bluuebunny/crossref_metadata_2025 huggingface dataset:
MNDA expression and its value in differential diagnosis of B-cell non-Hodgkin lymphomas: a comprehensive analysis of a large series of 1293 cases
Authors: Zhang Li-Fen , Zhang Yan , Shui Rou-Hong , Lu Hong-Fen , Jiang Wen-Hua , Cai Xu , Li Xiao-Qiu , Yu Bao-Hua
Published: April 2024

Aims

MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgkin lymphomas (B-NHLs) and its clinicopathologic relevance in diffuse large B-cell lymphoma (DLBCL) are ambiguous. We comprehensively investigated MNDA expression in a large series of B-NHLs and evaluated its diagnostic value.

Methods

MNDA expression in a cohort of 1293 cases of B-NHLs and 338  cases of reactive lymphoid hyperplasia (RLH) was determined using immunohistochemistry and compared among different types of B-NHL. The clinicopathologic relevance of MNDA in DLBCL was investigated.

Results

MNDA was highly expressed in MZLs (437/663, 65.9%), compared with the confined staining in marginal zone B-cells in RLH; whereas neoplastic cells with plasmacytic differentiation lost MNDA expression. MNDA expression was significantly higher in mantle cell lymphoma (MCL, 79.6%, p = 0.006), whereas lower in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, 44.8%, p = 0.001) and lymphoplasmacytic lymphoma (LPL, 25%, p = 0.016), and dramatically lower in follicular lymphoma (FL, 5.2%, p < 0.001), compared with MZL. 29.6% (63/213) of DLBCLs were positive for MNDA. The cases in non-GCB group exhibited a higher rate of MNDA positivity (39.8%) compared to those in GCB group (16.3%) (p < 0.001), and MNDA staining was more frequently observed in DLBCLs with BCL2/MYC double-expression (50%) than those without BCL2/MYC double-expression (24.8%) (p = 0.001). Furthermore, there was a significant correlation between MNDA and CD5 expression in DLBCL (p = 0.036).

Conclusions

MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated.
Assessment of a novel electrochemically deposited smart bioactive trabecular coating (SBTC®): a randomized controlled clinical trial
Authors: Antal Mark Adam , Kiscsatári Ramóna , Braunitzer Gábor , Piffkó József , Varga Endre , Eliaz Noam
Published: April 2024

Objectives

A randomized controlled clinical trial of dental implants was conducted to compare the clinical properties of a novel electrochemically deposited calcium phosphate coating to those of a common marketed surface treatment.

Material and methods

Forty implants of the same brand and type were placed in 20 fully edentulous participants requiring mandibular implantation. The two study groups were defined by the surface treatment of the implants. 20 implants in the control group were coated via a commercial electrochemical surface treatment that forms a mixture of brushite and hydroxyapatite, while the remaining 20 in the test group were coated with a novel electrochemical Smart Bioactive Trabecular Coating (SBTC®). A split-mouth design was employed, with each participants receiving one control implant in one mandibular side and a test implant in the other. To mitigate potential operator-handedness bias, control and test implants were randomly assigned to mandibular sides. All cases underwent digital planning, implant placement with a static surgical guide, and participants received locator-anchored full-arch dentures. The primary outcome was implant stability (measured using Osstell ISQ) assessed at insertion, loading, and then 3 months, 9 months, and 2 years post-insertion. The secondary outcome was bone level change (in millimeters) over the 2-year observation period. Oral health-related quality of life (OHRQL) was monitored using the OHIP-14 questionnaire. Complications and adverse events were recorded.

Results

Successful osseointegration and implant stability were achieved in all cases, allowing loading. ISQ values steadily increased throughout the observation period. While no significant differences were observed between the SBTC® and control coatings, the test group exhibited a higher ISQ gain. Bone resorption was somewhat lower in the SBTC® but not significantly so. Patients' OHRQL significantly improved after denture delivery and remained stable throughout the follow-up. No complications or adverse events were observed.

Conclusions

Based on the study results, we conclude that the new surface treatment is a safe alternative to the widely used control surface, demonstrating similar osseointegrative properties and time-dependent bone level changes. Further research may explore the broader implications of these findings.

Trial registration

The study is registered on clinicaltrials.gov under the identifier ID: NCT06034171.
Clinical outcome of a branch-first approach with a novel continuous whole-brain perfusion strategy for total arch surgery
Authors: Zhao Zezheng , Chi Haitao , Chen Lei , Wang Junhui , Xiao Cangsong
Published: April 2024

Background

Cerebral protection strategies have been investigated since the introduction of aortic arch surgery and have been modified over the centuries. However, the cerebral protective effects of unilateral and bilateral antegrade cerebral perfusion are similar, with opportunities for further improvement.

Methods

A total of 30 patients who underwent total arch surgery were enrolled in this study. Patients were assigned to the novel continuous whole-brain or unilateral antegrade cerebral perfusion group according to the cerebral perfusion technique used. Preoperative clinical data and 1-year postoperative follow-up data were collected and analyzed.

Results

There were no significant differences between the two groups in terms of the incidence of permanent neurological deficit, mortality, or therapeutic efficacy. However, the incidence of temporary neurological dysfunction in the novel whole-brain perfusion group was significantly lower than that in the unilateral antegrade cerebral perfusion group.

Conclusions

In this study, the branch-first approach with a novel whole-brain perfusion strategy had no obvious disadvantages compared with unilateral antegrade cerebral perfusion in terms of cerebral protection and surgical safety. These findings suggest that this new technique is feasible and has application value for total arch surgery.
Diagnostic value of the creatine kinase-MB/creatine kinase and neutrophil/lymphocyte ratios in acute myocardial infarction
Authors: Liu Yin , Tang Xiao-Lei , Ni Yong , Duan Li-Zhong , Jing Feng-Jun
Published: April 2024

Objective

To investigate the clinical significance of the creatine kinase (CK)-MB/total CK ratio, neutrophil/lymphocyte ratio (NLR) and red blood cell distribution width in acute myocardial infarction (AMI).

Methods

A retrospective analysis was conducted of 196 AMI cases from our hospital’s cardiology department; healthy people were selected over the same period as the control. The two groups’ test indexes were compared through multivariate logistic regression analysis to screen for AMI risk factors; the receiver operating characteristic (ROC) curve was used to evaluate their AMI predictive values.

Results

The serum CK, CK-MB, CK index, neutrophils and NLR values in the AMI group were significantly higher compared with those in the control group (p < 0.05); however, the levels of serum lymphocytes were significantly lower compared with those in the control group (p < 0.05). Multivariate logistic regression analysis showed that elevated CK-MB and NLR levels were risk factors for AMI (p < 0.05). The ROC curve showed that the area under the curve of the NLR and CK levels were 0.917 and 0.594, respectively.

Conclusion

The CK index and NLR have a clinical predicting value for AMI and could be used as a clinical auxiliary diagnostic index for the assessment of patients with AMI.
Unusual cerebral intraventricular hemorrhage and cardiomyopathy related to congenital cytomegalovirus from non-primary maternal infection: a case report
Authors: Malherbe Victoria , Celen Stefanie , Carkeek Katherine , Carapancea Evelina , Auriti Cinzia , Piersigilli Fiammetta
Published: April 2024

Background

Congenital cytomegalovirus (cCMV) infection, resulting from non-primary maternal infection or reactivation during pregnancy, can cause serious fetal abnormalities, complications in the immediate neonatal period, and severe sequelae later in childhood. Maternal non-primary cytomegalovirus infection in pregnancy is transmitted to the fetus in 0.5-2% of cases (1).

Case presentation

An African full term male newbornwas delivered by emergency caesarean section. Due to signs of asphyxia at birth and clinical moderate encephalopathy, he underwent therapeutic hypothermia. Continuous full video-electroencephalography monitoring showed no seizures during the first 72 h, however, soon after rewarming, he presented refractory status epilepticus due to an intracranial hemorrhage, related to severe thrombocytopenia. The patient also presented signs of sepsis (hypotension and signs of reduced perfusions). An echocardiography revealed severe cardiac failure with an ejection fraction of 33% and signs suggestive of cardiomyopathy. Research for CMV DNA Polymerase Chain Reaction (PCR) on urine, blood, cerebrospinal fluid, and nasopharyngeal secretions was positive.The mother had positive CMV IgG with negative IgM shortly before pregnancy. Serology for CMV was therefore not repeated during pregnancy, but CMV DNA performed on the Guthrie bloodspot taken at birth yielded a positive result, confirming the intrauterine transmission and congenital origin of the infection. The baby was discharged in good general condition and follow up showed a normal neurodevelopmental outcome at 9 months.

Conclusion

Although uncommon, congenital cytomegalovirus infection should be included in the differential diagnosis of intraventricular hemorrhage and cardiomyopathy. Furthermore, this case highlights the possible severity of congenital cytomegalovirus infection, even in cases of previous maternal immunity.
Synthesis, characterization, and antibacterial activity studies of two Co(II) complexes with 2-[(E)-(3-acetyl-4-hydroxyphenyl)diazenyl]-4-(2-hydroxyphenyl)thiophene-3-carboxylic acid as a ligand
Authors: Sopbué Fondjo Emmanuel , Songmi Feuze Sorelle , Tamokou Jean-de-Dieu , Tsopmo Apollinaire , Doungmo Giscard , Friedrich Wilhelm Peter Simon , Feugap Tsamo Donald Léonel , Lenta Ndjakou Bruno , Kuiate Jules Roger
Published: April 2024

Two new Cobalt(II) complexes 12 and 13 have been synthesized from 2-[(E)-(3-acetyl-4-hydroxyphenyl)diazenyl]-4-(2-hydroxyphenyl)thiophene-3-carboxylic acid (11) as a novel ligand. These three new compounds were characterized on the basis of their powder X-Ray Diffraction, UV–Vis, IR, NMR, elemental analysis and MS spectral data. DFT/B3LYP mode of calculations were carried out to determine some theorical parameters of the molecular structure of the ligand. The purity of the azoic ligand and the metal complexes were ascertained by TLC and melting points. The analysis of the IR spectra of the polyfunctionalized azo compound 11 and its metal complexes 12 and 13, reveals that the coordination patterns of the ligand are hexadentate and tetradentate respectively. Based on the UV–Vis electronic spectral data and relevant literature reports, the ligand and derived complexes were assigned the E (trans) isomer form. Likewise, octahedral and square-planar geometries were respectively assigned to the cobalt(II) complexes. The broth microdilution method was used for antibacterial assays through the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The ligand 11 displayed moderate antibacterial activity (MIC = 32–128 μg/mL) against Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Pseudomonas aeruginosa and Klebsiella pneumoniae 22. The octahedral cobalt(II) complex 12 showed moderate activity against Pseudomonas aeruginosa (MIC = 128 μg/mL) and Klebsiella pneumoniae 22 (MIC = 64 μg/mL) and none against Staphylococcus aureus ATCC25923 and Escherichia coli ATCC25922, whereas the square-planar complex 13 displayed moderate activity only on Klebsiella pneumoniae 22 (MIC = 64 μg/mL).

Graphical abstract
Pathophysiology characterization of Alzheimer’s disease in South China’s aging population: for the Greater-Bay-Area Healthy Aging Brain Study (GHABS)
Authors: Liu Zhen , Shi Dai , Cai Yue , Li Anqi , Lan Guoyu , Sun Pan , Liu Lin , Zhu Yalin , Yang Jie , Zhou Yajing , Guo Lizhi , Zhang Laihong , Deng Shuqing , Chen Shuda , Yu Xianfeng , Chen Xuhui , Zhao Ruiyue , Wang Qingyong , Ran Pengcheng , Xu Linsen , Zhou Liemin , Sun Kun , Wang Xinlu , Peng Qiyu , Han Ying , Guo Tengfei
Published: April 2024

Introduction

The Guangdong-Hong Kong-Macao Greater-Bay-Area of South China has an 86 million population and faces a significant challenge of Alzheimer’s disease (AD). However, the characteristics and prevalence of AD in this area are still unclear due to the rarely available community-based neuroimaging AD cohort.

Methods

Following the standard protocols of the Alzheimer’s Disease Neuroimaging Initiative, the Greater-Bay-Area Healthy Aging Brain Study (GHABS) was initiated in 2021. GHABS participants completed clinical assessments, plasma biomarkers, genotyping, magnetic resonance imaging (MRI), β-amyloid (Aβ) positron emission tomography (PET) imaging, and tau PET imaging. The GHABS cohort focuses on pathophysiology characterization and early AD detection in the Guangdong-Hong Kong-Macao Greater Bay Area. In this study, we analyzed plasma Aβ42/Aβ40 (A), p-Tau181 (T), neurofilament light, and GFAP by Simoa in 470 Chinese older adults, and 301, 195, and 70 had MRI, Aβ PET, and tau PET, respectively. Plasma biomarkers, Aβ PET, tau PET, hippocampal volume, and temporal-metaROI cortical thickness were compared between normal control (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia groups, controlling for age, sex, and APOE-ε4. The prevalence of plasma A/T profiles and Aβ PET positivity were also determined in different diagnostic groups.

Results

The aims, study design, data collection, and potential applications of GHABS are summarized. SCD individuals had significantly higher plasma p-Tau181 and plasma GFAP than the NC individuals. MCI and dementia patients showed more abnormal changes in all the plasma and neuroimaging biomarkers than NC and SCD individuals. The frequencies of plasma A+/T+ (NC; 5.9%, SCD: 8.2%, MCI: 25.3%, dementia: 64.9%) and Aβ PET positivity (NC: 25.6%, SCD: 22.5%, MCI: 47.7%, dementia: 89.3%) were reported.

Discussion

The GHABS cohort may provide helpful guidance toward designing standard AD community cohorts in South China. This study, for the first time, reported the pathophysiology characterization of plasma biomarkers, Aβ PET, tau PET, hippocampal atrophy, and AD-signature cortical thinning, as well as the prevalence of Aβ PET positivity in the Guangdong-Hong Kong-Macao Greater Bay Area of China. These findings provide novel insights into understanding the characteristics of abnormal AD pathological changes in South China’s older population.
A Hierarchical Bayesian approach to small area estimation of health insurance coverage in Ethiopian administrative zones for better policies and programs
Authors: Shiferaw Yegnanew A. , Yilema Seyifemickael Amare , Moyehodie Yikeber Abebaw
Published: April 2024

Sample surveys are extensively used to provide reliable direct estimates for large areas or domains with enough sample sizes at national and regional levels. However, zones are unplanned domains by the Demographic and Health Survey (DHS) program and need more sample sizes to produce direct survey estimates with adequate precision. Conducting surveys in small areas (like zones) is too expensive and time-consuming, making it unfeasible for developing countries like Ethiopia. Therefore, this study aims to use the Hierarchical Bayes (HB) Small Area Estimation (SAE) model to estimate the Community-Based Health Insurance (CBHI) coverage at the zone levels in Ethiopia. To achieve this, we combined the 2019 Ethiopia Mini-Demographic and Health Survey (EMDHS) data with the 2007 population census data. SAE has addressed the challenge of producing reliable parameter estimates for small or even zero sample sizes across Ethiopian zones by utilizing auxiliary information from the population census. The results show that model-based estimates generated by the SAE approach are more accurate than direct survey estimates of CBHI. A map of CBHI scheme coverage was also used to visualize the spatial variation in the distribution of CBHI scheme coverage. From the CBHI scheme coverage map, we noticed notable variations in CBHI scheme coverage across Ethiopian zones. Additionally, this research identified areas with high and low CBHI scheme coverage to improve decision-making and increase coverage in Ethiopia. One of the novelties of this paper is estimating the non-sampled zones; therefore, the policymakers will give equal attention similar to the sampled zones.
Implementation of an antimicrobial stewardship program for urinary tract infections in long-term care facilities: a cluster-controlled intervention study
Authors: König Elisabeth , Kriegl Lisa , Pux Christian , Uhlmann Michael , Schippinger Walter , Avian Alexander , Krause Robert , Zollner-Schwetz Ines
Published: April 2024

Background

Widespread inappropriate use of antimicrobial substances drives resistance development worldwide. In long-term care facilities (LTCF), antibiotics are among the most frequently prescribed medications. More than one third of antimicrobial agents prescribed in LTCFs are for urinary tract infections (UTI). We aimed to increase the number of appropriate antimicrobial treatments for UTIs in LTCFs using a multi-faceted antimicrobial stewardship intervention.

Methods

We performed a non-randomized cluster-controlled intervention study. Four LTCFs of the Geriatric Health Centers Graz were the intervention group, four LTCFs served as control group. The main components of the intervention were: voluntary continuing medical education for primary care physicians, distribution of a written guideline, implementation of the project homepage to distribute guidelines and videos and onsite training for nursing staff. Local nursing staff recorded data on UTI episodes in an online case report platform. Two blinded reviewers assessed whether treatments were adequate.

Results

326 UTI episodes were recorded, 161 in the intervention group and 165 in the control group. During the intervention period, risk ratio for inadequate indication for treatment was 0.41 (95% CI 0.19–0.90), p = 0.025. In theintervention group, the proportion of adequate antibiotic choices increased from 42.1% in the pre-intervention period, to 45.9% during the intervention and to 51% in the post-intervention period (absolute increase of 8.9%). In the control group, the proportion was 36.4%, 33.3% and 33.3%, respectively. The numerical difference between intervention group and control group in the post-intervention period was 17.7% (difference did not reach statistical significance). There were no significant differences between the control group and intervention group in the safety outcomes (proportion of clinical failure, number of hospital admissions due to UTI and adverse events due to antimicrobial treatment).

Conclusions

An antimicrobial stewardship program consisting of practice guidelines, local and web-based education for nursing staff and general practitioners resulted in a significant increase in adequate treatments (in terms of decision to treat the UTI) during the intervention period. However, this difference was not maintained in the post-intervention phase. Continued efforts to improve the quality of prescriptions further are necessary.

Trial registration

The trial was registered at ClinicalTrials.gov NCT04798365.
Assessment of urban greenhouse gas emissions towards reduction planning and low-carbon city: a case study of Montreal, Canada
Authors: Pashaei Shadnoush , An Chunjiang
Published: April 2024

Greenhouse gases (GHGs) can be produced from a broad range of anthropogenic activities at different spatial and temporal scales. In particular, emissions from urban area are an import source of GHGs. City is a complicated system consisting of various component and processes. Efforts have been made to reduce urban GHG emissions. However, there is a lack of available methods for effective assessment of such emissions. Many urban sources and factors which can influence the emissions are still unknown. In the present study, the GHG emissions from municipal activities was assessed. A model for the assessment of urban GHG emissions was developed. Based on the collected data, a case study was conducted to evaluate urban GHG emissions. The comprehensive assessment included the emissions from transportation, electricity consumption, natural gas, waste disposal, and wastewater treatment. There was a variation for GHG emissions from these sectors in different years. This study provided a new approach for comprehensive evaluation of urban GHG emissions. The results can help better understand the emission process and identify the major emission sources.
A Fab of trastuzumab to treat HER2 overexpressing breast cancer brain metastases
Authors: Angeli Eurydice , Paris Justine , Le Tilly Olivier , Desvignes Céline , Gapihan Guillaume , Boquet Didier , Pamoukdjian Frédéric , Hamdan Diaddin , Rigal Marthe , Poirier Florence , Lutomski Didier , Azibani Feriel , Mebazaa Alexandre , Herbet Amaury , Mabondzo Aloïse , Falgarone Géraldine , Janin Anne , Paintaud Gilles , Bousquet Guilhem
Published: April 2024

Despite major therapeutic advances for two decades, including the most recently approved anti-HER2 drugs, brain metastatic localizations remain the major cause of death for women with metastatic HER2 breast cancer. The main reason is the limited drug passage of the blood-brain barrier after intravenous injection and the significant efflux of drugs, including monoclocal antibodies, after administration into the cerebrospinal fluid. We hypothesized that this efflux was linked to the presence of a FcRn receptor in the blood-brain barrier. To overcome this efflux, we engineered two Fab fragments of trastuzumab, an anti-HER2 monoclonal antibody, and did a thorough preclinical development for therapeutic translational purpose. We demonstrated the safety and equal efficacy of the Fabs with trastuzumab in vitro, and in vivo using a patient-derived xenograft model of HER2 overexpressing breast cancer. For the pharmacokinetic studies of intra-cerebrospinal fluid administration, we implemented original rat models with catheter implanted into the cisterna magna. After intraventricular administration in rats, we demonstrated that the brain-to-blood efflux of Fab was up to 10 times lower than for trastuzumab, associated with a two-fold higher brain penetration compared to trastuzumab. This Fab, capable of significantly reducing brain-to-blood efflux and enhancing brain penetration after intra-cerebrospinal fluid injection, could thus be a new and original effective drug in the treatment of HER2 breast cancer brain metastases, which will be demonstrated by a phase I clinical trial dedicated to women in resort situations.

Graphical Abstract
Mutations and intron polymorphisms in voltage-gated sodium channel genes of different geographic populations of Culex pipiens pallens/Culex pipiens quinquefasciatus in China
Authors: Li Wenyu , Ma Delong , Mu Qunzheng , Zhou Xinxin , Hua Dongdong , Zhao Chunchun , Liu Qiyong , Wang Jun , Meng Fengxia
Published: April 2024

Background

Culex pipiens pallens and Culex pipiens quinquefasciatus are the dominant species of Culex mosquitoes in China and important disease vectors. Long-term use of insecticides can cause mutations in the voltage-gated sodium channel (vgsc) gene of mosquitoes, but little is known about the current status and evolutionary origins of vgsc gene in different geographic populations. Therefore, this study aimed to determine the current status of vgsc genes in Cx. p. pallens and Cx. p. quinquefasciatus in China and to investigate the evolutionary inheritance of neighboring downstream introns of the vgsc gene to determine the impact of insecticides on long-term evolution.

Methods

Sampling was conducted from July to September 2021 in representative habitats of 22 provincial-level administrative divisions in China. Genomic DNA was extracted from 1308 mosquitoes, the IIS6 fragment of the vgsc gene on the nerve cell membrane was amplified using polymerase chain reaction, and the sequence was used to evaluate allele frequency and knockdown resistance (kdr) frequency. MEGA 11 was used to construct neighbor-joining (NJ) tree. PopART was used to build a TCS network.

Results

There were 6 alleles and 6 genotypes at the L1014 locus, which included the wild-type alleles TTA/L and CTA/L and the mutant alleles TTT/F, TTC/F, TCT/S and TCA/S. The geographic populations with a kdr frequency less than 20.00% were mainly concentrated in the regions north of 38° N, and the geographic populations with a kdr frequency greater than 80.00% were concentrated in the regions south of 30° N. kdr frequency increased with decreasing latitude. And within the same latitude, the frequency of kdr in large cities is relatively high. Mutations were correlated with the number of introns. The mutant allele TCA/S has only one intron, the mutant allele TTT/F has three introns, and the wild-type allele TTA/L has 17 introns.

Conclusions

Cx. p. pallens and Cx. p. quinquefasciatus have developed resistance to insecticides in most regions of China. The neighboring downstream introns of the vgsc gene gradually decreased to one intron with the mutation of the vgsc gene. Mutations may originate from multiple mutation events rather than from a single origin, and populations lacking mutations may be genetically isolated.

Graphical Abstract
Global research hotspots, development trends and prospect discoveries of phase separation in cancer: a decade-long informatics investigation
Authors: Guo Song-Bin , Feng Xue-Zhao , Huang Wei-Juan , Zhou Zhen-Zhong , Tian Xiao-Peng
Published: April 2024

Liquid-liquid phase separation (LLPS) is a complex and subtle phenomenon whose formation and regulation take essential roles in cancer initiation, growth, progression, invasion, and metastasis. This domain holds a wealth of underutilized unstructured data that needs further excavation for potentially valuable information. Therefore, we retrospectively analyzed the global scientific knowledge in the field over the last decade by using informatics methods (such as hierarchical clustering, regression statistics, hotspot burst, and Walktrap algorithm analysis). Over the past decade, this area enjoyed a favorable development trend (Annual Growth Rate: 34.98%) and global collaboration (International Co-authorship: 27.31%). Through unsupervised hierarchical clustering based on machine learning, the global research hotspots were divided into five dominant research clusters: Cluster 1 (Effects and Mechanisms of Phase Separation in Drug Delivery), Cluster 2 (Phase Separation in Gene Expression Regulation), Cluster 3 (Phase Separation in RNA-Protein Interaction), Cluster 4 (Reference Value of Phase Separation in Neurodegenerative Diseases for Cancer Research), and Cluster 5 (Roles and Mechanisms of Phase Separation). And further time-series analysis revealed that Cluster 5 is the emerging research cluster. In addition, results from the regression curve and hotspot burst analysis point in unison to super-enhancer (a=0.5515, R2=0.6586, p=0.0044) and stress granule (a=0.8000, R2=0.6000, p=0.0085) as the most potential star molecule in this field. More interestingly, the Random-Walk-Strategy-based Walktrap algorithm further revealed that “phase separation, cancer, transcription, super-enhancer, epigenetics”(Relevance Percentage[RP]=100%, Development Percentage[DP]=29.2%), “stress granule, immunotherapy, tumor microenvironment, RNA binding protein”(RP=79.2%, DP=33.3%) and “nanoparticle, apoptosis”(RP=70.8%, DP=25.0%) are closely associated with this field, but are still under-developed and worthy of further exploration. In conclusion, this study profiled the global scientific landscape, discovered a crucial emerging research cluster, identified several pivotal research molecules, and predicted several crucial but still under-developed directions that deserve further research, providing an important reference value for subsequent basic and clinical research of phase separation in cancer.
Unlocking the potential of β-1,3-xylooligosaccharides from Caulerpa lentillifera: structural characterization, antioxidative and anti-osteoarthritis applications
Authors: Cai Lixi , Zheng Jinlin , Liu Lixing , Chen Xiaoping , Wang Honglin
Published: April 2024

Background

β-1,3-Xylooligosaccharides (XOS-3) extracted from Caulerpa lentillifera have shown potential antioxidative and anti-tumor properties, but research on their biological activities, particularly their anti-osteoarthritis effects, is still in early stages.

Results

XOS-3 were produced by eco-friendly enzymatic hydrolysis, displaying a semi-crystalline structure with predominant xylose, xylobiose, xylotriose, and xylotetraose components which were confirmed by IC, SEM, FT-IR, and XRD analysis. Compared with β-1,4-xylooligosaccharides, XOS-3 had stronger antioxidant properties, and the scavenging rate of O2•− and DPPH• radicals was 82.31% and 58.44% at 2.0 mg/mL respectively. In vitro studies, XOS-3 significantly improved cell viability in IL-1β-induced rat chondrocytes from 43.41 to 73.5% at 100 μg/mL, demonstrating anti-inflammatory and cartilage-protective effects by modulating MMP13 and COL2A1 expression.

Conclusions

The study displayed the potential antioxidative and anti-osteoarthritis effects of XOS-3, offering new visuals for the development of marine polysaccharides in the treatment of osteoarthritis.

Graphical Abstract
Ocular metastases profile in a tertiary hospital in São Paulo, Brazil
Authors: Ogata Matheus Senna Pereira , Ferreira Guilherme Rodrigues , Morales Melina Correia , Fernandes Arthur Gustavo
Published: April 2024

Objective

Ocular metastases are the most common intraocular tumours in adults. Data regarding the occurrence of these tumours in the Brazilian population is scarce. We aimed to investigate the profile of ocular metastases of patients referred to tertiary hospital service in São Paulo, Brazil.

Design

Retrospective study.

Participants

Patients referred to the Ocular Oncology service of the Federal University of São Paulo with initial diagnostic hypothesis of ocular metastasis.

Methods

Data was retrospectively collected from medical records from June 2017 to June 2023. Age, sex, primary tumour site, previous knowledge of the systemic diagnosis, laterality, initial visual acuity (VA), local or systemic treatment and mean follow-up period were obtained.

Results

A total of 37 cases were referred to the ocular oncology division due to a suspected ocular metastasis, 15 (40.5%) were confirmed. Mean age at diagnosis was 53.47 ± 16.01 years old, the majority (86.7%) of patients already knew the systemic diagnosis. Breast cancer (66.7%) was the most common primary site, followed by Lung cancer (26.7%). Both eyes were affected in 66.67% of the cases, all patients had metastases at the choroid (100.0%), and the mean initial VA was 1.37 ± 1.04 logMAR. Chemotherapy was the main systemic treatment modality (73.3%), and most patients had no ocular treatment (53.3%). The mortality rate along the follow-up period was 30.0%.

Conclusions

Considering the number of new patients absorbed by the Ocular Oncology service over the study period, the frequency of ocular metastases was relatively low. The patients’ characteristics was comparable to data published in the international literature.
Comparison of approaches for increasing affinity of affibody molecules for imaging of B7-H3: dimerization and affinity maturation
Authors: Oroujeni Maryam , Carlqvist Matilda , Ryer Eva , Orlova Anna , Tolmachev Vladimir , Frejd Fredrik Y.
Published: April 2024

Background

Radionuclide molecular imaging can be used to visualize the expression levels of molecular targets. Affibody molecules, small and high affinity non-immunoglobulin scaffold-based proteins, have demonstrated promising properties as targeting vectors for radionuclide tumour imaging of different molecular targets. B7-H3 (CD276), an immune checkpoint protein belonging to the B7 family, is overexpressed in different types of human malignancies. Visualization of overexpression of B7-H3 in malignancies enables stratification of patients for personalized therapies. Affinity maturation of anti-B7-H3 Affibody molecules as an approach to improve the binding affinity and targeting properties was recently investigated. In this study, we tested the hypothesis that a dimeric format may be an alternative option to increase the apparent affinity of Affibody molecules to B7-H3 and accordingly improve imaging contrast.

Results

Two dimeric variants of anti-B7-H3 Affibody molecules were produced (designated ZAC12*-ZAC12*-GGGC and ZAC12*-ZTaq_3-GGGC). Both variants were labelled with Tc-99m (99mTc) and demonstrated specific binding to B7-H3-expressing cells in vitro. [99mTc]Tc-ZAC12*-ZAC12*-GGGC showed subnanomolar affinity (KD1=0.28 ± 0.10 nM, weight = 68%), which was 7.6-fold higher than for [99mTc]Tc-ZAC12*-ZTaq_3-GGGC (KD=2.1 ± 0.9 nM). Head-to-head biodistribution of both dimeric variants of Affibody molecules compared with monomeric affinity matured SYNT-179 (all labelled with 99mTc) in mice bearing B7-H3-expressing SKOV-3 xenografts demonstrates that both dimers have lower tumour uptake and lower tumour-to-organ ratios compared to the SYNT-179 Affibody molecule.

Conclusion

The improved functional affinity by dimerization does not compensate the disadvantage of increased molecular size for imaging purposes.
Constructive alignment in a graduate-level project management course: an innovative framework using large language models
Authors: Pereira Estacio , Nsair Sumaya , Pereira Leticia Radin , Grant Kimberley
Published: April 2024

Constructive alignment is a learning design approach that emphasizes the direct alignment of the intended learning outcomes, instructional strategies, learning activities, and assessment methods to ensure students are engaged in a meaningful learning experience. This pedagogical approach provides clarity and coherence, aiding students in understanding the connection of their learning activities and assessments with the overall course objectives. This paper explores the use of constructive alignment principles in designing a graduate-level Introduction to Project Management course by leveraging Large Language Models (LLMs), specifically ChatGPT. We introduce an innovative framework that embodies an iterative process to define the course learning outcomes, learning activities and assessments, and lecture content. We show that the implemented framework in ChatGPT was adept at autonomously establishing the course's learning outcomes, delineating assessments with their respective weights, mapping learning outcomes to each assessment method, and formulating a plan for learning activities and the course's schedule. While the framework can significantly reduce the time instructors spend on initial course planning, the results demonstrate that ChatGPT often lacks the specificity and contextual awareness necessary for effective implementation in diverse classroom settings. Therefore, the role of the instructor remains crucial in customizing and finalizing the course structure. The implications of this research are vast, providing insights for educators and curriculum designers looking to infuse LLMs systems into course development without compromising effective pedagogical practices.
The clay-shoveler’s fracture, a rare occupational injury in the modern era: a case report
Authors: Bello Juan Sebastián Reyes , Varón Diego Fernando Castiblanco , Saavedra Jose Luis Rozo , Lugo Claudia Marcela Restrepo , Mendez Juan Nicolas Perez , Salazar Luis Rafael Moscote
Published: April 2024

Background

The clay-shoveler fracture, named after Australian clay shovelers from the 1930s, results from high-energy, repetitive pulling mechanisms and is commonly associated with shoveling or digging. This injury primarily affects the lower cervical and upper thoracic vertebrae, particularly the C7 and T1 vertebrae. The avulsion mechanism, caused by stress on the spinous processes, may lead to sudden, severe upper back pain, limiting the affected individual’s ability to work effectively.

Case presentation

This report presents the case of a 27-year-old boiler operator who experienced persistent neck pain, which did not respond to conservative management. Imaging studies revealed a T1 spinous process fracture with associated soft tissue edema, diagnosed as a clay-shoveler fracture. Conventional treatment with a semirigid cervical collar, analgesia, and rest was administered, leading to a favorable outcome.

The clay-shoveler fracture, though rare, should be considered in cases involving repetitive stress on the cervical and thoracic spine, especially in occupations that require heavy lifting. In most instances, conservative management proves effective in relieving pain and enabling recovery.

Conclusion

Recognizing the clay-shoveler fracture is crucial for timely diagnosis and treatment. This case report underscores the occupational nature of the injury and its association with specific work activities. Further research and reporting of similar cases will contribute to a deeper understanding of this unusual fracture pattern, its risk factors, and optimal management strategies.
Efficacy and safety of cangrelor as compared to ticagrelor in patients with ST-elevated myocardial infarction (STEMI): a systematic review and meta-analysis
Authors: Chakraborty Subhro , Sarkar Debalina , Samajdar Shambo Samrat , Biswas Pallab , Mohapatra Debasish , Halder Saptarshi , Yunus Mohammad
Published: April 2024

Background

This systematic review and meta-analysis aimed to compare the efficacy and safety of cangrelor as compared to ticagrelor in patients with ST-elevated myocardial infarction (STEMI) who underwent percutaneous intervention.

Methods

PubMed, Embase, Scopus, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov databases were searched for relevant head-on-comparison or swapping studies. The primary outcome was the rate of high platelet reactivity (HPR) at specific time intervals after stopping cangrelor infusion during the first 24 h. Secondary outcomes were the risks of thrombosis, all-cause mortality and bleeding. Pooled odds ratios (ORs) were calculated using random-effects models.

Results

A total of 1018 studies were screened and eight were included in the analysis. There were four head-on-comparison studies and four swapping studies. There was no significant difference in the proportion of patients achieving a high platelet reactivity in swapping studies [OR, 0.71 (95% CI 0.04, 13.87), p = 0.82, i2 = 88%]. In head-on-comparison studies, PRU from Fig. 2B shows there was no significant reduction in high platelet reactivity [mean difference – 77.83 (95% CI − 238.84, 83.18), p < 0.001, i2 = 100%]. PRU results from (Fig. 2C) show a mean difference of 7.38 (95% CI − 29.74, 44.51), p < 0.001, i2 = 97%. There was no significant difference in the risks of thrombosis [OR, 0.91 (95% CI 0.20, 4.13), p = 0.81, i2 = 0%], all-cause mortality [OR, 3.52 (95% CI 0.44, 27.91), p = 0.24, i2 = 26%] and bleeding [OR, 0.89 (95% CI 0.37, 2.17), p = 0.93, i2 = 0%] between the two groups as revealed in the head-on-comparison studies.

Conclusion

The efficacy and safety profiles of cangrelor and ticagrelor were similar in patients with STEMI.
Identifying barriers and facilitators to primary care practitioners implementing health assessments for people with intellectual disability: a Theoretical Domains Framework-informed scoping review
Authors: Caltabiano Paul , Bailie Jodie , Laycock Alison , Shea Bradley , Dykgraaf Sally Hall , Lennox Nicholas , Ekanayake Kanchana , Bailie Ross
Published: April 2024

Introduction

People with intellectual disability experience poorer health outcomes compared with the general population, partly due to the difficulties of accessing preventive care in primary care settings. There is good evidence that structured annual health assessments can enhance quality of care for people with intellectual disability, and their use has become recommended policy in several high-income countries. However, uptake remains low. The Theoretical Domains Framework (TDF) offers a conceptual structure for understanding barriers to implementation and has been usefully applied to inform implementation of health assessments for other high-need groups, but not for people with intellectual disability. We conducted a scoping review of the literature, using the TDF, to identify barriers and facilitators influencing primary care practitioners’ implementation of annual health assessments for people with intellectual disability as part of routine primary care practice.

Methods

This study was conducted according to the JBI methodological approach for scoping reviews. Searches were conducted in Medline (OVID-SP), Embase (OVID-SP), PsycINFO (OVID-SP), CINHAL (EBSCO), Scopus (Elsevier) and Web of Science (Clarivate) for relevant peer-reviewed publications up to May 2023. Screening, full-text review and data extraction were completed by two independent reviewers. Data were extracted and mapped to the TDF to identify relevant barriers and facilitators.

Results

The search yielded 1057 publications, with 21 meeting the inclusion criteria. Mapping data to the TDF, the most frequently identified domains were (a) environmental context and resources, (b) skills, (c) knowledge and (d) emotion. Predominant factors impacting on implementation included practitioners’ lack of awareness about health assessments and their identified benefits; inadequate training and experience by practitioners in the delivery of health assessments for people with intellectual disability; insufficient time to provide health assessments; and practitioner burnout.

Conclusion

Using a theory-informed behavioural framework, our review aids understanding of the barriers and facilitators to improving the implementation of health assessments as part of routine care for people with intellectual disability. However, there is a clear need for further qualitative research to examine the perceptions of primary care practitioners regarding implementation barriers and facilitators to health assessments in general, including views from practitioners who are not currently undertaking health assessments.
Assessing organizational readiness for the Clean Cuts and Sharp Minds Collective: a barbershop health promotion network
Authors: Wippold Guillermo M. , Crichlow Zion R. , Garcia Kaylyn A. , Domlyn Ariel , Sanchez Shane , Frank Lucina , Mote Thrisha , Frary Sarah Grace , Woods Terry
Published: April 2024

Background

Black men have among the lowest life expectancy in the United States. Alarmingly, these men are underrepresented in health promotion efforts. There are well-documented barriers to recruiting and retaining Black men in health promotion efforts, such as exclusionary research practices – many researchers may be hesitant to reach Black men in culturally unique spaces, such as barbershops. Despite these practices, qualitative research among Black men unanimously find that Black men are interested in health promotion efforts. The Clean Cuts and Sharp Minds Collective (CCSMC) was designed to bridge this gap. The objectives of the CCSMC are to train barbers to be lay advocates for their clients, train barbers to be research partners, and serve as a nexus between barbers interested in health promotion at their shops and researchers interested in implementing such efforts. The present study sought to assess the organizational readiness of barbershops in South Carolina (SC) to participate in the CCSMC.

Methods

Barbers in SC were invited to complete a modified version of the Readiness Thinking Tool to assess organizational readiness to participate in the CCSMC.

Results

Thirty-six (36; mean age = 41.12; 94.4% identified as Black; 91.7% identified as male) barbers completed the organizational readiness assessment. Results indicated that there was a high level of motivation, innovation-specific capacity, and general capacity within barbershops to participate in the CCSMC. Additionally, many barbers indicated that there would be widespread support to join the CCSMC.

Conclusions

The results from the present study highlight exciting opportunities and future directions for barbershop-academic partnerships. Such partnerships have the potential to promote health equity among, and in partnership with, Black men.
Three-dimensional dipole orientation mapping with high temporal-spatial resolution using polarization modulation
Authors: Zhong Suyi , Qiao Liang , Ge Xichuan , Xu Xinzhu , Fu Yunzhe , Gao Shu , Zhanghao Karl , Hao Huiwen , Wang Wenyi , Li Meiqi , Xi Peng
Published: April 2024

Fluorescence polarization microscopy is widely used in biology for molecular orientation properties. However, due to the limited temporal resolution of single-molecule orientation localization microscopy and the limited orientation dimension of polarization modulation techniques, achieving simultaneous high temporal-spatial resolution mapping of the three-dimensional (3D) orientation of fluorescent dipoles remains an outstanding problem. Here, we present a super-resolution 3D orientation mapping (3DOM) microscope that resolves 3D orientation by extracting phase information of the six polarization modulation components in reciprocal space. 3DOM achieves an azimuthal precision of 2° and a polar precision of 3° with spatial resolution of up to 128 nm in the experiments. We validate that 3DOM not only reveals the heterogeneity of the milk fat globule membrane, but also elucidates the 3D structure of biological filaments, including the 3D spatial conformation of λ-DNA and the structural disorder of actin filaments. Furthermore, 3DOM images the dipole dynamics of microtubules labeled with green fluorescent protein in live U2OS cells, reporting dynamic 3D orientation variations. Given its easy integration into existing wide-field microscopes, we expect the 3DOM microscope to provide a multi-view versatile strategy for investigating molecular structure and dynamics in biological macromolecules across multiple spatial and temporal scales.