bluuebunny/crossref_metadata_2025 huggingface dataset:
EFEKTIVITAS PEMBELAJARAN MATEMATIKA MELALUI PENERAPAN MODEL KOOPERATIF TIPE TEAMS GAMES TOURNAMENTS (TGT) PADA SISWA KELAS VII.5 SMP NEGERI 3 PALLANGGA
Authors: Novianty Evi
Published: March 2022

This study is an experimental study that aims to determine the effectiveness cooperative learning model type of the Teams Games Tournament (TGT) in learning mathematics in class VII.5 students of SMP Negeri 3 Pallangga, Gowa Regency. The research design used was a one group pretest-posttest design and carried out for 6 meetings. Data collection techniques used were learning outcomes tests given to students, student activity observation sheets and teacher's ability to manage learning and student response questionnaires. The results of the descriptive analysis show that: (1) the average score of students' mathematics learning outcomes is 84.90 and is in the high category with a standard deviation of 10.89 where the lowest score obtained is 55 and the highest score is 100.00 from the ideal score of 100; (2) the average frequency of student activities in learning activities has increased; (3) student response questionnaires showed that 82.66% of students gave positive responses to TGT cooperative learning; (4). Based on the results of the study, the cooperative learning model of the Teams Games Tournament (TGT) type is effectively applied in learning mathematics in class VII students of SMP Negeri 3 Pallangga, Gowa Regency.

Keywords : Efektivitas, Experimental, dan Teams Games Tournament
Settler-Colonialism and the Diary of an Israeli Settler in the Golan Heights: The Notebooks of Izhaki Gal
Authors: Sulimani Gideon , Kletter Raz
Published: March 2022

In 1967 the Golan Heights saw a dramatic change: a hundred villages were destroyed and replaced by new Israeli settlements. We study the beginning of this settlement through the lens of settler-colonialism, using documents of the time. The settlers claim to be ‘original natives’, ‘returning’ to the land and, like other colonial settlers elsewhere, bringing culture and civilisation to a terra nullius. To justify the settlement, they create a ‘deep’ narrative that combines the ancient past and the new settlement, erasing the in-between Arab past. The settlement — and the destruction — are on-going processes. The settler appears as a young, heroic figure, who patronises the ‘Others’ as weaklings (tourists, women, etc.) and is oblivious to the tragedy of the displaced Syrian inhabitants of the Golan Heights.
Superwettable Biosensor for Disease Biomarker Detection
Authors: Yang Yun Jun , Gao Zhong Feng
Published: March 2022

Bioinspired superwettable materials have aroused wide interests in recent years for their promising application fields from service life to industry. As one kind of emerging application, the superwettable surfaces used to fabricate biosensors for the detection of disease biomarkers, especially tumor biomarkers, have been extensively studied. In this mini review, we briefly summarized the sensing strategy for disease biomarker detection based on superwettable biosensors, including fluorescence, electrochemistry, surface-enhanced Raman scattering, and visual assays. Finally, the challenges and direction for future development of superwettable biosensors are also discussed.
Injectable Photo-Crosslinked Bioactive BMSCs-BMP2-GelMA Scaffolds for Bone Defect Repair
Authors: Chai Senlin , Huang Jianhao , Mahmut Abdurahman , Wang Bin , Yao Yao , Zhang Xiaofeng , Zhuang Zaikai , Xie Chunmei , Xu Zhihong , Jiang Qing
Published: March 2022

Injectable hydrogels offer a new therapy option for irregular bone deformities. Based on gelatin methacryloyl (GelMA), bone marrow mesenchymal stem cells (BMSCs), and bone morphogenetic protein 2 (BMP2), we created a photo-crosslinked composite bioactive scaffold. The composite scaffolds had appropriate mechanical properties for stem cells adhesion and proliferation, as well as good biocompatibility and the ability to stimulate BMSCs osteogenic differentiation in vitro. The synergistic effect of BMSCs and BMP2 enabled the composite bioactive scaffold to exhibit higher osteogenic potential in vivo than scaffolds loaded alone with BMSCs or BMP2, according to imaging and histology studies. In conclusion, by promoting the osteogenic differentiation of BMSCs, the composite bioactive scaffold based on BMSCs-BMP2-GelMA has demonstrated remarkable application potential in bone regeneration and bone defects repair.
Case Report: Three-Dimensional Printing Model for Surgical Planning of Left Ventricular Aneurysm: Evolution Toward Tailoring Surgery
Authors: Carrabba Nazario , Buonamici Francesco , Furferi Rocco , Carfagni Monica , Vannini Matteo , Valenti Renato , Cerillo Alfredo Giuseppe , Marchionni Niccolò , Stefàno Pierluigi
Published: March 2022

A 59-year-old woman was admitted to the emergency department for heart failure (HF), New York Heart Association (NYHA) IV, showing an anterior, evolved myocardial infarction (MI) with a wide apical left ventricular aneurysm (LVA), ejection fraction (EF) 24%, and global longitudinal strain (GLS) −5. 5% by echo. Cardiac magnetic resonance imaging (MRI) confirmed an apical LVA without thrombus, EF 20%, and a transmural delayed enhancement in the myocardium wall. Coronarography showed a three-vessel disease with occluded proximal left anterior descending (LAD) and proximal right coronary artery (RCA). Based on the cardiac CT scan, we decided to generate a three-dimensional (3D) print model of the heart, for better prediction of residual LV volumes. After LVA surgery plus complete functional revascularization, an optimal agreement was found between predicted and surgical residual LV end-diastolic (24.7 vs. 31.8 ml/m2) and end-systolic (54.1 vs. 69.4 ml/m2) volumes, with an improvement of NYHA class, from IV to I. The patient was discharged uneventfully and at 6- and 12-month follow-up, the NYHA class, and LV volumes were found unchanged. This is a second report describing the use of the 3D print model for the preoperative planning of surgical management of LVA; the first report was described by Jacobs et al. among three patients, one with a malignant tumor and the remaining two patients with LVA. This article focused on the use of the 3D print model to optimize surgical planning and individualize treatment of LVA associated with complete functional revascularization, leading to complete recovery of LV function with a favorable outcome.
Virtual Reality in the Pediatric Intensive Care Unit: Patient Emotional and Physiologic Responses
Authors: Badke Colleen M. , Krogh-Jespersen Sheila , Flynn Rachel M. , Shukla Avani , Essner Bonnie S. , Malakooti Marcelo R.
Published: March 2022

Context

Patients in the Pediatric Intensive Care Unit (PICU) are limited in their ability to engage in developmentally typical activity. Long-term hospitalization, especially with minimal interpersonal engagement, is associated with risk for delirium and delayed recovery. Virtual reality (VR) has growing evidence as a safe, efficacious, and acceptable intervention for pain and distress management in the context of uncomfortable healthcare procedures, and for enhancing engagement in, and improving outcomes of rehabilitation therapy.

Hypothesis

Critically ill children may experience high levels of engagement and physiologic effects while engaging with VR.

Methods and Models

This cross-sectional study of 3–17-year-old children admitted to a PICU used a VR headset to deliver 360-degree immersive experiences. This study had a mixed-method approach, including standardized behavioral coding, participant and parent surveys, and participant physiologic responses. Investigators noted comments the child made about VR, observed emotional responses, and documented an engagement score. To determine physiologic response to VR, integer heart rate variability (HRVi) was collected 30 min before, during, and 30 min after VR.

Results

One hundred fifteen participants were enrolled from 6/18 to 10/19, and they interacted with VR for a median of 10 min (interquartile range 7–17). Most children enjoyed the experience; 83% of participants smiled and 36% laughed while using VR. Seventy-two percent made positive comments while using VR. The strongest age-related pattern regarding comments was that the youngest children were more likely to share the experience with others. Seventy-nine percent of participants were highly engaged with VR. Ninety-two percent of parents reported that VR calmed their child, and 78% of participants felt that VR was calming. HRVi Minimum scores were significantly higher during VR than pre- (p < 0.001) or post-VR (p < 0.001). There was no significant difference between pre-and post-VR (p = 0.387); therefore, children returned to their pre-intervention state following VR.

Interpretations and Conclusions

Children admitted to the PICU are highly engaged with and consistently enjoyed using VR. Both participants and parents found VR to be calming, consistent with intra-intervention physiologic improvements in HRVi. VR is an immersive tool that can augment the hospital environment for children.
Stress Analysis of the Effect of Additional Load on the Butt Weld of Suspended Pipeline With Variable Wall Thickness
Authors: Yingchao Fang , Dongliang Yu , Binbin Wang , Jian Xu , Heng Xuan , Hao Hou , lin Wang
Published: March 2022

Under the special geological environment of the buried pipe, the ground is lost at the bottom of the pipe, which is created by various kinds of external factors. The pipe in the suspended state would be greatly deformed due to its own weight, internal pressure, and other factors, resulting in the failure of the pipeline. When a variable wall thickness weld occurs in the suspended section of the pipeline, the change of the pipeline stress will be more complicated and changeable. In this study, ABAQUS software is used to establish a pipe–soil model of variable wall thickness butt welds of suspended pipelines. The axial stress distribution with different affected factors in the pipe, the change of curvature, and Mises stress change of the entire pipe along the axial direction are obtained by analyzing the internal pressure, wall thickness ratio, suspended length, weld position, and cone length. The results show that the stress at the root of the weld changes significantly; therefore, the weld has a greater impact on the stress of the entire pipeline. The change of internal pressure has little effect on the stress at the pipe weld. As the suspended length increases, the change in stress at the weld is more obvious. When the weld seam is close to the soil, the support of the soil will gradually shift the maximum stress position of the pipe from the top of the pipe to the bottom of the pipe. With the increase in cone length, it will reduce the sudden change of pipe section and the change in stress effectively. The places where the curvature greatly changes along the axial direction are at the pipe–soil separation and the middle of the pipeline, while the stress reaches the maximum at the pipe–soil separation, and the place with the largest stress change is the weld in the middle of the pipeline.
Decreased Internal Phosphorus Loading From Eutrophic Sediment After Artificial Light Supplement: Preliminary Evidence From a Microcosm Experiment
Authors: Zhang Miao , Li Yan , Wang Hai-Jun , Yu Ye-Xin , Liu Jia-Hao , Qiao Rui-Ting , Liu Miao , Ma Shuo-Nan , Wang Hong-Zhu
Published: March 2022

Nutrient loading reduction is an essential approach for controlling eutrophication. In addition to external nutrient loading, internal phosphorus (P) loading is usually considered one of the most important factors determining nutrient levels in water. The underwater light climate plays a pivotal role. However, few studies have been reported on the effect of light intensity on P release, and the existing studies have not drawn a definitive conclusion on whether underwater light has a positive or negative effect on P release. To confirm the effect of underwater light on internal P release, a 1-month microcosm experiment was carried out (18 November–15 December 2020) under three light intensities. The P release flux (FP) was significantly higher in the control (no light) group than in the low light group during the first 2 weeks (p = 0.03). No difference among treatments occurred for accumulative FP in the past 4 weeks, although it tended to be higher in the control than in both the low and high light groups (p > 0.05). Spearman rank correlations showed that photosynthetic photon flux density (PPFD) was positively correlated with DO, pH, phytoplankton chlorophyll a (Chl aPhyt) and benthic algae chlorophyll a (Chl aBent). DO was positively correlated with Chl aPhyt and Chl aBent. The results indicate that light may promote the growth of phytoplankton and benthic algae, both of which may increase DO and pH. DO inhibits P release from sediment and pH promotes P release from sediment. Lake-scale studies are needed to fully evaluate its effect under natural conditions, as many other factors (e.g., wind or fish disturbance) in natural lakes could regulate P release from sediment.
Response of Mixed-Phase Cloud Microphysical Properties to Cloud-Seeding Near Cloud Top Over Hebei, China
Authors: Yang Yang , Zhao Chuanfeng , Fu Jiao , Cui Yi , Dong Xiaobo , Mai Rong , Xu Feng
Published: March 2022

On November 29, 2019, an aircraft observation during the period of cloud-seeding was carried out for a mixed-phase cloud over Xingtai, Hebei Province, China. This study investigates the response of mixed-phase cloud microphysical properties to cloud-seeding near cloud top. Before cloud seeding, the cloud droplet concentration from fast cloud droplet probe (NC_FCDP) presented a multi-peak vertical distribution structure, with a maximum concentration of 192 cm−3 at a height of 3,322 m; the maximum concentration of ice crystals from cloud imaging probe (NC_CIP) was 10 L−1, which appeared at 4,500 m in the upper part of cloud; and the peak value of liquid water content (LWC) in the cloud also appeared at 4,500 m, with a value of 0.15 g/m3. The coexistence of supercooled liquid water and ice crystals implies that they are particularly suitable for cloud seeding at the height of 4,550 m. About 7–8 min later after cloud seeding at this height, the average NC_FCDP decreased from 160.3 to 129 cm−3, and the average NC_CIP increased from 7.1 to 10 L−1. Moreover, after cloud seeding, high NC_CIP as well as larger and more ice crystals appeared almost in the same areas within the cloud, and LWC presented an obvious decreasing trend. In contrast, the concentration of small cloud droplets and LWC decreased obviously after seeding. The findings suggest that the cloud microphysical properties showed obvious responses to the artificial introduction of silver iodide, which is important for human weather modification.
Which is More Effective: The Carrot or the Stick? Environmental Policy, Green Innovation and Enterprise Energy Efficiency–A Quasi-Natural Experiment From China
Authors: Wang Yuan , Hu Jiali , Hu Yi , Wang Yu
Published: March 2022

As the concept of carbon neutralization is valued, attention is paid to how environmental protection policies affect enterprises. However, little is known about how environmental policies affect enterprise energy utilization efficiency and green innovation. Based on Porter’s effectuation and deterrence theory, this paper proposes that an incentive environmental protection policy (environmental protection incentive) and punitive environmental protection policy (environmental protection regulation) have different impact mechanisms on enterprise green innovation and energy utilization efficiency. The following conclusions are drawn by using the data of listed enterprises since implementing the new environmental protection law in China and using the PSM-DID method to construct a quasi-natural experiment. 1) Environmental protection incentives are not conducive to improving energy utilization efficiency; 2) Environmental protection regulation can improve enterprise energy utilization efficiency; 3) Environmental protection incentives are not conducive to green innovation; 4) Environmental protection regulation is conducive to the green innovation of enterprises; 5) Green innovation plays a complete intermediary role in the relationship between environmental protection policies and enterprise energy utilization efficiency; 6) Different policies have heterogeneity on Enterprises: environmental protection incentives are conducive to the improvement of energy utilization efficiency of state-owned enterprises but not conducive to non-state-owned enterprises; The effect of environmental protection regulation on non-state-owned enterprises is more potent than that of state-owned enterprises. This study compares the impact of different environmental protection policies on enterprise green innovation and energy utilization efficiency and puts forward more effective and realistic targeted policy suggestions. This paper tries to understand the policy mechanism through comparison; The government has promoted green innovation and efficient and clean production by implementing policies for enterprises.
Addressing Privacy Concerns in Sharing Viral Sequences and Minimum Contextual Data in a Public Repository During the COVID-19 Pandemic
Authors: Song Lingqiao , Liu Hanshi , Brinkman Fiona S. L , Gill Erin , Griffiths Emma J. , Hsiao William W. L , Savić-Kallesøe Sarah , Moreira Sandrine , Van Domselaar Gary , Zawati Ma’n H. , Joly Yann
Published: March 2022

COVID-19 was declared to be a pandemic in March 2020 by the World Health Organization. Timely sharing of viral genomic sequencing data accompanied by a minimal set of contextual data is essential for informing regional, national, and international public health responses. Such contextual data is also necessary for developing, and improving clinical therapies and vaccines, and enhancing the scientific community’s understanding of the SARS-CoV-2 virus. The Canadian COVID-19 Genomics Network (CanCOGeN) was launched in April 2020 to coordinate and upscale existing genomics-based COVID-19 research and surveillance efforts. CanCOGeN is performing large-scale sequencing of both the genomes of SARS-CoV-2 virus samples (VirusSeq) and affected Canadians (HostSeq). This paper addresses the privacy concerns associated with sharing the viral sequence data with a pre-defined set of contextual data describing the sample source and case attribute of the sequence data in the Canadian context. Currently, the viral genome sequences are shared by provincial public health laboratories and their healthcare and academic partners, with the Canadian National Microbiology Laboratory and with publicly accessible databases. However, data sharing delays and the provision of incomplete contextual data often occur because publicly releasing such data triggers privacy and data governance concerns. The CanCOGeN Ethics and Governance Expert Working Group thus has investigated several privacy issues cited by CanCOGeN data providers/stewards. This paper addresses these privacy concerns and offers insights primarily in the Canadian context, although similar privacy considerations also exist in other jurisdictions. We maintain that sharing viral sequencing data and its limited associated contextual data in the public domain generally does not pose insurmountable privacy challenges. However, privacy risks associated with reidentification should be actively monitored due to advancements in reidentification methods and the evolving pandemic landscape. We also argue that during a global health emergency such as COVID-19, privacy should not be used as a blanket measure to prevent such genomic data sharing due to the significant benefits it provides towards public health responses and ongoing research activities.
Full-Length Transcriptome Sequences Provide Insight Into Hermaphroditism of Freshwater Pearl Mussel Hyriopsis schlegelii
Authors: Zeng Qi , Hu Beijuan , Blanco Andres Hortas , Zhang Wanchang , Zhao Daxian , Martínez Paulino , Hong Yijiang
Published: March 2022

The freshwater mussel Hyriopsis schlegelii is a cultured bivalve in China, and the quality of the pearls produced is affected by the type of gonads. However, because of the lack of a published genome and the complexity of sex determination, research on sex reversal and development of this species is limited. In this study, Illumina RNA-seq and PacBio Isoform Sequencing (Iso-Seq) were combined to analyze the gonads of H. schlegelii. A total of 201,481 high-quality transcripts were generated. The study identified 7,922 differentially expressed genes in three comparison group (females versus males, hermaphrodites versus females, and hermaphrodites versus males). Twenty-four genes were identified as potential sex-related genes, including sox9 and wnt4 involved in sex determination, and vtg, cyp17a1 and 17β-hsd2 involved in gonadal development. We also speculated a possible pathways for the formation of hermaphroditism in H. schlegelii. The data provide a clear view of the transcriptome for H. schlegelii gonads and will be valuable in elucidating the mechanisms of gonad development.
Cell-Crossing Functional Network Driven by microRNA-125a Regulates Endothelial Permeability and Monocyte Trafficking in Acute Inflammation
Authors: Müller Martin Bernhard , Hübner Max , Li Lei , Tomasi Stephanie , Ließke Valena , Effinger David , Hirschberger Simon , Pogoda Kristin , Sperandio Markus , Kreth Simone
Published: March 2022

Opening of the endothelial barrier and targeted infiltration of leukocytes into the affected tissue are hallmarks of the inflammatory response. The molecular mechanisms regulating these processes are still widely elusive. In this study, we elucidate a novel regulatory network, in which miR-125a acts as a central hub that regulates and synchronizes both endothelial barrier permeability and monocyte migration. We found that inflammatory stimulation of endothelial cells induces miR-125a expression, which consecutively inhibits a regulatory network consisting of the two adhesion molecules VE-Cadherin (CDH5) and Claudin-5 (CLDN5), two regulatory tyrosine phosphatases (PTPN1, PPP1CA) and the transcription factor ETS1 eventually leading to the opening of the endothelial barrier. Moreover, under the influence of miR-125a, endothelial expression of the chemokine CCL2, the most predominant ligand for the monocytic chemokine receptor CCR2, was strongly enhanced. In monocytes, on the other hand, we detected markedly repressed expression levels of miR-125a upon inflammatory stimulation. This induced a forced expression of its direct target gene CCR2, entailing a strongly enhanced monocyte chemotaxis. Collectively, cell-type-specific differential expression of miR-125a forms a synergistic functional network controlling monocyte trafficking across the endothelial barrier towards the site of inflammation. In addition to the known mechanism of miRNAs being shuttled between cells via extracellular vesicles, our study uncovers a novel dimension of miRNA function: One miRNA, although disparately regulated in the cells involved, directs a biologic process in a synergistic and mutually reinforcing manner. These findings provide important new insights into the regulation of the inflammatory cascade and may be of great use for future clinical applications.
Swine Interferon-Inducible Transmembrane Proteins Potently Inhibit African Swine Fever Virus Replication
Authors: Cai Siqi , Zheng Zezhong , Cheng JiaoJiao , Zhong Lintao , Shao Ran , Zheng Feiyan , Lai Zhiying , Ou Jiajun , Xu Liang , Zhou Pei , Lu Gang , Zhang Guihong
Published: March 2022

African swine fever virus (ASFV) causes an acute, hemorrhagic, and highly contagious disease in domestic swine, leading to significant economic losses to the global porcine industry. Restriction factors of innate immunity play a critical in host antiviral action. However, function of swine restriction factors of innate immunity on ASFV has been seldomly investigated. In this study, we determined five homologues of swine interferon-induced transmembrane proteins (SwIFITM [named SwIFITM1a, -1b, -2, -3, and -5]), and we found that they all exhibit potent antiviral activity against ASFV. Expression profile analysis indicated that these SwIFITMs are constitutively expressed in most porcine tissues. Whether infected with ASFV or treated with swine interferon, the expression levels of SwIFITMs were induced in vitro. The subcellular localization of SwIFITMs was similar to that of their human homologues. SwIFITM1a and -1b localized to the plasma membrane, SwIFITM2 and -3 focused on the cytoplasm and the perinuclear region, while SwIFITM5 accumulated in the cell surface and cytoplasm. The overexpression of SwIFITM1a, -1b, -2, -3, or -5 could significantly inhibit ASFV replication in Vero cells, whereas knockdown of these genes could enhance ASFV replication in PAMs. We blocked the constitutive expression of endogenous IFITMs in Vero cells using a CRISPR-Cas9 system and then infected them with ASFV. The results indicated that the knockout of endogenous IFITMs could enhance ASFV replication. Finally, we expressed five SwIFITMs in knockout Vero cell lines and then challenged them with ASFV. The results showed that all of the SwIFITMs had a strong antiviral effect on ASFV. This research will further expand the understanding of the anti-ASFV activity of porcine IFITMs.
Protein Disulfide-Isomerase A3 Is a Robust Prognostic Biomarker for Cancers and Predicts the Immunotherapy Response Effectively
Authors: Tu Zewei , Ouyang Qin , Long Xiaoyan , Wu Lei , Li Jingying , Zhu Xingen , Huang Kai
Published: March 2022

Background

Protein disulfide isomerase A3 (PDIA3) is a member of the protein disulfide isomerase (PDI) family that participates in protein folding through its protein disulfide isomerase function. It has been reported to regulate the progression of several cancers, but its function in cancer immunotherapy is unknown.

Methods

The RNA-seq data of cancer and normal tissues were downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. The Cbioportal dataset was used to explore the genomic alteration information of PDIA3 in pan-cancer. Human Protein Atlas (HPA) and ComPPI websites were employed to mine the protein information of PDIA3, and western blot assay was performed to monitor the upregulated PDIA3 expression in clinical GBM samples. The univariate Cox regression and the Kaplan–Meier method were utilized to appraise the prognostic role of PDIA3 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was applied to search the associated cancer hallmarks with PDIA3 expression. TIMER2.0 was the main platform to investigate the immune cell infiltrations related to PDIA3 in pan-cancer. The associations between PDIA3 and immunotherapy biomarkers were performed by Spearman correlation analysis. The immunoblot was used to quantify the PDIA3 expression levels, and the proliferative and invasive ability of glioma cells was determined by colony formation and transwell assays.

Findings

PDIA3 is overexpressed in most cancer types and exhibits prognosis predictive ability in various cancers, and it is especially expressed in the malignant cells and monocytes/macrophages. In addition, PDIA3 is significantly correlated with immune-activated hallmarks, cancer immune cell infiltrations, and immunoregulators, and the most interesting finding is that PDIA3 could significantly predict anti-PDL1 therapy response. Besides, specific inhibitors that correlated with PDIA3 expression in different cancer types were also screened by using Connectivity Map (CMap). Finally, knockdown of PDIA3 significantly weakened the proliferative and invasive ability of glioma cells.

Interpretation

The results revealed that PDIA3 acts as a robust tumor biomarker. Its function in protein disulfide linkage regulation could influence protein synthesis, degradation, and secretion, and then shapes the tumor microenvironment, which might be further applied to develop novel anticancer inhibitors.
Biomarkers to Predict DMARDs Efficacy and Adverse Effect in Rheumatoid Arthritis
Authors: Wei Kai , Jiang Ping , Zhao Jianan , Jin Yehua , Zhang Runrun , Chang Cen , Xu Lingxia , Xu Linshuai , Shi Yiming , Guo Shicheng , He Dongyi
Published: March 2022

Rheumatoid arthritis (RA), one of the most common immune system diseases, mainly affects middle-aged and elderly individuals and has a serious impact on the quality of life of patients. Pain and disability caused by RA are significant symptoms negatively affecting patients, and they are especially seen when inappropriate treatment is administered. Effective therapeutic strategies have evolved over the past few decades, with many new disease-modifying antirheumatic drugs (DMARDs) being used in the clinic. Owing to the breakthrough in the treatment of RA, the symptoms of patients who could not be treated effectively in the past few years have been relieved. However, some patients complain about symptoms that have not been reported, implying that there are still some limitations in the RA treatment and evaluation system. In recent years, biomarkers, an effective means of diagnosing and evaluating the condition of patients with RA, have gradually been used in clinical practice to evaluate the therapeutic effect of RA, which is constantly being improved for accurate application of treatment in patients with RA. In this article, we summarize a series of biomarkers that may be helpful in evaluating the therapeutic effect and improving the efficiency of clinical treatment for RA. These efforts may also encourage researchers to devote more time and resources to the study and application of biomarkers, resulting in a new evaluation system that will reduce the inappropriate use of DMARDs, as well as patients’ physical pain and financial burden.
Prevalence and Risk for Bundle Branch Block, Atrioventricular Block and Pacemaker Implantation in Spondyloarthritis. A Systematic Review of the Literature
Authors: Park Hye Sang , Laiz Ana , Díaz del Campo Petra , Martín Martínez María A. , Guerra-Rodriguez M. , Alonso-Martin Concepcion , Sanchez-Vega Jesus , Corominas Hector
Published: March 2022

Objective

To evaluate the evidence regarding the prevalence and risk of bundle branch block (BBB), atrioventricular block (AVB) and pacemaker implantation (PMI) in patients with spondyloarthritis compared to a control group without spondyloarthritis.

Methods

A systematic review of the literature was performed using Pubmed (Medline), EMBASE (Elsevier) and Cochrane Library (Wiley) databases until December 2021. The prevalence and risk for AVB, BBB and PMI were analyzed. Cohort, case control and cross-sectional studies in patients ≥18 years meeting the classification criteria for spondyloarthritis were included. The Odds ratio (OR), risk ratio (RR), or Hazard ratio (HR) and prevalence difference were considered as outcomes. Data was synthesized in a previously defined extraction form which included a risk of bias assessment using the Newcastle-Ottawa Scale.

Results

In total, eight out of 374 studies were included. None of the studies provided results regarding the risk of low grade AVB and BBB in SpA patients. Only indirect results comparing prevalences from low to medium quality studies were found. According to population based registries, the sex and age adjusted HR of AVB was 2.3 (95% CI 1.6–3.3) in ankylosing spondylitis, 2.9 (95% CI 1.8–4.7) in undifferentiated spondyloarthritis and 1.5 (95% CI 1.1 a 1.9) in psoriatic arthritis. The absolute risk for AVB was 0.4% (moderate to high; 95% CI 0.34%-0.69%) for AS, 0.33% (moderate to high; 95% CI 0.21%-0.53%) for uSpA and 0.34% (moderate to high; 95% CI 0.26%-0.45%) for PsA.The RR for PMI in AS patients was 1.3 (95% CI 1.16–1.46) for groups aged between 65 and 69 years, 1.33 (95% CI 1.22–1.44) for 70–75 years, 1.24 (95% CI 1.55–1.33) for 75–79 years and 1.11 (95% CI 1.06–1.17) for groups older than 80 years. The absolute risk for PMI in AS patients was 0.7% (moderate to high risk; 95% CI 0.6–0.8%) for groups aged between 65–69, 1.44% (high risk; 95% CI 1.33–1.6%) for 70–75 years, 2.09% (high risk; 95% CI 2.0–2.2%) for 75–79 years and 4.15% (high risk; 95% CI 4.0–4.3%) for groups older than 80 years

Conclusions

Very few cases of low grade AVB and BBB were observed in observational studies. No study evaluated association measures for low grade AVB and BBB but the differences of prevalence were similar in SpA and control groups even though studies lacked the power to detect statistical differences. According to population based registries there was an approximately two fold-increased risk of high grade AVB in SpA patients. RR for PMI was higher in younger age groups.
Cronkhite-Canada Syndrome Associated With Superficial Esophageal Carcinoma: A Case Report and Literature Review
Authors: Zhao Yan , Lv Fujing , Yang Xun , Wang Yongjun , Zhang Shutian , Li Peng
Published: March 2022

Introduction

Cronkhite-Canada syndrome is a rare disease characterized by generalized gastrointestinal polyposis, alopecia, skin pigmentation, and onychotrophia with no generally recognized mechanism of pathogenesis. There is a tendency of malignant transformation or coexistence of gastrointestinal malignancies in patients with Cronkhite-Canada syndrome.

Case Description

The patient was a 67-year-old man who complained of dyspepsia, hair loss, skin hyperpigmentation, and pedal edema. Lab tests showed hypoalbuminemia. Endoscopic findings included superficial esophageal carcinoma and numerous polyps in the stomach, duodenum, and colon. The patient was treated with endoscopic submucosal dissection for the esophagus lesion, endoscopic mucosal resection for colon polyps, and glucocorticoids for Cronkhite-Canada syndrome.

Conclusion

Esophagus cancer is a rare comorbidity of Cronkhite-Canada syndrome. Endoscopic examination and surveillance are critical for patients with Cronkhite-Canada syndrome for malignant gastrointestinal tumors.
Sleep Facilitates Extraction of Temporal Regularities With Varying Timescales
Authors: Lerner Itamar , Gluck Mark A.
Published: March 2022

Evidence suggests that memory consolidation is facilitated by sleep, both through the strengthening of existing memories and by extracting regularities embedded in those memories. We previously observed that one sleep stage, Slow-Wave sleep (SWS), is particularly involved in the extraction of temporal regularities. We suggested that this attribute can naturally stem from the time-compressed memory replay known to occur in the hippocampus during SWS. A prediction coming out of this “temporal scaffolding” hypothesis is that sleep would be especially influential on extraction of temporal regularities when the time gap between the events constituting the regularities is shortish. In this study, we tested this prediction. Eighty-three participants performed a cognitive task in which hidden temporal regularities of varying time gaps were embedded. Detecting these regularities could significantly improve performance. Participants performed the task in two sessions with an interval filled with either wake or sleep in between. We found that sleep improved performance across all time gaps and that the longer the gap had been, the smaller was the improvement across both sleep and wake. No interaction between sleep and gap size was observed; however, unlike sleeping participants, awake participants did not exhibit any further performance improvement for the long gaps following the interval. In addition, across all participants, performance for the long gaps was associated with the development of conscious awareness to the regularities. We discuss these results in light of the temporal scaffolding hypothesis and suggest future directions to further elucidate the mechanisms involved.
The Effects of CPAP Treatment on Resting-State Network Centrality in Obstructive Sleep Apnea Patients
Authors: Li Panmei , Shu Yongqiang , Liu Xiang , Kong Linghong , Li Kunyao , Xie Wei , Zeng Yaping , Li Haijun , Peng Dechang
Published: March 2022

Background and Objectives

Obstructive sleep apnea (OSA) is the most common sleep disorder and previous studies have shown that OSA patients suffer from brain network impairments associated with cognitive deficits, and continuous positive airway pressure (CPAP) treatment can improve clinical symptoms. However, the relationship between CPAP treatment and brain network changes remains unclear. This study explored the characteristics of brain network changes in OSA patients before (pre-CPAP) and after one month of CPAP treatment (post-CPAP).

Methods

We collected data, including sleep monitoring, clinical assessment, and magnetic resonance imaging scans, from 21 OSA patients and 21 age-matched healthy controls (HCs). Voxel-level degree centrality (DC) was used to assess whole-brain network connectivity characteristics, a two-sample t-test was used to compare network differences between pre-CPAP OSA patients and HCs, and a paired sample t-test was used to compare the characteristics of brain network changes in OSA patients before and after treatment. The correlations between the DC value and each of the clinical variables were analyzed in the OSA patients.

Results

Compared with HCs, pre-CPAP OSA patients showed increased DC values in the bilateral cerebellar posterior lobes (CPLs) and decreased DC values in the right superior temporal gyrus, left superior frontal gyrus and right middle frontal gyrus. Compared with pre-CPAP OSA patients, post-CPAP OSA patients showed reduced DC values in the bilateral CPL and increased DC values in several brain regions in the frontal, temporal, and insular lobes after CPAP treatment. The Montreal Cognitive Assessment MoCA (MoCA) scores were positively correlated with the DC value of the bilateral cerebellum posterior lobe, right middle temporal gyrus, left superior temporal gyrus, left paracentral lobule and left paracentral lobule. Also, Pittsburgh Sleep Quality Index (PSQI) scores were negatively correlated with the DC value of the right middle temporal gyrus in post-CPAP OSA patients.

Conclusion

CPAP treatment can effectively reverse the compensatory response of the bilateral CPL and functional network damage brought about by OSA, which may provide potential neuroimaging biomarkers for CPAP treatment evaluation.
Prognostic Evaluation of Metastasis-Related Lymphocyte/Monocyte Ratio in Stage Ⅰ-Ⅲ Breast Cancer Receiving Chemotherapy
Authors: Zhang Zihan , Lin Qian , Chen Yi , Su Chenlin , Lin Wuye , Wei Daoyu , Zhang Litu , Liu Haizhou
Published: March 2022

Purpose

This study aims to clarify the prognostic significance of metastasis-related indicators in peripheral blood in stage I-III breast cancer (BC).

Methods

The clinicopathological data of 938 breast cancer patients and 509 benign breast disease patients were retrospectively analyzed, and fasting blood samples were collected before treatment. Univariate and multivariate regression analyses were used to evaluate factors related to metastasis risk and prognosis. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was used to measure differences in survival between groups.

Results

Use the cut-off value (3.433) of LMR, the logistic regression analysis revealed that high carbohydrate antigen 153 (CA153), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), killer T cell level, and low lymphocyte to monocyte ratio (LMR) level were significantly associated with BC distant metastasis. In contrast, LMR>=3.433 (HR: 0.409, 95%CI: 0.193–0.867, P = 0.020), Th/Tc ratio >=1.946 (HR: 0.378, 95% CI: 0.158–0.904, P =0.029) is regarded as a protective factor in the multivariate cox analyses. LMR is an independent prognostic factor for DFS in HER2-negative BC patients.

Conclusion

Peripheral blood parameters play an important role in predicting distant metastasis and prognosis of BC patients. As a potential marker, LMR can predict the metastasis and prognosis of patients with stage I-III BC.
Novel Ex Vivo Models of Epithelial Ovarian Cancer: The Future of Biomarker and Therapeutic Research
Authors: Clark James , Fotopoulou Christina , Cunnea Paula , Krell Jonathan
Published: March 2022

Epithelial ovarian cancer (EOC) is a heterogenous disease associated with variations in presentation, pathology and prognosis. Advanced EOC is typified by frequent relapse and a historical 5-year survival of less than 30% despite improvements in surgical and systemic treatment. The advent of next generation sequencing has led to notable advances in the field of personalised medicine for many cancer types. Success in achieving cure in advanced EOC has however been limited, although significant prolongation of survival has been demonstrated. Development of novel research platforms is therefore necessary to address the rapidly advancing field of early diagnostics and therapeutics, whilst also acknowledging the significant tumour heterogeneity associated with EOC. Within available tumour models, patient-derived organoids (PDO) and explant tumour slices have demonstrated particular promise as novel ex vivo systems to model different cancer types including ovarian cancer. PDOs are organ specific 3D tumour cultures that can accurately represent the histology and genomics of their native tumour, as well as offer the possibility as models for pharmaceutical drug testing platforms, offering timing advantages and potential use as prospective personalised models to guide clinical decision-making. Such applications could maximise the benefit of drug treatments to patients on an individual level whilst minimising use of less effective, yet toxic, therapies. PDOs are likely to play a greater role in both academic research and drug development in the future and have the potential to revolutionise future patient treatment and clinical trial pathways. Similarly, ex vivo tumour slices or explants have also shown recent renewed promise in their ability to provide a fast, specific, platform for drug testing that accurately represents in vivo tumour response. Tumour explants retain tissue architecture, and thus incorporate the majority of tumour microenvironment making them an attractive method to re-capitulate in vivo conditions, again with significant timing and personalisation of treatment advantages for patients. This review will discuss the current treatment landscape and research models for EOC, their development and new advances towards the discovery of novel biomarkers or combinational therapeutic strategies to increase treatment options for women with ovarian cancer.
Construction and Validation of Convenient Clinicopathologic Signatures for Predicting the Prognosis of Stage I-III Gastric Cancer
Authors: You Weiqiang , Cai Zerong , Sheng Nengquan , Yan Li , Wan Huihui , Wang Yongkun , Ouyang Jian , Xie Lu , Wu Xiaojian , Wang Zhigang
Published: March 2022

Background

Patients with stage I-III gastric cancer (GC) undergoing R0 radical resection display extremely different prognoses. How to discriminate high-risk patients with poor survival conveniently is a clinical conundrum to be solved urgently.

Methods

Patients with stage I-III GC from 2010 to 2016 were included in our study. The associations of clinicopathological features with disease-free survival (DFS) and overall survival (OS) were examined via Cox proportional hazard model. Nomograms were developed which systematically integrated prognosis-related features. Kaplan–Meier survival analysis was performed to compare DFS and OS among groups. The results were then externally validated by The Sixth Affiliated Hospital, Sun Yat-sen University.

Results

A total of 585 and 410 patients were included in the discovery cohort and the validation cohort, respectively. T stage, N stage, lymphatic/vascular/nerve infiltration, preoperative CEA, and CA19-9 were independent prognostic factors (P < 0.05). Two prognostic signatures with a concordance index (C-index) of 0.7502 for DFS and 0.7341 for OS were developed based on the nomograms. The 3-year and 5-year calibration curves showed a perfect correlation between predicted and observed outcomes. Patients were divided into three risk groups (low, intermediate, high), and distinct differences were noticed (p < 0.001). Similar results were achieved in the validation cohort. Notably, a free website was constructed based on our signatures to predict the recurrence risk and survival time of patients with stage I-III GC.

Conclusions

The signatures demonstrate the powerful ability to conveniently identify distinct subpopulations, which may provide significant suggestions for individual follow-up and adjuvant therapy.
Dosimetric Evaluation and Clinical Application of Radioactive Iodine-125 Brachytherapy Stent in the Treatment of Malignant Esophageal Obstruction
Authors: Ji Zhe , Yuan Qianqian , Lin Lei , Xing Chao , Zhang Xusheng , Yang Sen , Jiang Yuliang , Sun Haitao , Zhang Kaixian , Wang Junjie
Published: March 2022

Objective

To evaluate the dosimetric characteristics and the clinical application of radioactive iodine-125 brachytherapy stent (RIBS) in malignant esophageal obstruction.

Methods

The dose distribution of RIBS with different seed spacing, diameter and length was studied by treatment planning system (TPS) calculation, thermoluminescence dosimeter (TLD) measurement and Monte Carlo (MC) data fitting. And the data of esophageal cancer patients who were treat with this type of RIBS was analyzed retrospectively.

Results

Doses around the RIBS calculated by the TPS lay between those measured by the TLDs and those simulated by the MC, and the differences between the three methods were significant (p<0.05), the overall absolute dose differences among the three methods were small. Dose coverage at 1.5 cm from the center was comprehensive when the activity reached 0.6 mCi. Both the conformability and the uniformity of isodose lines produced by a seed spacing of 1.0 cm were superior to those produced by a seed spacing of 1.5 cm. The data of 50 patients treated with RIBS was analyzed. They were followed up until February 2020 when all of the patients died. The overall improvement rate of dysphagia after RIBS implant was 90%. Moderate and severe complications with an incidence of more than 10% were hematemesis (28%), pain (20%), and lung infection (10%). Stent restenosis occurred in 4 patients at a median interval of 108 days from the procedure. The overall incidence of fatal complications was 38% (including hematemesis, infection and asphyxia). The median survival time of patients with and without a history of radiotherapy were 3.4 months and 6 months, respectively, the difference of which was significant (p=0.021). No other factors affecting survival were identified. For patients with and without a history of radiotherapy, the incidences of fatal complications were 51.7% and 19%, respectively (p=0.019). No correlation between dose and stent restenosis was found.

Conclusion

TPS calculations are suitable for clinical applications. RIBS can effectively alleviate obstructive symptoms for patients with malignant esophageal obstruction, but the incidence of fatal complications was high, care should be taken when choosing this treatment.