bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Presence of Vacuolated Kupffer Cells Raises a Clinical Suspicion of Niemann-Pick Disease Type C in Neonatal Cholestasis
Authors: Wang Neng-Li , Chen Lian , Lu Yi , Xie Xin-Bao , Lin Jing , Abuduxikuer Kuerbanjiang , Wang Jian-She 
Published: March 2022

Early diagnosis of Niemann-Pick disease type C (NP-C) in neonatal cholestasis is still challenging because splenomegaly is non-specific and oxysterol profiling studies also have a relatively low specificity. This study explores a method for identifying infants with a high clinical suspicion of NP-C in neonatal cholestasis. We reviewed the clinical findings of 9 neonatal cholestatic infants with NP-C genetically diagnosed between January 2015 and December 2020. Seven underwent liver biopsy at ages ranging from 35 to 112 d. Foam cells were only detected in 2 (28.6%, 2/7) liver tissues obtained beyond 3 months of age. However, vacuolated Kupffer cells were detected in all 7 liver tissues. Their significance was explored by using 168 neonatal cholestatic infants, who underwent genetic tests and liver biopsy between January 2018 and December 2020. Of them, 26 detected vacuolated Kupffer cells. Six (23.1%, 6/26) were diagnosed as NP-C, comparing to none of the 142 neonatal cholestatic infants without vacuolated Kupffer cells (χ2 = 33.983, p &lt; 0.001). The ratio of positive diagnosis of NP-C was 31.6% (6/19) in neonatal cholestatic infants with both vacuolated Kupffer cells and splenomegaly. Therefore, we conclude that the presence of vacuolated Kupffer cells can raise a high clinical suspicion of NP-C in neonatal cholestatic infants, especially in those with splenomegaly.
Influence of CYP2D6, CYP3A4 and CYP2C19 Genotypes on Recurrence of Plasmodium vivax
Authors: Cardoso Jaiana L. M. , Salazar Yanka E. A. R. , Almeida Anne C. G. , Barbosa Laila R. A. , Silva Emanuelle L. , Rodrigues Maria Gabriela Almeida , Rodrigues-Soares Fernanda , Sampaio Vanderson S. , Siqueira André M. , Lacerda Marcus V. G. , Monteiro Wuelton M. , Melo Gisely C. 
Published: March 2022

BackgroundThe influence of the CYPs (cytochrome P-450) in the success of antimalarial therapy remains uncertain. In this study, the association of CYP2D6, CYP2C19 and CYP3A4 polymorphisms and predicted phenotypes with malaria recurrence was investigated.MethodsAfter diagnosis of vivax malaria, individuals treated at a reference center in Manaus were followed up for 180 days. Patients were separated into two groups: a recurrence group and a non-recurrence group. Genotyping of CYP2D6, CYP2C19 and CYP3A4 was performed using a TaqMan™ assay and real-time PCR.FindingsThe frequencies of decreased-function and normal-function alleles and phenotypes for all CYPs were similar between the groups, except for the CYP2D6*2xN allele (p=0.047) and the CYP2D6 gUM phenotype (p=0.057), which were more frequent in individuals without recurrence. Despite this, the CYP2D6, CYP2C19 and CYP3A4 genotypes had no association with an increased risk of recurrence. CYPs polymorphisms also had no influence in parasite clearance, neither in the time nor the number of recurrence episodes. MAINConclusionThis prospective cohort study demonstrated that CYP2D6, CYP2C19 and CYP3A4 polymorphisms have no influence on malaria recurrence. Nonetheless, our findings suggest that the CYP2D6 predicted ultrarapid phenotype was less susceptible to recurrence, and that patients with the CYP2D6 gUM phenotype are less susceptible to primaquine failure. Additional investigation of pharmacogenetics and pharmacokinetics are needed before implementing CYP analysis to better orientate individualized radical treatment of vivax malaria in reference centers that treat patients with multiple recurrences.
Polymeric Organo-Hydrogels: Novel Biomaterials for Medical, Pharmaceutical, and Drug Delivery Platforms
Authors: Aktas Nahit , Alpaslan Duygu , Dudu Tuba Erşen 
Published: March 2022

In the recent two decades, tremendous devices and materials such as stents, biomimetic organs, scaffolds, and vessels have been developed for medical purposes. When such devices are utilized in the body, the side effects or biocompatibility of the materials have to be studied extensively. Interdisciplinary studies have reviled numerous strategies to overcome adverse body reactions against implanted devices. Besides naturally occurring materials such as collagen, chitosan, hyaluronic acid, and dextran, various synthetic and modified materials such as poly(lactic acid), poly(ethylene glycol), poly(vinyl alcohol), and poly(acrylamide) have been accomplished. In this context, progress in polymer science makes hydrogels a valuable candidate for those utilizations. Moreover, hydrogels received enormous attention as drug delivery devices because of their unique properties, such as soft structure and responsive capabilities based on the functional group attached. Particularly, the developments in synthetic materials have brought out numerous materials for medical and pharmaceutical applications. In recent studies, organo-hydrogels, a branch of hydrogels, have drawn considerable attention over hydrogels because of superior properties such as the coexistence of organic and aqueous phases and viscoelastic bi-phasic natures. They were prepared in bulk forms and nano-scale dimensions, which allow them to be utilized more extensively. These incredible structures provide them with extensive features to be utilized from head to toe in every aspect of health care application. In this short review, we will focus on some of the pioneering perspectives of organo-hydrogels particularly accomplished in clinical therapy and the use of their biodegradable, target-responsive properties as sensing components in novel microscale apertures.
Effect of Fufang Huangqi Decoction on the Gut Microbiota in Patients With Class I or II Myasthenia Gravis
Authors: Chen Yanghong , Lin Yi , Shan Caifeng , Li Zhaoqing , Xiao Bo , He Rencai , Huang Xueshi , Wang Zhanyou , Zhang Jingsheng , Qiao Wenjun 
Published: March 2022

ObjectiveTo investigate the effect of Fufang Huangqi Decoction on the gut microbiota in patients with class I or II myasthenia gravis (MG) and to explore the correlation between gut microbiota and MG (registration number, ChiCTR2100048367; registration website, http://www.chictr.org.cn/listbycreater.aspx; NCBI: SRP338707).MethodsIn this study, microbial community composition and diversity analyses were carried out on fecal specimens from MG patients who did not take Fufang Huangqi Decoction (control group, n = 8) and those who took Fufang Huangqi Decoction and achieved remarkable alleviation of symptoms (medication group, n = 8). The abundance, diversity within and between habitats, taxonomic differences and corresponding discrimination markers of gut microbiota in the control group and medicated group were assessed.ResultsCompared with the control group, the medicated group showed a significantly decreased abundance of Bacteroidetes (P &lt; 0.05) and significantly increased abundance of Actinobacteria at the phylum level, a significantly decreased abundance of Bacteroidaceae (P &lt; 0.05) and significantly increased abundance of Bifidobacteriaceae at the family level and a significantly decreased abundance of Blautia and Bacteroides (P &lt; 0.05) and significantly increased abundance of Bifidobacterium, Lactobacillus and Roseburia at the genus level. Compared to the control group, the medicated group had decreased abundance, diversity, and genetic diversity of the communities and increased coverage, but the differences were not significant (P &gt; 0.05); the markers that differed significantly between communities at the genus level and influenced the differences between groups were Blautia, Bacteroides, Bifidobacterium and Lactobacillus.ConclusionsMG patients have obvious gut microbiota-associated metabolic disorders. Fufang Huangqi Decoction regulates the gut microbiota in patients with class I or II MG by reducing the abundance of Blautia and Bacteroides and increasing the abundance of Bifidobacterium and Lactobacillus. The correlation between gut microbiota and MG may be related to cell-mediated immunity.
Predictive Value of the Systemic Immune Inflammation Index for Adverse Outcomes in Patients With Acute Ischemic Stroke
Authors: Zhou Yun-Xiang , Li Wen-Cai , Xia Shao-Huai , Xiang Ting , Tang Can , Luo Jia-Li , Lin Ming-Jian , Xia Xue-Wei , Wang Wen-Bo 
Published: March 2022

Background and PurposeThe systemic immune-inflammation index, a new index based on platelets, neutrophils and lymphocytes, has been shown to be associated with outcomes of patients with venous sinus thrombosis and cancer. However, its application in acute ischemic stroke has rarely been reported. Therefore, we examined the relationship between systemic immune-inflammation index levels at hospital admission and the outcomes of patients 3 months after onset, and plotted a nomogram to predict the probability of adverse outcomes in patients with acute ischemic stroke.MethodsWe retrospectively analyzed a total of 208 patients with acute ischemic stroke who were admitted between January 2020 and December 2020, and recorded the modified Rankin score 3 months later. A modified Rankin score ≥ 3 was defined as an adverse outcome. Age, sex, NIHSS score, SII, hypertension and coronary heart disease were included in the binary logistic regression, and the nomogram was plotted with a regression equation.ResultsReceiver operating characteristic (ROC) curve analysis indicated that the best cutoff value of the systemic immune-inflammation index was 802.8, with a sensitivity of 70.9% and specificity of 58.2% (area under the curve: 0.657, 95% confidence interval: 0.572–0.742). The nomogram had a C index of 0.802. The average error of the calibration curves of the training set and the validation set was 0.021 and 0.034, respectively.ConclusionThe systemic immune-inflammation index is associated with short-term adverse outcomes in patients with acute ischemic stroke, and the nomograms can predict the risk of adverse outcomes in patients with acute ischemic stroke.
The Effect of Galvanic Vestibular Stimulation on Visuospatial Cognition in an Incomplete Bilateral Vestibular Deafferentation Mouse Model
Authors: Nguyen Thanh Tin , Nam Gi-Sung , Han Gyu Cheol , Le Chuyen , Oh Sun-Young 
Published: March 2022

ObjectivesTo evaluate the efficacy of galvanic vestibular stimulation (GVS) for recovering from the locomotor and spatial memory deficits of a murine bilateral vestibular deafferentation (BVD) model.MethodsMale C57BL/6 mice (n = 36) were assigned to three groups: bilateral labyrinthectomy with (BVD_GVS group) and without (BVD_non-GVS group) the GVS intervention, and a control group with the sham operation. We used the open field and Y maze, and Morris water maze (MWM) tests to assess locomotor and visuospatial cognitive performance before (baseline) and 3, 7, and 14 days after surgical bilateral labyrinthectomy. For the GVS group, a sinusoidal current at the frequency at 1 Hz and amplitude 0.1 mA was delivered for 30 min daily from the postoperative day (POD) 0 to 4 via electrodes inserted subcutaneously close to both the bony labyrinths.ResultsShort-term spatial memory was significantly impaired in bilaterally labyrinthectomized mice (BVD_non-GVS group), as reflected by decreased spontaneous alternation performance in the place recognition test and time spent in the novel arm and increased same arm return in the Y-maze test, compared with the control. Long-term spatial memory was also impaired, as indicated by a longer escape latency in the hidden platform trial and a lower percentage of time spent in the target quadrant in the probe trial of the MWM. GVS application significantly accelerated the recovery of locomotion and short-term and long-term spatial memory deficits in the BVD mice.ConclusionsOur data demonstrate that locomotion, short-term, and long-term (at least 2 weeks) spatial memory were impaired in BVD mice. The early administration of sinusoidal GVS accelerated the recovery of those locomotion and spatial memory deficiencies. GVS could be applied to patients with BVD to improve their locomotion and vestibular cognitive functioning.
Neural Correlates of Executed Compared to Imagined Writing and Drawing Movements: A Functional Magnetic Resonance Imaging Study
Authors: Baumann Alexander , Tödt Inken , Knutzen Arne , Gless Carl Alexander , Granert Oliver , Wolff Stephan , Marquardt Christian , Becktepe Jos S. , Peters Sönke , Witt Karsten , Zeuner Kirsten E. 
Published: March 2022

ObjectiveIn this study we used functional magnetic resonance imaging (fMRI) to investigate whether motor imagery (MI) of handwriting and circle drawing activates a similar handwriting network as writing and drawing itself.MethodsEighteen healthy right-handed participants wrote the German word “Wellen” and drew continuously circles in a sitting (vertical position) and lying position (horizontal position) to capture kinematic handwriting parameters such as velocity, pressure and regularity of hand movements. Afterward, they performed the same tasks during fMRI in a MI and an executed condition.ResultsThe kinematic analysis revealed a general correlation of handwriting parameters during sitting and lying except of pen pressure during drawing. Writing compared to imagined writing was accompanied by an increased activity of the ipsilateral cerebellum and the contralateral sensorimotor cortex. Executed compared to imagined drawing revealed elevated activity of a fronto–parieto-temporal network. By contrasting writing and drawing directly, executed writing induced an enhanced activation of the left somatosensory and premotor area. The comparison of the MI of these tasks revealed a higher involvement of occipital activation during imagined writing.ConclusionThe kinematic results pointed to a high comparability of writing in a vertical and horizontal position. Overall, we observed highly overlapping cortical activity except of a higher involvement of motor control areas during motor execution. The sparse difference between writing and drawing can be explained by highly automatized writing in healthy individuals.
Second Primary Malignancies in Patients With Melanoma Subtypes: Analysis of 120,299 Patients From the SEER Database (2000-2016)
Authors: Loya Asad , Gombos Dan S. , Patel Sapna P. 
Published: March 2022

PurposeEvaluate incidence of second primary malignancies (SPM) after non-acral cutaneous melanoma (NACM), acral lentiginous melanoma (ALM), mucosal melanoma (MM), and uveal melanoma (UM).Patients and MethodsFirst primary NACM, ALM, MM, and UM cases diagnosed 2000-2016 were extracted from SEER. Seer*Stat was used to calculate excess absolute risks (EAR) and standardized incidence ratios (SIR) of SPMs relative to a matched cohort from the general population. P-value of 0.05 determined significance.ResultsInclusion criteria was met by 109,385 patients with NACM, 2166 with ALM, 2498 with MM, and 6250 with UM. Increased incidence of malignancies occurred after NACM (SIR 1.51; 95%CI, 1.49-1.54), ALM (SIR 1.59; 95%CI, 1.40-1.81), MM (SIR 2.14; 95%CI, 1.85-2.45), and UM (SIR 1.24; 95%CI, 1.14-1.34) relative to the general population. Cutaneous melanoma occurred more frequently after NACM (SIR 9.54; 95%CI, 9.27-9.83), ALM (SIR 12.19; 95%CI, 9.70-15.14), MM (SIR 10.05; 95%CI, 7.18-13.68), and UM (SIR 2.91; 95%CI, 2.27-3.66). Patients with initial NACM (SIR 2.44; 95%CI, 1.64-3.51) and UM (SIR 44.34; 95%CI, 29.91-63.29) demonstrated increased incidence of eye and orbit melanoma. Renal malignancies occurred more frequently after NACM (SIR 1.24; 95%CI, 1.11-1.38), MM (SIR 3.54; 95%CI, 1.62-6.72) and UM (SIR 1.68; 95%CI, 1.09-2.48). Increased incidence of thyroid malignancies was observed after NACM (SIR 1.83; 95%CI, 1.61-2.06), ALM (SIR 3.74; 95%CI, 1.71-7.11), MM (SIR 4.40; 95%CI, 1.77-9.06), and UM (SIR 3.79; 95%CI, 2.52-5.47). Increased incidence of lymphoma was observed after NACM (SIR 1.20; 95%CI, 1.09-1.31) and ALM (SIR 2.06; 95%CI, 1.13-3.46).ConclusionPatients with NACM, ALM, MM, and UM have increased incidence of SPMs compared to that expected from the general population. Each of these melanoma subtypes had increased occurrence of cutaneous melanoma and thyroid cancer; some, but not all, had increased occurrence of renal malignancies, eye and orbit melanoma, and lymphoma.
Text Mining-Based Drug Discovery for Connective Tissue Disease–Associated Pulmonary Arterial Hypertension
Authors: Tan Jiang-Shan , Hu Song , Guo Ting-Ting , Hua Lu , Wang Xiao-Jian 
Published: March 2022

Background: The current medical treatments for connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH) do not show favorable efficiency for all patients, and identification of novel drugs is desired.Methods: Text mining was performed to obtain CTD- and PAH-related gene sets, and the intersection of the two gene sets was analyzed for functional enrichment through DAVID. The protein–protein interaction network of the overlapping genes and the significant gene modules were determined using STRING. The enriched candidate genes were further analyzed by Drug Gene Interaction database to identify drugs with potential therapeutic effects on CTD-PAH.Results: Based on text mining analysis, 179 genes related to CTD and PAH were identified. Through enrichment analysis of the genes, 20 genes representing six pathways were obtained. To further narrow the scope of potential existing drugs, we selected targeted drugs with a Query Score ≥5 and Interaction Score ≥1. Finally, 13 drugs targeting the six genes were selected as candidate drugs, which were divided into four drug–gene interaction types, and 12 of them had initial drug indications approved by the FDA. The potential gene targets of the drugs on this list are IL-6 (one drug) and IL-1β (two drugs), MMP9 (one drug), VEGFA (three drugs), TGFB1 (one drug), and EGFR (five drugs). These drugs might be used to treat CTD-PAH.Conclusion: We identified 13 drugs targeting six genes that may have potential therapeutic effects on CTD-PAH.
Multiple Criterion and Multiple Stimulus Signal Detection Theory Analysis of Corneal Painful and Cool Pneumatic Stimuli
Authors: Jayakumar Varadharajan , Simpson Trefford 
Published: March 2022

Purpose:To evaluate the detectability of pneumatic corneal stimuli and response bias using multi-stimuli multi-criterion signal detection theory (MSDT).Methods:Thirty-six participants were recruited using convenience sampling. A Waterloo Belmonte esthesiometer was used to deliver cold, mechanical, and chemical stimuli to the center of the cornea at three separate study visits. The stimulus type was assigned randomly to each visit at the start of the study. The threshold (baseline for detection theory experiment) for the assigned stimulus type was obtained using the ascending method of limits. In the cold and mechanical MSDT experiments, 100 trials (80 signal (20 each for 4 intensities) and 20 catch trials) were presented in randomized order, and participants responded with a 5-point confidence rating to each trial. In the chemical MSDT experiments, 50 trials (20 signal trials each for two intensities and 10 catch trials) were presented, and responses were provided using 4-point confidence ratings. Detection theory indices were calculated individually and as groups, which were then analyzed using mixed models and paired t-tests.Results:Detectability (da) and the area under the curve (Az) were significantly different between stimulus intensities within each stimulus type (allp&lt; 0.001) but were not different between the stimulus types. Receiver operating characteristics (ROC) curves were separable between the scaled intensities for all stimulus types, and no overlaps were observed in the z-ROC space. The log-likelihood ratio (lnβ) depended on stimulus intensity and psychophysical criterion for all stimulus types.Conclusion:It is feasible to use MSDT for analyzing ocular surface sensory processing and the theory provides insight into the possible bias associated with the use of pneumatic stimuli. With noxious and non-noxious pneumatic stimulation, detectability and criteria vary systematically with stimulus intensity, a result that cannot be derived using classical psychophysics and this highlights the importance of signal detection theory and its approaches in studying ocular surface pain and thermal processing.
Cost-Effectiveness of Sequential Denosumab/Zoledronic Acid Compared With Zoledronic Acid Monotherapy for Postmenopausal Osteoporotic Women in China
Authors: You Ruxu , Liu Jinyu , Ke Lei , Wan Min , Zhang Yu , Yu Guangyi , Mori Takahiro 
Published: March 2022

Objective: The primary purpose of this study was to estimate the cost-effectiveness of sequential denosumab/zoledronic acid versus zoledronic acid monotherapy for postmenopausal osteoporotic women in China.Methods: We updated and utilized a previously validated Markov microsimulation model to obtain the cost-effectiveness of two strategies for treating postmenopausal osteoporotic women. We compared the incremental cost-effectiveness ratios (ICERs) (US dollars [$] per quality-adjusted life year [QALY]) of sequential denosumab/zoledronic acid (i.e., biannual subcutaneous denosumab for 3 years followed by annual intravenous zoledronic acid for 3 years) with zoledronic acid monotherapy for 3 years in Chinese women with postmenopausal osteoporosis at ages 65, 70, 75, and 80 from the health care payer perspective. Our study’s willingness-to-pay (WTP) threshold was set to three times the value of China’s per capita GDP in 2020 ($31,512).Results: The ICERs of sequential denosumab/zoledronic acid versus zoledronic acid monotherapy were $59,389/QALY, $23,821/QALY, $22,710/QALY, and $14,027/QALY at age 65, 70, 75, and 80 years, respectively. One-way sensitivity analyses showed that the most impactful parameter was the persistence rate of the medications. If the persistence rate of denosumab or zoledronic acid was increased by 10%, sequential denosumab/zoledronic acid would be cost-effective at age 65. In probabilistic sensitivity analyses, the probabilities of sequential denosumab/zoledronic being cost-effective compared to zoledronic acid monotherapy were approximately 29.3%, 68.7%, 86.1%, and 99.4% for ages 65, 70, 75, and 80 years, respectively, at the WTP threshold of $31,512/QALY.Conclusion: Among Chinese postmenopausal osteoporosis women over 70 years old, sequential denosumab/zoledronic acid was cost-effective compared with zoledronic acid monotherapy at the pre-determined WTP threshold.