bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-analysis of fungal plant pathogen Fusarium oxysporum infection-related gene profiles using transcriptome datasets
Authors: Cai Hongsheng , Yu Na , Liu Yingying , Wei Xuena , Guo Changhong
Published: August 2022

Fusarium oxysporum is a serious soil-borne fungal pathogen that affects the production of many economically important crops worldwide. Recent reports suggest that this fungus is becoming the dominant species in soil and could become the main infectious fungus in the future. However, the infection mechanisms employed by F. oxysporum are poorly understood. In the present study, using a network meta-analysis technique and public transcriptome datasets for different F. oxysporum and plant interactions, we aimed to explore the common molecular infection strategy used by this fungus and to identify vital genes involved in this process. Principle component analysis showed that all the fungal culture samples from different datasets were clustered together, and were clearly separated from the infection samples, suggesting the feasibility of an integrated analysis of heterogeneous datasets. A total of 335 common differentially expressed genes (DEGs) were identified among these samples, of which 262 were upregulated and 73 were downregulated significantly across the datasets. The most enriched functional categories of the common DEGs were carbohydrate metabolism, amino acid metabolism, and lipid metabolism. Nine co-expression modules were identified, and two modules, the turquoise module and the blue module, correlated positively and negatively with all the infection processes, respectively. Co-expression networks were constructed for these two modules and hub genes were identified and validated. Our results comprise a cross fungal-host interaction resource, highlighting the use of a network biology approach to gain molecular insights.
Neurotransmitters and molecular chaperones interactions in cerebral malaria: Is there a missing link?
Authors: Daniyan Michael Oluwatoyin , Fisusi Funmilola Adesodun , Adeoye Olufunso Bayo
Published: August 2022

Plasmodium falciparum is responsible for the most severe and deadliest human malaria infection. The most serious complication of this infection is cerebral malaria. Among the proposed hypotheses that seek to explain the manifestation of the neurological syndrome in cerebral malaria is the vascular occlusion/sequestration/mechanic hypothesis, the cytokine storm or inflammatory theory, or a combination of both. Unfortunately, despite the increasing volume of scientific information on cerebral malaria, our understanding of its pathophysiologic mechanism(s) is still very limited. In a bid to maintain its survival and development, P. falciparum exports a large number of proteins into the cytosol of the infected host red blood cell. Prominent among these are the P. falciparum erythrocytes membrane protein 1 (PfEMP1), P. falciparum histidine-rich protein II (PfHRP2), and P. falciparum heat shock proteins 70-x (PfHsp70-x). Functional activities and interaction of these proteins with one another and with recruited host resident proteins are critical factors in the pathology of malaria in general and cerebral malaria in particular. Furthermore, several neurological impairments, including cognitive, behavioral, and motor dysfunctions, are known to be associated with cerebral malaria. Also, the available evidence has implicated glutamate and glutamatergic pathways, coupled with a resultant alteration in serotonin, dopamine, norepinephrine, and histamine production. While seeking to improve our understanding of the pathophysiology of cerebral malaria, this article seeks to explore the possible links between host/parasite chaperones, and neurotransmitters, in relation to other molecular players in the pathology of cerebral malaria, to explore such links in antimalarial drug discovery.
Perspectives on the complex links between depression and dementia
Authors: Hakim Antoine
Published: August 2022

This review highlights that depression is a growing health problem for the individual, and because of its high frequency in most societies, a growing burden on health care budgets. The focus of the review is the physiological links between depression and dementia, specifically Alzheimer’s disease. It suggests that depression is a significant risk factor for cognitive decline and explores the pathways that may lead depressed individuals to suffer this outcome. This review shows that depression and a number of its precursors activate pro-inflammatory mediators. These lead to cerebral small vessel disease with the consequent reduction in cerebral blood flow, which is known to precede cognitive decline. Thus, the impact of depression on the physiological events that lead to dementia is identical to the impact of other dementia risk factors recently reviewed. Depression is distinct, however, in being a relatively treatable condition, but the impact of treating depression on later cognitive decline is not always positive, leading to the hypothesis that only the antidepressants that attenuate inflammation alleviate subsequent cognitive decline.
Infusion of C20:0 ceramide into ventral hippocampus triggers anhedonia-like behavior in female and male rats
Authors: Sambolín-Escobales Lubriel , Feliciano-Quiñones Adariana , Tirado-Castro Lizmarie , Suárez Cristina , Pacheco-Cruz Dariangelly , Irizarry-Méndez Nashaly , Fonseca-Ferrer Wilfred , Hernández-López Anixa , Colón-Romero María , Porter James T.
Published: August 2022

Increased long-chain C20:0 ceramides have been found in the serum of patients with depression. Moreover, ceramides are linked with increased microglia reactivity and inflammatory cytokine production, which are associated with depression. Since ceramides can readily cross the blood brain barrier, peripheral C20:0 ceramides could enter the brain, activate microglia, and induce depressive-like behavior. In this study, we determined whether localized infusion of C20:0 ceramides into the ventral hippocampus (VH) of rats is sufficient to activate microglia and induce depressive-like behaviors. Adult male and female rats received infusions of C20:0 ceramides or vehicle solution every other day for 2 weeks. After the third infusion, C20:0-infused animals showed reduced sucrose preference suggesting anhedonia-like behavior. In contrast, infusions of C20:0 ceramides did not affect immobility in the forced swim test or sucrose grooming suggesting that the behavioral effects of ceramides are task dependent. Furthermore, C20:0-infusions did not increase Iba-1 + microglia or inflammatory markers in the VH suggesting that localized increases in C20:0 ceramides in the VH are sufficient to induce anhedonia-like behavior without microglia activation.
Using animal models for the studies of schizophrenia and depression: The value of translational models for treatment and prevention
Authors: Uliana Daniela L. , Zhu Xiyu , Gomes Felipe V. , Grace Anthony A.
Published: August 2022

Animal models of psychiatric disorders have been highly effective in advancing the field, identifying circuits related to pathophysiology, and identifying novel therapeutic targets. In this review, we show how animal models, particularly those based on development, have provided essential information regarding circuits involved in disorders, disease progression, and novel targets for intervention and potentially prevention. Nonetheless, in recent years there has been a pushback, largely driven by the US National Institute of Mental Health (NIMH), to shift away from animal models and instead focus on circuits in normal subjects. This has been driven primarily from a lack of discovery of new effective therapeutic targets, and the failure of targets based on preclinical research to show efficacy. We discuss why animal models of complex disorders, when strongly cross-validated by clinical research, are essential to understand disease etiology as well as pathophysiology, and direct new drug discovery. Issues related to shortcomings in clinical trial design that confound translation from animal models as well as the failure to take patient pharmacological history into account are proposed to be a source of the failure of what are likely effective compounds from showing promise in clinical trials.
Exploring the effects of serial and parallel elasticity on a hopping robot
Authors: Zhao Guoping , Mohseni Omid , Murcia Marc , Seyfarth Andre , Sharbafi Maziar A.
Published: August 2022

The interaction between the motor control and the morphological design of the human leg is critical for generating efficient and robust locomotion. In this paper, we focus on exploring the effects of the serial and parallel elasticity on hopping with a two-segmented robotic leg called electric-pneumatic actuation (EPA)-Hopper. EPA-Hopper uses a hybrid actuation system that combines electric motors and pneumatic artificial muscles (PAM). It provides direct access to adjust the physical compliance of the actuation system by tuning PAM pressures. We evaluate the role of the serial and parallel PAMs with different levels of compliance with respect to four criteria: efficiency, performance, stability, and robustness of hopping against perturbations. The results show that the serial PAM has a more pronounced impact than the parallel PAM on these criteria. Increasing the stiffness of the serial PAM decreases the leg stiffness of the unloading phase during hopping. The stiffer the leg, the more efficient and the less robust the movement. These findings can help us further understand the human hopping mechanism and support the design and control of legged robots and assistive devices.
ClC-3 regulates the excitability of nociceptive neurons and is involved in inflammatory processes within the spinal sensory pathway
Authors: Sierra-Marquez Juan , Willuweit Antje , Schöneck Michael , Bungert-Plümke Stefanie , Gehlen Jana , Balduin Carina , Müller Frank , Lampert Angelika , Fahlke Christoph , Guzman Raul E.
Published: August 2022

ClC-3 Cl–/H+ exchangers are expressed in multiple endosomal compartments and likely modify intra-endosomal pH and [Cl–] via the stoichiometrically coupled exchange of two Cl– ions and one H+. We studied pain perception in Clcn3–/– mice and found that ClC-3 not only modifies the electrical activity of peripheral nociceptors but is also involved in inflammatory processes in the spinal cord. We demonstrate that ClC-3 regulates the number of Nav and Kv ion channels in the plasma membrane of dorsal root ganglion (DRG) neurons and that these changes impair the age-dependent decline in excitability of sensory neurons. To distinguish the role of ClC-3 in Cl–/H+ exchange from its other functions in pain perception, we used mice homozygous for the E281Q ClC-3 point mutation (Clcn3E281Q/E281Q), which completely eliminates transport activity. Since ClC-3 forms heterodimers with ClC-4, we crossed these animals with Clcn4–/– to obtain mice completely lacking in ClC-3-associated endosomal chloride–proton transport. The electrical properties of Clcn3E281Q/E281Q/Clcn4–/– DRG neurons were similar to those of wild-type cells, indicating that the age-dependent adjustment of neuronal excitability is independent of ClC-3 transport activity. Both Clcn3–/– and Clcn3E281Q/E281Q/Clcn4–/– animals exhibited microglial activation in the spinal cord, demonstrating that competent ClC-3 transport is needed to maintain glial cell homeostasis. Our findings illustrate how reduced Cl–/H+ exchange contributes to inflammatory responses and demonstrate a role for ClC-3 in the homeostatic regulation of neuronal excitability beyond its function in endosomal ion balance.
Putative COVID-19 therapies imatinib, lopinavir, ritonavir, and ivermectin cause hair cell damage: A targeted screen in the zebrafish lateral line
Authors: Coffin Allison B. , Dale Emily , Doppenberg Emilee , Fearington Forrest , Hayward Tamasen , Hill Jordan , Molano Olivia
Published: August 2022

The biomedical community is rapidly developing COVID-19 drugs to bring much-need therapies to market, with over 900 drugs and drug combinations currently in clinical trials. While this pace of drug development is necessary, the risk of producing therapies with significant side-effects is also increased. One likely side-effect of some COVID-19 drugs is hearing loss, yet hearing is not assessed during preclinical development or clinical trials. We used the zebrafish lateral line, an established model for drug-induced sensory hair cell damage, to assess the ototoxic potential of seven drugs in clinical trials for treatment of COVID-19. We found that ivermectin, lopinavir, imatinib, and ritonavir were significantly toxic to lateral line hair cells. By contrast, the approved COVID-19 therapies dexamethasone and remdesivir did not cause damage. We also did not observe damage from the antibiotic azithromycin. Neither lopinavir nor ritonavir altered the number of pre-synaptic ribbons per surviving hair cell, while there was an increase in ribbons following imatinib or ivermectin exposure. Damage from lopinavir, imatinib, and ivermectin was specific to hair cells, with no overall cytotoxicity noted following TUNEL labeling. Ritonavir may be generally cytotoxic, as determined by an increase in the number of TUNEL-positive non-hair cells following ritonavir exposure. Pharmacological inhibition of the mechanotransduction (MET) channel attenuated damage caused by lopinavir and ritonavir but did not alter imatinib or ivermectin toxicity. These results suggest that lopinavir and ritonavir may enter hair cells through the MET channel, similar to known ototoxins such as aminoglycoside antibiotics. Finally, we asked if ivermectin was ototoxic to rats in vivo. While ivermectin is not recommended by the FDA for treating COVID-19, many people have chosen to take ivermectin without a doctor’s guidance, often with serious side-effects. Rats received daily subcutaneous injections for 10 days with a clinically relevant ivermectin dose (0.2 mg/kg). In contrast to our zebrafish assays, ivermectin did not cause ototoxicity in rats. Our research suggests that some drugs in clinical trials for COVID-19 may be ototoxic. This work can help identify drugs with the fewest side-effects and determine which therapies warrant audiometric monitoring.
Temporally optimized patterned stimulation (TOPS®) as a therapy to personalize deep brain stimulation treatment of Parkinson’s disease
Authors: Okun Michael S. , Hickey Patrick T. , Machado Andre G. , Kuncel Alexis M. , Grill Warren M.
Published: August 2022

Deep brain stimulation (DBS) is a well-established therapy for the motor symptoms of Parkinson’s disease (PD), but there remains an opportunity to improve symptom relief. The temporal pattern of stimulation is a new parameter to consider in DBS therapy, and we compared the effectiveness of Temporally Optimized Patterned Stimulation (TOPS) to standard DBS at reducing the motor symptoms of PD. Twenty-six subjects with DBS for PD received three different patterns of stimulation (two TOPS and standard) while on medication and using stimulation parameters optimized for standard DBS. Side effects and motor symptoms were assessed after 30 min of stimulation with each pattern. Subjects experienced similar types of side effects with TOPS and standard DBS, and TOPS were well-tolerated by a majority of the subjects. On average, the most effective TOPS was as effective as standard DBS at reducing the motor symptoms of PD. In some subjects a TOPS pattern was the most effective pattern. Finally, the TOPS pattern with low average frequency was found to be as effective or more effective in about half the subjects while substantially reducing estimated stimulation energy use. TOPS DBS may provide a new programing option to improve DBS therapy for PD by improving symptom reduction and/or increasing energy efficiency. Optimizing stimulation parameters specifically for TOPS DBS may demonstrate further clinical benefit of TOPS DBS in treating the motor symptoms of Parkinson’s disease.
Frontostriatal circuitry as a target for fMRI-based neurofeedback interventions: A systematic review
Authors: Orth Linda , Meeh Johanna , Gur Ruben C. , Neuner Irene , Sarkheil Pegah
Published: August 2022

Dysregulated frontostriatal circuitries are viewed as a common target for the treatment of aberrant behaviors in various psychiatric and neurological disorders. Accordingly, experimental neurofeedback paradigms have been applied to modify the frontostriatal circuitry. The human frontostriatal circuitry is topographically and functionally organized into the “limbic,” the “associative,” and the “motor” subsystems underlying a variety of affective, cognitive, and motor functions. We conducted a systematic review of the literature regarding functional magnetic resonance imaging-based neurofeedback studies that targeted brain activations within the frontostriatal circuitry. Seventy-nine published studies were included in our survey. We assessed the efficacy of these studies in terms of imaging findings of neurofeedback intervention as well as behavioral and clinical outcomes. Furthermore, we evaluated whether the neurofeedback targets of the studies could be assigned to the identifiable frontostriatal subsystems. The majority of studies that targeted frontostriatal circuitry functions focused on the anterior cingulate cortex, the dorsolateral prefrontal cortex, and the supplementary motor area. Only a few studies (n = 14) targeted the connectivity of the frontostriatal regions. However, post-hoc analyses of connectivity changes were reported in more cases (n = 32). Neurofeedback has been frequently used to modify brain activations within the frontostriatal circuitry. Given the regulatory mechanisms within the closed loop of the frontostriatal circuitry, the connectivity-based neurofeedback paradigms should be primarily considered for modifications of this system. The anatomical and functional organization of the frontostriatal system needs to be considered in decisions pertaining to the neurofeedback targets.
The comorbidity and cognition in multiple sclerosis (CCOMS) neuroimaging protocol: Study rationale, MRI acquisition, and minimal image processing pipelines
Authors: Uddin Md Nasir , Figley Teresa D. , Kornelsen Jennifer , Mazerolle Erin L. , Helmick Carl A. , O'Grady Christopher B. , Pirzada Salina , Patel Ronak , Carter Sean , Wong Kaihim , Essig Marco R. , Graff Lesley A. , Bolton James M. , Marriott James J. , Bernstein Charles N. , Fisk John D. , Marrie Ruth Ann , Figley Chase R.
Published: August 2022

The Comorbidity and Cognition in Multiple Sclerosis (CCOMS) study represents a coordinated effort by a team of clinicians, neuropsychologists, and neuroimaging experts to investigate the neural basis of cognitive changes and their association with comorbidities among persons with multiple sclerosis (MS). The objectives are to determine the relationships among psychiatric (e.g., depression or anxiety) and vascular (e.g., diabetes, hypertension, etc.) comorbidities, cognitive performance, and MRI measures of brain structure and function, including changes over time. Because neuroimaging forms the basis for several investigations of specific neural correlates that will be reported in future publications, the goal of the current manuscript is to briefly review the CCOMS study design and baseline characteristics for participants enrolled in the three study cohorts (MS, psychiatric control, and healthy control), and provide a detailed description of the MRI hardware, neuroimaging acquisition parameters, and image processing pipelines for the volumetric, microstructural, functional, and perfusion MRI data.
Translational neuronal ensembles: Neuronal microcircuits in psychology, physiology, pharmacology and pathology
Authors: Lara-González Esther , Padilla-Orozco Montserrat , Fuentes-Serrano Alejandra , Bargas José , Duhne Mariana
Published: August 2022

Multi-recording techniques show evidence that neurons coordinate their firing forming ensembles and that brain networks are made by connections between ensembles. While “canonical” microcircuits are composed of interconnected principal neurons and interneurons, it is not clear how they participate in recorded neuronal ensembles: “groups of neurons that show spatiotemporal co-activation”. Understanding synapses and their plasticity has become complex, making hard to consider all details to fill the gap between cellular-synaptic and circuit levels. Therefore, two assumptions became necessary: First, whatever the nature of the synapses these may be simplified by “functional connections”. Second, whatever the mechanisms to achieve synaptic potentiation or depression, the resultant synaptic weights are relatively stable. Both assumptions have experimental basis cited in this review, and tools to analyze neuronal populations are being developed based on them. Microcircuitry processing followed with multi-recording techniques show temporal sequences of neuronal ensembles resembling computational routines. These sequences can be aligned with the steps of behavioral tasks and behavior can be modified upon their manipulation, supporting the hypothesis that they are memory traces. In vitro, recordings show that these temporal sequences can be contained in isolated tissue of histological scale. Sequences found in control conditions differ from those recorded in pathological tissue obtained from animal disease models and those recorded after the actions of clinically useful drugs to treat disease states, setting the basis for new bioassays to test drugs with potential clinical use. These findings make the neuronal ensembles theoretical framework a dynamic neuroscience paradigm.
Preventive and therapeutic effect of Lactobacillus paracasei ZFM54 on Helicobacter pylori-induced gastritis by ameliorating inflammation and restoring gastric microbiota in mice model
Authors: Zhou Qingqing , Qureshi Nuzhat , Xue Bingyao , Xie Zuorui , Li Ping , Gu Qing
Published: August 2022

Helicobacter pylori is the most prevalent pathogen causing chronic gastritis, gastroduodenal ulcers, and gastric tumors and is asymptomatically present in 50% of the world's population. This research is focused on investigating the effect of Lactobacillus paracasei ZFM 54 (CCTCC NO:2016667) on attenuating H. pylori-induced gastritis. H. pylori ZJC03 isolated from a patient with gastritis harbored the virulence genes of vacA and cagA and was highly resistant to metronidazole (MIC > 256 μg/mL). In vitro analysis revealed that the potential anti-H. pylori characteristics of L. paracasei ZFM54 in terms of 65.57 ± 1.87% survival rate in simulated gastric juices at a pH of 2.0, 69.00 ± 2.73% auto-aggregation, 30.28 ± 2.24% co-aggregation, 70.27 ± 2.23% urease inhibition, and 57.89 ± 1.27% radical scavenging. In H. pylori infectious mice, L. paracasei ZFM54 pre- and post-treatment reduced the levels of malondialdehyde in liver tissues to 0.71 ± 0.04 nmol/mgprot (p < 0.05) and 0.70 ± 0.06 nmol/mgprot (p < 0.05), respectively. Glutathione levels were increased to 1.78 ± 0.02 μmol/gprot (p < 0.05) and 1.76 ± 0.52 μmol/gprot (p < 0.05), respectively. L. paracasei ZFM54 significantly inhibited H. pylori-mediated inflammation observed in gastric mucosal repair and downregulated the mRNA expression of pro-inflammatory cytokines IFN-γ, IL-1β, and IL-6 (p < 0.01). Importantly, L. paracasei ZFM54 increased Firmicutes and Actinobacteriota and decreased the relative abundance of bacterial taxa belonging to Campilobacterota and Proteobacteria. With the preventive and therapeutic administration of L. paracasei ZFM54, significant reductions in the average relative abundance of genera Helicobacter, Muribaculum, Staphylococcus, Lachnospiraceae_NK4A136_group, Prevotellaceae_UCG-001, Alloprevotella, and Oscillibacter were observed compared to infected mice. These findings suggest that L. paracasei ZFM 54 has the potential to protect against H. pylori infection by ameliorating inflammation and restoring the gastric microbiota.
The molecular mechanisms of ferroptosis and its role in glioma progression and treatment
Authors: Lu Mengyang , Zhou Yuanshuai , Sun Linjuan , Shafi Shaheryar , Ahmad Nafees , Sun Minxuan , Dong Jun
Published: August 2022

Ferroptosis is one of the programmed modes of cell death that has attracted widespread attention recently and is capable of influencing the developmental course and prognosis of many tumors. Glioma is one of the most common primary tumors of the central nervous system, but effective treatment options are very limited. Ferroptosis plays a critical role in the glioma progression, affecting tumor cell proliferation, angiogenesis, tumor necrosis, and shaping the immune-resistant tumor microenvironment. Inducing ferroptosis has emerged as an attractive strategy for glioma. In this paper, we review ferroptosis-related researches on glioma progression and treatment.
Serum cytokine levels for predicting immune-related adverse events and the clinical response in lung cancer treated with immunotherapy
Authors: Zhao Ni , Yi Ye , Cao Wen , Fu Xiao , Mei Nan , Li Chunli
Published: August 2022

Background

At present, immunotherapy has become an important treatment for lung cancer. With the widespread use of immune checkpoint inhibitors (ICIs), we must be strict with the emergence of immune related adverse events (irAEs). There are also some patients who do not respond to immunotherapy. However, there was no biomarkers to predict the safety and efficacy of immunotherapy. The selection of immunotherapy beneficiaries contributes to improving the efficacy and safety of lung cancer treatment.

Method

The electronic medical records of 221 lung cancer patients with complete clinical data who received immunotherapy from the First Affiliated Hospital of Xi ‘an Jiaotong University from November 2020 to October 2021 were collected and followed up. IBM SPSS Statistic 26.0 and R 4.1.2 software were used for statistical analysis and mapping.

Results

1. A total of 221 lung cancer patients receiving immunotherapy were included in the study. Higher baseline levels of IL-1β (7.88 vs 16.16pg/mL,P=0.041) and IL-2 (1.28 vs 2.48pg/mL,P=0.001) were significantly associated with irAEs. Higher levels of IL-5 (2.64 vs 5.68pg/mL,P=0.013), IFN-α (1.70 vs 3.56pg/mL,P=0.004) and IFN-γ (6.14 vs 21.31pg/mL,P=0.022) after the first cycle therapy were associated with irAEs. There was no statistical significance between cytokines and irAEs after the second cycle therapy. Higher IL-5 levels in peripheral blood (9.50 vs 3.57pg/mL,P=0.032) were associated with the occurrence of irAEs after the third cycle therapy. 2.The efficacy of immunotherapy was assessed in 142 lung cancer patients. There was no statistical significance between baseline cytokine levels and clinical benefit. After the first cycle therapy, the level of serum cytokines had no statistical significance with the occurrence of immunotherapy clinical benefit. Lower serum levels of IL-10 (2.66 vs 1.26pg/mL,P=0.016) and IL-17 (8.47 vs 2.81pg/mL, P=0.015) were associated with clinical benefit after the second cycle therapy. Lower serum levels of IL-6 (10.19 vs 41.07pg/mL,P=0.013) and IL-8 (8.01 vs 17.22pg/mL,P=0.039) were associated with clinical benefit of immunotherapy after the third cycle therapy.

Conclusion

1. Baseline IL-1β and IL-2 levels in peripheral blood were associated with the occurrence of irAEs in lung cancer patients. The levels of IL-5, IFN-α and IFN-γ during treatment were associated with irAEs. 2. Baseline cytokine levels in peripheral blood were not associated with immunotherapy efficacy. The levels of IL-6, IL-8, IL-10, and IL-17 levels during treatment were associated with immunotherapy efficacy.
National prevalence of IC/BPS in women and men utilizing veterans health administration data
Authors: Anger Jennifer T. , Dallas Kai B. , Bresee Catherine , De Hoedt Amanda M. , Barbour Kamil E. , Hoggatt Katherine J. , Goodman Marc T. , Kim Jayoung , Freedland Stephen J.
Published: August 2022

Importance

Interstitial cystitis/bladder pain syndrome (IC/BPS) is an immense burden to both patients and the American healthcare system; it is notoriously difficult to diagnose. Prevalence estimates vary widely (150-fold range in women and >500-fold range in men).

Objectives

We aimed to create accurate national IC/BPS prevalence estimates by employing a novel methodology combining a national population-based dataset with individual chart abstraction.

Study design

In this epidemiological survey, all living patients, with ≥2 clinic visits from 2016 to 2018 in the Veterans Health Administration, with an ICD-9/10 code for IC/BPS (n = 9,503) or similar conditions that may represent undiagnosed IC/BPS (n = 124,331), were identified (other were controls n = 5,069,695). A detailed chart review of random gender-balanced samples confirmed the true presence of IC/PBS, which were then age- and gender-matched to the general US population.

Results

Of the 5,203,529 patients identified, IC/BPS was confirmed in 541 of 1,647 sampled charts with an IC/BPS ICD code, 10 of 382 charts with an ICD-like code, and 3 of 916 controls. After age- and gender-matching to the general US population, this translated to national prevalence estimates of 0.87% (95% CI: 0.32, 1.42), with female and male prevalence of 1.08% (95% CI: 0.03, 2.13) and 0.66% (95% CI: 0.44, 0.87), respectively.

Conclusions

We estimate the prevalence of IC/BPS to be 0.87%, which is lower than prior estimates based on survey data, but higher than prior estimates based on administrative data. These potentially represent the most accurate estimates to date, given the broader and more heterogeneous population studied and our novel methodology of combining in-depth chart abstraction with administrative data.
Craniofacial development in patients of Tessier No.0 cleft with a bifid nose using 3D computed tomography
Authors: Wang Xin , Wang Huan , You Jianjun , Zheng Ruobing , Xu Yihao , Fan Fei
Published: August 2022

Objective

Considerable studies have focused mainly on the facial deformity of Tessier No.0 cleft with a bifid nose, but the deformity of the skull is not well understood. Therefore, our study aimed to explore the evolution of cranial dysmorphology and the chronology of Tessier No.0 cleft with a bifid nose, by three-dimensional measurements.

Methods

Ninety-six non-surgical patients and computed tomographic scans were included (Tessier No.0 cleft with a bifid nose, n = 48; controls, n = 48) and divided into five age subgroups. Craniofacial cephalometric measurements were analyzed by Mimics software.

Results

The widening of nasal bone was the most remarkable and persistent from 2 years old appropriately. The overall cranial base length in patients compared with controls increased 11.8% (p < 0.01) on average. The middle and posterior cranial fossa increasing accounted for most of this change. The cranial base angles also showed increased obviously. By analyzing the linear of the nasopharynx and respiratory tract, it was found that its development did not affect respiration.

Conclusions

The cranial base deformity of Tessier No.0 cleft with a bifid nose consists of the whole skull base and particularly the middle and posterior cranial base length increase. At the same time, there may be late closure of the spheno-occipital synchondrosis and sella displacement. We believe this study is unique in providing valuable data for elucidating the pathological and morphological abnormalities of skull base development in Tessier No.0 cleft with a bifid nose.
Disulfiram in glioma: Literature review of drug repurposing
Authors: Zhong Shiyu , Shengyu Liu  , Xin Shi  , Zhang Xudong , Li Kunhang , Liu Guojun , Li Lishuai , Tao Shanwei , Zheng Bowen , Sheng Weichen , Ye Ziyin , Xing Qichen , Zhai Qingqing , Ren Lijie , Wu Ying , Bao Yijun
Published: August 2022

Gliomas are the most common malignant brain tumors. High-grade gliomas, represented by glioblastoma multiforme (GBM), have a poor prognosis and are prone to recurrence. The standard treatment strategy is tumor removal combined with radiotherapy and chemotherapy, such as temozolomide (TMZ). However, even after conventional treatment, they still have a high recurrence rate, resulting in an increasing demand for effective anti-glioma drugs. Drug repurposing is a method of reusing drugs that have already been widely approved for new indication. It has the advantages of reduced research cost, safety, and increased efficiency. Disulfiram (DSF), originally approved for alcohol dependence, has been repurposed for adjuvant chemotherapy in glioma. This article reviews the drug repurposing method and the progress of research on disulfiram reuse for glioma treatment.
The efficacy and safety of JAK inhibitors for alopecia areata: A systematic review and meta-analysis of prospective studies
Authors: Yan Diqin , Fan Huaying , Chen Min , Xia Lin , Wang Simin , Dong Wenliang , Wang Qian , Niu Suping , Rao Huiying , Chen Liming , Nie Xiaoyan , Fang Yi
Published: August 2022

Background: Due to the lack of comprehensive evidence based on prospective studies, the efficacy and safety of Janus Kinase (JAK) inhibitors (including tofacitinib, ruxolitinib, baricitinib, ritlecitinib and brepocitinib) for alopecia areata (AA) are yet to be proved.

Methods: The systematic review and meta-analysis was performed pursuant to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline and registered on PROSPERO (CRD42022303007).

Results: Fourteen prospective studies (5 RCTs and 9 non-RCTs), enrolling a total of 1845 patients with AA, were included for quantitative analysis. In RCTs, oral JAK inhibitors resulted in higher good response rate compared with control (RR: 6.86, 95% CI: 2.91–16.16); topical JAK inhibitors did not show any difference compared with control (RR: 1.00, 95% CI: 0.31–3.18). In non-RCTs, the pooled rate of good response to oral, topical and sublingual JAK inhibitors were 63% (95% CI: 44%–80%), 28% (95% CI: 1%–72%) and 11% (95% CI: 1%–29%), respectively. The pooled recurrence rate in patients treated with JAK inhibitors was 54% (95% CI: 39%–69%), mainly due to the withdrawal of JAK inhibitors. In RCTs, no difference was found in the risk of experiencing most kind of adverse events; in non-RCTs, the reported adverse events with high incidence rate were mostly mild and manageable.

Conclusion: JAK inhibitors are efficacious and generally well-tolerated in treating AA with oral administration, whereas topical or sublingual administration lacks efficacy. Subgroup analyses indicate that baricitinib, ritlecitinib and brepocitinib seem to have equal efficacy for AA in RCTs; ruxolitinib (vs. tofacitinib) and AA (vs. AT/AU) are associated with better efficacy outcomes in non-RCT. Due to the high recurrence rate after withdrawal of JAK inhibitors, continuous treatment should be considered to maintain efficacy.

Systematic Review Registration: PROSPERO: CRD 42022303007
An improved voterank algorithm to identifying a set of influential spreaders in complex networks
Authors: Li Yaxiong , Yang Xinzhi , Zhang Xinwei , Xi Mingyuan , Lai Xiaochang
Published: August 2022

Identifying a set of critical nodes with high propagation in complex networks to achieve maximum influence is an important task in the field of complex network research, especially in the background of the current rapid global spread of COVID-19. In view of this, some scholars believe that nodes with high importance in the network have stronger propagation, and many classical methods are proposed to evaluate node importance. However, this approach makes it difficult to ensure that the selected spreaders are dispersed in the network, which greatly affects the propagation ability. The VoteRank algorithm uses a voting-based method to identify nodes with strong propagation in the network, but there are some deficiencies. Here, we solve this problem by proposing the DILVoteRank algorithm. The VoteRank algorithm cannot properly reflect the importance of nodes in the network topology. Based on this, we redefine the initial voting ability of nodes in the VoteRank algorithm and introduce the degree and importance of the line (DIL) ranking method to calculate the voting score so that the algorithm can better reflect the importance of nodes in the network structure. In addition, the weakening mechanism of the VoteRank algorithm only weakens the information of neighboring nodes of the selected nodes, which does not guarantee that the identified initial spreaders are sufficiently dispersed in the network. On this basis, we consider all the neighbors nodes of the node’s nearest and next nearest neighbors, so that the crucial spreaders identified by our algorithm are more widely distributed in the network with the same initial node ratio. In order to test the algorithm performance, we simulate the DILVoteRank algorithm with six other benchmark algorithms in 12 real-world network datasets based on two propagation dynamics model. The experimental results show that our algorithm identifies spreaders that achieve stronger propagation ability and propagation scale and with more stability compared to other benchmark algorithms.
Associations among sleep, hematologic profile, and aerobic and anerobic capacity of young swimmers: A complex network approach
Authors: Kraemer Mauricio Beitia , Garbuio Ana Luíza Paula , Kaneko Luisa Oliveira , Gobatto Claudio Alexandre , Manchado-Gobatto Fúlvia Barros , dos Reis Ivan Gustavo Masseli , Messias Leonardo Henrique Dalcheco
Published: August 2022

Although the link between sleep and hematological parameters is well-described, it is unclear how this integration affects the swimmer’s performance. The parameters derived from the non-invasive critical velocity protocol have been extensively used to evaluate these athletes, especially the aerobic capacity (critical velocity—CV) and the anaerobic work capacity (AWC). Thus, this study applied the complex network model to verify the influence of sleep and hematological variables on the CV and AWC of young swimmers. Thirty-eight swimmers (male, n = 20; female, n = 18) completed five experimental evaluations. Initially, the athletes attended the laboratory facilities for venous blood collection, anthropometric measurements, and application of sleep questionnaires. Over the 4 subsequent days, athletes performed randomized maximal efforts on distances of 100, 200, 400, and 800-m. The aerobic and anerobic parameters were determined by linear function between distance vs. time, where CV relates to the slope of regression and AWC to y-intercept. Weighted but untargeted networks were generated based on significant (p < 0.05) correlations among variables regardless of the correlation coefficient. Betweenness and eigenvector metrics were used to highlight the more important nodes inside the complex network. Regardless of the centrality metric, basophils and red blood cells appeared as influential nodes in the networks with AWC or CV as targets. The role of other hematologic components was also revealed in these metrics, along with sleep total time. Overall, these results trigger new discussion on the influence of sleep and hematologic profile on the swimmer’s performance, and the relationships presented by this targeted complex network can be an important tool throughout the athlete’s development.
Computational models of ventricular mechanics and adaptation in response to right-ventricular pressure overload
Authors: Odeigah Oscar O. , Valdez-Jasso Daniela , Wall Samuel T. , Sundnes Joakim
Published: August 2022

Pulmonary arterial hypertension (PAH) is associated with substantial remodeling of the right ventricle (RV), which may at first be compensatory but at a later stage becomes detrimental to RV function and patient survival. Unlike the left ventricle (LV), the RV remains understudied, and with its thin-walled crescent shape, it is often modeled simply as an appendage of the LV. Furthermore, PAH diagnosis is challenging because it often leaves the LV and systemic circulation largely unaffected. Several treatment strategies such as atrial septostomy, right ventricular assist devices (RVADs) or RV resynchronization therapy have been shown to improve RV function and the quality of life in patients with PAH. However, evidence of their long-term efficacy is limited and lung transplantation is still the most effective and curative treatment option. As such, the clinical need for improved diagnosis and treatment of PAH drives a strong need for increased understanding of drivers and mechanisms of RV growth and remodeling (G&R), and more generally for targeted research into RV mechanics pathology. Computational models stand out as a valuable supplement to experimental research, offering detailed analysis of the drivers and consequences of G&R, as well as a virtual test bench for exploring and refining hypotheses of growth mechanisms. In this review we summarize the current efforts towards understanding RV G&R processes using computational approaches such as reduced-order models, three dimensional (3D) finite element (FE) models, and G&R models. In addition to an overview of the relevant literature of RV computational models, we discuss how the models have contributed to increased scientific understanding and to potential clinical treatment of PAH patients.
Transcriptome analysis revealed the expression levels of genes related to abscisic acid and auxin biosynthesis in grapevine (Vitis vinifera L.) under root restriction
Authors: Wang Lei , Li Hui , Li Jiajia , Li Guanhan , Zahid Muhammad Salman , Li Dongmei , Ma Chao , Xu Wenping , Song Shiren , Li Xiangyi , Wang Shiping
Published: August 2022

The root system is essential for the stable growth of plants. Roots help anchor plants in the soil and play a crucial role in water uptake, mineral nutrient absorption and endogenous phytohormone formation. Root-restriction (RR) cultivation, a powerful technique, confines plant roots to a specific soil space. In the present study, roots of one-year-old “Muscat Hamburg” grapevine under RR and control (nR) treatments harvested at 70 and 125 days after planting were used for transcriptome sequencing, and in total, 2031 (nR7 vs. nR12), 1445 (RR7 vs. RR12), 1532 (nR7 vs. RR7), and 2799 (nR12 vs. RR12) differentially expressed genes (DEGs) were identified. Gene Ontology (GO) enrichment analysis demonstrated that there were several genes involved in the response to different phytohormones, including abscisic acid (ABA), auxin (IAA), ethylene (ETH), gibberellins (GAs), and cytokinins (CTKs). Among them, multiple genes, such as PIN2 and ERF113, are involved in regulating vital plant movements by various phytohormone pathways. Moreover, following RR cultivation, DEGs were enriched in the biological processes of plant-type secondary cell wall biosynthesis, the defense response, programmed cell death involved in cell development, and the oxalate metabolic process. Furthermore, through a combined analysis of the transcriptome and previously published microRNA (miRNA) sequencing results, we found that multiple differentially expressed miRNAs (DEMs) and DEG combinations in different comparison groups exhibited opposite trends, indicating that the expression levels of miRNAs and their target genes were negatively correlated. Furthermore, RR treatment indeed significantly increased the ABA content at 125 days after planting and significantly decreased the IAA content at 70 days after planting. Under RR cultivation, most ABA biosynthesis-related genes were upregulated, while most IAA biosynthesis-related genes were downregulated. These findings lay a solid foundation for further establishing the network through which miRNAs regulate grapevine root development through target genes and for further exploring the molecular mechanism through which endogenous ABA and IAA regulate root architecture development in grapevine.
Ca2+ mediates transcription factor PuDof2.5 and suppresses stone cell production in pear fruits
Authors: Zhang He , Gao Siyang , Wang Tianye , Xu Mingyang , Li Xinyue , Du Guodong
Published: August 2022

Stone cells are sclerenchyma cells formed by deposition of lignin, which is the most significant factor limiting the quality of pears. Ca2+ was known to inhibit stone cells in pear fruits, but the underlying molecular mechanism remains unclear. Our study revealed that exogenous CaCl2 (Ca2+) treatment of “Nanguo” pear (Pyrus ussuriensis) suppressed the synthesis of lignin and stone cell production. We further analysed the transcriptomes using RNA-seq, identified a transcription factor, PuDof2.5, and its targets gene PuPRX42-like (lignin polymerase gene) expression decreased in CaCl2-treated samples, which are involved in suppressing lignin biosynthesis in pear fruit. PuDof2.5 was found to bind directly to the PuPRX42-like promoter and induced its transcription. Taken together, our results revealed that Ca2+ modulated the key lignin biosynthetic transcription factor PuDof2.5 to suppress stone cell production in pear fruits.
Relationship between emotion regulation strategies and total conviction in promoting behavior change
Authors: Shigematsu Jun , Kobayashi Ryota
Published: August 2022

Research conducted in the recent past have proposed total conviction as a factor associated with cognitive reappraisal that may produce changes in emotion and behavior. However, the factors that influence total conviction are not yet clearly identified. In this study, we focused on daily emotion regulation strategies and examined the relationship between emotion regulation strategies and total conviction. A total of 42 undergraduate and graduate students participated in this study. They measured their tendency toward daily emotion regulation strategies and then engaged in the cold pressor task (CPT) which is a distress tolerance task. Participants were then presented with information that encouraged them to engage in the task while enduring distress, creating a context for cognitive reappraisal of the task. Thereafter, they engaged in a second CPT. Finally, the degree of total conviction to the information that prompted reappraisal was measured. The results showed that total conviction in the experimental situation predicted behavior change. We found that the tendency to use routine cognitive reappraisal was not associated with total conviction, while the tendency to use expressive suppression would have a negative effect on total conviction. Furthermore, the expressive suppression tendency was found to moderate the relationship between total conviction and behavior change. These results indicate that the occurrence of total conviction in cognitive reappraisal leads to behavior change, though the tendency toward daily cognitive reappraisal is not related to the occurrence of total conviction in the experimental setting. The results also suggest that daily expressive suppression inhibits total conviction, particularly in situations where cognitive reappraisal is required.