bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH PENAMBAHAN EKSTRAK BAWANG PUTIH DAN CABAI PADA TELUR ASIN ITIK TERHADAP KANDUNGAN PROTEIN, TOTAL MIKROBA, DAN TINGKAT KESUKAAN KONSUMEN
Authors: Sumarsih  , Fauziyyah Athiefah
Published: August 2021

Penelitian ini bertujuan untuk mengetahui pengaruh penambahan ekstrak bawang putih dan cabai pada telur asin itik terhadap kandungan protein, total mikroba dan tingkat kesukaan konsumen. Metode penelitian memakai metode eksperimen Rancangan Acak Lengkap (RAL) faktor tunggal menggunakan 3 variabel perlakuan dan tiap perlakuan diulang tiga (3) kali. Perlakuan yang diujikan adalah penambahan ekstrak bawang putih 100% dan bawang putih-cabai dengan perbandingan 50% : 50% dengan waktu pemeraman 7 hari dan inkubasi 3 hari. Parameter yang diamati merupakan kadar protein, total mikroba, dan tingkat kesukaan konsumen. Analisis data hasil penelitian memakai teknik analisis sidik ragam ANOVA 5% dan uji lanjut Duncan’s Multiple Range Test (DMRT). Hasil penelitian menunjukan penambahan ekstrak bawang putih dan cabai dengan perbandingan 50% : 50% pada pemeraman 7 hari dan inkubasi 3 hari dapat meningkatkan nilai gizi protein telur asin, namun tidak dapat meningkatkan tampilan fisik baik warna, tekstur dan kenampakan serta jumlah mikroba.
Differential and Prognostic Significance of HOXB7 in Gliomas
Authors: Zhou Xingang , Liang Tingyu , Deng Jinhai , Ng Kenrick , Li Man , Lv Chunxin , Chen Jiamin , Yang Kun , Ma Zhiyuan , Ma Wenping , Wang Peng
Published: August 2021

Diffuse glioma is the most common primary tumor of the central nervous system. The prognosis of the individual tumor is heavily dependent on its grade and subtype. Homeobox B7 (HOXB7), a member of the homeobox family, is abnormally overexpressed in a variety of tumors. However, its function in glioma is unclear. In this study, HOXB7 mRNA and protein expression levels were analyzed in 401 gliomas from the CGGA RNA-seq database (325 cases) and our hospital (76 cases). HOXB7 expression, at both mRNA and protein levels, were upregulated in glioblastoma (GBM) and isocitrate dehydrogenase 1 (IDH1) wild-type glioma tissues. Kaplan–Meier with log-rank test showed that patients with high HOXB7 expression had a poor prognosis (p < 0.0001). Moreover, HOXB7 protein was deleted in 90.9% (20/22) of oligodendrogliomas and 13.0% (3/23) of astrocytomas. The sensitivity and specificity of HOXB7 protein deletion in oligodendroglioma were 90.9% (20/22) and 87.0% (20/23), respectively. To verify the reliability of using HOXB7 in differentiating oligodendroglioma, we used 1p/19q fluorescence in situ hybridization (FISH) testing as a positive control. The Cohen’s kappa coefficient of HOXB7 immunohistochemistry staining and 1p/19q FISH testing was 0.778 (95% CI: 0.594–0.962, p < 0.001). In conclusion, HOXB7 is an independent predictor of poor prognosis in all grade gliomas. Additionally, HOXB7 is also a highly sensitive and specific indicator to differentiate oligodendroglioma from astrocytoma.
Calculation of Average Reservoir Pore Pressure Based on Surface Displacement Using Image-To-Image Convolutional Neural Network Model
Authors: Hu Chaoyang , Wang Fengjiao , Ai Chi
Published: August 2021

The average pore pressure during oil formation is an important parameter for measuring the energy required for the oil formation and the capacity of injection–production wells. In past studies, the average pore pressure has been derived mainly from pressure build-up test results. However, such tests are expensive and time-consuming. The surface displacement of an oilfield is the result of change in the formation pore pressure, but no method is available for calculating the formation pore pressure based on the surface displacement. Therefore, in this study, the vertical displacement of the Earth’s surface was used to calculate changes in reservoir pore pressure. We employed marker-stakes to measure ground displacement. We used an improved image-to-image convolutional neural network (CNN) that does not include pooling layers or full-connection layers and uses a new loss function. We used the forward evolution method to produce training samples with labels. The CNN completed self-training using these samples. Then, machine learning was used to invert the surface vertical displacement to change the pore pressure in the oil reservoir. The method was tested in a block of the Sazhong X development zone in the Daqing Oilfield in China. The results showed that the variation in the formation pore pressure was 83.12%, in accordance with the results of 20 groups of pressure build-up tests within the range of the marker-stake measurements. Thus, the proposed method is less expensive, and faster than existing methods.
Current Progress in Evolutionary Comparative Genomics of Great Apes
Authors: Yousaf Aisha , Liu Junfeng , Ye Sicheng , Chen Hua
Published: August 2021

The availability of high-quality genome sequences of great ape species provides unprecedented opportunities for genomic analyses. Herein, we reviewed the recent progress in evolutionary comparative genomic studies of the existing great ape species, including human, chimpanzee, bonobo, gorilla, and orangutan. We elaborate discovery on evolutionary history, natural selection, structural variations, and new genes of these species, which is informative for understanding the origin of human-specific phenotypes.
Identification of Key Genes and Pathways Associated With Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis
Authors: Shen Zhimin , Chen Mingduan , Luo Fei , Xu Hui , Zhang Peipei , Lin Jihong , Kang Mingqiang
Published: August 2021

Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of cancer-related death in China. Although paclitaxel has been shown to be effective in treating ESCC, the prolonged use of this chemical will lead to paclitaxel resistance. In order to uncover genes and pathways driving paclitaxel resistance in the progression of ESCC, bioinformatics analyses were performed based on The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database including GSE86099 and GSE161533. Differential expression analysis was performed in TCGA data and two GEO datasets to obtain differentially expressed genes (DEGs). Based on GSE161533, weighted gene co-expression network analysis (WGCNA) was conducted to identify the key modules associated with ESCC tumor status. The DEGs common to the two GEO datasets and the genes in the key modules were intersected to obtain the paclitaxel resistance-specific or non-paclitaxel resistance-specific genes, which were subjected to subsequent least absolute shrinkage and selection operator (LASSO) feature selection, whereby paclitaxel resistance-specific or non-paclitaxel resistance-specific key genes were selected. Ten machine learning models were used to validate the biological significance of these key genes; the potential therapeutic drugs for paclitaxel resistance-specific genes were also predicted. As a result, we identified 24 paclitaxel resistance-specific genes and 18 non-paclitaxel resistance-specific genes. The ESCC machine classifiers based on the key genes achieved a relatively high AUC value in the cross-validation and in an independent test set, GSE164158. A total of 207 drugs (such as bevacizumab) were predicted to be alternative therapeutics for ESCC patients with paclitaxel resistance. These results might shed light on the in-depth research of paclitaxel resistance in the context of ESCC progression.
SEC23A Is an Independent Prognostic Biomarker in Bladder Cancer Correlated With MAPK Signaling
Authors: Zeng Bin , Zhao Qiting , Sun Zhiwei , Liu Doudou , Chen Hao , Li Xiaoshuang , Wang Jianyu , Xing H. Rosie
Published: August 2021

Clinical data mining and bioinformatics analysis can be employed effectively to elucidate the function and underlying mechanisms of the gene of interest. Here, we have proposed a framework for the identification and validation of independent biomarkers in human cancer and for mechanistic profiling using gene sets enrichment analysis and pathway analysis. This is followed by validation within vitroexperiments. Using this framework to analyze the clinical relevance of SEC23A, we have discovered the prognostic potential of SEC23A in different cancers and identified SEC23A as an independent prognostic factor for poor prognosis in bladder cancer, which implicates SEC23A, for the first time, as an oncogene. Bioinformatic analyses have elucidated an association between SEC23A expression and the upregulation of the MAPK signaling pathway. Using the T24 human bladder cell line, we confirmed that knockdown of SEC23A expression could effectively impact the MAPK signaling pathway. Further, through PCR verification, we showed that MEF2A, one of the key genes of the MAPK signaling pathway, might be a downstream factor of the SEC23A gene.
Coadministration of Anti-Viral Monoclonal Antibodies With Routine Pediatric Vaccines and Implications for Nirsevimab Use: A White Paper
Authors: Esposito Susanna , Abu-Raya Bahaa , Bonanni Paolo , Cahn-Sellem Fabianne , Flanagan Katie L. , Martinon Torres Federico , Mejias Asuncion , Nadel Simon , Safadi Marco A. P. , Simon Arne
Published: August 2021

Routine childhood vaccinations are key for the protection of children from a variety of serious and potentially fatal diseases. Current pediatric vaccine schedules mainly cover active vaccines. Active vaccination in infants is a highly effective approach against several infectious diseases; however, thus far, for some important viral pathogens, including respiratory syncytial virus (RSV), vaccine development and license by healthcare authorities have not been accomplished. Nirsevimab is a human-derived, highly potent monoclonal antibody (mAb) with an extended half-life for RSV prophylaxis in all infants. In this manuscript, we consider the potential implications for the introduction of an anti-viral mAb, such as nirsevimab, into the routine pediatric vaccine schedule, as well as considerations for coadministration. Specifically, we present evidence on the general mechanism of action of anti-viral mAbs and experience with palivizumab, the only approved mAb for the prevention of RSV infection in preterm infants, infants with chronic lung disease of prematurity and certain infants with hemodynamically significant heart disease. Palivizumab has been used for over two decades in infants who also receive routine vaccinations without any alerts concerning the safety and efficacy of coadministration. Immunization guidelines (Advisory Committee on Immunization Practices, Joint Committee on Vaccination and Immunization, National Advisory Committee on Immunization, Centers for Disease Control and Prevention, American Academy of Pediatrics, The Association of the Scientific Medical Societies in Germany) support coadministration of palivizumab with routine pediatric vaccines, noting that immunobiologics, such as palivizumab, do not interfere with the immune response to licensed live or inactivated active vaccines. Based on the mechanism of action of the new generation of anti-viral mAbs, such as nirsevimab, which is highly specific targeting viral antigenic sites, it is unlikely that it could interfere with the immune response to other vaccines. Taken together, we anticipate that nirsevimab could be concomitantly administered to infants with routine pediatric vaccines during the same clinic visit.
Gut Microbiota Dysbiosis Is a Crucial Player for the Poor Outcomes for COVID-19 in Elderly, Diabetic and Hypertensive Patients
Authors: Magalhães Nathalia Santos , Savino Wilson , Silva Patrícia Machado Rodrigues , Martins Marco Aurélio , Carvalho Vinicius Frias
Published: August 2021

A new infectious disease, named COVID-19, caused by the coronavirus associated to severe acute respiratory syndrome (SARS-CoV-2) has become pandemic in 2020. The three most common pre-existing comorbidities associated with COVID-19-related death are elderly, diabetic, and hypertensive people. A common factor among these risk groups for the outcome of death in patients infected with SARS-CoV-2 is dysbiosis, with an increase in the proportion of bacteria with a pro-inflammatory profile. Due to this dysbiosis, elderly, diabetic, and hypertensive people present a higher propensity to mount an inflammatory environment in the gut with poor immune editing, culminating in a weakness of the intestinal permeability barrier and high bacterial product translocation to the bloodstream. This scenario culminates in a low-grade, persistent, and systemic inflammation. In this context, we propose here that high circulating levels of bacterial products, like lipopolysaccharide (LPS), can potentiate the SARS-CoV-2-induced cytokines, including IL-6, being crucial for development of the cytokine storm in the severe form of the disease. A better understanding on the possible correlation between gut dysbiosis and poor outcomes observed in elderly, diabetic, and hypertensive people can be useful for the development of new therapeutic strategies based on modulation of the gut microbiota.
Isoflurane Suppresses Proliferation, Migration, and Invasion and Facilitates Apoptosis in Colorectal Cancer Cells Through Targeting miR-216
Authors: Cai Zhe , Suo Liangyuan , Huang Zeqing
Published: August 2021

Objective: Surgery is the first line treatment of colorectal cancer (CRC). Anesthetic isoflurane may improve outcomes of cancer surgery. Herein, we investigated the effects of isoflurane on malignant behaviors of CRC cells and its underlying therapeutic target.

Methods: SW620 and HCT116 CRC cells were exposed to a series of concentrations of isoflurane. CCK-8 assay was utilized for determination of the optimal concentration of isoflurane. Under treatment with isoflurane, proliferation, migration, and invasion were separately assessed via clone formation and transwell assays. Apoptotic levels were observed via flow cytometry and expression of Bax, Bcl-2, and Caspase3 proteins was quantified through western blot. MiR-216 expression was detected in isoflurane-induced SW620 and HCT116 cells by RT-qPCR. Following transfection with miR-216 mimic, malignant biological behaviors were examined in isoflurane-treated SW620 and HCT116 cells.

Results: 40 μM isoflurane distinctly restrained proliferative, migrated, and invasive capacities and elevated apoptotic levels in SW620 and HCT116 cells. Up-regulation of miR-216 was found in CRC cells. Its expression was suppressed by isoflurane. MiR-216 mimic ameliorated the reduction in proliferation, migration, and invasion and the increase in apoptosis for 40 μM isoflurane-induced SW620 and HCT116 cells.

Conclusion: Isoflurane, a promising drug of CRC, may suppress malignant biological behaviors of tumor cells. Furthermore, miR-216 is an underlying target of isoflurane. Thus, isoflurane could be adopted for CRC treatment.
Case Report: Management of Malignancy-Exacerbated Pemphigus Vulgaris During COVID-19 Pandemic
Authors: Corrà Alberto , Cammelli Francesca , Quintarelli Lavinia , Barbato Giuseppe , Le Rose Ornella , Salemme Adele , Di Zenzo Giovanni , Coratti Francesco , Verdelli Alice , Aimo Cristina , Mariotti Elena Biancamaria , Bianchi Beatrice , Cianchi Fabio , Caproni Marzia
Published: August 2021

Pemphigus vulgaris is an intraepidermal autoimmune mucocutaneous blistering disease whose etiopathogenesis includes various trigger factors, i.e., drugs and malignancies. We present a case of malignancy-exacerbated pemphigus vulgaris which required a careful diagnostic process in order to rule out paraneoplastic pemphigus, along with the challenges posed by the need of treating both cutaneous and oncologic diseases. Possible post-operative complications post-poned the start of first-line immunosuppressive treatment of pemphigus. Moreover, the infective risks had to be minimized during the peak of the COVID-19 pandemic in Italy. Intravenous immunoglobulins were chosen as “bridge” therapy before the tumor surgical excision, followed by rituximab in post-operative phase.
An Approach to Maximize Retrograde Transport Based on the Spatial Distribution of Motor Endplates in Mouse Hindlimb Muscles
Authors: Xu Jianyi , Xuan Ang , Liu Zhang , Li Yusha , Zhu Jingtan , Yao Yingtao , Yu Tingting , Zhu Dan
Published: August 2021

Knowledge regarding the relationship between muscles and the corresponding motor neurons would allow therapeutic genes to transport into specific spinal cord segments. Retrograde tracing technique by targeting the motor endplate (MEP), a highly specialized structure that offers direct access to the spinal motor neurons, has been used to elucidate the connectivity between skeletal muscles and the innervating motor neuron pools. However, current injection strategies mainly based on blind injection or the local MEP region might lead to an underestimation of the motor neuron number due to the uneven distribution of MEP in skeletal muscles. In this work, we proposed a novel intramuscular injection strategy based on the 3D distribution of the MEPs in skeletal muscles, applied the 3D intramuscular injection to the gastrocnemius and tibialis anterior for retrograde tracing of the corresponding motor neurons, and compared this with the existing injection strategy. The intramuscular diffusion of the tracer demonstrated that 3D injection could maximize the retrograde transport by ensuring a greater uptake of the tracer by the MEP region. In combination with optical clearing and imaging, we performed 3D mapping and quantification of the labeled motor neurons and confirmed that 3D injection could label more motor neurons than the current injection method. It is expected that 3D intramuscular injection strategy will help elucidate the connective relationship between muscles and motor neurons faithfully and becomes a promising tool in the development of gene therapy strategies for motor neuron diseases.
Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet
Authors: Liśkiewicz Daniela , Liśkiewicz Arkadiusz , Nowacka-Chmielewska Marta M. , Grabowski Mateusz , Pondel Natalia , Grabowska Konstancja , Student Sebastian , Barski Jaroslaw J. , Małecki Andrzej
Published: August 2021

Experimental and clinical data support the neuroprotective properties of the ketogenic diet and ketone bodies, but there is still a lot to discover to comprehensively understand the underlying mechanisms. Autophagy is a key mechanism for maintaining cell homeostasis, and therefore its proper function is necessary for preventing accelerated brain aging and neurodegeneration. Due to many potential interconnections, it is possible that the stimulation of autophagy may be one of the mediators of the neuroprotection afforded by the ketogenic diet. Recent studies point to possible interconnections between ketone body metabolism and autophagy. It has been shown that autophagy is essential for hepatic and renal ketogenesis in starvation. On the other hand, exogenous ketone bodies modulate autophagy both in vitro and in vivo. Many regional differences occur between brain structures which concern i.e., metabolic responses and autophagy dynamics. The aim of the present study was to evaluate the influence of the ketogenic diet on autophagic markers and the ketone body utilizing and transporting proteins in the hippocampus and frontal cortex. C57BL/6N male mice were fed with two ketogenic chows composed of fat of either animal or plant origins for 4 weeks. Markers of autophagosome formation as well as proteins associated with ketolysis (BDH1—3-hydroxybutyrate dehydrogenase 1, SCOT/OXCT1—succinyl CoA:3-oxoacid CoA transferase), ketone transport (MCT1—monocarboxylate transporter 1) and ketogenesis (HMGCL, HMGCS2) were measured. The hippocampus showed a robust response to nutritional ketosis in both changes in the markers of autophagy as well as the levels of ketone body utilizing and transporting proteins, which was also accompanied by increased concentrations of ketone bodies in this brain structure, while subtle changes were observed in the frontal cortex. The magnitude of the effects was dependent on the type of ketogenic diet used, suggesting that plant fats may exert a more profound effect on the orchestrated upregulation of autophagy and ketone body metabolism markers. The study provides a foundation for a deeper understanding of the possible interconnections between autophagy and the neuroprotective efficacy of nutritional ketosis.
Speech Fluency Improvement in Developmental Stuttering Using Non-invasive Brain Stimulation: Insights From Available Evidence
Authors: Busan Pierpaolo , Moret Beatrice , Masina Fabio , Del Ben Giovanni , Campana Gianluca
Published: August 2021

Developmental stuttering (DS) is a disturbance of the normal rhythm of speech that may be interpreted as very debilitating in the most affected cases. Interventions for DS are historically based on the behavioral modifications of speech patterns (e.g., through speech therapy), which are useful to regain a better speech fluency. However, a great variability in intervention outcomes is normally observed, and no definitive evidence is currently available to resolve stuttering, especially in the case of its persistence in adulthood. In the last few decades, DS has been increasingly considered as a functional disturbance, affecting the correct programming of complex motor sequences such as speech. Compatibly, understanding of the neurophysiological bases of DS has dramatically improved, thanks to neuroimaging, and techniques able to interact with neural tissue functioning [e.g., non-invasive brain stimulation (NIBS)]. In this context, the dysfunctional activity of the cortico-basal-thalamo-cortical networks, as well as the defective patterns of connectivity, seems to play a key role, especially in sensorimotor networks. As a consequence, a direct action on the functionality of “defective” or “impaired” brain circuits may help people who stutter to manage dysfluencies in a better way. This may also “potentiate” available interventions, thus favoring more stable outcomes of speech fluency. Attempts aiming at modulating (and improving) brain functioning of people who stutter, realized by using NIBS, are quickly increasing. Here, we will review these recent advancements being applied to the treatment of DS. Insights will be useful not only to assess whether the speech fluency of people who stutter may be ameliorated by acting directly on brain functioning but also will provide further suggestions about the complex and dynamic pathophysiology of DS, where causal effects and “adaptive''/‘‘maladaptive” compensation mechanisms may be strongly overlapped. In conclusion, this review focuses future research toward more specific, targeted, and effective interventions for DS, based on neuromodulation of brain functioning.
Evidence for an A-Modal Number Sense: Numerosity Adaptation Generalizes Across Visual, Auditory, and Tactile Stimuli
Authors: Togoli Irene , Arrighi Roberto
Published: August 2021

Humans and other species share a perceptual mechanism dedicated to the representation of approximate quantities that allows to rapidly and reliably estimate the numerosity of a set of objects: an Approximate Number System (ANS). Numerosity perception shows a characteristic shared by all primary visual features: it is susceptible to adaptation. As a consequence of prolonged exposure to a large/small quantity (“adaptor”), the apparent numerosity of a subsequent (“test”) stimulus is distorted yielding a robust under- or over-estimation, respectively. Even if numerosity adaptation has been reported across several sensory modalities (vision, audition, and touch), suggesting the idea of a central and a-modal numerosity processing system, evidence for cross-modal effects are limited to vision and audition, two modalities that are known to preferentially encode sensory stimuli in an external coordinate system. Here we test whether numerosity adaptation for visual and auditory stimuli also distorts the perceived numerosity of tactile stimuli (and vice-versa) despite touch being a modality primarily coded in an internal (body-centered) reference frame. We measured numerosity discrimination of stimuli presented sequentially after adaptation to series of either few (around 2 Hz; low adaptation) or numerous (around 8 Hz; high adaptation) impulses for all possible combinations of visual, auditory, or tactile adapting and test stimuli. In all cases, adapting to few impulses yielded a significant overestimation of the test numerosity with the opposite occurring as a consequence of adaptation to numerous stimuli. The overall magnitude of adaptation was robust (around 30%) and rather similar for all sensory modality combinations. Overall, these findings support the idea of a truly generalized and a-modal mechanism for numerosity representation aimed to process numerical information independently from the sensory modality of the incoming signals.
Dynamic Causal Modeling Self-Connectivity Findings in the Functional Magnetic Resonance Imaging Neuropsychiatric Literature
Authors: Snyder Andrew D. , Ma Liangsuo , Steinberg Joel L. , Woisard Kyle , Moeller Frederick G.
Published: August 2021

Dynamic causal modeling (DCM) is a method for analyzing functional magnetic resonance imaging (fMRI) and other functional neuroimaging data that provides information about directionality of connectivity between brain regions. A review of the neuropsychiatric fMRI DCM literature suggests that there may be a historical trend to under-report self-connectivity (within brain regions) compared to between brain region connectivity findings. These findings are an integral part of the neurologic model represented by DCM and serve an important neurobiological function in regulating excitatory and inhibitory activity between regions. We reviewed the literature on the topic as well as the past 13 years of available neuropsychiatric DCM literature to find an increasing (but still, perhaps, and inadequate) trend in reporting these results. The focus of this review is fMRI as the majority of published DCM studies utilized fMRI and the interpretation of the self-connectivity findings may vary across imaging methodologies. About 25% of articles published between 2007 and 2019 made any mention of self-connectivity findings. We recommend increased attention toward the inclusion and interpretation of self-connectivity findings in DCM analyses in the neuropsychiatric literature, particularly in forthcoming effective connectivity studies of substance use disorders.
On Perception and Consciousness in HPPD: A Systematic Review
Authors: Vis Pieter J. , Goudriaan Anneke E. , ter Meulen Bastiaan C. , Blom Jan Dirk
Published: August 2021

Hallucinogen-persisting perception disorder (HPPD) features as a diagnostic category in the DSM-5, ICD-11, and other major classifications, but our knowledge of the phenomenology of the perceptual symptoms involved and the changes in consciousness during the characteristic “flashbacks” is limited. We systematically evaluated original case reports and case series on HPPD to define its phenomenology, associated (psycho)pathology, and course. Our search of PubMed and Embase yielded 66 relevant publications that described 97 people who, together, experienced 64 unique symptoms of HPPD. Of these, 76% concerned symptoms characteristic of Alice in Wonderland syndrome, over 50% non-visual symptoms, and 38% perceptual symptoms not clearly linked to prior intoxication states. This is in contrast with the DSM-5 diagnostic criteria for HPPD. Even though less than half of the patients showed a protracted disease course of over a year, a third achieved remission. However, in patients with co-occurring depression (with or without anxiety) HPPD symptoms persisted longer and treatment outcomes were more often negative. Thus, unlike the acute stages of psychedelic drug intoxication, which may be accompanied by altered states of consciousness, HPPD is rather characterized by changes in the content of consciousness and an attentional shift from exogenous to endogenous phenomena. Since HPPD is a more encompassing nosological entity than suggested in the DSM-5, we recommend expanding its diagnostic criteria. In addition, we make recommendations for clinical practice and future research.
Dynamic Functional Connectivity of EEG: From Identifying Fingerprints to Gender Differences to a General Blueprint for the Brain's Functional Organization
Authors: Gschwandtner Ute , Bogaarts Guy , Chaturvedi Menorca , Hatz Florian , Meyer Antonia , Fuhr Peter , Roth Volker
Published: August 2021

An individual's brain functional organization is unique and can reliably be observed using modalities such as functional magnetic resonance imaging (fMRI). Here we demonstrate that a quantification of the dynamics of functional connectivity (FC) as measured using electroencephalography (EEG) offers an alternative means of observing an individual's brain functional organization. Using data from both healthy individuals as well as from patients with Parkinson's disease (PD) (n = 103 healthy individuals, n = 57 PD patients), we show that “dynamic FC” (DFC) profiles can be used to identify individuals in a large group. Furthermore, we show that DFC profiles predict gender and exhibit characteristics shared both among individuals as well as between both hemispheres. Furthermore, DFC profile characteristics are frequency band specific, indicating that they reflect distinct processes in the brain. Our empirically derived method of DFC demonstrates the potential of studying the dynamics of the functional organization of the brain using EEG.
Role of DPP-4 and SGLT2 Inhibitors Connected to Alzheimer Disease in Type 2 Diabetes Mellitus
Authors: Sim A Young , Barua Sumit , Kim Jong Youl , Lee Yong-ho , Lee Jong Eun
Published: August 2021

Alzheimer’s disease (AD) is characterized by memory loss and cognitive decline. Additionally, abnormal extracellular amyloid plaques accumulation and nerve damage caused by intracellular neurofibrillary tangles, and tau protein are characteristic of AD. Furthermore, AD is associated with oxidative stress, impaired mitochondrial structure and function, denormalization, and inflammatory responses. Recently, besides the amyloid β hypothesis, another hypothesis linking AD to systemic diseases has been put forth by multiple studies as a probable cause for AD. Particularly, type 2 diabetes mellitus (T2DM) and its features, including hyperinsulinemia, and chronic hyperglycemia with an inflammatory response, have been shown to be closely related to AD through insulin resistance. The brain cannot synthesize or store glucose, but it does require glucose, and the use of glucose in the brain is higher than that in any other organ in the mammalian body. One of the therapeutic drugs for T2DM, dipeptidyl peptidase-4 (DPP-4) inhibitor, suppresses the degradation of incretins, glucagon-like peptides and glucose-dependent insulinotropic peptide. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, recently used in T2DM treatment, have a unique mechanism of action via inhibition of renal glucose reabsorption, and which is different from the mechanisms of previously used medications. This manuscript reviews the pathophysiological relationship between the two diseases, AD and T2DM, and the pharmacological effects of therapeutic T2DM drugs, especially DPP-4 inhibitors, and SGLT2 inhibitors.
Classifying Ruptured Middle Cerebral Artery Aneurysms With a Machine Learning Based, Radiomics-Morphological Model: A Multicentral Study
Authors: Zhu Dongqin , Chen Yongchun , Zheng Kuikui , Chen Chao , Li Qiong , Zhou Jiafeng , Jia Xiufen , Xia Nengzhi , Wang Hao , Lin Boli , Ni Yifei , Pang Peipei , Yang Yunjun
Published: August 2021

Objective

Radiomics and morphological features were associated with aneurysms rupture. However, the multicentral study of their predictive power for specific-located aneurysms rupture is rare. We aimed to determine robust radiomics features related to middle cerebral artery (MCA) aneurysms rupture and evaluate the additional value of combining morphological and radiomics features in the classification of ruptured MCA aneurysms.

Methods

A total of 632 patients with 668 MCA aneurysms (423 ruptured aneurysms) from five hospitals were included. Radiomics and morphological features of aneurysms were extracted on computed tomography angiography images. The model was developed using a training dataset (407 patients) and validated with the internal (152 patients) and external validation (73 patients) datasets. The support vector machine method was applied for model construction. Optimal radiomics, morphological, and clinical features were used to develop the radiomics model (R-model), morphological model (M-model), radiomics-morphological model (RM-model), clinical-morphological model (CM-model), and clinical-radiomics-morphological model (CRM-model), respectively. A comprehensive nomogram integrating clinical, morphological, and radiomics predictors was generated.

Results

We found seven radiomics features and four morphological predictors of MCA aneurysms rupture. The R-model obtained an area under the receiver operating curve (AUC) of 0.822 (95% CI, 0.776, 0.867), 0.817 (95% CI, 0.744, 0.890), and 0.691 (95% CI, 0.567, 0.816) in the training, temporal validation, and external validation datasets, respectively. The RM-model showed an AUC of 0.848 (95% CI, 0.810, 0.885), 0.865 (95% CI, 0.807, 0.924), and 0.721 (95% CI, 0.601, 0.841) in the three datasets. The CRM-model obtained an AUC of 0.856 (95% CI, 0.820, 0.892), 0.882 (95% CI, 0.828, 0.936), and 0.738 (95% CI, 0.618, 0.857) in the three datasets. The CRM-model and RM-model outperformed the CM-model and M-model in the internal datasets (p < 0.05), respectively. But these differences were not statistically significant in the external dataset. Decision curve analysis indicated that the CRM-model obtained the highest net benefit for most of the threshold probabilities.

Conclusion

Robust radiomics features were determined related to MCA aneurysm rupture. The RM-model exhibited good ability in classifying ruptured MCA aneurysms. Integrating radiomics features into conventional models might provide additional value in ruptured MCA aneurysms classification.
Clinical Applications of MicroRNAs in Acute Myeloid Leukemia: A Mini-Review
Authors: Bhatnagar Bhavana , Garzon Ramiro
Published: August 2021

MicroRNAs (miRs) are short non-coding RNAs, typically 18-25 nucleotides in length, that are critically important, through their direct effects on target mRNAs, in a variety of cellular processes including cell differentiation, proliferation and survival. Dysregulated miR expression has been identified in numerous cancer types including acute myeloid leukemia (AML). From a clinical standpoint, several miRs have been shown to associate with prognosis in AML patients. Furthermore, they also carry the potential to be used as biomarkers and to inform medical decision making. In addition, several preclinical studies have provided strong rationale to develop novel therapeutic strategies to target miRs in AML. This review will focus on potential clinical applications of miRs in adult AML and will discuss unique miR signatures in specific AML subtypes, their role in prognostication and response to therapy, as well as miRs that are promising therapeutic targets and ongoing clinical trials directed towards targeting clinically relevant miRs in AML that could allow for improvements in current treatment strategies.
Why Does Child Mortality Decrease With Age? Modeling the Age-Associated Decrease in Mortality Rate Using WHO Metadata From 25 Countries
Authors: Dolejs Josef , Homolková Helena
Published: August 2021

Background: Our previous study analyzed the age trajectory of mortality (ATM) in 14 European countries, while this study aimed at investigating ATM in other continents and in countries with a higher level of mortality. Data from 11 Non-European countries were used.

Methods: The number of deaths was extracted from the WHO mortality database. The Halley method was used to calculate the mortality rates in all possible calendar years and all countries combined. This method enables us to combine more countries and more calendar years in one hypothetical population.

Results: The age trajectory of total mortality (ATTM) and also ATM due to specific groups of diseases were very similar in the 11 non-European countries and in the 14 European countries. The level of mortality did not affect the main results found in European countries. The inverse proportion was valid for ATTM in non-European countries with two exceptions.

Slower or no mortality decrease with age was detected in the first year of life, while the inverse proportion model was valid for the age range (1, 10) years in most of the main chapters of ICD10.

Conclusions: The decrease in child mortality with age may be explained as the result of the depletion of individuals with congenital impairment. The majority of deaths up to the age of 10 years were related to congenital impairments, and the decrease in child mortality rate with age was a demonstration of population heterogeneity. The congenital impairments were latent and may cause death even if no congenital impairment was detected.
Association Analysis Revealed That TaPYL4 Genes Are Linked to Plant Growth Related Traits in Multiple Environment
Authors: Xue Yinghong , Wang Jingyi , Mao Xinguo , Li Chaonan , Li Long , Yang Xi , Hao Chenyang , Chang Xiaoping , Li Runzhi , Jing Ruilian
Published: August 2021

Abscisic acid (ABA), one of phytohormones, plays an important regulatory role in plant growth and development. ABA receptor PYL4 (pyrabactin resistance 1-like 4) was previously detected to be involved in plant response to a variety of stresses. TaPYL4 overexpression could enhance wheat (Triticum aestivum) drought resistance. In order to further investigate TaPYL4’s role in regulating development of other major agronomic traits in wheat, genes of TaPYL4-2A, TaPYL4-2B, and TaPYL4-2D were cloned from wheat, respectively. Polymorphism analysis on TaPYL4 sequences revealed that encoding regions of the three genes were highly conserved, without any SNP (single nucleotide polymorphism) presence. However, nine SNPs and four SNPs were identified in the promoter regions of TaPYL4-2A and TaPYL4-2B, respectively. Functional molecular markers were developed based on these polymorphisms, which were then used to scan a natural population of 323 common wheat accessions for correlation analysis between genotype and the target phenotypic traits. Both TaPYL4-2A and TaPYL4-2B markers were significantly correlated with plant growth-related traits under multiple environments (well-watered, drought and heat stress treatments). The additive effects of TaPYL4-2A and TaPYL4-2B were verified by the combinational haplotype (Hap-AB1∼Hap-AB4) effects determined from field data. Cis-acting elements were analyzed in the promoters of TaPYL4-2A and TaPYL4-2B, showing that a TGA-element bound by ARFs (auxin response factors) existed only in Hap-2A-1 of TaPYL4-2A. Gene expression assays indicated that TaPYL4-2A was constitutively expressed in various tissues, with higher expression in Hap-2A-1 genotypes than in Hap-2A-2 materials. Notably, TaARF4 could act as TaPYL4-2A transcription activator in Hap-2A-1 materials, but not in Hap-2A-2 genotypes. Analysis of geographic distribution and temporal frequency of haplotypes indicated that Hap-AB1 was positively selected in wheat breeding in China. Therefore, TaPYL4-2A and TaPYL4-2B could be a valuable target gene in wheat genetic improvement to develop the ideal plant architecture.
Targeting Cis-Regulatory Elements for Rice Grain Quality Improvement
Authors: Ding Yu , Zhu Jiannan , Zhao Dongsheng , Liu Qiaoquan , Yang Qingqing , Zhang Tao
Published: August 2021

Rice is the most important source of food worldwide, providing energy, and nutrition for more than half of the population worldwide. Rice grain quality is a complex trait that is affected by several factors, such as the genotype and environment, and is a major target for rice breeders. Cis-regulatory elements (CREs) are the regions of non-coding DNA, which play a critical role in gene expression regulation. Compared with gene knockout, CRE modifications can fine-tune the expression levels of target genes. Genome editing has provided opportunities to modify the genomes of organisms in a precise and predictable way. Recently, the promoter modifications of coding genes using genome editing technologies in plant improvement have become popular. In this study, we reviewed the results of recent studies on the identification, characterization, and application of CREs involved in rice grain quality. We proposed CREs as preferred potential targets to create allelic diversity and to improve quality traits via genome editing strategies in rice. We also discussed potential challenges and experimental considerations for the improvement in grain quality in crop plants.
Defense Mechanism Functioning in Patients With Breast Cancer: Using the Defense Mechanism Rating Scale
Authors: Saab Marwa , Hartmann Matias , Han Xue
Published: August 2021

Background: Breast cancer (BC) is one of the highest incidence rates in Lebanon. Previous studies had focused scarcely on the unconscious protective shield of patients with BC or BC survivors against cancer, while only some studies had focused on the relationship between defense mechanisms (DMs) and high adaptation with the disease process and progress. Therefore, this study aimed to investigate the reaction of inpatients with BC toward the disease by measuring DMs in the Lebanon context.

Methods: Seventy inpatients with BC were recruited randomly from six hospitals. Their DMs were measured using the Defense Mechanism Rating Scale. Moreover, the Relationship Anecdotes Paradigm (RAP) was used with three recent life vignettes of initial diagnosis, family, and daily life. The data were analyzed using repeated measure ANOVA, Wilcoxon rank-sum test, and Spearman's rank.

Results: Patients with stage 2 BC used more high-adaptive defense levels than patients with stage 4 BC who used more minor image distorting defense levels. Moreover, patients with stage 2 BC used more self-observation and undoing, while patients with stage 4 BC used more devaluation.

Conclusion: The severity of BC, the age of carriers, and the social status may lead to higher use of DMs, at the level of the individual defense and the hierarchal or the tripartite levels.
Negative Emotion Differentiation Attenuates the Within-Person Indirect Effect of Daily Stress on Nightly Sleep Quality Through Calmness
Authors: Lischetzke Tanja , Schemer Lea , Glombiewski Julia A. , In-Albon Tina , Karbach Julia , Könen Tanja
Published: August 2021

The ability to differentiate between negative emotional states [negative emotion differentiation (NED)] has been conceptualized as a trait that facilitates effective emotion regulation and buffers stress reactivity. In the present research, we investigated the role of NED in within-person processes of daily affect regulation and coping during times of stress (the first COVID-19-related pandemic lockdown in April 2020). Using intensive longitudinal data, we analyzed whether daily stress had an indirect effect on sleep quality through calmness in the evening, and we tested whether NED moderated this within-person indirect effect by buffering the link between daily stress and calmness in the evening. A non-representative community sample (n = 313, 15–82 years old) participated in a 21-day ambulatory assessment with twice-daily surveys. The results of multilevel mediation models showed that higher daily stress was related to within-day change in calmness from morning to evening, resulting in less calmness in the evening within persons. Less calmness in the evening, in turn, was related to poorer nightly sleep quality within persons. As expected, higher NED predicted a less negative within-person link between daily stress and calmness in the evening, thereby attenuating the indirect effect of daily stress on nightly sleep quality through calmness. This effect held when we controlled for mean negative emotions and depression. The results provide support for a diathesis-stress model of NED, and hence, for NED as a protective factor that helps to explain why some individuals remain more resilient during times of stress than others.
Internal Consistency and Structural Validity of the Norwegian Translation of the Ten-Item Personality Inventory
Authors: Thørrisen Mikkel Magnus , Sadeghi Talieh , Wiers-Jenssen Jannecke
Published: August 2021

Background: The Ten-Item Personality Inventory (TIPI) is a validated brief instrument measuring the five-factor model (FFM) personality dimensions, developed for instances where more comprehensive FFM instruments are impractical to use. The TIPI has been translated into several languages, but psychometric properties of the Norwegian version (N-TIPI) have not been systematically explored.

Objectives: This study aimed to explore the psychometric properties of the N-TIPI, in terms of internal consistency and structural validity.

Methods: In a cross-sectional study, responses on the N-TIPI were collected from 5,009 Norwegian master graduates. Descriptive statistics for the subscales and correlations between subscales were calculated. Internal consistency was assessed with inter-item correlations, Cronbach’s α and Spearman-Brown coefficients. Structural validity was explored with principal component analysis, parallel analysis, and visual scree plot inspection. Results for the N-TIPI were compared with those previously reported for the original TIPI as well as the German, French, Spanish, and Portuguese versions.

Results: Compared with the original and non-English versions of TIPI, results for N-TIPI showed comparable subscale rank order of means, standard deviations, and pattern of correlations between subscales, as well as inter-item correlations and Cronbach’s α. The 10 N-TIPI items were adequately reduced to five components, theoretically corresponding with the FFM personality domains.

Conclusion: The N-TIPI demonstrated acceptable internal consistency and satisfactory structural validity. Although further research is warranted, the instrument stands out as feasible when it is essential to minimize participants’ response burden in studies that aim to explore personality as one among several concepts or utilize personality traits as covariates.
Privacy-Preserving Social Ambiance Measure From Free-Living Speech Associates With Chronic Depressive and Psychotic Disorders
Authors: Chen Wenwan , Sabharwal Ashutosh , Taylor Erica , Patel Ankit B. , Moukaddam Nidal
Published: August 2021

A social interaction consists of contributions by the individual, the environment and the interaction between the two. Ideally, to enable effective assessment and interventions for social isolation, an issue inherent to depressive and psychotic illnesses, the isolation must be identified in real-time and at an individual level. However, research addressing sociability deficits is largely focused on determining loneliness, rather than isolation, and lacks focus on the richness of the social environment the individual revolves in. In this paper, We describe the development of an automated, objective and privacy-preserving Social Ambiance Measure (SAM) that converts unconstrained audio recordings collected from wrist-worn audio-bands into four levels, ranging from none to active. The ambiance levels are based on the number of simultaneous speakers, which is a proxy for overall social activity in the environment. Results show that social ambiance patterns and time spent at each ambiance level differed between participants with depressive or psychotic disorders and healthy controls. Individuals with depression/psychosis spent less time in diverse environments and less time in moderate/active ambiance levels. Moreover, social ambiance patterns are found associated with the severity of self-reported depression, anxiety symptoms and personality traits. The results in this paper suggest that objectively measured social ambiance can be used as a marker of sociability, and holds potential to be leveraged to better understand social isolation and develop effective interventions for sociability challenges, thus improving mental health outcomes.