bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent advances of responsive scaffolds in bone tissue engineering
Authors: Zhu Tongyu , Zhou Hongbo , Chen Xiaojing , Zhu Yuanjing
Published: November 2023

The investigation of bone defect repair has been a significant focus in clinical research. The gradual progress and utilization of different scaffolds for bone repair have been facilitated by advancements in material science and tissue engineering. In recent times, the attainment of precise regulation and targeted drug release has emerged as a crucial concern in bone tissue engineering. As a result, we present a comprehensive review of recent developments in responsive scaffolds pertaining to the field of bone defect repair. The objective of this review is to provide a comprehensive summary and forecast of prospects, thereby contributing novel insights to the field of bone defect repair.
Machine learning-based predictor for neurologic outcomes in patients undergoing extracorporeal cardiopulmonary resuscitation
Authors: Kim Tae Wan , Ahn Joonghyun , Ryu Jeong-Am
Published: November 2023

Background

We investigated the predictors of poor neurological outcomes in extracorporeal cardiopulmonary resuscitation (ECPR) patients using machine learning (ML) approaches.

Methods

This study was a retrospective, single-center, observational study that included adult patients who underwent ECPR while hospitalized between January 2010 and December 2020. The primary outcome was neurologic status at hospital discharge as assessed by the Cerebral Performance Categories (CPC) score (scores range from 1 to 5). We trained and tested eight ML algorithms for a binary classification task involving the neurological outcomes of survivors after ECPR.

Results

During the study period, 330 patients were finally enrolled in this analysis; 143 (43.3%) had favorable neurological outcomes (CPC score 1 and 2) but 187 (56.7%) did not. From the eight ML algorithms initially considered, we refined our analysis to focus on the three algorithms, eXtreme Gradient Boosting, random forest, and Stochastic Gradient Boosting, that exhibited the highest accuracy. eXtreme Gradient Boosting models exhibited the highest accuracy among all the machine learning algorithms (accuracy: 0.739, area under the curve: 0.837, Kappa: 0.450, sensitivity: 0.700, specificity: 0.740). Across all three ML models, mean blood pressure emerged as the most influential variable, followed by initial serum lactate, and arrest to extracorporeal membrane oxygenation (ECMO) pump-on-time as important predictors in machine learning models for poor neurological outcomes following successful ECPR.

Conclusions

In conclusion, machine learning methods showcased outstanding predictive accuracy for poor neurological outcomes in patients who underwent ECPR.
Improving health literacy using the power of digital communications to achieve better health outcomes for patients and practitioners
Authors: Fitzpatrick Patrick J.
Published: November 2023

Digital communication tools have demonstrated significant potential to improve health literacy which ultimately leads to better health outcomes. In this article, we examine the power of digital communication tools such as mobile health apps, telemedicine and online health information resources to promote health and digital literacy. We outline evidence that digital tools facilitate patient education, self-management and empowerment possibilities. In addition, digital technology is optimising the potential for improved clinical decision-making, treatment options and communication among providers. We also explore the challenges and limitations associated with digital health literacy, including issues related to access, reliability and privacy. We propose leveraging digital communication tools is key to optimising engagement to enhance health literacy across demographics leading to transformation of healthcare delivery and driving better outcomes for all.
Factors influencing the development of pre-service science teachers’ technological pedagogical content knowledge in a pedagogical makerspace
Authors: Max Anna-Lisa , Weitzel Holger , Lukas Sarah
Published: November 2023

In an increasingly digitalized world, pre-service and in-service teachers need subject-specific didactic competencies to be able to plan their lessons appropriately and use their knowledge to promote digital competencies among students. Building on competency models such as the Technological pedagogical content knowledge (TPACK) framework, this article explores the extent to which specific digital competencies relevant to pre-service teachers can be developed through project work in a pedagogical makerspace and examines the extent to which contextual factors such as technological self-efficacy, motivation and technology acceptance influence the development of pre-service teachers’ TPACK and their intention to use digital media. To this end, 495 pre-service science teachers from both intervention and control groups completed a pre-post digital questionnaire before and after the intervention. The data were used for structural equation modeling. The results show that the level of TPACK before the intervention is an important predictor of TPACK after project work. Furthermore, TPACK before the intervention positively influences pre-service teachers’ intention to use digital media in the future. Also, the perceived usefulness for professional use and the intention to use information and communication technologies (ICT) are strongly influenced by TPACK. Consequently, it appears significant to enable a low-threshold entry point at the beginning of the study to provide a solid foundation upon which more advanced TPACK can be built. Motivation and technology acceptance are strongly correlated. Therefore, teacher training should focus on motivation and acceptance of technology.
Analysis of the impact of transient overvoltage on grid-connected PMSG-based wind turbine systems
Authors: Cao Bin , Liu Hongqing , Xie Qi
Published: November 2023

The annual increase in installation capacity and electrical production of renewable energy sources, primarily wind turbine generators (WTG), is shaping a renewable energy dominated power system. WTGs are susceptible to the temporary overvoltage caused by reactive power surplus following low-voltage ride through (LVRT). This can lead to the large-scale trip-off of WTGs and pose significant risks to the secure and stable operation of power systems. An insightful elaboration of the underlying mechanisms determining the occurrence of temporary overvoltage, and an analysis of influencing factors, is pivotal to ensure the reliable integration of WTGs. This paper investigates the temporary overvoltage in the AC systems integrated with multiple renewable energy stations. A temporary overvoltage model that accounts for various types of equipment has been derived. Resorting to the model, the influence of LVRT parameters of WTGs, SCR and IR of the AC system on the maximum terminal overvoltage has been quantitatively assessed. Simulations and semi-physical validations have been conducted to verify the effectiveness and accuracy of the theoretical analysis.
Projected incidence trends of need for long-term care in German men and women from 2011 to 2021
Authors: Voß Sabrina , Knippschild Stephanie , Haß Luisa , Tönnies Thaddäus , Brinks Ralph
Published: November 2023

Background

The German Federal Statistical Office routinely collects and reports aggregated numbers of people in need of long-term care (NLTC) stratified by age and sex. Age- and sex-specific prevalence of NLTC from 2011 to 2021 is reported as well. One estimation of the incidence rate of NLTC based on the age- and sex-specific prevalence exists that did not explore possible trends in incidence [based on MRR (mortality rate ratio)], which is important for an adequate projection of the future number of people with NLTC.

Objective

We aim to explore possible trends in age-specific incidence of NLTC in German men and women from 2011 to 2021 based on different scenarios about excess mortality (in terms of MRR).

Methods

The incidence of NLTC was calculated based on an illness-death model and a related partial differential equation based on data from the Federal Statistical Office. Estimation of annual percent change (APC) of the incidence rate was conducted in eight scenarios.

Results

There are consistent indications for trends in incidence for men and women aged 50–79 years with APC in incidence rate of more than +9% per year (up to nearly 19%). For ages 80+ the APC is between +0.4% and +12.5%. In all scenarios, women had higher age-specific APCs than men.

Conclusion

We performed the first analysis of APC in the age- and sex-specific incidence rate of NLTC in Germany and revealed an increasing trend in the incidences. With these findings, a future prevalence of NLTC can be estimated which may exceed current prognoses.
Development of novel parameters for pathogen identification in clinical metagenomic next-generation sequencing
Authors: Jiang Xiwen , Yan Jinghai , Huang Hao , Ai Lu , Yu Xuegao , Zhong Pengqiang , Chen Yili , Liang Zhikun , Qiu Wancen , Huang Huiying , Yan Wenyan , Liang Yan , Chen Peisong , Wang Ruizhi
Published: November 2023

Introduction: Metagenomic next-generation sequencing (mNGS) has emerged as a powerful tool for rapid pathogen identification in clinical practice. However, the parameters used to interpret mNGS data, such as read count, genus rank, and coverage, lack explicit performance evaluation. In this study, the developed indicators as well as novel parameters were assessed for their performance in bacterium detection.

Methods: We developed several relevant parameters, including 10M normalized reads, double-discard reads, Genus Rank Ratio, King Genus Rank Ratio, Genus Rank Ratio*Genus Rank, and King Genus Rank Ratio*Genus Rank. These parameters, together with frequently used read indicators including raw reads, reads per million mapped reads (RPM), transcript per kilobase per million mapped reads (TPM), Genus Rank, and coverage were analyzed for their diagnostic efficiency in bronchoalveolar lavage fluid (BALF), a common source for detecting eight bacterium pathogens: Acinetobacter baumannii, Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Aspergillus fumigatus.

Results: The results demonstrated that these indicators exhibited good diagnostic efficacy for the eight pathogens. The AUC values of all indicators were almost greater than 0.9, and the corresponding sensitivity and specificity values were almost greater than 0.8, excepted coverage. The negative predictive value of all indicators was greater than 0.9. The results showed that the use of double-discarded reads, Genus Rank Ratio*Genus Rank, and King Genus Rank Ratio*Genus Rank exhibited better diagnostic efficiency than that of raw reads, RPM, TPM, and in Genus Rank. These parameters can serve as a reference for interpreting mNGS data of BALF. Moreover, precision filters integrating our novel parameters were built to detect the eight bacterium pathogens in BALF samples through machine learning.

Summary: In this study, we developed a set of novel parameters for pathogen identification in clinical mNGS based on reads and ranking. These parameters were found to be more effective in diagnosing pathogens than traditional approaches. The findings provide valuable insights for improving the interpretation of mNGS reports in clinical settings, specifically in BALF analysis.
The safety and efficacy of endoscopic ultrasound-guided portal pressure gradient measurement with concomitant endoscopic ultrasound-guided liver biopsy: a systematic review
Authors: Malik Alexander , Yousaf Muhammad Nadeem , Hammoud Ghassan M.
Published: November 2023

Introduction

Portal hypertension (PH) is a complication of advanced liver disease. Traditionally, PH has been quantified using hepatic venous pressure gradient (HVPG) through an indirect transjugular approach requiring ionizing radiation exposure. Endoscopic ultrasound-guided porto-systemic pressure gradient (EUS-PPG) measurement is an emerging alternative, minimally invasive technique that provides direct portal pressure measurement. The aim of this systematic review is to evaluate the safety and efficacy of EUS-PPG measurement and concomitant EUS-guided liver biopsy (EUS-LB) in patients with chronic liver disease.

Methods

The preferred reporting items for systematic reviews and meta-analyses method was used. A PubMed, Medline, Web of Science, Google Scholar, and CINAHL search for terms “endoscopic ultrasound,” “EUS,” and “portal pressure gradient” was used to identify qualifying studies. Eligible studies included those which were published before 2022, reporting outcomes of EUS-PPG measurement, simultaneous EUS-LB if applicable, and adverse events rate. Risk of bias was assessed by Egger’s test. Results were synthesized using I2 to test heterogeneity.

Results

Four published studies including 147 patients met inclusion criteria, with mean age 59.6 years, 59% male. Indications for EUS-PPG measurement were history of chronic liver disease or suspected cirrhosis, viral hepatitis, alcohol associated liver disease, hepatic sinusoidal obstruction or Budd Chiari syndrome. The pooled technical success rate of EUS-PPG measurements was 98.61% with 95% confidence interval of 95.20% - 99.82%. A 25-gauge needle was used in 92% (135/147) of patients. EUS-PPG measurement was performed through a transgastric approach in all 147 (100%) patients using a compact manometer with pressure transducer and non-compressible tubing. The mean PPG was 10.07 (range 6.44 – 13.70) mmHg. Ninety-five patients underwent simultaneous EUS-LB using 19G needle with wet suction technique. Technical success rate of EUS-LB was 100% and specimen was adequate in 99% (94/95) patients to establish histological diagnosis. There were no major life-threatening complications of the EUS-PPG procedure. Predominant adverse events were abdominal pain 6.1% (9/147) and sore throat 5.4% (8/147).

Conclusion

EUS-PPG measurement is safe and useful in providing an assessment of portal pressure in patients with chronic liver disease. Future studies are needed to evaluate whether there is consistent correlation between EUS-PPG measurements and histologic fibrosis stage by liver biopsy.
Experimental validation of immunogenic SARS-CoV-2 T cell epitopes identified by artificial intelligence
Authors: Federico Lorenzo , Malone Brandon , Tennøe Simen , Chaban Viktoriia , Osen Julie Røkke , Gainullin Murat , Smorodina Eva , Kared Hassen , Akbar Rahmad , Greiff Victor , Stratford Richard , Clancy Trevor , Munthe Ludvig Andre
Published: November 2023

During the COVID-19 pandemic we utilized an AI-driven T cell epitope prediction tool, the NEC Immune Profiler (NIP) to scrutinize and predict regions of T cell immunogenicity (hotspots) from the entire SARS-CoV-2 viral proteome. These immunogenic regions offer potential for the development of universally protective T cell vaccine candidates. Here, we validated and characterized T cell responses to a set of minimal epitopes from these AI-identified universal hotspots. Utilizing a flow cytometry-based T cell activation-induced marker (AIM) assay, we identified 59 validated screening hits, of which 56% (33 peptides) have not been previously reported. Notably, we found that most of these novel epitopes were derived from the non-spike regions of SARS-CoV-2 (Orf1ab, Orf3a, and E). In addition, ex vivo stimulation with NIP-predicted peptides from the spike protein elicited CD8+ T cell response in PBMC isolated from most vaccinated donors. Our data confirm the predictive accuracy of AI platforms modelling bona fide immunogenicity and provide a novel framework for the evaluation of vaccine-induced T cell responses.
Immune activation and inflammation in lactating women on combination antiretroviral therapy: role of gut dysfunction and gut microbiota imbalance
Authors: Munjoma Privilege Tendai , Chandiwana Panashe , Wyss Jacqueline , Mazhandu Arthur John , Jordi Sebastian Bruno Ulrich , Gutsire Rutendo , Katsidzira Leolin , Yilmaz Bahtiyar , Misselwitz Benjamin , Duri Kerina
Published: November 2023

Introduction

Combination antiretroviral therapy (cART) effectively controls HIV; however, chronic low-level viremia and gut microbiota dysbiosis remain significant drivers of gut and systemic inflammation. In this study, we explored the relationship between gut microbiota composition, intestinal inflammation, microbial translocation, and systemic inflammation in women on cART in Sub-Saharan Africa.

Methods

We conducted a study in HIV-infected and HIV-uninfected lactating women followed up at 6 weeks and 6 months postpartum in Harare, Zimbabwe. We used 16S ribosomal Ribonucleic Acid (rRNA) sequencing and MesoScale Discovery V-Plex assays to examine the gut microbiome and to quantify plasma inflammatory biomarkers, respectively. In addition, we measured fecal calprotectin, plasma lipopolysaccharide-binding protein (LBP), and soluble cluster of differentiation 14 (sCD14) by enzyme-linked immunosorbent assay to assess gut inflammation, microbial translocation, and monocyte/macrophage activation.

Results

A group of 77 lactating women were studied, of which 35% were HIV-infected. Fecal calprotectin levels were similar by HIV status at both follow-up time points. In the HIV-infected group at 6 weeks postpartum, fecal calprotectin was elevated: median (interquartile range) [158.1 µg/g (75.3–230.2)] in women who had CD4+ T-lymphocyte counts <350 cells/µL compared with those with ≥350 cells/µL [21.1 µg/g (0–58.4)], p = 0.032. Plasma sCD14 levels were significantly higher in the HIV-infected group at both 6 weeks and 6 months postpartum, p < 0.001. Plasma LBP levels were similar, but higher levels were observed in HIV-infected women with elevated fecal calprotectin. We found significant correlations between fecal calprotectin, LBP, and sCD14 with proinflammatory cytokines. Gut microbial alpha diversity was not affected by HIV status and was not affected by use of antibiotic prophylaxis. HIV significantly affected microbial beta diversity, and significant differences in microbial composition were noted. The genera Slackia and Collinsella were relatively more abundant in the HIV-infected group, whereas a lower relative abundance of Clostriduim sensu_stricto_1 was observed. Our study also found correlations between gut microbial taxa abundance and systemic inflammatory biomarkers.

Discussion and conclusion

HIV-infected lactating women had increased immune activation and increased microbial translocation associated with increased gut inflammation. We identified correlations between the gut inflammation and microbial composition, microbial translocation, and systemic inflammation. The interplay of these parameters might affect the health of this vulnerable population.
Impact of SARS-CoV-2 vaccination on FcγRIIIA/CD16 dynamics in Natural Killer cells: relevance for antibody-dependent functions
Authors: Capuano Cristina , De Federicis Davide , Ciuti Daniel , Turriziani Ombretta , Angeloni Antonio , Anastasi Emanuela , Giannini Giuseppe , Belardinilli Francesca , Molfetta Rosa , Alvaro Domenico , Palmieri Gabriella , Galandrini Ricciarda
Published: November 2023

Introduction

Natural Killer (NK) cells contribute to the protective effects of vaccine-induced antibodies thanks to the low affinity receptor for IgG, FcγRIIIA/CD16, whose aggregation leads to the killing of infected cells and IFNγ release, through which they potentiate adaptive immune responses.

Methods

Forty-seven healthy young individuals undergoing either homologous (ChAdOx1-S/ChAdOx1-S) or heterologous (ChAdOx1-S/BNT162B2) SARS-CoV-2 vaccination settings were recruited. Peripheral blood samples were collected immediately prior to vaccination and 8 weeks after the booster dose. The phenotypic and functional profile of NK cells was evaluated by flow cytometry at both time points. Serum samples were tested to evaluate circulating anti-Spike IgG levels and cytomegalovirus serostatus. CD16 F158V polymorphism was assessed by sequencing analysis.

Results

The downregulation of CD16 and the selective impairment of antibody-dependent cytotoxicity and IFNγ production in CD56dim NK population, persisting 8 weeks after boosting, were observed in heterologous, but not in homologous SARS-CoV-2 vaccination scheme. While the magnitude of CD16-dependent functions of the global CD56dim pool correlated with receptor levels before and after vaccination, the responsivity of NKG2C+ subset, that displays amplified size and functionality in HCMV+ individuals, resulted intrinsically insensitive to CD16 levels. Individual CD16 responsiveness was also affected by CD16F158V polymorphism; F/F low affinity individuals, characterized by reduced CD16 levels and functions independently of vaccination, did not show post-vaccinal functional impairment with respect to intermediate and high affinity ones, despite a comparable CD16 downregulation. Further, CD16 high affinity ligation conditions by means of afucosylated mAb overcame vaccine-induced and genotype-dependent functional defects. Finally, the preservation of CD16 expression directly correlated with anti-Spike IgG titer, hinting that the individual magnitude of receptor-dependent functions may contribute to the amplification of the vaccinal response.

Conclusion

This study demonstrates a durable downmodulation of CD16 levels and Ab-dependent NK functions after SARS-CoV-2 heterologous vaccination, and highlights the impact of genetic and environmental host-related factors in modulating NK cell susceptibility to post-vaccinal Fc-dependent functional impairment.
The genetics and breeding of the Portuguese oyster, Crassostrea angulata: lessons, experiences, and challenges in Vietnam
Authors: Le Thi Nhu Phuong , Vu Sang Van , Ugalde Sarah C. , Subramanian Sankar , Gilmour Arthur , Dove Michael , Vu In Van , Geist Juergen , Tran Thi Nang Thu , Gondro Cedric , Cao Giang Truong , Le Tat Thanh , Nguyen Thi Mai , Ngo Thi Khanh Ngoc , Vu Thi Thanh Hương , H. K. A. Premachandra , Knibb Wayne , O’Connor Wayne
Published: November 2023

Aquaculture mollusc production is predominantly from Asia, with more than 80% of the total biomass produced in China. Vietnam’s annual mollusc production is growing rapidly but is comparatively small given its coastal resources. A significant challenge for future mollusc production, and oysters in particular, is the supply of high-quality spat. Most mollusc spat in Vietnam comes from local wild sources or is imported from China. Particularly in the case of oysters, where wild collection is low and importation of oyster spat into Vietnam from other jurisdictions is not controlled, supply is unreliable and presents a biosecurity risk to the industry. Controlling the life cycle in hatcheries can increase the sustainability and reliability of spat supply with the advantages of genetic enhancement in the long term. Beyond well-established selection methods based on phenotypic data for pedigreed families, the rapid development of genomic technology has enabled innovation in hatchery production based on genetic programs. This technology allows greater insight into oyster genetics in intensive aquaculture production systems. Recent reviews of selection programs demonstrate that inbreeding control via mate selection is an effective strategy for oyster species. Genetic response through combinations of individual and family-based selection can enhance morphometric traits by 10% per generation and disease resistance by 15% per generation in many aquaculture species. Genomic techniques provide information for selecting candidates at an earlier stage and improve prediction accuracy. In this paper, we review the literature on popular genomic tools and breeding techniques used for molluscs, focusing on the Portuguese oyster, Crassostrea angulata. This is to better comprehend how modern quantitative and molecular genetic technologies are being applied in mollusc breeding programs. It considers opportunities for and the feasibility of using genomic-based selection as well as the challenges that are faced in breeding programs transitioning to these new methods.
Mechanical analysis of helmeted headforms under ballistic impact with implications in performance evaluation of ballistic helmets
Authors: Harmukh Atul , Singh Abhilash , Kumar Praveen , Verma Sanjeev K. , Kumar Pal Dinesh , Ganpule S. G.
Published: November 2023

Behind helmet blunt trauma is a significant health concern in modern warfare. The ballistic response of the human head under ballistic impact is highly sought. Towards this end, we conducted ballistic experiments on three different headforms. The following headforms were considered: a) National Institute of Justice based rigid headform, b) Hybrid-III based flexible headform, and c) head model based headform. Headforms b, c were assembled with the Hybrid-III neck. An advanced combat helmet was fitted to the headforms. Helmet-head assembly was subjected to a 9 mm × 19 mm full metal jacket projectile having velocities of 430 ± 15 m/s. The response of the head surrogate in the front, back, side, and crown orientations was studied. Back face deformation (BFD), head kinematics, and intracranial pressures in headforms were measured. In addition, equivalent stress and maximum principal strain in the brain were obtained using concurrent finite element simulations. Results suggest that both local (i.e., due to the localized crushing of the helmet) and global (i.e., due to the bulk motion of the helmet-head parenchyma) responses were dominant under investigated ballistic impacts. Further, the type of the headform affected the biomechanical response. As compared to the rigid headform, a statistically significant increase in head kinematics was observed with the flexible headforms; changes in BFD were statistically insignificant. The orientation dependent responses have been observed. Overall, these results provide novel insights regarding the ballistic response of the headforms with the combat helmet and underscore critical considerations during the ballistic evaluation of helmets.
Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis
Authors: Zhao Jianan , Wei Kai , Shi Yiming , Jiang Ping , Xu Lingxia , Chang Cen , Xu Linshuai , Zheng Yixin , Shan Yu , Liu Jia , Li Li , Guo Shicheng , Schrodi Steven J. , Wang Rongsheng , He Dongyi
Published: November 2023

Objective: To investigate the potential association between Anoikis-related genes, which are responsible for preventing abnormal cellular proliferation, and rheumatoid arthritis (RA).

Methods: Datasets GSE89408, GSE198520, and GSE97165 were obtained from the GEO with 282 RA patients and 28 healthy controls. We performed differential analysis of all genes and HLA genes. We performed a protein-protein interaction network analysis and identified hub genes based on STRING and cytoscape. Consistent clustering was performed with subgrouping of the disease. SsGSEA were used to calculate immune cell infiltration. Spearman’s correlation analysis was employed to identify correlations. Enrichment scores of the GO and KEGG were calculated with the ssGSEA algorithm. The WGCNA and the DGIdb database were used to mine hub genes’ interactions with drugs.

Results: There were 26 differentially expressed Anoikis-related genes (FDR = 0.05, log2FC = 1) and HLA genes exhibited differential expression (P < 0.05) between the disease and control groups. Protein-protein interaction was observed among differentially expressed genes, and the correlation between PIM2 and RAC2 was found to be the highest; There were significant differences in the degree of immune cell infiltration between most of the immune cell types in the disease group and normal controls (P < 0.05). Anoikis-related genes were highly correlated with HLA genes. Based on the expression of Anoikis-related genes, RA patients were divided into two disease subtypes (cluster1 and cluster2). There were 59 differentially expressed Anoikis-related genes found, which exhibited significant differences in functional enrichment, immune cell infiltration degree, and HLA gene expression (P < 0.05). Cluster2 had significantly higher levels in all aspects than cluster1 did. The co-expression network analysis showed that cluster1 had 51 hub differentially expressed genes and cluster2 had 72 hub differentially expressed genes. Among them, three hub genes of cluster1 were interconnected with 187 drugs, and five hub genes of cluster2 were interconnected with 57 drugs.

Conclusion: Our study identified a link between Anoikis-related genes and RA, and two distinct subtypes of RA were determined based on Anoikis-related gene expression. Notably, cluster2 may represent a more severe state of RA.
A non-expensive bidimensional kinematic balance assessment can detect early postural instability in people with Parkinson’s disease
Authors: Santos Gabriel Venas , d'Alencar Matheus Silva , Helene Andre Frazão , Roque Antonio C. , Miranda José Garcia Vivas , Piemonte Maria Elisa Pimentel
Published: November 2023

Background

Postural instability is a debilitating cardinal symptom of Parkinson’s disease (PD). Its onset marks a pivotal milestone in PD when balance impairment results in disability in many activities of daily living. Early detection of postural instability by non-expensive tools that can be widely used in clinical practice is a key factor in the prevention of falls in widespread population and their negative consequences.

Objective

This study aimed to investigate the effectiveness of a two-dimensional balance assessment to identify the decline in postural control associated with PD progression.

Methods

This study recruited 55 people with PD, of which 37 were men. Eleven participants were in stage I, twenty-three in stage II, and twenty-one in stage III. According to the Hoehn and Yahr (H&Y) rating scale, three clinical balance tests (Timed Up and Go test, Balance Evaluation Systems Test, and Push and Release test) were carried out in addition to a static stance test recorded by a two-dimensional movement analysis software. Based on kinematic variables generated by the software, a Postural Instability Index (PII) was created, allowing a comparison between its results and those obtained by clinical tests.

Results

There were differences between sociodemographic variables directly related to PD evolution. Although all tests were correlated with H&Y stages, only the PII was able to differentiate the first three stages of disease evolution (H&Y I and II: p = 0.03; H&Y I and III: p = 0.00001; H&Y II and III: p = 0.02). Other clinical tests were able to differentiate only people in the moderate PD stage (H&Y III).

Conclusion

Based on the PII index, it was possible to differentiate the postural control decline among the first three stages of PD evolution. This study offers a promising possibility of a low-cost, early identification of subtle changes in postural control in people with PD in clinical practice.
Urinary extracellular vesicle dynamics in Parkinson's disease patients with urinary dysfunction
Authors: Roy Santanu , Kashyap Namita N. , Anchan Abigail Sheldon , Punja Dhiren , Jasti Dushyanth Babu , Upadhya Dinesh
Published: November 2023

Parkinson's disease (PD) presents with severe motor manifestations and a plethora of non-motor symptoms. Urinary dysfunctions are one of the most common non-motor symptoms of PD patients responsible for reduced quality of life. Urinary extracellular vesicles (EVs) are mostly considered to originate from the cells in the urogenital tract. In this study, we have performed urinary EV analysis in 29 PD cases with varied severity of urinary dysfunction and correlated it with the EV dynamics in 29 age-matched controls. In the studied cases, apart from urinary dysfunction, symptoms of depression, anxiety, cognitive dysfunction, sleep, and wakefulness were observed in >75% of the cases. No significant difference in urinary EV size, concentration and urinary EV protein concentration was observed between PD cases with urinary dysfunction and controls. However, a significant positive association was observed between urinary EV concentration and motor scores (p = 0.042), while no association was observed between urinary EV concentration and urinary dysfunction scores. Chronic stress induced by motor symptoms could be one of the reasons for excessive EV production in PD patients with urinary dysfunctions. Large-scale studies on the association of urinary EV dynamics with motor and non-motor symptoms may provide additional information on urinary dysfunction in PD.
Psychometric evaluation and reference values for the German Postconcussion Symptom Inventory (PCSI-SR8) in children aged 8–12 years
Authors: Zeldovich Marina , Krol Leonie , Timmermann Dagmar , Krenz Ugne , Arango-Lasprilla Juan Carlos , Gioia Gerard , Brockmann Knut , Koerte Inga K. , Buchheim Anna , Roediger Maike , Kieslich Matthias , von Steinbuechel Nicole , Cunitz Katrin
Published: November 2023

Background

Post-concussion symptoms (PCS) are a common consequence of pediatric traumatic brain injury (pTBI). They include cognitive, emotional, and physical disturbances. To address the lack of age-adapted instruments assessing PCS after pTBI, this study examines the psychometric properties of the German 17-item post-TBI version of the Postconcussion Symptom Inventory (PCSI-SR8) in children aged 8–12 years. The study also aims to establish reference values based on data from a pediatric general population sample to better estimate the prevalence and clinical relevance of PCS after pTBI in clinical and research settings.

Methods

A total of 132 children aged 8–12 years from a post-acute TBI sample and 1,047 from a general population sample were included in the analyses. The questionnaire was translated from English into German and linguistically validated using forward and backward translation and cognitive debriefing to ensure comprehensibility of the developed version. Reliability and validity were examined; descriptive comparisons were made with the results of the English study. Measurement invariance (MI) analyses between TBI and general population samples were conducted prior to establishing reference values. Factors contributing to the total and scale scores of the PCSI-SR8 were identified using regression analyses. Reference values were calculated using percentiles.

Results

Most children (TBI: 83%; general population: 79%) rated at least one symptom as “a little” bothersome. The German PCSI-SR8 met the psychometric assumptions in both samples and was comparable to the English version. The four-factor structure comprising physical, emotional, cognitive, and fatigue symptoms could be replicated. The MI assumption was retained. Therefore, reference values could be provided to determine the symptom burden of patients in relation to a comparable general population. Clinical relevance of reported symptoms is indicated by a score of 8, which is one standard deviation above the mean of the general population sample.

Conclusion

The German version of the PCSI-SR8 is suitable for assessment of PCS after pTBI. The reference values allow for a more comprehensive evaluation of PCS following pTBI. Future research should focus on validation of the PCSI-SR8 in more acute phases of TBI, psychometric examination of the pre-post version, and child-proxy comparisons.
A model for predicting return of spontaneous circulation and neurological outcomes in adults after in-hospital cardiac arrest: development and evaluation
Authors: Li Zheng , Xing Jihong
Published: November 2023

Introduction

In-hospital CA (IHCA) is associated with rates of high incidence, low return of spontaneous circulation (ROSC), low survival to discharge, and poor neurological outcomes. We aimed to construct and evaluate prediction models for non-return of spontaneous circulation (non-ROSC) and poor neurological outcomes 12 months after ROSC (PNO-12).

Methods

We retrospectively analyzed baseline and clinical data from patients experiencing cardiac arrest (CA) in a big academic hospital of Jilin University in China. Patients experiencing CA between September 1, 2019 and December 31, 2020 were categorized into the ROSC and non-ROSC groups. Patients maintaining ROSC >20 min were divided into the good and PNO-12 subgroups.

Results

Univariate and multivariate logistic regression identified independent factors associated with non-ROSC and PNO-12. Two nomogram prediction models were constructed and evaluated. Of 2,129 patients with IHCA, 851 were included in the study. Multivariate logistic regression analysis revealed that male sex, age >80 years, CPR duration >23 min, and total dose of adrenaline >3 mg were significant risk factors for non-ROSC. Before CA, combined arrhythmia, initial defibrillation rhythm, and advanced airway management (mainly as endotracheal intubation) also influenced outcomes. The area under the receiver operating characteristic curve in the prediction model was 0.904 (C-index: 0.901). Respiratory failure, shock, CA in the monitoring area, advanced airway management, and noradrenaline administration were independent risk factors for PNO-12. The AUC was 0.912 (C-index: 0.918).

Conclusions

Prediction models based on IHCA data could be helpful to reduce mortality rates and improve prognosis.
Identification of Luminal A breast cancer by using deep learning analysis based on multi-modal images
Authors: Liu Menghan , Zhang Shuai , Du Yanan , Zhang Xiaodong , Wang Dawei , Ren Wanqing , Sun Jingxiang , Yang Shiwei , Zhang Guang
Published: November 2023

Purpose

To evaluate the diagnostic performance of a deep learning model based on multi-modal images in identifying molecular subtype of breast cancer.

Materials and methods

A total of 158 breast cancer patients (170 lesions, median age, 50.8 ± 11.0 years), including 78 Luminal A subtype and 92 non-Luminal A subtype lesions, were retrospectively analyzed and divided into a training set (n = 100), test set (n = 45), and validation set (n = 25). Mammography (MG) and magnetic resonance imaging (MRI) images were used. Five single-mode models, i.e., MG, T2-weighted imaging (T2WI), diffusion weighting imaging (DWI), axial apparent dispersion coefficient (ADC), and dynamic contrast-enhanced MRI (DCE-MRI), were selected. The deep learning network ResNet50 was used as the basic feature extraction and classification network to construct the molecular subtype identification model. The receiver operating characteristic curve were used to evaluate the prediction efficiency of each model.

Results

The accuracy, sensitivity and specificity of a multi-modal tool for identifying Luminal A subtype were 0.711, 0.889, and 0.593, respectively, and the area under the curve (AUC) was 0.802 (95% CI, 0.657- 0.906); the accuracy, sensitivity, and AUC were higher than those of any single-modal model, but the specificity was slightly lower than that of DCE-MRI model. The AUC value of MG, T2WI, DWI, ADC, and DCE-MRI model was 0.593 (95%CI, 0.436-0.737), 0.700 (95%CI, 0.545-0.827), 0.564 (95%CI, 0.408-0.711), 0.679 (95%CI, 0.523-0.810), and 0.553 (95%CI, 0.398-0.702), respectively.

Conclusion

The combination of deep learning and multi-modal imaging is of great significance for diagnosing breast cancer subtypes and selecting personalized treatment plans for doctors.
Incidence and associated factors of developing second pelvic malignant neoplasms among prostate cancer patients treated with radiotherapy
Authors: Wang Youbiao , Chen Ru , Deng Xinxi , Jiang Xinghua
Published: November 2023

Objective

To identify risk factors of secondary pelvic malignant neoplasms (SPMNs) among prostate cancer (PCa) patients treated with radiotherapy. Simultaneously, population-based data were used to validate the high risk of SPMNs in PCa patients with radiotherapy.

Materials and methods

We identified male patients diagnosed with PCa (localized and regional) as the first primary cancer and pelvic malignant neoplasm (including bladder and rectal cancer) as secondary cancer from Surveillance, Epidemiology, and End Results database (1975-2020). An external validation cohort was obtained from the First Affiliated Hospital of Nanchang University. The Fine-Gray competing risk regression and Poisson regression were utilized to evaluate the risk of SPMNs development. Poisson regression was also performed to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to assess the overall survival (OS) of patients with SPMNs.

Results

89397 PCa patients treated with radiotherapy were enrolled. We identified associated factors of SPMNs, including age at diagnosis, race, year of diagnosis, marital status, radiation strategy and latency. In the multivariable competing risk regression model and Poisson regression model, a significantly higher risk of SPMNs development was observed in patients over 50 years(P<0.05), white patients(P<0.001), unmarried patients and treated with brachytherapy combined with external beam radiotherapy or brachytherapy(P<0.05). Patients treated with radiotherapy had a higher bladder and rectal cancer incidence than the general population. Patients who developed SPMNs showed poorer OS.

Conclusion

We identified several risk factors associated with SPMNs and confirmed a relatively higher incidence of bladder and rectal cancer among PCa patients with radiotherapy. These results help tailor treatment and surveillance strategies.
Lymphovascular invasion is an independent prognostic factor in breast cancer irrespective of axillary node metastasis and molecular subtypes
Authors: Lee Suk Jun , Go Jieon , Ahn Byung Soo , Ahn Jee Hyun , Kim Jee Ye , Park Hyung Seok , Kim Seung Il , Park Byeong-Woo , Park Seho
Published: November 2023

Purpose

Lymphovascular invasion (LVI) is a well-known poor prognostic factor for early breast cancer. However, the effect of LVI on breast cancer subtype and node status remains unknown. In this study, we aimed to evaluate the clinical significance of LVI on the recurrence and long-term survival of patients with early breast cancer by comparing groups according to the subtype and node status.

Methods

We retrospectively reviewed the medical records of 4554 patients with breast cancer who underwent breast cancer surgery between January 2010 and December 2017. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors related to the DFS and OS according to the nodal status and breast cancer subtype.

Results

During a follow-up period of 94 months, the median OS and DFS were 92 and 90 months, respectively. The LVI expression rate was 8.4%. LVI had a negative impact on the DFS and OS, regardless of the lymph node status. LVI was associated with higher recurrence and lower survival in the luminal A, human epidermal growth factor receptor 2-positive, and triple-negative breast cancer subtypes. The Cox proportional hazards model showed that LVI was a significant prognostic factor for both DFS and OS. No correlation has been observed between LVI and the Oncotype Dx results in terms of prognostic value in early breast cancer.

Conclusion

LVI is an independent poor prognostic factor in patients with early breast cancer, regardless of the node status and molecular subtype. Therefore, the LVI status should be considered when making treatment decisions for patients with early stage breast cancer; however, further prospective studies are warranted.
Identifying clinical features and molecular characteristics of the endometrial clear cell carcinoma
Authors: Cai Yuhan , Han Qin , Guo Hongyan
Published: November 2023

Objective

The aim of this study was to verify TCGA subtypes in endometrial clear cell carcinoma (ECCC) and determine their clinical and molecular characteristics.

Methods

We summarized and compared the clinical features of 28 clear cell carcinoma and 112 endometrioid carcinoma patients. Of the 28 ECCCs, 19 underwent TCGA classification, and other markers (ER, PR, ARID1A, ARIB1B, TAF1, and HER-2) were also detected by IHC, and outcomes were assessed.

Results

Compared to endometrioid carcinoma, ECCC had an older age of onset (median age, 64.5 years, range 31–81 years), higher rate of myometrial invasion (42.8% vs. 21.5% in endometrioid carcinoma), LVSI (33% vs. 16%), and more advanced FIGO stage. Among the ECCCs, LVSI was a poor prognostic factor. TCGA classification was performed for 19 ECCCs: two POLEmut cases (10.5%), three MMRd (15.8%), 11 p53wt (57.9%), and three p53abn (15.8%). Of the 19 ECCCs, six (31.6%) showed HER-2 positive expression, and eight (42.1%) had TAF1 expression loss. ECCCs possessed HER-2 and TAF1 expression had worse outcomes.

Conclusion

Our study summarized the clinical features of ECCC. The outcomes of patients with ECCC with TCGA subtypes differed from those of patients with endometrioid carcinoma. HER-2 and TAF1 may be new prognostic factors.
Quantitative melanoma diagnosis using spectral phasor analysis of hyperspectral imaging from label-free slices
Authors: Schuty Bruno , Martínez Sofía , Guerra Analía , Lecumberry Federico , Magliano Julio , Malacrida Leonel
Published: November 2023

Introduction

Melanoma diagnosis traditionally relies on microscopic examination of hematoxylin and eosin (H&E) slides by dermatopathologists to search for specific architectural and cytological features. Unfortunately, no single molecular marker exists to reliably differentiate melanoma from benign lesions such as nevi. This study explored the potential of autofluorescent molecules within tissues to provide molecular fingerprints indicative of degenerated melanocytes in melanoma.

Methods

Using hyperspectral imaging (HSI) and spectral phasor analysis, we investigated autofluorescence patterns in melanoma compared to intradermal nevi. Using UV excitation and a commercial spectral confocal microscope, we acquired label-free HSI data from the whole-slice samples.

Results

Our findings revealed distinct spectral phasor distributions between melanoma and intradermal nevi, with melanoma displaying a broader phasor phase distribution, signifying a more heterogeneous autofluorescence pattern. Notably, longer wavelengths associated with larger phases correlated with regions identified as melanoma by expert dermatopathologists using H&E staining. Quantitative analysis of phase and modulation histograms within the phasor clusters of five melanomas (with Breslow thicknesses ranging from 0.5 mm to 6 mm) and five intradermal nevi consistently highlighted differences between the two groups. We further demonstrated the potential for the discrimination of several melanocytic lesions using center-of-mass comparisons of phase and modulation variables. Remarkably, modulation versus phase center of mass comparisons revealed strong statistical significance among the groups. Additionally, we identified the molecular endogenous markers responsible for tissue autofluorescence, including collagen, elastin, NADH, FAD, and melanin. In melanoma, autofluorescence is characterized by a higher phase contribution, indicating an increase in FAD and melanin in melanocyte nests. In contrast, NADH, elastin, and collagen dominate the autofluorescence of the nevus.

Discussion

This work underscores the potential of autofluorescence and HSI-phasor analysis as valuable tools for quantifying tissue molecular fingerprints, thereby supporting more effective and quantitative melanoma diagnosis.