bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Microenvironment Characterization for Assessment of Recurrence and Survival Outcome in Gastric Cancer to Predict Chemotherapy and Immunotherapy Response
Authors: Chen Yan , Sun Zepang , Wan Li , Chen Hongzhuan , Xi Tieju , Jiang Yuming
Published: April 2022

Background

The tumor microenvironment (TME) is crucial for tumor recurrence, prognosis, and therapeutic responses. We comprehensively investigated the TME characterization associated with relapse and survival outcomes of gastric cancer (GC) to predict chemotherapy and immunotherapy response.

Methods

A total of 2,456 GC patients with complete gene-expression data and clinical annotations from twelve cohorts were included. The TME characteristics were evaluated using three proposed computational algorithms. We then developed a TME-classifier, a TME-cluster, and a TME-based risk score for the assessment of tumor recurrence and prognosis in patients with GC to predict chemotherapy and immunotherapy response.

Results

Patients with tumor recurrence presented with inactive immunogenicity, namely, high infiltration of tumor-associated stromal cells, low infiltration of tumor-associated immunoactivated lymphocytes, high stromal score, and low immune score. The TME-classifier of 4 subtypes with distinct clinicopathology, genomic, and molecular characteristics was significantly associated with tumor recurrence (P = 0.002), disease-free survival (DFS, P <0.001), and overall survival (OS, P <0.001) adjusted by confounding variables in 1,193 stage I–III GC patients who underwent potential radical surgery. The TME cluster and TME-based risk score can also predict DFS (P <0.001) and OS (P <0.001). More importantly, we found that patients in the TMEclassifier-A, TMEclassifier-C, and TMEclassifier-D groups benefited from adjuvant chemotherapy, and patients in the TMEclassifier-B group without chemotherapy benefit responded best to pembrolizumab treatment (PD-1 inhibitor), followed by patients in the TMEclassifier-A, while patients in the C and D groups of the TMEclassifier responded poorly to immunotherapy.

Conclusion

We determined that TME characterization is significantly associated with tumor recurrence and prognosis. The TME-classifier we proposed can guide individualized chemotherapy and immunotherapy decision-making.
Mitogenome Analyses Reveal Limited Introduction of Anopheles coluzzii Into the Central African Islands of São Tomé and Príncipe
Authors: Ditter Robert E. , Campos Melina , Pinto João , Cornel Anthony J. , Rompão Herodes , Lanzaro Gregory C.
Published: April 2022

Islands possess physical characteristics that make them uniquely well-suited for initial field trials of new genetic-based technologies applied to African malaria vectors. This has led to efforts to characterize the degree of isolation of island mosquito populations. São Tomé and Príncipe (STP) is a country composed of two small islands in the Gulf of Guinea (Central Africa) where Anopheles coluzzii is the primary malaria vector. Several studies have shown a relatively high degree of genetic isolation between A. coluzzii populations in STP and the mainland compared with pairs of mainland populations separated by equivalent distances. Here, we analyzed complete mitochondrial genomes of individual A. coluzzii specimens from STP and neighboring mainland countries. The objectives are to describe the history of A. coluzzii establishment in STP, specifically to address several questions germane to their suitability as sites for a field trial release of genetically engineered mosquitoes (GEMs). These questions include: (i) What are the origins of A. coluzzii populations in STP?; (ii) How many introductions occurred?; (iii) When was A. coluzzii introduced into STP? and (iv) Is there ongoing, contemporary gene flow into STP from mainland populations? Phylogenetic analysis and haplotype networks were constructed from sequences of 345 A. coluzzii from STP, and 107 individuals from 10 countries on or near the west coast of Africa. Analysis of these data suggest that there have been two introductions of A. coluzzii onto the island of São Tomé that occurred roughly 500 years ago and that these originated from mainland West Africa. It appears that A. coluzzii has never been introduced into Príncipe Island directly from mainland Africa, but there have been at least four introductions originating from São Tomé. Our findings provide further support for the notion that contemporary populations of A. coluzzii on São Tomé and Príncipe are genetically isolated from mainland populations of this mosquito species.
The Promise of Blue Carbon Climate Solutions: Where the Science Supports Ocean-Climate Policy
Authors: Christianson Anne B. , Cabré Anna , Bernal Blanca , Baez Stacy K. , Leung Shirley , Pérez-Porro Alicia , Poloczanska Elvira
Published: April 2022

The ocean is gaining prominence in climate change policy circles as a tool for addressing the climate crisis. Blue carbon, the carbon captured and stored by marine and coastal ecosystems and species, offers potential as a “nature-based solution” to climate change. The protection and restoration of specific ocean ecosystems can form part of a climate response within climate mitigation policies such as Nationally Determined Contributions under the United Nations Framework Convention on Climate Change. For mitigation policies that seek to implement management actions that drawdown carbon, ecosystem sequestration and emissions must be measurable across temporal and spatial scales, and management must be practical leading to improved sequestration and avoided emissions. However, some blue carbon interventions may not be suitable as a climate mitigation response and better suited for other policy instruments such as those targeted toward biodiversity conservation. This paper gives context to numerous blue carbon sequestration pathways, quantifying their potential to sequester carbon from the atmosphere, and comparing these sequestration pathways to point-source emissions reductions. The applicability of blue carbon is then discussed in terms of multiple international policy frameworks, to help individuals and institutions utilize the appropriate framework to reach ocean conservation and climate mitigation goals.
Observational Study on the Variability of Mixed Layer Depth in the Bering Sea and the Chukchi Sea in the Summer of 2019
Authors: Jiao Xiaohui , Zhang Jicai , Li Qun , Li Chunyan
Published: April 2022

Based on the CTD data from 58 stations in the Bering Sea and the Chukchi Sea in the summer of 2019, the values of mixed layer depth (MLD) were obtained by using the density difference threshold method. It was concluded that the MLD can be estimated more accurately by using a criterion of 0.125 kg/m3 in this region. The average MLD in the Bering Sea basin was larger than that in the Bering Sea shelf, and both of them were smaller than that in the Bering Sea slope. The MLD increased northward in both the Chukchi Sea shelf and the Chukchi Sea slope. The farther northward, the greater the difference between the MLD calculated from temperature (MLDt) and the MLD calculated from density (MLDd). The water masses and their interaction played an important role in the variation of MLD in the northern Bering Sea shelf and Chukchi Sea. The MLD was large due to the vertically homogeneous Anadyr Water in the northwestern Bering Sea shelf. The horizontal advection of Bering Sea Anadyr Water and Alaska Coastal Water in the Bering Sea shelf led to shallower MLD in the central northern Bering Sea shelf. The westward advection of the Alaska Coastal Water caused shallow mixed layers (MLs) in some regions of the Chukchi Sea shelf in the summer of 2019. The observed large MLD at BL01 station near the Aleutian Island was caused by an anticyclonic eddy. The northward increase in the MLD in the Chukchi Sea was related to the low-salinity seawater from sea ice melting in summer. The spatial variation of MLD was also closely related to the surface momentum flux and the sea surface buoyancy flux. Stratification plays an even more important role in determining the variation of MLD. The ML in 2019 was shallower and warmer than those in previous years, especially in the Bering Sea shelf and Chukchi Sea where sea ice volume, thickness, and coverage were significantly larger than the Bering Sea basin, which was related to the small sea ice volume in winter and spring of 2019 compared to previous years.
Understanding of Wood Anomalies in Metallic Gratings From Phase Gradient Metasurfaces
Authors: Quan Jiaqi , Zhou Qingjia , Cao Yanyan , Xu Yadong
Published: April 2022

Phase-gradient metasurfaces (PGMs) have provided unprecedented opportunities for manipulating light. Here, we reexamine ordinary and well-studied subwavelength metallic gratings (OMGs) from the concept of PGMs to provide more insight into their diffraction properties. We will show that due to the existence of gauge invariance in PGMs, i.e., the diffraction law of PGMs is independent of the choice of initial value of abrupt phase shift that induces the phase gradient, the well-studied OMGs can be regarded as a PGM strictly, with its diffraction properties can be fully predicted by generalized diffraction law with phase gradient. In particular, the generalized diffraction law reveals that the phase gradient plays a significant role in the famous effect of Wood’s anomalies and Rayleigh’s conjecture.
Efficacy and Safety of Electro-Thumbtack Needle Therapy for Patients With Chronic Neck Pain: Protocol for a Randomized, Sham-Controlled Trial
Authors: Shi Hangyu , Wang Xinlu , Yan Yan , Zhu Lili , Chen Yu , Gao Shuai , Liu Zhishun
Published: April 2022

Background

Chronic neck pain is a prevalent condition adversely impacting patients' wellbeing in both life and work experience. Electro-thumbtack needle (ETN) therapy, combining acupuncture with transcutaneous stimulation, might be one of the effective complementary and alternative medicine (CAM) therapies in treating chronic neck pain, although the evidence is scarce. This study aims to estimate the efficacy and safety of ETN therapy for chronic neck pain.

Methods and Analysis

This is a sham-controlled, randomized clinical trial. A total of 180 subjects will be randomly allocated to either the ETN group or the sham ETN group. Treatment will be administrated three times a week for four consecutive weeks, with a 6-month follow-up. The primary outcome measure will be the Numerical Rating Scale for neck pain (NRS-NP) over a period of the 4 weeks. Secondary outcome measures include the Northwick Park Neck Pain Questionnaire (NPQ), Neck Disability Index (NDI), Patient Global Impression of Change (PGIC), patient expectation, and preference assessment. The chi-square test or Fisher's exact test will be used for proportions of participants having clinically meaningful improvement. Analysis of covariance or repeated-measures analysis of variance will be applied to examine changes in the outcome measures from baseline.

Discussions

This prospective trial will contribute to evaluating the efficacy and safety of ETN in the treatment of chronic neck pain, with an intermediate-term follow-up. This study will provide further evidence for clinical neck pain management.

Ethics and Dissemination

This trial has been approved by the Research Ethical Committee of Guang'anmen Hospital (ethical approval number: 2021-039-KY-01). Recruitment began in March 2022 and will continue until December 2023. Dissemination plans include posters, WeChat, websites, and bulletin boards in hospital and communities.

Clinical Trial Registration

This trial is registered at ClinicalTrials.gov (identifier: NCT04981171).
HTLV-1 Transmission and HIV Pre-exposure Prophylaxis: A Scoping Review
Authors: Bradshaw Daniel , Taylor Graham Philip
Published: April 2022

HIV pre-exposure prophylaxis (HIV-PrEP) is effective in reducing the likelihood of HIV acquisition in HIV-negative people at high risk of exposure. Guidelines recommend testing for sexually transmitted infections (STIs) before starting, and periodically on PrEP, including bacterial infections, HIV, hepatitis C virus, and, for those who are non-immune, hepatitis B virus. Diagnosed infections can be promptly treated to reduce onward transmission. HTLV-1 is not mentioned; however, it is predominantly sexually transmitted, causes adult T-cell leukaemia/lymphoma (ATL) or myelopathy in 10% of those infected, and is associated with an increased risk of death in those without any classically HTLV-associated condition. The 2021 WHO Technical Report on HTLV-1 called for the strengthening of global public health measures against its spread. In this scoping review, we, therefore, (1) discuss the epidemiological context of HIV-PrEP and HTLV-1 transmission; (2) present current knowledge of antiretrovirals in relation to HTLV-1 transmission prevention, including nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs); and (3) identify knowledge gaps where data are urgently required to inform global public health measures to protect HIV-PrEP users from HTLV-1 acquisition. We suggest that systematic seroprevalence studies among PrEP-using groups, including men who have sex with men (MSM), people who inject drugs (PWIDs), and female sex workers (FSWs), are needed. Further data are required to evaluate antiretroviral efficacy in preventing HTLV-1 transmission from in vitro studies, animal models, and clinical cohorts. PrEP delivery programmes should consider prioritizing the long-acting injectable INSTI, cabotegravir, in HTLV-1 endemic settings.
Case Report: A Rare Case of Benign Recurrent Intrahepatic Cholestasis-Type 1 With a Novel Heterozygous Pathogenic Variant of ATP8B1
Authors: Suzuki Hiroyuki , Arinaga-Hino Teruko , Sano Tomoya , Mihara Yutaro , Kusano Hironori , Mizuochi Tatsuki , Togawa Takao , Ito Shogo , Ide Tatsuya , Kuwahara Reiichiro , Amano Keisuke , Kawaguchi Toshihiro , Yano Hirohisa , Kage Masayoshi , Koga Hironori , Torimura Takuji
Published: April 2022

Benign recurrent intrahepatic cholestasis type 1 (BRIC1) is a rare autosomal recessive disorder that is characterized by intermittent episodes of jaundice and intense pruritus and caused by pathogenic variants of adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1). The presence of genetic heterogeneity in the variants of ATP8B1 is suggested. Herein, we describe a unique clinical course in a patient with BRIC1 and a novel heterozygous pathogenic variant of ATP8B1. A 20-year-old Japanese man experienced his first cholestasis attack secondary to elevated transaminase at 17 years of age. Laboratory examinations showed no evidence of liver injury caused by viral, autoimmune, or inborn or acquired metabolic etiologies. Since the patient also had elevated transaminase and hypoalbuminemia, he was treated with ursodeoxycholic acid and prednisolone. However, these treatments did not relieve his symptoms. Histopathological assessment revealed marked cholestasis in the hepatocytes, Kupffer cells, and bile canaliculi, as well as a well-preserved intralobular bile duct arrangement and strongly expressed bile salt export pump at the canalicular membrane. Targeted next-generation sequencing detected a novel heterozygous pathogenic variant of ATP8B1 (c.1429 + 2T > G). Taken together, the patient was highly suspected of having BRIC1. Ultimately, treatment with 450 mg/day of rifampicin rapidly relieved his symptoms and shortened the symptomatic period.
RpuS/R Is a Novel Two-Component Signal Transduction System That Regulates the Expression of the Pyruvate Symporter MctP in Sinorhizobium fredii NGR234
Authors: Ramos Ana Laura , Aquino Maria , García Gema , Gaspar Miriam , de la Cruz Cristina , Saavedra-Flores Anaid , Brom Susana , Cervantes-Rivera Ramón , Galindo-Sánchez Clara Elizabeth , Hernandez Rufina , Puhar Andrea , Lupas Andrei N. , Sepulveda Edgardo
Published: April 2022

The SLC5/STAC histidine kinases comprise a recently identified family of sensor proteins in two-component signal transduction systems (TCSTS), in which the signaling domain is fused to an SLC5 solute symporter domain through a STAC domain. Only two members of this family have been characterized experimentally, the CrbS/R system that regulates acetate utilization in Vibrio and Pseudomonas, and the CbrA/B system that regulates the utilization of histidine in Pseudomonas and glucose in Azotobacter. In an attempt to expand the characterized members of this family beyond the Gammaproteobacteria, we identified two putative TCSTS in the Alphaproteobacterium Sinorhizobium fredii NGR234 whose sensor histidine kinases belong to the SLC5/STAC family. Using reverse genetics, we were able to identify the first TCSTS as a CrbS/R homolog that is also needed for growth on acetate, while the second TCSTS, RpuS/R, is a novel system required for optimal growth on pyruvate. Using RNAseq and transcriptional fusions, we determined that in S. fredii the RpuS/R system upregulates the expression of an operon coding for the pyruvate symporter MctP when pyruvate is the sole carbon source. In addition, we identified a conserved DNA sequence motif in the putative promoter region of the mctP operon that is essential for the RpuR-mediated transcriptional activation of genes under pyruvate-utilizing conditions. Finally, we show that S. fredii mutants lacking these TCSTS are affected in nodulation, producing fewer nodules than the parent strain and at a slower rate.
Qualification of Membrane Filtration for Planetary Protection Flight Implementation
Authors: Stott Kristina Vaikovna , Morgan Lyssa , Shearer Caitlin , Steadham Morgan Byrd , Ballarotto Mihaela , Hendrickson Ryan
Published: April 2022

Planetary protection is the practice of preventing forward and backward contamination of solar system bodies. Spacecraft and associated surfaces are sampled to ensure compliance with bioburden requirements. Current planetary protection sampling and processing methodologies consist of extracting microbial cells from wipe or swab samples through a procedure (NASA Standard Assay) that includes sonication, heat shock, and pour-plate steps. The pour-plate steps are laborious and prolonged. Moreover, results can be imprecise because only a fraction of the sample fluid is plated for CFU enumeration (80% for swabs and 25% for wipes). Thus, analysis requires that a pour fraction extrapolation factor be applied to CFU counts to account for bioburden in the remaining sample volume that is not plated. This extrapolation results in large variances for data, decreasing the accuracy of spore bioburden estimation of spacecraft hardware. In this study, we investigated the use of membrane filtration as an alternative method to pour-plate processing. Membrane filtration is an appealing methodology for planetary protection because it can process greater sample volumes and reduces the data variance for bioburden enumeration. A pour fraction extrapolation factor is still applied for both swabs and wipes (92%), however, it is a greater pour fraction than the pour-plate method. Here we present data collected by the Jet Propulsion Laboratory and the Applied Physics Laboratory to experimentally determine the equivalency of membrane filtration to pour-plate methodology for implementation during the NASA Standard Assay. Additionally, we outline the planned procedures for two membrane filtration systems: Pall® Laboratory Manifold system and Milliflex® Plus Vacuum Pump System. Both systems demonstrated equivalence of the membrane filtration method to the pour-plate method.
Rotary Nanomotors in the Rear View Mirror
Authors: Manson Michael D.
Published: April 2022

Rotation is part of our everyday lives. For most of human history, rotation was considered a uniquely human invention, something beyond the anatomical capabilities of organisms. In 1973, Howard Berg made the audacious proposal that the common gut bacterium Escherichia coli swims by rotating helical flagellar filaments. In 1987, Paul Boyer suggested that the FoF1 ATP synthase of E. coli is also a rotary device. Now we know that rotating nanomachines evolved independently at least three times. They power a wide variety of cellular processes. Here, the study of flagellar rotation in E. coli is briefly summarized. In 2020, the Cryo-EM structure of the MotAB stator element of the bacterial flagellum was described. The structure strongly suggests that the MotAB stator rotates to drive flagellar rotation. Similar motors are coupled to other diverse processes. The following articles in this issue review the current knowledge and speculation about rotating biological nanomachines.
SGLT2 Inhibitors: A Broad Impact Therapeutic Option for the Nephrologist
Authors: Granata Antonio , Pesce Francesco , Iacoviello Massimo , Anzaldi Massimiliano , Amico Francesco , Catalano Maria , Leonardi Giuseppe , Gatta Carmela , Costanza Giusy , Corrao Salvatore , Gesualdo Loreto
Published: April 2022

Since their introduction as antidiabetic drugs, SGLT2 inhibitors (SGLT2i) have come a long way, proving to be beneficial on cardiovascular and renal outcomes independently of diabetes status. The benefits go far beyond glycemic control, and both the cardio- and nephroprotection are underpinned by diverse mechanisms. From the activation of tubule glomerular feedback and the consequent reduction in hyperfiltration to the improvement of hypoxia and oxidative stress in the renal cortex, SGLT2i have also been shown to inhibit hepcidin and limit podocyte damage. Likewise, they improve cardiac metabolism and bioenergetics, and reduce necrosis and cardiac fibrosis and the production of adipokines, cytokines, and epicardial adipose tissue mass. In terms of outcomes, the efficacy has been demonstrated on blood pressure control, BMI, albuminuria, stroke, heart disease, and mortality rate due to cardiovascular events. Patients with chronic kidney disease and proteinuria, with or without diabetes, treated with some SGLT2i have a reduced risk of progression. The analysis of subgroups of individuals with specific diseases such as IgA nephropathy has confirmed this solid effect on renal outcomes. Given these overarching activities on such a broad pathophysiological background and the favorable safety profile that goes with the use of SGLT2i, it is now certain that they are changing our approach to clinical interventions for important outcomes with an impressive impact.
Association Between Various Types or Statuses of Smoking and Subjective Cognitive Decline Based on a Community Health Survey of Korean Adults
Authors: Kim Ji Hee , Chang In Bok , Kim Yoo Hwan , Min Chan Yang , Yoo Dae Myoung , Choi Hyo Geun
Published: April 2022

Objectives

The relationship between smoking and subjective cognitive decline (SCD), which is defined as the subjective perception of cognitive decline, is not well known. This study aimed to investigate the relationship of various types of smoking, including E-cigarette smoking and the use of E-liquid, with the incidence of SCD among Korean adults.

Methods

We evaluated the 2018 Korean Community Health Survey data collected from community-dwelling people in Korea. A total of 104,453 non-smokers, 38,607 past smokers, and 26,776 current smokers with eligible data were included in the study. SCD was assessed using the Behavioral Risk Factor Surveillance System. The past or current smoking pack-years throughout each participant's entire life were calculated. Multiple regression analyses were carried out to estimate the adjusted odds ratios (ORs) as measures of the association between each type of smoking and SCD after adjustment for potential confounders.

Results

Compared to no exposure, passive smoking was associated with higher odds of SCD. Compared to non-smokers, past smokers had a higher OR for SCD; however, current smokers did not. There were no significant associations between passive smoking and SCD in the non-smoker and past smoker groups, but there was a significant relationship between them in the current smoker group. While the cumulative dose of smoking was correlated with an increased OR of SCD in each group of current smokers and past smokers, E-cigarette smoking and the use of E-liquid were not associated with higher ORs in the current smoker group.

Conclusion

Our findings support that passive smoking and past smoking are significantly associated with SCD and that more cumulative exposure to smoking is correlated with a higher OR of SCD.
Comparison of Sex Differences in Outcomes of Patients With Aneurysmal Subarachnoid Hemorrhage: A Single-Center Retrospective Study
Authors: Cai Yuankun , Liu Zheng , Jia Chenguang , Zhao Jingwei , Chai Songshan , Li Zhengwei , Xu Chengshi , Zhang Tingbao , Ma Yihui , Ma Chao , Chen Xinjun , Jiang Pucha , Zhao Wenyuan , Chen Jincao , Xiong Nanxiang
Published: April 2022

Background

Sex differences in the outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. The aim of this study was to evaluate sex differences in the outcomes of patients with aSAH.

Method

This study retrospectively analyzed the clinical data of consecutive patients with aSAH, admitted to the Department of Neurosurgery, Wuhan University Zhongnan Hospital, from May 1, 2020 to December 31, 2020. The modified Rankin Scale (mRS) score was used to evaluate the prognosis of patients at discharge. Outcome indicators included cerebral ischemia, hydrocephalus, and mRS ≥ 2 at discharge.

Results

The majority (65%) of the 287 patients with aSAH included in the study were females. Patients were divided into female (n = 184) and male (n = 99) groups; the female patients were significantly older than the male patients (61.3 ± 8.5 years vs. 60.0 ± 8.5 years, p = 0.032). The incidence of comorbidities (hypertension, diabetes, and heart disease) was higher in the female group than in the male group, but the difference was not statistically significant. Although more female patients than male patients underwent endovascular treatment, there was no statistical difference in the treatment approach between the two groups. Comparison of post-operative complications and mRS scores at discharge revealed that the rate of cerebral ischemia and mRS ≥ 2 at discharge were significantly higher among female patients than among male patients. Moreover, this difference persisted after propensity adjustment for age and treatment approach. Analysis of risk factors for poor prognosis at discharge in both pre- and post-adjustment patients revealed cerebral ischemia and high mFisher score (mFisher = 3/4) to be independent risk factors.

Conclusion

Female patients with aSAH have a worse prognosis than male patients, and this difference may be because women are more susceptible to cerebral ischemia.
Cerebellar and/or Brainstem Lesions Indicate Poor Prognosis in Multiple Sclerosis: A Systematic Review
Authors: Yang Yuyuan , Wang Meng , Xu Lulu , Zhong Meixiang , Wang Yajuan , Luan Moxin , Li Xingao , Zheng Xueping
Published: April 2022

Multiple sclerosis is a serious neurological disease that affects millions of people worldwide. Cerebellar and brainstem symptoms are common in the course of multiple sclerosis, but their prognostic value is unclear. This systematic review aimed to determine the relationship between the location of lesions in the cerebellum and/or brainstem and the prognosis in multiple sclerosis. In this systematic review, we searched and comprehensively read articles related to this research topic in Chinese and English electronic databases (PubMed, Embase, Cochrane Library, CNKI, and CBM) using search terms “multiple sclerosis,” “cerebellum,” “brainstem,” “prognosis,” and others. Cerebellar and brainstem clinically isolated syndromes and clinically definite multiple sclerosis were important predictors of transformation (hazard ratio, 2.58; 95% confidence interval, 1.58–4.22). Cerebellar and/or brainstem lesions indicate a poor overall prognosis in multiple sclerosis, but because of inconsistency, more clinical data are needed.
A Machine Learning Approach for Detecting Cognitive Interference Based on Eye-Tracking Data
Authors: Rizzo Antonio , Ermini Sara , Zanca Dario , Bernabini Dario , Rossi Alessandro
Published: April 2022

The Stroop test evaluates the ability to inhibit cognitive interference. This interference occurs when the processing of one stimulus characteristic affects the simultaneous processing of another attribute of the same stimulus. Eye movements are an indicator of the individual attention load required for inhibiting cognitive interference. We used an eye tracker to collect eye movements data from more than 60 subjects each performing four different but similar tasks (some with cognitive interference and some without). After the extraction of features related to fixations, saccades and gaze trajectory, we trained different Machine Learning models to recognize tasks performed in the different conditions (i.e., with interference, without interference). The models achieved good classification performances when distinguishing between similar tasks performed with or without cognitive interference. This suggests the presence of characterizing patterns common among subjects, which can be captured by machine learning algorithms despite the individual variability of visual behavior.
Altered Resting Brain Functions in Patients With Irritable Bowel Syndrome: A Systematic Review
Authors: Yu Zheng , Liu Li-Ying , Lai Yuan-Yuan , Tian Zi-Lei , Yang Lu , Zhang Qi , Liang Fan-Rong , Yu Si-Yi , Zheng Qian-Hua
Published: April 2022

Background

The neural activity of irritable bowel syndrome (IBS) patients in the resting state without any intervention has not been systematically studied. The purpose of this study was to compare the resting-state brain functions of IBS patients with healthy controls (HCs).

Methods

The published neuroimage studies were obtained from electronic databases including PubMed, EMBASE, PsycINFO, Web of Science Core, CNKI Database, Wanfang Database, VIP Database, and CBMdisc. Search dates were from inception to March 14th, 2022. The studies were identified by the preidentified inclusion and exclusion criteria. Two independent reviewers compiled the studies and evaluated them for quality and bias.

Results

Altogether 22 fMRI studies were included in this review. The risk of bias of the included studies was generally low. The findings indicated that in IBS patients, increased or decreased brain areas were mostly associated with visceral sensations, emotional processing, and pain processing. According to brain network research, IBS may exhibit anomalies in the DMN, CEN, and emotional arousal networks. The fluctuations in emotion (anxiety, sadness) and symptoms in IBS patients were associated with alterations in the relevant brain regions.

Conclusion

This study draws a preliminary conclusion that there are insufficient data to accurately distinguish the different neurological features of IBS in the resting state. Additional high-quality research undertaken by diverse geographic regions and teams is required to reach reliable results regarding resting-state changed brain regions in IBS.
Adaptive Multimodal Neuroimage Integration for Major Depression Disorder Detection
Authors: Wang Qianqian , Li Long , Qiao Lishan , Liu Mingxia
Published: April 2022

Major depressive disorder (MDD) is one of the most common mental health disorders that can affect sleep, mood, appetite, and behavior of people. Multimodal neuroimaging data, such as functional and structural magnetic resonance imaging (MRI) scans, have been widely used in computer-aided detection of MDD. However, previous studies usually treat these two modalities separately, without considering their potentially complementary information. Even though a few studies propose integrating these two modalities, they usually suffer from significant inter-modality data heterogeneity. In this paper, we propose an adaptive multimodal neuroimage integration (AMNI) framework for automated MDD detection based on functional and structural MRIs. The AMNI framework consists of four major components: (1) a graph convolutional network to learn feature representations of functional connectivity networks derived from functional MRIs, (2) a convolutional neural network to learn features of T1-weighted structural MRIs, (3) a feature adaptation module to alleviate inter-modality difference, and (4) a feature fusion module to integrate feature representations extracted from two modalities for classification. To the best of our knowledge, this is among the first attempts to adaptively integrate functional and structural MRIs for neuroimaging-based MDD analysis by explicitly alleviating inter-modality heterogeneity. Extensive evaluations are performed on 533 subjects with resting-state functional MRI and T1-weighted MRI, with results suggesting the efficacy of the proposed method.
Eye-Movements During Navigation in a Virtual Environment: Sex Differences and Relationship to Sex Hormones
Authors: Harris TiAnni , Hagg Johanna , Pletzer Belinda
Published: April 2022

Sex differences in spatial navigation have been related to different navigation strategies. For example, women are more likely to utilize local landmark-information in the environment compared to men. Furthermore, sex differences appear to be more pronounced when distances need to be judged in Euclidian terms and an allocentric representation of the environment is necessary. This suggests differential attentional processes during spatial navigation in men and women. However, eye-tracking studies on spatial navigation exploring these attentional processes are rare. The present study (39 men and 36 women) set out to investigate sex differences in eye-movements during spatial navigation in a 3D environment using virtual reality goggles. While we observed the expected sex differences in overall navigation performance, women did not benefit from the landmark-based instructions. Gaze fixations were in accordance with the preferred Euclidian strategy in men, but did not confirm the expected landmark-based strategy in women. However, high estradiol levels where related to an increased focus on landmark information. Surprisingly, women showed longer gaze distances than men, although the utilization of distal landmarks has been related to allocentric representations preferred by men. In fact, larger gaze distances related to slower navigation, even though previous studies suggest that the utilization of distal landmarks is beneficial for navigation. The findings are discussed with respect to the utility of virtual reality presentation for studies on sex differences in navigation. While virtual reality allows a full first-person immersion in the environment, proprioceptive and vestibular information is lacking.
The Implication of Pathway Turn and Task Condition on Gait Quantified Using SmartWalk: Changes With Age and Parkinson’s Disease With Relevance to Postural Strategy and Risk of Fall
Authors: Pallavi Priya , Jariwala Neeti , Patel Niravkumar , Kanetkar Manasi , Diwan Shraddha , Lahiri Uttama
Published: April 2022

One’s gait can be affected by aging, pathway with turns, task demands, etc., causing changes in gait-related indices and knee flexion (influencing posture). Walking on pathways with turns threatens stability, affecting one’s gait-related indices and posture. The ability to overcome such deficits is compromised with age and neurological disorders, e.g., Parkinson’s Disease (PD) leading to falls. Also, task demands imposed by single and dual-task (e.g., counting backward while walking) conditions affect the gait of individuals using different postural strategies varying with age and neurological disorder. Existing research has investigated either the effect of the pathway with turn or task condition on one’s gait. However, none (to our knowledge) have explored the differentiated implications of the pathway with turn and task conditions on one’s gait-related indices and knee flexion while walking. Our study had two phases with 30 participants. Phase 1 had healthy adults (young and old) and Phase 2 had age and gender-matched healthy elderly and individuals with Parkinson’s disease (PD) who walked on pathways having turns under single and dual-task conditions. We analysed gait in terms of (i) gait-related indices (Phases 1 and 2) and (ii) knee flexion (Phase 2). Also, we analysed one’s counting performance during dual task. One’s gait-related indices and knee flexion were measured using a portable gait quantifier. The aim was to (i)understand whether both pathways with turn and task conditions are equally effective in affecting the gait of (a)individuals of varying ages and (b) gender-matched healthy older adults and individuals with PD, (ii)study variations of knee joint angles while walking on pathways having turns (under different task conditions) in terms of its clinical relevance, and (iii) explore the implication of pathway with turn on counting performance (with relevance to postural strategy) with varying age and PD. Results indicated that for the younger group, the task condition caused statistical variations in gait-related indices. For the older group, both pathways with turn and task conditions had statistical implications on gait-related indices. Additionally, individuals with PD demonstrated a higher variation in knee flexion than their healthy counterparts. Again, pathways with varying turns elicited variations in counting performance indicating different postural strategies being employed by the three groups.
White Matter Injury in Preterm Infants: Pathogenesis and Potential Therapy From the Aspect of the Gut–Brain Axis
Authors: He Yu , Zhang Yuni , Li Fang , Shi Yuan
Published: April 2022

Very preterm infants who survive are at high risk of white matter injury (WMI). With a greater understanding of the pathogenesis of WMI, the gut microbiota has recently drawn increasing attention in this field. This review tries to clarify the possible mechanisms behind the communication of the gut bacteria and the immature brain via the gut–brain axis. The gut microbiota releases signals, such as microbial metabolites. These metabolites regulate inflammatory and immune responses characterized by microglial activation, which ultimately impact the differentiation of pre-myelinating oligodendrocytes (pre-OLs) and lead to WMI. Moreover, probiotics and prebiotics emerge as a promising therapy to improve the neurodevelopmental outcome. However, future studies are required to clarify the function of these above products and the optimal time for their administration within a larger population. Based on the existing evidence, it is still too early to recommend probiotics and prebiotics as effective treatments for WMI.
Effects of Septin-14 Gene Deletion on Adult Cognitive/Emotional Behavior
Authors: Chen Kuan-Ru , Wang Han-Yu , Liao Yi-Han , Sun Li-Han , Huang Yu-Han , Yu Lung , Kuo Pao-Lin
Published: April 2022

While various septin GTPases have been reported for their physiological functions, their roles in orchestrating complex cognitive/emotional functions in adult mammals remained scarcely explored. A comprehensive behavioral test battery was administered to two sexes of 12-week-old Septin-14 (SEPT14) knockout (KO) and wild-type (WT) mice. The sexually dimorphic effects of brain SEPT14 KO on inhibitory avoidance (IA) and hippocampal mGluR5 expression were noticed with greater IA latency and elevated mGluR5 level exclusively in male KO mice. Moreover, SEPT14 KO appeared to be associated with stress-provoked anxiety increase in a stress-related navigation task regardless of animals’ sexes. While male and female WT mice demonstrated comparable cell proliferation in the dorsal and ventral hippocampal dentate gyrus (DG), both sexes of SEPT14 KO mice had increased cell proliferation in the ventral DG. Finally, male and female SEPT14 KO mice displayed dampened observational fear conditioning magnitude and learning-provoked corticosterone secretion as compared to their same-sex WT mice. These results, taken together, prompt us to conclude that male, but not female, mice lacking the Septin-14 gene may exhibit increased aversive emotion-related learning and dorsal/ventral hippocampal mGluR5 expressions. Moreover, deletion of SEPT14 may be associated with elevated ventral hippocampal DG cell proliferation and stress-provoked anxiety-like behavior, while dampening vicarious fear conditioning magnitudes.
COVID-19 Illness Severity in the Elderly in Relation to Vegetarian and Non-vegetarian Diets: A Single-Center Experience
Authors: Hou Yi-Cheng , Su Wen-Lin , Chao You-Chen
Published: April 2022

The first wave of the coronavirus disease 2019 (COVID-19) outbreak in Taiwan occurred in May 2021. The risk for and severity of this disease vary and are highly dependent on personal habits and comorbidities. Moreover, the gut microbiome, which may be affected by diet, is highly susceptible with regard to the risk and severity of infectious diseases such as COVID-19. The relationship between dietary habits, nutritional status, and the effects of these factors on the immune system in the context of a global pandemic is an extremely important topic of immediate concern. Hence, the aim of this study was to explore the effect of vegetarian and non-vegetarian diets on COVID-19 severity during the pandemic. We conducted a retrospective evaluation of 509 patients who had been diagnosed with COVID-19 at a single medical center between May 2021 and August 2021. Patients were divided into three groups according to disease severity. For patients aged ≥65 years, COVID-19 symptom severity was statistically significantly and inversely associated with the adherence to a vegetarian diet (p = 0.013). Moreover, subgroup analysis results showed that older COVID-19 patients and those with a non-vegetarian diet had a higher risk of contracting critically severe COVID-19 [adjusted odds ratio (OR) = 5.434, p = 0.005]. Further research is needed to determine the effects of dietary habits on COVID-19 risk and severity during the global pandemic.
Systemic Evaluation of the Effect of Diabetes Mellitus on Breast Cancer in a Mouse Model
Authors: Wei Nana , Lu Jinmiao , Lin Zhibing , Wang Xiaoyu , Cai Mengmeng , Jiang Shengyao , Chen Xiaoyu , Zhu Shilan , Zhang Dong , Cui Li
Published: April 2022

Breast cancer complicated with diabetes mellitus (DM) is a common disease. To evaluate the effect of preexisting DM on breast cancer progression without drug interference, we used a streptozotocin (STZ)-induced type 2 diabetes mellitus BALB/c mouse model. We found that 4T1 breast cancer complicated with DM decreased the mouse survival time compared with 4T1-bearing mice. The diversity of gut microbiome was affected by DM. The infiltration of mucosal-associated invariant T cell (MAIT), CD8+ T cell, and CD4+ T cell in the tumor was significantly decreased in the DM-4T1 group compared with the 4T1 group. The transcriptome data of tumor tissues indicated that the expressions of inflammatory C–C chemokine- and metabolism-related genes were greatly changed. The abnormal expression of these genes may be related with the decreased T-cell infiltration in DM-4T1. In conclusion, the gut microbiome and tumor microenvironment of diabetic breast cancer patients have unique features. The effect of diabetes on breast cancer should be considered in the treatment for diabetic breast cancer patients.
Glucose-Restricted Diet Regulates the Tumor Immune Microenvironment and Prevents Tumor Growth in Lung Adenocarcinoma
Authors: Gähler Alexander , Trufa Denis I. , Chiriac Mircea T. , Tausche Patrick , Hohenberger Katja , Brunst Ann-Kathrin , Rauh Manfred , Geppert Carol I. , Rieker Ralf J. , Krammer Susanne , Leberle Anna , Neurath Markus F. , Sirbu Horia , Hartmann Arndt , Finotto Susetta
Published: April 2022

Background

Lung cancer is the second common cancer type in western countries and has a high mortality. During the development and progression of the tumor, the nutrients in its environment play a central role. The tumor cells depend crucially on glucose metabolism and uptake. Tumor cell metabolism is dominated by the Warburg effect, where tumor cells produce large amounts of lactate from pyruvate under aerobic conditions. We thus reasoned that, reducing carbohydrates in the diet might support anti-tumoral effects of current immunotherapy and additionally target tumor immune escape.

Objectives

The link between reducing carbohydrates to improve current immunotherapy is not clear. We thus aimed at analyzing the effects of different glucose levels on the tumor development, progression and the anti-tumoral immune response.

Methods

We correlated the clinical parameters of our LUAD cohort with different metabolic markers. Additionally, we performed cell culture experiments with A549 tumor cell line under different glucose levels. Lastly, we investigated the effect of low and high carbohydrate diet in an experimental murine model of lung cancer on the tumor progression and different immune subsets.

Results

Here we found a positive correlation between the body mass index (BMI), blood glucose levels, reduced overall survival (OS) and the expression of Insulin-like growth factor-1 receptor (IGF1R) in the lung tumoral region of patients with lung adenocarcinoma (LUAD). Furthermore, increasing extracellular glucose induced IGF1R expression in A549 LUAD cells. Functional studies in a murine model of LUAD demonstrated that, glucose restricted diet resulted in decreased tumor load in vivo. This finding was associated with increased presence of lung infiltrating cytotoxic CD8+ T effector memory (TEM), tissue resident memory T (TRM) and natural killer cells as well as reduced IGFR mRNA expression, suggesting that glucose restriction regulates lung immunity in the tumor microenvironment.

Conclusions

These results indicate that, glucose restricted diet improves lung immune responses of the host and suppresses tumor growth in experimental lung adenocarcinoma. As glucose levels in LUAD patients were negatively correlated to postoperative survival rates, glucose-restricted diet emerges as therapeutic avenue for patients with LUAD.
Prognostic Significance of the Loss of Heterozygosity of KRAS in Early-Stage Lung Adenocarcinoma
Authors: Khadse Anand , Haakensen Vilde D. , Silwal-Pandit Laxmi , Hamfjord Julian , Micke Patrick , Botling Johan , Brustugun Odd Terje , Lingjærde Ole Christian , Helland Åslaug , Kure Elin H.
Published: April 2022

Lung cancer is a common disease with a poor prognosis. Genomic alterations involving the KRAS gene are common in lung carcinomas, although much is unknown about how different mutations, deletions, and expressions influence the disease course. The first approval of a KRAS-directed inhibitor was recently approved by the FDA. Mutations in the KRAS gene have been associated with poor prognosis for lung adenocarcinomas, but implications of the loss of heterozygosity (LOH) of KRAS have not been investigated. In this study, we have assessed the LOH of KRAS in early-stage lung adenocarcinoma by analyzing DNA copy number profiles and have investigated the effect on patient outcome in association with mRNA expression and somatic hotspot mutations. KRAS mutation was present in 36% of cases and was associated with elevated mRNA expression. LOH in KRAS was associated with a favorable prognosis, more prominently in KRAS mutated than in wild-type patients. The presence of both LOH and mutation in KRAS conferred a better prognosis than KRAS mutation alone. For wild-type tumors, no difference in prognosis was observed between patients with and without LOH in KRAS. Our study indicates that LOH in KRAS is an independent prognostic factor that may refine the existing prognostic groups of lung adenocarcinomas.