bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining albumin as a glycoprotein with multiple N-linked glycosylation sites
Authors: Garapati Kishore , Jain Anu , Madden Benjamin J. , Mun Dong-Gi , Sharma Jyoti , Budhraja Rohit , Pandey Akhilesh
Published: May 2024

Background

Glycosylation is an enzyme-catalyzed post-translational modification that is distinct from glycation and is present on a majority of plasma proteins. N-glycosylation occurs on asparagine residues predominantly within canonical N-glycosylation motifs (Asn-X-Ser/Thr) although non-canonical N-glycosylation motifs Asn-X-Cys/Val have also been reported. Albumin is the most abundant protein in plasma whose glycation is well-studied in diabetes mellitus. However, albumin has long been considered a non-glycosylated protein due to absence of canonical motifs. Albumin contains two non-canonical N-glycosylation motifs, of which one was recently reported to be glycosylated.

Methods

We enriched abundant serum proteins to investigate their N-linked glycosylation followed by trypsin digestion and glycopeptide enrichment by size-exclusion or mixed-mode anion-exchange chromatography. Glycosylation at canonical as well as non-canonical sites was evaluated by liquid chromatography–tandem mass spectrometry (LC–MS/MS) of enriched glycopeptides. Deglycosylation analysis was performed to confirm N-linked glycosylation at non-canonical sites. Albumin-derived glycopeptides were fragmented by MS3 to confirm attached glycans. Parallel reaction monitoring was carried out on twenty additional samples to validate these findings. Bovine and rabbit albumin-derived glycopeptides were similarly analyzed by LC–MS/MS.

Results

Human albumin is N-glycosylated at two non-canonical sites, Asn68 and Asn123. N-glycopeptides were detected at both sites bearing four complex sialylated glycans and validated by MS3-based fragmentation and deglycosylation studies. Targeted mass spectrometry confirmed glycosylation in twenty additional donor samples. Finally, the highly conserved Asn123 in bovine and rabbit serum albumin was also found to be glycosylated.

Conclusions

Albumin is a glycoprotein with conserved N-linked glycosylation sites that could have potential clinical applications.
Neuroprotective effects of apigenin on retinal ganglion cells in ischemia/reperfusion: modulating mitochondrial dynamics in in vivo and in vitro models
Authors: Wu Jiawen , zhang Daowei , Liu Hongli , Li Jufeng , Li Ting , Wu Jihong , Zhang Shenghai
Published: May 2024

Background

Retinal ischemia/reperfusion (RIR) is implicated in various forms of optic neuropathies, yet effective treatments are lacking. RIR leads to the death of retinal ganglion cells (RGCs) and subsequent vision loss, posing detrimental effects on both physical and mental health. Apigenin (API), derived from a wide range of sources, has been reported to exert protective effects against ischemia/reperfusion injuries in various organs, such as the brain, kidney, myocardium, and liver. In this study, we investigated the protective effect of API and its underlying mechanisms on RGC degeneration induced by retinal ischemia/reperfusion (RIR).

Methods

An in vivo model was induced by anterior chamber perfusion following intravitreal injection of API one day prior to the procedure. Meanwhile, an in vitro model was established through 1% oxygen and glucose deprivation. The neuroprotective effects of API were evaluated using H&E staining, spectral-domain optical coherence tomography (SD-OCT), Fluoro-Gold retrograde labeling, and Photopic negative response (PhNR). Furthermore, transmission electron microscopy (TEM) was employed to observe mitochondrial crista morphology and integrity. To elucidate the underlying mechanisms of API, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, flow cytometry assay, western blot, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, JC-1 kit assay, dichlorofluorescein-diacetate (DCFH-DA) assay, as well as TMRE and Mito-tracker staining were conducted.

Results

API treatment protected retinal inner plexiform layer (IPL) and ganglion cell complex (GCC), and improved the function of retinal ganglion cells (RGCs). Additionally, API reduced RGC apoptosis and decreased lactate dehydrogenase (LDH) release by upregulating Bcl-2 and Bcl-xL expression, while downregulating Bax and cleaved caspase-3 expression. Furthermore, API increased mitochondrial membrane potential (MMP) and decreased extracellular reactive oxygen species (ROS) production. These effects were achieved by enhancing mitochondrial function, restoring mitochondrial cristae morphology and integrity, and regulating the expression of OPA1, MFN2, and DRP1, thereby regulating mitochondrial dynamics involving fusion and fission.

Conclusion

API protects RGCs against RIR injury by modulating mitochondrial dynamics, promoting mitochondrial fusion and fission.
Guideline for the application of heart rate and heart rate variability in occupational medicine and occupational health science
Authors: Sammito Stefan , Thielmann Beatrice , Klussmann Andre , Deußen Andreas , Braumann Klaus-Michael , Böckelmann Irina
Published: May 2024

This updated guideline replaces the “Guideline for the application of heart rate and heart rate variability in occupational medicine and occupational health science” first published in 2014. Based on the older version of the guideline, the authors have reviewed and evaluated the findings on the use of heart rate (HR) and heart rate variability (HRV) that have been published in the meantime and incorporated them into a new version of this guideline.

This guideline was developed for application in clinical practice and research purposes in the fields of occupational medicine and occupational science to complement evaluation procedures with respect to exposure and risk assessment at the workplace by the use of objective physiological workload indicators. In addition, HRV is also suitable for assessing the state of health and for monitoring the progress of illnesses and preventive medical measures. It gives an overview of factors influencing the regulation of the HR and HRV at rest and during work. It further illustrates methods for measuring and analyzing these parameters under standardized laboratory and real workload conditions, areas of application as well as the quality control procedures to be followed during the recording and evaluation of HR and HRV.
The World Federation of Chiropractic Global Patient Safety Task Force: a call to action
Authors: Coleman Brian C. , Rubinstein Sidney M. , Salsbury Stacie A. , Swain Michael , Brown Richard , Pohlman Katherine A.
Published: May 2024

Background

The Global Patient Safety Action Plan, an initiative of the World Health Organization (WHO), draws attention to patient safety as being an issue of utmost importance in healthcare. In response, the World Federation of Chiropractic (WFC) has established a Global Patient Safety Task Force to advance a patient safety culture across all facets of the chiropractic profession. This commentary aims to introduce principles and call upon the chiropractic profession to actively engage with the Global Patient Safety Action Plan beginning immediately and over the coming decade.

Main text

This commentary addresses why the chiropractic profession should pay attention to the WHO Global Patient Safety Action Plan, and what actions the chiropractic profession should take to advance these objectives. Each strategic objective identified by WHO serves as a focal point for reflection and action. Objective 1 emphasizes the need to view each clinical interaction as a chance to improve patient safety through learning. Objective 2 urges the implementation of frameworks that dismantle systemic obstacles, minimizing human errors and strengthening patient safety procedures. Objective 3 supports the optimization of clinical process safety. Objective 4 recognizes the need for patient and family engagement. Objective 5 describes the need for integrated patient safety competencies in training programs. Objective 6 explains the need for foundational data infrastructure, ecosystem, and culture. Objective 7 emphasizes that patient safety is optimized when healthcare professionals cultivate synergy and partnerships.

Conclusions

The WFC Global Patient Safety Task Force provides a structured framework for aligning essential considerations for patient safety in chiropractic care with WHO strategic objectives. Embracing the prescribed action steps offers a roadmap for the chiropractic profession to nurture an inclusive and dedicated culture, placing patient safety at its core. This commentary advocates for a concerted effort within the chiropractic community to commit to and implement these principles for the collective advancement of patient safety.
Diagnosis and treatment of the Ehlers-Danlos syndromes in China: synopsis of the first guidelines
Authors: Xu Kexin , Li Guozhuang , Wu Zhihong , Zhang Terry Jianguo , Wu Nan ,   On behalf of the Chinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes
Published: May 2024

Background

The Ehlers-Danlos syndromes (EDS) are a group of rare hereditary connective tissue disorders. EDS is clinically and genetically heterogeneous and usually involves multiple systems. There are 14 subtypes of EDS with hallmark features including joint hypermobility, skin hyperextensibility, and tissue fragility. The clinical manifestations and their severity differ among the subtypes, encompassing recurrent joint dislocations, scoliosis, arterial aneurysm and dissection, and organ rupture. Challenges in diagnosis and management arise from the complexity of the disease, which is further complicated by its rarity. The development of clinical guidelines and implementation of coordinated multi-disciplinary team (MDT) approaches have emerged as global priorities.

Main body

Chinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes was therefore established. Healthcare professionals were recruited from 25 top hospitals across China. The experts are specialized in 24 fields, including genetics, vascular surgery, dermatology, and orthopedics, as well as nursing care, rehabilitation, psychology, and nutrition. Based on GRADE methodology, the Guidelines were written by the Group supervised by methodologists, following a systemic review of all 4453 articles in PubMed published before August 9, 2023, using the search term “Ehlers Danlos”. A coordinated MDT approach for the diagnosis and management of EDS is highly recommended by the Group, along with 29 specific recommendations addressing key clinical questions. In addition to the treatment plan, the Guidelines also emphasize integrating support from nursing care, rehabilitation, psychology, and nutrition. This integration not only facilitates recovery in hospital settings, but most importantly, the transition from an illness-defined life to a more “normalized” life.

Conclusion

The first guidelines on EDS will shorten the diagnostic odyssey and solve the unmet medical needs of the patients. This article is a synopsis of the full guidelines.
The pathophysiology of pelvic ring injuries: a review
Authors: Stahel Philip F. , Ziran Navid
Published: May 2024

Traumatic pelvic ring injuries continue to represent a major challenge due to the high rates of post-injury mortality of around 30-40% in the peer-reviewed literature. The main root cause of potentially preventable mortality relates to the delayed recognition of the extent of retroperitoneal hemorrhage and post-injury coagulopathy. The understanding of the underlying pathophysiology of pelvic trauma is predicated by classification systems for grading of injury mechanism and risk stratification for developing post-injury coagulopathy with subsequent uncontrolled exsanguinating hemorrhage. This review article elaborates on the current understanding of the pathophysiology of severe pelvic trauma with a focus on the underlying mechanisms of retroperitoneal bleeding and associated adverse outcomes.
Efficiency of copy number variation sequencing combined with karyotyping in fetuses with congenital heart disease and the following outcomes
Authors: Wang Xuezhen , Sha Jing , Han Yu , Pang Min , Liu Min , Liu Mengna , Zhang Bei , Zhai Jingfang
Published: May 2024

Background

Both copy number variant-sequencing (CNV-seq) and karyotype analysis have been used as powerful tools in the genetic aetiology of fetuses with congenital heart diseases (CHD). However, CNV-seq brings clinicians more confusions to interpret the detection results related to CHD with or without extracardiac abnormalities. Hence, we conducted this study to investigate the clinical value of CNV-seq in fetuses with CHD.

Results

A total of 167 patients with fetal CHD including 36 single CHD (sCHD), 41 compound CHD (cCHD) and 90 non-isolated CHD (niCHD) were recruited into the study. 28 cases (16.77%, 28/167) were revealed with chromosomal abnormalities at the level of karyotype. The pathogenic detection rate (DR) of CNV-seq (23.17%, 19/82) was higher than that of karyotyping (15.85%, 13/82) in 82 cases by CNV-seq and karyotyping simultaneously. The DR of pathogenic copy number variations (PCNVs) (31.43%) was higher in niCHD subgroup than that in sCHD and cCHD (9.52% and 23.08%). Conotruncal defect (CTD) was one of the most common heart malformations with the highest DR of PCNVs (50%) in 7 categories of CHD. In terms of all the pregnancy outcomes, 67 (40.12%) cases were terminated and 100 (59.88%) cases were live neonates. Only two among 34 cases with a pathogenic genetic result chose to continue the pregnancy.

Conclusions

CNV-seq combined with karyotyping is a reliable and accurate prenatal technique for identifying pathogenic chromosomal abnormalities associated with fetal CHD with or without extracardiac abnormalities, which can assist clinicians to perform detailed genetic counselling with regard to the etiology and related outcomes of CHD.
The risk of skin cancer in women who carry BRCA1 or BRCA2 mutations
Authors: Narod Steven A. , Metcalfe Kelly , Finch Amy , Chan An-Wen , Armel Susan Randall , Aeilts Amber , Eisen Andrea , Karlan Beth , Bordeleau Louise , Tung Nadine , Foulkes William D. , Neuhausen Susan L. , Eng Charis , Olopade Olufunmilayo , Zakalik Dana , Couch Fergus , Cullinane Carey , Pal Tuya , Sun Ping , Kotsopoulos Joanne ,   the Hereditary Breast Cancer Clinical Research Group, Poll Aletta , Kim Raymond , Fruscio Robert , Lemire Edmond , Serfas Kim , Sweet Kevin , Senter Leigha , Panchal Seema , Elser Christine , Blum Joanne L. , Rayson Daniel , Isaacs Claudine , Dungan Jeffrey , Cohen Stephanie
Published: May 2024

Background

It has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations.

Methods

We report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations. Women were followed from the date of baseline questionnaire to the diagnosis of skin cancer, to age 80 years, death from any cause, or the date of last follow-up.

Results

During the mean follow-up period of eight years, 3.7% of women with a BRCA1 mutation (133 of 3,623) and 3.8% of women with a BRCA2 mutation (99 of 2,584) reported a diagnosis of skin cancer (including both keratinocyte carcinomas and melanoma). The cumulative risk of all types of skin cancer from age 20 to 80 years was 14.1% for BRCA1 carriers and 10.7% for BRCA2 carriers. The cumulative risk of melanoma was 2.5% for BRCA1 carriers and 2.3% for BRCA2 carriers, compared to 1.5% for women in the general population in the United States. The strongest risk factor for skin cancer was a prior diagnosis of skin cancer.

Conclusion

The risk of non-melanoma skin cancer in women who carry a mutation in BRCA1 or BRCA2 is similar to that of non-carrier women. The risk of melanoma appears to be slightly elevated. We suggest that a referral to a dermatologist or primary care provider for BRCA mutation carriers for annual skin examination and counselling regarding limiting UV exposure, the use of sunscreen and recognizing the early signs of melanoma might be warranted, but further studies are necessary.
EmptyDropsMultiome discriminates real cells from background in single-cell multiomics assays
Authors: Megas Stathis , Lorenzi Valentina , Marioni John C.
Published: May 2024

Multiomic droplet-based technologies allow different molecular modalities, such as chromatin accessibility and gene expression (scATAC-seq and scRNA-seq), to be probed in the same nucleus. We develop EmptyDropsMultiome, an approach that distinguishes true nuclei-containing droplets from background. Using simulations, we show that EmptyDropsMultiome has higher statistical power and accuracy than existing approaches, including CellRanger-arc and EmptyDrops. On real datasets, we observe that CellRanger-arc misses more than half of the nuclei identified by EmptyDropsMultiome and, moreover, is biased against certain cell types, some of which have a retrieval rate lower than 20%.
SCIPAC: quantitative estimation of cell-phenotype associations
Authors: Gan Dailin , Zhu Yini , Lu Xin , Li Jun
Published: May 2024

Numerous algorithms have been proposed to identify cell types in single-cell RNA sequencing data, yet a fundamental problem remains: determining associations between cells and phenotypes such as cancer. We develop SCIPAC, the first algorithm that quantitatively estimates the association between each cell in single-cell data and a phenotype. SCIPAC also provides a p-value for each association and applies to data with virtually any type of phenotype. We demonstrate SCIPAC’s accuracy in simulated data. On four real cancerous or noncancerous datasets, insights from SCIPAC help interpret the data and generate new hypotheses. SCIPAC requires minimum tuning and is computationally very fast.
Targeting strategies for balanced energy and protein (BEP) supplementation in pregnancy: study protocol for the TARGET-BEP cluster-randomized controlled trial in rural Bangladesh
Authors: Zavala Eleonor , Mohan Diwakar , Ali Hasmot , Siddiqua Towfida J. , Haque Rezwanul , Ayesha Kaniz , Ahsan Khalid Bin , Sujan Hasan Mahmud , Khaled Nazrana , Rahman Atiya , Chakraborty Barnali , Dyer Brian , Wu Lee S. F. , Kalbarczyk Anna , Erchick Daniel J. , Thorne-Lyman Andrew L. , Tumilowicz Alison , Afsana Kaosar , Christian Parul
Published: May 2024

Background

The World Health Organization (WHO) recommends balanced energy and protein (BEP) supplementation be provided to all pregnant women living in undernourished populations, usually defined as having a prevalence > 20% of underweight women, to reduce the risk of stillbirths and small-for-gestational-age neonates. Few geographies meet this threshold, however, and a large proportion of undernourished women and those with inadequate gestational weight gain could miss benefiting from BEP. This study compares the effectiveness of individual targeting approaches for supplementation with micronutrient-fortified BEP vs. multiple micronutrient supplements (MMS) alone as control in pregnancy in improving birth outcomes.

Methods

The TARGET-BEP study is a four-arm, cluster-randomized controlled trial conducted in rural northwestern Bangladesh. Eligible participants are married women aged 15–35 years old identified early in pregnancy using a community-wide, monthly, urine-test-based pregnancy detection system. Beginning at 12–14 weeks of gestation, women in the study area comprising 240 predefined sectors are randomly assigned to one of four intervention arms, with sector serving as the unit of randomization. The interventions involving daily supplementation through end of pregnancy are as follows: (1) MMS (control); (2) BEP; (3) targeted BEP for those with pre-pregnancy body mass index (BMI) < 18.5 kg/m2 and MMS for others; (4) targeted BEP for those with pre-pregnancy BMI < 18.5 kg/m2, MMS for others, and women with inadequate gestational weight gain switched from MMS to BEP until the end of pregnancy. Primary outcomes include birth weight, low birth weight (< 2500 g), and small for gestational age, defined using the 10th percentile of the INTERGROWTH-21st reference, for live-born infants measured within 72 h of birth. Project-hired local female staff visit pregnant women monthly to deliver the assigned supplements, monitor adherence biweekly, and assess weight regularly during pregnancy. Trained data collectors conduct pregnancy outcome assessment and measure newborn anthropometry in the facility or home depending on the place of birth.

Discussion

This study will assess the effectiveness of targeted balanced energy and protein supplementation to improve birth outcomes among pregnant women in rural Bangladesh and similar settings.

Trial registration

ClinicalTrials.gov NCT05576207. Registered on October 5th, 2022.
Efficacy of ganglion impar block combined with pudendal nerve pulsed radiofrequency for pudendal neuralgia management—a randomized clinical trial
Authors: Ran Jiao , Lu Fan , Xu Le , Du Yu , Liu Li , Qi Tao , Zhou Xiaoli , Zhang Yulin , Liu Dong , Wang Rurong , Li Xuehan
Published: May 2024

Background

Pudendal neuralgia is a chronic and debilitating condition. Its prevalence ranges from 5 to 26%. Currently, therapeutic approaches to treat pudendal neuralgia include patient education, medication management, psychological and physical therapy, and procedural interventions, such as nerve block, trigger point injections, and surgery. Drug therapy has a limited effect on pain relief. A pudendal nerve block may cause a significant decrease in pain scores for a short time; however, its efficacy significantly decreases over time. In contrast, pudendal nerve pulsed radiofrequency can provide pain relief for 3 months, and ganglion impar block has been widely used for treating chronic perineal pain and chronic coccygodynia. This study aimed to determine the efficacy and safety of monotherapy (pudendal nerve pulsed radiofrequency) and combination therapy (pudendal nerve pulsed radiofrequency plus ganglion impar block) in patients with pudendal neuralgia.

Methods

This randomized, controlled clinical trial will include 84 patients with pudendal neuralgia who failed to respond to drug or physical therapy. Patients will be randomly assigned into one of the two groups: mono or combined treatment groups. The primary outcome will be a change in pain intensity measured using the visual analog scale. The secondary outcomes will include a Self-Rating Anxiety Scale score, Self-Rating Depression Scale score, the use of oral analgesics, the Medical Outcomes Study Health Survey Short Form-36 Item score, and the occurrence of adverse effects. The study results will be analyzed using intention-to-treat and per-protocol analyses. Primary and secondary outcomes will be evaluated between the mono and combined treatment groups. Subgroup analyses will be conducted based on the initial ailment, age, and baseline pain intensity. The safety of the treatment will be assessed by monitoring adverse events, which will be compared between the two groups.

Discussion

This study protocol describes a randomized, controlled clinical trial to determine the efficacy and safety of mono and combination therapies in patients with pudendal neuralgia. The study results will provide valuable information on the potential benefits of this combination therapy and contribute to the development of more effective and safer treatments for patients with pudendal neuralgia.

Trial registration

Chinese Clinical Trial Registry (ChiCTR2200061800).
Vector competence of Swedish Culex pipiens mosquitoes for Japanese encephalitis virus
Authors: Krambrich Janina , Akaberi Dario , Lindahl Johanna F. , Lundkvist Åke , Hesson Jenny C.
Published: May 2024

Background

Japanese encephalitis virus (JEV) is an emerging mosquito-borne Orthoflavivirus that poses a significant public health risk in many temperate and tropical regions in Asia. Since the climate in some endemic countries is similar to temperate climates observed in Europe, understanding the role of specific mosquito species in the transmission of JEV is essential for predicting and effectively controlling the potential for the introduction and establishment of JEV in Europe.

Methods

This study aimed to investigate the vector competence of colonized Culex pipiens biotype molestus mosquitoes for JEV. The mosquitoes were initially collected from the field in southern Sweden. The mosquitoes were offered a blood meal containing the Nakayama strain of JEV (genotype III), and infection rates, dissemination rates, and transmission rates were evaluated at 14, 21, and 28 days post-feeding.

Results

The study revealed that colonized Swedish Cx. pipiens are susceptible to JEV infection, with a stable infection rate of around 10% at all timepoints. However, the virus was only detected in the legs of one mosquito at 21 days post-feeding, and no mosquito saliva contained JEV.

Conclusions

Overall, this research shows that Swedish Cx. pipiens can become infected with JEV, and emphasizes the importance of further understanding of the thresholds and barriers for JEV dissemination in mosquitoes.

Graphical Abstract
Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states
Authors: Wang Frank Qingyun , Shao Li , Dang Xiao , Wang Yong-Fei , Chen Shuxiong , Liu Zhongyi , Mao Yujing , Jiang Yuping , Hou Fei , Guo Xianghua , Li Jian , Zhang Lili , Sang Yuting , Zhao Xuan , Ma Ruirui , Zhang Kai , Zhang Yanfang , Yang Jing , Wen Xiwu , Liu Jiong , Wei Wei , Zhang Chuanpeng , Li Weiyang , Qin Xiao , Lei Yao , Feng Hong , Yang Xingtian , She Chun Hing , Zhang Caicai , Su Huidong , Chen Xinxin , Yang Jing , Lau Yu Lung , Wu Qingjun , Ban Bo , Song Qin , Yang Wanling
Published: May 2024

Objectives

This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission.

Methods

We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks.

Results

Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse.

Conclusion

Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.
Identification and verification of a novel signature that combines cuproptosis-related genes with ferroptosis-related genes in osteoarthritis using bioinformatics analysis and experimental validation
Authors: He Baoqiang , Liao Yehui , Tian Minghao , Tang Chao , Tang Qiang , Ma Fei , Zhou Wenyang , Leng Yebo , Zhong Dejun
Published: May 2024

Background

Exploring the pathogenesis of osteoarthritis (OA) is important for its prevention, diagnosis, and treatment. Therefore, we aimed to construct novel signature genes (c-FRGs) combining cuproptosis-related genes (CRGs) with ferroptosis-related genes (FRGs) to explore the pathogenesis of OA and aid in its treatment.

Materials and methods

Differentially expressed c-FRGs (c-FDEGs) were obtained using R software. Enrichment analysis was performed and a protein–protein interaction (PPI) network was constructed based on these c-FDEGs. Then, seven hub genes were screened. Three machine learning methods and verification experiments were used to identify four signature biomarkers from c-FDEGs, after which gene set enrichment analysis, gene set variation analysis, single-sample gene set enrichment analysis, immune function analysis, drug prediction, and ceRNA network analysis were performed based on these signature biomarkers. Subsequently, a disease model of OA was constructed using these biomarkers and validated on the GSE82107 dataset. Finally, we analyzed the distribution of the expression of these c-FDEGs in various cell populations.

Results

A total of 63 FRGs were found to be closely associated with 11 CRGs, and 40 c-FDEGs were identified. Bioenrichment analysis showed that they were mainly associated with inflammation, external cellular stimulation, and autophagy. CDKN1A, FZD7, GABARAPL2, and SLC39A14 were identified as OA signature biomarkers, and their corresponding miRNAs and lncRNAs were predicted. Finally, scRNA-seq data analysis showed that the differentially expressed c-FRGs had significantly different expression distributions across the cell populations.

Conclusion

Four genes, namely CDKN1A, FZD7, GABARAPL2, and SLC39A14, are excellent biomarkers and prospective therapeutic targets for OA.
Peridynamic numerical investigation of asymmetric strain-controlled fatigue behaviour using the kinetic theory of fracture
Authors: Vaitkunas Tomas , Griskevicius Paulius , Dundulis Gintautas , Courtin Stephan
Published: May 2024

Numerical fatigue process modelling is complex and still an open task. Discontinuity caused by fatigue cracks requires special finite element techniques based on additional parameters, the selection of which has a strong effect on the simulation results. Moreover, the calculation of fatigue life according to empirical material coefficients (e.g., Paris law) does not explain the process, and coefficients should be set from experimental testing, which is not always possible. A new nonlocal continuum mechanics formulation without spatial derivative of coordinates, namely, peridynamics (PD), which was created 20 y ago, provides new opportunities for modelling discontinuities, such as fatigue cracks. The fatigue process can be better described by using the atomistic approach-based kinetic theory of fracture (KTF), which includes the process temperature, maximum and minimum stresses, and loading frequency in its differential fatigue damage equation. Standard 316L stainless steel specimens are tested, and then the KTF-PD fatigue simulation is run in this study. In-house MATLAB code, calibrated from the material S‒N curve, is used for the KTF-PD simulation. A novel KTF equation based on the cycle stress‒strain hysteresis loop is proposed and applied to predict fatigue life. The simulation results are compared with the experimental results, and good agreement is observed for both symmetric and asymmetric cyclic loading.
Patient-reported outcomes during accelerating the en-masse retraction of the upper anterior teeth using low-intensity electrical stimulation: a randomized controlled trial
Authors: Shaadouh Rashad I. , Hajeer Mohammad Y. , Mahmoud Ghiath A. , Almasri Imad Addin , Jaber Samer T. , Alam Mohammad Khursheed
Published: May 2024

Background

Low-intensity electrical stimulation (LIES) is considered a relatively recent technology that has received little attention in orthodontics as a method of acceleration. This study aimed to evaluate patient-reported outcome measures when LIES is used to accelerate the en-masse retraction of the upper anterior teeth.

Materials and methods

The sample consisted of 40 patients (8 males, 32 females; mean age 21.1 ± 2.3 years), with Class II division I malocclusion who required extraction of the first premolars to retract upper anterior teeth. They were randomly assigned to the LIES group (n = 20) and the conventional en-masse retraction group (CER; n = 20). Patient responses regarding pain, discomfort, burning sensation, swelling, chewing difficulty, speech difficulty, and painkillers’ consumption were recorded at these nine assessment times: 24 h (T1), 3 days (T2), and 7 days (T3) after force application, then in the second month after 24 h (T4), 3 days (T5), and 7 days (T6) of force re-activation, and finally after 24 h (T7), 3 days (T8), and 7 days (T9) of force re-activation in the third month.

Results

The mean values of pain perception were smaller in the LIES group than those in the CER group at all assessment times with no statistically significant differences between the two groups except during the second and third months (T5, T6, T8, and T9; P < 0.005). However, discomfort mean values were greater in the LIES group with significant differences compared to CER group during the first week of the follow-up only (T1, T2, and T3; P < 0.005). Burning sensation levels were very mild in the LIES group, with significant differences between the two groups at T1 and T2 only (P < 0.001). Speech difficulty was significantly greater in the LIES group compared to CER group at all studied times (P < 0.001). High levels of satisfaction and acceptance were reported in both groups, without any significant difference.

Conclusion

Both the LIES-based acceleration of en-masse retraction of upper anterior teeth and the conventional retraction were accompanied by mild to moderate pain, discomfort, and chewing difficulty on the first day of retraction. These sensations gradually decreased and almost disappeared over a week after force application or re-activation.

Trial registration

ClinicalTrials.gov, ClinicalTrials.gov, NCT05920525. Registered 17 June 2023 - retrospectively registered, http://clinicaltrials.gov/study/NCT05920525?term=NCT05920525&rank=1.
The impact of mobile-assisted project-based learning on developing EFL students' speaking skills
Authors: Benlaghrissi Hassane , Ouahidi L. Meriem
Published: May 2024

Combining mobile-assisted language learning (MALL) with project-based learning (PBL) might be the potential framework for enhancing EFL learners' speaking skills. However, only a few studies have scrutinised the impact of modern technologies on project work. More importantly, investigating how MALL, as a new field within ICT with unique pedagogical affordances, and PBL can enhance learners' speaking skills is still lacking in the literature. Accordingly, this study examines how integrating MALL through mobile phones and PBL, defined as mobile-assisted project-based learning or mobile-assisted projects, improves Moroccan secondary school students’ speaking performance. A true experimental study was conducted with 91 students assigned randomly to one experimental group and two control groups. The experimental group received instruction through mobile-assisted projects over one semester. In contrast, participants in the first control group taught speaking through project-based learning, and participants in the second control group received traditional teaching. Two instruments were employed to collect data: a speaking pre- and post-test to evaluate the three groups’ oral proficiency and a 5-Likert scale survey to detect the experimental group participants’ experience and attitudes toward the implementation. Based on independent sample t tests and paired sample t tests (SPSS-26), it was found that instruction through mobile-assisted projects was considerably more effective than project-based learning and conventional teaching in enhancing learners’ overall speaking performance and sub-skills: fluency and coherence, lexical resource, grammatical range and accuracy, and pronunciation. Further, the results of the attitude post-questionnaire demonstrated a very high positive perception of the participants toward the implementation. As a result, these findings confirm the pedagogical role of combining MALL with PBL as an innovative mode of instruction in enhancing EFL learners’ speaking performance.
Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions
Authors: Choi Hye Kyu , Chen Meizi , Goldston Li Ling , Lee Ki-Bum
Published: May 2024

Central Nervous System (CNS) disorders represent a profound public health challenge that affects millions of people around the world. Diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and traumatic brain injury (TBI) exemplify the complexities and diversities that complicate their early detection and the development of effective treatments. Amid these challenges, the emergence of nanotechnology and extracellular vesicles (EVs) signals a new dawn for treating and diagnosing CNS ailments. EVs are cellularly derived lipid bilayer nanosized particles that are pivotal in intercellular communication within the CNS and have the potential to revolutionize targeted therapeutic delivery and the identification of novel biomarkers. Integrating EVs with nanotechnology amplifies their diagnostic and therapeutic capabilities, opening new avenues for managing CNS diseases. This review focuses on examining the fascinating interplay between EVs and nanotechnology in CNS theranostics. Through highlighting the remarkable advancements and unique methodologies, we aim to offer valuable perspectives on how these approaches can bring about a revolutionary change in disease management. The objective is to harness the distinctive attributes of EVs and nanotechnology to forge personalized, efficient interventions for CNS disorders, thereby providing a beacon of hope for affected individuals. In short, the confluence of EVs and nanotechnology heralds a promising frontier for targeted and impactful treatments against CNS diseases, which continue to pose significant public health challenges. By focusing on personalized and powerful diagnostic and therapeutic methods, we might improve the quality of patients.
Preoperative CT-based radiomic prognostic index to predict the benefit of postoperative radiotherapy in patients with non-small cell lung cancer: a multicenter study
Authors: Ma Zeliang , Men Yu , Liu Yunsong , Bao Yongxing , Liu Qian , Yang Xu , Wang Jianyang , Deng Lei , Zhai Yirui , Bi Nan , Wang Luhua , Hui Zhouguang
Published: May 2024

Background

The value of postoperative radiotherapy (PORT) for patients with non-small cell lung cancer (NSCLC) remains controversial. A subset of patients may benefit from PORT. We aimed to identify patients with NSCLC who could benefit from PORT.

Methods

Patients from cohorts 1 and 2 with pathological Tany N2 M0 NSCLC were included, as well as patients with non-metastatic NSCLC from cohorts 3 to 6. The radiomic prognostic index (RPI) was developed using radiomic texture features extracted from the primary lung nodule in preoperative chest CT scans in cohort 1 and validated in other cohorts. We employed a least absolute shrinkage and selection operator-Cox regularisation model for data dimension reduction, feature selection, and the construction of the RPI. We created a lymph-radiomic prognostic index (LRPI) by combining RPI and positive lymph node number (PLN). We compared the outcomes of patients who received PORT against those who did not in the subgroups determined by the LRPI.

Results

In total, 228, 1003, 144, 422, 19, and 21 patients were eligible in cohorts 1–6. RPI predicted overall survival (OS) in all six cohorts: cohort 1 (HR = 2.31, 95% CI: 1.18–4.52), cohort 2 (HR = 1.64, 95% CI: 1.26–2.14), cohort 3 (HR = 2.53, 95% CI: 1.45–4.3), cohort 4 (HR = 1.24, 95% CI: 1.01–1.52), cohort 5 (HR = 2.56, 95% CI: 0.73–9.02), cohort 6 (HR = 2.30, 95% CI: 0.53–10.03). LRPI predicted OS (C-index: 0.68, 95% CI: 0.60–0.75) better than the pT stage (C-index: 0.57, 95% CI: 0.50–0.63), pT + PLN (C-index: 0.58, 95% CI: 0.46–0.70), and RPI (C-index: 0.65, 95% CI: 0.54–0.75). The LRPI was used to categorize individuals into three risk groups; patients in the moderate-risk group benefited from PORT (HR = 0.60, 95% CI: 0.40–0.91; p = 0.02), while patients in the low-risk and high-risk groups did not.

Conclusions

We developed preoperative CT-based radiomic and lymph-radiomic prognostic indexes capable of predicting OS and the benefits of PORT for patients with NSCLC.
Biomaterials science and surface engineering strategies for dental peri-implantitis management
Authors: Yu Ya-Meng , Lu Yu-Pu , Zhang Ting , Zheng Yu-Feng , Liu Yun-Song , Xia Dan-Dan
Published: May 2024

Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.
Malignant perineurioma derived from the retroperitoneum with an aggressive clinical course: a case report
Authors: Kunugitani Ken , Ogiso Satoshi , Fujimoto Masakazu , Yoh Tomoaki , Shirai Hisaya , Okumura Shinya , Hirao Hirofumi , Ishii Takamichi , Yoshida Akihiko , Hatano Etsuro
Published: May 2024

Background

Malignant perineurioma is a rare malignant counterpart of perineurioma derived from perineural cells. Resection is the primary option for the treatment of malignant perineuriomas; however, patients often develop recurrence after resection, and effective treatment for advanced or recurrent lesions needs to be established. This report describes a 51-year-old female with a rare malignant perineurioma in the retroperitoneum, which contributing valuable insights to the literature.

Case presentation

The patient presented with abdominal distension and the imaging work-up revealed a huge hemorrhagic tumor in the retroperitoneum and obstruction of inferior vena cava by the tumor. The patient underwent surgery retrieving the tumor combined with left hemiliver and retrohepatic vena cava, which confirmed the diagnosis of a malignant perineurioma based on histopathological and immunohistochemical examination. Cancer gene panel testing identified mutations in NF2. Radiotherapy was administered for peritoneal dissemination 2 months after surgery, and the patient died from disease progression 6 months after surgery.

Conclusions

This rare case highlights the challenges in managing retroperitoneal malignant perineuriomas. The aggressive characteristics and limited treatment options for advanced malignant perineuriomas underscore the need for understanding the pathogenesis and developing effective systemic therapies. The identification of an NF2 mutation provides significant insights into potential therapeutic target.
Assessment of using different ozone-friendly R22 alternative refrigerants in residential air conditioners in a high-ambient temperature country
Authors: Sarsam Wail Sami
Published: May 2024

The performance of a vapor compression refrigeration system (VCRS)-based residential air conditioner operating in a high-ambient temperature (HAT) country was investigated using six zero-ODP (ozone depletion potential) refrigerants as replacements to R22. The non-flammable alternative refrigerants considered in the present research were R134a, R404A, R407C, R410A, R448A, and R507A. Using the basic conservation laws, the VCRS was modeled during steady-state operation and solved using engineering equation solver (EES) software. Coefficient of performance (COP), pressures and temperatures at compressor suction and discharge, Global Warming Potential (GWP), critical pressure and temperature, compressor pressure ratio, volumetric cooling capacity (VCC) specific cooling capacity (SCC), and refrigeration effect were utilized as assessment criteria for the alternative refrigerants considered. From these refrigerants, the highest values of suction pressure, discharge temperature, and condenser pressure were attained by R410A. In addition, the discharge temperatures for all refrigerants, except R134a, were all higher than their corresponding critical values, causing a quicker drop in the VCRS’s performance. As an alternative refrigerant, R407C showed the highest SCC of 141.0 kJ/kg followed directly by 139.2 and 138.0 kJ/kg for R410A and R448A, respectively. A reverse trend was found for VCC with respective values of 4722 and 3775 kJ/m3 for R410A and R448A. Lower volume flow rates and smaller-sized compressors are expected for higher VCC refrigerants. The same trend was found for the compressor’s specific work input and condenser’s specific heat transfer with values of (51.14, 46.82, and 45.38 kJ/kg) and (190.3, 187.8, and 183.4 kJ/kg) for R410A, R407C, and R448A, respectively. For applications in HAT countries, larger condenser’s specific heat transfer makes the refrigerant more applicable. Conversely, with respect to COP, refrigerant R134a with a value of 3.075 was the superior alternative followed by R448A and R407C with respective COPs of 3.042 and 3.011. Based on the overall assessment in terms of environmental obligation, COP, compressor input power, refrigerant flow rate required, and all the evaluations made in this research, refrigerant R448A was recommended as the most appropriate substitute to R22 which can effectively be used in residential air conditioners in a HAT country.