bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Study of Specific Loss Power and Transverse Relaxivity of Spinel Ferrite Nanoensembles Coated With Chitosan and Polyethylene Glycol
Authors: Hoque S. Manjura , Islam M. Khairul , Hoq Amitra , Haque M. Manjurul , Maritim Samuel , Coman Daniel , Hyder Fahmeed 
Published: April 2021

We synthesized spinel ferrite nanoensembles (MnFe2O4, CoFe2O4, and Fe3O4) using the chemical co-precipitation method and characterized their physical, chemical, and magnetic properties by X-ray diffraction (XRD), transmission electron microscopy (TEM), physical properties measurement system (PPMS), Mössbauer spectroscopy, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and Raman spectroscopy. Their relaxation properties and potential for hyperthermia therapy were determined using nuclear magnetic resonance (NMR) and cell viability assay, respectively. XRD and TEM data confirmed that the particle core sizes were 6–9 nm before coating while their sizes increased to 10–14 nm and 14–20 nm after coating with chitosan and polyethylene glycol (PEG), respectively. Mössbauer spectroscopy showed superparamagnetic behavior for MnFe2O4 nanoparticles and ferrimagnetic behavior for the CoFe2O4 and Fe3O4 nanoparticles. A detailed studies of MH loops of all three ferrites before and after coating showed surface functionalization by a large reduction of coercivity and anisotropy. The successful coating was further confirmed by the peak shifts in the FTIR spectra of the particles whereas Raman spectra of coated ferrites also displayed the characteristic absorption patterns and suppression of the ferrite peaks suggesting successful coating. The induced heating profile of the nanoparticles in stable suspension was tested with a radio frequency magnetic field of 76 mT and a frequency of 400 kHz. High mortality (&gt;98%) of 9 L gliosarcoma cancer cells by hyperthermia suggested that these nanoparticles could be used for cancer therapy. Transverse relaxivities (r2) determined by NMR for chitosan-coated MnFe2O4, CoFe2O4, and Fe3O4 nanoparticles were 297 (±22), 353 (±26), and 345 (±13), mM−1S−1, while for PEG-coated nanoparticles are 165 (±22), 146 (±14), and 159 (±07) mM−1S−1, respectively. Overall these spinel ferrite nanoensembles show great promise for cancer theranostics research applications.
Comparisons Between Frontline Therapy and a Combination of Eltrombopag Plus Immunosuppression Therapy and Human Leukocyte Antigen-Haploidentical Hematopoietic Stem Cell Transplantation in Patients With Severe Aplastic Anemia: A Systematic Review
Authors: Yang Yuan , Ji Jiang , Tang Zengwei , Han Bing 
Published: April 2021

Background and Aims: This study aimed at comparing the efficacy and safety of eltrombopag (EPAG) plus immunosuppressive therapies (ISTs) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the frontline treatment for severe aplastic anemia (SAA) patients.Methods: Four electronic databases and Clinicaltrials.gov were comprehensively searched from January 2010 to August 2020. Studies that aimed at evaluating the efficacy and safety of EPAG+IST or haplo-HSCT in SAA patients were included. One-/2-year overall survival (OS), complete response (CR), and overall response rates (ORRs) were indirectly compared between EPAG+IST and haplo-HSCT.Results: A total of 447 patients involved in 10 cohort studies were found to be eligible for this study. A narrative synthesis was performed due to lack of data directly comparing the outcome of EPAG+IST and haplo-HSCT. Consistent with the analysis results in the whole population, subgroup analyses in the age-matched population showed that there was no significant difference in ORR between EPAG+IST and haplo-HSCT groups. However, the CR rate was lower in the EPAG+IST group when compared with the haplo-HSCT group. The incidence rate of clonal evolution/SAA relapse ranged at 8–14 and 19–31% in the EPAG+IST group but not reported in the haplo-HSCT group. The incidence rate for acute graft vs. host disease (aGVHD) and chronic graft vs. host disease (cGVHD) ranged at 52–57 and 12–67%, respectively, for the haplo-HSCT group. The main causes of deaths were infections in the EPAG+IST group, and GVHD and infections in the haplo-HSCT group.Conclusion: EPAG+IST has a comparable ORR and 1-/2-year OS but lower CR rate when indirectly compared with haplo-HSCT in the frontline treatment of patients with SAA. Patients treated with haplo-HSCT may exhibit a high incidence of GVHD, whereas patients treated with EPAG+IST may experience more relapses or clone evolution.
Prognostic Models for Patients With Gleason Score 9 Prostate Cancer: A Population-Based Study
Authors: Qiu Jianhui , Cai Desheng , Wang Zixin , Zhou Jingcheng , Gong Yanqing , Cai Lin , Gong Kan 
Published: April 2021

Purpose: Gleason score (GS) system is one of the most widely used histological grading methods for prostate cancer (PCa) all over the world. GS can be obtained by adding the primary Gleason pattern (GP) and secondary GP. Different proportions of GP 4 and GP 5 in prostate specimens can both lead to GS 9. In this study, we explored whether GP 5 + 4 or GP 4 + 5 was associated with different prognoses among patients with GS 9 PCa.Materials and methods: A retrospective population-based study was conducted on 10,124 subjects diagnosed with GS 9 PCa between 2004 and 2009 from the Surveillance, Epidemiology, and End Results program. A 1:1 propensity-score matching (PSM) was performed to balance the baseline characteristics between the GP 4 + 5 and 5 + 4 groups and to compare the prognoses between the two groups. Cox regression analysis and Fine-Gray competing risk regression models were adopted to screen the covariates significantly associated with all-cause mortality (ACM) and cancer-specific mortality (CAM).Results: GP 5 + 4 was associated with higher risks of ACM and CSM before or after PSM than GP 4 + 5. In the original cohort, there were eight independent predictors for ACM, which were age at diagnosis, race, AJCC NM stage, PSA levels, treatments, GP, and marital status, confirmed by the Cox analysis; and nine independent predictors for CSM, which were age at diagnosis, race, AJCC TNM stage, PSA levels, treatments, GP, and marital status, confirmed by the competing-risk model.Conclusion: GP 5 + 4 was associated with a poorer overall survival and cancer-specific survival compared with GP 4 + 5.
Small Cell Lung Cancer Transformation as a Resistance Mechanism to Osimertinib in Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma: Case Report and Literature Review
Authors: Leonetti Alessandro , Minari Roberta , Mazzaschi Giulia , Gnetti Letizia , La Monica Silvia , Alfieri Roberta , Campanini Nicoletta , Verzè Michela , Olivani Andrea , Ventura Luigi , Tiseo Marcello 
Published: April 2021

Introduction: Small cell lung cancer (SCLC) transformation represents a mechanism of resistance to osimertinib in EGFR-mutated lung adenocarcinoma, which dramatically impacts patients' prognosis due to high refractoriness to conventional treatments.Case Description: We present the case of a patient who developed a SCLC phenotypic transformation as resistance mechanism to second-line osimertinib for T790M-positive EGFR-mutated NSCLC. Our patient received platinum–etoposide doublet following SCLC switch and achieved a modest clinical benefit which lasted 4 months. NGS and IHC analyses for p53 and Rb were performed on subsequent liver biopsies, revealing baseline TP53 mutation and complete absence of p53 and Rb expression. Primary cell cultures were established following a liver biopsy at the time of SCLC transformation, and drug sensitivity assays showed meaningful cell growth inhibition when osimertinib was added to platinum–etoposide compared with control (p &lt; 0.05). A review of the current literature regarding SCLC transformation after failure of osimertinib was performed.Conclusions: Based on retrospective data available to date, platinum–etoposide chemotherapy is the preferred treatment choice in the occurrence of SCLC transformation after osimertinib failure. The extension of osimertinib in combination with chemotherapy in the occurrence of SCLC transformation as resistance mechanism to osimertinib is a matter of debate. The combination of osimertinib and platinum–etoposide was effective in inhibiting cell growth in our primary cell cultures. Clinical studies are needed to further explore this combination in the occurrence of SCLC transformation as a resistance mechanism to osimertinib.
Mapping of Cervical and Upper Mediastinal Lymph Node Recurrence for Guiding Clinical Target Delineation of Postoperative Radiotherapy in Thoracic Esophageal Squamous Cell Carcinoma
Authors: Wang Yichun , Ye Dongmei , Kang Mei , Zhu Liyang , Yang Mingwei , Jiang Jun , Xia Wanli , Kang Ningning , Chen Xiangcun , Wang Jie , Wang Fan 
Published: April 2021

BackgroundThe lower neck and upper mediastinum are the major regions for postoperative radiotherapy (PORT) in thoracic esophageal squamous cell carcinoma (TESCC). However, there is no uniform standard regarding the delineation of nodal clinical target volume (CTVnd). This study aimed to map the recurrent lymph nodes in the cervical and upper mediastinal regions and explore a reasonable CTVnd for PORT in TESCC.MethodsWe retrospectively reviewed patients in our hospital with first cervical and/or upper mediastinal lymph node recurrence (LNR) after upfront esophagectomy. All of these recurrent lymph nodes were plotted on template computed tomography (CT) images with reference to surrounding structures. The recurrence frequency at different stations was investigated and the anatomic distribution of recurrent lymph nodes was analyzed.ResultsA total of 119 patients with 215 recurrent lymph nodes were identified. There were 47 (39.5%) patients with cervical LNR and 102 (85.7%) patients with upper mediastinal LNR. The high-risk regions were station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. LNR in the external group of station 104L/R was not common, and LNR was not found in the narrow spaces where the trachea was in close contact with the innominate artery, aortic arch and mediastinal pleura. LNR below the level of the cephalic margin of the superior vena cava was also not common for upper TESCC.ConclusionsThe CTVnd of PORT in the cervical and upper mediastinal regions should cover station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. Based on our results, we proposed a useful atlas for guiding the delineation of CTVnd in TESCC.
Identification of a Rare Exon 19 Skipping Mutation in ALMS1 Gene in Alström Syndrome Patients From Two Unrelated Saudi Families
Authors: Saadah Omar I. , Banaganapalli Babajan , Kamal Naglaa M. , Sahly Ahmed N. , Alsufyani Hadeel A. , Mohammed Arif , Ahmad Aftab , Nasser Khalidah Khalid , Al-Aama Jumana Y. , Shaik Noor Ahmad , Elango Ramu 
Published: April 2021

Background: Alström syndrome (AS) is a very rare childhood disorder characterized by cardiomyopathy, progressive hearing loss and blindness. Inherited genetic variants of ALMS1 gene are the known molecular cause of this disease. The objective of this study was to characterize the genetic basis and understand the genotype–phenotype relationship in Saudi AS patients.Methods: Clinical phenotyping and whole-exome sequencing (WES) analysis were performed on six AS patients belonging to two unrelated consanguineous Saudi families. Sanger sequencing was performed to determine the mode of inheritance of ALMS1 variant in first-degree family relatives and also to ensure its rare prevalence in 100 healthy population controls.Results: We identified that Alström patients from both the families were sharing a very rare ALMS1, 3′-splice site acceptor (c.11873−2 A&gt;T) variant, which skips entire exon-19 and shortens the protein by 80 amino acids. This disease variant was inherited by AS patients in autosomal recessive mode and is not yet reported in any population-specific genetic databases. AS patients carrying this mutation showed heterogeneity in clinical presentations. Computational analysis of the mutant centroid structure of ALMS1 mRNA revealed that exon-19 skipping enlarges the hairpin loop and decreases the free energy, eventually affecting its folding pattern, stability, and function. Hence, we propose c.11873–2A as an AS causative potential founder mutation in Saudi Arabia because it is found in two families lacking a common lineage.Conclusions: We conclude that WES analysis potentially helps in clinical phenotyping, early diagnosis, and better clinical management of Alström patients showing variable clinical expressivity.
Danshen (Salvia miltiorrhiza) on the Global Market: What Are the Implications for Products’ Quality?
Authors: Kum Ka Yui , Kirchhof Rainer , Luick Rainer , Heinrich Michael 
Published: April 2021

Background: Danshen (Radix et rhizoma Salviae miltiorrhizae; Salvia miltiorrhiza Bunge, Lamiaceae) is commonly used in Asia, including China, Japan, and Korea with markets in America and Europe growing substantially. It is included in multiple pharmacopeias and salvianolic acid B and tanshinone IIA are used as quality markers. However, on the markets, substitutes and different processing methods often are a concern. a concern regarding patients’ safety and expected outcomes.Aims: This study aims at understanding the quality of Danshen-derived products on the market, and the relationship between the chemistry, biological activity and the processing and storage methods.Methods: For heavy metal analysis, inductively coupled plasma optical emission spectrometry was used. High performance thin-layer chromatography and proton nuclear magnetic resonance coupled with principal component analysis were used to understand the variation of metabolite composition. MTT assay and LPS induced NO production assay were used to evaluate the cytotoxicity effect and anti-inflammatory activity, respectively.Result and Discussion: Six out of sixty samples exceed the limits of cadmium according to the Chinese or United States Pharmacopoeia. Arsenic, lead and copper contents are all below pharmacopoeial thresholds. With more complex processing procedure, the risk of heavy metal contamination increases, especially with arsenic and cadmium. The metabolite compositions show a variability linked to processing and storage methods. Authenticated samples and Vietnamese primary samples contain higher salvianolic acid B, and their chemical compositions are more consistent compared to Chinese online store samples. Overall, a significant chemical variation can be observed in Danshen products directly linked to processing and storage method. In the MTT assay, fourteen samples show cytotoxicity while seven samples increase the proliferation of RAW264.7. In the LPS induced NO production of RAW 264.7, only seven samples show significant inhibitory effects.Conclusion: This is the first interdisciplinary investigation focusing on understanding the current market and the quality of Danshen. The quality of Danshen products on the high street are inferior to the authenticated samples. The results of the bioassays selected is not useful to differentiate the quality and composition according to the current definition in the pharmacopoeias. Overall, this approach highlights the tremendous variability of the products linked to processing and the need for more systematic and stringent quality assurance.
Lentivirus-Carried microRNA-195 Rescues Memory Deficits of Alzheimer’s Disease Transgenic Mouse by Attenuating the Generation of Amyloid Plaques
Authors: Su Dan , Chai Yani , Yang Junkai , Wang Xuqiao , Liu Ying , Ma Jing , Tang Xin , Mishra Chandan , Chandra Shah Ram , Yue Weidong , Ai Jing 
Published: April 2021

Although lots of new drugs are developed to treat Alzheimer’s disease (AD), many clinical trials of monotherapy have failed to affect disease progression or symptoms compared with placebo. Recently, scientists believe that combination treatment is more promising than monotherapy. Previous studies found that microRNA-195 (miR-195) was down-regulated in the hippocampi and cortices of chronic brain hypoperfusion (CBH) rats and ApoE4(+/+) mice, and up-regulation of miR-195 can improve the declined cognitive function of ApoE4(+/+) mice and CBH rats by targeting multi-genes that are related to AD pathology, including amyloid precursor protein (APP) and β-site APP cleaving enzyme 1 (BACE1) genes. However, whether the gain-of-function of miR-195 could improve the impaired learning and memory ability of APP/PS1 transgenic mouse has not been reported. In this study, we stereotaxically injected lentiviral-carried miR-195 into the bilateral hippocampus of 4-month-old (4M) APP/PS1 mice. Morris water maze (MWM) was performed to detect the effect of miR-195 on the cognitive function of APP/PS1 mice after 1M, 2M, and 3M treatment. Western blot was used to detect the expression of APP, BACE1, and AT8. Aβ plagues were quantitatively assessed by immunofluorescence technique. We found that the declined cognitive phenotype of APP/PS1 mice occurred at the age of 6M, not at the age of 5M. And treatment of Lv-pre-miR-195 to APP/PS1 mice for 1M did not achieve any changes. Although Lv-pre-miR-195 treatment for 2M improved the declined learning ability of APP/PS1 mice, it did not affect the memory functions. However, Lv-pre-miR-195 treatment in APP/PS1 mice for 3M can effectively improve both the learning and memory ability of APP/PS1 mice at the age of 7M. Further studies demonstrated that gain-of-function of miR-195 by Lv-pre-miR-195 injection could inhibit the increased APP and AT8 expression of APP/PS1 mice but did not affect BACE1 level that was not changed in both hippocampus and cortex. By counting the number of Aβ plaques of different sizes, we found that Lv-pre-miR-195 treatment mainly reduced the number of Aβ plaques of less than 20 μm, but did not affect the number of Aβ plaques of greater than 50 μm. Taken together, the gain-of -function of miR-195 in the hippocampus can improve the cognition of APP/PS1 mice, probably by blocking the formation of Aβ plagues rather than clearing those that have already formed Aβ plagues.
A Retrospective Cohort Study on the Clinical Course of Patients With Moderate-Type COVID-19
Authors: Liao Xiaohua , Lv Xin , Song Cheng , Jiang Mao , He Ronglin , Han Yuanyuan , Li Mengyu , Zhang Yan , Jiang Yupeng , Meng Jie 
Published: April 2021

Background: A large number of people contracted moderate-type COVID-19 around the world. However, to our knowledge no studies have covered the clinical course of patients with moderate-type COVID-19. This study describes the clinical course of moderate-type patients with COVID-19 from Wuhan City and Yiyang City, and explores factors relevant to the length of hospitalization and symptoms relief.Methods: The study analyzed the clinical course of 107 moderate-type patients with COVID-19 from the outbreak area (Wuhan) and the imported area (Yiyang), and used automatic linear modeling and multivariate linear regression analysis to explore the factors relevant to the length of hospitalization and symptoms relief. Furthermore, we created a scoring system to value the length of hospitalization and symptoms relief.Results: Lymphopenia, elevated C-reactive protein, increased LDH, bilateral lung GGO (ground glass opacity), and lung consolidation were more likely to appear in ordinary inpatients with moderate-type COVID-19 from Wuhan (P &lt; 0.05), compared to infected medical staff from Wuhan and ordinary inpatients with moderate-type COVID-19 from Yiyang. Meanwhile, the length of hospitalization and symptoms relief was longer in ordinary patients with moderate-type COVID-19 from Wuhan (P &lt; 0.05). Onset of symptoms to admission, ESR, leucocytes count, and bilateral lung GGO were linearly related to the length of hospitalization (P &lt; 0.05); onset of symptoms to admission, leucocytes count, bilateral lung GGO, and lung consolidation were linearly related to the length of symptoms relief (P &lt; 0.05). By using the scoring system, we found that the time of hospitalization and symptoms relief lengthened as the scores increased.Conclusions: This study described the clinical course of patients with moderate-type COVID-19, and found that ordinary patients with moderate-type COVID-19 in outbreak areas were more serious and needed stronger treatment and longer treatment time. Onset of symptoms to admission, ESR, leucocytes count, and bilateral lung GGO can be effective predictors of the length of hospitalization. And onset of symptoms to admission, leucocytes count, bilateral lung GGO, and lung consolidation can be effective predictors of the amount of time until symptoms relief. Most importantly, we have created a scoring system, which could contribute to the diagnosis and treatment of COVID-19.
Impact of COVID-19 on the Mental Health of Healthcare Workers: A Cross-Sectional Study From Pakistan
Authors: Hayat Khezar , Arshed Muhammad , Fiaz Iqra , Afreen Urooj , Khan Faiz Ullah , Khan Tahir Abbas , Kadirhaz Muhtar , Shukar Sundus , Saeed Azwa , Gill Muhammad Rouf , Fang Yu 
Published: April 2021

Background: The novel coronavirus (COVID-19) pandemic has significantly increased the rate of mortality and morbidity worldwide due to its rapid transmission rate. The mental health status of individuals could have a negative impact attributed to this global situation. Therefore, this study was intended to explore the symptoms of depression and anxiety among healthcare workers (HCWs) of Pakistan during the ongoing COVID-19 pandemic.Methods: A cross-sectional survey was undertaken by administering a web-based questionnaire between May and June 2020. Two tools, including the Patient Health Questionnaire (PHQ9) and Generalized Anxiety Disorder-7 (GAD-7), were employed to measure anxiety and depression symptoms among HCWs. The data analyses were carried out using descriptive statistics, Man Whitney, and Kruskal Wallis tests.Results: Of 1094 HCWs who participated in this online survey, 742 (67.8%) were physicians, followed by nurses (n = 277, 25.3%) and pharmacists (n = 75, 6.9%). The survey respondents had a median depression and anxiety score of 5.00 (7.00–3.00) and 8.00 (11.00–5.00), respectively. A considerable number of HCWs (82.2%) utilized online psychological resources to deal with their psychological distress. Female HCWs, nurses, frontline HCWs, and HCWs aged 30–49 years were more likely to suffer from depression and anxiety (p &lt; 0.05).Conclusion: During the recent ongoing pandemic of COVID-19, there is a mild level of symptoms of depression and anxiety among HCWs. Our findings call for urgent psychological interventions for vulnerable groups of Pakistani HCWs.