bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in the water retention of mountainous landscapes since the 1820s in the Austrian Alps
Authors: Stecher Gabriel , Hohensinner Severin , Herrnegger Mathew
Published: July 2023

Interactions of humans with the environment are strongly related to land use and land cover changes (LULCCs). In the last decades, these changes have led to a degradation of ecosystem services, including water regulation and flood control. In the Alpine areas of Austria, land cover changes have increased flood risk since the middle of the 19th century. In this paper, we assess the influence of these long-term land use changes on the landscape’s ability to retain water using the qualitative Water Retention Index (WRI). The changes are thereby evaluated on the basis of the historical (1826–1859) and present (2016) land cover situation, which is to our knowledge the first high-resolution and regional application of the WRI. The results show that the water retention potential mimics the mountainous characteristic and features. Except for areas strongly dominated by settlement areas, the highest retention potentials are found in valley floors and the lowest values are depicted along the main Alpine complex. In low-lying areas, the retention decreased by over 10%. It was found that this decrease can be mostly attributed to settlement expansion. Above 1,250 m, land use transformations led to slightly increasing water retention values owing to the transformation of wasteland or glaciers to stagnant waters and to the expansion of forest and grassland in high elevations. This examination allows for a holistic and spatially distributed LULCC impact assessment on the landscape’s water regulation capacities and offers valuable high-resolution information for future land use planning and sustainable land development.
Genome-wide diversity and admixture of five indigenous cattle populations from the Tigray region of northern Ethiopia
Authors: Zegeye Tsadkan , Belay Gurja , Vallejo-Trujillo Adriana , Han Jianlin , Hanotte Olivier
Published: July 2023

The Tigray region, where we found around eight per cent of the indigenous cattle population of Ethiopia, is considered as the historic centre of the country, with the ancient pre-Aksumite and Aksumite civilisations in contact with the civilisations of the Fertile Crescent and the Indian subcontinent. Here, we used whole genome sequencing data to characterise the genomic diversity, relatedness, and admixture of five cattle populations (Abergelle, Arado, Begait, Erob, and Raya) indigenous to the Tigray region of Ethiopia. We detected 28 to 29 million SNPs and 2.7 to 2.9 million indels in each population, of which 7% of SNPs and 34% of indels were novel. Functional annotation of the variants showed around 0.01% SNPs and 0.22%–0.27% indels in coding regions. Enrichment analysis of genes overlapping missense private SNPs revealed 20 significant GO terms and KEGG pathways that were shared by or specific to breeds. They included important genes associated with morphology (SCN4A, TAS1R2 and KCNG4), milk yield (GABRG1), meat quality (MMRN2, VWC2), feed efficiency (PCDH8 and SLC26A3), immune response (LAMC1, PCDH18, CELSR1, TLR6 and ITGA5), heat resistance (NPFFR1 and HTR7) and genes belonging to the olfactory gene family, which may be related to adaptation to harsh environments. Tigray indigenous cattle are very diverse. Their genome-wide average nucleotide diversity ranged from 0.0035 to 0.0036. The number of heterozygous SNPs was about 0.6–0.7 times higher than homozygous ones. The within-breed average number of ROHs ranged from 777.82 to 1000.45, with the average sum of the length of ROHs ranging from 122.01 Mbp to 163.88 Mbp. The genomic inbreeding coefficients differed among animals and breeds, reaching up to 10% in some Begait and Raya animals. Tigray indigenous cattle shared a common ancestry with Asian indicine (85.6%–88.7%) and African taurine (11.3%–14.1%) cattle, with very small, if any, European taurine introgression. This study identified high within-breed genetic diversity representing an opportunity for breeding improvement programs and, also, significant novel variants that could increase the number of known cattle variants, an important contribution to the knowledge of domestic cattle genetic diversity.
Transcriptomic analysis of paired healthy human skeletal muscles to identify modulators of disease severity in DMD
Authors: Nieves-Rodriguez Shirley , Barthélémy Florian , Woods Jeremy D. , Douine Emilie D. , Wang Richard T. , Scripture-Adams Deirdre D. , Chesmore Kevin N. , Galasso Francesca , Miceli M. Carrie , Nelson Stanley F.
Published: July 2023

Muscle damage and fibro-fatty replacement of skeletal muscles is a main pathologic feature of Duchenne muscular dystrophy (DMD) with more proximal muscles affected earlier and more distal affected later in the disease course, suggesting that different skeletal muscle groups possess distinctive characteristics that influence their susceptibility to disease. To explore transcriptomic factors driving differential gene expression and modulating DMD skeletal muscle severity, we characterized the transcriptome of vastus lateralis (VL), a more proximal and susceptible muscle, relative to tibialis anterior (TA), a more distal and protected muscle, in 15 healthy individuals using bulk RNA sequencing to identify gene expression differences that may mediate their relative susceptibility to damage with loss of dystrophin. Matching single nuclei RNA sequencing data was generated for 3 of the healthy individuals, to infer cell composition in the bulk RNA sequencing dataset and to improve mapping of differentially expressed genes to their cell source of expression. A total of 3,410 differentially expressed genes were identified and mapped to cell type using single nuclei RNA sequencing of muscle, including long non-coding RNAs and protein coding genes. There was an enrichment of genes involved in calcium release from the sarcoplasmic reticulum, particularly in the myofibers and these myofiber genes were higher in the VL. There was an enrichment of genes in “Collagen-Containing Extracellular Matrix” expressed by fibroblasts, endothelial, smooth muscle and pericytes, with most genes higher in the TA, as well as genes in “Regulation Of Apoptotic Process” expressed across all cell types. Previously reported genetic modifiers were also enriched within the differentially expressed genes. We also identify 6 genes with differential isoform usage between the VL and TA. Lastly, we integrate our findings with DMD RNA sequencing data from the TA, and identify “Collagen-Containing Extracellular Matrix” and “Negative Regulation Of Apoptotic Process” as differentially expressed between DMD compared to healthy. Collectively, these findings propose novel candidate mechanisms that may mediate differential muscle susceptibility in muscular dystrophies and provide new insight into potential therapeutic targets.
The arms race between bacteria CBASS and bacteriophages
Authors: Wang Lan , Zhang Leiliang
Published: July 2023

The Bacterial Cyclic oligonucleotide-Based Anti-phage Signaling System (CBASS) is an innate immune system that induces cell suicide to defend against phage infections. This system relies on cGAS/DncV-like nucleotidyltransferases (CD-NTase) to synthesize cyclic oligonucleotides (cOs) and CD-NTase-associated proteins (Caps) to execute cell death through DNA cleavage, membrane damage, and NAD depletion, thereby inhibiting phage replication. Ancillary proteins expressed in CBASS, in combination with CD-NTase, ensure the normal synthesis of cOs and prepare CD-NTase for full activation by binding to phage genomes, proteins, or other unknown products. To counteract cell death induced by CBASS, phage genes encode immune evasion proteins that curb Cap recognition of cOs, allowing for phage replication, assembly, and propagation in bacterial cells. This review provides a comprehensive understanding of CBASS immunity, comparing it with different bacterial immune systems and highlighting the interplay between CBASS and phage. Additionally, it explores similar immune escape methods based on shared proteins and action mechanisms between prokaryotic and eukaryotic viruses.
A novel quantitative analysis for diurnal dynamics of Ulva prolifera patch in the Yellow Sea from Geostationary Ocean Color Imager observation
Authors: Cui He , Chen Jianyu , Jiang Xiaoyi , Fu Yu , Qiao Feng
Published: July 2023

Introduction

In the last decade, the outbreak of large-scale green tides caused by Ulva prolifera has continuously occurred in the Yellow Sea. Satellite remote sensing techniques have been widely used to monitor the distribution area and duration of green tides due to their advantages of their large-area synchronous observation. Ulva prolifera in the Yellow Sea is mainly distributed in bands or large patches during its flourishing stage. Previous studies have rarely reported the quantitative analysis of a single Ulva prolifera patch and its changes in the short term.

Methods

Considering the high temporal resolution of the Geostationary Ocean Color Imager (GOCI) sensor and the patchy distribution of Ulva prolifera floating on the sea surface, we developed a feasible method for monitoringUlva prolifera by performing clustering analysis with density-based spatial clustering of applications with noise (DBSCAN) to capture the diurnal variation characteristics of a single Ulva prolifera patch.

Results

This new approach was used to extract informationfrom a single Ulva prolifera patch in the Yellow Sea in 2012 and 2017. The results showed that during the time of GOCI imaging, the tidal current was the main factor driving the drift of Ulva prolifera, and the drifting direction of Ulva prolifera was consistent with the direction of the local tidal current, with a coefficient of determination of 0.94.

Discussion

By changing the normalized difference vegetation index (NDVI) threshold, further more accurate atmospheric correction (AC) of GOCI data during the twilight periods was indirectly achieved. By comparing the areal change in the single patch before and after AC, we speculated that the daily change in signal intensity received by the GOCI sensor may be the main reason for the diurnal variation in the Ulva proliferacoverage area. The results showed the details of the diurnal variation in Ulvaprolifera patches in the dynamic marine environment, and the main reason that may cause this variation was speculated.
Simulated and projected SST of Asian marginal seas based on CMIP6 models
Authors: Jin Shanshan , Wei Zexun , Wang Dingqi , Xu Tengfei
Published: July 2023

Sea surface temperature (SST) is an important element in studying the global ocean-atmospheric system, as well as its simulation and projection in climate models. In this study, we evaluate the simulation skill of the Coupled Model Intercomparison Project Phase 6 (CMIP6) models in simulating the climatological SST in the Asian Marginal Seas (AMS), known as the most rapidly warming region over the global ocean. The results show that the spatial patterns and seasonal variability of Asian Marginal Seas (AMS) climatological SST simulated by the CMIP6 models are generally in good agreement with the observations, but there are simulation biases in the values. In boreal winter, the simulated climatological SST tends to be overestimated in the Japan/East Sea and the East China Seas (ECSs) by up to 2°C, while being underestimated in the Sea of Okhotsk by up to 2°C. In boreal summer, the simulated climatological SSTs are overestimated in the Indonesian seas and western Arabian Sea, while being underestimated in the Sea of Okhotsk and the northern ECSs by 1.2–1.5 and 2°C, respectively. Furthermore, we calculate the projected sea surface warming trends in the AMS under different future scenarios in the CMIP6 models. The results show warming trends of 0.8–1.8, 1.7–3.4, and 3.8–6.5°C/century for the Shared Socio-Economic Pathway (SSP) of low- (global radiative forcing of 2.6 W/m² by the year 2100), medium- (global radiative forcing of 4.5 W/m² by 2100) and high-end (8.5 W/m² by 2100) pathways, respectively. In addition, the middle and high latitudes of the AMS are found to have faster warming trends than the low latitudes, with the most rapidly warming occurring in the Sea of Okhotsk, which is around 2 times larger than the global mean SST warming trend. The SST warming trends are relatively slow in the South China Sea and the Indonesian seas, roughly equal to the global mean SST warming trend.
Professional medical education approaches: mobilizing evidence for clinicians
Authors: Lyu Xiafei , Li Sheyu
Published: July 2023

Rapidly proliferating high-quality evidence supports daily decision-making in clinical practice. Continuing professional medical education links this evidence to practicing clinicians who are strongly motivated to improve the quality of their care by using the latest information. Approaches to professional education vary, and their effects depend on specific scenarios. This narrative review summarizes the main approaches for professional medical education that facilitate the mobilization of evidence for clinicians. It includes traditional learning (passive and active dissemination of educational materials, lectures, and mass media dissemination), constructivist learning (engaging in local consensus processes and education outreach visits, interfacing with local opinion leaders, conducting patient-mediated interventions, employing audit and feedback processes, and utilizing clinical decision-supporting systems), and blended learning approaches (the integration of in-person or online passive learning with active and creative learning by the learners). An optimized selection from these approaches is challenging but critical to clinicians and healthcare systems.
Work climate from the perspective of nurses: qualitative research
Authors: Kosydar-Bochenek Justyna , Krupa Sabina , Semań Tomasz , Mędrzycka-Dąbrowska Wioletta
Published: July 2023

Introduction

This study aims to determine the nurses’ view of the work climate. A positive work climate is one of the keys determining factors in improving nurse outcomes and affects patient satisfaction with care.

Methods

In this qualitative research, a semi-structured interview was used to understand nurses’ perceptions of their work environment. The participants’ responses were recorded and transcribed. Between November and December 2021, 22 nurses participated in the study. Purposive sampling was used to choose nurses for the research, and interviews were performed with these nurses utilizing a semi-structured interview form. The interviews were analyzed using a theme analysis.

Results

The themes identified in the data centered on four dominant elements that together shaped the prevailing work climate: participation in making decisions, companionship, job satisfaction, and changes they expect.

Conclusion

It is necessary to implement meetings at the level of departments and hospitals, where employees will receive support from the authorities and learn how they can improve the working climate.

Implications for nursing management

Research findings on the working climate can help hospital managers makers design interventions to create a good working environment for nurses.
One year of SARS-CoV-2 circulation in the Nouvelle-Aquitaine region, February 2021–2022, France
Authors: Deroche Luc , Bellecave Pantxika , David Romain , Ouattara Eric , Garcia Magali , Roblot France , Boinot Laurence , Faucher Jean-François , Rejasse Aurélie , Gschwind Guillaume , Malvy Denis , Filleul Laurent , Rogez Sylvie , Lévêque Nicolas , Lafon Marie-Edith
Published: July 2023

Background

Since 2021, 3 variants of concern (VOC) have spread to France, causing successive epidemic waves.

Objectives

To describe the features of Alpha, Delta and Omicron VOC circulation in the Nouvelle-Aquitaine region, France, between February 2021 and February 2022.

Study design

Data from the three university hospitals (UH) of Nouvelle-Aquitaine were used to describe regional SARS-CoV-2 circulation (RT-PCR positive rates and identified VOC) as well as its consequences (total number of hospitalizations and admissions in intensive care unit). They were analyzed according to the predominant variant and compared with national data.

Results

A total of 611,106 SARS-CoV-2 RT-PCR tests were performed in the 3 Nouvelle-Aquitaine UH during the study period. The 37,750 positive samples were analyzed by variant-specific RT-PCR or whole-genome sequencing. In 2021, Alpha VOC was detected from week 5 until week 35. Delta became the most prevalent variant (77.3%) in week 26, reaching 100% in week 35. It was replaced by Omicron, which was initially detected week 48, represented 77% of positive samples in week 52 and was still predominant in February 2022. The RT-PCR positive rates were 4.3, 4.2, and 21.9% during the Alpha, Delta and Omicron waves, respectively. The ratio between intensive care unit admissions and total hospitalizations was lower during the Omicron wave than during the two previous waves due to the Alpha and Delta variants.

Conclusion

This study highlighted the need for strong regional cooperation to achieve effective SARS-CoV-2 epidemiological surveillance, in close association with the public health authorities.
Gut microbiota and transcriptome dynamics in every-other-day fasting are associated with neuroprotection in rats with spinal cord injury
Authors: Wang Junyu , Zhao Xiaohua , Zhou Ruihan , Wang Meiyu , Xiang Wu , You Zilong , Li Min , Tang Ruiling , Zheng Jingqi , Li Jiayu , Zhu Li , Gao Jiaxin , Li Huaqiang , Pang Rizhao , Zhang Anren
Published: July 2023

Introduction

Every-other-day fasting (EODF) is a classical intermittent fasting (IF) mode with neuroprotective effects that promotes motor function recovery after spinal cord injury (SCI) in rats. However, its dynamic effects on the gut microbiota and spinal cord transcriptome remain unknown.

Methods

In this study, 16S rRNA sequencing and RNA-seq analysis were used to investigate the effects of ad libitum (AL) and EODF dietary modes on the structural characteristics of rat gut microbiota in rats and the spinal cord transcriptome at various time points after SCI induction.

Results

Our results showed that both dietary modes affected the bacterial community composition in SCI rats, with EODF treatment inducing and suppressing dynamic changes in the abundances of potentially anti-inflammatory and pro-inflammatory bacteria. Furthermore, the differentially expressed genes (DEGs) enriched after EODF intervention in SCI rats were associated with various biological events, including immune inflammatory response, cell differentiation, protein modification, neural growth, and apoptosis. In particular, significant spatiotemporal differences were apparent in the DEGs associated with neuroprotection between the EODF and AL interventions. These DGEs were mainly focused on days 1, 3, and 7 after SCI. The relative abundance of certain genera was significantly correlated with DEGs associated with neuroprotective effects in the EODF-SCI group.

Discussion

Our results showed that EODF treatment may exert neuroprotective effects by modulating the transcriptome expression profile following SCI in rats. Furthermore, gut microbiota may be partially involved in mediating these effects.
Fibroblast activation in response to TGFβ1 is modulated by co-culture with endothelial cells in a vascular organ-on-chip platform
Authors: Luu Rebeccah J. , Hoefler B. Christopher , Gard Ashley L. , Ritenour Casey R. , Rogers Miles T. , Kim Ernest S. , Coppeta Jonathan R. , Cain Brian P. , Isenberg Brett C. , Azizgolshani Hesham , Fajardo-Ramirez Oscar R. , García-Cardeña Guillermo , Lech Matthew P. , Tomlinson Lindsay , Charest Joseph L. , Williams Corin
Published: July 2023

Background: Tissue fibrosis is a major healthcare burden that affects various organs in the body for which no effective treatments exist. An underlying, emerging theme across organs and tissue types at early stages of fibrosis is the activation of pericytes and/or fibroblasts in the perivascular space. In hepatic tissue, it is well known that liver sinusoidal endothelial cells (EC) help maintain the quiescence of stellate cells, but whether this phenomenon holds true for other endothelial and perivascular cell types is not well studied.

Methods: The goal of this work was to develop an organ-on-chip microvascular model to study the effect of EC co-culture on the activation of perivascular cells perturbed by the pro-fibrotic factor TGFβ1. A high-throughput microfluidic platform, PREDICT96, that was capable of imparting physiologically relevant fluid shear stress on the cultured endothelium was utilized.

Results: We first studied the activation response of several perivascular cell types and selected a cell source, human dermal fibroblasts, that exhibited medium-level activation in response to TGFβ1. We also demonstrated that the PREDICT96 high flow pump triggered changes in select shear-responsive factors in human EC. We then found that the activation response of fibroblasts was significantly blunted in co-culture with EC compared to fibroblast mono-cultures. Subsequent studies with conditioned media demonstrated that EC-secreted factors play at least a partial role in suppressing the activation response. A Luminex panel and single cell RNA-sequencing study provided additional insight into potential EC-derived factors that could influence fibroblast activation.

Conclusion: Overall, our findings showed that EC can reduce myofibroblast activation of perivascular cells in response to TGFβ1. Further exploration of EC-derived factors as potential therapeutic targets in fibrosis is warranted.
Percutaneous lordoplasty for the treatment of severe osteoporotic vertebral compression fractures with kyphosis
Authors: Song Tengfei , Sun Fan , Liu Shu , Ye Tianwen
Published: July 2023

Objective

The study aimed to explore the safety and effectiveness of percutaneous lordoplasty (PLP) in the treatment of severe osteoporotic vertebral compression fracture (OVCF).

Methods

Included in this prospective study were patients with single-segment acute severe OVCF who were treated with PLP in our institution from July 2016 to October 2019. Patients' back pain and quality of life were assessed using the visual analog scale (VAS) and SF-36 scores. Lateral X-ray radiography of the spine was performed to measure the vertebral height, vertebral kyphotic angle, and segmental kyphotic angle, and to evaluate the outcome of fracture reduction and kyphotic correction. Intra-and postoperative complications were recorded.

Results

Of the 51 included patients, 47 patients were followed up for 12 months. The VAS score decreased from preoperative 7.33 ± 1.92 to postoperative 1.76 ± 0.85 at the 12th month (p < 0.05), and the SF-36 score increased from preoperative 79.50 ± 9.22 to postoperative 136.94 ± 6.39 at the 12th month (p < 0.05). During the 1-year follow-up period, the anterior height of the vertebral body increased significantly from preoperative 10.49 ± 1.93 mm to 19.33 ± 1.86 mm (p < 0.05); the posterior height of the vertebral body increased insignificantly from preoperative 22.23 ± 2.36 mm to 23.05 ± 1.86 mm (p > 0.05); the vertebral kyphotic angle decreased significantly from preoperative 18.33° ± 11.49° to 8.73° ± 1.21° (p < 0.05); and the segmental kyphotic angle decreased significantly from preoperative 24.48° ± 4.64° to 11.70° ± 1.34° (p < 0.05). During the 1-year follow-up period, there was no significant difference in the radiologic parameters, VAS scores, and SF-36 scores, between the 1st day and the 12th month of post-operation (P > 0.05). No nerve damage occurred in any of the cases. Intraoperative cement leakage occurred in six cases, and the fracture of the adjacent vertebral body occurred in one case.

Conclusion

PLP can well reduce the risk of fracture and achieve good kyphotic correction and may prove to be a safe, cost-effective and minimally invasive alternative option for the treatment of severe OVCF with kyphotic deformity.
Automated acute ischemic stroke lesion delineation based on apparent diffusion coefficient thresholds
Authors: Gosch Vitus , Villringer Kersten , Galinovic Ivana , Ganeshan Ramanan , Piper Sophie K. , Fiebach Jochen B. , Khalil Ahmed
Published: July 2023

Purpose

Automated lesion segmentation is increasingly used in acute ischemic stroke magnetic resonance imaging (MRI). We explored in detail the performance of apparent diffusion coefficient (ADC) thresholding for delineating baseline diffusion-weighted imaging (DWI) lesions.

Methods

Retrospective, exploratory analysis of the prospective observational single-center 1000Plus study from September 2008 to June 2013 (clinicaltrials.org; NCT00715533). We built a fully automated lesion segmentation algorithm using a fixed ADC threshold (≤620 × 10–6 mm2/s) to delineate the baseline DWI lesion and analyzed its performance compared to manual assessments. Diagnostic capabilities of best possible ADC thresholds were investigated using receiver operating characteristic curves. Influential patient factors on ADC thresholding techniques’ performance were studied by conducting multiple linear regression.

Results

108 acute ischemic stroke patients were selected for analysis. The median Dice coefficient for the algorithm was 0.43 (IQR 0.20–0.64). Mean ADC values in the DWI lesion (β = −0.68, p < 0.001) and DWI lesion volumes (β = 0.29, p < 0.001) predicted performance. Optimal individual ADC thresholds differed between subjects with a median of ≤691 × 10−6 mm2/s (IQR ≤660–750 × 10−6 mm2/s). Mean ADC values in the DWI lesion (β = −0.96, p < 0.001) and mean ADC values in the brain parenchyma (β = 0.24, p < 0.001) were associated with the performance of individual thresholds.

Conclusion

The performance of ADC thresholds for delineating acute stroke lesions varies substantially between patients. It is influenced by factors such as lesion size as well as lesion and parenchymal ADC values. Considering the inherent noisiness of ADC maps, ADC threshold-based automated delineation of very small lesions is not reliable.
The incidence of medium vessel occlusions: a population-based study
Authors: Liu Michael , Nasr Deena , Brinjikji Waleed
Published: July 2023

Introduction

The incidence of medium vessel occlusion (MeVO) is not well known. The objective of our study is to perform a population-based assessment to estimate the incidence of MeVOs.

Methods

Consecutive patients from Olmsted County, Minnesota who presented for acute ischemic stroke seen at Mayo Clinic Hospital from 1/1/2018 to 12/31/2020 who were found to have a MeVO were included in this study. MeVO was defined as occlusion at or beyond the level of the middle cerebral artery M2 segment, anterior cerebral artery A2 segment, posterior cerebral artery P1 segment, and cerebellar arteries. Census data for Olmsted County was obtained from the United States Census Bureau from the year 2020.

Results

A total of 1,718 patients were screened for the study, 77 patients fulfilled inclusion criteria to be included in the study. Presenting NIHSS was 9 (± 7). The population of Olmsted County was estimated to be 162,847. The incidence rate for MeVO was 16 cases (95% CI 12–19) per 100,000 people per year. Based on estimates of the US population in 2020 of 331,449,281 people, we estimate there are 52,236 (95% CI 40,635-64,002) new cases of MeVOs per year.

Conclusion

As the only stroke center in Olmsted County, we have been able to estimate the incidence of ischemic stroke due to MeVO. While the incidence of MeVOs is less than both large and small vessel occlusions, they still represent a significant proportion of strokes with significant morbidity and mortality that would benefit from further studies in both acute intervention and prevention.
Potential antidepressant effects of a dietary supplement from Huáng qí and its complex in aged senescence-accelerated mouse prone-8 mice
Authors: Chou Ming-Yu , Wong Yue-Ching , Wang Shih-Yi , Chi Ching-Hsin , Wang Teng-Hsu , Huang Mao-Jung , Huang Ping-Hsiu , Li Po-Hsien , Wang Ming-Fu
Published: July 2023

Healthcare is an emerging industry with significant market potential in the 21st century. Therefore, this study aimed to evaluate the benefits of tube feeding Huáng qí and its complexes for 8 weeks on 3-month-old senescence-accelerated mouse prone-8 (SAMP8) mice, 48 in total, randomly divided into 3 groups including control, Huáng qí extract [820 mg/kg Body weight (BW)/day], and Huáng qí complexes (6.2 mL /kg BW/day), where each group consisted of males (n = 8) and females (n = 8). Behavioral tests (locomotion test and aging score assessment on week 6, the single-trial passive avoidance test on week 7, and the active shuttle avoidance test on week 8) were conducted to evaluate the ability of the mice to learn and remember. In addition, after sacrificing the animals, the blood and organs were measured for antioxidant and aging bioactivities, including malondialdehyde (MDA) content and superoxide dismutase (SOD) activity and catalase activities (CAT), and the effects on promoting aging in SAMP8 mice were investigated. The findings showed that Huáng qí enhanced locomotor performance and had anti-aging effects, with positive effects on health, learning, and memory in SAMP-8 mice (p < 0.05), whether applied as a single agent (820 mg/kg BW/day) or as a complex (6.2 mL/kg BW/day) (p < 0.05). Based on existing strengths, a more compelling platform for clinical validation of human clinical evidence will be established to enhance the development and value-added of astragalus-related products while meeting the diversified needs of the functional food market.
Identification of non-small cell lung cancer with chronic obstructive pulmonary disease using clinical symptoms and routine examination: a retrospective study
Authors: Zhuan Bing , Ma Hong-Hong , Zhang Bo-Chao , Li Ping , Wang Xi , Yuan Qun , Yang Zhao , Xie Jun
Published: July 2023

Background

Patients with non-small cell lung cancer (NSCLC) and patients with NSCLC combined with chronic obstructive pulmonary disease (COPD) have similar physiological conditions in early stages, and the latter have shorter survival times and higher mortality rates. The purpose of this study was to develop and compare machine learning models to identify future diagnoses of COPD combined with NSCLC patients based on the patient’s disease and routine clinical data.

Methods

Data were obtained from 237 patients with COPD combined with NSCLC as well as NSCLC admitted to Ningxia Hui Autonomous Region People’s Hospital from October 2013 to July 2022. Six machine learning algorithms (K-nearest neighbor, logistic regression, eXtreme gradient boosting, support vector machine, naïve Bayes, and artificial neural network) were used to develop prediction models for NSCLC combined with COPD. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, F1 score, Mathews correlation coefficient (MCC), Kappa, area under the receiver operating characteristic curve (AUROC)and area under the precision-recall curve (AUPRC) were used as performance indicators to evaluate the performance of the models.

Results

135 patients with NSCLC combined with COPD, 102 patients with NSCLC were included in the study. The results showed that pulmonary function and emphysema were important risk factors and that the support vector machine-based identification model showed optimal performance with accuracy:0.946, recall:0.940, specificity:0.955, precision:0.972, npv:0.920, F1 score:0.954, MCC:0.893, Kappa:0.888, AUROC:0.975, AUPRC:0.987.

Conclusion

The use of machine learning tools combining clinical symptoms and routine examination data features is suitable for identifying the risk of concurrent NSCLC in COPD patients.
Recent advances microRNAs and metabolic reprogramming in colorectal cancer research
Authors: Xiong Bin , Huang Qiaoyi , Zheng Huida , Lin Shu , Xu Jianhua
Published: July 2023

Colorectal cancer (CRC) is a cancer with the highest incidence and mortality. Alteration of gene expression is the main pathophysiological mechanism of CRC, which results in disturbed signaling pathways and cellular metabolic processes. MicroRNAs are involved in almost all pathophysiological processes and are correlative with colorectal cancer metabolism, proliferation, and chemotherapy resistance. Metabolic reprogramming, an important feature of cancer, is strongly correlative with the development and prognosis of cancers, including colorectal cancer. MicroRNAs can target enzymes involved in metabolic processes, thus playing a regulatory role in tumor metabolism. The disorder of the signaling pathway is another characteristic of tumor, which induces the occurrence and proliferation of tumors, and is closely correlative with the prognosis and chemotherapy resistance of tumor patients. MicroRNAs can target the components of the signaling pathways to regulate their transduction. Understanding the function of microRNAs in the occurrence and proliferation of CRC provides novel insights into the optimal treatment strategies, prognosis, and development of diagnosis in CRC. This article reviews the relationship between CRC and microRNA expression and hopes to provide new options for the diagnosis and treatment of CRC.
A nomogram for individually predicting overall survival for elderly patients with early breast cancer: a consecutive cohort study
Authors: Zhong Ying , Zhou Yidong , Xu Yali , Wang Zhe , Mao Feng , Shen Songjie , Lin Yan , Sun Qiang , Sun Kai
Published: July 2023

Background

Elderly patients with breast cancer are highly heterogeneous, and tumor load and comorbidities affect patient prognosis. Prediction models can help clinicians to implement tailored treatment plans for elderly patients with breast cancer. This study aimed to establish a prediction model for breast cancer, including comorbidities and tumor characteristics, in elderly patients with breast cancer.

Methods

All patients were ≥65 years old and admitted to the Peking Union Medical College Hospital. The clinical and pathological characteristics, recurrence, and death were observed. Overall survival (OS) was analyzed using the Kaplan–Meier curve and a prediction model was constructed using Cox proportional hazards model regression. The discriminative ability and calibration of the nomograms for predicting OS were tested using concordance (C)-statistics and calibration plots. Clinical utility was demonstrated using decision curve analysis (DCA).

Results

Based on 2,231 patients, the 5- and 10-year OS was 91.3% and 78.4%, respectively. We constructed an OS prediction nomogram for elderly patients with early breast cancer (PEEBC). The C-index for OS in PEEBC in the training and validation cohorts was 0.798 and 0.793, respectively. Calibration of the nomogram revealed a good predictive capability, as indicated by the calibration plot. DCA demonstrated that our model is clinically useful.

Conclusion

The nomogram accurately predicted the 3-year, 5-year, and 10-year OS in elderly patients with early breast cancer.
Radiomic signatures based on pretreatment 18F-FDG PET/CT, combined with clinicopathological characteristics, as early prognostic biomarkers among patients with invasive breast cancer
Authors: Jia Tongtong , Lv Qingfu , Cai Xiaowei , Ge Shushan , Sang Shibiao , Zhang Bin , Yu Chunjing , Deng Shengming
Published: July 2023

Purpose

The aim of this study was to investigate the predictive role of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the prognostic risk stratification of patients with invasive breast cancer (IBC). To achieve this, we developed a clinicopathologic-radiomic-based model (C-R model) and established a nomogram that could be utilized in clinical practice.

Methods

We retrospectively enrolled a total of 91 patients who underwent preoperative 18F-FDG PET/CT and randomly divided them into training (n=63) and testing cohorts (n=28). Radiomic signatures (RSs) were identified using the least absolute shrinkage and selection operator (LASSO) regression algorithm and used to compute the radiomic score (Rad-score). Patients were assigned to high- and low-risk groups based on the optimal cut-off value of the receiver operating characteristic (ROC) curve analysis for both Rad-score and clinicopathological risk factors. Univariate and multivariate Cox regression analyses were performed to determine the association between these variables and progression-free survival (PFS) or overall survival (OS). We then plotted a nomogram integrating all these factors to validate the predictive performance of survival status.

Results

The Rad-score, age, clinical M stage, and minimum standardized uptake value (SUVmin) were identified as independent prognostic factors for predicting PFS, while only Rad-score, age, and clinical M stage were found to be prognostic factors for OS in the training cohort. In the testing cohort, the C-R model showed superior performance compared to single clinical or radiomic models. The concordance index (C-index) values for the C-R model, clinical model, and radiomic model were 0.816, 0.772, and 0.647 for predicting PFS, and 0.882, 0.824, and 0.754 for OS, respectively. Furthermore, decision curve analysis (DCA) and calibration curves demonstrated that the C-R model had a good ability for both clinical net benefit and application.

Conclusion

The combination of clinicopathological risks and baseline PET/CT-derived Rad-score could be used to evaluate the prognosis in patients with IBC. The predictive nomogram based on the C-R model further enhanced individualized estimation and allowed for more accurate prediction of patient outcomes.
Common nutritional/inflammatory indicators are not effective tools in predicting the overall survival of patients with small cell lung cancer undergoing first-line chemotherapy
Authors: Tian Huohuan , Li Guo , Hou Wang , Jin Jing , Wang Chengdi , Ren Pengwei , Wang Haoyu , Wang Jie , Li Weimin , Liu Dan
Published: July 2023

Objective

Various studies have investigated the predictive significance of numerous peripheral blood biomarkers in patients with small cell lung cancer (SCLC). However, their predictive values have not been validated. This study assessed and evaluated the ability of common nutritional or inflammatory indicators to predict overall survival (OS) in patients with SCLC who received first-line chemotherapy.

Methods

Between January 2008 and July 2019, 560 patients with SCLC were enrolled at the Sichuan University West China Hospital. Eleven nutritional or inflammatory indices obtained before chemotherapy were evaluated. The cutoff values of continuous peripheral blood indices were confirmed through maximally selected rank statistics. The relationship of peripheral blood indices with OS was investigated through univariate and multivariate Cox regression analyses. Harrell’s concordance (C-index) and time-dependent receiver operating characteristic curve were used to evaluate the performance of these indices.

Results

A total of 560 patients with SCLC were enrolled in the study. All the patients received first-line chemotherapy. In the univariate Cox analysis, all indices, except the Naples score, were related to OS. In the multivariate analysis, albumin–globulin ratio was an independent factor linked with prognosis. All indices exhibited poor performance in OS prediction, with the area under the curve ranging from 0.500 to 0.700. The lactic dehydrogenase (LDH) and prognostic nutritional index (PNI) were comparatively superior predictors with C-index of 0.568 and 0.550, respectively. The LDH showed incremental predictive values, whereas the PNI showed diminishing values as survival time prolonged, especially for men or smokers. The LDH with highest sensitivity (0.646) and advanced lung cancer inflammation index (ALI) with highest specificity (0.952) were conducive to identifying death and survival at different time points.

Conclusion

Common inflammatory or nutritional biomarkers are only marginally useful in predicting outcomes in patients with SCLC receiving first-line chemotherapy. Among them, LDH, PNI, and ALI are relatively promising biomarkers for prognosis evaluation.
WR1065 conjugated to thiol-PEG polymers as novel anticancer prodrugs: broad spectrum efficacy, synergism, and drug resistance reversal
Authors: Walker Dale M. , Lazarova Tsvetelina I. , Riesinger Steven W. , Poirier Miriam C. , Messier Terri , Cunniff Brian , Walker Vernon E.
Published: July 2023

The lack of anticancer agents that overcome innate/acquired drug resistance is the single biggest barrier to achieving a durable complete response to cancer therapy. To address this issue, a new drug family was developed for intracellular delivery of the bioactive aminothiol WR1065 by conjugating it to discrete thiol-PEG polymers: 4-star-PEG-S-S-WR1065 (4SP65) delivers four WR1065s/molecule and m-PEG6-S-S-WR1065 (1LP65) delivers one. Infrequently, WR1065 has exhibited anticancer effects when delivered via the FDA-approved cytoprotectant amifostine, which provides one WR1065/molecule extracellularly. The relative anticancer effectiveness of 4SP65, 1LP65, and amifostine was evaluated in a panel of 15 human cancer cell lines derived from seven tissues. Additional experiments assessed the capacity of 4SP65 co-treatments to potentiate the anticancer effectiveness and overcome drug resistance to cisplatin, a chemotherapeutic, or gefitinib, a tyrosine kinase inhibitor (TKI) targeting oncogenic EGFR mutations. The CyQUANT®-NF proliferation assay was used to assess cell viability after 48-h drug treatments, with the National Cancer Institute COMPARE methodology employed to characterize dose-response metrics. In normal human epithelial cells, 4SP65 or 1LP65 enhanced or inhibited cell growth but was not cytotoxic. In cancer cell lines, 4SP65 and 1LP65 induced dose-dependent cytostasis and cytolysis achieving 99% cell death at drug concentrations of 11.2 ± 1.2 µM and 126 ± 15.8 µM, respectively. Amifostine had limited cytostatic effects in 11/14 cancer cell lines and no cytolytic effects. Binary pairs of 4SP65 plus cisplatin or gefitinib increased the efficacy of each partner drug and surmounted resistance to cytolysis by cisplatin and gefitinib in relevant cancer cell lines. 4SP65 and 1LP65 were significantly more effective against TP53-mutant than TP53-wild-type cell lines, consistent with WR1065-mediated reactivation of mutant p53. Thus, 4SP65 and 1LP65 represent a unique prodrug family for innovative applications as broad-spectrum anticancer agents that target p53 and synergize with a chemotherapeutic and an EGFR-TKI to prevent or overcome drug resistance.
Mechanisms underlying response and resistance to immune checkpoint blockade in cancer immunotherapy
Authors: Lee Junghwa , Kim Eui Ho
Published: July 2023

Cancer immunotherapies targeting immune checkpoint pathways, such as programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), have achieved unprecedented therapeutic success in treating various types of cancer. The prominent and persistent clinical responses to immune checkpoint blockade (ICB) therapy are currently constrained to a subset of patients. Owing to discrete individual tumor and immune heterogeneity, most patients fail to benefit from ICB treatment, demonstrating either primary or acquired resistance. A thorough comprehension of the mechanisms restricting the efficacy of immune checkpoint inhibitors (ICIs) is required to extend their clinical applicability to a broader spectrum of patients and cancer types. Numerous studies are presently investigating potential prognostic markers of responsiveness, the complex dynamics underlying the therapeutic and adverse effects of ICB, and tumor immune evasion throughout the course of immunotherapy. In this article, we have reviewed the extant literature elucidating the mechanisms underlying the response and resistance to ICB, with a particular emphasis on PD-1 and CTLA-4 pathway blockade in the context of anti-tumor immunity. Furthermore, we aimed to explore potential approaches to overcome cancer therapeutic resistance and develop a rational design for more personalized ICB-based combinational regimens.
Identifying predictors of clinical outcomes using the projection-predictive feature selection—a proof of concept on the example of Crohn’s disease
Authors: Wirthgen Elisa , Weber Frank , Kubickova-Weber Laura , Schiller Benjamin , Schiller Sarah , Radke Michael , Däbritz Jan
Published: July 2023

Objectives

Several clinical disease activity indices (DAIs) have been developed to noninvasively assess mucosal healing in pediatric Crohn’s disease (CD). However, their clinical application can be complex. Therefore, we present a new way to identify the most informative biomarkers for mucosal inflammation from current markers in use and, based on this, how to obtain an easy-to-use DAI for clinical practice. A further aim of our proof-of-concept study is to demonstrate how the performance of such a new DAI can be compared to that of existing DAIs.

Methods

The data of two independent study cohorts, with 167 visits from 109 children and adolescents with CD, were evaluated retrospectively. A variable selection based on a Bayesian ordinal regression model was applied to select clinical or standard laboratory parameters as predictors, using an endoscopic outcome. The predictive performance of the resulting model was compared to that of existing pediatric DAIs.

Results

With our proof-of-concept dataset, the resulting model included C-reactive protein (CRP) and fecal calprotectin (FC) as predictors. In general, our model performed better than the existing DAIs. To show how our Bayesian approach can be applied in practice, we developed a web application for predicting disease activity for a new CD patient or visit.

Conclusions

Our work serves as a proof-of-concept, showing that the statistical methods used here can identify biomarkers relevant for the prediction of a clinical outcome. In our case, a small number of biomarkers is sufficient, which, together with the web interface, facilitates the clinical application. However, the retrospective nature of our study, the rather small amount of data, and the lack of an external validation cohort do not allow us to consider our results as the establishment of a novel DAI for pediatric CD. This needs to be done with the help of a prospective study with more data and an external validation cohort in the future.
A review of the Rett Syndrome Behaviour Questionnaire and its utilization in the assessment of symptoms associated with Rett syndrome
Authors: Percy Alan K. , Neul Jeffrey L. , Benke Timothy A. , Marsh Eric D. , Glaze Daniel G.
Published: July 2023

The Rett Syndrome Behaviour Questionnaire (RSBQ), which is completed by the caregiver, is one of the most widely used efficacy measures in clinical studies of Rett syndrome (RTT) due to its specificity to the core features of RTT. As healthcare providers participate in routine healthcare assessments of individuals with RTT in clinical practice, there is a need for these providers to understand the psychometric properties of the RSBQ and how it relates to the core clinical features of RTT. Here, we describe the characteristics of the RSBQ, review the literature on its validity and reliability as well as its performance in a phase 2 study and the recent phase 3 LAVENDER study. The RSBQ was first shown to discriminate RTT from other intellectual disorders with good inter-rater and test–retest reliability scores. It was subsequently validated as an appropriate instrument for measuring behavior in females with RTT and adopted as a clinical trial outcome. In LAVENDER, the FDA-approved drug trofinetide significantly improved the RSBQ total score over placebo in girls and women with RTT and change from baseline for all RSBQ subscores were directionally in favor of trofinetide. The change in RSBQ was aligned with the Clinical Global Impression-Improvement scale, suggesting that improvement in behavioral components may be related to overall clinical status. Given its validity and ubiquity in RTT clinical studies, it is important that the interplay of the domains and the psychometric profile of the RSBQ are understood.