bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA
Authors: Thakral Deepshi , Gupta Ritu , Sahoo Ranjit Kumar , Verma Pramod , Kumar Indresh , Vashishtha Sangeeta
Published: December 2020

The clonal evolution of acute myeloid leukemia (AML), an oligoclonal hematological malignancy, is driven by a plethora of cytogenetic abnormalities, gene mutations, abnormal epigenetic patterns, and aberrant gene expressions. These alterations in the leukemic blasts promote clinically diverse manifestations with common characteristics of high relapse and drug resistance. Defining and real-time monitoring of a personalized panel of these predictive genetic biomarkers is rapidly being adapted in clinical setting for diagnostic, prognostic, and therapeutic decision-making in AML. A major challenge remains the frequency of invasive biopsy procedures that can be routinely performed for monitoring of AML disease progression. Moreover, a single-site biopsy is not representative of the tumor heterogeneity as it is spatially and temporally constrained and necessitates the understanding of longitudinal and spatial subclonal dynamics in AML. Hematopoietic cells are a major contributor to plasma cell-free DNA, which also contain leukemia-specific aberrations as the circulating tumor-derived DNA (ctDNA) fraction. Plasma cell-free DNA analysis holds immense potential as a minimally invasive tool for genomic profiling at diagnosis as well as clonal evolution during AML disease progression. With the technological advances and increasing sensitivity for detection of ctDNA, both genetic and epigenetic aberrations can be qualitatively and quantitatively evaluated. However, challenges remain in validating the utility of liquid biopsy tools in clinics, and universal recommendations are still awaited towards reliable diagnostics and prognostics. Here, we provide an overview on the scope of ctDNA analyses for prognosis, assessment of response to treatment and measurable residual disease, prediction of disease relapse, development of acquired resistance and beyond in AML.
A Suite of Tools for Continuous Land Change Monitoring in Google Earth Engine
Authors: Arévalo Paulo , Bullock Eric L. , Woodcock Curtis E. , Olofsson Pontus
Published: December 2020

Land cover has been designated by the Global Climate Observing System (GCOS) as an Essential Climate Variable due to its integral role in many climate and environmental processes. Land cover and change affect regional precipitation patterns, surface energy balance, the carbon cycle and biodiversity. Accurate information on land cover and change is essential for climate change mitigation programs such as UN-REDD+. Still, uncertainties related to land change are large, in part due to the use of traditional land cover and change mapping techniques that use one or a few remotely sensed images, preventing a comprehensive analysis of ecosystem change processes. The opening of the Landsat archive and the initiation of the Copernicus Program have enabled analyses based on time series data, allowing the scientific community to explore global land cover dynamics in ways that were previously limited by data availability. One such method is the Continuous Change Detection and Classification algorithm (CCDC), which uses all available Landsat data to model temporal-spectral features that include seasonality, trends, and spectral variability. Until recently, the CCDC algorithm was restricted to academic environments due to computational requirements and complexity, preventing its use by local practitioners. The situation has changed with the recent implementation of CCDC in the Google Earth Engine, which enables analyses at global scales. What is still missing are tools that allow users to explore, analyze and process CCDC outputs in a simplified way. In this paper, we present a suite of free tools that facilitate interaction with CCDC outputs, including: (1) time series viewers of CCDC-generated time segments; (2) a spatial data viewer to explore CCDC model coefficients and derivatives, and visualize change information; (3) tools to create land cover and land cover change maps from CCDC outputs; (4) a tool for unbiased area estimation of key climate-related variables like deforestation extent; and (5) an API for accessing the functionality underlying these tools. We illustrate the usage of these tools at different locations with examples that explore Landsat time series and CCDC coefficients, and a land cover change mapping example in the Southeastern USA that includes area and accuracy estimates.
Spatial Distribution of the Input of Insoluble Particles Into the Surface of the Qaanaaq Glacier, Northwestern Greenland
Authors: Matoba Sumito , Hazuki Ryo , Kurosaki Yutaka , Aoki Teruo
Published: December 2020

From glaciological observations, we found spatial variation in the input of insoluble particles (ISP) on a glacier surface from atmospheric deposition and outcropping at the surface of the glacier by surface ablation at the ablation area of the Qaanaaq Ice Cap in northwestern Greenland. Possible sources of ISP input to the glacier surface were outcropping at the surface of the glacier by ablation at intermediate and low elevations, and from atmospheric deposition at high elevations. The annual atmospheric deposition of ISP was larger at high elevations than at intermediate and low elevations. The annual abundance of outcropping ISP was larger at intermediate elevations than at low elevations, where the annual ablation rate of the glacier surface was 1.5 times larger than at intermediate elevations. The ISP concentration in the glacier ice at intermediate sites was approximately 10 times larger than at low sites. The water stable isotopes of glacier ice at intermediate sites indicated that glacier ice at the intermediate sites did not form since the last glacial maximum, possibly the Holocene Thermal Maximum. Therefore, the accumulation of the ISP, which is outcropping at the intermediate site, occurred at high elevations after Holocene Thermal Maximum.
Mesozoic Paleo-Pacific Subduction Beneath SW Borneo: U-Pb Geochronology of the Schwaner Granitoids and the Pinoh Metamorphic Group
Authors: Breitfeld H. Tim , Davies Lorin , Hall Robert , Armstrong Richard , Forster Marnie , Lister Gordon , Thirlwall Matthew , Grassineau Nathalie , Hennig-Breitfeld Juliane , van Hattum Marco W. A.
Published: December 2020

The Schwaner Mountains in southwestern Borneo form a large igneous province with a complex magmatic history and poorly known tectonic history. Previously it was known that Cretaceous granitoids intruded metamorphic rocks of the Pinoh Metamorphic Group assumed to be of Paleozoic age. Jurassic granitoids had been reported from the southern Schwaner Mountains. Most ages were based on K-Ar dating. We present new geochemistry, zircon U-Pb and40Ar/39Ar age data from igneous and metamorphic rocks from the Schwaner Mountains to investigate their tectono-magmatic histories. We subdivide the Schwaner Mountains into three different zones which record rifting, subduction-related and post-collisional magmatism. The Northwest Schwaner Zone (NWSZ) is part of the West Borneo Block which in the Triassic was within the Sundaland margin. It records Triassic to Jurassic magmatism during early Paleo-Pacific subduction. In contrast, the North Schwaner Zone (NSZ) and South Schwaner Zone (SSZ) are part of the SW Borneo (Banda) Block that separated from NW Australia in the Jurassic. Jurassic granitoids in the SSZ are within-plate (A-type) granites interpreted to have formed during rifting. The SW Borneo (Banda) Block collided with eastern Sundaland at c. 135 Ma. Following this, large I-type granitoid plutons and arc volcanics formed in the NWSZ and NSZ between c. 90 and 132 Ma, associated with Cretaceous Paleo-Pacific subduction. The largest intrusion is the c. 110 to 120 Ma Sepauk Tonalite. After collision of the East Java-West Sulawesi (Argo) Block, subduction ceased and post-collisional magmatism produced the c. 78 to 85 Ma Sukadana Granite and the A-type 72 Ma Sangiyang Granite in the SSZ. Rocks of the Pinoh Metamorphic Group mainly exposed in the NSZ, previously assumed to represent Paleozoic basement, contain abundant Early Cretaceous (110 to 135 Ma) zircons. They are interpreted as volcaniclastic sediments that formed contemporaneously with subduction-related volcanic rocks of the NSZ subsequently metamorphosed during intrusion of Cretaceous granitoids. There are no igneous rocks older than Cretaceous in the NSZ and older than Jurassic in the SSZ and there is no evidence for a continuation of a Triassic volcanic arc crossing Borneo from Sundaland to the east.
Prevalence of Diabetes and Its Determinants in the Young Adults Indian Population-Call for Yoga Intervention
Authors: Nagarathna Raghuram , Bali Parul , Anand Akshay , Srivastava Vinod , Patil Suchitra , Sharma Guruprasad , Manasa Krishna , Pannu Viraaj , Singh Amit , Nagendra Hongasandra R.
Published: December 2020

Background

The young Indian population, which constitutes 65% of the country, is fast adapting to a new lifestyle, which was not known earlier. They are at a high risk of the increasing burden of diabetes and associated complications. The new evolving lifestyle is not only affecting people’s health but also mounting the monetary burden on a developing country such as India.

Aim

We aimed to collect information regarding the prevalence of risk of diabetes in young adults (<35 years) in the 29 most populous states and union territories (7 zones) of India, using a validated questionnaire.

Methods

A user-friendly questionnaire-based survey using a mobile application was conducted on all adults in the 29 most populous states/union territories of India, after obtaining ethical clearance for the study. Here, we report the estimation of the prevalence of the risk of diabetes and self-reported diabetes on 58,821 young individuals below the age of 35 years. Risk for diabetes was assessed using a standardized instrument, the Indian diabetes risk score (IDRS), that has 4 factors (age, family history of diabetes, waist circumference, and physical activity). Spearman’s correlation coefficient was used to check the correlations.

Results

The prevalence of high (IDRS score > 60), moderate (IDRS score 30–50), and low (IDRS < 30) diabetes risk in young adults (<35 years) was 10.2%, 33.1%, and 56.7%, respectively. Those with high-risk scores were highest (14.4%) in the Jammu zone and lowest (4.1%) in the central zone. The prevalence of self-reported diabetes was 1.8% with a small difference between men (1.7%) and women (1.9%), and the highest (8.4%) in those with a parental history of diabetes. The south zone had the highest (2.5%), and the north west zone had the lowest (4.4%) prevalence.

Conclusions

Indian youth are at high risk for diabetes, which calls for an urgent action plan through intensive efforts to promote lifestyle behavior modifications during the pandemics of both communicable and noncommunicable diseases.
Cytokines, Adipokines, and Bone Markers at Rest and in Response to Plyometric Exercise in Obese vs Normal Weight Adolescent Females
Authors: Kurgan Nigel , McKee Katherine , Calleja Melissa , Josse Andrea R. , Klentrou Panagiota
Published: December 2020

Background

In adults, excess adiposity has been associated with low-grade, chronic inflammation and compromised bone health, but less is known about these linkages in children. The purpose of this study was to compare the circulating levels of inflammatory cytokines, adipokines, osteokines, and bone markers at rest and in response to plyometric exercise between obese and normal weight adolescent females.

Methods

Ten normal weight (BMI = 21.3 ± 2) and 10 obese (BMI = 32.9 ± 4), postmenarcheal females, aged 13–17 years, performed one bout of plyometric exercise (5 circuits; 120 jumps). Blood samples were taken at rest, 5 min, 1 h, and 24 h post-exercise. Tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), insulin, leptin, osteocalcin, carboxy-terminal telopeptide (CTX), sclerostin, and parathyroid hormone (PTH) were measured in serum.

Results

Cytokines were not different between groups at rest or over time with IL-6 increasing (+31%; p = 0.04) 5 min post-exercise and TNF-α decreasing (-9%; p = 0.001) 1 h post-exercise. Insulin and leptin were higher in the obese compared to the normal weight females. In both groups, insulin significantly increased 5 min post-exercise but remained elevated 1 h post-exercise only in the obese group. Leptin did not change in response to exercise. Osteocalcin was lower in the obese group across time and increased (+12%; p = 0.02) 24 h post-exercise in both groups. CTX was similar between groups at rest and decreased (-24%; p < 0.001) 1 h post-exercise. Sclerostin was similar between groups at rest, but there was a significant interaction reflecting a significant increase (+29%; p = 0.04) 5 min post-exercise in the obese group and a non-significant decrease (-13%; p = 0.08) in normal weight controls. PTH increased 5 min post-exercise, dropped 1 h post-exercise to lower than pre-exercise, and returned to baseline 24 h post-exercise in both groups.

Conclusion

Obese adolescent females from our study had no evidence of resting inflammation or differences in bone resorption but show blunted bone formation when compared to normal weight controls. The direction and temporal changes in inflammatory cytokines, adipokines, and bone turnover markers to exercise were similar in both groups, reflecting an overall bone anabolic response for most biomarkers, except sclerostin, which increased only in the obese females immediately post-exercise, suggesting a different systemic regulation of sclerostin depending on adiposity.
Bio-Functional Sperm Parameters: Does Age Matter?
Authors: Condorelli Rosita A. , La Vignera Sandro , Barbagallo Federica , Alamo Angela , Mongioì Laura M. , Cannarella Rossella , Aversa Antonio , Calogero Aldo E.
Published: December 2020

The evaluation of biofunctional sperm parameters can explain some cases of idiopathic male infertility. Among these, sperm DNA fragmentation (fDNA) is the most studied biofunctional sperm parameter. Mitochondrial membrane potential (MMP) correlates positively with sperm motility, the evaluation of sperm apoptosis by flow cytometry allows us to identify a population of spermatozoa not recognizable at the optical microscopy and finally, lipid peroxidation (LP) and mitochondrial superoxide levels measurements are rational oxidative stress indices. Male age seems to affect sperm concentration and sperm fDNA. For these reasons, this study was undertaken to evaluate the correlation, if any, between male age and biofunctional sperm parameters evaluating their possible impact on fDNA. To accomplish this, MMP, degree of chromatin compactness, sperm apoptosis/vitality, fDNA, LP, and mitochondrial superoxide levels were evaluated by flow cytometry in a cohort of 874 men. A significant negative correlation was found between age and the percentage of alive spermatozoa (r = -0.75, p < 0.05). The percentage of spermatozoa with low MMP (L-MMP) correlated positively with the percentage of spermatozoa with abnormal chromatin compactness (r = 0.24, p < 0.05). Spermatozoa with abnormal chromatin compactness and L-MMP correlated negatively with the percentage of alive spermatozoa (r = 0.83, p < 0.05) and positively with spermatozoa with PS externalization (r = 0.13, p < 0.01). The percentage of alive spermatozoa correlated negatively with both the percentage of spermatozoa with PS externalization (r = 0.24, p < 0.01) and of the spermatozoa with fDNA (r = 0.10, p < 0.05). Spermatozoa with PS externalization correlated positively with the percentage of spermatozoa with fDNA (r = 0.09, p < 0.05). Spermatozoa with LP correlated positively with the percentage of spermatozoa with increased mitochondrial superoxide (r = 0.11, p < 0.01) In conclusion, these findings in a large number of men suggest that age, mitochondrial damage, and alteration of chromatin compactness could activate the apoptotic cascade which could result in an increased fDNA rate.
Genetic and Clinical Profiles of Pheochromocytoma and Paraganglioma: A Single Center Study
Authors: Ma Xiaosen , Li Ming , Tong Anli , Wang Fen , Cui Yunying , Zhang Xuebin , Zhang Yushi , Chen Shi , Li Yuxiu
Published: December 2020

Pheochromocytoma/paraganglioma (PPGL) has a high genetic heterogeneity with 40% germline variants in known pathogenic genes. Data in Chinese on this aspect are scanty. To detect the genetic and clinical profile of Chinese PPGL patients, we examined the variants of 12 known germline pathogenic genes (SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, VHL, RET, NF1, MAX, TMEM127, and KIF1B) by next-generation sequencing and Sanger sequencing in 314 Chinese PPGL subjects. Twenty nine percent of Chinese PPGL patients had germline variants and SDHB was the most frequently mutated (14.6%). The most frequent SDHB variants were in exon 2, exon 7, and IVS 7. Pathogenic variants were more likely to occur in metastatic PPGL patients, paragangliomas, and patients under 30, with the ratio being 50.7% (35/69), 35.9% (56/156), and 49.5% (52/105), respectively. Our cohort included 314 patients from a single setting. The genetic and clinical features of Chinese PPGL patients were unique in some aspects compared to their non-Chinese counterparts. Identification of genotype-phenotype relation can serve as an effective tool for genetic prioritization and clinical decision-making.
Icaritin Enhancing Bone Formation Initiated by Sub-Microstructured Calcium Phosphate Ceramic for Critical Size Defect Repair
Authors: Peng Haitao , Li Jianxiao , Xu Yanan , Lv Guoyu
Published: December 2020

Adequate bone tissue regeneration has been challenging to achieve at critical-sized bone defects caused by disease. Bone tissue engineering using a combination of scaffolds and bioactive factors provides new hope for the treatment of this extreme condition. Icaritin, a herb-derived chemical, has shown its ability to enhance bone formation both in vitro and in vivo, and it has been found that sub-micron surface structure instructs bone formation in calcium phosphate ceramics (CaPs). Here, we evaluated the possibility of using a submicron surface structured CaP ceramic as the carrier of icaritin for bone tissue regeneration in critical-sized bone defects. Icaritin, an herb-derived chemical, was loaded into a submicron surface structured porous calcium phosphate ceramic (Ø12.8 × 3 mm) to get samples with 0, 10, 50, 250, and 1,250 µg icaritin per CaP disc (M0, M10, M50, M250, M1250 groups, respectively). In vitro evaluation with the certain dosages correlated to those released from the samples showed a dose-dependent enhancement of osteogenic differentiation and mineralization of human bone marrow stromal cells with the presence of osteogenic factors in the culture medium, indicating icaritin is an osteopromotive factor. After intramuscular implantation of the samples in dogs for 8 weeks, a dose-dependent of bone formation was seen with enhanced bone formation at the dosage of 50 and 250 µg. To evaluate the in vivo osteogenic potentials of icaritin-containing CaP ceramic scaffolds in the orthopedic site, a 12.8 mm calvarial defect model in rabbits was established. Micro-computed tomography (micro-CT) and histology results at weeks 4, 8 and 12 post-surgery showed more newly formed bone in M250 group, with correspondingly more new vessel ingrowth. The results presented herein suggested that being osteopromotive, icaritin could enhance bone formation initiated by sub-microstructured CaP ceramics and the CaP ceramics scaffold incorporating icaritin is a promising biomaterial for the treatment of critical-sized defect.
A Contemporary View of the Diagnosis of Osteoporosis in Patients With Axial Spondyloarthritis
Authors: Lim Mie Jin , Kang Kwi Young
Published: December 2020

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily affects the axial joints. Altered bone metabolism associated with chronic inflammation leads to both new bone formation in the spine and increased bone loss. It is known that patients with axSpA have a high prevalence of osteoporosis and fractures. However, there is no consensus on which imaging modality is the most appropriate for diagnosing osteoporosis in axSpA. Bone mineral density measurement using dual-energy X-ray absorptiometry is the primary diagnostic method for osteoporosis, but it has notable limitations in patients with axSpA. This method may lead to the overestimation of bone density in patients with axSpA because they often exhibit abnormal calcification of spinal ligaments or syndesmophytes. Therefore, the method may not provide adequate information about bone microarchitecture. These limitations result in the underdiagnosis of osteoporosis. Recently, new imaging techniques, such as high-resolution peripheral quantitative computed tomography, and trabecular bone score have been introduced for the evaluation of osteoporosis risk in patients with axSpA. In this review, we summarize the current knowledge regarding imaging techniques for diagnosing osteoporosis in patients with axSpA.
Increased Red Cell Distribution Width Is Associated With Disease Severity in Hospitalized Adults With SARS-CoV-2 Infection: An Observational Multicentric Study
Authors: Karampitsakos Theodoros , Akinosoglou Karolina , Papaioannou Ourania , Panou Vassiliki , Koromilias Athanasios , Bakakos Petros , Loukides Stelios , Bouros Demosthenes , Gogos Charalampos , Tzouvelekis Argyrios
Published: December 2020

Background: There is an amenable need for clinically applicable biomarkers in patients with SARS-CoV-2 infection. Red Cell Distribution Width (RDW) has been recently suggested as a prognostic biomarker for COVID-19.

Methods: This was an observational study enrolling patients between February 26 and May 15 2020. We aimed to validate the association of the previously published RDW threshold of 14.5% with markers of disease progression and mortality.

Results: A total number of 193 hospitalized patients with COVID-19 were enrolled and analyzed. Median age was 61 years (95% CI: 58–64). Patients with baseline RDW ≥14.5% (n = 41, 19.2%) presented with more progressive disease compared to patients with baseline RDW <14.5% (n = 156, 80.8%) as indicated by significant differences in maximum FiO2% during hospitalization (median: 100, 95% CI: 45.2–100, vs. 35, 95% CI: 31–40, p = 0.0001, respectively). Values of RDW ≥14.5% were also strongly associated with increased risk of mortality (HR: 4.1, 95% CI: 0.88–19.23), (p = 0.02).

Conclusion: Our study provides evidence to support reproducibility and validity of a specified cut-off threshold of RDW as biomarker of disease severity and mortality in patients with COVID-19.
Mode-of-Action of Antimicrobial Peptides: Membrane Disruption vs. Intracellular Mechanisms
Authors: Benfield Aurélie H. , Henriques Sónia Troeira
Published: December 2020

Antimicrobial peptides are an attractive alternative to traditional antibiotics, due to their physicochemical properties, activity toward a broad spectrum of bacteria, and mode-of-actions distinct from those used by current antibiotics. In general, antimicrobial peptides kill bacteria by either disrupting their membrane, or by entering inside bacterial cells to interact with intracellular components. Characterization of their mode-of-action is essential to improve their activity, avoid resistance in bacterial pathogens, and accelerate their use as therapeutics. Here we review experimental biophysical tools that can be employed with model membranes and bacterial cells to characterize the mode-of-action of antimicrobial peptides.
Effect of Bone Marrow Stromal Cells in Parkinson's Disease Rodent Model: A Meta-Analysis
Authors: Liu Jianyang , He Jialin , Huang Yan , Hu Zhiping
Published: December 2020

Background: Bone marrow stromal cells (BMSCs) has been reported to have beneficial effects in improving behavioral deficits, and rescuing dopaminergic neuron loss in rodent models of Parkinson's disease (PD). However, their pooled effects for dopaminergic neuron have yet to be described.

Objective: To review the neuroprotective effect of naïve BMSCs in rodent models of PD.

Methods: The PubMed, EMBASE, and Web of Science databases were searched up to September 30, 2020. Inclusion criteria according to PICOS criteria were as follows: (1) population: rodents; (2) intervention: unmodified BMSCs; (3) comparison: not specified; (4) primary outcome: tyrosine hydroxylase level in the substantia nigra pars compacta and rotational behavior; secondary outcome: rotarod test, and limb function; (5) study: experimental studies. Multiple prespecified subgroup and meta-regression analysis were conducted. Following quality assessment, random effects models were used for this meta-analysis.

Results: Twenty-seven animal studies were included. The median quality score was 4.7 (interquartile range, 2–8). Overall standardized mean difference between animals treated with naïve BMSCs and controls was 2.79 (95% confidence interval: 1.70, 3.87; P < 0.001) for densitometry of tyrosine hydroxylase-positive staining; −1.54 (95% confidence interval: −2.11, −0.98; P < 0.001) for rotational behavior. Significant heterogeneity among studies was observed.

Conclusions: Results of this meta-analysis suggest that naïve BMSCs therapy increased dopaminergic neurons and ameliorated behavioral deficits in rodent models of PD.
The Olfactory Bulb Facilitates Use of Category Bounds for Classification of Odorants in Different Intensity Groups
Authors: Losacco Justin , George Nicholas M. , Hiratani Naoki , Restrepo Diego
Published: December 2020

Signal processing of odor inputs to the olfactory bulb (OB) changes through top-down modulation whose shaping of neural rhythms in response to changes in stimulus intensity is not understood. Here we asked whether the representation of a high vs. low intensity odorant in the OB by oscillatory neural activity changed as the animal learned to discriminate odorant concentration ranges in a go-no go task. We trained mice to discriminate between high vs. low concentration odorants by learning to lick to the rewarded group (low or high). We recorded the local field potential (LFP) in the OB of these mice and calculated the theta-referenced beta or gamma oscillation power (theta phase-referenced power, or tPRP). We found that as the mouse learned to differentiate odorant concentrations, tPRP diverged between trials for the rewarded vs. the unrewarded concentration range. For the proficient animal, linear discriminant analysis was able to predict the rewarded odorant group and the performance of this classifier correlated with the percent correct behavior in the odor concentration discrimination task. Interestingly, the behavioral response and decoding accuracy were asymmetric as a function of concentration when the rewarded stimulus was shifted between the high and low odorant concentration ranges. A model for decision making motivated by the statistics of OB activity that uses a single threshold in a logarithmic concentration scale displays this asymmetry. Taken together with previous studies on the intensity criteria for decisions on odorant concentrations, our finding suggests that OB oscillatory events facilitate decision making to classify concentrations using a single intensity criterion.
Rehabilitation Before and After Autologous Haematopoietic Stem Cell Transplantation (AHSCT) for Patients With Multiple Sclerosis (MS): Consensus Guidelines and Recommendations for Best Clinical Practice on Behalf of the Autoimmune Diseases Working Party, Nurses Group, and Patient Advocacy Committee of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Roberts Fiona , Hobbs Helen , Jessop Helen , Bozzolini Cristina , Burman Joachim , Greco Raffaella , Ismail Azza , Kazmi Majid , Kirgizov Kirill , Mancardi Gianluigi , Mawson Susan , Muraro Paolo A. , Puyade Mathieu , Saccardi Riccardo , Withers Barbara , Verhoeven Bregje , Sharrack Basil , Snowden John A.
Published: December 2020

Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly used to treat people with multiple sclerosis (MS). Supported by an evolving evidence base, AHSCT can suppress active inflammation in the central nervous system and induce long-term changes in immune cell populations, thereby stabilizing, and, in some cases, reversing disability in carefully selected MS patients. However, AHSCT is an intensive chemotherapy-based procedure associated with intrinsic risks, including profound cytopenia, infection, and organ toxicity, accompanied by an on-going degree of immuno-compromise and general deconditioning, which can be associated with a transient increase in functional impairment in the early stages after transplantation. Although international guidelines and recommendations have been published for clinical and technical aspects of AHSCT in MS, there has been no detailed appraisal of the rehabilitation needed following treatment nor any specific guidelines as to how this is best delivered by hospital and community-based therapists and wider multidisciplinary teams in order to maximize functional recovery and quality of life. These expert consensus guidelines aim to address this unmet need by summarizing the evidence-base for AHSCT in MS and providing recommendations for current rehabilitation practice along with identifying areas for future research and development.
Clinical Relevance of State-of-the-Art Analysis of Surface Electromyography in Cerebral Palsy
Authors: Cappellini Germana , Sylos-Labini Francesca , Assenza Carla , Libernini Laura , Morelli Daniela , Lacquaniti Francesco , Ivanenko Yury
Published: December 2020

Surface electromyography (sEMG) can be used to assess the integrity of the neuromuscular system and its impairment in neurological disorders. Here we will consider several issues related to the current clinical applications, difficulties and limited usage of sEMG for the assessment and rehabilitation of children with cerebral palsy. The uniqueness of this methodology is that it can determine hyperactivity or inactivity of selected muscles, which cannot be assessed by other methods. In addition, it can assist for intervention or muscle/tendon surgery acts, and it can evaluate integrated functioning of the nervous system based on multi-muscle sEMG recordings and assess motor pool activation. The latter aspect is especially important for understanding impairments of the mechanisms of neural controllers rather than malfunction of individual muscles. Although sEMG study is an important tool in both clinical research and neurorehabilitation, the results of a survey on the clinical relevance of sEMG in a typical department of pediatric rehabilitation highlighted its limited clinical usage. We believe that this is due to limited knowledge of the sEMG and its neuromuscular underpinnings by many physiotherapists, as a result of lack of emphasis on this important methodology in the courses taught in physical therapy schools. The lack of reference databases or benchmarking software for sEMG analysis may also contribute to the limited clinical usage. Despite the existence of educational and technical barriers to a widespread use of, sEMG does provide important tools for planning and assessment of rehabilitation treatments for children with cerebral palsy.
Prognostic Value of Preoperative Hydronephrosis in Patients Undergoing Radical Nephroureterectomy for Upper Tract Urinary Carcinoma: A Systematic Review and Meta-Analysis
Authors: Ye Tao , Yang Xiaoqi , Lv Peng , Liu Haoran , Ye Zhangqun
Published: December 2020

Background

Several recent publications have evaluated the prognostic value of preoperative hydronephrosis (HN) in patients with upper tract urinary carcinoma (UTUC). The aim of this meta-analysis was to explore the pooled effect of preoperative HN on the prognosis of UTUC patients treated with radical nephroureterectomy (RNU) based on current evidence.

Methods

We performed a systematic search of Pubmed, Cochrane library, and Web of Science databases from inception to June 2020. The outcomes of interest included overall survival (OS), cancer-special survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IVRFS).

Results

Twenty-two studies with a total of 7,542 patients satisfied the eligibility criteria and were finally included in this meta-analysis. The percent of patients with preoperative HN varied in the eligible studies, ranging from 18 to 81%. The pooled results showed that preoperative HN was significantly associated with worse OS (P = 0.004), CSS (P < 0.001), and DFS (P = 0.005), but not IVRFS (P = 0.12). No obvious publication bias was detected by Begg’s test in all the analyses.

Conclusions

The results drawn in our meta-analysis suggest that the presence of preoperative HN is associated with worse prognosis in patients treated with RNU for UTUC. Therefore, closer surveillance and more aggressive therapy may be needed for UTUC patients present with preoperative HN. Well-designed prospective studies are necessary to substantiate the prognostic value of HN in UTUC.
Case Report: Management of Cholestasis Associated With Congenital Syphilis
Authors: Ogawa Kotaro , Kawase Koya , Sugiura Tokio , Yasui Toshihiro , Yamagata Seiya , Watanabe Tamao , Kawabe Yoshikazu
Published: December 2020

Cholestasis is a rare but life-threatening complication of congenital syphilis. However, standard management methods for this disease have not been established. Here, we report a case of congenital syphilis presenting with progressively worsening cholestasis, and we review the clinical features and management practices. In these cases, differentiation from other diseases presenting with cholestasis during the neonatal period, such as biliary atresia, is critical. In this regard, operative cholangiogram and histopathological analysis of the liver are required. Moreover, comprehensive genetic analysis can be useful. Although there is no specific treatment for cholestasis associated with congenital syphilis, appropriate nutritional management and supplementation with fat-soluble vitamins, especially vitamin K, should be provided. The severity of liver fibrosis may affect the prognosis of cholestasis associated with congenital syphilis. Therefore, attention should be paid to liver fibrosis in these patients.
Scutellarin Reduce the Homocysteine Level and Alleviate Liver Injury in Type 2 Diabetes Model
Authors: Wang Yiyu , Fan Xiaoming , Fan Biao , Jiang Kerong , Zhang Haoxin , Kang Feng , Su Hui , Gu Danshan , Li Shude , Lin Shaofang
Published: December 2020

Scutellarin (SCU) is an active ingredient extracted from Erigeron breviscapus (Vaniot) Hand.-Mazz. Its main physiological functions are anti-inflammatory and antioxidant. In this study, we established a STZ-induced model of type 2 diabetes (T2DM) and a homocysteine (Hcy)-induced apoptosis model of LO2 to investigate whether SCU can alleviate liver damage by regulating Hcy in type 2 diabetes. Biochemical analysis indicated that SCU could improve the lipid metabolism disorder and liver function in diabetic rats by downregulating the levels of triglycerides (TG), cholesterol (CHO), low-density lipoprotein (LDL), alanine transaminase (ALT) and aspartate transaminase (AST), and by upregulating the level of high-density lipoprotein (HDL). Interestingly, SCU also could down-regulate the levels of Hcy and insulin and enhance the ability of type 2 diabetic rats to regulate blood glucose. Mechanistically, our results indicated that SCU may control the level of Hcy through regulating the levels of β-Cystathionase (CBS), γ-Cystathionase (CSE) and 5,10-methylenetetrahydrofolate (MTHFR) in liver tissue, and up-regulate folic acid, VitB6 and VitB12 levels in serum. Furthermore, SCU inhibits apoptosis in the liver of T2DM rats and in cultured LO2 cells treated with Hcy. Together, our findings suggest that SCU may alleviate the liver injury thorough downregulating the level of Hcy in T2DM rats.
Bortezomib-Based Regimens for Newly Diagnosed Multiple Myeloma in China: A Report of 12-Year Real-World Data
Authors: He Jingsong , He Donghua , Han Xiaoyan , Zheng Gaofeng , Wei Guoqing , Zhao Yi , Yang Yang , Wu Wenjun , Fu Jiaping , Shou Lihong , Kong Hongwei , Huang He , Cai Zhen
Published: December 2020

Background: Improve the treatment quality might affect patients’ efficacy and survival.

Methods: Five hundred thirty multiple myeloma patients treated in four hematological centers in China from February 2006 to August 2018 were enrolled. General characteristics, treatment regimens and cycles, efficacy, survival and adverse events of the patients treated before and after August 2013 (later refer to as the before-2013 and after-2013 group) were analyzed and compared.

Results: The results suggested that patients who received optimized treatment regimen and route of administration completed more cycles of treatment in the after-2013 group. Although the overall response rate was similar between the two groups (88.6 vs. 90.5%), patients in the after-2013 group had higher complete remission rate (39.1 vs. 28.6%) and better progression-free survival. Subgroup analysis suggested that patients aged 65 years and older, with non-high-risk D-S, ISS, and R-ISS stages, had a significant benefit in progression-free survival.

Conclusion: Therefore, in clinical practice in China, by reducing the economic burden brought by the treatment on patients and optimizing the treatment regimen, more patients can be treated with better regimens in a prolonged duration to achieve better efficacy and survival, especially in elderly and non-high-risk patients.
Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood–Air Barrier Hyperpermeability
Authors: Wang Tiantian , Liu Chunxia , Pan Ling-hui , Liu Zhen , Li Chang-long , Lin Jin-yuan , He Yi , Xiao Jing-yuan , Wu Siyi , Qin Yi , Li Zhao , Lin Fei
Published: December 2020

Background: Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process activated by lung transplantation and acute lung injury. The p38 mitogen-activated protein kinase (MAPK) is involved in breakdown of the endothelial barrier during LIRI, but the mechanism is still unclear. Therefore, we investigated the function of p38 MAPK in LIRI in vivo and in vitro.

Methods: Sprague–Dawley rats were subjected to ischemia reperfusion with or without pretreatment with a p38 MAPK inhibitor. Lung injury was assessed using hematoxylin and eosin staining, and pulmonary blood–air barrier permeability was evaluated using Evans blue staining. A rat pulmonary microvascular endothelial cell line was infected with lentiviral expressing short hairpin (sh)RNA targeting p38 MAPK and then cells were subjected to oxygen/glucose deprivation and reoxygenation (OGD/R). Markers of endothelial destruction were measured by western blot and immunofluorescence.

Results:In vivo LIRI models showed structural changes indicative of lung injury and hyperpermeability of the blood–air barrier. Inhibiting p38 MAPK mitigated these effects. Oxygen/glucose deprivation and reoxygenation promoted hyperpermeability of the endothelial barrier in vitro, but knockdown of p38 MAPK attenuated cell injury; maintained endothelial barrier integrity; and partially reversed injury-induced downregulation of permeability protein AQP1, endothelial protective protein eNOS, and junction proteins ZO-1 and VE-cadherin while downregulating ICAM-1, a protein involved in destroying the endothelial barrier, and ET-1, a protein involved in endothelial dysfunction.

Conclusion: Inhibition of p38 MAPK alleviates LIRI by decreasing blood–air hyperpermeability. Blocking p38 MAPK may be an effective treatment against acute lung injury.
Cellular Senescence in Kidney Fibrosis: Pathologic Significance and Therapeutic Strategies
Authors: Xu Jie , Zhou Lili , Liu Youhua
Published: December 2020

Age-related disorders such as chronic kidney disease (CKD) are increasingly prevalent globally and pose unprecedented challenges. In many aspects, CKD can be viewed as a state of accelerated and premature aging. Aging kidney and CKD share many common characteristic features with increased cellular senescence, a conserved program characterized by an irreversible cell cycle arrest with altered transcriptome and secretome. While developmental senescence and acute senescence may positively contribute to the fine-tuning of embryogenesis and injury repair, chronic senescence, when unresolved promptly, plays a crucial role in kidney fibrogenesis and CKD progression. Senescent cells elicit their fibrogenic actions primarily by secreting an assortment of inflammatory and profibrotic factors known as the senescence-associated secretory phenotype (SASP). Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. In this review, we discuss current understanding of the role and mechanism of cellular senescence in kidney fibrosis. We also highlight potential options of targeting senescent cells for the treatment of CKD.
Alpha-1 Antitrypsin for COVID-19 Treatment: Dual Role in Antiviral Infection and Anti-Inflammation
Authors: Yang Chengliang , Keshavjee Shaf , Liu Mingyao
Published: December 2020

Many drugs have been approved for clinical trials for the treatment of COVID-19 disease, focusing on either antiviral or anti-inflammatory approaches. Combining antiviral and anti-inflammatory drugs or therapies together may be more effective. Human alpha-1 antitrypsin (A1AT) is a blood circulating glycoprotein that is best known as a protease inhibitor. It has been used to treat emphysema patients with A1AT deficiency for decades. We and others have demonstrated its role in reducing acute lung injury by inhibiting inflammation, cell death, coagulation, and neutrophil elastase activation. Recently, A1AT has been found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by inhibiting transmembrane serine protease 2 (TMPRSS2), a protease involved in the entry of SARS-CoV-2 into host cells. This dual role of both antiviral infection and anti-inflammation makes A1AT a unique and excellent candidate for COVID-19 treatment. Three clinical trials of A1AT for COVID-19 treatment have recently been approved in several countries. It is important to determine whether A1AT can prevent the progress from moderate to severe lung injury and eventually to be used to treat COVID-19 patients with acute respiratory distress syndrome.
A Postcard From Italy: Challenges and Psychosocial Resources of Partners Living With and Without a Chronic Disease During COVID-19 Epidemic
Authors: Rapelli Giada , Lopez Giulia , Donato Silvia , Pagani Ariela Francesca , Parise Miriam , Bertoni Anna , Iafrate Raffaella
Published: December 2020

The new Coronavirus (COVID-19) has been declared a global pandemic by the World Health Organization (WHO). The sudden outbreak of this new virus and the measure of lockdown adopted to contain the epidemic have profoundly changed the lifestyles of the Italian population, with an impact on people’s quality of life and on their social relationships. In particular, due to forced and prolonged cohabitation, couples may be subject to specific stressors during the epidemic. In addition, living with a chronic health condition may add specific challenges to the ones posed by the epidemic itself. The present cross-sectional study aimed to provide a picture of the challenges as well as the resources for both individual and relational well-being of Italian individuals in a couple relationship (N= 1921), with a specific attention to the comparison between individuals living with and without a chronic disease. Results showed that people with a chronic disease had lower psychological well-being and more fears and worries about the COVID-19. People with a chronic disease perceived fewer resources than healthy people. Moreover, the challenges are shown to be associated with less psychological well-being and high pessimism about the future. Instead individual, relational, and social resources play a protective role during the pandemic for both healthy and chronically ill people.
Affects as Mediators of the Negative Effects of Discrimination on Psychological Well-Being in the Migrant Population
Authors: Urzúa Alfonso , Henríquez Diego , Caqueo-Urízar Alejandra
Published: December 2020

There is abundant empirical evidence on the negative effects of discrimination on psychological well-being. However, little research has focused on exploring the factors that can mitigate this effect. Within this framework, the present study examined the mediating role of positive and negative affects in the relationship between ethnic and racial discrimination and psychological well-being in the migrant population. About 919 Colombians, first-generation migrants, residing in Chile (Arica, Antofagasta, and Santiago) were evaluated, of which 50.5% were women, and the participants’ average age was 35 years (range: 18–65 years). Krieger’s discrimination questionnaires, Watson’s Positive and Negative Affect Schedule (PANAS), and Ryff’s Psychological Well-Being Scale were applied. The measurement models of each variable were estimated, and then the structural equation models were used. The results of the hypothesized multiple mediation model showed that the main mediator in the relationship between ethnic-racial discrimination and psychological well-being was positive affects over negative ones.