bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Potential of “Mobility as a Service” in Passenger Maritime Transport
Authors: Papaioannou Georgios , Polydoropoulou Amalia , Tsirimpa Athena , Pagoni Ioanna
Published: January 2022

This article assesses the potential of Mobility as a Service in passenger maritime transport from the supply perspective by collecting and analyzing data provided by interviews to key experts in passenger transport from both industry and academia. “Mobility as a service” in passenger maritime transport (also in this article referred as “Maritime MaaS”) describes the integration of passenger maritime services with land mobility into a single mobility service delivered through a unique platform for planning, booking, ticketing, and payment. The scope of this article is to explore the potential interest of mobility service providers to develop a MaaS that has as a backbone coastal shipping at the Aegean Archipelagos, in Greece. The Maritime MaaS ecosystem with its key actors is identified, while the perceived challenges, opportunities, and benefits envisaged by the adaptation of this innovative concept from urban transport to the maritime sector are recorded. Computer-assisted interviews were performed at a panel of 17 experts representing different types of decision makers. Participants were selected according to their current industry position or their academic profile. A content analysis with the use of NVIVO was conducted, followed by a SWOT (strengths, weaknesses, opportunities, and threats) analysis based on the experts’ input, in order to assess the MaaS business environment. Results indicate that the maritime transport sector is relatively ready to adopt MaaS from a technological readiness perspective, while land transport seems to be in a lower level of technological readiness. PAYG (pay as you go) MaaS business model is preferred than a “MaaS package” model by most stakeholders. Finally, main challenges toward MaaS implementation are the discrepancies in reliability of service among different transport modes and the ferry fleet operational flexibility ceilings that are imposed by legal framework for ferry routings in Greece.
Gene Therapy Potential for Genetic Disorders of Surfactant Dysfunction
Authors: Cooney Ashley L. , Wambach Jennifer A. , Sinn Patrick L. , McCray Paul B.
Published: January 2022

Pulmonary surfactant is critically important to prevent atelectasis by lowering the surface tension of the alveolar lining liquid. While respiratory distress syndrome (RDS) is common in premature infants, severe RDS in term and late preterm infants suggests an underlying genetic etiology. Pathogenic variants in the genes encoding key components of pulmonary surfactant including surfactant protein B (SP-B, SFTPB gene), surfactant protein C (SP-C, SFTPC gene), and the ATP-Binding Cassette transporter A3 (ABCA3, ABCA3 gene) result in severe neonatal RDS or childhood interstitial lung disease (chILD). These proteins play essential roles in pulmonary surfactant biogenesis and are expressed in alveolar epithelial type II cells (AEC2), the progenitor cell of the alveolar epithelium. SP-B deficiency most commonly presents in the neonatal period with severe RDS and requires lung transplantation for survival. SFTPC mutations act in an autosomal dominant fashion and more commonly presents with chILD or idiopathic pulmonary fibrosis than neonatal RDS. ABCA3 deficiency often presents as neonatal RDS or chILD. Gene therapy is a promising option to treat monogenic lung diseases. Successes and challenges in developing gene therapies for genetic disorders of surfactant dysfunction include viral vector design and tropism for target cell types. In this review, we explore adeno-associated virus (AAV), lentiviral, and adenoviral (Ad)-based vectors as delivery vehicles. Both gene addition and gene editing strategies are compared to best design treatments for lung diseases resulting from pathogenic variants in the SFTPB, SFTPC, and ABCA3 genes.
Antagonistic Activities of Lactobacillus rhamnosus JB3 Against Helicobacter pylori Infection Through Lipid Raft Formation
Authors: Do Anh Duy , Su Chiu-Hsian , Hsu Yuan-Man
Published: January 2022

Helicobacter pylori is a Gram-negative pathogen that can increase the risk of stomach cancer in infected patients. H. pylori exploits lipid rafts to infect host cells. Infection triggers clustering of Lewis x antigen (Lex) and integrins in lipid rafts to facilitate H. pylori adherence to the gastric epithelium. H. pylori infection can be treated with probiotics containing lactic acid bacteria that offer numerous benefits to the host while lacking the side effects associated with antibiotic therapy. Previously, we showed that the cell-free supernatant (CFS) derived from Lactobacillus rhamnosus JB3 (LR-JB3) at a multiplicity of infection (MOI) of 25 attenuated the pathogenicity of H. pylori. In this study, we established a mucin model to simulate the gastric environment and to further understand the influence of mucin on the pathogenesis of H. pylori. Porcine stomach mucin dramatically upregulated H. pylori virulence gene expression, including that of babA, sabA, fucT, vacA, hp0499, cagA, and cagL, as well as the adhesion and invasion ability of H. pylori and induced increased levels of IL-8 in infected-AGS cells. The CFS derived from LR-JB3 at a MOI of 25 reduced the expression of H. pylori sabA, fucT, and hp0499 in mucin, as well as that of the Lex antigen and the α5β1 integrin in AGS cells during co-cultivation. These inhibitory effects of LR-JB3 also suppressed lipid raft clustering and attenuated Lewis antigen-dependent adherence, type IV secretion system-mediated cell contact, and lipid raft-mediated entry of VacA to host cells. In conclusion, LR-JB3 could affect H. pylori infection through mediating lipid raft formation of the host cells. The currently unknown cues secreted from LR-JB3 are valuable not only for treating H. pylori infection, but also for treating diseases that are also mediated by lipid raft signaling, such as cancer and aging-associated and neurodegenerative conditions.
Liver and Hepatocyte Transplantation: What Can Pigs Contribute?
Authors: Li Xiaoxue , Wang Ying , Yang Haiyuan , Dai Yifan
Published: January 2022

About one-fifth of the population suffers from liver diseases in China, meaning that liver disorders are prominent causative factors relating to the Chinese mortality rate. For patients with end-stage liver diseases such as hepatocellular carcinoma or acute liver diseases with life-threatening liver dysfunction, allogeneic liver transplantation is the only life-saving treatment. Hepatocyte transplantation is a promising alternative for patients with acute liver failure or those considered high risk for major surgery, particularly for the bridge-to-transplant period. However, the lack of donors has become a serious global problem. The clinical application of porcine xenogeneic livers and hepatocytes remains a potential solution to alleviate the donor shortage. Pig grafts of xenotransplantation play roles in providing liver support in recipients, together with the occurrence of rejection, thrombocytopenia, and blood coagulation dysfunction. In this review, we present an overview of the development, potential therapeutic impact, and remaining barriers in the clinical application of pig liver and hepatocyte xenotransplantation to humans and non-human primates. Donor pigs with optimized genetic modification combinations and highly effective immunosuppressive regimens should be further explored to improve the outcomes of xenogeneic liver and hepatocyte transplantation.
Tumor-Infiltrating Lymphocytes in Colorectal Cancer: The Fundamental Indication and Application on Immunotherapy
Authors: Bai Ziyi , Zhou Yao , Ye Zifan , Xiong Jialong , Lan Hongying , Wang Feng
Published: January 2022

The clinical success of immunotherapy has revolutionized the treatment of cancer patients, bringing renewed attention to tumor-infiltrating lymphocytes (TILs) of various cancer types. Immune checkpoint blockade is effective in patients with mismatched repair defects and high microsatellite instability (dMMR-MSI-H) in metastatic colorectal cancer (CRC), leading the FDA to accelerate the approval of two programmed cell death 1 (PD-1) blocking antibodies, pembrolizumab and nivolumab, for treatment of dMMR-MSI-H cancers. In contrast, patients with proficient mismatch repair and low levels of microsatellite stability or microsatellite instability (pMMR-MSI-L/MSS) typically have low tumor-infiltrating lymphocytes and have shown unsatisfied responses to the immune checkpoint inhibitor. Different TILs environments reflect different responses to immunotherapy, highlighting the complexity of the underlying tumor-immune interaction. Profiling of TILs fundamental Indication would shed light on the mechanisms of cancer-immune evasion, thus providing opportunities for the development of novel therapeutic strategies. In this review, we summarize phenotypic diversities of TILs and their connections with prognosis in CRC and provide insights into the subsets-specific nature of TILs with different MSI status. We also discuss current clinical immunotherapy approaches based on TILs as well as promising directions for future expansion, and highlight existing clinical data supporting its use.
The Improvement in Surface Properties of Metallic Implant via Magnetron Sputtering: Recent Progress and Remaining Challenges
Authors: Akhtar Memoona , Uzair Syed Ahmed , Rizwan Muhammad , Ur Rehman Muhammad Atiq
Published: January 2022

Bioceramic coatings on metallic implants provide a wear-resistant and biocompatible layer, that own ability to develop bone-like apatite in physiological environments to ensure bonding with hard tissues. These bioceramics primarily belong to Calcium Phosphates (CaPs), bioactive glasses, and glass-ceramics. Several techniques are used to deposit these coatings such as; electrophoretic deposition (EPD), plasma spray (PS), and Radio frequency magnetron sputtering (RFMS). Most of these techniques require a high-temperature operation or sintering treatment. This causes either thermal decomposition of bioceramic or results in delamination and cracking of the bioceramic coating due to differences in thermal expansion behavior of metals and bioceramics. RFMS is primarily carried out either at room temperature. However, annealing is performed or substrate is heated at various temperatures ∼400–1,200°C for 2 or 4 h under dry argon (very low temperature compared to other techniques) to ensure crystallization of bioceramics and improve coating adhesion. Chemical composition stability and excellent surface finish are the premium features of RFMS, due to less heat involvement. Moreover, RFMS has the unique ability to develop one-unit/ multilayered composite coatings and the flexibility of in-situ reactions to yield oxides and nitrides. Single or multiple targets can be employed with the insertion of Oxygen and Nitrogen to yield versatile coatings. Due to this attractive set of features RFMS has a strong potential in the field of bioceramic coatings. In recent years, several multifunctional bioceramic coatings have been deposited on metallic substrates using RFMS for biomedical applications. This review focuses on the recent efforts made in order to deposit multifunctional bioceramic RFMS coatings with surface characteristics necessary for biomedical applications and highlights future directions for the improved biological performance of RFMS bioceramic coatings.
Hepatitis B Virus Reactivation Associated With Therapeutic Interventions
Authors: Chang Young , Jeong Soung Won , Jang Jae Young
Published: January 2022

Hepatitis B virus (HBV) reactivation associated with various therapeutic interventions is an important cause of morbidity and mortality in patients with current or resolved HBV infection. Because no curative treatment for HBV infection is yet available, there are many individuals at risk for HBV reactivation in the general population. Populations at risk for HBV reactivation include patients who are currently infected with HBV or who have been exposed to HBV in the past. HBV reactivation and its potential consequences is a concern when these populations are exposed to anti-cancer chemotherapy, immunosuppressive or immunomodulatory therapies for the management of various malignancies, rheumatologic diseases, inflammatory bowel disease, or solid-organ or hematologic stem cell transplantation. Accordingly, it has become important to understand the basics of HBV reactivation and the mechanisms by which certain therapies are more susceptible to HBV reactivation. This review aims to raise the awareness of HBV reactivation and to understand the mechanisms and the risks of HBV reactivation in various clinical settings.
Association Between Epidural Analgesia and Cancer Recurrence or Survival After Surgery for Renal Cell Carcinoma: A Propensity Weighted Analysis
Authors: Yen Fang-Yu , Chang Wen-Kuei , Lin Shih-Pin , Lin Tzu-Ping , Chang Kuang-Yi
Published: January 2022

Whether epidural anesthesia and analgesia (EA) is beneficial for postoperative cancer outcomes remains controversial and we conducted this historical cohort study to evaluate the association between EA and long-term outcomes following surgery for renal cell carcinoma (RCC). We collected patients receiving RCC surgery from 2011 to 2017 and followed up them until February 2020. Patient attributes, surgical factors and pathological features were gathered through electronic medical chart review. The association between EA and recurrence-free and overall survival after surgery was evaluated using Cox regression models with inverse probability of treatment weighting (IPTW) to balance the observed covariates. The median follow-up time for the 725 included patients was 50 months (interquartile range: 25.3–66.5) and 145 of them (20%) received perioperative EA. We demonstrated EA use was associated with better recurrence-free survival [IPTW adjusted hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.49–0.83, p < 0.001] and overall survival [IPTW adjusted HR: 0.66, 95% CI: 0.49–0.89, p = 0.006] in patients receiving surgical resection for RCC. More prospective studies are needed to verify this connection between EA and superior cancer outcomes after RCC surgery.
Coronary Heart Disease and Cardiovascular Risk Factors in Patients With Idiopathic Inflammatory Myopathies: A Systemic Review and Meta-Analysis
Authors: Qin Li , Li Fang , Luo Qiang , Chen Lifang , Yang Xiaoqian , Wang Han
Published: January 2022

Objectives:

It is well-established that the association between atherosclerotic cardiovascular diseases (ASCVD) and connective tissue diseases (CTDs), but the relationship between coronary heart disease (CHD) and idiopathic inflammatory myopathies (IIMs) remains controversial yet. The aim of this meta-analysis is to systematically evaluate the risk of CHD in IIMs patients. In addition, we explore differences in traditional cardiovascular risk factors between IIMs patients and controls.

Methods:

We searched Pubmed, EMBASE and Cochrane databases to identify relevant observational studies published in English up to August 2021. Pooled relative risk (RR) and 95% confidence interval (CI) was calculated using the generic inverse variance method for the risk of CHD. A meta-proportion analysis was conducted to assess differences in cardiovascular risk factors between two groups.

Results:

A total of 15 studies met inclusion criteria: seven studies focused on CHD and nine studies focused on traditional cardiovascular risk factors. The results demonstrated that IIMs patients had a higher risk of CHD (RR = 2.19, 95% CI: 1.40–3.42). Hypertension (OR = 1.44, 95% CI: 1.28–1.61), diabetes mellitus (OR = 1.67, 95% CI: 1.55–1.81) and dyslipidemia (OR = 1.48, 95% CI: 1.19–1.84) were more prevalent in IIMs patients compared with controls. However, there was a significant heterogeneity among studies assessing the risk of CHD and hypertension. Subgroup analysis demonstrated that definition of CHD, country and sample size may be potential sources of heterogeneity.

Conclusions:

IIMs patients were at increased risk of CHD, and traditional cardiovascular risk factors appeared more prevalent in IIMs patients. This systemic review offers the proof that early appropriate interventions could reduce cardiovascular-associated morbidity and mortality in IIMs patients.
Molecular Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Isolates From Central Inner Sardinia
Authors: Malune Paolo , Piras Giovanna , Monne Maria , Fiamma Maura , Asproni Rosanna , Fancello Tatiana , Manai Antonio , Carta Franco , Pira Giovanna , Fancello Patrizia , Rosu Valentina , Uras Antonella , Mereu Caterina , Mameli Giuseppe , Lo Maglio Iana , Garau Maria Cristina , Palmas Angelo Domenico
Published: January 2022

Background

The SARS-CoV-2 pandemic stimulated an outstanding global sequencing effort, which allowed to monitor viral circulation and evolution. Nuoro province (Sardinia, Italy), characterized by a relatively isolated geographical location and a low population density, was severely hit and displayed a high incidence of infection.

Methods

Amplicon approach Next Generation Sequencing and subsequent variant calling in 92 respiratory samples from SARS-CoV-2 infected patients involved in infection clusters from March 2020 to May 2021.

Results

Phylogenetic analysis displayed a coherent distribution of sequences in terms of lineage and temporal evolution of pandemic. Circulating lineage/clade characterization highlighted a growing diversity over time, with an increasingly growing number of mutations and variability of spike and nucleocapsid proteins, while viral RdRp appeared to be more conserved. A total of 384 different mutations were detected, of which 196 were missense and 147 synonymous ones. Mapping mutations along the viral genome showed an irregular distribution in key genes. S gene was the most mutated gene with missense and synonymous variants frequencies of 58.8 and 23.5%, respectively. Mutation rates were similar for the S and N genes with one mutation every ∼788 nucleotides and every ∼712 nucleotides, respectively. Nsp12 gene appeared to be more conserved, with one mutation every ∼1,270 nucleotides. The frequency of variant Y144F in the spike protein deviated from global values with higher prevalence of this mutation in the island.

Conclusion

The analysis of the 92 viral genome highlighted evolution over time and identified which mutations are more widespread than others. The high number of sequences also permits the identification of subclusters that are characterized by subtle differences, not only in terms of lineage, which may be used to reconstruct transmission clusters. The disclosure of viral genetic diversity and timely identification of new variants is a useful tool to guide public health intervention measures.
Striatal Chloride Dysregulation and Impaired GABAergic Signaling Due to Cation-Chloride Cotransporter Dysfunction in Huntington’s Disease
Authors: Serranilla Melissa , Woodin Melanie A.
Published: January 2022

Intracellular chloride (Cl–) levels in mature neurons must be tightly regulated for the maintenance of fast synaptic inhibition. In the mature central nervous system (CNS), synaptic inhibition is primarily mediated by gamma-amino butyric acid (GABA), which binds to Cl– permeable GABAA receptors (GABAARs). The intracellular Cl– concentration is primarily maintained by the antagonistic actions of two cation-chloride cotransporters (CCCs): Cl–-importing Na+-K+-Cl– co-transporter-1 (NKCC1) and Cl– -exporting K+-Cl– co-transporter-2 (KCC2). In mature neurons in the healthy brain, KCC2 expression is higher than NKCC1, leading to lower levels of intracellular Cl–, and Cl– influx upon GABAAR activation. However, in neurons of the immature brain or in neurological disorders such as epilepsy and traumatic brain injury, impaired KCC2 function and/or enhanced NKCC1 expression lead to intracellular Cl– accumulation and GABA-mediated excitation. In Huntington’s disease (HD), KCC2- and NKCC1-mediated Cl–-regulation are also altered, which leads to GABA-mediated excitation and contributes to the development of cognitive and motor impairments. This review summarizes the role of Cl– (dys)regulation in the healthy and HD brain, with a focus on the basal ganglia (BG) circuitry and CCCs as potential therapeutic targets in the treatment of HD.
Automatic Radiotherapy Planning for Glioblastoma Radiotherapy With Sparing of the Hippocampus and nTMS-Defined Motor Cortex
Authors: Schuermann Michaela , Dzierma Yvonne , Nuesken Frank , Oertel Joachim , Rübe Christian , Melchior Patrick
Published: January 2022

Background

Navigated transcranial magnetic stimulation (nTMS) of the motor cortex has been successfully implemented into radiotherapy planning by a number of studies. Furthermore, the hippocampus has been identified as a radiation-sensitive structure meriting particular sparing in radiotherapy. This study assesses the joint protection of these two eloquent brain regions for the treatment of glioblastoma (GBM), with particular emphasis on the use of automatic planning.

Patients and Methods

Patients with motor-eloquent brain glioblastoma who underwent surgical resection after nTMS mapping of the motor cortex and adjuvant radiotherapy were retrospectively evaluated. The radiotherapy treatment plans were retrieved, and the nTMS-defined motor cortex and hippocampus contours were added. Four additional treatment plans were created for each patient: two manual plans aimed to reduce the dose to the motor cortex and hippocampus by manual inverse planning. The second pair of re-optimized plans was created by the Auto-Planning algorithm. The optimized plans were compared with the “Original” plan regarding plan quality, planning target volume (PTV) coverage, and sparing of organs at risk (OAR).

Results

A total of 50 plans were analyzed. All plans were clinically acceptable with no differences in the PTV coverage and plan quality metrics. The OARs were preserved in all plans; however, overall the sparing was significantly improved by Auto-Planning. Motor cortex protection was feasible and significant, amounting to a reduction in the mean dose by >6 Gy. The dose to the motor cortex outside the PTV was reduced by >12 Gy (mean dose) and >5 Gy (maximum dose). The hippocampi were significantly improved (reduction in mean dose: ipsilateral >6 Gy, contralateral >4.6 Gy; reduction in maximum dose: ipsilateral >5 Gy, contralateral >5 Gy). While the dose reduction using Auto-Planning was generally better than by manual optimization, the radiated total monitor units were significantly increased.

Conclusion

Considerable dose sparing of the nTMS-motor cortex and hippocampus could be achieved with no disadvantages in plan quality. Auto-Planning could further contribute to better protection of OAR. Whether the improved dosimetric protection of functional areas can translate into improved quality of life and motor or cognitive performance of the patients can only be decided by future studies.
Potential Pitfalls of Using Fractional Anisotropy, Axial Diffusivity, and Radial Diffusivity as Biomarkers of Cerebral White Matter Microstructure
Authors: Figley Chase R. , Uddin Md Nasir , Wong Kaihim , Kornelsen Jennifer , Puig Josep , Figley Teresa D.
Published: January 2022

Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) are commonly used as MRI biomarkers of white matter microstructure in diffusion MRI studies of neurodevelopment, brain aging, and neurologic injury/disease. Some of the more frequent practices include performing voxel-wise or region-based analyses of these measures to cross-sectionally compare individuals or groups, longitudinally assess individuals or groups, and/or correlate with demographic, behavioral or clinical variables. However, it is now widely recognized that the majority of cerebral white matter voxels contain multiple fiber populations with different trajectories, which renders these metrics highly sensitive to the relative volume fractions of the various fiber populations, the microstructural integrity of each constituent fiber population, and the interaction between these factors. Many diffusion imaging experts are aware of these limitations and now generally avoid using FA, AD or RD (at least in isolation) to draw strong reverse inferences about white matter microstructure, but based on the continued application and interpretation of these metrics in the broader biomedical/neuroscience literature, it appears that this has perhaps not yet become common knowledge among diffusion imaging end-users. Therefore, this paper will briefly discuss the complex biophysical underpinnings of these measures in the context of crossing fibers, provide some intuitive “thought experiments” to highlight how conventional interpretations can lead to incorrect conclusions, and suggest that future studies refrain from using (over-interpreting) FA, AD, and RD values as standalone biomarkers of cerebral white matter microstructure.
Altered Functional Network in Infants With Profound Bilateral Congenital Sensorineural Hearing Loss: A Graph Theory Analysis
Authors: Cui Wenzhuo , Wang Shanshan , Chen Boyu , Fan Guoguang
Published: January 2022

Functional magnetic resonance imaging (fMRI) studies have suggested that there is a functional reorganization of brain areas in patients with sensorineural hearing loss (SNHL). Recently, graph theory analysis has brought a new understanding of the functional connectome and topological features in central neural system diseases. However, little is known about the functional network topology changes in SNHL patients, especially in infants. In this study, 34 infants with profound bilateral congenital SNHL and 28 infants with normal hearing aged 11–36 months were recruited. No difference was found in small-world parameters and network efficiency parameters. Differences in global and nodal topologic organization, hub distribution, and whole-brain functional connectivity were explored using graph theory analysis. Both normal-hearing infants and SNHL infants exhibited small-world topology. Furthermore, the SNHL group showed a decreased nodal degree in the bilateral thalamus. Six hubs in the SNHL group and seven hubs in the normal-hearing group were identified. The left middle temporal gyrus was a hub only in the SNHL group, while the right parahippocampal gyrus and bilateral temporal pole were hubs only in the normal-hearing group. Functional connectivity between auditory regions and motor regions, between auditory regions and default-mode-network (DMN) regions, and within DMN regions was found to be decreased in the SNHL group. These results indicate a functional reorganization of brain functional networks as a result of hearing loss. This study provides evidence that functional reorganization occurs in the early stage of life in infants with profound bilateral congenital SNHL from the perspective of complex networks.
Electroencephalographic Evidence for Individual Neural Inertia in Mice That Decreases With Time
Authors: Wasilczuk Andrzej Z. , Meng Qing Cheng , McKinstry-Wu Andrew R.
Published: January 2022

Previous studies have demonstrated that the brain has an intrinsic resistance to changes in arousal state. This resistance is most easily measured at the population level in the setting of general anesthesia and has been termed neural inertia. To date, no study has attempted to determine neural inertia in individuals. We hypothesize that individuals with markedly increased or decreased neural inertia might be at increased risk for complications related to state transitions, from awareness under anesthesia, to delayed emergence or confusion/impairment after emergence. Hence, an improved theoretical and practical understanding of neural inertia may have the potential to identify individuals at increased risk for these complications. This study was designed to explicitly measure neural inertia in individuals and empirically test the stochastic model of neural inertia using spectral analysis of the murine EEG. EEG was measured after induction of and emergence from isoflurane administered near the EC50 dose for loss of righting in genetically inbred mice on a timescale that minimizes pharmacokinetic confounds. Neural inertia was assessed by employing classifiers constructed using linear discriminant or supervised machine learning methods to determine if features of EEG spectra reliably demonstrate path dependence at steady-state anesthesia. We also report the existence of neural inertia at the individual level, as well as the population level, and that neural inertia decreases over time, providing direct empirical evidence supporting the predictions of the stochastic model of neural inertia.
Association Between Dietary Patterns and Dyslipidemia in Korean Women
Authors: Lee Jeonghee , Hoang Tung , Lee Seohyun , Kim Jeongseon
Published: January 2022

Background:

The prevalence of dyslipidemia among Korean women differs significantly according to menopausal status. This study aimed to identify major dietary patterns among Korean women and examine their associations with the prevalence of dyslipidemia and its components.

Methods:

This study recruited 6,166 women from the Cancer Screenee Cohort 2007–2019 from the National Cancer Center of Korea. Dietary patterns were identified using factor analysis. Multivariable logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between dietary patterns and the prevalence of dyslipidemia and its components, including hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein (HDL) cholesterol, and hyper-low-density lipoprotein (LDL) cholesterol. Stratification analyses were performed for the premenopausal and postmenopausal subgroups.

Results:

The factor analysis identified three main dietary patterns, including traditional, western, and prudent dietary patterns. Compared with those with the lowest pattern scores, those with the highest pattern scores of the traditional (OR = 1.32, 95% CI = 1.05–1.67) and western (OR = 1.40, 95% CI = 1.11–1.78) diets had a higher prevalence of hyper-LDL cholesterol. When accounting for menopausal status in the analysis, traditional (OR = 1.44, 95% CI = 1.10–1.89) and western (OR = 1.43, 95% CI = 1.09–1.88) diets were still associated with hyper-LDL cholesterol in postmenopausal women. Additionally, consumption of a traditional diet was associated with a decreased prevalence of hypertriglyceridemia (OR = 0.73, 95% CI = 0.54–0.99), and consumption of a western diet was associated with an increased prevalence of hypercholesterolemia (OR = 1.41, 95% CI = 1.11–1.79) but a reduced prevalence of hypo-HDL cholesterol (OR = 0.60, 95% CI = 0.36–0.99). However, the prudent dietary pattern was not significantly associated with dyslipidemia and its components in the group of all women or the subgroups according to menopausal status.

Conclusion:

There were significant associations between the traditional and western dietary patterns and hyper-LDL cholesterol in the entire group and postmenopausal subgroup of women. In the perspective of energy restriction, our findings recommend women not to eat either traditional or western diets excessively or too frequently. Menopause may induce the effect of both the traditional diet on triglyceride reduction and the western diet on increasing total cholesterol.
The Prognostic Value of the Prognostic Nutritional Index in Operable High-Grade Glioma Patients and the Establishment of a Nomogram
Authors: He Qian , Zhao Wei , Ren Qinglan
Published: January 2022

Background

Studies confirmed the predictive value of the prognostic nutrition index (PNI) in many malignant tumors. However, it did not reach a consensus in glioma. Therefore, this study investigated the prognostic value of preoperative PNI in operable high-grade glioma and established a nomogram.

Methods

Clinical data of high-grade glioma patients were retrospectively analyzed. The primary endpoint was overall survival (OS). Survival analysis was conducted by the Kaplan–Meier method, log-rank test, and Cox regression analysis. A nomogram was established. The prediction effect of the nomogram covering PNI was verified by area under the curve (AUC).

Results

A total of 91 operable high-grade glioma patients were included. Kaplan–Meier analysis showed that among grade IV gliomas (n = 55), patients with higher PNI (>44) showed a trend of OS benefit (p = 0.138). In grade III glioma (n = 36), patients with higher PNI (>47) had longer OS (p = 0.023). However, the intersecting Kaplan–Meier curve suggested that there may be some confounding factors. Cox regression analysis showed that higher PNI was an independent prognostic factor for grade IV glioma (HR = 0.388, p = 0.040). In grade III glioma, there was no statistically relationship between PNI levels and prognosis. When evaluating the prognostic ability of PNI alone by ROC, the AUC in grade III and IV gliomas was low, indicating that PNI alone had poor predictive power for OS. Interestingly, we found that the nomogram including preoperative PNI, age, extent of resection, number of gliomas, and MGMT methylation status could predict the prognosis of patients with grade IV glioma well.

Conclusion

The PNI level before surgery was an independent prognostic factor for patients with grade IV glioma. The nomogram covering PNI in patients with grade IV glioma also proved the value of PNI. However, the value of PNI in grade III glioma needs to be further evaluated. More prospective studies are needed to verify this conclusion.
Prediction of Microvascular Invasion and Its M2 Classification in Hepatocellular Carcinoma Based on Nomogram Analyses
Authors: Chen Shengsen , Wang Chao , Gu Yuwei , Ruan Rongwei , Yu Jiangping , Wang Shi
Published: January 2022

Background and Aims

As a key pathological factor, microvascular invasion (MVI), especially its M2 grade, greatly affects the prognosis of liver cancer patients. Accurate preoperative prediction of MVI and its M2 classification can help clinicians to make the best treatment decision. Therefore, we aimed to establish effective nomograms to predict MVI and its M2 grade.

Methods

A total of 111 patients who underwent radical resection of hepatocellular carcinoma (HCC) from January 2017 to December 2019 were retrospectively collected. We utilized logistic regression and least absolute shrinkage and selection operator (LASSO) regression to identify the independent predictive factors of MVI and its M2 classification. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to select the potential predictive factors from the results of LASSO and logistic regression. Nomograms for predicting MVI and its M2 grade were then developed by incorporating these factors. Area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were respectively used to evaluate the efficacy, accuracy, and clinical utility of the nomograms.

Results

Combined with the results of LASSO regression, logistic regression, and IDI and NRI analyses, we founded that clinical tumor-node-metastasis (TNM) stage, tumor size, Edmondson–Steiner classification, α-fetoprotein (AFP), tumor capsule, tumor margin, and tumor number were independent risk factors for MVI. Among the MVI-positive patients, only clinical TNM stage, tumor capsule, tumor margin, and tumor number were highly correlated with M2 grade. The nomograms established by incorporating the above variables had a good performance in predicting MVI (AUCMVI = 0.926) and its M2 classification (AUCM2 = 0.803). The calibration curve confirmed that predictions and actual observations were in good agreement. Significant clinical utility of our nomograms was demonstrated by DCA.

Conclusions

The nomograms of this study make it possible to do individualized predictions of MVI and its M2 classification, which may help us select an appropriate treatment plan.
Tumor Reduction in Multiple Myeloma: New Concepts for New Therapeutics
Authors: Alonso Rafael , Lahuerta Juan José
Published: January 2022

The development of new resources for a more accurate diagnosis and response assessment in multiple myeloma has been a long process for decades, mainly since the middle of the 20th century. During this time, the succession of technical advances has run parallel to the better knowledge of disease biology and the availability of novel therapeutic strategies. The cornerstone of standardized criteria to uniformly evaluate the disease response in myeloma dates back to the 1990s when the key role of complete remission was established. Since then, different updates have been implemented according to available scientific evidences not always without certain controversies. The progressive improvements in survival results of myeloma patients and the growing quality of responses due to the novel therapies have led to the need of developing new tools for better monitoring of tumor burden. In this way, the concept of minimal residual disease and its key value based on the prognostic significance and the clinical relevance has been consolidated during the last years, overcoming the value of conventional response criteria or classical adverse prognosis markers. Nevertheless, its precise role in the clinical management of myeloma patients to detect early treatment failure and trigger early rescue strategies is still pending to be defined. In this review, we revisit the major milestones in the understanding of tumor reduction in multiple myeloma until the most recent imaging techniques or liquid biopsy approaches, including a critical view of conventional response criteria, whose backbone has remained unchanged during the last 20 years.
Associations Between Polymorphisms in Genes Related to Oxidative Stress and DNA Repair, Interactions With Serum Antioxidants, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial
Authors: Gong Zhihong , Platek Mary E. , Till Cathee , Goodman Phyllis J. , Tangen Catherine M. , Platz Elizabeth A. , Neuhouser Marian L. , Thompson Ian M. , Santella Regina M. , Ambrosone Christine B.
Published: January 2022

Study of polymorphisms in genes related to the generation and removal of oxidative stress and repair of oxidative DNA damage will lead to new insights into the genetic basis of prostate cancer. In the Prostate Cancer Prevention Trial (PCPT), a double-blind, randomized controlled trial testing finasteride versus placebo for prostate cancer prevention, we intend to investigate the role of oxidative stress/DNA repair mechanisms in prostate cancer etiology and whether these polymorphisms modify prostate cancer risk by interacting with antioxidant status in both placebo and finasteride arms. We evaluated associations of selected candidate polymorphisms in genes in these pathways, and interactions with pre-diagnostic serum antioxidants, and the risk of prostate cancer among 1,598 cases and 1,706 frequency-matched controls enrolled in the PCPT. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted logistic regression models. While there were no statistically significant associations observed in the placebo arm, several SNPs were associated with prostate cancer in the finasteride arm. Specifically, APEX1-rs1760944 was associated with increased risk of total prostate cancer (per minor allele: p-trend=0.04). OGG1-rs1052133 was positively (CG/GG vs. CC: OR=1.32, 95% CI: 1.01-1.73) and NOS3-rs1799983 was inversely (per minor allele: p-trend=0.04) associated with risk of low-grade prostate cancer. LIG3-rs1052536 and XRCC1-rs25489 were suggestively associated with reduced risk of high-grade prostate cancer (per minor allele: both p-trend=0.04). In the placebo arm, significant associations were observed among men with higher serum lycopene for APEX1-rs1760944 and NQO1-rs1800566, or higher serum β-cryptoxanthin for ERCC4-rs1800067. In the finasteride arm, stronger associations were observed among men with lower serum lycopene for NOS3-rs1799983, higher serum α-carotene, β-carotene, and β-cryptoxanthin for LIG3-rs1052536, or lower serum retinol for SOD2-rs1799725. These results suggest that germline variations in oxidative stress and DNA repair pathways may contribute to prostate carcinogenesis and that these associations may differ by intraprostatic sex steroid hormone status and be further modified by antioxidant status. Findings provide insights into the complex role of gene, gene-antioxidant and -finasteride interactions in prostate cancer etiology, and thus may lead to the development of preventative strategies.
The Emerging Role of Tissue-Resident Memory CD8+ T Lymphocytes in Human Digestive Tract Cancers
Authors: Mei Xinyu , Li Huan , Zhou Xinpeng , Cheng Min , Cui Kele
Published: January 2022

Malignant digestive tract tumors are a great threat to human public health. In addition to surgery, immunotherapy brings hope for the treatment of these tumors. Tissue-resident memory CD8+T (Trm) cells are a focus of tumor immunology research and treatment due to their powerful cytotoxic effects, ability to directly kill epithelial-derived tumor cells, and overall impact on maintaining mucosal homeostasis and antitumor function in the digestive tract. They are a group of noncirculating immune cells expressing adhesion and migration molecules such as CD69, CD103, and CD49a that primarily reside on the barrier epithelium of nonlymphoid organs and respond rapidly to both viral and bacterial infection and tumorigenesis. This review highlights new research exploring the role of CD8+Trm cells in a variety of digestive tract malignant tumors, including esophageal cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma. A summary of CD8+Trm cell phenotypes and characteristics, tissue distribution, and antitumor functions in different tumor environments is provided, illustrating how these cells may be used in immunotherapies against digestive tract tumors.
Crocetin: A Systematic Review
Authors: Guo Zi-Liang , Li Mao-Xing , Li Xiao-Lin , Wang Peng , Wang Wei-Gang , Du Wei-Ze , Yang Zhi-Qiang , Chen Sheng-Fu , Wu Di , Tian Xiu-Yu
Published: January 2022

Crocetin is an aglycone of crocin naturally occurring in saffron and produced in biological systems by hydrolysis of crocin as a bioactive metabolite. It is known to exist in several medicinal plants, the desiccative ripe fruit of the cape jasmine belonging to the Rubiaceae family, and stigmas of the saffron plant of the Iridaceae family. According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties. Although poor bioavailability hinders therapeutic applications, derivatization and formulation preparation technologies have broadened the application prospects for crocetin. To promote the research and development of crocetin, we summarized the distribution, preparation and production, total synthesis and derivatization technology, pharmacological activity, pharmacokinetics, drug safety, drug formulations, and preparation of crocetin.
Decrease of IL-1β and TNF in the Spinal Cord Mediates Analgesia Produced by Ankle Joint Mobilization in Complete Freund Adjuvant-Induced Inflammation Mice Model
Authors: Omura Carlos Minoru , Lüdtke Daniela Dero , Horewicz Verônica Vargas , Fernandes Paula Franson , Galassi Taynah de Oliveira , Salgado Afonso Shiguemi Inoue , Palandi Juliete , Baldança Heloiza dos Santos , Bittencourt Edsel B. , Mack Josiel Mileno , Seim Lynsey A. , Martins Daniel Fernandes , Bobinski Franciane
Published: January 2022

Objective

This study aims to investigate the effects of ankle joint mobilization (AJM) on mechanical hyperalgesia and peripheral and central inflammatory biomarkers after intraplantar (i.pl.) Complete Freund’s Adjuvant (CFA)-induced inflammation.

Methods

Male Swiss mice were randomly assigned to 3 groups (n = 7): Saline/Sham, CFA/Sham, and CFA/AJM. Five AJM sessions were carried out at 6, 24, 48, 72, and 96 h after CFA injection. von Frey test was used to assess mechanical hyperalgesia. Tissues from paw skin, paw muscle and spinal cord were collected to measure pro-inflammatory (TNF, IL-1β) and anti-inflammatory cytokines (IL-4, IL-10, and TGF-β1) by ELISA. The macrophage phenotype at the inflammation site was evaluated by Western blotting assay using the Nitric Oxide Synthase 2 (NOS 2) and Arginase-1 immunocontent to identify M1 and M2 macrophages, respectively.

Results

Our results confirm a consistent analgesic effect of AJM following the second treatment session. AJM did not change cytokines levels at the inflammatory site, although it promoted a reduction in M2 macrophages. Also, there was a reduction in the levels of pro-inflammatory cytokines IL-1β and TNF in the spinal cord.

Conclusion

Taken together, the results confirm the anti-hyperalgesic effect of AJM and suggest a central neuroimmunomodulatory effect in a model of persistent inflammation targeting the pro-inflammatory cytokines IL-1β and TNF.
A High-Throughput Screening System for Populus Wood-Associated Transcription Factors and Its Application to Lignin Regulation
Authors: Zhuang Yamei , Chen Sihui , Lian Wenjun , Xu Li , Wang Dian , Wang Congpeng , Meng Jie , Tang Xianfeng , Xu Hua , Wang Shumin , Du Lin , Zhang Yang , Zhou Gongke , Chai Guohua
Published: January 2022

Wood formation of trees is a complex and costly developmental process, whose regulatory network is involved in the protein-protein and protein-DNA interactions. To detect such interactions in wood development, we developed a high-throughput screening system with 517 Gal4-AD-wood-associated transcription factors (TFs) library from Populus alba × P. glandulosa cv “84K.” This system can be used for screening the upstream regulators and interacting proteins of targets by mating-based yeast-one hybrid (Y1H) and yeast-two-hybrid (Y2H) method, respectively. Multiple regulatory modules of lignin biosynthesis were identified based on this Populus system. Five TFs interacted with the 500-bp promoter fragment of PHENYLALANINE AMMONIA-LYASE 2 (PAL2), the first rate-limiting enzyme gene in the lignin biosynthesis pathway, and 10 TFs interacted with PaMYB4/LTF1, a key regulator of lignin biosynthesis. Some of these interactions were further validated by EMSA and BiFC assays. The TF-PaPAL2 promoter interaction and TF-PaMYB4 interaction revealed a complex mechanism governing the regulation of lignin synthesis in wood cells. Our high-throughput Y1H/Y2H screening system may be an efficient tool for studying regulatory network of wood formation in tree species.