bluuebunny/crossref_metadata_2025 huggingface dataset:
Chondrocyte autophagy mechanism and therapeutic prospects in osteoarthritis
Authors: Li Lan , Li Jie , Li Jian-Jiang , Zhou Huan , Zhu Xing-Wang , Zhang Ping-Heng , Huang Bo , Zhao Wen-Ting , Zhao Xiao-Feng , Chen En-Sheng
Published: October 2024

Osteoarthritis (OA) is the most common type of arthritis characterized by progressive cartilage degradation, with its pathogenesis closely related to chondrocyte autophagy. Chondrocytes are the only cells in articular cartilage, and the function of chondrocytes plays a vital role in maintaining articular cartilage homeostasis. Autophagy, an intracellular degradation system that regulates energy metabolism in cells, plays an incredibly important role in OA. During the early stages of OA, autophagy is enhanced in chondrocytes, acting as an adaptive mechanism to protect them from various environmental changes. However, with the progress of OA, chondrocyte autophagy gradually decreases, leading to the accumulation of damaged organelles and macromolecules within the cell, prompting chondrocyte apoptosis. Numerous studies have shown that cartilage degradation is influenced by the senescence and apoptosis of chondrocytes, which are associated with reduced autophagy. The relationship between autophagy, senescence, and apoptosis is complex. While autophagy is generally believed to inhibit cellular senescence and apoptosis to promote cell survival, recent studies have shown that some proteins are degraded by selective autophagy, leading to the secretion of the senescence-associated secretory phenotype (SASP) or increased SA-β-Gal activity in senescent cells within the damaged region of human OA cartilage. Autophagy activation may lead to different outcomes depending on the timing, duration, or type of its activation. Thus, our study explored the complex relationship between chondrocyte autophagy and OA, as well as the related regulatory molecules and signaling pathways, providing new insights for the future development of safe and effective drugs targeting chondrocyte autophagy to improve OA.
Changes functional prediction of ear canal flora in chronic bacterial otitis externa
Authors: Duan Tingting , Li Zhiqun , Han Xiaoyong , Hong Qichao , Yang Yunan , Yan Jinren , Xing Chengliang
Published: October 2024

Objective

To investigate ear canal microflora’s structure, composition and function in patients with chronic bacterial otitis externa.

Methods

A case-control study design method was used to collect the ear canal secretions from 14 patients with chronic bacterial external otitis (CB group) and 14 healthy controls (H group) treated in the Department of Otolaryngology and Head and Neck Surgery in the First Affiliated Hospital of Hainan Medical University. 16S rRNA high-throughput sequencing technology was used to sequence the ear canal microflora’s V3 ~ V4 region gene amplification products in the participating population. The α diversity of ear canal microflora in 2 groups was analyzed. Based on the weighted Unifrac distance, principal coordinate analysis was performed to compare the β diversity of ear tract microflora between the two groups. The differences in ear microflora at phylum and genus levels were analyzed. PICRUSt2 function prediction and BugBase phenotype prediction were also performed.

Results

α diversity analysis showed that the diversity and richness of auricular microflora in the CB group were significantly lower than those in the H group. β diversity analysis showed that there were some differences between the two groups. At the phylum level, the relative abundance of Bdellovibrionota, Campylobacterota, and WPS-2 in the microbiota of patients in the CB group was significantly lower than that in the H group, and the differences were statistically significant. At the genus level, the relative abundance of Pseudomonas, Acinetobacter, Pelomonas, Sphingomonas, Bradyrhizobium, Brevundimonas, Enhydrobacter, Actinomyces, Paracoccus and Chryseobacterium in the ear canal of Group H is significantly higher than that of Group CB. Functional prediction of PICRUSt2 suggests that amino acid biosynthesis and bacterial microbiota may be related. In BugBase phenotypic prediction, the contribution of aerobic phenotype in group CB was significantly lower than that in group H.

Conclusion

The diversity and abundance of the ear canal flora of patients with chronic bacterial otitis externa were significantly lower than those of the healthy population, and their bacterial colony structure was significantly altered. Dysbiosis of the ear canal flora may be an important cause of chronic bacterial otitis externa.
Target antigen screening and development of a multi-component subunit vaccine against Mycoplasma synoviae in chickens
Authors: Sun Xiaomei , Deng Mingyong , Cheng Chuxing , Zhao Ya , Liu Zuqing , Yang Yu , Xu Qiaoxia , Yao Rong , Hu Min , Jin Meilin , Kang Chao
Published: October 2024

Introduction

Mycoplasma synoviae (MS) is a globally important avian pathogen causing infectious synovitis and respiratory diseases in poultry, leading to significant economic losses. Despite advances in vaccine development, a commercially viable subunit vaccine against MS remains elusive.

Methods

We sequenced whole genomes of six clinical MS strains isolated from different Chinese provinces. Common genes were analyzed using Biopython software, identifying those with high copy numbers in virulent strains and shared among all strains. Vaxign2 and IEDB Antibody Epitope Prediction were used to analyze protein properties. We assessed immune protective effects of candidate proteins and developed a multivalent subunit vaccine.

Results

Ten candidate vaccine proteins were initially selected. A multivalent subunit vaccine composed of MSPB, Ppht, Cfba, and EF-G displayed the best protective effect. The optimal immunization dosage was 20μg, with each protein accounting for 25%. The immune production period was determined to be 28 days post-first immunization, lasting 180 days. The immune protection rate against highly virulent strains reached 90%∼100%.

Discussion

This study provides a new approach for screening vaccine antigens and develops an effective candidate vaccine for MS prevention. The multivalent subunit vaccine shows promising results in protecting against MS infections, potentially offering a solution to reduce economic losses in the poultry industry.
The correlation between stable angina and inflammatory factors and blood lipids: a case-control study
Authors: Xiang Lei
Published: October 2024

Objective

In this study, we aimed to compare the levels of inflammatory markers (C-reactive protein, CRP; procalcitonin, PCT) and blood lipids (total cholesterol, TC; triglyceride, TG; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C) between patients with stable angina and control group, and to explore the correlation between these parameters and the severity and prognosis of stable angina.

Methods

We retrospectively selected 113 patients with stable angina and 128 control group from the medical record system, and compared their inflammatory factors and blood lipids. We also assessed the severity of angina using the Canadian Cardiovascular Society (CCS) classification and followed up the patients for 1 year to record any cardiovascular events.

Results

We found that patients with stable angina had significantly higher levels of CRP, TC, TG, and LDL-C, and lower levels of HDL-C than control group. Moreover, CRP, TC, TG, and LDL-C were positively correlated with the severity of angina, while HDL-C was negatively correlated. During the follow-up period, 37 patients with stable angina experienced cardiovascular events, and they had higher levels of CRP, TC, TG, and LDL-C, and lower levels of HDL-C than those who did not.

Conclusion

Our study suggests that inflammation and dyslipidemia are closely related to stable angina, and that inflammatory factors and blood lipids can be used as indicators of the severity and prognosis of stable angina.
Influence of CyGNSS L2 wind data on tropical cyclone analysis and forecasts in the coupled HAFS/HYCOM system
Authors: Annane Bachir , Gramer Lewis J.
Published: October 2024

This study examines the influence of NASA Cyclone Global Navigation Satellite System (CyGNSS) Level 2-derived 10 m (near-surface) wind speed over the ocean on analyses and forecasts within the NOAA operational Hurricane Analysis and Forecast System (HAFS). HAFS is coupled with a regional configuration of the HYCOM ocean model. The primary advantages of data from the CyGNSS constellation of satellites include higher revisit frequency compared to polar-orbiting satellites, and the availability of reliable wind observations over the ocean surface during convective precipitation. CyGNSS data are available early in the life cycle of tropical cyclones (TCs) when aerial reconnaissance observations are not available. We focus on TCs whose forecasts were initialized when the TC was a depression or tropical storm. In the present study, we find first, that assimilation of CyGNSS near-surface winds improves storm track, intensity, and structure statistics in the analysis and early in the forecast, for many cases. Second, we find that assimilation of CyGNSS observations provides additional insights into the evolution of air-sea interaction in intensifying TCs: In effect, the ocean responds in the coupled model to modifications in the initial 10 m wind field, thereby impacting forecasts of intensity, storm structure, and sea surface height, as demonstrated by two case studies. We also discuss some forecasts where assimilating CYGNSS appears to degrade performance for either intensity or structure.
A nonlinear inversion method for Young’s modulus and shear modulus based on the exact Zoeppritz equations
Authors: Cheng Yao , Song Sha , Li Dan
Published: October 2024

Introduction

Young’s modulus and shear modulus are essential mechanical parameters for evaluating subsurface rocks, playing a pivotal role in the exploration and development of unconventional resources. Young’s modulus indicates the brittleness of the reservoir, while shear modulus determines the ease of fracturing rock layers.

Methods

Traditional methods estimate these moduli through indirect calculations and approximate expressions, which are prone to cumulative errors and rely on multiple assumptions, reducing inversion accuracy. This paper presents a direct inversion method for acquiring of Young’s modulus and shear modulus using the exact Zoeppritz equations, integrated within a Bayesian framework for pre-stack inversion. The quantum particle swarm optimization (QPSO) algorithm is introduced to achieve a nonlinear solution to the objective function.

Results

Tests on synthetic and actual field data demonstrate the feasibility and effectiveness of the proposed method, yielding more accurate inversion results compared to traditional methods.

Discussion

These findings provide valuable insights for predicting reservoir brittleness and characterizing reservoirs in unconventional shale gas exploration and development.
A preliminary examination of teachers’ and parents’ perspective on sexually inclusive primary education: The role of homophobic prejudice and moral disengagement
Authors: Touloupis Thanos , Pnevmatikos Dimitrios
Published: October 2024

Sexually inclusive primary education, namely a school environment that uses inclusive practices toward sexual minorities contributes to students’ psychological and learning adaptation. Therefore, it is essential primary school stakeholders’ perspective on sexually inclusive education to be explored, since this could facilitate the effective implementation of related prevention/awareness programs targeted at students. Nevertheless, teachers’ and parents’ related perspective, as main school stakeholders, as well as the predictive value of their homophobic prejudice and moral disengagement remain an under-investigated research field. The present study examined comparatively teachers’ and parents’ perspective on sexually inclusive primary education. Furthermore, the predictive role of homophobic prejudice and moral disengagement was investigated for each subgroup. Overall, 249 primary school teachers (78% women) of the fifth and sixth grades from randomly selected Greek public schools and 268 parents (81% mothers) of children who attended the above grades of the participating schools completed an online self-reported questionnaire on the variables involved. In general, participants expressed a relatively conservative perspective on sexually inclusive primary education, with teachers’ perspective being less inclusive than that of the parents. Teachers’ related perspective was predicted negatively mainly by homophobic prejudice and secondarily by moral disengagement. Parents’ corresponding perspective was predicted negatively only by moral disengagement. Despite the differentiated perspective between the two subgroups, the findings imply that both teachers and parents need to attend prevention/awareness actions regarding students’ sexual diversity and their school inclusion. Within these actions, differentiated experiential activities could be implemented for teachers and parents to combat homophobic prejudice and/or moral disengagement.
The impact of a metacognition-based course on school students’ metacognitive skills and biology comprehension
Authors: Sadykova Ainur , Iskakova Marzhan , Ismailova Gulnara , Ishmukhametova Albina , Sovetova Anar , Mukasheva Kuralay
Published: October 2024

The fast-paced and intricate nature of the current society, coupled with the ongoing changes in educational requirements, calls for the cultivation of higher-order thinking skills. To that end, adopting metacognitive strategies could be instrumental. This paper aimed to evaluate the effects of a 10-week-long metacognition-based biology course on school students’ metacognition and biology comprehension. Employing a mixed-methods quasi-experimental design, the study involved 120 eighth-graders from two public schools. One group was exposed to metacognitive questioning, while the other one continued with regular classroom activities. The results showed that participants who received metacognition-guided instruction achieved higher scores on the biology test and reported improved metacognition as compared to those who followed the standard curriculum. These outcomes were consistent across genders and regardless of whether a student reported a deep or surface learning approach. Qualitative analysis extracted themes of collaboration and understanding among the students. They appreciated the specificity of tasks, which deepened their comprehension, and valued collaborative learning facilitated by metacognitive prompts. These prompts not only enhanced their understanding but also contributed to fostering a positive classroom environment. This research underscores the effectiveness of metacognitive support in enhancing biology education. It advocates for the integration of metacognitive strategies into classroom practices, emphasizing the positive impact they can have on students’ learning experiences and outcomes.
Employing structural equation modeling to discern teachers’ perspectives and their embrace of the Metaverse within the classroom setting
Authors: Mendonça Yuri V. S. , Vinueza-Naranjo Paola G. , Pinto Diego Costa
Published: October 2024

The rise of smart learning environments and the transformative potential of the Metaverse are increasingly evident across various sectors, particularly in education. While substantial attention has been directed toward student engagement within the Metaverse, the evolution of teaching methodologies enabled by this technology remains under-examined. This study investigates the influence of teachers’ prior experience with technology on their willingness to adopt the Metaverse in diverse educational contexts. Utilizing a sample of 311 educators from the Brazilian Amazon, partial least squares structural equation modeling (PLS-SEM) was employed to validate the theoretical model. The findings emphasize the significant relationship between previous technological experiences, the mediating role of social influence in adoption, and performance expectations. Furthermore, the results underscore the pivotal role of technological engagement in shaping educators’ perceptions and their readiness to adopt emerging innovations, such as the Metaverse.
Causal associations between the insulin-like growth factor family and sarcopenia: a bidirectional Mendelian randomization study
Authors: Liu Jili , Chen Meng , Xia Xin , Wang Zhaolin , Wang Yanqin , Xi Ling
Published: October 2024

Objective

Insulin-like growth factor (IGF) is closely associated with sarcopenia, yet the causal relationship of this association remains unclear. This study aims to explore the potential causal relationship between members of the IGF family and sarcopenia from a genetic perspective through bidirectional Mendelian randomization (MR) analysis using two-sample datasets.

Methods

Five genetically predicted factors of the IGF family (IGF-1, IGF-1R, IGF-2R, IGFBP-3, IGFBP-7) as one sample, while four relevant features of sarcopenia (low hand grip strength, appendicular lean mass, whole body fat-free mass, and walking pace) as another sample, in conducting a two-sample MR analysis.

Results

The forward MR results of the relationship between IGF and sarcopenia showed that elevated levels of IGF-1 reduced the risk of low hand grip strength (OR = 0.936, 95% CI=0.892-0.983, P = 0.008) and increased appendicular lean mass of the extremities and whole body fat-free mass (OR = 1.125, 95% CI=1.070-1.182,P = 0.000; OR =1.076, 95% CI=1.047-1.106, P=0.000), reduced the risk of sarcopenia. Elevated IGF-1R also favored an increase in whole body fat-free mass (OR=1.023, 95% CI=1.008-1.038, P =0.002), and the appendicular lean mass trait was more pronounced with elevated IGFBP-3 and IGFBP-7 (OR=1.034, 95% CI=1.024-1.044, P =0.000; OR=1.020, 95% CI=1.010-1.030, P=0.000). Inverse MR results of the effect of sarcopenia on IGF showed that decreased hand grip strength may elevate IGF-1 levels (OR=1.243, 95% CI=1.026-1.505,P =0.027), whereas improvements in appendicular lean mass, whole body fat-free mass traits, and increased walking pace decreased IGF-1 levels (OR=0.902, 95% CI: 0.877-0.927, P = 0.000; OR=0.903, 95% CI=0.859-0.949,P = 0.000; OR=0.209, 95% CI=0.051-0.862,P = 0.045). Also decreased hand grip strength may elevate IGF-1R levels (OR=1.454, 95% CI=1.108-1.909, P =0.007), and appendicular lean mass stimulated high expression of IGFBP-1 (OR=1.314, 95% CI=1.003-1.722, P =0.047). Heterogeneity and pleiotropy were not detected in all results, and the results were stable and reliable.

Conclusion

There is a bi-directional causal association between IGF family members and the risk of sarcopenia, which provides a more adequate basis for early biological monitoring of sarcopenia and may provide new targets for early intervention and treatment of sarcopenia.
Research on leakage characteristics of working clearances of hydrogen circulation pump
Authors: Zhai Huanle , Li Wei , Chu Xiaomeng , Mu Honggang , Shen Chungen
Published: October 2024

The volumetric efficiency of the hydrogen circulation pump (HCP) is mainly affected by the amount of leakage in working clearances. Studying the leakage characteristics of working clearances is of great significance for optimizing the performance of the HCP. Therefore, this paper developed a three-blade elliptical conjugate rotor HCP, and compared the results of experiments and simulations for different working conditions. On this basis, the flow rate, pressure, and internal flow field changes of radial clearance models and axial clearance models with four different scales of 0.1mm, 0.14mm, 0.18mm, and 0.22 mm were studied. The results indicate that: under four different pressure ratios and rotational speeds, the simulation results using the overlapping grid method showed a maximum difference of 4.17% compared to the experimental results, verifying the reliability of the simulation calculation method; the average flow rate of the HCP is linearly inversely proportional to both the radial clearance and the axial clearance, with a decrease rate of 11.6 Nm3/h and 5.8 Nm3/h as the clearance size increases by 0.04 mm; the radial clearance leakage of the same size is higher than the axial clearance, the leakage value in the radial clearance between the rotors is higher than that between the rotor and the pump casing, and the internal leakage of axial clearance is not evenly distributed, with higher leakage value in the middle area than that in the left and right areas.
Biodegradation of insecticides: oligonucleotide insecticides and double-stranded RNA biocontrols paving the way for eco-innovation
Authors: Oberemok Vol V. , Laikova Kateryna V. , Andreeva Oksana A. , Gal’chinsky Nikit V.
Published: October 2024

Each new class of insecticides that emerged during the development of plant protection gradually found the most suitable group of insect pests for application. At the same time, for each individual insecticide, a balance was sought between its effectiveness, on the one hand, and its safety for non-target organisms and the ecosystem as a whole, on the other hand. Neonicotinoids, diamides and pyrethroids, as effective control agents, dominate the insecticide market, but do not have outstanding performance in selectivity and biodegradation. The biodegradation of insecticides is one of the most important indicators, representing what will be said about the hidden costs for the resulting harvest paid by the environment and human health. Oligonucleotide insecticides (contact unmodified antisense DNA (CUAD) biotechnology, or ‘genetic zipper’ method) and RNA biocontrols (double-stranded RNA technology) as natural polymers and the next-generation classes of insecticides possess unique characteristics in fast biodegradation and high selectivity in action. While current chemical insecticides require days, months and even years for biodegradation by bacteria and fungi, oligonucleotide insecticides and RNA biocontrols are substantially biodegraded within hours in the presence of nucleases. Nucleic acid-based insecticides have the potential to complement the existing insecticide market and set an eco-precedent for crop protection products where the effectiveness of the insecticide will be determined by its safety for non-target organisms, and other factors being equal, the choice of a particular control agent will be determined by its biodegradability. It should be noted that not a single class of insecticides that once appeared has completely disappeared; rather, it has occupied its niche, gradually declining under the pressure of new classes of insecticides. At the same time, the common trend in plant protection is towards use of insecticides with higher biodegradability, which gives hope for a safer future of the planet.
Chloroplast genome sequencing and divergence analysis of 18 Pyrus species: insights into intron length polymorphisms and evolutionary processes
Authors: Kim Jung Sun , Chung Hoyong , Park Bohyeon , Veerappan Karpagam , Kim Yoon-Kyung
Published: October 2024

Pears constitute an essential temperate crop and are primarily produced through interspecific hybridization owing to self-incompatibility that complicates their breeding history. To address this, we sequenced the complete chloroplast (cp) genomes of 18 Pyrus and one Malus species using the Illumina HiSeq4000 platform. The cp genomes ranged from 159,885 bp to 160,153 bp and exhibited a conserved circular DNA structure with an average GC content of 36.5%. Each cp genome contained 127 genes, including 83 protein-coding, 36 tRNA, and 8 rRNA genes. Divergence analysis with mVISTA showed high conservation in the coding regions and notable variations in the non-coding regions. All species shared 17 intron-containing genes, with ycf3 and clpP each having two introns. Five intron-containing genes (ndhB, rpl2, rps12, trnA-UGC, and trnE-UUC) were located in the inverted repeat regions, while trnL-UAA was located in the large single-copy region, with conserved intron lengths across Pomoideae. We identified polymorphic intron sequences in the rpl22, petB, clpP, ndhA, and rps16 genes and designed primers for these regions. Notably, the two Pyrus ussuriensis accessions Doonggeullebae and Cheongdangrori showed intron-length polymorphisms despite being classified as the same species. Phylogenetic analysis of the cp genome sequences revealed two major clusters, indicating distinct maternal lineages and evolutionary origins. This study underscores the importance of cp gene polymorphisms in P. fauriei, P. calleryana, P. ussuriensis, and P. pyrifolia, providing valuable insights into Pyrus evolution as well as aiding in the conservation and breeding of pear germplasm.
Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach
Authors: de Bruijn Suzanne E. , Panneman Daan M. , Weisschuh Nicole , Cadena Elizabeth L. , Boonen Erica G. M. , Holtes Lara K. , Astuti Galuh D. N. , Cremers Frans P. M. , Leijsten Nico , Corominas Jordi , Gilissen Christian , Skowronska Anna , Woodley Jessica , Beggs Andrew D. , Toulis Vasileios , Chen Di , Cheetham Michael E. , Hardcastle Alison J. , McLaren Terri L. , Lamey Tina M. , Thompson Jennifer A. , Chen Fred K. , de Roach John N. , Urwin Isabella R. , Sullivan Lori S. , Roosing Susanne
Published: October 2024

Introduction

Autosomal dominant retinitis pigmentosa type 17 (adRP, type RP17) is caused by complex structural variants (SVs) affecting a locus on chromosome 17 (chr17q22). The SVs disrupt the 3D regulatory landscape by altering the topologically associating domain (TAD) structure of the locus, creating novel TAD structures (neo-TADs) and ectopic enhancer-gene contacts. Currently, screening for RP17-associated SVs is not included in routine diagnostics given the complexity of the variants and a lack of cost-effective detection methods. The aim of this study was to accurately detect novel RP17-SVs by establishing a systematic and efficient workflow.

Methods

Genetically unexplained probands diagnosed with adRP (n = 509) from an international cohort were screened using a smMIPs or genomic qPCR-based approach tailored for the RP17 locus. Suspected copy number changes were validated using high-density SNP-array genotyping, and SV breakpoint characterization was performed by mutation-specific breakpoint PCR, genome sequencing and, if required, optical genome mapping. In silico modeling of novel SVs was performed to predict the formation of neo-TADs and whether ectopic contacts between the retinal enhancers and the GDPD1-promoter could be formed.

Results

Using this workflow, potential RP17-SVs were detected in eight probands of which seven were confirmed. Two novel SVs were identified that are predicted to cause TAD rearrangement and retinal enhancer-GDPD1 contact, one from Germany (DE-SV9) and three with the same SV from the United States (US-SV10). Previously reported RP17-SVs were also identified in three Australian probands, one with UK-SV2 and two with SA-SV3.

Discussion

In summary, we describe a validated multi-step pipeline for reliable and efficient RP17-SV discovery and expand the range of disease-associated SVs. Based on these data, RP17-SVs can be considered a frequent cause of adRP which warrants the inclusion of RP17-screening as a standard diagnostic test for this disease.
Case report: Adult patient with WWOX developmental and epileptic encephalopathy: 40 years of observation
Authors: Teplyshova Anna , Sharkov Artem
Published: October 2024

WWOX developmental and epileptic encephalopathy is characterised by drug-resistant epilepsy with onset within the first year of life and severe psychomotor developmental delay. This report presents for the first time a clinical case of an adult patient with a homozygous likely pathogenic variant (p.Thr12Met) in the WWOX gene, with more than 40 years of follow-up. The patient had refractory epilepsy with various types of seizures during his life: mainly epileptic spasms, autonomic, myoclonic, tonic seizures, and absences. The patient had a prominent developmental delay with a lack of expressive speech, but by the age of 3, he had acquired the skills to sit, crawl, and walk with support. In adolescence, there was an acute regression of acquired skills to a total absence of independent motor activity. The patient had dysmorphic features, such as upslanting palpebral fissures, arched eyebrows, and hypertelorism. For many years, the patient was given a diagnosis of cerebral palsy; 38 years after the onset of the disease, he was given a molecular genetic diagnosis of WWOX-associated developmental and epileptic encephalopathy. Our observation illustrates the natural history of WWOX-DEE and the high clinical significance of early genetic diagnostics for identifying the cause of developmental delay and resistant epilepsy.
Pre-training with a rational approach for antibody sequence representation
Authors: Gao Xiangrui , Cao Changling , He Chenfeng , Lai Lipeng
Published: October 2024

Introduction

Antibodies represent a specific class of proteins produced by the adaptive immune system in response to pathogens. Mining the information embedded in antibody amino acid sequences can benefit both antibody property prediction and novel therapeutic development. However, antibodies possess unique features that should be incorporated using specifically designed training methods, leaving room for improvement in pre-training models for antibody sequences.

Methods

In this study, we present a Pre-trained model of Antibody sequences trained with a Rational Approach for antibodies (PARA). PARA employs a strategy conforming to antibody sequence patterns and an advanced natural language processing self-encoding model structure. This approach addresses the limitations of existing protein pre-training models, which primarily utilize language models without fully considering the differences between protein sequences and language sequences.

Results

We demonstrate PARA’s performance on several tasks by comparing it to various published pre-training models of antibodies. The results show that PARA significantly outperforms existing models on these tasks, suggesting that PARA has an advantage in capturing antibody sequence information.

Discussion

The antibody latent representation provided by PARA can substantially facilitate studies in relevant areas. We believe that PARA’s superior performance in capturing antibody sequence information offers significant potential for both antibody property prediction and the development of novel therapeutics. PARA is available at https://github.com/xtalpi-xic.
Prognostic implications of a CD8+ TEMRA to CD4+Treg imbalance in mandibular fracture healing: a prospective analysis of immune profiles
Authors: Voss Jan Oliver , Pivetta Fabio , Elkilany Aboelyazid , Schmidt-Bleek Katharina , Duda Georg N. , Odaka Kento , Dimitriou Ioanna Maria , Ort Melanie Jasmin , Streitz Mathias , Heiland Max , Koerdt Steffen , Reinke Simon , Geissler Sven
Published: October 2024

Introduction

Open reduction and fixation are the standard of care for treating mandibular fractures and usually lead to successful healing. However, complications such as delayed healing, non-union, and infection can compromise patient outcomes and increase healthcare costs. The initial inflammatory response, particularly the response involving specific CD8+ T cell subpopulations, is thought to play a critical role in healing long bone fractures. In this study, we investigated the role of these immune cell profiles in patients with impaired healing of mandibular fractures.

Materials and methods

In this prospective study, we included patients with mandibular fractures surgically treated at Charité – Universitätsmedizin Berlin, Germany, between September 2020 and December 2022. We used follow-up imaging and clinical assessment to evaluate bone healing. In addition, we analyzed immune cell profiles using flow cytometry and quantified cytokine levels using electrochemiluminescence-based multiplex immunoassays in preoperative blood samples.

Results

Out of the 55 patients enrolled, 38 met the inclusion criteria (30 men and 8 women; mean age 32.18 years). Radiographic evaluation revealed 31 cases of normal healing and 7 cases of incomplete consolidation, including 1 case of non-union. Patients with impaired healing exhibited increased levels of terminally differentiated effector memory CD8+ T cells (TEMRA) and a higher TEMRA to regulatory T cell (Treg) ratio, compared with those with normal healing.

Conclusions

Our analysis of mandibular fracture cases confirms our initial hypothesis derived from long bone fracture healing: monitoring the TEMRA to Treg ratio in preoperative blood can be an early indicator of patients at risk of impaired bone healing. Radiologic follow-up enabled us to detect healing complications that might not be detected by clinical assessment only. This study highlights the potential of individual immune profiles to predict successful healing and may form the basis for future strategies to manage healing complications.
Neutrophil extracellular traps as immunofibrotic mediators in RA-ILD; pilot evaluation of the nintedanib therapy
Authors: Venetsanopoulou Aliki I. , Ntinopoulou Maria , Papagianni Eleni , Koletsos Nikolaos , Voulgari Paraskevi V. , Chrysanthopoulou Akrivi
Published: October 2024

Objective

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a significant pulmonary complication of RA. This study tried to elucidate the mechanisms enhancing inflammation and causing lung injury in RA-ILD, focusing on the role of neutrophil extracellular traps (NETs). The study also investigated the potential benefits of nintedanib in advanced disease.

Methods

Nine RA-ILD patients and nine healthy controls were included in the study. Inflammatory markers in patients’ circulation were evaluated with immunoassays. The formation of NETs was examined using a citrullinated histone H3 (CitH3) ELISA and cell immunofluorescence. Inflammatory proteins expressed in neutrophils/NETs were studied with real-time qPCR and NET ELISA. To assess the effect of nintedanib, an intracellular tyrosine kinase inhibitor with antifibrotic properties, in RA-ILD a paired study was conducted in five patients before treatment administration and 16 weeks later.

Results

The soluble terminal complement complex sC5b-9 and the levels of CitH3 were significantly elevated in patients with RA-ILD, compared to healthy controls. In addition, neutrophils isolated from RA-ILD patients released NETs enriched with tissue factor and interleukin-17A. Inflammatory NETs had a dynamic role, increasing the fibrotic potential of human pulmonary fibroblasts (HPFs). On the other hand, nintedanib treatment decreased NETs and sC5b-9 levels in RA-ILD patients.

Conclusion

The findings propose an interplay between circulating NETs and HPFs, establishing the immunofibrotic aspects of RA-ILD. They also support the effectiveness of nintedanib in reducing key pathological processes of the disease. Further research is needed to fully understand these mechanisms and optimize treatment strategies for RA-ILD.
Enhancement of a one-step membrane technique for the treatment of large bone defects by pre-seeding the membrane with CD8 lymphocyte depleted bone marrow mononuclear cells in a rat femoral defect model
Authors: Penna-Martinez Marissa , Kammerer Andreas , Stützle Pia , Fees Sabatian , Behr Savina , Schaible Inna , Schröder Katrin , Verboket René Danilo , Neijhoft Jonas , Marzi Ingo , Nau Christoph , Henrich Dirk
Published: October 2024

Background

The one-step membrane technique, using a human acellular dermal matrix (hADM), is an experimental method for treating large bone defects. This eliminates the need for the Masquelet membrane induction step, shortening the procedure while maintaining effectiveness. However, previous studies showed that colonizing hADM with bone marrow mononuclear cells (BMC) worsens healing, likely due to the presence of CD8+ lymphocytes, which negatively affect bone regeneration. This study aims to investigate whether the negative impact of BMC on bone healing in this technique is due to the CD8+ cell population.

Materials and methods

A 5 mm femoral defect was created in 25 male Sprague-Dawley rats, divided into three groups (G1-G3). BMC were isolated from syngenic donor rats, with CD8+ lymphocytes removed magnetically from the BMC fraction in one group. The defects were filled with bone chips and wrapped with differently treated hADM: G1 received native hADM, G2 received hADM+BMC, and G3 received hADM+BMC-CD8. After 8 weeks, the femurs were evaluated through radiological, biomechanical, and histological examinations.

Results

Bone defects and bone mineral density (BMD) were significantly improved in G3 (hADM+BMC-CD8) compared to G2 (hADM+BMC). Bone volume, bone formation, and median bending stiffness were higher in G3. Immunohistological analysis showed a significant decrease in CD8 cell count in G3, with a lower percentage of IFNγ-producing cells compared to G2.

Conclusion

Depleting CD8+ cells from BMC before colonizing hADM significantly improved bone healing, likely due to changes in the local mediator environment. This suggests that preoperative colonization with CD8+-depleted BMC could enhance the one-step membrane technique.
Comparing PD-L1 with PD-1 antibodies combined with lenvatinib and hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma
Authors: Li Shaohua , Mei Jie , Zhao Rongce , Zhou Jing , Wang Qiaoxuan , Lu Lianghe , Li Jibin , Zheng Lie , Wei Wei , Guo Rongping
Published: October 2024

Background

A combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and immune checkpoint inhibitors (ICIs) yields a high tumor response rate and survival benefit in unresectable hepatocellular carcinoma (uHCC). However, the selection criteria for different ICIs remain unclear. This study aims to compare the efficacy and safety of PD-1/PD-L1 antibodies combined with HAIC and lenvatinib.

Methods

This retrospective study included 184 patients with uHCC treated with HAIC+lenvatinib+PD-1/PD-L1 antibody from June 2019 to January 2022. We utilized propensity score matching (PSM) to select and match 60 patients treated with HAIC + durvalumab + lenvatinib (HDL) against 60 patients treated with HAIC + PD-1 antibodies + lenvatinib (HPL) to compare the efficacy and safety profiles of these two groups.

Results

After PSM, the baseline characteristics were well-balanced between the HDL and HPL groups. The overall survival (p = 0.293) and progression-free survival (p = 0.146) showed no significant difference. The objective response rate (ORR) was higher in the HDL group compared to the HPL group according to modified RECIST (74.1% vs. 53.6%, p = 0.022) and RECIST 1.1 (60.3% vs. 41.1%, p = 0.040), respectively. The incidence of grade 3 or 4 adverse events (AEs) was 10.0% and 18.3% (p = 0.191) in the HDL and HPL groups, respectively.

Conclusions

PD-L1 antibody appears to be a preferable companion in the combination therapy of HAIC + ICIs + lenvatinib compared to PD-1 antibody, showing higher ORR and relatively lower incidence of severe AEs. Further prospective studies involving a larger patient population are warranted.
Perceived quality of maternal care and its barriers based on women’s perspective in hospitals of Northwest Ethiopia: a qualitative study
Authors: Mekie Maru , Belachew Yismaw Yimam , Chanie Ermias Sisay , Bayih Wubet Alebachew , Fenta Setegn Muche , Masresha Gedefew Abeje , Ferede Wassie Yazie , Addisu Dagne
Published: October 2024

Background

The Sustainable Development Goals (SDGs) in health focus on achieving equity to reduce maternal mortality disparities among subpopulations globally. The goal is to lower the maternal mortality ratio (MMR) to below 70 per 100,000 live births by 2030 for countries with an MMR below 420 in 2010. For those exceeding 420, the target is to keep the MMR below 140 by 2030. This target could not be achieved unless quality maternal health care service is implemented in all health care settings. This study aimed to assess the quality of maternal care and perceived barriers based on women’s perspectives among women who receive delivery services in hospitals of South Gondar Zone, Northwest, Ethiopia.

Methods

A phenomenological method was implemented to explore women’s perspectives on quality maternal care and its perceived barriers. An in-depth interview (IDI) was used to collect data using a semi-structured in-depth interview guide. The study was conducted from January 1–30, 2021. All in-depth interview notes were translated into meaningful notes. Then notes were organized by coding texts into meaningful elements using open code version 4.03 software.

Results

The majority (14 in 20) tried to interpret quality care in terms of respect during procedures, providing family support, and timely care. Some (6 in 20) tried to associate quality care with the competency of care providers, the cleanliness of the procedure, and privacy during care. With regards to perceived barriers to quality care, the majority (15 in 20) of the IDI participants agreed that a high caseload, limited drugs, and administrative problems were barriers to providing quality maternal care.

Conclusion

Participants articulate a multifaceted understanding of quality maternal care that encompasses emotional support, accessibility, cleanliness, timely interventions, and respectful treatment. They also identify significant barriers that stem from facility limitations, provider attitudes and knowledge, and administrative inefficiencies. Addressing these barriers is essential for enhancing the quality of maternal health services.
Case report: A rare case of meningoencephalitis caused by Mycobacterium gordonae
Authors: Yuan Dezhi , Ding Xiaomi , Chen Jing , Zhao Ying , Wang Xing , Zhu Jie
Published: October 2024

Meningoencephalitis, an infectious disease affecting the nervous system, is primarily caused by a variety of pathogens. Non-tuberculous mycobacteria (NTM) have emerged as the leading causative agent of infections worldwide, but central nervous system infections resulting from NTM are infrequent in individuals with functioning immune systems. This case report highlights the diagnosis and treatment of a 26-year-old female patient who developed headaches 2 months post double eyelid surgery and was subsequently diagnosed with NTM meningoencephalitis through metagenomic next-generation sequencing (mNGS) analysis of cerebrospinal fluid. The patient underwent a comprehensive diagnostic and therapeutic protocol, resulting in a positive clinical outcome.
Integrating planetary health education into tertiary curricula: a practical toolbox for implementation
Authors: Lokmic-Tomkins Zerina , Barbour Liza , LeClair Jessica , Luebke Jeneile , McGuinness Sarah L. , Limaye Vijay S. , Pillai Parvathy , Flynn Maxfield , Kamp Michael A. , Leder Karin , Patz Jonathan A.
Published: October 2024

Objective

To present a series of case studies from our respective countries and disciplines on approaches to implementing the Planetary Health Education Framework in university health professional education programs, and to propose a curriculum implementation and evaluation toolbox for educators to facilitate the adoption of similar initiatives in their programs. We emphasize the importance of applying an Indigenous lens to curriculum needs assessment, development, implementation, and evaluation.

Methods

Case studies from Australia and United States were collated using a six-stage design-based educational research framework (Focus, Formulation, Contextualization, Definition, Implementation, Evaluation) for teaching planetary health and methods of curriculum evaluation. These components were then mapped to derive the curriculum implementation toolbox reflecting the six-stage design-based educational research framework.

Results

The case studies demonstrated different approaches to successful integration of the Planetary Health Education Framework in medicine, nursing, public health, and allied health disciplines. This integration often involved Indigenous perspectives on environmental stewardship, holistic health, and community well-being into the curriculum. The case studies also highlighted the importance of community engagement, cultural competency, and interdisciplinary collaboration in curriculum development. Findings from case studies were used to propose a curriculum implementation toolbox to assist educators in adapting and integrating planetary health education into their own programs.

Discussion

While valuable frameworks for teaching planetary health in health science programs exist, challenges remain in implementing these frameworks in real-world educational environments. The proposed curriculum implementation toolbox offers practical strategies and resources for educators to incorporate these principles into their teaching. Additionally, the case studies reported here contribute to the growing body of literature on planetary health education pertinent to addressing the triple planetary crisis.
Clinical efficacy of Endostar continuous infusion combined with concurrent chemoradiotherapy in the treatment of oesophageal squamous cell carcinoma
Authors: Du Xinglong , Ji Yuting , Qin Wenqiang , Wei Jie
Published: October 2024

Objective

To evaluate the effectiveness and safety of concurrent chemoradiotherapy using Endostar continuous infusion for treating oesophageal squamous cell carcinoma (OSCC).

Method

A total of 62 patients with oesophageal carcinoma were divided into three groups: the Endostar continuous infusion group (n = 27), the Endostar intravenous drip group (n = 21) and the concurrent chemoradiotherapy group (n = 14). All patients underwent oesophageal radiotherapy (56–60 Gy) alongside concurrent chemotherapy (4 mg of raltitrexed +100 mg of oxaliplatin, two cycles). In the Endostar continuous infusion group, 210 mg of Endostar was administered via infusion once every 3 weeks for 72 h, repeated for two cycles. The Endostar intravenous drip group received a dosage of 15 mg/day of Endostar, administered once daily for 14 days, repeated for two cycles. The objective response rate (ORR) (complete remission + partial remission), progression-free survival (PFS), 2-year overall survival (2y-OS) and adverse reactions were observed.

Results

In the Endostar continuous infusion, intravenous drip and concurrent chemoradiotherapy groups, the ORR was 100, 95.2 and 78.6%, respectively (p < 0.05). There was a statistically significant difference between the continuous infusion and concurrent chemoradiotherapy groups (p < 0.05). However, there was no statistically significant difference between the continuous infusion and intravenous drip groups or the intravenous drip and concurrent chemoradiotherapy groups (p > 0.05). The continuous infusion and intravenous drip groups had higher PFS rates than the concurrent chemoradiotherapy group (p < 0.05). Regarding the 2y-OS rate, no statistically significant difference was observed among the three groups (p > 0.05). Furthermore, there was no statistically significant difference in adverse reactions among the groups (p > 0.05).

Conclusion

Concurrent chemotherapy based on endostatin is effective and safe in the treatment of OSCC. Continuous 3-day Endostar infusion treatment can significantly enhance both short-and long-term therapy efficacy in patients while maintaining a high level of safety.