bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of white matter over 1–2 years in small vessel disease using MR-based quantitative susceptibility mapping and free-water mapping
Authors: Sun Yawen , Hu Ying , Qiu Yage , Zhang Yuyao , Jiang Changhao , Lu Peiwen , Xu Qun , Shi Yuting , Wei Hongjiang , Zhou Yan 
Published: September 2022

PurposeThe aim of this study was to investigate alterations in white matter lesions (WMLs) and normal-appearing white matter (NAWM) with small vessel disease (SVD) over 1–2 years using quantitative susceptibility mapping (QSM) and free-water (FW) mapping.MethodsFifty-one SVD patients underwent MRI brain scans and neuropsychological testing both at baseline and follow-up. The main approach for treating these patients is the management of risk factors. Quantitative susceptibility (QS), fractional anisotropy (FA), mean diffusivity (MD), FW, FW-corrected FA (FAT), and FW-corrected MD (MDT) maps within WMLs and NAWM were generated. Furthermore, the JHU-ICBM-DTI label atlas was used as an anatomic guide, and the measurements of the segmented NAWMs were calculated. The average regional values were extracted, and a paired t-test was used to analyze the longitudinal change. Partial correlations were used to assess the relationship between the MRI indices changes (e.g., ΔQSfollowup − baseline/QSbaseline) and the cognitive function changes (e.g., ΔMoCAfollowup − baseline/MoCAbaseline).ResultsAfter SVD risk factor control, no gradual cognitive decline occurred during 1–2 years. However, we still found that the QS values (index of demyelination) increased in the NAWM at follow-up, especially in the NAWM part of the left superior frontal blade (SF), left occipital blade, right uncinate fasciculus, and right corticospinal tract (CST). FW (index of neuroinflammation/edema) analysis revealed that the follow-up group differed from the baseline group in the NAWM part of the right CST and inferior frontal blade (IF). Decreased FAT (index of axonal loss) was observed in the NAWM part of the right SF and IF at follow-up. In addition, the FAT changes in the NAWM part of the right IF were associated with overall cognitive performance changes. In contrast, no significant differences were found in the WMLs.ConclusionThe NAWM was still in the progressive injury process over time, while WMLs remained relatively stable, which supports the notion that SVD is a chronic progressive disease. The process of axonal loss in the NAWM part of the prefrontal lobe might be a biomarker of cognitive changes in the evolution of SVD.
Thirty-six months recurrence after acute ischemic stroke among patients with comorbid type 2 diabetes: A nested case-control study
Authors: Wang Lu , Li Hongyun , Hao Jiheng , Liu Chao , Wang Jiyue , Feng Jingjun , Guo Zheng , Zheng Yulu , Zhang Yanbo , Li Hongxiang , Zhang Liyong , Hou Haifeng 
Published: September 2022

BackgroundStroke patients have to face a high risk of recurrence, especially for those with comorbid T2DM, which usually lead to much more serious neurologic damage and an increased likelihood of death. This study aimed to explore determinants of stroke relapse among patients with comorbid T2DM.Materials and methodsWe conducted this case-control study nested a prospective cohort of ischemic stroke (IS) with comorbid T2DM. During 36-month follow-up, the second stroke occurred in 84 diabetic IS patients who were allocated into the case group, while 613 patients without recurrence were the controls. We collected the demographic data, behaviors and habits, therapies, and family history at baseline, and measured the variables during follow-up. LASSO and Logistic regression analyses were carried out to develop a prediction model of stroke recurrence. The receiver operator characteristic (ROC) curve was employed to evaluate the performance of the prediction model.ResultsCompared to participants without recurrence, the higher levels of pulse rate (78.29 ± 12.79 vs. 74.88 ± 10.93) and hypertension (72.6 vs. 61.2%) were recorded at baseline. Moreover, a lower level of physical activity (77.4 vs. 90.4%), as well as a higher proportion of hypoglycemic therapy (36.9 vs. 23.3%) was also observed during 36-month follow-up. Multivariate logistic regression revealed that higher pulse rate at admission (OR = 1.027, 95 %CI = 1.005–1.049), lacking physical activity (OR = 2.838, 95% CI = 1.418–5.620) and not receiving hypoglycemic therapy (OR = 1.697, 95% CI = 1.013–2.843) during follow-up increased the risk of stroke recurrence. We developed a prediction model using baseline pulse rate, hypoglycemic therapy, and physical activity, which produced an area under ROC curve (AUC) of 0.689.ConclusionPhysical activity and hypoglycemic therapy play a protective role for IS patients with comorbid diabetes. In addition to targeted therapeutics, the improvement of daily-life habit contributes to slowing the progress of the IS.
Urinary sodium excretion is low prior to acute kidney injury in patients in the intensive care unit
Authors: de Morais David Gomes , Sanches Talita Rojas Cunha , Santinho Mirela Aparecida Rodrigues , Yada Eduardo Yuki , Segura Gabriela Cardoso , Lowe Diogo , Navarro Guilherme , Seabra Victor Faria , Taniguchi Leandro Utino , Malbouisson Luiz Marcelo Sá , de André Carmen Diva Saldiva , Andrade Lúcia , Rodrigues Camila Eleuterio 
Published: September 2022

BackgroundThe incidence of acute kidney injury (AKI) is high in intensive care units (ICUs), and a better understanding of AKI is needed. Early chronic kidney disease is associated with urinary concentration inability and AKI recovery with increased urinary solutes in humans. Whether the inability of the kidneys to concentrate urine and excrete solutes at appropriate levels could occur prior to the diagnosis of AKI is still uncertain, and the associated mechanisms have not been studied.MethodsIn this single-center prospective observational study, high AKI risk in ICU patients was followed up for 7 days or until ICU discharge. They were grouped as “AKI” or “No AKI” according to their AKI status throughout admission. We collected daily urine samples to measure solute concentrations and osmolality. Data were analyzed 1 day before AKI, or from the first to the fifth day of admission in the “No AKI” group. We used logistic regression models to evaluate the influence of the variables on future AKI diagnosis. The expression of kidney transporters in urine was evaluated by Western blotting.ResultsWe identified 29 patients as “No AKI” and 23 patients as “AKI,” the latter being mostly low severity AKI. Urinary sodium excretion was lower in “AKI” patients prior to AKI diagnosis, particularly in septic patients. The expression of Na+/H+ exchanger (NHE3), a urinary sodium transporter, was higher in “AKI” patients.ConclusionsUrinary sodium excretion is low before an AKI episode in ICU patients, and high expressions of proximal tubule sodium transporters might contribute to this.
Case report: Blepharospasm in peak-dose dyskinesia may benefit from amantadine in Parkinson's disease
Authors: Fan Qian-Ya , Zhang Xiao-Dong , Hu Ze-Di , Huang Shi-Shi , Zhu Shi-Guo , Chen Cai-Ping , Zhang Xiong , Wang Jian-Yong 
Published: September 2022

IntroductionBlepharospasm is uncommon in Parkinson's disease, especially in the peak-dose dyskinesia period.Case presentationWe herein present the case of a patient with PD who developed blepharospasm in the peak-dose dyskinesia period. The symptom was improved by taking amantadine.ConclusionThe current report expands the phenomenology of peak-dose dykinesia in PD to include dystonic blepharospasm. This complication of levodopa therapy may respond to amantadine despite the dystonic appearance of movements.
Effects of age and sex on outcomes of the Q-Motor speeded finger tapping and grasping and lifting tests-findings from the population-based BiDirect Study
Authors: Teismann Henning , Schubert Robin , Reilmann Ralf , Berger Klaus 
Published: September 2022

BackgroundQ-Motor is a suite of motor tests originally designed to assess motor symptoms in Huntington's disease. Among others, Q-Motor encompasses a finger tapping task and a grasping and lifting task. To date, there are no systematic investigations regarding effects of variables which may affect the performance in specific Q-Motor tests per se, and normative Q-Motor data based on a large population-based sample are not yet available.ObjectiveWe investigated effects of age and sex on five selected Q-Motor outcomes representing the two core Q-Motor tasks speeded finger tapping and grasping and lifting in a community sample of middle-aged to elderly adults. Furthermore, we explored effects of the potentially mediating variables educational attainment, alcohol consumption, smoking status, and depressive symptoms. Moreover, we explored inter-examiner variability. Finally, we compared the findings to findings for the Purdue Pegboard test.MethodsBased on a sample of 726 community-dwelling adults and using multiple (Gaussian) regression analysis, we modeled the motor outcomes using age, sex, years in full-time education, depressive symptoms in the past seven days, alcohol consumption in the past seven days, and smoking status as explanatory variables.ResultsWith regard to the Q-Motor tests, we found that more advanced age was associated with reduced tapping speed, male sex was associated with increased tapping speed and less irregularity, female sex was associated with less involuntary movement, more years of education were associated with increased tapping speed and less involuntary movement, never smoking was associated with less involuntary movement compared to current smoking, and more alcohol consumed was associated with more involuntary movement.ConclusionThe present results show specific effects of age and sex on Q-Motor finger tapping and grasping and lifting performance. In addition, besides effects of education, there also were specific effects of smoking status and alcohol consumption. Importantly, the present study provides normative Q-Motor data based on a large population-based sample. Overall, the results are in favor of the feasibility and validity of Q-Motor finger tapping and grasping and lifting for large observational studies. Due to their low task-complexity and lack of placebo effects, Q-Motor tests may generate additional value in particular with regard to clinical conditions such as Huntington's or Parkinson's disease.
Increased PRR14 and VCAM-1 level in serum of patients with Parkinson's disease
Authors: Zheng Huimin , Wang Tai , Shi Changhe , Fan Liyuan , Su Yun , Fan Yu , Li Xinwei , Yang Jing , Mao Chengyuan , Xu Yuming 
Published: September 2022

BackgroundRegarding the complexity of Parkinson's disease (PD), the identification of reliable biomarkers is of great significance for improving the accuracy of diagnosis and monitoring disease progression. Recently, some studies suggested that serum proline-rich protein 14 (PRR14), vascular cell adhesion molecule-1 (VCAM-1), and soluble CD163 (sCD163) factors may be associated with PD, even as potential biomarkers. However, the role of these serum factors is still unclear.ObjectivesThis study aimed to explore the alterations of serum PRR14, VCAM-1, and sCD163 levels during PD progression, and their association with disease-related variables of PD.MethodsWe performed the assessment of scale tests and the detection of serum samples in patients with PD (n = 100) and healthy controls (HCs, n = 100). Furthermore, we investigated the association between serum factors and sex, cognitive impairments, H&amp;Y (Hohn and Yahr), age at onset (AAO), and other variables in patients with PD.ResultsPatients with PD exhibited increased PRR14 and VCAM-1 serum levels compared with HCs. No significant differences were found in serum levels of sCD163. Subgroup analysis uncovered increased VCAM-1 in the female and male subgroups (PD and HCs). Among patients with PD, decreased PRR14 and increased VCAM-1 were associated with severer cognitive impairments and severer PD (H&amp;Y), respectively. Bivariate correlation analysis revealed that there was a positive correlation between VCAM-1 and AAO.ConclusionsIncreased serum levels of PRR14 and VCAM-1 suggest that inflammation and defective autophagy may play vital roles in the pathogenesis of PD. However, the potential mechanisms remain to be elucidated.
Unrelated umbilical cord blood transplantation for children with hereditary leukodystrophy: A retrospective study
Authors: Wang Ping , Du Xiaonan , Shen Quanli , Jiang Wenjin , Shen Chen , Wang Hongsheng , Zhou Shuizhen , Wang Yi , Qian Xiaowen , Zhai Xiaowen 
Published: September 2022

ObjectiveTo analyze the efficiency of unrelated umbilical cord blood transplantation (UCBT) in the treatment of hereditary leukodystrophy following busulfan- and cyclophosphamide-based myeloablative chemotherapy.MethodsA retrospective study was performed in patients with hereditary leukodystrophy who underwent UCBT after myeloablative chemotherapy between April 2015 and March 2020.ResultsThe study cohort included 12 pediatric patients (ten males), nine with cerebral adrenoleukodystrophy (ALD) and three with juvenile globoid cell leukodystrophy (GLD). All received HLA-matched or partially mismatched unrelated UCBT. There were no cases of graft rejection. Median neutrophil engraftment time was 20 days [12–33 days] and median platelet engraftment time was 29 days [14–65 days]. Median follow-up was 36 months [1–86 months], and the overall survival rate for patients with cerebral ALD and juvenile GLD after UCBT was 77.8% (7/9) and 100% (3/3), respectively. In patients with ALD, although lipid profiles (serum very-long-chain fatty acid) were improved post-UCBT, six patients demonstrated worse neurologic function score and performance status post-UCBT, and six patients had higher Loes scores at last follow-up compared with baseline. In patients with juvenile GLD, all patients showed stable neurologic function score and performance status despite the Loes score of one patient increased slightly after transplantation.ConclusionIn patients with cerebral ALD, patients with no or mild neurological symptoms can benefit from UCBT, while UCBT cannot reverse advanced disease. In patients with juvenile GLD, UCBT is safe and contributes to stabilize neurological function.
Selective vulnerability of ARID1A deficient colon cancer cells to combined radiation and ATR-inhibitor therapy
Authors: Xu Shan , Sak Ali , Niedermaier Ben , Erol Yasin Bahadir , Groneberg Michael , Mladenov Emil , Kang MingWei , Iliakis George , Stuschke Martin 
Published: September 2022

ARID1A is frequently mutated in colorectal cancer (CRC) cells. Loss of ARID1A function compromises DNA damage repair and increases the reliance of tumor cells on ATR-dependent DNA repair pathways. Here, we investigated the effect of ionizing radiation (IR), in combination with ATR inhibitors (ATRi) in CRC cell lines with proficient and deficient ARID1A. The concept of selective vulnerability of ARID1A deficient CRC cells to ATRi was further tested in an ex vivo system by using the ATP-tumor chemosensitivity assay (ATP-TCA) in cells from untreated CRC patients, with and without ARID1A expression. We found selective sensitization upon ATRi treatment as well as after combined treatment with IR (P&lt;0.001), especially in ARID1A deficient CRC cells (P &lt;0.01). Knock-down of ARID1B further increased the selective radiosensitivity effect of ATRi in ARID1A negative cells (P&lt;0.01). Mechanistically, ATRi abrogates the G2 checkpoint (P&lt;0.01) and homologous recombination repair (P&lt;0.01) in ARID1A deficient cells. Most importantly, ex-vivo experiments showed that ATRi had the highest radiosensitizing effect in ARID1A negative cells from CRC patients. Collectively, our results generate pre-clinical and clinical mechanistic rationale for assessing ARID1A defects as a biomarker for ATR inhibitor response as a single agent, or in a synthetic lethal approach in combination with IR.
Intraocular Amphiregulin antibody and axial elongation in nonhuman primates
Authors: Wang Wenyao , Nan Yan , Huang Tiejun , Pu Mingliang , Jonas Jost B. 
Published: September 2022

PurposeTo examine the effect of intraocularly applied amphiregulin antibody on physiological axial elongation in young nonhuman primates.MethodsThe experimental study included six male 12-months-old macaque nonhuman primates (body weight:2.46 ± 0.25kg;range:2.20-2.90kg). In the experimental group (n=3 animals), three intravitreal injections of amphiregulin antibody (100μg/50μl) were applied to the left eyes at intervals of 4-6 weeks, and injections of phosphate buffered solution (50μl) were applied to the right eyes. Three other animals were assigned to a blank control group.ResultsDuring the study period of 23.6 weeks, axial length in the experimental group did not change in the left eyes (18.91 ± 0.37mm to 18.94 ± 0.67mm;P=0.90), while it linearly increased in the right eyes (18.87 ± 0.38mm to 19.24 ± 0.53mm;P=0.056) and in the control group (left eyes:19.15 ± 0.22mm to 19.48 ± 0.22mm;P=0.009; right eyes:19.17 ± 0.15 mm to 19.46 ± 0.23 mm;P=0.024). The interocular difference in axial elongation increased in the experimental group from -0.11 ± 0.12mm at 4 weeks after baseline to -0.34 ± 0.15mm at the study end, while in the control group, the interocular side difference did not change significantly (from 0.01 ± 0.10 mm to 0.03 ± 0.08 mm;P=0.38). The difference in the interocular difference in axial elongation between the two groups was significant at 8 weeks (P=0.01), 15 weeks (P=0.007), and at study end (P=0.02). The interocular difference in axial length correlated with the interocular difference in vitreous cavity length (standardized regression coefficient beta:0.85;P&lt;0.001). The interocular axial length difference was inversely associated with the interocular refractive error difference (beta:-0.49;P&lt;0.001).ConclusionsIntraocularly applied amphiregulin antibody (100μg) reduced the physiological ocular axial elongation in juvenile nonhuman primates.
Yi Shen Juan Bi Pill alleviates bone destruction in inflammatory arthritis under postmenopausal conditions by regulating ephrinB2 signaling
Authors: Xu Huihui , Tao Li , Cao Jinfeng , Zhang Peng , Zeng Hui , Zhao Hongyan 
Published: September 2022

Yi Shen Juan Bi Pill (YSJB) is a traditional Chinese medicine (TCM) formulation that has a therapeutic effect upon rheumatoid arthritis (RA), but how YSJB affects bone destruction in arthritis under postmenopausal conditions is not known. We evaluated the therapeutic role of YSJB in bone destruction in postmenopausal arthritis, We used collagen-induced arthritis (CIA) rats who had been ovariectomized (OVX) as models and explored the possible mechanism from the synovium and bone marrow (BM). Arthritis was generated after ovariectomy or sham surgery for 12 weeks. After 14 days of primary immunization, rats were administered YSJB or estradiol valerate (EV) for 28 days. YSJB could prevent bone destruction in the inflamed joints of rats in the OVX + CIA group. CIA promoted osteoclast differentiation significantly in the synovial membrane according to tartrate resistant acid phosphatase (TRACP) staining, and OVX tended to aggravate the inflammatory reaction of CIA rats according to hematoxylin-and-eosin staining. Immunohistochemistry revealed that the synovium did not have significant changes in erythropoietin-producing hepatocellular interactor (ephrin)B2 or erythropoietin-producing hepatocellular (eph) B4 expression after YSJB treatment, but YSJB treatment reduced nuclear factor of activated T cells (NFATc)1 expression. The BM of rats in the OVX + CIA exhibited remarkable increases in the number of osteoclasts and NFATc1 expression, as well as significantly reduced expression of ephrinB2 and ephB4 compared with the CIA group and sham group. YSJB treatment reduced NFATc1 expression significantly but also increased ephrinB2 expression in the BM markedly. These data suggest that YSJB exhibit a bone-protective effect, it may be a promising therapeutic strategy for alleviating bone destruction in arthritis under postmenopausal conditions, and one of the mechanisms is associated with the modulation of ephrinB2 signaling.
Salusin-β, a TOR2A gene product, promotes proliferation, migration, fibrosis, and calcification of smooth muscle cells and accelerates the imbalance of vasomotor function and vascular remodeling in monocrotaline-induced pulmonary hypertensive rats
Authors: Wang Xingxing , Chen Aidong , Hu Ruihua , Zhang Feng , Liang Shuxin , Bao Changlei , Liu Xuanxuan , Tang Haiyang , Han Ying 
Published: September 2022

Purpose: The hyper-proliferation, promoted migration, fibrosis, and calcification of pulmonary arterial smooth muscle cells (PASMCs) play critical roles in pulmonary artery (PA) continuous contraction and vascular remodeling, leading to elevated pulmonary arterial resistance and pulmonary hypertension (PH). In this study, we sought to ascertain the effects of a TOR2A gene product, salusin-β, on PASMCs’ proliferation, migration, fibrosis, calcification, and the imbalance of vasomotor function as well as pulmonary vascular remodeling in monocrotaline (MCT)-induced PH rats and their underlying mechanisms.Methods: Knockdown or overexpression of salusin-β in rats or PASMCs was performed through tail vein injection or cell transfection of virus. The right ventricular systolic pressure (RVSP) of the rat was measured by right ventricle catheterization. Sodium nitroprusside (SNP) or acetylcholine (ACh)-induced dose-dependent relaxation was used to evaluate the vasodilatation function. Primary PASMCs were isolated from the PAs of control and PH rats.Results: The salusin-β protein expressions were significantly increased in PAs and PASMCs isolated from PH rats compared with control rats. Knockdown of salusin-β in rats decreased high K+ solution-induced contraction, RVSP and RV hypertrophy index, improved SNP or ACh-induced vascular relaxation of PAs, and relieved vascular remodeling and calcification of PAs from PH rats. Silencing salusin-β in PASMCs isolated from PH rats alleviated the proliferation, migration, fibrosis, and calcification, as well as the NAD(P)H oxidase activity and reactive oxygen species (ROS) level. Overexpression of salusin-β exerted the opposite effects on vasomotor function and vascular remodeling, and PASMCs proliferation, migration, fibrosis and calcification.Conclusion: Increased salusin-β activity in PAs from PH rats contributes to PASMCs proliferation, migration, fibrosis, and calcification, leading to the imbalance of vascular contraction and relaxation and vascular remodeling through stimulating the production of NAD(P)H oxidase derived ROS.