bluuebunny/crossref_metadata_2025 huggingface dataset:
Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2
Authors: Wang Huan , Luo Wenqin , Wang Xuliang , Xue Dingwei , Ren Liangliang , Xu Li , Ge Guangju , Xia Liqun , Yu Shicheng , Wang Mingchao , Zhou Zhenwei , Li Gonghui , Wu Haiyang
Published: September 2021

Testicular nuclear receptor 4 (TR4) is a member of the nuclear hormone receptor family and acts as a ligand-activated transcription factor and functions in many biological processes, such as development, cellular differentiation, and homeostasis. Recent studies have shown that TR4 plays an important role in prostate cancer, renal cell carcinoma, and hepatocellular carcinoma; however, its potential link to bladder cancer (BC) remains unknown. This study found that bladder cancer exhibited a higher expression of TR4 compared to normal tissues. Overexpressed TR4 promoted the bladder cancer cell proliferation, and knocked down TR4 with TR4-siRNA suppressed the bladder cancer cell proliferation. Mechanistic studies reveal that TR4 functions by altering the expression of Bcl-2 to regulate apoptosis in bladder cancer cells. Furthermore, knocking down Bcl-2 reversed the BC proliferation induced by TR4. In vivo, we also confirmed that TR4 knockdown mice (TR4+/−) showed slower bladder cancer growth than wild-type mice (TR4+/+) induced by the carcinogenic chemicals. Moreover, TR4+/− mice showed a lower grade of histopathology than the control group. In conclusion, these results indicate that TR4 plays a key role in bladder cancer proliferation, and targeting TR4 would probably be a potential strategy for bladder cancer treatment.
Otic Neurogenesis in Xenopus laevis: Proliferation, Differentiation, and the Role of Eya1
Authors: Almasoudi Suad Hamdan , Schlosser Gerhard
Published: September 2021

Using immunostaining and confocal microscopy, we here provide the first detailed description of otic neurogenesis in Xenopus laevis. We show that the otic vesicle comprises a pseudostratified epithelium with apicobasal polarity (apical enrichment of Par3, aPKC, phosphorylated Myosin light chain, N-cadherin) and interkinetic nuclear migration (apical localization of mitotic, pH3-positive cells). A Sox3-immunopositive neurosensory area in the ventromedial otic vesicle gives rise to neuroblasts, which delaminate through breaches in the basal lamina between stages 26/27 and 39. Delaminated cells congregate to form the vestibulocochlear ganglion, whose peripheral cells continue to proliferate (as judged by EdU incorporation), while central cells differentiate into Islet1/2-immunopositive neurons from stage 29 on and send out neurites at stage 31. The central part of the neurosensory area retains Sox3 but stops proliferating from stage 33, forming the first sensory areas (utricular/saccular maculae). The phosphatase and transcriptional coactivator Eya1 has previously been shown to play a central role for otic neurogenesis but the underlying mechanism is poorly understood. Using an antibody specifically raised against Xenopus Eya1, we characterize the subcellular localization of Eya1 proteins, their levels of expression as well as their distribution in relation to progenitor and neuronal differentiation markers during otic neurogenesis. We show that Eya1 protein localizes to both nuclei and cytoplasm in the otic epithelium, with levels of nuclear Eya1 declining in differentiating (Islet1/2+) vestibulocochlear ganglion neurons and in the developing sensory areas. Morpholino-based knockdown of Eya1 leads to reduction of proliferating, Sox3- and Islet1/2-immunopositive cells, redistribution of cell polarity proteins and loss of N-cadherin suggesting that Eya1 is required for maintenance of epithelial cells with apicobasal polarity, progenitor proliferation and neuronal differentiation during otic neurogenesis.
Calcium and Spike Timing-Dependent Plasticity
Authors: Inglebert Yanis , Debanne Dominique
Published: September 2021

Since its discovery, spike timing-dependent synaptic plasticity (STDP) has been thought to be a primary mechanism underlying the brain’s ability to learn and to form new memories. However, despite the enormous interest in both the experimental and theoretical neuroscience communities in activity-dependent plasticity, it is still unclear whether plasticity rules inferred from in vitro experiments apply to in vivo conditions. Among the multiple reasons why plasticity rules in vivo might differ significantly from in vitro studies is that extracellular calcium concentration use in most studies is higher than concentrations estimated in vivo. STDP, like many forms of long-term synaptic plasticity, strongly depends on intracellular calcium influx for its induction. Here, we discuss the importance of considering physiological levels of extracellular calcium concentration to study functional plasticity.
Dual-Antiplatelet Therapy May Not Be Associated With an Increased Risk of In-hospital Bleeding in Patients With Moderate or Severe Ischemic Stroke
Authors: Khazaal Ossama , Rothstein Aaron , Husain Muhammad R. , Broderick Matthew , Cristancho Daniel , Reyes-Esteves Sahily , Khan Farhan , Favilla Christopher G. , Messé Steven R. , Mullen Michael T.
Published: September 2021

Background and Purpose: Dual antiplatelet therapy (DAPT), compared to single antiplatelet therapy (SAPT), lowers the risk of stroke or death early after TIA and minor ischemic stroke. Prior trials excluded moderate to severe strokes, due to a potential increased risk of bleeding. We aimed to compare in-hospital bleeding rates in SAPT and DAPT patients with moderate or severe stroke (defined by NIHSS ≥4).

Methods: We performed a retrospective cohort study of ischemic stroke over a 2-year period with admission NIHSS ≥4. The primary outcome was symptomatic intracranial hemorrhage (ICH) with any change in NIHSS. Secondary outcomes included systemic bleeding and major bleeding, a composite of serious systemic bleeding and symptomatic ICH. We performed analyses stratified by stroke severity (NIHSS 4–7 vs. 8+) and by preceding use of tPA and/or thrombectomy. Univariate followed by multivariate logistic regression evaluated whether DAPT was independently associated with bleeding.

Results: Of 377 patients who met our inclusion criteria, 148 received DAPT (39%). Symptomatic ICH was less common with DAPT compared to SAPT (0.7 vs. 6.4%, p < 0.01), as was the composite of major bleeding (2.1 vs. 7.6%, p = 0.03). Symptomatic ICH was numerically less frequent in the DAPT group, but not statistically significant, when stratified by stroke severity (NIHSS 4–7: 0 vs. 5.9%, p = 0.06; NIHSS 8+: 1.5 vs. 6.6%, p = 0.18) and by treatment with tPA and/or thrombectomy (Yes: 2.6 vs. 9.1%, p = 0.30; No: 0 vs. 2.9%, p = 0.25). DAPT was not associated with major bleeding in either the univariate or the multivariate regression.

Conclusions: In this single center cohort, symptomatic ICH and the composite of serious systemic bleeding and symptomatic ICH was rare in patients on DAPT. Relative to single antiplatelet therapy DAPT was not associated with an increased risk of in-hospital bleeding in patients with moderate and severe ischemic stroke.
Mirror Movements in Acquired Neurological Disorders: A Mini-Review
Authors: Liu Ping , Yuan Yuan , Zhang Ning , Liu Xiaoyan , Yu Lihua , Luo Benyan
Published: September 2021

Mirror movements (MMs) are specifically defined as involuntary movements occurring on one side of homologous muscles when performing unilateral movements with the contralateral limb. MMs have been considered a kind of soft neurological signs, and the persistence or reappearance of MMs in adults is usually pathologic. In addition to some congenital syndrome, MMs have been also described in age-related neurological diseases including pyramidal system diseases (e.g., stroke, amyotrophic lateral sclerosis) and extrapyramidal disorders (e.g., Parkinson's disease, essential tremor). With the advances in instrumentation and detection means, subtle or subclinical MMs have been deeply studied. Furthermore, the underlying mechanism is also being further elucidated. In this mini-review, we firstly discuss the MM examination means, and then review the literature regarding MMs in individuals with acquired neurological disorders, in order to further understand the pathogenesis of MMs.
Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson’s Disease
Authors: Iarkov Alexandre , Mendoza Cristhian , Echeverria Valentina
Published: September 2021

Parkinson’s disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) in the midbrain resulting in progressive impairment in cognitive and motor abilities. The physiological and molecular mechanisms triggering dopaminergic neuronal loss are not entirely defined. PD occurrence is associated with various genetic and environmental factors causing inflammation and mitochondrial dysfunction in the brain, leading to oxidative stress, proteinopathy, and reduced viability of dopaminergic neurons. Oxidative stress affects the conformation and function of ions, proteins, and lipids, provoking mitochondrial DNA (mtDNA) mutation and dysfunction. The disruption of protein homeostasis induces the aggregation of alpha-synuclein (α-SYN) and parkin and a deficit in proteasome degradation. Also, oxidative stress affects dopamine release by activating ATP-sensitive potassium channels. The cholinergic system is essential in modulating the striatal cells regulating cognitive and motor functions. Several muscarinic acetylcholine receptors (mAChR) and nicotinic acetylcholine receptors (nAChRs) are expressed in the striatum. The nAChRs signaling reduces neuroinflammation and facilitates neuronal survival, neurotransmitter release, and synaptic plasticity. Since there is a deficit in the nAChRs in PD, inhibiting nAChRs loss in the striatum may help prevent dopaminergic neurons loss in the striatum and its pathological consequences. The nAChRs can also stimulate other brain cells supporting cognitive and motor functions. This review discusses the cholinergic system as a therapeutic target of cotinine to prevent cognitive symptoms and transition to dementia in PD.
Neuroimaging Studies of Acupuncture on Low Back Pain: A Systematic Review
Authors: Wen Qiao , Ma Peihong , Dong Xiaohui , Sun Ruirui , Lan Lei , Yin Tao , Qu Yuzhu , Liu Yalan , Xiao Qingqing , Zeng Fang
Published: September 2021

Objectives: This study was conducted in order to investigate the study design and main outcomes of acupuncture neuroimaging studies on low back pain (LBP).

Methods: Neuroimaging studies of acupuncture on LBP were collected from three English databases such as PubMed and four Chinese databases such as China National Knowledge Infrastructure (CNKI) from inception to December 31, 2020. Study selection, data extraction, and assessment of risk of bias were performed independently by two investigators. The quality of studies was appraised with the Cochrane's risk of bias tools. Information on basic information, methodology, and brain imaging data were extracted.

Results: The literature search returned 310 potentially eligible studies and 19 articles met inclusion criteria; 78.9% of studies chose manual acupuncture as the intervention, 89.5% of studies evaluated functional changes elicited by acupuncture, and 68.4% of studies used resting-state fMRI as imaging condition. The most frequently reported acupuncture-induced brain alterations of LBP patients were in the prefrontal cortex, insula, cerebellum, primary somatosensory cortex, and anterior cingulate cortex. There was a significant correlation between improved clinical outcomes and changes in the brain.

Conclusions: The results suggested that improving abnormal structure and functional activities in the brain of the LBP patient is an important mechanism of acupuncture treatment for LBP. The brain regions involved in acupuncture analgesia for LBP were mainly located in the pain matrix, default mode network (DMN), salience network (SN), and descending pain modulatory system (DPMS). However, it was difficult to draw a generalized conclusion due to the heterogeneity of study designs. Further well-designed multimodal neuroimaging studies investigating the mechanism of acupuncture on LBP are warranted.
Room for Two: The Synaptophysin/Synaptobrevin Complex
Authors: White Dustin N. , Stowell Michael H. B.
Published: September 2021

Synaptic vesicle release is regulated by upwards of 30 proteins at the fusion complex alone, but disruptions in any one of these components can have devastating consequences for neuronal communication. Aberrant molecular responses to calcium signaling at the pre-synaptic terminal dramatically affect vesicle trafficking, docking, fusion, and release. At the organismal level, this is reflected in disorders such as epilepsy, depression, and neurodegeneration. Among the myriad pre-synaptic proteins, perhaps the most functionally mysterious is synaptophysin (SYP). On its own, this vesicular transmembrane protein has been proposed to function as a calcium sensor, a cholesterol-binding protein, and to form ion channels across the phospholipid bilayer. The downstream effects of these functions are largely unknown. The physiological relevance of SYP is readily apparent in its interaction with synaptobrevin (VAMP2), an integral element of the neuronal SNARE complex. SNAREs, soluble NSF attachment protein receptors, comprise a family of proteins essential for vesicle fusion. The complex formed by SYP and VAMP2 is thought to be involved in both trafficking to the pre-synaptic membrane as well as regulation of SNARE complex formation. Recent structural observations specifically implicate the SYP/VAMP2 complex in anchoring the SNARE assembly at the pre-synaptic membrane prior to vesicle fusion. Thus, the SYP/VAMP2 complex appears vital to the form and function of neuronal exocytotic machinery.
Pituitary Adenylate Cyclase Activating Polypeptide Has Inhibitory Effects on Melanoma Cell Proliferation and Migration In Vitro
Authors: Hajdú Tibor , Kovács Patrik , Zsigrai Emese , Takács Roland , Vágó Judit , Cho Sinyoung , Sasi-Szabó László , Becsky Dániel , Keller-Pinter Aniko , Emri Gabriella , Rácz Kálmán , Reglodi Dora , Zákány Róza , Juhász Tamás
Published: September 2021

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide which is distributed throughout the body. PACAP influences development of various tissues and exerts protective function during cellular stress and in some tumour formation. No evidence is available on its role in neural crest derived melanocytes and its malignant transformation into melanoma. Expression of PACAP receptors was examined in human skin samples, melanoma lesions and in a primary melanocyte cell culture. A2058 and WM35 melanoma cell lines, representing two different stages of melanoma progression, were used to investigate the effects of PACAP. PAC1 receptor was identified in melanocytes in vivo and in vitro and in melanoma cell lines as well as in melanoma lesions. PACAP administration did not alter viability but decreased proliferation of melanoma cells. With live imaging random motility, average speed, vectorial distance and maximum distance of migration of cells were reduced upon PACAP treatment. PACAP administration did not alter viability but decreased proliferation capacity of melanoma cells. On the other hand, PACAP administration decreased the migration of melanoma cell lines towards fibronectin chemoattractant in the Boyden chamber. Furthermore, the presence of the neuropeptide inhibited the invasion capability of melanoma cell lines in Matrigel chambers. In summary, we provide evidence that PACAP receptors are expressed in melanocytes and in melanoma cells. Our results also prove that various aspects of the cellular motility were inhibited by this neuropeptide. On the basis of these results, we propose PACAP signalling as a possible target in melanoma progression.
Identification, Verification and Pathway Enrichment Analysis of Prognosis-Related Immune Genes in Patients With Hepatocellular Carcinoma
Authors: Zhu Zhipeng , Song Mengyu , Li Wenhao , Li Mengying , Chen Sihan , Chen Bo
Published: September 2021

Hepatocellular carcinoma is a common malignant tumor with poor prognosis, poor treatment effect, and lack of effective biomarkers. In this study, bioinformatics analysis of immune-related genes of hepatocellular carcinoma was used to construct a multi-gene combined marker that can predict the prognosis of patients. The RNA expression data of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and immune-related genes were obtained from the IMMPORT database. Differential analysis was performed by Wilcox test to obtain differentially expressed genes. Univariate Cox regression analysis, lasso regression analysis and multivariate Cox regression analysis were performed to establish a prognostic model of immune genes, a total of 5 genes (HDAC1, BIRC5, SPP1, STC2, NR6A1) were identified to construct the models. The expression levels of 5 genes in HCC tissues were significantly different from those in paracancerous tissues. The Kaplan-Meier survival curve showed that the risk score calculated according to the prognostic model was significantly related to the overall survival (OS) of HCC. The receiver operating characteristic (ROC) curve confirmed that the prognostic model had high accuracy. Independent prognostic analysis was performed to prove that the risk value can be used as an independent prognostic factor. Then, the gene expression data of hepatocellular carcinoma in the ICGC database was used as a validation data set for the verification of the above steps. In addition, we used the CIBERSORT software and TIMER database to conduct immune infiltration research, and the results showed that the five genes of the model and the risk score have a certain correlation with the content of immune cells. Moreover, through Gene Set Enrichment Analysis (GSEA) and the construction of protein interaction networks, we found that the p53-mediated signal transduction pathway is a potentially important signal pathway for hepatocellular carcinoma and is positively regulated by certain genes in the prognostic model. In conclusion, this study provides potential targets for predicting the prognosis and treatment of hepatocellular carcinoma patients, and also provides new ideas about the correlation between immune genes and potential pathways of hepatocellular carcinoma.
Indocyanine Green–Guided Pediatric Tumor Resection: Approach, Utility, and Challenges
Authors: Abdelhafeez Abdelhafeez , Talbot Lindsay , Murphy Andrew J. , Davidoff Andrew M.
Published: September 2021

Incomplete tumor resection increases the risk of local recurrence. However, the standard of care approach to distinguishing tumor tissue is less than optimal, as it depends on a conglomeration of preoperative imaging and visual and tactile indicators in real time. This approach is associated with a significant risk of inadequate resection; therefore, a novel approach that delineates the accurate intraoperative definition of pediatric tumors is urgently needed. To date, there is no reliable method for the intraoperative assessment of tumor extent and real-time differentiation between tumor- involved tissues and tumor-free tissues. Use of intraoperative frozen sections is challenging, time consuming, and covers a small surface area. Increased vascular permeability and impaired lymphatic drainage in the tumor microenvironment leads to an enhanced permeability and retention effect of small molecules. ICG is a fluorescent dye that when administered intravenously accumulates passively in the tumor because of EPR, thereby providing some tumor contrast for intraoperative real-time tumor recognition. Preclinical and clinical studies suggest that the tumor-to-background fluorescence ratio is optimized when imaging is obtained 24 h after dye injection, and many studies suggest using a high dose of ICG to optimize dye retention in the tumor tissue. However, in childhood cancers, little is known about the ideal dosing, applications, and challenges of ICG-guided tumor resection. This retrospective study examines the feasibility of ICG-guided tumor resection in common childhood solid tumors such as neuroblastoma, sarcomas, hepatic tumors, pulmonary metastases, and other rare tumors. Pediatric dosing and challenges related to the optimization of tumor-to-background ratio are also examined.
The Neurometabolic Basis of Mood Instability: The Parvalbumin Interneuron Link—A Systematic Review and Meta-Analysis
Authors: Pinna Antonello , Colasanti Alessandro
Published: September 2021

The neurobiological bases of mood instability are poorly understood. Neuronal network alterations and neurometabolic abnormalities have been implicated in the pathophysiology of mood and anxiety conditions associated with mood instability and hence are candidate mechanisms underlying its neurobiology. Fast-spiking parvalbumin GABAergic interneurons modulate the activity of principal excitatory neurons through their inhibitory action determining precise neuronal excitation balance. These interneurons are directly involved in generating neuronal networks activities responsible for sustaining higher cerebral functions and are especially vulnerable to metabolic stress associated with deficiency of energy substrates or mitochondrial dysfunction. Parvalbumin interneurons are therefore candidate key players involved in mechanisms underlying the pathogenesis of brain disorders associated with both neuronal networks’ dysfunction and brain metabolism dysregulation. To provide empirical support to this hypothesis, we hereby report meta-analytical evidence of parvalbumin interneurons loss or dysfunction in the brain of patients with Bipolar Affective Disorder (BPAD), a condition primarily characterized by mood instability for which the pathophysiological role of mitochondrial dysfunction has recently emerged as critically important. We then present a comprehensive review of evidence from the literature illustrating the bidirectional relationship between deficiency in mitochondrial-dependent energy production and parvalbumin interneuron abnormalities. We propose a mechanistic explanation of how alterations in neuronal excitability, resulting from parvalbumin interneurons loss or dysfunction, might manifest clinically as mood instability, a poorly understood clinical phenotype typical of the most severe forms of affective disorders. The evidence we report provides insights on the broader therapeutic potential of pharmacologically targeting parvalbumin interneurons in psychiatric and neurological conditions characterized by both neurometabolic and neuroexcitability abnormalities.
A Qualitative Study on Medication Taking Behaviour Among People With Diabetes in Australia
Authors: Ahmad Akram , Khan Muhammad Umair , Aslani Parisa
Published: September 2021

Background: Australia has a high proportion of migrants with an increasing migration rate from India. Type II diabetes is a long-term condition common amongst the Indian population.

Aims: To investigate patients’ medication-taking behaviour and factors that influence adherence at the three phases of adherence.

Methods: Semi-structured interviews were conducted with a convenience sample of 23 Indian migrants living in Sydney. All interviews were audio-recorded, transcribed verbatim and thematically analysed.

Results: 1) Initiation: The majority of participants were initially prescribed oral antidiabetic medicine and only two were started on insulin. Most started taking their medicine immediately while some delayed initiating therapy due to fear of side-effects. 2) Implementation: Most participants reported taking their medicine as prescribed. However, some reported forgetting their medicine especially when they were in a hurry for work or were out for social events. 3) Discontinuation: A few participants discontinued taking their medicine. Those who discontinued did so to try Ayurvedic medicine. Their trial continued for a few weeks to a few years. Those who did not receive expected results from the Ayurvedic medicine restarted their prescribed conventional medicine.

Conclusion: A range of medication-taking behaviours were observed, ranging from delays in initiation to long-term discontinuation, and swapping of prescribed medicine with Ayurvedic medicine. This study highlights the need for tailored interventions, including education, that focus on factors that impact medication adherence from initiation to discontinuation of therapy.
Evaluation of the Anticancer Properties of Geranyl Isovalerate, an Active Ingredient of Argyreia nervosa Extract in Colorectal Cancer Cells
Authors: Rasool Fayyaz , Sharma Deepu , Anand P. Shanmukha , Magani SKJ , Tantravahi Srinivasan
Published: September 2021

Chemotherapy is a general treatment procedure for cancer. The diversity in cancer incidence and the failure of therapy due to chemoresistance lead to increased cancer-related deaths. Therefore, new drugs with fewer secondary complications targeting diverse pathways are the need of the hour. Geranyl isovalerate (GIV), one of the active ingredients of ethyl acetate fraction of Argyreia nervosa is routinely used as a food flavoring agent. In this study, we found that GIV also exhibits anticancer activity when tested against the HCT116 cell line. It influenced the viability of the cells in a dose- and time-dependent manner. We examined whether GIV could induce oxidative stress and affect the mitochondrial membrane potential, thereby leading to apoptosis induction. Moreover, GIV could suppress the expression of antiapoptotic genes, such as BCl2 and PARP, and induce the expression of proapoptotic genes, such as Caspase 3 and 9. This is the first study demonstrating the anticancer activity of GIV and providing evidence for its mechanism of action. In conclusion, this study proposes GIV as a potential lead or supplementary molecule in treating and preventing colorectal cancer (CRC). Based on our findings, we conclude that GIV may be a viable lead or supplementary molecule for treating and preventing CRC.
Minimally Invasive Image-Guided Gut Transport Function Measurement Probe
Authors: Otuya David O. , Gavgiotaki Evangelia , Carlson Camella J. , Shi Serena Q. , Lee Ariel J. , Krall Alexander A. , Chung Anita , Grant Catriona G. , Bhat Nitasha M. , Choy Peter , Giddings Sarah L. , Gardecki Joseph A. , Thiagarajah Jay R. , Rowe Steven M. , Tearney Guillermo J.
Published: September 2021

Introduction: Diseases such as celiac disease, environmental enteric dysfunction, infectious gastroenteritis, type II diabetes and inflammatory bowel disease are associated with increased gut permeability. Dual sugar absorption tests, such as the lactulose to rhamnose ratio (L:R) test, are the current standard for measuring gut permeability. Although easy to administer in adults, the L:R test has a number of drawbacks. These include an inability to assess for spatial heterogeneity in gut permeability that may distinguish different disease severity or pathology, additional sample collection for immunoassays, and challenges in carrying out the test in certain populations such as infants and small children. Here, we demonstrate a minimally invasive probe for real-time localized gut permeability evaluation through gut potential difference (GPD) measurement.

Materials and Methods: The probe has an outer diameter of 1.2 mm diameter and can be deployed in the gut of unsedated subjects via a transnasal introduction tube (TNIT) that is akin to an intestinal feeding tube. The GPD probe consists of an Ag/AgCl electrode, an optical probe and a perfusion channel all housed within a transparent sheath. Lactated Ringer’s (LR) solution is pumped through the perfusion channel to provide ionic contact between the electrodes and the gut lining. The optical probe captures non-scanning (M-mode) OCT images to confirm electrode contact with the gut lining. A separate skin patch probe is placed over an abraded skin area to provide reference for the GPD measurements. Swine studies were conducted to validate the GPD probe. GPD in the duodenum was modulated by perfusing 45 ml of 45 mM glucose.

Results: GPD values of −13.1 ± 2.8 mV were measured in the duodenum across four swine studies. The change in GPD in the duodenum with the addition of glucose was −10.5 ± 2.4 mV (p < 0.001). M-mode OCT images provided electrode-tissue contact information, which was vital in ascertaining the probe’s proximity to the gut mucosa.

Conclusion: We developed and demonstrated a minimally invasive method for investigating gastrointestinal permeability consisting of an image guided GPD probe that can be used in unsedated subjects.
Performance Evaluation of a 4 × 20-Gbps OFDM-Based FSO Link Incorporating Hybrid W-MDM Techniques
Authors: Singh Mehtab , Chebaane Saleh , Ben Khalifa Sana , Grover Amit , Dewra Sanjeev , Angurala Mohit
Published: September 2021

Free space optics (FSO) has been recognized as a crucial technique to meet the high-bandwidth requirements in future wireless information transmission links. It provides a feasible solution to the last-mile bottleneck problem due to its merits that include high-speed data transportation and secure and low-latency networks. Due to these merits, FSO is a reliable technology for future health-care and biomedical services like the transmission of biomedical sensor signals. But the main limiting factor in the data transmission employing FSO links is adverse atmospheric weather conditions. This research work reports the designing and simulative evaluation of the performance of a high-speed orthogonal frequency division multiplexing–based free space optics link by incorporating wavelength division multiplexing of two independent frequency channels (193.1 THz and 193.2 THz) along with mode division multiplexing of distinct spatial laser Hermite–Gaussian modes (HG01 and HG03). Four independent 20-Gbps quadrature amplitude-modulated data signals are transported simultaneously under different atmospheric weather conditions using the proposed link. Also, the link performance has been investigated for an increasing beam divergence angle.
The Signaling Pathways Involved in Ovarian Follicle Development
Authors: Li Liyuan , Shi Xiaojin , Shi Yun , Wang Zhao
Published: September 2021

The follicle is the functional unit of the ovary, which is composed of three types of cells: oocytes, granulosa cells, and theca cells. Ovarian follicle development and the subsequent ovulation process are coordinated by highly complex interplay between endocrine, paracrine, and autocrine signals, which coordinate steroidogenesis and gametogenesis. Follicle development is regulated mainly by three organs, the hypothalamus, anterior pituitary, and gonad, which make up the hypothalamic-pituitary-gonadal axis. Steroid hormones and their receptors play pivotal roles in follicle development and participate in a series of classical signaling pathways. In this review, we summarize and compare the role of classical signaling pathways, such as the WNT, insulin, Notch, and Hedgehog pathways, in ovarian follicle development and the underlying regulatory mechanism. We have also found that these four signaling pathways all interact with FOXO3, a transcription factor that is widely known to be under control of the PI3K/AKT signaling pathway and has been implicated as a major signaling pathway in the regulation of dormancy and initial follicular activation in the ovary. Although some of these interactions with FOXO3 have not been verified in ovarian follicle cells, there is a high possibility that FOXO3 plays a core role in follicular development and is regulated by classical signaling pathways. In this review, we present these signaling pathways from a comprehensive perspective to obtain a better understanding of the follicular development process.
The Effect of Physical Therapy on Regional Lung Function in Critically Ill Patients
Authors: Eimer Christine , Freier Katharina , Weiler Norbert , Frerichs Inéz , Becher Tobias
Published: September 2021

Early mobilization has become an important aspect of treatment in intensive care medicine, especially in patients with acute pulmonary dysfunction. As its effects on regional lung physiology have not been fully explored, we conceived a prospective observational study (Registration number: DRKS00023076) investigating regional lung function during a 15-min session of early mobilization physiotherapy with a 30-min follow-up period. The study was conducted on 20 spontaneously breathing adult patients with impaired pulmonary gas exchange receiving routine physical therapy during their intensive care unit stay. Electrical impedance tomography (EIT) was applied to continuously monitor ventilation distribution and changes in lung aeration during mobilization and physical therapy. Baseline data was recorded in the supine position, the subjects were then transferred into the seated and partly standing position for physical therapy. Afterward, patients were transferred back into the initial position and followed up with EIT for 30 min. EIT data were analyzed to assess changes in dorsal fraction of ventilation (%dorsal), end-expiratory lung impedance normalized to tidal variation (ΔEELI), center of ventilation (CoV) and global inhomogeneity index (GI index).Follow-up was completed in 19 patients. During exercise, patients exhibited a significant change in ventilation distribution in favor of dorsal lung regions, which did not persist during follow-up. An identical effect was shown by CoV. ΔEELI increased significantly during follow-up. In conclusion, mobilization led to more dorsal ventilation distribution, but this effect subsided after returning to initial position. End-expiratory lung impedance increased during follow-up indicating a slow increase in end-expiratory lung volume following physical therapy.
Phosphoproteomic Profiling Reveals Early Salt-Responsive Mechanisms in Two Foxtail Millet Cultivars
Authors: Pan Jiaowen , Li Zhen , Wang Qingguo , Guan Yanan , Li Xiaobo , Huangfu Yongguan , Meng Fanhua , Li Jinling , Dai Shaojun , Liu Wei
Published: September 2021

Excess soluble salts in saline soils are harmful to most plants. Understanding the biochemical responses to salts in plants and studying the salt tolerance-associated genetic resources in nature will contribute to the improvement of salt tolerance in crops. As an emerging model crop, foxtail millet (Setaria italica L.) has been regarded as a novel species for stress resistance investigation. Here, the dynamic proteomic and phosphoproteomic profiling of two foxtail millet varieties of An04 and Yugu2 with contrasting salt tolerance characteristics were investigated under salt stress. In total, 10,366 sites representing to 2,862 proteins were detected and quantified. There were 759 and 990 sites corresponding to 484 and 633 proteins identified under salinity in An04 and Yugu2, respectively, and 1,264 and 1,131 phosphorylation sites corresponding to 789 and 731 proteins were identified between these two varieties before and after salt stress, respectively. The differentially-regulated phosphoproteins (DRPPs) were mainly involved in signal transduction, regulation of gene expression, translation, ion transport, and metabolism processes. Yugu2 possessed signal perception and transduction capabilities more rapidly and had a more intense response compared with An04 upon salinity. The sucrose metabolism pathway, in particularly, might play a vital role in salt response in foxtail millet, which not only provides UDP-glucose for the cellulose synthesis and energy production, but also promotes flavonoid related synthesis to enhance the salt tolerance ability. Over-expressing the phospho-mimic sucrose synthase (SuS) (SuSS10D) in soybean roots enhanced salt tolerance compared with over-expressing SuS lines. The knowledge of this research will shed light on elucidating the mechanisms of salt response, and pave the way for crop varieties innovation and cultivation under salinity and stresses.
Advances on the Visualization of the Internal Structures of the European Mistletoe: 3D Reconstruction Using Microtomography
Authors: Mylo Max D. , Hofmann Mara , Delp Alexander , Scholz Ronja , Walther Frank , Speck Thomas , Speck Olga
Published: September 2021

The European mistletoe (Viscum album) is a dioecious epiphytic evergreen hemiparasite that develops an extensive endophyte enabling the absorption of water and mineral salts from the host tree, whereas the exophytic leaves are photosynthetically active. The attachment mode and host penetration are well studied, but little information is available about the effects of mistletoe age and sex on haustorium-host interactions. We harvested 130 plants of Viscum album ssp. album growing on host branches of Aesculus flava for morphological and anatomical investigations. Morphometric analyses of the mistletoe and the (hypertrophied) host interaction site were correlated with mistletoe age and sex. We recorded the morphology of the endophytic systems of various ages by using X-ray microtomography scans and corresponding stereomicroscopic images. For detailed anatomical studies, we examined thin stained sections of the mistletoe-host interface by light microscopy. The diameter and length of the branch hypertrophy showed a positive linear correlation with the age of the mistletoe. Correlations with their sex were only found for ratios between host branch and hypertrophy size. A female bias of about 76% was found. In a 4-year-old mistletoe, several small, almost equally sized sinkers and the connected cortical strands extend over more than 5 cm within the host branch. In older mistletoes, one main sinker was predominant and occupied an increasingly large proportion of the stem cross-section. Bands of vessels ran along the axis of the wedge-shaped haustoria and sinkers and bent sideways toward the mistletoe-host interface. At the interface, the vascular elements of the host wood changed their direction and formed vortices near the haustorium.
EMDR as Treatment Option for Conditions Other Than PTSD: A Systematic Review
Authors: Scelles Charles , Bulnes Luis Carlo
Published: September 2021

Eye Movement Desensitisation and Reprocessing (EMDR) is a treatment for post-traumatic stress disorder (PTSD). The technique is known to facilitate reprocessing of maladaptive memories that are thought to be central to this pathology. Here we investigate if EMDR therapy can be used in other conditions. We conducted a systematic literature search on PubMed, ScienceDirect, Scopus, and Web of Science. We searched for published empirical findings on EMDR, excluding those centred on trauma and PTSD, published up to 2020. The results were classified by psychiatric categories. Ninety articles met our research criteria. A positive effect was reported in numerous pathological situations, namely in addictions, somatoform disorders, sexual dysfunction, eating disorders, disorders of adult personality, mood disorders, reaction to severe stress, anxiety disorders, performance anxiety, Obsessive-Compulsive Disorder (OCD), pain, neurodegenerative disorders, mental disorders of childhood and adolescence, and sleep. Some studies reported that EMDR was successful in usually uncooperative (e.g., Dementia) or unproductive cases (e.g., aphasia). Moreover, in some severe medical conditions, when psychological distress was an obstacle, EMDR allowed the continuation of treatment-as-usual. Furthermore, the effects observed in non-pathological situations invite for translational research. Despite a generally positive outlook of EMDR as an alternative treatment option, more methodologically rigorous studies are needed. We discuss the advantages and limitations and possible implications for the hypothesised mechanisms of action.
Reflective Functioning in Children and Adolescents With and Without an Anxiety Disorder
Authors: Chevalier Valérie , Simard Valérie , Achim Julie , Burmester Pamela , Beaulieu-Tremblay Thalie
Published: September 2021

Reflective functioning (RF), meaning the capacity to interpret mental states (intentions, emotions, thoughts, desires, and beliefs) underlying one’s own and others’ behaviors, may help understand the dysfunctional self-regulation associated with anxiety disorders. However, research on anxiety and RF in clinical samples is scarce. This study aimed to assess whether mothers’ and youths’ RF was associated with youths’ (a) anxiety disorders and symptoms and (b) internalizing symptoms. Another goal was to explore whether RF predicted anxiety and internalizing symptoms beyond the more commonly established effect of attachment. Canadian children and adolescents aged between 8 and 16years, and their mothers were recruited in an outpatient psychiatric clinic (clinical group with a diagnosed anxiety disorder, n=30, mean age=11.5±2.8years) and in the general population (non-clinical group, n=23, mean age=11.5±2.1years). The Child Attachment Interview was used to assess youths’ attachment along with three dimensions of RF (global, regarding self, regarding others). Mothers’ attachment and RF were assessed with the Adult Attachment Interview. Children’s and adolescents’ anxiety and internalizing symptoms were measured with the Behavior Assessment Scale for Children, second version. The clinical and non-clinical groups did not differ in mothers’ or youths’ RF. However, in the overall sample, youths’ RF regarding themselves and maternal attachment preoccupation were associated with internalizing symptoms. Sequential regression analyses revealed that higher RF regarding self predicted a higher level of self-reported internalizing symptoms, beyond the effect of maternal attachment (β=0.43, p<0.05). This study’s finding suggests that clinically anxious children and adolescents have adequate RF. We propose that the sustained hypervigilance and apprehension associated with anxiety make anxious youths sensitive to their own and others’ mental states. Our findings suggest that psychotherapeutic treatments for anxiety should make use of patients’ RF abilities to help them make sense of their symptoms and thus reduce them.
Dynamic Evolution Mechanism of Digital Entrepreneurship Ecosystem Based on Text Sentiment Computing Analysis
Authors: Li Jiahui , Yao Meifang
Published: September 2021

To solve the limitations of the current entrepreneurial ecosystem, the research on the digital entrepreneurial ecosystem is more meaningful. This article aims to study the dynamic evolution mechanism of the digital entrepreneurship ecosystem based on text sentiment computing analysis. It proposes an improved Bi-directional long short-term memory (Bi-LSTM) model, which uses a multilayer neural network to deal with classification problems. It has a higher accuracy rate, recall rate, and F1 value than the traditional LSTM model and can better perform sentiment analysis on text. The algorithm uses the optimized Naive Bayes algorithm, which is based on Euclidean distance weighting and can assign different weights to the final classification results according to different attributes. Compared with the general Bayes algorithm, it improves the calculation efficiency and can better match the digital entrepreneurial ecosystem, which is evolving dynamically, predicting and analyzing its future development. The experimental results in this article show that the improved Bi-LSTM is better than the traditional Bi-LSTM model in terms of accuracy and F1 value. The accuracy rate is increased by 1.1%, the F1 value is increased by 0.6%, and the recall rate is only <0.2%. Running on the Spark platform, although 3% accuracy is sacrificed, the running time is increased by 320%. Compared with the traditional cellular neural network (CNN) algorithm, the accuracy rate is increased by 4%, the recall rate is increased by 14%, and the F1 value is increased by 9%, which proves that it has a strong non-linear fitting ability. The performance improvement brought by the huge data set is very huge, which fully proves the feasibility of the digital entrepreneurship ecosystem.
Squats in Surveys: Investigating the Feasibility of, Compliance With, and Respondents' Performance on Fitness Tasks in Self-Administered Smartphone Surveys Using Acceleration Data
Authors: Elevelt Anne , Höhne Jan Karem , Blom Annelies G.
Published: September 2021

Digital health data that accompany data from traditional surveys are becoming increasingly important in health-related research. For instance, smartphones have many built-in sensors, such as accelerometers that measure acceleration so that they offer many new research possibilities. Such acceleration data can be used as a more objective supplement to health and physical fitness measures (or survey questions). In this study, we therefore investigate respondents' compliance with and performance on fitness tasks in self-administered smartphone surveys. For this purpose, we use data from a cross-sectional study as well as a lab study in which we asked respondents to do squats (knee bends). We also employed a variety of questions on respondents' health and fitness level and additionally collected high-frequency acceleration data. Our results reveal that observed compliance is higher than hypothetical compliance. Respondents gave mainly health-related reasons for non-compliance. Respondents' health status positively affects compliance propensities. Finally, the results show that acceleration data of smartphones can be used to validate the compliance with and performance on fitness tasks. These findings indicate that asking respondents to conduct fitness tasks in self-administered smartphone surveys is a feasible endeavor for collecting more objective data on physical fitness levels.
The Impact of Rainfall Variability on Diets and Undernutrition of Young Children in Rural Burkina Faso
Authors: Mank Isabel , Belesova Kristine , Bliefernicht Jan , Traoré Issouf , Wilkinson Paul , Danquah Ina , Sauerborn Rainer
Published: September 2021

Background: Climate change and consequent increases in rainfall variability may have negative consequences for the food production of subsistence farmers in West Africa with adverse impacts on nutrition and health. We explored the pathway from rainfall through diet up to child undernutrition for rural Burkina Faso.

Methods: The study used data of a dynamic cohort with 1,439 children aged 7–60 months from the Nouna Health and Demographic Surveillance Site (HDSS) for 2017 to 2019. We assessed data on diets, height, weight, household characteristics, and daily precipitation (from 1981 to 2019). Principal component analysis was used to identify distinct child dietary patterns (Dietary Pattern Scores, DPS). These were related to 15 rainfall indicators by area to obtain a precipitation variability score (PVS) through reduced rank regression (RRR). Associations between the PVS and anthropometric measures, height-for-age (HAZ), and weight-for-height (WHZ), were examined using multi-level regression analysis.

Results: Stunting (HAZ < −2) and wasting (WHZ < −2) were seen in 24 and 6% of the children. Three main dietary patterns were identified (market-based, vegetable-based, and legume-based diets) and showed mixed evidence for associations with child undernutrition. The RRR-derived PVS explained 14% of the total variance in these DPS. The PVS was characterized by more consecutive dry days during the rainy season, higher cumulative rainfall in July and more extremely wet days. A 1-point increase in the PVS was associated with a reduction of 0.029 (95% CI: −0.06, 0.00, p < 0.05) in HAZ in the unadjusted, and an increase by 0.032 (95% CI: 0.01, 0.06, p < 0.05) in WHZ in the fully adjusted model.

Conclusion: Rainfall variability was associated with dietary patterns in young children of a rural population of Burkina Faso. Increased rainfall variability was associated with an increase in chronic undernutrition, but not in acute undernutrition among young children.