bluuebunny/crossref_metadata_2025 huggingface dataset:
Feel Your Reach: An EEG-Based Framework to Continuously Detect Goal-Directed Movements and Error Processing to Gate Kinesthetic Feedback Informed Artificial Arm Control
Authors: Müller-Putz Gernot R. , Kobler Reinmar J. , Pereira Joana , Lopes-Dias Catarina , Hehenberger Lea , Mondini Valeria , Martínez-Cagigal Víctor , Srisrisawang Nitikorn , Pulferer Hannah , Batistić Luka , Sburlea Andreea I.
Published: March 2022

Establishing the basic knowledge, methodology, and technology for a framework for the continuous decoding of hand/arm movement intention was the aim of the ERC-funded project “Feel Your Reach”. In this work, we review the studies and methods we performed and implemented in the last 6 years, which build the basis for enabling severely paralyzed people to non-invasively control a robotic arm in real-time from electroencephalogram (EEG). In detail, we investigated goal-directed movement detection, decoding of executed and attempted movement trajectories, grasping correlates, error processing, and kinesthetic feedback. Although we have tested some of our approaches already with the target populations, we still need to transfer the “Feel Your Reach” framework to people with cervical spinal cord injury and evaluate the decoders’ performance while participants attempt to perform upper-limb movements. While on the one hand, we made major progress towards this ambitious goal, we also critically discuss current limitations.
Effect of Anesthetics on Functional Connectivity of Developing Brain
Authors: Chen Xu , Zheng Xuemei , Cai Jianghui , Yang Xiao , Lin Yonghong , Wu Mengjun , Deng Xiaofan , Peng Yong G.
Published: March 2022

The potential anesthetic neurotoxicity on the neonate is an important focus of research investigation in the field of pediatric anesthesiology. It is essential to understand how these anesthetics may affect the development and growth of neonatal immature and vulnerable brains. Functional magnetic resonance imaging (fMRI) has suggested that using anesthetics result in reduced functional connectivity may consider as core sequence for the neurotoxicity and neurodegenerative changes in the developed brain. Anesthetics either directly impact the primary structures and functions of the brain or indirectly alter the hemodynamic parameters that contribute to cerebral blood flow (CBF) in neonatal patients. We hypothesis that anesthetic agents may either decrease the brain functional connectivity in neonatal patients or animals, which was observed by fMRI. This review will summarize the effect and mechanism of anesthesia on the rapid growth and development infant and neonate brain with fMRI through functional connectivity. It is possible to provide the new mechanism of neuronal injury induced by anesthetics and objective imaging evidence in animal developing brain.
Integrated Metabolomics and Proteomics Analysis of Urine in a Mouse Model of Posttraumatic Stress Disorder
Authors: Zhou Daxue , Long Chengyan , Shao Yan , Li Fei , Sun Wei , Zheng Zihan , Wang Xiaoyang , Huang Yiwei , Pan Feng , Chen Gang , Guo Yanlei , Huang Yi
Published: March 2022

Posttraumatic stress disorder (PTSD) is a serious stress disorder that occurs in individuals who have experienced major traumatic events. The underlying pathological mechanisms of PTSD are complex, and the related predisposing factors are still not fully understood. In this study, label-free quantitative proteomics and untargeted metabolomics were used to comprehensively characterize changes in a PTSD mice model. Differential expression analysis showed that 12 metabolites and 27 proteins were significantly differentially expressed between the two groups. Bioinformatics analysis revealed that the differentiated proteins were mostly enriched in: small molecule binding, transporter activity, extracellular region, extracellular space, endopeptidase activity, zymogen activation, hydrolase activity, proteolysis, peptidase activity, sodium channel regulator activity. The differentially expressed metabolites were mainly enriched in Pyrimidine metabolism, D-Glutamine and D-glutamate metabolism, Alanine, aspartate and glutamate metabolism, Arginine biosynthesis, Glutathione metabolism, Arginine, and proline metabolism. These results expand the existing understanding of the molecular basis of the pathogenesis and progression of PTSD, and also suggest a new direction for potential therapeutic targets of PTSD. Therefore, the combination of urine proteomics and metabolomics explores a new approach for the study of the underlying pathological mechanisms of PTSD.
The Slack Channel Deletion Causes Mechanical Pain Hypersensitivity in Mice
Authors: Liu Ye , Zhang Fang-Fang , Song Ying , Wang Ran , Zhang Qi , Shen Zhong-Shan , Zhang Fei-Fei , Zhong Dan-Ya , Wang Xiao-Hui , Guo Qing , Tang Qiong-Yao , Zhang Zhe
Published: March 2022

The role of the Slack (also known as Slo2.2, KNa1.1, or KCNT1) channel in pain-sensing is still in debate on which kind of pain it regulates. In the present study, we found that the Slack–/– mice exhibited decreased mechanical pain threshold but normal heat and cold pain sensitivity. Subsequently, X-gal staining, in situ hybridization, and immunofluorescence staining revealed high expression of the Slack channel in Isolectin B4 positive (IB4+) neurons in the dorsal root ganglion (DRG) and somatostatin-positive (SOM+) neurons in the spinal cord. Patch-clamp recordings indicated the firing frequency was increased in both small neurons in DRG and spinal SOM+ neurons in the Slack–/– mice whereas no obvious slow afterhyperpolarization was observed in both WT mice and Slack–/– mice. Furthermore, we found Kcnt1 gene expression in spinal SOM+ neurons in Slack–/– mice partially relieved the mechanical pain hypersensitivity of Slack–/– mice and decreased AP firing rates of the spinal SOM+ neurons. Finally, deletion of the Slack channel in spinal SOM+ neurons is sufficient to result in mechanical pain hypersensitivity in mice. In summary, our results suggest the important role of the Slack channel in the regulation of mechanical pain-sensing both in small neurons in DRG and SOM+ neurons in the spinal dorsal horn.
Sensing Qualia
Authors: Skokowski Paul
Published: March 2022

Accounting for qualia in the natural world is a difficult business, and it is worth understanding why. A close examination of several theories of mind—Behaviorism, Identity Theory, Functionalism, and Integrated Information Theory—will be discussed, revealing shortcomings for these theories in explaining the contents of conscious experience: qualia. It will be argued that in order to overcome the main difficulty of these theories the senses should be interpreted as physical detectors. A new theory, Grounded Functionalism, will be proposed, which retains multiple realizability while allowing for a scientifically based approach toward accounting for qualia in the natural world.
Carbohydrate Intake Practices and Determinants of Food Choices During Training in Recreational, Amateur, and Professional Endurance Athletes: A Survey Analysis
Authors: Reinhard Corinne , Galloway Stuart D. R.
Published: March 2022

Carbohydrate (CHO) intake during exercise can optimize endurance performance. However, there is limited information regarding fueling practices of endurance athletes during training. Accordingly, an anonymous German-language online survey was circulated examining the determinants of CHO choices, and intake practices among runners, triathletes, and cyclists during training. Survey questions included predefined answers, and a Likert scale with response of CHO food choice intakes from 1 = never to 5 = always. 1,081 endurance participants (58.0% male, 68.6% aged 18–39 years) of varying competitive levels were included in the analysis. Overall, most participants consumed a combination of commercial sport nutrition products and everyday foods (67.4%, n = 729) with their primary reason that food-first was preferred, but in some exercise scenarios, commercial sport nutrition products were deemed more convenient (61.3%, n = 447). Participants consuming commercial sport nutrition products only (19.3%, n = 209) most often valued their ease of intake during exercise (85.2%, n = 178). Among those consuming everyday foods only (13.2%, n = 143), the most common reason was the perceived importance of eating wholesome foods/natural ingredients (84.6%, n = 121). Between the most frequently consumed CHO sources during training at low-to-moderate intensities (n = 1032), sports drinks (mean ± SD; 2.56 ± 1.33) were consumed significantly more often than bananas (2.27 ± 1.14, p < 0.001), with no significant difference in intake frequency between bananas and traditional muesli/fruit/energy bars (2.25 ± 1.14, p = 0.616). Whereas during high intensities (n = 1,077), sports drinks (3.31 ± 1.51) were significantly more often consumed than gels (2.79 ± 1.37), and gels significantly more often than energy bars (2.43 ± 1.28), all commercial sport nutrition products (all, p < 0.001). Overall, 95.1% (n = 1028) of all participants consumed CHO during training at all exercise intensities, with males (n = 602; 2.35 ± 0.70) consuming significantly more often commercial sport nutrition products than females (n = 424; 2.14 ± 0.79, p < 0.001); females consumed significantly more often everyday foods than males (1.66 ± 0.47 vs. 1.54 ± 0.42, p < 0.001). Most participants used mixed CHO forms during low-to-moderate (87.9%), and high exercise intensities (94.7%). 67.6% (n = 731) of all participants reported guiding their CHO intake rates during training by gut feeling. These large-scale survey findings suggest a preference of endurance participants’ CHO intake during training in liquid form independent of exercise intensities and offer novel insights into CHO intake practices to guide sports nutrition strategies and education.
Integration of an Independent Monitor Unit Check for High-Magnetic-Field MR-Guided Radiation Therapy System
Authors: Yang Jie , Zhang Pengpeng , Tyagi Neelam , Scripes Paola Godoy , Subashi Ergys , Liang Jiayi , Lovelock Dale , Mechalakos James , Li Anyi , Lim Seng B.
Published: March 2022

Purpose

Commercial independent monitor unit (IMU) check systems for high-magnetic-field MR-guided radiation therapy (RT) systems are lacking. We investigated the feasibility of adopting an existing treatment planning system (TPS) as an IMU check for online adaptive radiotherapy using 1.5-Tesla MR-Linac.

Methods

The 7-MV flattening filter free (FFF) beam and multi-leaf collimator (MLC) models of a 1.5-T Elekta Unity MR-Linac within Monte Carlo-based Monaco TPS were used to generate an optimized beam model in Eclipse TPS. The MLC dosimetric leaf gap of the beam in Eclipse was determined by matching the dose distribution of Eclipse-generated intensity-modulated radiation therapy (IMRT) plans using the Analytical Anisotropic Algorithm (AAA) algorithm to Monaco plans. The plans were automatically adjusted for different source-to-axis distances (SADs) between the two systems. For IMU check, the treatment plans developed in Monaco were transferred to Eclipse to recalculate the dose using AAA. A plug-in within Eclipse was created to perform a 2D gamma analysis of the AAA and Monte Carlo dose distribution on a beam’s eye view parallel plane. Monaco dose distribution was shifted laterally by 2 mm during gamma analysis to account for the impact of magnetic field on electron trajectories. Eclipse doses for posterior beams were corrected for both the Unity couch and the posterior MR coil attenuation. Thirteen patients, each with 4–5 fractions for a variety of tumor sites (pancreas, rectum, and prostate), were tested.

Results

After thorough commissioning, the method was implemented as part of the standard clinical workflow. A total of 62 online plans, each with approximately 15 beams, were evaluated. The average per-beam gamma (3%/3 mm) pass rate for plans was 97.9% (range, 95.9% to 98.8%). The average pass rate per beam for all 932 beams used in these plans was 97.9% ± 1.9%, with the lowest per-beam gamma pass rate at 88.4%. The time for the process was within 3.2 ± 0.9 min.

Conclusion

The use of a second planning system provides an efficient way to perform IMU checks with clinically acceptable accuracy for online adaptive plans on Unity MR-Linac. This is essential for meeting the safety requirements for second checks as outlined in American Association of Physicists in Medicine Task Group (AAPM TG) reports 114 and 219.
Evaluation of Deep Learning-Based Automated Detection of Primary Spine Tumors on MRI Using the Turing Test
Authors: Ouyang Hanqiang , Meng Fanyu , Liu Jianfang , Song Xinhang , Li Yuan , Yuan Yuan , Wang Chunjie , Lang Ning , Tian Shuai , Yao Meiyi , Liu Xiaoguang , Yuan Huishu , Jiang Shuqiang , Jiang Liang
Published: March 2022

Background

Recently, the Turing test has been used to investigate whether machines have intelligence similar to humans. Our study aimed to assess the ability of an artificial intelligence (AI) system for spine tumor detection using the Turing test.

Methods

Our retrospective study data included 12179 images from 321 patients for developing AI detection systems and 6635 images from 187 patients for the Turing test. We utilized a deep learning-based tumor detection system with Faster R-CNN architecture, which generates region proposals by Region Proposal Network in the first stage and corrects the position and the size of the bounding box of the lesion area in the second stage. Each choice question featured four bounding boxes enclosing an identical tumor. Three were detected by the proposed deep learning model, whereas the other was annotated by a doctor; the results were shown to six doctors as respondents. If the respondent did not correctly identify the image annotated by a human, his answer was considered a misclassification. If all misclassification rates were >30%, the respondents were considered unable to distinguish the AI-detected tumor from the human-annotated one, which indicated that the AI system passed the Turing test.

Results

The average misclassification rates in the Turing test were 51.2% (95% CI: 45.7%–57.5%) in the axial view (maximum of 62%, minimum of 44%) and 44.5% (95% CI: 38.2%–51.8%) in the sagittal view (maximum of 59%, minimum of 36%). The misclassification rates of all six respondents were >30%; therefore, our AI system passed the Turing test.

Conclusion

Our proposed intelligent spine tumor detection system has a similar detection ability to annotation doctors and may be an efficient tool to assist radiologists or orthopedists in primary spine tumor detection.
Analysis of Genetic Alterations in Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma With Whole-Exome Sequencing
Authors: Zhao Andi , Wu Fangtian , Wang Yue , Li Jianyong , Xu Wei , Liu Hu
Published: March 2022

Next-generation sequencing studies on ocular adnexal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML) have to date revealed several targets of genetic aberrations. However, most of our current understanding of the pathogenesis and prognosis of OAML is primarily based on studies conducted in populations from Europe and the US. Furthermore, the majority were based on formalin-fixed paraffin-embedded (FFPE) tissue, which generally has poor integrity and creates many sequencing artifacts. To better investigate the coding genome landscapes of OAML, especially in the Chinese population, we performed whole-exome sequencing of 21 OAML cases with fresh frozen tumor tissue and matched peripheral blood samples. IGLL5, as a novel recurrently mutated gene, was found in 24% (5/21) of patients, with a higher relapse rate (P=0.032). In addition, mutations of MSH6, DIS3, FAT1, and TMEM127 were found in 10% of cases. These novel somatic mutations indicate the existence of additional/alternative lymphomagenesis pathways in OAML. Moreover, the difference between our and previous studies suggests genetic heterogeneity of OAML between Asian and Western individuals.
Knockdown of AKR1C3 Promoted Sorafenib Sensitivity Through Inhibiting the Phosphorylation of AKT in Hepatocellular Carcinoma
Authors: Zheng Jia , Yang Zhihong , Li Yanlei , Yang Li , Yao Ruili
Published: March 2022

Background

Sorafenib, which can induce ferroptosis, is a multikinase inhibitor for enhancing survival in advanced hepatocellular carcinoma (HCC). However, a considerable challenge for the treatment of HCC is sorafenib resistance. Therefore, targeting the relationship between sorafenib resistance and ferroptosis genes may provide a novel approach for the treatment of HCC.

Materials and Methods

We analyzed the gene expression and clinicopathological factors from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases (GSE109211/GSE62813). The statistical analysis was conducted in R. Cell proliferation was assayed by MTT, cell colony-forming assay, and wound healing assay. Immunofluorescence assay and Western blot were used to evaluate the expression of AKT.

Results

Many ferroptosis-related genes were upregulated in the sorafenib-resistant group. Aldo-keto reductase 1C3 (AKR1C3) was highly expressed in sorafenib-resistant patients, and the high expression of AKR1C3 was associated with the poor prognosis of patients from the TCGA and ICGC databases. MTT and colony-forming assays showing AKR1C3 overexpression enhanced the proliferation of HCC cells and acute sorafenib resistance. Knockdown of AKR1C3 inhibited the proliferation of HCC cells and increased the drug sensitivity of sorafenib. Immunofluorescence assay and Western blot proved that AKR1C3 promoted the phosphorylation of AKT.

Conclusion

AKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in HCC. AKR1C3 inhibitors may be used in conjunction with sorafenib to become a better therapeutic target for HCC.
Acetyl-CoA Carboxylases and Diseases
Authors: Wang Yu , Yu Weixing , Li Sha , Guo Dingyuan , He Jie , Wang Yugang
Published: March 2022

Acetyl-CoA carboxylases (ACCs) are enzymes that catalyze the carboxylation of acetyl-CoA to produce malonyl-CoA. In mammals, ACC1 and ACC2 are two members of ACCs. ACC1 localizes in the cytosol and acts as the first and rate-limiting enzyme in the de novo fatty acid synthesis pathway. ACC2 localizes on the outer membrane of mitochondria and produces malonyl-CoA to regulate the activity of carnitine palmitoyltransferase 1 (CPT1) that involves in the β-oxidation of fatty acid. Fatty acid synthesis is central in a myriad of physiological and pathological conditions. ACC1 is the major member of ACCs in mammalian, mountains of documents record the roles of ACC1 in various diseases, such as cancer, diabetes, obesity. Besides, acetyl-CoA and malonyl-CoA are cofactors in protein acetylation and malonylation, respectively, so that the manipulation of acetyl-CoA and malonyl-CoA by ACC1 can also markedly influence the profile of protein post-translational modifications, resulting in alternated biological processes in mammalian cells. In the review, we summarize our understandings of ACCs, including their structural features, regulatory mechanisms, and roles in diseases. ACC1 has emerged as a promising target for diseases treatment, so that the specific inhibitors of ACC1 for diseases treatment are also discussed.
Clinical Evaluation of an Auto-Segmentation Tool for Spine SBRT Treatment
Authors: Chen Yingxuan , Vinogradskiy Yevgeniy , Yu Yan , Shi Wenyin , Liu Haisong
Published: March 2022

Purpose

Spine SBRT target delineation is time-consuming due to the complex bone structure. Recently, Elements SmartBrush Spine (ESS) was developed by Brainlab to automatically generate a clinical target volume (CTV) based on gross tumor volume (GTV). The aim of this project is to evaluate the accuracy and efficiency of ESS auto-segmentation.

Methods

Twenty spine SBRT patients with 21 target sites treated at our institution were used for this retrospective comparison study. Planning CT/MRI images and physician-drawn GTVs were inputs for ESS. ESS can automatically segment the vertebra, split the vertebra into 6 sectors, and generate a CTV based on the GTV location, according to the International Spine Radiosurgery Consortium (ISRC) Consensus guidelines. The auto-segmented CTV can be edited by including/excluding sectors of the vertebra, if necessary. The ESS-generated CTV contour was then compared to the clinically used CTV using qualitative and quantitative methods. The CTV contours were compared using visual assessment by the clinicians, relative volume differences (RVD), distance of center of mass (DCM), and three other common contour similarity measurements such as dice similarity coefficient (DICE), Hausdorff distance (HD), and 95% Hausdorff distance (HD95).

Results

Qualitatively, the study showed that ESS can segment vertebra more accurately and consistently than humans at normal curvature conditions. The accuracy of CTV delineation can be improved significantly if the auto-segmentation is used as the first step. Conversely, ESS may mistakenly split or join different vertebrae when large curvatures in anatomy exist. In this study, human interactions were needed in 7 of 21 cases to generate the final CTVs by including/excluding sectors of the vertebra. In 90% of cases, the RVD were within ±15%. The RVD, DCM, DICE, HD, and HD95 for the 21 cases were 3% ± 12%, 1.9 ± 1.5 mm, 0.86 ± 0.06, 13.34 ± 7.47 mm, and 4.67 ± 2.21 mm, respectively.

Conclusion

ESS can auto-segment a CTV quickly and accurately and has a good agreement with clinically used CTV. Inter-person variation and contouring time can be reduced with ESS. Physician editing is needed for some occasions. Our study supports the idea of using ESS as the first step for spine SBRT target delineation to improve the contouring consistency as well as to reduce the contouring time.
Efficacy of Intermittent, Oral Famciclovir Prophylaxis for Bortezomib-Induced Herpes Zoster in Multiple Myeloma Patients
Authors: Zheng Gaofeng , Guan Fangshu , Han Xiaoyan , Yang Li , Zhao Yi , Yang Yang , Zhang Enfang , He Jingsong , He Donghua , Wu Wenjun , Huang He , Cai Zhen
Published: March 2022

Objective

To explore the efficacy and safety of intermittent, oral famciclovir prophylaxis for bortezomib-induced herpes zoster in multiple myeloma patients.

Method

We retrospectively analyzed the incidence of bortezomib treatment-related varicella-zoster virus reactivation in 719 newly-diagnosed multiple myeloma patients receiving intermittent oral famciclovir prophylaxis, continuous oral acyclovir prophylaxis or no prophylaxis. The definition of intermittent oral famciclovir prophylaxis was oral famciclovir at a dose of 250mg twice daily for 9 days after finishing the last dose of bortezomib therapy every cycle. Age, gender, stage per the International Staging System, type of M protein, baseline of absolute lymphocyte count, absolute neutrophil count, and absolute monocyte count were analyzed to find the potential factors that could predispose to herpes zoster infections.

Results

Varicella-zoster virus infection occurred in 96 patients (13.4%) during bortezomib treatment. The incidence of herpes zoster was significantly higher in the non-prophylaxis group compared with the prophylaxis group (22.9% vs 8.2% P<0.001), while the rate was similar between the intermittent oral famciclovir group and the continuous oral acyclovir group (8.4% vs 7.9% P=0.835). Hepatic and renal toxicity were observed in 12% and 2.8% of the patient respectively in the intermittent famciclovir group, which was similar in the continuous acyclovir group (18.1% and 4.2%). The prophylactic use of antiviral agents is a predictive factor for varicella-zoster virus reactivation.

Conclusion

Intermittent famciclovir prophylaxis is effective and safe in preventing herpes zoster development and can markedly reduce the duration of oral medicine treatment compared with continuous acyclovir prophylaxis.
Comprehensive Assessment of Selected Immune Cell Subpopulations Changes in Chemotherapy-Naïve Germ Cell Tumor Patients
Authors: Kalavska Katarina , Sestakova Zuzana , Mlcakova Andrea , Gronesova Paulina , Miskovska Viera , Rejlekova Katarina , Svetlovska Daniela , Sycova-Mila Zuzana , Obertova Jana , Palacka Patrik , Mardiak Jozef , Chovanec Miroslav , Chovanec Michal , Mego Michal
Published: March 2022

The pattern of immune cell distribution in testicular germ cell tumors (GCT) significantly differs from the immune environment in normal testicular tissues. The present study aimed to evaluate the role of different leukocyte subpopulation in GCTs. A cohort of 84 chemotherapy-naïve GCT patients was analyzed. Immunophenotyping of peripheral blood leukocyte subpopulations was carried out by flow cytometry. In addition, the data assessing the immunophenotypes and the baseline clinicopathological characteristics of the included subjects were statistically evaluated. Their prognostic value for the assessment of progression-free survival (PFS) and overall survival (OS) was estimated. The percentage of different innate/adaptive immune cell subpopulations was significantly associated with poor risk-related clinical features, including the number of metastatic sites, presence of retroperitoneal, mediastinal, lung, brain and non-pulmonary visceral metastases as well as with the S-stage and International Germ Cell Consensus Classification Group (IGCCCG) risk groups. In univariate analysis, the percentages of neutrophils, eosinophils, dendritic cells type 2, lymphocytes and T cytotoxic cells were significantly associated with PFS, while the neutrophil, non-classical monocyte and lymphocyte percentage were associated with OS. However, all these outcome correlations were not independent of IGCCCG in multivariate analysis. The data indicated a link among different innate/adaptive peripheral immune cell subpopulations in GCT patients. In addition, the association between these subpopulations and tumor characteristics was also investigated. The findings of the present study may contribute to a deeper understanding of the interactions between cancer and innate/adaptive immune response in GCT patients.
Neuroimaging in Visual Snow - A Review of the Literature
Authors: Raviskanthan Subahari , Ray Jason C. , Mortensen Peter W. , Lee Andrew G.
Published: March 2022

Since the first description of visual snow syndrome (VSS) in 1995, there has been increasing interest particularly within the past 5-10 years in phenotyping the condition and differentiating it from conditions such as migraine with aura and hallucinogen persisting perception disorder. Structural and functional neuroimaging has provided valuable insights in this regard, yielding functional networks and anatomical regions of interest, of which the right lingual gyrus is of particular note. Various modalities, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT), have all been studied in patients with visual snow. In this article, we conduct a comprehensive literature review of neuroimaging in VSS.
Performance Comparison of Infection Prediction Scores in a South African Neonatal Unit: A Retrospective Case-Control Study
Authors: Lloyd Lizel Georgi , Dramowski Angela , Bekker Adrie , Malou Nada , Ferreyra Cecilia , Van Weissenbruch Mirjam Maria
Published: March 2022

Background and objectives

Infection prediction scores are useful ancillary tests in determining the likelihood of neonatal hospital-acquired infection (HAI), particularly in very low birth weight (VLBW; <1,500 g) infants who are most vulnerable to HAI and have high antibiotic utilization rates. None of the existing infection prediction scores were developed for or evaluated in South African VLBW neonates.

Methods

We identified existing infection prediction scores through literature searches and assessed each score for suitability and feasibility of use in resource-limited settings. Performance of suitable scores were compared using a retrospective dataset of VLBW infants (2016–2017) from a tertiary hospital neonatal unit in Cape Town, South Africa. Sensitivity, specificity, predictive values, and likelihood ratios were calculated for each score.

Results

Eleven infection prediction scores were identified, but only five were suitable for use in resource-limited settings (NOSEP1, Singh, Rosenberg, and Bekhof scores). The five selected scores were evaluated using data from 841 episodes of HAI in 659 VLBW infants. The sensitivity for the scores ranged between 3% (NOSEP1 ≥14; proven and presumed infection), to a maximum of 74% (Singh score ≥1; proven infection). The specificity of these scores ranged from 31% (Singh score ≥1; proven and presumed infection) to 100% (NOSEP1 ≥11 and ≥14, NOSEP-NEW-1 ≥11; proven and presumed infection).

Conclusion

Existing infection prediction scores did not achieve comparable predictive performance in South African VLBW infants and should therefore only be used as an adjunct to clinical judgment in antimicrobial decision making. Future studies should develop infection prediction scores that have high diagnostic accuracy and are feasible to implement in resource-limited neonatal units.
Addressing the Ethical Challenges of Providing Kidney Failure Care for Children: A Global Stance
Authors: Pais Priya , Wightman Aaron
Published: March 2022

Children with kidney failure require kidney replacement therapy (KRT), namely maintenance dialysis and kidney transplant. Adequate kidney failure care consists of KRT or conservative treatment with palliative care. In the context of kidney failure, children depend on parents who are their surrogate decision-makers, and the pediatric nephrology team for taking decisions about KRT or conservative care. In this paper, we discuss the ethical challenges that arise relating to such decision-making, from a global perspective, using the framework of pediatric bioethics. While many ethical dilemmas in the care of children with KRT are universal, the most significant ethical dilemma is the inequitable access to KRT in low & middle income countries (LMICs) where rates of morbidity and mortality depend on the family's ability to pay. Children with kidney failure in LMICs have inadequate access to maintenance dialysis, timely kidney transplant and palliative care compared to their counterparts in high income countries. Using case vignettes, we highlight how these disparities place severe burdens on caregivers, resulting in difficult decision-making, and lead to moral distress among pediatric nephrologists. We conclude with key action points to change this status-quo, the most important being advocacy by the global pediatric nephrology community for better access to affordable kidney failure care for children.
Iron Promotes Cardiac Doxorubicin Retention and Toxicity Through Downregulation of the Mitochondrial Exporter ABCB8
Authors: Menon Archita Venugopal , Kim Jonghan
Published: March 2022

In several cancers, the efflux and resistance against doxorubicin (DOX), an effective anticancer drug, are associated with cellular iron deficiency and overexpression of the mitochondrial exporter ABCB8. Conversely, decreased ABCB8 expression and disrupted iron homeostasis in the heart have been implicated in DOX-associated cardiotoxicity. While studies have demonstrated that altered iron status can modulate the susceptibility to DOX cardiotoxicity, the exact molecular mechanisms have not been clearly understood. Here, we hypothesized that iron stores influence cardiac ABCB8 expression and consequently cardiac retention and toxicity of DOX. First, we found that ABCB8 deficiency in cardiomyocytes decreased DOX efflux, increased DOX-induced toxicity, and decreased cell viability. Conversely, intracellular DOX retention and toxicity were ameliorated by ABCB8 overexpression. To determine if altered cardiac iron status modifies ABCB8 expression, we treated cardiomyocytes with high iron or iron chelators. Western blot and qPCR analyses revealed that ABCB8 levels were decreased in iron overload and increased in iron deficiency. Subsequently, DOX retention and toxicity were increased in cardiomyocytes with iron overload, whereas iron deficiency ameliorated these effects. Next, we validated our results using a mouse model of hereditary hemochromatosis (HH), a genetic iron overload disorder. HH mice exhibited decreased ABCB8 expression and increased DOX retention and toxicity. These changes were abolished by the treatment of HH mice with a low-iron diet. Finally, cardiac-specific overexpression of ABCB8 in HH mice prevented cardiac DOX accumulation and abrogated DOX-induced cardiotoxicity without altering iron overload in the heart. Together, our results demonstrate that ABCB8 mediates DOX efflux and that iron regulates DOX retention and toxicity by altering cardiac ABCB8 expression. Our study identifies a novel role of iron in DOX-induced cardiotoxicity and suggests potential therapeutic intervention for DOX and anthracycline-based cancer pharmacology.
Effects of Fuyou Formula on GnRH Secretion and Related Gene Expression in Treating Precocious Puberty
Authors: Zhang Yi , Sun Ning , Zhang Meng , Ding Qian , Wang Qian , Liang Yuguang , He Huan , Yang Yuxin , Guo Chunyan
Published: March 2022

The Fuyou (Fy) formula is an in-hospital preparation consisting of traditional Chinese medicine (TCM) that has been used for treating precocious puberty (PP) for more than 20 years. In this study, we aimed to clarify the effect of the Fy formula and its major components on PP. To confirm the effect of the Fy formula on the release of hypothalamic gonadotropin-releasing hormone (GnRH), GT1-7 cells were treated with estrogen to build the model group and subsequently treated with the Fy formula and its major components to explore their effects on the secretion of GnRH. The level of GnRH in GT1-7 cells was determined using enzyme-linked immunosorbent assay. The results illustrated that, compared to the model group, the Fy formula inhibited the release of GnRH. In addition, the expression levels of proteins related to GnRH secretion, including GnRH, gonadotropin-releasing hormone receptor (GnRHR), Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), estrogen receptor α (ERα), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-1 receptor (IGF-1R), were detected by real-time polymerase chain reaction (RT-qPCR). The results demonstrated that the Fy formula significantly reduced the level of GnRH secretion in the GT1-7 cell lines compared with the model group. Moreover, it significantly downregulated the expression of GnRH, GnRHR, Kiss1, GPR54, ERα, IGF-1, and IGF-1R. In summary, our results indicate that the Fy formula and its major components may inhibit the effects of estrogen, which alleviates PP through transcriptional regulation of target genes.
Ovarian Sensitivity Decreased Significantly in Patients With Insulin Resistance Undergoing in vitro Fertilization and Embryo Transfer
Authors: Zheng Yanjun , Pan Ye , Li Ping , Wang Zhongyuan , Wang Ze , Shi Yuhua
Published: March 2022

Ovarian sensitivity could affect the outcome of in vitro fertilization and embryo transfer (IVF-ET). The objective of this study was to explore the relationship between the ovarian sensitivity index (OSI) and traditional ovarian response makers and observe the relationship between OSI and insulin resistance (IR). The patients enrolled in this study included 131 patients with polycystic ovary syndrome (PCOS) with IR (PCOS-IR), 52 patients with PCOS without IR (PCOS-N), 164 patients with control with IR (control-IR), 133 patients with control without IR (control-N), 295 patients with IR, 184 patients with non-IR, 183 patients with PCOS, and 297 patients with control (patients with non-PCOS). All patients received standard long protocol or the gonadotropin-releasing hormone (GnRH) antagonist protocol to induce follicular development. The two protocols downregulated the pituitary function or blocked the pituitary luteinizing hormone (LH) secretion with a GnRH antagonist. Both protocols can block premature LH surges because premature luteinization is not conducive to follicular development. All patients underwent IVF or intracytoplasmic sperm injection (ICSI). Embryo transfer was carried out according to the specific situation of each patient. The OSI was significantly reduced in patients with IR. The OSI had a significant positive relationship with anti-Müllerian hormone (AMH), antral follicle count (AFC), basal LH/follicle-stimulating hormone (FSH), dominant follicle number on trigger day, retrieved oocytes, embryo number, and high-quality embryo number. OSI had a significant negative relationship with age, body mass index (BMI), basal FSH, initial dose of Gn, and total dose of Gn. The receiver operating characteristic (ROC) curve of OSI demonstrated a better accuracy in distinguishing patients with positive pregnancy and clinical pregnancy, with an area under the curve (AUC) of 0.662 (95% CI, 0.598–0.727) and 0.636 (95% CI, 0.577–0.695), respectively. Patients could get a higher rate of dominant follicle count (p < 0.0001) through the treatment of standard long protocol when compared with GnRH antagonist protocol. The OSI has a significant correlation with traditional ovarian response markers and could be a good predictor of positive pregnancy and clinical pregnancy for patients with IR.
Genome-Wide Identification, Evolution and Expression Analysis of the Glutathione S-Transferase Supergene Family in Euphorbiaceae
Authors: Duan Qiang , Li Guo-Rui , Qu Yi-Peng , Yin Dong-Xue , Zhang Chun-Ling , Chen Yong-Sheng
Published: March 2022

Euphorbiaceae, a family of plants mainly grown in the tropics and subtropics, is also widely distributed all over the world and is well known for being rich in rubber, oil, medicinal materials, starch, wood and other economically important plant products. Glutathione S-transferases (GSTs) constitute a family of proteins encoded by a large supergene family and are widely expressed in animals, bacteria, fungi and plants, but with few reports of them in Euphorbiaceae plants. These proteins participate in and regulate the detoxification and oxidative stress response of heterogeneous organisms, resistance to stress, growth and development, signal transduction and other related processes. In this study, we identified and analyzed the whole genomes of four species of Euphorbiaceae, namely Ricinus communis, Jatropha curcas, Hevea brasiliensis, and Manihot esculenta, which have high economic and practical value. A total of 244 GST genes were identified. Based on their sequence characteristics and conserved domain types, the GST supergene family in Euphorbiaceae was classified into 10 subfamilies. The GST supergene families of Euphorbiaceae and Arabidopsis have been found to be highly conserved in evolution, and tandem repeats and translocations in these genes have made the greatest contributions to gene amplification here and have experienced strong purification selection. An evolutionary analysis showed that Euphorbiaceae GST genes have also evolved into new subtribes (GSTO, EF1BG, MAPEG), which may play a specific role in Euphorbiaceae. An analysis of expression patterns of the GST supergene family in Euphorbiaceae revealed the functions of these GSTs in different tissues, including resistance to stress and participation in herbicide detoxification. In addition, an interaction analysis was performed to determine the GST gene regulatory mechanism. The results of this study have laid a foundation for further analysis of the functions of the GST supergene family in Euphorbiaceae, especially in stress and herbicide detoxification. The results have also provided new ideas for the study of the regulatory mechanism of the GST supergene family, and have provided a reference for follow-up genetics and breeding work.
Political Cohesion and Fiscal Systems in the Roman Republic
Authors: Tan James
Published: March 2022

For over two centuries, the largest public revenue of the Roman Republic was a levy on property that was earmarked for infantry pay. It was collected by wealthy local landowners and redistributed to soldiers in the district. This article argues that the period oftributumwas largely one of political calm because the tax systems effectively reinforced social and political hierarchies. Within three to four decades oftributum's invention, intra-elite politics began to stabilize, and within three to four decades of its cancellation, intra-elite politics began to destabilize. With little role for a central bureaucracy, local elites across the countryside used their roles as tax collectors to derive bargaining power in politics, but also to control local economies and to demonstrate their high rank in a society that revered public leadership in service of the military.
Keystone Institutions of Democratic Governance Across Indigenous North America
Authors: Holland-Lulewicz Jacob , Thompson Victor D. , Birch Jennifer , Grier Colin
Published: March 2022

Defining and examining democracy in non-Western contexts is a conceptual challenge. This is largely because scholars of contemporary political systems outside of anthropology can envision no alternative pathways other than Western expressions of democracy. Such thinking inhibits our understanding of past, and indeed future, democratic systems. In this paper, we argue that there is no such thing as a “democracy, ” but rather there are institutions that facilitate democratic governance. More specifically, we argue that in Indigenous North America “keystone institutions” facilitated complex institutional arrangements and broad participation by a citizenry in the distribution of power and authority. While these characteristics define such Western democratic institutions as the Athenian assembly, the Icelandic Althing, or the U.S. Congress, we argue that comparable keystone institutions of governance can be identified across Indigenous North America. To illustrate these points, we provide a series of cases that demonstrate the variability in the forms that democratic keystone institutions might take. We specifically focus on axes of variability related to the scale and scope of participation facilitated by each institution, the degree to which the institutions distribute power equitably, and the complexity and formality of the institutional arrangements held together by the keystone institution. Importantly, we argue that the concept of the keystone institution as an analytical tool for seeking out the emergence and role of democratic forms of governance transcends the utility of dichotomous categories such as Western/non-Western or state/non-state that limit productive comparative frameworks and the inclusion of non-traditional case studies of democracy in global conversations.
Knowledge Representations Derived From Semantic Fluency Data
Authors: Zemla Jeffrey C.
Published: March 2022

The semantic fluency task is commonly used as a measure of one’s ability to retrieve semantic concepts. While performance is typically scored by counting the total number of responses, the ordering of responses can be used to estimate how individuals or groups organize semantic concepts within a category. I provide an overview of this methodology, using Alzheimer’s disease as a case study for how the approach can help advance theoretical questions about the nature of semantic representation. However, many open questions surrounding the validity and reliability of this approach remain unresolved.
The Mediating Role of Forgiveness and Self-Efficacy in the Relationship Between Childhood Maltreatment and Treatment Motivation Among Malaysian Male Drug Addicts
Authors: See Mey Loy , Khairudin Rozainee , Tengku Muda Tengku Elmi Azlina , Abdullah @ Mohd Nor Hilwa , Kamaluddin Mohammad Rahim
Published: March 2022

Studies have reported high rates of childhood maltreatment among individuals with drug addiction problems; however, investigation about the potentially protective factors to mitigate the effects of maltreatment experiences on motivation to engage in addiction treatment has received less attention. This study aims at exploring the mediating effects of forgiveness and self-efficacy on the association between childhood maltreatment and treatment motivation among drug addicts. A total of 360 male drug addicts (mean age = 33.34, SD = 7.25) were recruited from three mandatory inpatient rehabilitation centers in Malaysia. Participants completed a package of self-report questionnaires including measures of childhood maltreatment experiences, forgiveness, self-efficacy, and motivation for treatment. The analysis conducted using the structural equation model (SEM) revealed that childhood maltreatment significantly predicted lower treatment motivation, while forgiveness and self-efficacy played a fully mediating role regarding the effect of childhood maltreatment on treatment motivation. In conclusion, these findings suggest that combining the element of forgiveness and self-efficacy in treatment programs appears to benefit the drug addicts with childhood maltreatment history.
Exploring Inequality Through Service Learning in Higher Education: A Bibliometric Review Study
Authors: Martínez-Heredia Nazaret , Corral-Robles Silvia , González-Gijón Gracia , Sánchez-Martín Micaela
Published: March 2022

Service learning (S-L) is an innovative methodology, which is extensively known worldwide. The implementation of this methodology involves classroom learning and real practice. It is based on a cooperative methodology, integrating community service and learning in a connected way. Its main strength lies in its great potential as a transformative social movement to reduce inequality. The main aim of this study was to understand and describe the field of S-L and inequality in higher education through a bibliometric analysis. A descriptive, retrospective, and cross-sectional methodology is used to describe the information obtained from the 20 references on the topic registered in the Scopus and Web of Science (WoS) databases using a mixed methodology. The quantitative and qualitative results show that most of the publications are concentrated in 2016, with the United States being the country with the largest amount of scientific production on this subject. It is also worth noting that most of the authors reported this approach as a powerful tool to develop consciousness, commitment, and responsibility toward inequality and social problems.
Monthly Trends in the Life Events Reported in the Prior Year and First Year of the COVID-19 Pandemic in New Zealand
Authors: Howard Chloe , Overall Nickola C. , Sibley Chris G.
Published: March 2022

The current study examines changes in the economic, social, and well-being life events that women and men reported during the first 7 months of the COVID-19 pandemic. Analyses compared monthly averages in cross-sectional national probability data from two annual waves of the New Zealand Attitudes and Values Study collected between October 2018–September 2019 (N = 17,924), and October 2019–September 2020 (N = 41,653), which included the first 7 months of the pandemic (Mar–Sep 2020). Results indicated that people (particularly women) reported increased job loss in the months following an initial COVID-19 lockdown relative to the same months the year earlier. Women also experienced an increase in family troubles when restrictions eased and reported increased negative lifestyle changes that persisted throughout the first 7 months of the pandemic. The proportion of people experiencing many other life events (e.g., mental health, financial concerns) in New Zealand did not differ reliably from the pre-pandemic monthly baseline. These results highlight resilience to many potential negative life events within the first 7 months of the COVID-19 pandemic. However, the pandemic did not affect everyone equally, and the burden of increased negative events appears more heavily borne by women. As the pandemic continues more than 18 months from initial community transmission of COVID-19, our findings provide important insight into the impact of the pandemic on potential negative life events, especially among women, that may have critical consequences for mental health, gender equality, and social well-being over time.