bluuebunny/crossref_metadata_2025 huggingface dataset:
A mesoporous superparamagnetic iron oxide nanoparticle as a generic drug delivery system for tumor ferroptosis therapy
Authors: Yang Jing , Xiong Wei , Huang Lin , Li Zongheng , Fan Qingdeng , Hu Fang , Duan Xiaopin , Fan Junbing , Li Bo , Feng Jie , Xu Yikai , Chen Xiaoyuan , Shen Zheyu
Published: April 2024

As a famous drug delivery system (DDS), mesoporous organosilica nanoparticles (MON) are degraded slowly in vivo and the degraded components are not useful for cell nutrition or cancer theranostics, and superparamagnetic iron oxide nanoparticles (SPION) are not mesoporous with low drug loading content (DLC). To overcome the problems of MON and SPION, we developed mesoporous SPIONs (MSPIONs) with an average diameter of 70 nm and pore size of 3.9 nm. Sorafenib (SFN) and/or brequinar (BQR) were loaded into the mesopores of MSPION, generating SFN@MSPION, BQR@MSPION and SFN/BQR@MSPION with high DLC of 11.5% (SFN), 10.1% (BQR) and 10.0% (SNF + BQR), demonstrating that our MSPION is a generic DDS. SFN/BQR@MSPION can be used for high performance ferroptosis therapy of tumors because: (1) the released Fe2+/3+ in tumor microenvironment (TME) can produce •OH via Fenton reaction; (2) the released SFN in TME can inhibit the cystine/glutamate reverse transporter, decrease the intracellular glutathione (GSH) and GSH peroxidase 4 levels, and thus enhance reactive oxygen species and lipid peroxide levels; (3) the released BQR in TME can further enhance the intracellular oxidative stress via dihydroorotate dehydrogenase inhibition. The ferroptosis therapeutic mechanism, efficacy and biosafety of MSPION-based DDS were verified on tumor cells and tumor-bearing mice.
Bioproduction of cerium-bearing magnetite and application to improve carbon-black supported platinum catalysts
Authors: Xie Jinxin , Zhao Ziyu , Coker Victoria S. , O’Driscoll Brian , Cai Rongsheng , Haigh Sarah J. , Holmes Stuart M. , Lloyd Jonathan R.
Published: April 2024

Background

Biogeochemical processing of metals including the fabrication of novel nanomaterials from metal contaminated waste streams by microbial cells is an area of intense interest in the environmental sciences.

Results

Here we focus on the fate of Ce during the microbial reduction of a suite of Ce-bearing ferrihydrites with between 0.2 and 4.2 mol% Ce. Cerium K-edge X-ray absorption near edge structure (XANES) analyses showed that trivalent and tetravalent cerium co-existed, with a higher proportion of tetravalent cerium observed with increasing Ce-bearing of the ferrihydrite. The subsurface metal-reducing bacterium Geobacter sulfurreducens was used to bioreduce Ce-bearing ferrihydrite, and with 0.2 mol% and 0.5 mol% Ce, an Fe(II)-bearing mineral, magnetite (Fe(II)(III)2O4), formed alongside a small amount of goethite (FeOOH). At higher Ce-doping (1.4 mol% and 4.2 mol%) Fe(III) bioreduction was inhibited and goethite dominated the final products. During microbial Fe(III) reduction Ce was not released to solution, suggesting Ce remained associated with the Fe minerals during redox cycling, even at high Ce loadings. In addition, Fe L2,3 X-ray magnetic circular dichroism (XMCD) analyses suggested that Ce partially incorporated into the Fe(III) crystallographic sites in the magnetite. The use of Ce-bearing biomagnetite prepared in this study was tested for hydrogen fuel cell catalyst applications. Platinum/carbon black electrodes were fabricated, containing 10% biomagnetite with 0.2 mol% Ce in the catalyst. The addition of bioreduced Ce-magnetite improved the electrode durability when compared to a normal Pt/CB catalyst.

Conclusion

Different concentrations of Ce can inhibit the bioreduction of Fe(III) minerals, resulting in the formation of different bioreduction products. Bioprocessing of Fe-minerals to form Ce-containing magnetite (potentially from waste sources) offers a sustainable route to the production of fuel cell catalysts with improved performance.

Graphical Abstract
Leisure-time and occupational physical activity and risk of cardiovascular disease incidence: a systematic-review and dose-response meta-analysis of prospective cohort studies
Authors: Kazemi Asma , Soltani Sepideh , Aune Dagfinn , Hosseini Elham , Mokhtari Zeinab , Hassanzadeh Zahra , Jayedi Ahmad , Pitanga Francisco , Akhlaghi Masoumeh
Published: April 2024

Background and objective

Physical activity has benefits for the cardiovascular system, however, what levels and types of activity provide optimal cardiovascular health is unclear. We aimed to determine the level of physical activity that has the most benefits against cardiovascular diseases (CVD).

Methods

PubMed, Scopus, and Web of Science were searched for prospective cohort studies on leisure-time (LTPA) or occupational physical activity (OPA) as the exposure and major types of CVD (total CVD, coronary heart disease [CHD], stroke, and atrial fibrillation [AF]) incidence as the outcome. Risk of bias of studies was evaluated using the ROBINS-I tool. Summary hazard ratios (HR) were calculated using random-effects pairwise model.

Results

A total of 103 studies were included in the analysis. The highest versus the lowest LTPA was associated with a lower risk of overall CVD (HR = 0.81; 95% CI: 0.77–0.86), CHD (HR = 0.83; 0.79–0.88), and stroke (HR = 0.83; 0.79–0.88), but not AF (HR = 0.98; 0.92–1.05). Linear dose-response analyses showed a 10%, 12%, 9%, and 8% risk reduction in CVD, CHD, stroke, and AF incidence, respectively, for every 20 MET-hours/week increase in LTPA. In nonlinear dose-response analyses, there were inverse associations up to 20 MET-hours/week with 19% and 20% reduction in CVD and CHD risk, and up to 25 MET-hours/week with 22% reduction in stroke, with no further risk reduction at higher LTPA levels. For AF, there was a U-shaped nonlinear association with the maximum 8% risk reduction at 10 MET-hours/week of LTPA. Higher levels of OPA were not associated with risk of CVD, CHD, stroke, or AF.

Conclusions

Overall, results showed an inverse dose-response relationship between LTPA and risk of CVD, CHD, stroke, and AF. Running was the most beneficial LTPA but the risk was similar among various LTPA intensities. OPA showed no benefits in total or any type of CVD.
Resistance to African swine fever virus among African domestic pigs appears to be associated with a distinct polymorphic signature in the RelA gene and upregulation of RelA transcription
Authors: Bisimwa Patrick N. , Ongus Juliette R. , Tonui Ronald , Bisimwa Espoir B. , Steinaa Lucilla
Published: April 2024

African swine fever virus (ASFV) is a highly contagious and fatal hemorrhagic disease of domestic pigs, which poses a major threat to the swine industry worldwide. Studies have shown that indigenous African pigs tolerate ASFV infection better than European pigs. The porcine v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) encoding a p65 kD protein, a major subunit of the NF-kB transcription factor, plays important roles in controlling both innate and adaptive immunity during infection with ASFV. In the present study, RelA genes from ASFV-surviving and symptomatic pigs were sequenced and found to contain polymorphisms revealing two discrete RelA amino acid sequences. One was found in the surviving pigs, and the other in symptomatic pigs. In total, 16 nonsynonymous SNPs (nsSNPs) resulting in codon changes were identified using bioinformatics software (SIFT and Polyphen v2) and web-based tools (MutPre and PredictSNP). Seven nsSNPs (P374-S, T448-S, P462-R, V464-P, Q478-H, L495-E, and P499-Q) were predicted to alter RelA protein function and stability, while 5 of these (P374-S, T448-S, P462-R, L495-E, and Q499-P) were predicted as disease-related SNPs.

Additionally, the inflammatory cytokine levels of IFN-α, IL-10, and TNF-α at both the protein and the mRNA transcript levels were measured using ELISA and Real-Time PCR, respectively. The resulting data was used in correlation analysis to assess the association between cytokine levels and the RelA gene expression. Higher levels of IFN-α and detectable levels of IL-10 protein and RelA mRNA were observed in surviving pigs compared to healthy (non-infected). A positive correlation of IFN-α cytokine levels with RelA mRNA expression was also obtained. In conclusion, 7 polymorphic events in the coding region of the RelA gene may contribute to the tolerance of ASFV in pigs.
Spexin ameliorated obesity-related metabolic disorders through promoting white adipose browning mediated by JAK2-STAT3 pathway
Authors: Zeng Bihe , Shen Qin , Wang Bo , Tang Xuan , Jiang Jiaqi , Zheng Yiming , Huang Hongbiao , Zhuo Wenyu , Wang Wang , Gao Yang , Li Xuan , Wang Shuhui , Li Wenjie , Qian Guanghui , Qin Jie , Hou Miao , Lv Haitao
Published: April 2024

Background

Spexin, a 14 amino acid peptide, has been reported to regulate obesity and its associated complications. However, little is known about the underlying molecular mechanism. Therefore, this study aimed to investigate the effects of spexin on obesity and explore the detailed molecular mechanisms in vivo and in vitro.

Methods

Male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity, and mice fed a standard fat diet were used as controls. Then, these mice were treated with SPX or Vehicle by intraperitoneal injection for an additional 12 weeks, respectively. The metabolic profile, fat-browning specific markers and mitochondrial contents were detected. In vitro, 3T3-L1 cells were used to investigate the molecular mechanisms.

Results

After 12 weeks of treatment, SPX significantly decreased body weight, serum lipid levels, and improved insulin sensitivity in HFD-induced obese mice. Moreover, SPX was found to promote oxygen consumption in HFD mice, and it increased mitochondrial content as well as the expression of brown-specific markers in white adipose tissue (WAT) of HFD mice. These results were consistent with the increase in mitochondrial content and the expression of brown-specific markers in 3T3-L1 mature adipocytes. Of note, the spexin-mediated beneficial pro-browning actions were abolished by the JAK2/STAT3 pathway antagonists in mature 3T3-L1 cells.

Conclusions

These data indicate that spexin ameliorates obesity-induced metabolic disorders by improving WAT browning via activation of the JAK2/STAT3 signaling pathway. Therefore, SPX may serve as a new therapeutic candidate for treating obesity.
Adaptive immune changes associate with clinical progression of Alzheimer’s disease
Authors: van Olst Lynn , Kamermans Alwin , Halters Sem , van der Pol Susanne M. A. , Rodriguez Ernesto , Verberk Inge M. W. , Verberk Sanne G. S. , Wessels Danielle W. R. , Rodriguez-Mogeda Carla , Verhoeff Jan , Wouters Dorine , Van den Bossche Jan , Garcia-Vallejo Juan J. , Lemstra Afina W. , Witte Maarten E. , van der Flier Wiesje M. , Teunissen Charlotte E. , de Vries Helga E.
Published: April 2024

Background

Alzheimer’s disease (AD) is the most frequent cause of dementia. Recent evidence suggests the involvement of peripheral immune cells in the disease, but the underlying mechanisms remain unclear.

Methods

We comprehensively mapped peripheral immune changes in AD patients with mild cognitive impairment (MCI) or dementia compared to controls, using cytometry by time-of-flight (CyTOF).

Results

We found an adaptive immune signature in AD, and specifically highlight the accumulation of PD1+ CD57+ CD8+ T effector memory cells re-expressing CD45RA in the MCI stage of AD. In addition, several innate and adaptive immune cell subsets correlated to cerebrospinal fluid (CSF) biomarkers of AD neuropathology and measures for cognitive decline. Intriguingly, subsets of memory T and B cells were negatively associated with CSF biomarkers for tau pathology, neurodegeneration and neuroinflammation in AD patients. Lastly, we established the influence of the APOE ε4 allele on peripheral immunity.

Conclusions

Our findings illustrate significant peripheral immune alterations associated with both early and late clinical stages of AD, emphasizing the necessity for further investigation into how these changes influence underlying brain pathology.
Exploring barriers to access to care following the 2021 socio-political changes in Afghanistan: a qualitative study
Authors: Lamberti-Castronuovo Alessandro , Valente Martina , Bocchini Francesca , Trentin Monica , Paschetto Michela , Bahdori Ghulam Ali , Khadem Jan Agha , Nadeem Mirza Sayed , Patmal Mohammad Hanif , Alizai Mohammad Tawoos , Miccio Rossella , Ragazzoni Luca
Published: April 2024

Background

Following the change of government in August 2021, the social and economic landscape of Afghanistan deteriorated into an economic and humanitarian crisis. Afghans continue to struggle to access basic healthcare services, making Universal Health Coverage (UHC) in the country a major challenge. The aim of this study was to perform a qualitative investigation into the main access to care challenges in Afghanistan and whether these challenges have been influenced by the recent socio-political developments, by examining the perspectives of health professionals and hospital directors working in the country.

Methods

Health professionals working in facilities run by an international non-government organisation, which has maintained continuous operations since 1999 and has become a key health reference point for the population, alongside the public health system, and hospital directors working in government hospitals were recruited to participate in an in-depth qualitative study using semi-structured interviews.

Results

A total of 43 participants from ten provinces were interviewed in this study. Four issues were identified as critical barriers to achieving UHC in Afghanistan: (1) the lack of quality human resources; (2) the suboptimal management of chronic diseases and trauma; (3) the inaccessibility of necessary health services due to financial hardship; (4) the unequal accessibility of care for different demographic groups.

Conclusions

Health professionals and hospital directors shed light on weaknesses in the Afghan health system highlighting chronic issues and issues that have deteriorated as a result of the 2021 socio-political changes. In order to improve access to care, future healthcare system reforms should consider the perspectives of Afghan professionals working in the country, who are in close contact with Afghan patients and communities.
Assessment of the measurement properties of the Peabody Developmental Motor Scales-2 by applying the COSMIN methodology
Authors: Zhu Yuanye , Hu Jiahui , Ye Weibing , Korivi Mallikarjuna , Qian Yongdong
Published: April 2024

The Peabody Developmental Motor Scales-2 (PDMS-2) has been used to assess the gross and fine motor skills of children (0–6 years); however, the measurement properties of the PDMS-2 are inconclusive. Here, we aimed to systematically review the measurement properties of PDMS-2, and synthesize the quality of evidence using the Consensus-based Standards for the Selection of Health Measurements Instruments (COSMIN) methodology. Electronic databases, including PubMed, EMBASE, Web of Science, CINAHL and MEDLINE, were searched for relevant studies through January 2023; these studies used PDMS-2. The methodological quality of each study was assessed by the COSMIN risk-of-bias checklist, and the measurement properties of PDMS-2 were evaluated by the COSMIN quality criteria. Modified GRADE was used to evaluate the quality of the evidence. We included a total of 22 articles in the assessment. Among the assessed measurement properties, the content validity of PDMS-2 was found to be sufficient with moderate-quality evidence. The structural validity, internal consistency, test-retest reliability and interrater reliability of the PDMS-2 were sufficient for high-quality evidence, while the intrarater reliability was sufficient for moderate-quality evidence. Sufficient high-quality evidence was also found for the measurement error of PDMS-2. The overall construct validity of the PDMS-2 was sufficient but showed inconsistent quality of evidence. The responsiveness of PDMS-2 appears to be sufficient with low-quality evidence. Our findings demonstrate that the PDMS-2 has sufficient content validity, structural validity, internal consistency, reliability and measurement error with moderate to high-quality evidence. Therefore, PDMS-2 is graded as ‘A’ and can be used in motor development research and clinical settings.
Subcutaneous injection of adipose stromal cell-secretome improves renal function and reduces inflammation in established acute kidney injury
Authors: Ullah Md Mahbub , Collett Jason A. , Monroe Jacob C. , Traktuev Dmitry , Coleman Michael , March Keith L. , Basile David P.
Published: April 2024

Background

Adipose stromal cells (ASC) are a form of mesenchymal stromal cells that elicit effects primarily via secreted factors, which may have advantages for the treatment of injury or disease. Several previous studies have demonstrated a protective role for MSC/ASC on mitigating acute kidney injury but whether ASC derived factors could hasten recovery from established injury has not been evaluated.

Methods

We generated a concentrated secretome (CS) of human ASC under well-defined conditions and evaluated its ability to improve the recovery of renal function in a preclinical model of acute kidney injury (AKI) in rats. 24 h following bilateral ischemia/reperfusion (I/R), rats were randomized following determination of plasma creatinine into groups receiving vehicle -control or ASC-CS treatment by subcutaneous injection (2 mg protein/kg) and monitored for evaluation of renal function, structure and inflammation.

Results

Renal function, assessed by plasma creatinine levels, recovered faster in ASC-CS treated rats vs vehicle. The most prominent difference between the ASC-CS treated vs vehicle was observed in rats with the most severe degree of initial injury (Pcr > 3.0 mg/dl 24 h post I/R), whereas rats with less severe injury (Pcr < 2.9 mg/dl) recovered quickly regardless of treatment. The quicker recovery of ASC-treated rats with severe injury was associated with less tissue damage, inflammation, and lower plasma angiopoietin 2. In vitro, ASC-CS attenuated the activation of the Th17 phenotype in lymphocytes isolated from injured kidneys.

Conclusions

Taken together, these data suggest that ASC-CS represents a potent therapeutic option to improve established AKI.
Construction and validation of machine learning algorithm for predicting depression among home-quarantined individuals during the large-scale COVID-19 outbreak: based on Adaboost model
Authors: Zhou Yiwei , Zhang Zejie , Li Qin , Mao Guangyun , Zhou Zumu
Published: April 2024

Objectives

COVID-19 epidemics often lead to elevated levels of depression. To accurately identify and predict depression levels in home-quarantined individuals during a COVID-19 epidemic, this study constructed a depression prediction model based on multiple machine learning algorithms and validated its effectiveness.

Methods

A cross-sectional method was used to examine the depression status of individuals quarantined at home during the epidemic via the network. Characteristics included variables on sociodemographics, COVID-19 and its prevention and control measures, impact on life, work, health and economy after the city was sealed off, and PHQ-9 scale scores. The home-quarantined subjects were randomly divided into training set and validation set according to the ratio of 7:3, and the performance of different machine learning models were compared by 10-fold cross-validation, and the model algorithm with the best performance was selected from 15 models to construct and validate the depression prediction model for home-quarantined subjects. The validity of different models was compared based on accuracy, precision, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC), and the best model suitable for the data framework of this study was identified.

Results

The prevalence of depression among home-quarantined individuals during the epidemic was 31.66% (202/638), and the constructed Adaboost depression prediction model had an ACC of 0.7917, an accuracy of 0.7180, and an AUC of 0.7803, which was better than the other 15 models on the combination of various performance measures. In the validation sets, the AUC was greater than 0.83.

Conclusions

The Adaboost machine learning algorithm developed in this study can be used to construct a depression prediction model for home-quarantined individuals that has better machine learning performance, as well as high effectiveness, robustness, and generalizability.
Immune cell trafficking: a novel perspective on the gut-skin axis
Authors: Zhang Jiayan , Yao Zhirong
Published: April 2024

Immune cell trafficking, an essential mechanism for maintaining immunological homeostasis and mounting effective responses to infections, operates under a stringent regulatory framework. Recent advances have shed light on the perturbation of cell migration patterns, highlighting how such disturbances can propagate inflammatory diseases from their origin to distal organs. This review collates and discusses current evidence that demonstrates atypical communication between the gut and skin, which are conventionally viewed as distinct immunological spheres, in the milieu of inflammation. We focus on the aberrant, reciprocal translocation of immune cells along the gut-skin axis as a pivotal factor linking intestinal and dermatological inflammatory conditions. Recognizing that the translation of these findings into clinical practices is nascent, we suggest that therapeutic strategies aimed at modulating the axis may offer substantial benefits in mitigating the widespread impact of inflammatory diseases.
Self-operation and low-carbon scheduling optimization of solar thermal power plants with thermal storage systems
Authors: Sun Jing
Published: April 2024

Photo thermal power generation, as a renewable energy technology, has broad development prospects. However, the operation and scheduling of photo thermal power plants rarely consider their internal structure and energy flow characteristics. Therefore, this study explains the structure of a solar thermal power plant with a thermal storage system and analyzes its main energy flow modes to establish a self-operation and low-carbon scheduling optimization model for the solar thermal power plant. The simulation results of the example showed that for the self-operating model oriented towards power generation planning and peak valley electricity prices, the existence of a thermal storage system could improve the power generation capacity and revenue of the photovoltaic power plant. For example, when the capacity of the thermal storage system was greater than 6 h, the penalty for insufficient power generation in the simulation result was 0 $, and the maximum increase in revenue reached 84.9% as the capacity of the thermal storage system increased. In addition, when the capacity of the thermal storage system increased from 0 to 8 h, the comprehensive operating cost decreased from 1635.2 k $ to 1224.6 k $, and the carbon emissions decreased from 26.4 × 103 ton to 22.1 × 103 ton. Compared with the existing literature, this study provides a more comprehensive and systematic solution through detailed energy flow analysis and optimization model. The research has practical and far-reaching significance for promoting the development of clean energy technology, improving the sustainable utilization of renewable energy, and optimizing the overall performance of the energy system.
Principles of fire ecology
Authors: Kobziar Leda N. , Hiers J. Kevin , Belcher Claire M. , Bond William J. , Enquist Carolyn A. , Loudermilk E. L. , Miesel Jessica R. , O’Brien Joseph J. , Pausas Juli G. , Hood Sharon , Keane Robert , Morgan Penelope , Pingree Melissa R. A. , Riley Karin , Safford Hugh , Seijo Francisco , Varner J. Morgan , Wall Tamara , Watts Adam C.
Published: April 2024

Fire ecology is a complex discipline that can only be understood by integrating biological, physical, and social sciences. The science of fire ecology explores wildland fire’s mechanisms and effects across all scales of time and space. However, the lack of defined, organizing concepts in fire ecology dilutes its collective impact on knowledge and management decision-making and makes the discipline vulnerable to misunderstanding and misappropriation. Fire ecology has matured as a discipline and deserves an enunciation of its unique emergent principles of organization. Most scientific disciplines have established theories, laws, and principles that have been tested, debated, and adopted by the discipline’s practitioners. Such principles reflect the consensus of current knowledge, guide methodology and interpretation, and expose knowledge gaps in a coherent and structured way. In this manuscript, we introduce five comprehensive principles to define the knowledge fire ecology has produced and provide a framework to support the continued development and impact of the fire ecology discipline.
Uncertainty assessment in unsupervised machine-learning methods for deepwater channel seismic facies using outcrop-derived 3D models and synthetic seismic data
Authors: La Marca Karelia , Bedle Heather , Stright Lisa , Marfurt Kurt
Published: April 2024

Unsupervised machine-learning (ML) techniques have been widely applied to analyze seismic reflection data, including the identification of seismic facies and structural features. However, interpreting the resulting clusters often relies on geoscientists’ expertise, necessitating a robustness assessment of these methods. To evaluate their reliability, synthetic data generated from an actual outcrop model are used to demonstrate how two unsupervised methods, self-organizing maps (SOMs) and generative topographic maps (GTMs), cluster deepwater channel-related seismic facies and then measure the associated error. Six seismic attributes, comprising root-mean-square amplitude, instantaneous envelope, peak magnitude, and spectral decomposition frequencies at 20, 40, and 55 Hz, served as input variables. Geobodies are assigned to each cluster formed, and the error in facies clustering is quantified by comparing the actual 3D model with the facies grouped by ML methods on a voxel-by-voxel basis. This allowed for error quantification and the computation of metrics such as F1 score and accuracy through correlation matrices. Key findings reveal that (1) GTM and SOM exhibit similar performance, with a clustering configuration of 81 for GTM slightly outperforming others. (2) Error rates are approximately 2% for the predominant facies (background shale) but significantly higher for individual channel-related facies, suggesting that channel clusters might represent multiple facies. (3) Resolution and imbalanced data distribution impact seismic facies predictability, resulting in nonuniqueness in cluster generation. (4) Using synthetic seismic data proved valuable for experimenting with different unsupervised MLs, highlighting the need for assessing uncertainty in these methods, given their implications for crucial economic decisions reliant on reservoir interpretation, modeling, and volumetric estimations.
NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer
Authors: Klümper Niklas , Tran Ngoc Khanh , Zschäbitz Stefanie , Hahn Oliver , Büttner Thomas , Roghmann Florian , Bolenz Christian , Zengerling Friedemann , Schwab Constantin , Nagy Dora , Toma Marieta , Kristiansen Glen , Heers Hendrik , Ivanyi Philipp , Niegisch Günter , Grunewald Camilla Marisa , Darr Christopher , Farid Arian , Schlack Katrin , Abbas Mahmoud , Aydogdu Can , Casuscelli Jozefina , Mokry Theresa , Mayr Michael , Niedersüß-Beke Dora , Rausch Steffen , Dietrich Dimo , Saal Jonas , Ellinger Jörg , Ritter Manuel , Alajati Abdullah , Kuppe Christoph , Meeks Joshua , Vera Badillo Francisco E. , Nakauma-González J. Alberto , Boormans Joost , Junker Kerstin , Hartmann Arndt , Grünwald Viktor , Hölzel Michael , Eckstein Markus
Published: April 2024

PURPOSE

The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC.

MATERIALS AND METHODS

We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non–EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for NECTIN4 CNVs.

RESULTS

NECTIN4 amplifications are frequent genomic events in muscle-invasive bladder cancer (TCGA bladder cancer data set: approximately 17%) and mUC (approximately 26% in our mUC cohorts). In mUC-EV, NECTIN4 amplification represents a stable genomic alteration during metastatic progression and associates with enhanced membranous NECTIN4 protein expression. Ninety-six percent (27 of 28) of patients with NECTIN4 amplifications demonstrated objective responses to EV compared with 32% (24 of 74) in the nonamplified subgroup ( P < .001). In multivariable Cox analysis adjusted for age, sex, and Bellmunt risk factors, NECTIN4 amplifications led to a 92% risk reduction for death (hazard ratio, 0.08 [95% CI, 0.02 to 0.34]; P < .001). In the mUC-non-EV, NECTIN4 amplifications were not associated with outcomes. TCGA Pan-Cancer analysis demonstrated that NECTIN4 amplifications occur frequently in other cancers, for example, in 5%-10% of breast and lung cancers.

CONCLUSION

NECTIN4 amplifications are genomic predictors of EV responses and long-term survival in patients with mUC.
Establishment of Human Pituitary Neuroendocrine Tumor Derived Organoid and Its Pilot Application for Drug Screening
Authors: Cui Run , Duan Hao , Hu Wanming , Li Chang , Zhong Sheng , Liang Lun , Chen Siyu , Hu Hongrong , He Zhenqiang , Wang Zhenning , Guo Xiaoyu , Chen Zexin , Xu Cong , Zhu Yu , Chen Yinsheng , Sai Ke , Yang Qunying , Guo Chengcheng , Mou Yonggao , Jiang Xiaobing
Published: April 2024

Context

Precision medicine for pituitary neuroendocrine tumors (PitNETs) is limited by the lack of reliable research models.

Objective

To generate patient-derived organoids (PDOs), which could serve as a platform for personalized drug screening for PitNET patients.

Design

From July 2019 to May 2022, a total of 32 human PitNET specimens were collected for the establishment of organoids with an optimized culture protocol.

Setting

This study was conducted at Sun Yat-Sen University Cancer Center.

Patients

PitNET patients who were pathologically confirmed were enrolled in this study.

Interventions

Histological staining and whole-exome sequencing were utilized to confirm the pathologic and genomic features of PDOs. A drug response assay on PDOs was also performed.

Main Outcome Measures

PDOs retained key genetic and morphological features of their parental tumors.

Results

PDOs were successfully established from various types of PitNET samples with an overall success rate of 87.5%. Clinical nonfunctioning PitNETs-derived organoids (22/23, 95.7%) showed a higher likelihood of successful generation compared to those from functioning PitNETs (6/9, 66.7%). Preservation of cellular structure, subtype-specific neuroendocrine profiles, mutational features, and tumor microenvironment heterogeneity from parental tumors was observed. A distinctive response profile in drug tests was observed among the organoids from patients with different subtypes of PitNETs. With the validation of key characteristics from parental tumors in histological, genomic, and microenvironment heterogeneity consistency assays, we demonstrated the predictive value of the PDOs in testing individual drugs.

Conclusion

The established PDOs, retaining typical features of parental tumors, indicate a translational significance in innovating personalized treatment for refractory PitNETs.
Mapping RNA-Protein Interactions with Subcellular Resolution Using Colocalization CLIP
Authors: Yi Soon , Singh Shashi S , Rozen-Gagnon Kathryn , Luna Joseph M
Published: April 2024

RNA binding proteins (RBPs) are essential for RNA metabolism and profoundly impact health and disease. The subcellular organization of RBP interaction networks with target RNAs remains largely unexplored. Here, we develop colocalization CLIP, a method that combines CrossLinking and ImmunoPrecipitation (CLIP) with proximity labeling, to explore in-depth the subcellular RNA interactions of the RNA-binding protein HuR. Using this method, we uncover HuR's dynamic and location-specific interactions with RNA, revealing alterations in sequence preferences and interactions in the nucleus, cytosol, or stress granule compartments. We uncover HuR's unique binding preferences within stress granules during arsenite stress, illuminating intricate interactions that conventional methodologies cannot capture. Overall, coCLIP provides a powerful method for revealing RBP:RNA interactions based on localization and lays the foundation for an advanced understanding of RBP models that incorporate subcellular location as a critical determinant of their functions.
Monitoramento de vetores do gênero Aedes durante o inverno no município de Barbacena, Minas Gerais, Brasil – 2018
Authors: Bergamaschine Juliano , Silveira Duarte Bernardo , Carvalho Nascimento de Andrade Matheus , Viana Vieira Arthur , Roman Amaral Marcela , Maia Lemos Barreto Larissa , Stelmo da Silva Márcio Heitor , Oliveira dos Santos Junior Ademir , Mayrink de Oliveira Dulcilene , Marques Campos Jonatan
Published: April 2024

Objetivo: estimar a oviposição e distribuição espacial de vetores Aedes durante a estação de inverno e correlacionar essas estimativas com dados climáticos do mesmo período. Métodos: estudo de campo conduzido no município de Barbacena-MG, em 2018. O monitoramento, a coleta de ovos e a estimativa de índices estegômicos de vetores Aedes foram obtidos por meio de ovitrampas. Os Índices de Densidade de Ovos (IDO) e de Positividade de Ovitrampas (IPO%) foram estimados conforme estações climáticas e semanas epidemiológicas. A correlação entre parâmetros meteorológicos (temperatura/pluviometria) e índices estegômicos (IDO/IPO) foi determinada pelo coeficiente de Spearman. Resultados: um total de 1.080 ovitrampas, instaladas em 39 bairros, foi analisado durante 10 semanas epidemiológicas, fornecendo um total de 970 ovos. Nas estações de outono, inverno e primavera, foram obtidos, respectivamente, 421, 470 e 70 ovos. Durante o outono, houve variação do IDO entre 14,2 e 34,2. O IPO manteve-se constante em 4,5%. Durante o inverno, houve variação do IDO entre 0,00 e 47,50 e do IPO entre 0,00% e 8,25%. Houve correlação negativa significativa tanto entre aumento da precipitação mensal e diminuição do número de ovos coletados (rho=-0.673) quanto entre aumento da precipitação mensal e diminuição do IPO (rho=-0.612). O valor geral do IDO e do IPO nas 10 semanas foi, respectivamente, 22,04 e 4,17% e, na estação de inverno, foi, respectivamente, 23,50 e 3,73%. Conclusão: os achados corroboram a presença de ovos e vetores do gênero Aedes mesmo em condições climáticas adversas para essas espécies e sustentam ações de manejo sanitário durante todo o ano.
Μέθοδοι εκτίμησης στάσης αισθητήρα LIDAR δισδιάστατων μετρήσεων μέσω ευθυγράμμισης πραγματικών με εικονικές σαρώσεις
Authors: Φιλοθέου Αλέξανδρος
Published: April 2024

Η ρομποτική κινητής βάσης είναι ένας ολοένα ανερχόμενος κλάδος της ρομποτικής, τόσο ως προς το εύρος των τομέων χρήσης της όσο και ως προς το περιεχόμενο των εφαρμογών της. Αυτόνομα επίγεια και ιπτάμενα ρομπότ χρησιμοποιούνται σε αποθήκες για την απογραφή προϊόντων και την εύρεση της θέσης τους, σε νοσοκομεία για την απολύμανση χώρων, στη γεωργία για παρακολούθηση καλλιεργειών και αυτοματοποίηση διαδικασιών, και για τη μεταφορά εμπορευμάτων ή ανθρώπων. Σε όλες τις περιπτώσεις είναι απαραίτητη η γνώση της στάσης ενός οχήματος στο χώρο από το ίδιο το όχημα, δηλαδή της θέσης και του προσανατολισμού του, για την αυτόνομη κίνησή του στο χώρο και για την ικανοποίηση των στόχων της αποστολής του. Σε εσωτερικούς χώρους, όπου είναι αδύνατη η πρόσβαση σε δορυφορικώς μεταδιδόμενες πληροφορίες στάσης, ή σε συμφραζόμενα όπου υποδομές μέτρησης εσωτερικού χώρου απουσιάζουν, η μόνη εναλλακτική είναι η εκτίμηση του διανύσματος στάσεως, και η διαδικασία εκτίμησης αναλαμβάνεται από το ίδιο το όχημα, με βάση τους αισθητήρες που αυτό φέρει.Το αντικείμενο της παρούσας διατριβής είναι η ρομποτική αυτόνομης επίγειας κινητής βάσης σε συμφραζόμενα απουσίας μέτρησης της στάσης της. Το κυρίως περιεχόμενο της αφορά στην εκτίμηση της στάσης μίας κινητής βάσης βάσει δισδιάστατων μετρήσεων που προέρχονται από έναν αισθητήρα αποστάσεων τύπου lidar, και στην ελάττωση του σφάλματος εκτίμησης, η οποία εκτίμηση προέρχεται από παραδοσιακές μεθόδους της βιβλιογραφίας. Πιο συγκεκριμένα ερευνούμε τρόπους με τους οποίους η ευθυγράμμιση μετρήσεων από τον φυσικό αισθητήρα με εικονικές σαρώσεις—υπολογιζόμενες με βάση είτε τον χάρτη του περιβάλλοντος είτε μία δεύτερη μέτρηση—μπορεί να χρησιμοποιηθεί για την ικανοποίηση των δύο παραπάνω στόχων, και με επίδοση καλύτερη από μεθόδους της καθιερωμένης και τρέχουσας βιβλιογραφίας. Αρχικά σχεδιάζουμε μία μεθοδολογία αξιολόγησης αλγορίθμων αυτόνομης πλοήγησης, και μέσω της εφαρμογής της παρατηρούμε την ύπαρξη σφαλμάτων εκτίμησης στάσης. Στη συνέχεια ερευνούμε τρόπους μείωσης αυτών των σφαλμάτων εντός και εκτός του μηχανισμού του φίλτρου σωματιδίων. Ένας από αυτούς τους εξωτερικούς τρόπους είναι η προσθετική ευθυγράμμιση μετρήσεων με εικονικές σαρώσεις. Ανακαλύπτοντας πως η ευθυγράμμιση σαρώσεων εκτελείται στη βιβλιογραφία με τρόπο μη εύρωστο ως προς το θόρυβο μέτρησης, το μέτρο των σφαλμάτων εκτίμησης θέσης, και ρυθμιστικές παραμέτρους, αντιπροτείνουμε μεθόδους ευθυγράμμισης πραγματικών με εικονικές σαρώσεις που αντικαθιστούν τους σχετικούς παθογόνους μηχανισμούς της βιβλιογραφίας με μηχανισμούς που βασίζονται στο μετασχηματισμό Fourier και τις ιδιότητές του. Σε επίπεδο εφαρμογών σχεδιάζουμε συστήματα που δεδομένου του χάρτη του περιβάλλοντος της κινητής βάσης στοχεύουν στην εκ του μηδενός εκτίμηση της στάσης του, και στην ελάττωση του σφάλματος παρατήρησής της. Στο τέλος γενικεύουμε την προσέγγισή μας απουσία χάρτη, προκειμένου για την παραγωγή οδομετρίας με βάση μετρήσεις πανοραμικού αισθητήρα αποστάσεων τύπου lidar.
Primary care prescribing prior to lung cancer diagnosis (PPP-Lung): protocol for a systematic review
Authors: Jacob Benjamin M. , Teng Vivian X. W. , Morris Delphi , Wickramsinghe Bethany , Moriarty Frank , Burns Heather , Bennett Kathleen , Redmond Patrick
Published: April 2024

Background Lung cancer is the second most common cancer and the leading cause of cancer death worldwide. A significant reason for its high mortality is delayed diagnosis, with lung cancer typically diagnosed at an advanced stage. Previous research has shown that prescribing rates of certain medications increase in the 24 months preceding a cancer diagnosis. This suggests a potential opportunity for early diagnosis of lung cancer by the identification of high-risk patients based on the prescribing of medications associated with a subsequent lung cancer diagnosis. Our aim is to identify all prescribing events associated within an increased incidence of primary lung cancer in the subsequent 24 months. Methods We will conduct a systematic review, and, where possible, a meta-analysis, reporting the findings in accordance with the PRISMA reporting guideline. All peer-reviewed studies in the English language that quantitatively describe an association between prescribing data and lung cancer diagnosis using a control group will be eligible. Details regarding prescribing rate in the lung cancer group versus the control group will be extracted with study characteristics. Quality appraisal of studies, using ROBINS-E will be used for assessing risk of bias. For each drug studied, we will report prescribing rate ratios (PRRs) with 95% confidence intervals (CIs). A meta-analysis using a pooled estimate of PRRs, either by fixed or random-effect models, will be performed if possible. Conclusions This systematic review will summarise the evidence on drugs that, when prescribed, suggest the possibility of an as-yet-undiagnosed lung cancer. This research has the potential to impact clinical practice by informing targeted screening strategies and refining early detection protocols for this harmful disease. If achieved, this could increase the numbers of lung cancers diagnosed at an earlier stage, with consequent improvements to patients in terms of survival, treatment tolerability and quality of life.
Decolonising student services: Implications for conflict management in higher education
Authors: Omodan Bunmi Isaiah
Published: April 2024

This theoretical argument explores the decolonisation of student services in higher education and its implications for conflict management. The study is based on a comprehensive literature review that incorporates decolonial theories, frameworks, and existing discourse on student services. It establishes a theoretical framework that integrates key concepts from decolonial perspectives and conflict management. Using a theory synthesis design and conceptual analysis to advance the argument, the article explores the transformative process of decolonising student services and how it affects conflict management in diverse academic communities. By examining the intersection between decolonial approaches and conflict management, this study highlights how restructuring student services through a decolonial lens contributes to the creation of inclusive and equitable environments. Real-world case studies are also considered, providing an understanding of successful instances where decolonisation positively impacts conflict dynamics. Moreover, the article discusses the challenges and opportunities associated with implementing decolonised student services, offering practical recommendations for educators, administrators, and policymakers. This work contributes to the ongoing discourse on higher education by providing insights into the complex relationship between decolonisation, student services, and conflict resolution. It envisions a future where culturally responsive and decolonised student service practices foster collaboration and prioritise equity, inclusivity, and collaborative conflict management in diverse academic communities.
TRENDS OF CHANGES IN THE LABOR MARKET FOR GRADUATES OF IT SPECIALTIES AND EMPLOYMENT OPPORTUNITIES IN STACK 1C
Authors: Posokhova Aleksandra L. , Ul'yanova Natal'ya D. , Milyutina Elena M.
Published: April 2024

Changes in the labor market are constantly occurring, and the IT specialist market is no exception. In this field, it is important to follow new trends in order to remain in demand as a specialist. In recent years, the demand for IT specialists has continued to grow, especially in the fields of software development, artificial intelligence, machine learning and cybersecurity. This opens up great opportunities for graduates of IT fields, especially in the light of universal digitalization and the transition to remote work.
Currently, the market in the IT sector is striving for saturation, the offer of vacancies practically corresponds to demand. Employers are interested in mid- and high-level specialists. Applicants for IT professions require high salaries. For successful employment, you need to be a professional or go into scarce areas.
The most in-demand and almost the only IT field where there is a shortage of specialists is 1C. The labor market in 1C is characterized by an excess of vacancies in relation to available resumes. A future specialist in this field should have skills in 1C programming, have knowledge in the subject areas of economics and continuously engage in their professional growth.
Purpose – identification of trends in the labor market of IT specialties and employment prospects in the 1C stack.
Methodology: the article used methods of analysis and synthesis of statistical information, methods of comparison and generalization.
Results: the trend of increasing demand for 1C specialists in the labor market has been revealed.
Practical implications it is advisable to apply the obtained results to enterprises, industries, municipalities, regions that monitor the labor market and the education system.
Defendido por ti de los peligros del mar. La estampación xilográfica y calcográfica en las patentes sanitarias malagueñas.
Authors: Castellón Serrano Federico
Published: April 2024

Las Patentes de Sanidad tuvieron una importancia fundamental durante las epidemias, al certificar que una población estaba libre de contagio, convirtiéndose en un documento indispensable para transitar por el territorio. Esta certificación se solía ilustrar con motivos religiosos, heráldicos o mitológicos, en estampaciones tanto en entalladura como en calcografía, algunas técnicamente muy rudimentarias y otras de esmerada composición y grabado. Afortunadamente en el caso malagueño se conserva un significativo número de patentes, que ha permitido su análisis.
Efectos del enfoque de comunidad digital en el mercado de derivados de pymes
Authors: Juárez Fernando , Useche Alejandro J.
Published: April 2024

Las dificultades de funcionamiento que tienen las pequeñas y medianas empresas se acentúan por su dificultad de apalancarse adecuadamente. Sin embargo, el acceso a recursos de derivados, en el segundo mercado de valores, mediante participación colectiva podría conducir a un mayor desarrollo de estas empresas. En este capítulo se determina el efecto que tiene en el mercado de derivados de pymes, en el segundo mercado de valores, la creación de comunidades digitales de clientes inversionistas y empresas. Para esto, se utilizaron fuentes documentales y publicaciones científicas; igualmente, se aportaron y analizaron datos sobre la relevancia estadística de la introducción de las pymes en el mercado de derivados y se elaboró un modelo financiero sobre los beneficios obtenidos al utilizar comunidades de empresas e inversionistas. Los resultados muestran cómo se ven afectados los indicadores bursátiles por el hecho de la existencia de dicho mercado, y cómo la creación de comunidades digitales favorece la introducción de las pymes en el segundo mercado de valores a través de modelos de redes digitales de colaboración, inversión y cobertura de riesgo, mediante el uso de tecnologías de la información y las comunicaciones, y las finanzas inclusivas.
Consecuencias agregadas y regionales de la epidemia de Covid en un modelo epidemiológico con inmunidad adquirida
Authors: Carranza-Romero Juan Esteban , Martín Juan D. , Riascos Álvaro J.
Published: April 2024

En este capítulo estudiamos la interacción entre el comportamiento de la economía colombiana y la evolución de la epidemia con un modelo macroeconómico en el que los agentes individuales deciden cuánto trabajar y consumir dependiendo del riesgo de contagio. Dado que los agentes son racionales, basan su percepción de riesgo en un modelo epidemiológico que representa correctamente la evolución de la epidemia y cómo esta se ve afectada por el comportamiento de todos. El modelo reproduce con éxito la relación negativa entre el contagio y la actividad económica que se observa en los datos. Luego, junto con datos colombianos, esto nos permite identificar la heterogeneidad de los efectos de la epidemia a nivel de cada región estudiada y cómo al ser agregados caracterizan su comportamiento a nivel nacional.