bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania
Authors: Topazian Hillary M. , Moser Kara A. , Ngasala Billy , Oluoch Peter O. , Forconi Catherine S. , Mhamilawa Lwidiko E. , Aydemir Ozkan , Kharabora Oksana , Deutsch-Feldman Molly , Read Andrew F. , Denton Madeline , Lorenzo Antonio , Mideo Nicole , Ogutu Bernhards , Moormann Ann M. , Mårtensson Andreas , Odwar Boaz , Bailey Jeffrey A. , Akala Hoseah , Ong'echa John Michael , Juliano Jonathan J. 
Published: June 2022

BackgroundPlasmodium falciparum resistance to artemisinin-based combination therapies (ACTs) is a threat to malaria elimination. ACT-resistance in Asia raises concerns for emergence of resistance in Africa. While most data show high efficacy of ACT regimens in Africa, there have been reports describing declining efficacy, as measured by both clinical failure and prolonged parasite clearance times.MethodsThree hundred children aged 2–10 years with uncomplicated P. falciparum infection were enrolled in Kenya and Tanzania after receiving treatment with artemether-lumefantrine. Blood samples were taken at 0, 24, 48, and 72 h, and weekly thereafter until 28 days post-treatment. Parasite and host genetics were assessed, as well as clinical, behavioral, and environmental characteristics, and host anti-malarial serologic response.ResultsWhile there was a broad range of clearance rates at both sites, 85% and 96% of Kenyan and Tanzanian samples, respectively, were qPCR-positive but microscopy-negative at 72 h post-treatment. A greater complexity of infection (COI) was negatively associated with qPCR-detectable parasitemia at 72 h (OR: 0.70, 95% CI: 0.53–0.94), and a greater baseline parasitemia was marginally associated with qPCR-detectable parasitemia (1,000 parasites/uL change, OR: 1.02, 95% CI: 1.01–1.03). Demographic, serological, and host genotyping characteristics showed no association with qPCR-detectable parasitemia at 72 h. Parasite haplotype-specific clearance slopes were grouped around the mean with no association detected between specific haplotypes and slower clearance rates.ConclusionsIdentifying risk factors for slow clearing P. falciparum infections, such as COI, are essential for ongoing surveillance of ACT treatment failure in Kenya, Tanzania, and more broadly in sub-Saharan Africa.
Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study
Authors: Gao Ning , Kong Minjian , Li Xuebiao , Wei Dongdong , Zhu Xian , Hong Ze , Ni Ming , Wang Yifan , Dong Aiqiang 
Published: June 2022

BackgroundPrevious studies have shown that patients with systemic lupus erythematosus (SLE) tend to have a higher risk of cardiovascular disease (CVD), but the potential causal relationship between genetic susceptibility to SLE and CVD risk is not clear. This study systematically investigated the potential association between genetically determined SLE and the risk of CVD.MethodsThe genetic tools were obtained from genome-wide association studies of SLE and CVD, with no overlap between their participating populations. Mendelian randomization (MR) analysis was performed using inverse variance weighting as the primary method. Simultaneously, a series of repeated analyses, sensitivity analyses, and instrumental variable strength evaluations were performed to verify the reliability of our results.ResultsMR analysis showed that genetic susceptibility to SLE was associated with a higher risk of heart failure (OR=1.025, 95% CI [1.009-1.041], P=0.002), ischemic stroke (OR=1.020, 95% CI [1.005-1.034], P=0.009), and venous thromboembolism (OR=1.001, 95% CI [1.000-1.002], P=0.014). However, genetic susceptibility to SLE was negatively correlated with the risk of type 2 diabetes (OR=0.968, 95% CI [0.947-0.990], P=0.004). Sensitivity analysis found no evidence of horizontal pleiotropy or heterogeneity.ConclusionOur MR study explored the causal role of SLE in the etiology of CVD, which would help improve our understanding of the basic disease mechanisms of SLE and provide comprehensive CVD assessment and treatment for SLE patients.
Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation
Authors: Betjes Michiel G. H. , Roelen Dave L. , van Agteren Madelon , Kal-van Gestel Judith 
Published: June 2022

BackgroundBiopsy-proven causes of graft loss many years after kidney transplantation are scarcely documented.MethodsPatients transplanted between 1995 and 2005 (n = 737) in a single center were followed on a regular basis until 2021. The recipients were divided according to age at transplantation into 3 groups; 18–39 years (young), 40–55 years (middle age), and older than 55 years (elderly). For cause biopsies of renal transplants were clustered into the categories, rejection, IFTA, return original disease, and diagnosis of de novo kidney disease.ResultsRejection was the main cause of graft failure censored for death at every time period after transplantation. The incidence of T cell-mediated rejection (TCMR) became rare 6 years after transplantation while the cumulative incidence of antibody-mediated rejection (ABMR) increased over time (1.1% per year). ABMR was not diagnosed anymore beyond 15 years of follow-up in recipients without pre-transplant donor-specific antibodies (DSA). An episode of TCMR was associated with an increased incidence of ABMR diagnosis in the short-term but did not increase the overall incidence of AMBR not in the long-term. Death as a cause of graft failure was an important competitive risk factor long after transplantation and resulted in a significantly lower frequency of rejection-related graft loss in the elderly group (11 vs. 23% in the young group at 15 year follow-up).ConclusionRejection is a major cause of graft loss but recipient’s age, time after transplantation, and the presence of DSA before transplantation determine the relative contribution to overall graft loss and the type of rejection involved.
Clinical Features, Diagnosis, and Treatment of Primary Intraventricular Lymphoma: Insights From a Monocentric Case Series
Authors: Cheng Lidong , Zhu Hongtao , Wang Jing , Wang Guanghui , Ma Xiaoyu , Zhao Kai , Wang Junwen , Shu Kai 
Published: June 2022

ObjectivePrimary ventricular lymphoma (PVL) is an extremely rare and commonly misdiagnosed disease. Previous studies were predominantly case reports, and literature regarding the diagnosis and treatment of PVL is limited. Therefore, this study aimed to evaluate the characteristics of patients with PVL.MethodsThe data of patients with pathologically confirmed PVL were assessed. Epidemiological data, imaging findings, surgery, pathological results, and prognosis were retrospectively analyzed. A systematic review of relevant literature was also conducted.ResultsA total of eight patients with PVL were identified. The main symptom was increased intracranial pressure. Radiographically, five patients had single lesion and three had multiple lesions; typical findings on magnetic resonance imaging included hypointensity on T1- and T2-weighted imaging, adjacent brain edema, and homogeneous enhancement on contrast-enhanced T1-weighted images. Preoperatively, six cases were misdiagnosed and two cases did not get a definite diagnosis. Craniotomy was performed on all patients, and four achieved gross total resection. Hydrocephalus was relieved after surgical resection in four patients. Pathology revealed diffuse large B-cell lymphoma in all patients. Only one patient had a severe complication. A total of three patients received concomitant adjuvant treatment, whereas five patients refused any adjuvant therapy. At the time of follow-up, the median survival time of patients was 15 months.ConclusionPrimary ventricular lymphoma mainly presented with symptoms of increased intracranial pressure and had several imaging characteristics for the diagnosis, but the condition still tends to be misdiagnosed. Surgical resection is a feasible treatment for patients with isolated nodules, especially those with acute obstructive hydrocephalus.
Association of Recent and Long-Term Supplement Intakes With Laboratory Indices in Patients With COVID-19 in Tehran, Iran, During 2020
Authors: Hashemi Rezvan , Montazer Mohsen , Salehi Zahra , Azadbakht Leila 
Published: June 2022

BackgroundAlthough previous studies observed the relationship between individual dietary supplements and enhancing body resistance against viruses, few studies have been conducted regarding the role of different supplements in treatment of COVID-19. This article aims to determine the association of recent and long-term supplement consumption on the biochemical indices and impatient duration among patients with COVID-19.MethodsIn this cross-sectional study on 300 adult men and women with COVID-19, recent and long-term supplement intakes were investigated by using a questionnaire. In addition, lifestyle was also assessed in aspects of fruits and vegetable consumption, physical activity, sleeping duration, fluid intake, and smoking status. Furthermore, the laboratory and paraclinical parameters were obtained from medical records. The relationship between supplement intake with the length of hospitalization and clinical laboratory tests was investigated by one-way analysis of variance (ANOVA).ResultsThose patients with supplement intake in the last 2 months had a significantly lower amount of blood urea nitrogen (BUN) (31.31 ± 13.87 vs. 37.57 ± 19.77 mg/dL, P: 0.002) and higher serum 25(OH)D (28.13 ± 14.09 vs. 23.81 ± 13.55 ng/mL, P: 0.03). Subjects with long-term supplement intake had a significantly lower invasive oxygen support (0.00 vs 5.10 %, P: 0.05), lactate dehydrogenase (LDH) (498.11 ± 221.43 vs. 576.21 ± 239.84 U/L, P: 0.02), fewer days of fever (0.49 ± 3.54 vs. 2.64 ± 9.21, P: 0.02), and higher serum 25(OH)D (31.03 ± 13.20 vs. 22.29± 13.42 ng/mL, P &lt; 0.001). The length of hospital stay was practically the same between groups who received and did not receive supplementation during the 2 months prior to hospitalization (6.36 ± 3.32 vs. 6.71 ± 4.33 days, P: 0.004). Similarly, people who took supplements during the past year had practically similar hospitalization lengths (6.29 ± 4.13 vs. 6.74 ± 3.55 days, P: 0.004).ConclusionIn conclusion, although practically the length of hospital stay was the same in both groups of supplement consumers and others, immune-boosting supplements were associated with improved several laboratory indices. However, due to the cross-sectional nature of our study, further longitudinal studies seem to be essential.
MRI-Based Radiomics for Preoperative Prediction of Lymphovascular Invasion in Patients With Invasive Breast Cancer
Authors: Nijiati Mayidili , Aihaiti Diliaremu , Huojia Aisikaerjiang , Abulizi Abudukeyoumujiang , Mutailifu Sailidan , Rouzi Nueramina , Dai Guozhao , Maimaiti Patiman 
Published: June 2022

ObjectivePreoperative identification of lymphovascular invasion (LVI) in patients with invasive breast cancer is challenging due to absence of reliable biomarkers or tools in clinical settings. We aimed to establish and validate multiparametric magnetic resonance imaging (MRI)-based radiomic models to predict the risk of lymphovascular invasion (LVI) in patients with invasive breast cancer.MethodsThis retrospective study included a total of 175 patients with confirmed invasive breast cancer who had known LVI status and preoperative MRI from two tertiary centers. The patients from center 1 was randomly divided into a training set (n=99) and a validation set (n = 26), while the patients from center 2 was used as a test set (n=50). A total of 1409 radiomic features were extracted from the T2-weighted imaging (T2WI), dynamic contrast-enhanced (DCE) imaging, diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC), respectively. A three-step feature selection including SelectKBest, interclass correlation coefficients (ICC), and least absolute shrinkage and selection operator (LASSO) was performed to identify the features most associated with LVI. Subsequently, a Support Vector Machine (SVM) classifier was trained to develop single-layer radiomic models and fusion radiomic models. Model performance was evaluated and compared by the area under the curve (AUC), sensitivity, and specificity.ResultsBased on one feature of wavelet-HLH_gldm_GrayLevelVariance, the ADC radiomic model achieved an AUC of 0.87 (95% confidence interval [CI]: 0.80–0.94) in the training set, 0.87 (0.70-1.00) in the validation set, and 0.77 (95%CI: 0.64-0.86) in the test set. However, the combination of radiomic features derived from other MR sequences failed to yield incremental value.ConclusionsADC-based radiomic model demonstrated a favorable performance in predicting LVI prior to surgery in patients with invasive breast cancer. Such model holds the potential for improving clinical decision-making regarding treatment for breast cancer.
Gene Mutations Related to Glucocorticoid Resistance in Pediatric Acute Lymphoblastic Leukemia
Authors: Zhang JinFang , Zeng LingJi , Wang YuLian , Pan JianWei , Li XingDong , Feng Bei , Yang Quan 
Published: June 2022

ObjectiveTo investigate the correlation between gene mutations and glucocorticoid resistance in pediatric acute lymphoblastic leukemia (ALL).MethodsA total of 71 children with ALL admitted to our center between September 2019 and September 2021 were enrolled. DNA obtained from bone marrow or peripheral blood samples at initial diagnosis was used for genetic testing via whole exome sequencing. Meanwhile, patient clinical information was collected. Subsequently, the correlations of gene mutations with clinical features and glucocorticoid resistance were analyzed.ResultsOf the 71 children enrolled, 61 (85.9%) had B-cell ALL (B-ALL) and 10 (14.1%) had T-cell ALL (T-ALL). The five genes with the highest mutation frequency in B-ALL were TTN (24.4%), FLT3 (14.6%), TP53 (14.6%), MUC16 (9.8%), and EPPK1 (9.8%). In contrast, those with the highest frequency in T-ALL were NOTCH1 (54.5%), FBXW7 (27.3%), TTN (27.3%), MUC16 (27.3%), and PHF6 (18.2%). Upon statistical analysis, TTN and NOTCH1 mutations were found to be associated with prednisone resistance. Further, TTN and MUC16 mutations were associated with a lower age at diagnosis, and NOTCH1 mutations were associated with T-ALL in female patients. Leukocyte counts and LDH levels did not differ based on the presence of any common gene mutation, and no association between these gene mutations and overall survival was observed.ConclusionsOur study is the first to demonstrate the association between TTN mutation and glucocorticoid resistance in ALL. Our findings could guide strategies for overcoming drug resistance and aid in the development of drug targets.
Indole-3-Carbinol (I3C) Protects the Heart From Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress, Inflammation, and Cellular Apoptosis in Mice
Authors: Li Qi , Xia Boyu , Wu Jingjing , Yuan Xiaomei , Lu Xu , Huang Chao , Gu Hongcheng , Zheng Koulong , You Qingsheng , Liu Kun 
Published: June 2022

Strategies for treating myocardial ischemia in the clinic usually include re-canalization of the coronary arteries to restore blood supply to the myocardium. However, myocardial reperfusion insult often leads to oxidative stress and inflammation, which in turn leads to apoptosis and necrosis of myocardial cells, for which there are no standard treatment methods. The aim of this study was to determine the pharmacological effect of indole-3-carbinol (I3C), a phytochemical found in most cruciferous vegetables, in a mouse model of myocardial ischemia/reperfusion injury (MIRI). Our results showed that I3C pretreatment (100 mg/kg, once daily, i. p.) prevented the MIRI-induced increase in infarct size and serum creatine kinase (CK) and lactate dehydrogenase (LDH) in mice. I3C pretreatment also suppressed cardiac apoptosis in MIRI mice by increasing the expression levels of the anti-apoptotic protein Bcl-2 and decreasing the expression levels of several apoptotic proteins, including Bax, caspase-3, and caspase-9. In addition, I3C pretreatment was found to reduce the levels of parameters reflecting oxidative stress, such as dihydroethidium (DHE), malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO), while increasing the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC) and glutathione (GSH), in MIRI-induced ischemic heart tissue. I3C pretreatment was also able to remarkably decrease the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) mRNA in ischemic heart tissue. These results demonstrate that administration of I3C protects the heart from MIRI through its anti-apoptotic, antioxidant, and anti-inflammatory effects.
An Endoplasmic Reticulum-Targeted Ratiometric Fluorescent Molecule Reveals Zn2+ Micro-Dynamics During Drug-Induced Organelle Ionic Disorder
Authors: Fang Hongbao , Li Yaheng , Yao Shankun , Geng Shanshan , Chen Yuncong , Guo Zijian , He Weijiang 
Published: June 2022

The endoplasmic reticulum (ER) is the main storage site of Zn2+, and Zn2+ plays an important role in regulating ER homeostasis. Therefore, we designed and synthesized a ratiometric fluorescent Zn2+ probe ER-Zn targeting ER stress. The probe displayed a specific Zn2+ induced blue shift at the spectral maximum values of excitation (80 nm) and emission (30 nm). The ratio imaging capability of Zn2+ under dual excitation mode can be applied not only to quantitative and reversible detection of exogenous Zn2+, but also the observation of the Zn2+ level change under ER stress, elucidating the different behaviors of Zn2+ release in ER stimulated by tunicamycin and thapsigargin. Additionally, the NIR imaging capability of ER-Zn provides an important basis for further research on animal models and is expected to realize the visualization and treatment of ER stress-related diseases through the regulation of ER stress by Zn2+. We envision that this probe can be applied to screen drugs for diseases related to ER stress regulation.
The Mechanical Properties of in Situ Canine Skeletal Muscle
Authors: Allen P. D. , Barclay J. K. 
Published: June 2022

This study was undertaken to determine if fiber arrangement was responsible for differences in the whole muscle mechanical properties. Experiments were carried out in situ in blood perfused dog skeletal muscles at approximately normal body temperature between 36° and 38°C. The following mechanical relationships were studied using a pneumatic muscle lever to measure Tension (P), length (L) and dP/dt: and dL/dt with a high frequency oscillograph (500–1000 Hz): 1.) Length:Tension; 2.) Force:Velocity; and 3.) Stress:Strain of Series Elastic. Electron microscopy and fiber typing were done as adjunctive studies. Muscles were stimulated by direct nerve stimulation with 0.1msec stimuli at a rate of 1 impulse per second for twitch contractions, or in 200 msec bursts of 100 Hz 0.1 msec stimuli for brief tetanic contractions. The pennate short fibered gastrocnemius plantaris developed 1.0 kg/g of tension during brief tetanic stimulation, at optimal length (Lo) with full stimulus voltage, while the parallel long fibered semitendinosus developed 0.5 kg/g under the same conditions. The Length:Tension relationship for these two muscles was qualitatively similar but quantitatively different. The Force:Velocity relationship (ΔL/L0 vs. P/P0) for both muscles were also qualitatively similar and could be described by the previously proposed rectangular hyperbola but a better predicted fit to the observed data could be produced by adding a descending exponential function to the rectangular hyperbola. Unlike previous studies, the Stress:Strain properties of the series elastic component measured by quick release (ΔL/Li vs. ΔP/Po) were linear and gastrocnemius was 25 per cent higher than the semitendinosus. Overall, both muscles were found to have mechanical properties that differed little from the previously reported literature for amphibian, cardiac and small mammalian muscles studied by others in vitro. The major differences that we found were in the shapes of the force:velocity curve of the contractile component, and the Stress:Strain curve of series elastic component. Equations and explanations for these differences are devised and presented.
Cinaciguat (BAY-582667) Modifies Cardiopulmonary and Systemic Circulation in Chronically Hypoxic and Pulmonary Hypertensive Neonatal Lambs in the Alto Andino
Authors: Beñaldo Felipe A. , Araya-Quijada Claudio , Ebensperger Germán , Herrera Emilio A. , Reyes Roberto V. , Moraga Fernando A. , Riquelme Alexander , Gónzalez-Candia Alejandro , Castillo-Galán Sebastián , Valenzuela Guillermo J. , Serón-Ferré María , Llanos Aníbal J. 
Published: June 2022

Neonatal pulmonary hypertension (NPHT) is produced by sustained pulmonary vasoconstriction and increased vascular remodeling. Soluble guanylyl cyclase (sGC) participates in signaling pathways that induce vascular vasodilation and reduce vascular remodeling. However, when sGC is oxidized and/or loses its heme group, it does not respond to nitric oxide (NO), losing its vasodilating effects. sGC protein expression and function is reduced in hypertensive neonatal lambs. Currently, NPHT is treated with NO inhalation therapy; however, new treatments are needed for improved outcomes. We used Cinaciguat (BAY-582667), which activates oxidized and/or without heme group sGC in pulmonary hypertensive lambs studied at 3,600 m. Our study included 6 Cinaciguat-treated (35 ug kg−1 day−1x 7 days) and 6 Control neonates. We measured acute and chronic basal cardiovascular variables in pulmonary and systemic circulation, cardiovascular variables during a superimposed episode of acute hypoxia, remodeling of pulmonary arteries and changes in the right ventricle weight, vasoactive functions in small pulmonary arteries, and expression of NO-sGC-cGMP signaling pathway proteins involved in vasodilation. We observed a decrease in pulmonary arterial pressure and vascular resistance during the acute treatment. In contrast, the pulmonary pressure did not change in the chronic study due to increased cardiac output, resulting in lower pulmonary vascular resistance in the last 2 days of chronic study. The latter may have had a role in decreasing right ventricular hypertrophy, although the direct effect of Cinaciguat on the heart should also be considered. During acute hypoxia, the pulmonary vascular resistance remained low compared to the Control lambs. We observed a higher lung artery density, accompanied by reduced smooth muscle and adventitia layers in the pulmonary arteries. Additionally, vasodilator function was increased, and vasoconstrictor function was decreased, with modifications in the expression of proteins linked to pulmonary vasodilation, consistent with low pulmonary vascular resistance. In summary, Cinaciguat, an activator of sGC, induces cardiopulmonary modifications in chronically hypoxic and pulmonary hypertensive newborn lambs. Therefore, Cinaciguat is a potential therapeutic tool for reducing pulmonary vascular remodeling and/or right ventricular hypertrophy in pulmonary arterial hypertension syndrome.