. The proposed protection system is able to detect the faults and also has the ability to determine the fault location. In addition, the relay offers dependability, and selectivity for differentiating between internal and external faults, thereby stays steady against external faults. The proposed method has been tested with varying fault resistances and under various fault conditions. The effectiveness, security, and dependability of the method are verified by the simulation results.

Choledochal cyst is a rare congenital dilatation of the common bile duct usually symptomatic within the first year of life with rare presentation in adulthood. Herein, we present a 17-year-old female with type 1A choledochal cyst who was managed by surgical excision, hepatico-jejunostomy and jejunojejunostomy who recovered uneventfully.