bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling of pulmonary deposition of agents of open and fixed dose triple combination therapies through two different low-resistance inhalers in COPD: a pilot study
Authors: Erdelyi Tamas , Lazar Zsofia , Farkas Árpád , Furi Peter , Nagy Attila , Müller Veronika 
Published: May 2023

IntroductionInhalation therapy is a cornerstone of treating patients with chronic obstructive pulmonary disease (COPD). Inhaler devices might influence the effectiveness of inhalation therapy. We aimed to model and compare the deposition of acting agents of an open and a fixed dose combination (FDC) triple therapy and examine their repeatability.MethodsWe recruited control subjects (Controls, n = 17) and patients with stable COPD (S-COPD, n = 13) and those during an acute exacerbation (AE-COPD, n = 12). Standard spirometry was followed by through-device inhalation maneuvers using a pressurized metered dose inhaler (pMDI) and a soft mist inhaler (SMI) to calculate deposition of fixed dose and open triple combination therapies by numerical modeling. Through-device inspiratory vital capacity (IVCd) and peak inspiratory flow (PIFd), as well as inhalation time (tin) and breath hold time (tbh) were used to calculate pulmonary (PD) and extrathoracic deposition (ETD) values. Deposition was calculated from two different inhalation maneuvers.ResultsThere was no difference in forced expiratory volume in 1 s (FEV1) between patients (S-COPD: 42 ± 5% vs. AE-COPD: 35 ± 5% predicted). Spiriva® Respimat® showed significantly higher PD and lower ETD values in all COPD patients and Controls compared with the two pMDIs. For Foster® pMDI and Trimbow® pMDI similar PD were observed in Controls, while ETD between Controls and AE-COPD patients did significantly differ. There was no difference between COPD groups regarding the repeatability of calculated deposition values. Ranking the different inhalers by differences between the two deposition values calculated from separate maneuvers, Respimat® produced the smallest inter-measurement differences for PD.DiscussionOur study is the first to model and compare PD using pMDIs and an SMI as triple combination in COPD. In conclusion, switching from FDC to open triple therapy in cases when adherence to devices is maintanined may contribute to better therapeutic effectiveness in individual cases using low resistance inhalers.
Thoracic pain in patients with chronic interstitial lung disease—an underestimated symptom
Authors: Scherer Manuela J. , Kampe Sandra , Fredebeul-Beverungen Jonas , Weinreich Gerhard , Costabel Ulrich , Bonella Francesco 
Published: May 2023

IntroductionPrevalence and predisposing factors for the development of thoracic pain (TP) in patients with chronic interstitial lung disease (cILD) are largely unknown. Underestimation and insufficient therapy of pain can lead to worsened ventilatory function. Quantitative sensory testing is an established tool for characterization of chronic pain and its neuropathic components. We investigated frequency and intensity of TP in cILD patients and the potential association with lung function and quality of life.Materials and methodsWe prospectively investigated patients with chronic interstitial lung disease to analyze risk factors for the development of thoracic pain and quantify thoracic pain through quantitative sensory testing. In addition, we studied the relationship between pain sensitivity and lung function impairment.ResultsSeventy-eight patients with chronic interstitial lung disease and 36 healthy controls (HCs) were included. Thoracic pain occurred in 38 of 78 patients (49%), most frequently in 13 of 18 (72%, p = 0.02) patients with pulmonary sarcoidosis. The occurrence was mostly spontaneous and not related to thoracic surgical interventions (76%, p = 0.48). Patients with thoracic pain showed a significant impairment of mental well-being (p = 0.004). A higher sensitivity to pinprick stimulation during QST can be observed in patients with thoracic pain (p &lt; 0.001). Steroid treatment was associated with lower sensitivity within thermal (p = 0.034 and p = 0.032) and pressure pain testing (p = 0.046). We observed a significant correlation between total lung capacity and thermal (p = 0.019 and p = 0.03) or pressure pain sensitivity (p = 0.006 and p = 0.024).ConclusionThis study was performed to investigate prevalence, risk factors and thoracic pain in patients with chronic interstitial lung disease. Thoracic pain mostly occurs spontaneous as a frequent symptom, and seems to be an underestimated symptom in patients with chronic interstitial lung disease, especially those with pulmonary sarcoidosis. Timely identification of thoracic pain may allow starting symptomatic treatment at early stage, before impairment in quality of life occurs.Clinical Trial Registrationhttps://www.drks.de/drks_web/, Deutsches Register Klinischer Studien (DRKS) DRKS00022978.
Rare variant burden analysis from exomes of three consanguineous families reveals LILRB1 and PRSS3 as potential key proteins in inflammatory bowel disease pathogenesis
Authors: Jan Rana Mohammed , Al-Numan Huda Husain , Al-Twaty Nada Hassan , Alrayes Nuha , Alsufyani Hadeel A. , Alaifan Meshari A. , Alhussaini Bakr H. , Shaik Noor Ahmad , Awan Zuhier , Qari Yousef , Saadah Omar I. , Banaganapalli Babajan , Mosli Mahmoud Hisham , Elango Ramu 
Published: May 2023

BackgroundInflammatory bowel disease (IBD) is a chronic autoimmune disorder characterized by severe inflammation and mucosal destruction of the intestine. The specific, complex molecular processes underlying IBD pathogenesis are not well understood. Therefore, this study is aimed at identifying and uncovering the role of key genetic factors in IBD.MethodThe whole exome sequences (WESs) of three consanguineous Saudi families having many siblings with IBD were analyzed to discover the causal genetic defect. Then, we used a combination of artificial intelligence approaches, such as functional enrichment analysis using immune pathways and a set of computational functional validation tools for gene expression, immune cell expression analyses, phenotype aggregation, and the system biology of innate immunity, to highlight potential IBD genes that play an important role in its pathobiology.ResultsOur findings have shown a causal group of extremely rare variants in the LILRB1 (Q53L, Y99N, W351G, D365A, and Q376H) and PRSS3 (F4L and V25I) genes in IBD-affected siblings. Findings from amino acids in conserved domains, tertiary-level structural deviations, and stability analysis have confirmed that these variants have a negative impact on structural features in the corresponding proteins. Intensive computational structural analysis shows that both genes have very high expression in the gastrointestinal tract and immune organs and are involved in a variety of innate immune system pathways. Since the innate immune system detects microbial infections, any defect in this system could lead to immune functional impairment contributing to IBD.ConclusionThe present study proposes a novel strategy for unraveling the complex genetic architecture of IBD by integrating WES data of familial cases, with computational analysis.
Characterization and genomic analysis of phage vB_ValR_NF, representing a new viral family prevalent in the Ulva prolifera blooms
Authors: Zhang Xinran , Liang Yantao , Zheng Kaiyang , Wang Ziyue , Dong Yue , Liu Yundan , Ren Linyi , Wang Hongmin , Han Ying , McMinn Andrew , Sung Yeong Yik , Mok Wen Jye , Wong Li Lian , He Jianfeng , Wang Min 
Published: May 2023

IntroductionVibrio is an important bacterial genus containing many pathogenic species. Although more and more Vibrio phages were isolated, the genome, ecology and evolution of Vibrio phages and their roles in bacteriophage therapy, have not been fully revealed.MethodsNovel Vibrio phage vB_ValR_NF infecting Vibrio alginolyticus was isolated from the coastal waters of Qingdao during the Ulva prolifera blooms, Characterization and genomic feature of phage vB_ValR_NF has been analysed using phage isolation, sequencing and metagenome method.Results and DiscussionPhage vB_ValR_NF has a siphoviral morphology (icosahedral head 114±1 nm in diameter; a tail length of 231±1 nm), a short latent period (30 minutes) and a large burst size (113 virions per cell), and the thermal/pH stability study showed that phage vB_ValR_NF was highly tolerant to a range of pHs (4-12) and temperatures (-20 - 45 °C), respectively. Host range analysis suggests that phage vB_ValR_NF not only has a high inhibitory ability against the host strain V. alginolyticus, but also can infect 7 other Vibrio strains. In addition, the phage vB_ValR_NF has a double-stranded 44, 507 bp DNA genome, with 43.10 % GC content and 75 open reading frames. Three auxiliary metabolic genes associated with aldehyde dehydrogenase, serine/threonine protein phosphatase and calcineurin-like phosphoesterase were predicted, might help the host V. alginolyticus occupy the survival advantage, thus improving the survival chance of phage vB_ValR_NF under harsh conditions. This point can be supported by the higher abundance of phage vB_ValR_NF during the U. prolifera blooms than in other marine environments. Further phylogenetic and genomic analysis shows that the viral group represented by Vibrio phage vB_ValR_NF is different from other well-defined reference viruses, and can be classified into a new family, named Ruirongviridae. In general, as a new marine phage infecting V. alginolyticus, phage vB_ValR_NF provides basic information for further molecular research on phage–host interactions and evolution, and may unravel a novel insight into changes in the community structure of organisms during the U. prolifera blooms. At the same time, its high tolerance to extreme conditions and excellent bactericidal ability will become important reference factors when evaluating the potential of phage vB_ValR_NF in bacteriophage therapy in the future.
Odor exploration behavior of the domestic pig (Sus scrofa) as indicator of enriching properties of odors
Authors: Rørvang Maria Vilain , Schild Sarah-Lina Aagaard , Stenfelt Johanna , Grut Rebecca , Gadri Moses A. , Valros Anna , Nielsen Birte L. , Wallenbeck Anna 
Published: May 2023

Introduction and aimAlthough the sense of smell in pigs is widely recognized as being highly developed, surprisingly little is known about their sensory ability. This study aimed to (a) identify which non-social odors pigs were able to detect and distinguish between, (b) investigate the types of behavior expressed when exploring odors and, (c) compare pigs’ responses to the different odors to evaluate their interest in the odors.MethodsGrowing pigs (N = 192) of crossbred commercial breeds were enrolled in the experiment (32–110 days of age, weighing 64.9 ± 10.1kg). Littermate pairs of opposite sex were tested in test pens with two odor insertion points in the pen wall, 55 cm apart. All pigs were habituated to the test pens and experimenters. Twelve odors were tested (eight essential oils and four synthetic perfumes) in groups of three odors, with each pig pair tested once with one set of three odors (all possible orders of the three odors were tested on 24 pairs in total), always against a non-odor control (demineralized water). In a test, each of the three odors were presented during three trials in a row (a total of 9 trials per test; trial duration: 1 min; inter-trial breaks: 2 min; total test duration: 25 min). Response variables included: duration of sniffing, feeding-related behavior (licking, biting and rooting), agonistic behavior (biting, displacement and pushing) and no approach of the odor or control, recorded throughout each 1-min odor presentation.ResultsAll pigs sniffed an odor less when repeatedly presented (LMM: all odors P &lt; 0.05), and significantly longer at the subsequent presentation of a new odor [LMM (3rd vs. 1st presentations): P &lt; 0.001]. Specific odor and odor type (essential oil vs. synthetic perfume) had no significant effect on sniffing duration. Overall, feeding-related behavior and agonistic behavior were expressed significantly more when pigs explored the odor compared with the control insertion point (Paired t-tests: P &lt; 0.001), and specific odor only affected the expression of feeding-related behavior.ConclusionCollectively, pigs express sniffing, agonistic, and feeding-related behavior when exploring odors, which suggests that pigs perceive odors of non-social origin as a resource. Odors may thus constitute relevant enrichment material for pigs.
Whole exome/genome sequencing in cyclic vomiting syndrome reveals multiple candidate genes, suggesting a model of elevated intracellular cations and mitochondrial dysfunction
Authors: Bar Omri , Ebenau Laurie , Weiner Kellee , Mintz Mark , Boles Richard G. 
Published: May 2023

ObjectiveTo utilize whole exome or genome sequencing and the scientific literature for identifying candidate genes for cyclic vomiting syndrome (CVS), an idiopathic migraine variant with paroxysmal nausea and vomiting.MethodsA retrospective chart review of 80 unrelated participants, ascertained by a quaternary care CVS specialist, was conducted. Genes associated with paroxysmal symptoms were identified querying the literature for genes associated with dominant cases of intermittent vomiting or both discomfort and disability; among which the raw genetic sequence was reviewed. “Qualifying” variants were defined as coding, rare, and conserved. Additionally, “Key Qualifying” variants were Pathogenic/Likely Pathogenic, or “Clinical” based upon the presence of a corresponding diagnosis. Candidate association to CVS was based on a point system.ResultsThirty-five paroxysmal genes were identified per the literature review. Among these, 12 genes were scored as “Highly likely” (SCN4A, CACNA1A, CACNA1S, RYR2, TRAP1, MEFV) or “Likely” (SCN9A, TNFRSF1A, POLG, SCN10A, POGZ, TRPA1) CVS related. Nine additional genes (OTC, ATP1A3, ATP1A2, GFAP, SLC2A1, TUBB3, PPM1D, CHAMP1, HMBS) had sufficient evidence in the literature but not from our study participants. Candidate status for mitochondrial DNA was confirmed by the literature and our study data. Among the above-listed 22 CVS candidate genes, a Key Qualifying variant was identified in 31/80 (34%), and any Qualifying variant was present in 61/80 (76%) of participants. These findings were highly statistically significant (p &lt; 0.0001, p = 0.004, respectively) compared to an alternative hypothesis/control group regarding brain neurotransmitter receptor genes. Additional, post-analyses, less-intensive review of all genes (exome) outside our paroxysmal genes identified 13 additional genes as “Possibly” CVS related.ConclusionAll 22 CVS candidate genes are associated with either cation transport or energy metabolism (14 directly, 8 indirectly). Our findings suggest a cellular model in which aberrant ion gradients lead to mitochondrial dysfunction, or vice versa, in a pathogenic vicious cycle of cellular hyperexcitability. Among the non-paroxysmal genes identified, 5 are known causes of peripheral neuropathy. Our model is consistent with multiple current hypotheses of CVS.
Clinical and genetic analysis of Christianson syndrome caused by variant of SLC9A6: case report and literature review
Authors: Dong Yan , Lian Ruofei , Jin Liang , Zhao Shichao , Tao Wenpeng , Wang Lijun , Li Mengchun , Jia Tianming , Chen Xuejing , Cao Shushi 
Published: May 2023

BackgroundIntellectual disability, X-linked, syndromic, Christianson type (MRXSCH, OMIM: 300243)—known as Christianson syndrome (CS)—is characterized by microcephaly, epilepsy, ataxia, and absence of verbal language ability. CS is attributed to mutations in the solute carrier family 9 member A6 gene (SLC9A6).Materials and methodsThis study reports the case of a boy 1 year and 3 months of age who was diagnosed with CS in our department. Genetic etiology was determined by whole-exome sequencing, and a minigene splicing assay was used to verify whether the mutation affected splicing. A literature review of CS cases was conducted and the clinical and genetic features were summarized.ResultsThe main clinical manifestations of CS include seizures, developmental regression, and exceptional facial features. Whole-exome sequencing revealed a de novo splice variant in intron 11 (c.1366 + 1G &gt; C) of SLC9A6. The mutation produced two abnormal mRNA products (verified by a minigene splicing assay), resulting in the formation of truncated protein. A total of 95 CS cases were identified in the literature, with various symptoms, such as delayed intellectual development (95/95, 100.00%), epilepsy (87/88, 98.86%), and absent verbal language (75/83, 90.36%). At least 50 pathogenic variants of SLC9A6 have been identified, with the highest frequency observed in exon 12.ConclusionOur patient is the first case with the c.1366 + 1G &gt; C variant of SLC9A6 in CS. The summary of known cases can serve as a reference for analyzing the mutation spectrum and pathogenesis of CS.
Topological abnormality of structural covariance network in MRI-negative frontal lobe epilepsy
Authors: Liu Yin , Li Quanji , Yi Dali , Duan Junhong , Zhang Qingxia , Huang Yunchen , He Haibo , Liao Yunjie , Song Zhi , Deng Lingling , Wang Wei , Liu Ding 
Published: May 2023

BackgroundFrontal lobe epilepsy (FLE) is the second most common type of focal epilepsy, however, imaging studies of FLE have been far less than Temporal lobe epilepsy (TLE) and the structural findings were not consistent in previous literature.ObjectInvestigate the changes in cortical thickness in patients with FLE and the alteration of the structural covariance networks (SCNs) of cortical thickness with graph-theory.MethodThirty patients with FLE (18 males/12 females; 28.33 ± 11.81 years) and 27 demographically matched controls (15 males/12 females; 29.22 ± 9.73 years) were included in this study with high-resolution structural brain MRI scans. The cortical thickness was calculated, and structural covariance network (SCN) of cortical thickness were reconstructed using 68 × 68 matrix and analyzed with graph-theory approach.ResultCortical thickness was not significantly different between two groups, but path length and node betweenness were significantly increased in patients with FLE, and the regional network alterations were significantly changed in right precentral gyrus and right temporal pole (FDR corrected,p &lt; 0.05). Comparing to HC group, network hubs were decreased and shifted away from frontal lobe.ConclusionThe topological properties of cortical thickness covariance network were significantly altered in patients with FLE, even without obvious surface-based morphological damage. Graph-theory based SCN analysis may provide sensitive neuroanatomical biomarkers for FLE.
Three-dimensional aneurysm wall enhancement in fusiform intracranial aneurysms is associated with aneurysmal symptoms
Authors: Chen Xuge , Peng Fei , Liu Xinmin , Xia Jiaxiang , Niu Hao , He Xiaoxin , Xu Boya , Bai Xiaoyan , Li Zhiye , Xu Peng , Duan Yonghong , Sui Binbin , Zhao Xingquan , Liu Aihua 
Published: May 2023

Background and purposeAneurysm wall enhancement (AWE) in high-resolution magnetic resonance imaging (HR-MRI) is a potential biomarker for evaluating unstable aneurysms. Fusiform intracranial aneurysms (FIAs) frequently have a complex and curved structure. We aimed to develop a new three-dimensional (3D) aneurysmal wall enhancement (AWE) characterization method to enable comprehensive FIA evaluation and to investigate the ability of 3D-AWE to predict symptomatic FIA.MethodsWe prospectively recruited patients with unruptured FIAs and received 3 T HR-MRI imaging from September 2017 to January 2019. 3D models of aneurysms and parent arteries were generated. Boundaries of the FIA were determined using 3D vessel diameter measurements. Dmax was the greatest diameter in the cross-section, while Lmax was the length of the centerline of the aneurysm. Signal intensity of the FIA was normalized to the pituitary stalk and then mapped onto the 3D model, then the average enhancement (3D-AWEavg), maximum enhancement (3D-AWEmax), enhancement area (AWEarea), and enhancement ratio (AWEratio) were calculated as AWE indicators, and the surface area of the entire aneurysm (Aarea) was also calculated. Areas with high AWE were defined as those with a value &gt;0.9 times the signal intensity of the pituitary stalk. Multivariable logistic regression analyses were performed to determine independent predictors of aneurysm-related symptoms. FIA subtypes were defined as fusiform, dolichoectasia, and transitional. Differences between the three FIA subtypes were also examined.ResultsForty-seven patients with 47 FIAs were included. Mean patient age was 55 ± 12.62 years and 74.5% were male. Twenty-nine patients (38.3%) were symptomatic. After adjusting for baseline differences in age, hypertension, Lmax, and FIA subtype, the multivariate logistics regression models showed that 3D-AWEavg (odds ratio [OR], 4.029; p = 0.019), 3D-AWEmax (OR, 3.437; p = 0.022), AWEarea (OR, 1.019; p = 0.008), and AWEratio (OR, 2.490; p = 0.045) were independent predictors of aneurysm-related symptoms. Dmax and Aarea were larger and 3D-AWEavg, 3D-AWEmax, AWEarea, and AWEratio were higher with the transitional subtype than the other two subtypes.ConclusionThe new 3D AWE method, which enables the use of numerous new metrics, can predict symptomatic FIAs. Different 3D-AWE between the three FIA subtypes may be helpful in understanding the pathophysiology of FIAs.
Case report of iatrogenic cerebral amyloid angiopathy after exposure to Lyodura: an Australian perspective
Authors: Muller Claire 
Published: May 2023

BackgroundRecently proposed diagnostic criteria for iatrogenic cerebral amyloid angiopathy (iCAA) have sparked increased recognition of cases across the globe. Whilst these patients tend to have a tumultuous course, much like sporadic CAA, there is a high degree of variability. What is unique in this case is the breadth of clinicoradiological data available, including handwritten surgical notes from 1985. In retrospect, early imaging changes of what would ultimately lead to profound morbidity, were apparent 30 years after inoculation with cadaveric dural tissue.AimIn this case study we examine the clinicoradiological features of a case of probable iCAA and draw awareness to the presence of this disease in Australia.MethodsThis case was admitted under the care of the author at the Royal Brisbane and Women's Hospital (RBWH). Clinical details and data were gathered during the patient's care and consent for publication provided by the enduring power of attorney.ResultsThis 56-year-old female presented in 2018 with left hemiparesis, neglect, and dysarthria secondary to a large right frontal lobe intracerebral hemorrhage (ICH) without an underlying macrovascular cause. MRI brain demonstrated diffuse superficial siderosis assumed related to previous surgical interventions during the mid-1980s for a Chiari malformation and cervical syrinx. There was evidence of extensive white matter disease, discordant with her lack of cerebrovascular disease risk factors. Brain biopsy confirmed CAA. Archived surgical notes confirmed exposure to Lyodura in 1985 and 1986. Two decades of MRI data were available for review and illustrate the evolution of CAA, from normal post-operative findings to marked and unrecognized abnormalities 4 years prior to her first ICH.DiscussionThis is the first Australian case of probable iatrogenic CAA (iCAA) to have such extensive documentation of clinicoradiological evolution. It demonstrates the aggressive course iCAA can take and provides insights into early disease manifestations, relevant to the more common sporadic cases. A brief review of the history of commercial cadaveric tissue use in Australia highlights enormous changes in medical practice over the last 50 years. Awareness within Australia should be raised for this clinical phenomenon, and cases collated to contribute to the growing international pool of evidence.