bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of drug resistance mutation and signature pattern in the archived DNA of HIV-1 infected North Indian patients
Authors: Barik Sushanta Kumar , Mohanty Keshar Kunja , Mohanty Partha Sarathi , Hanna Luke Elizabeth , Karunaianantham Ramesh , Tripathy Srikanth Prasad , Tandon Rekha , Singh Tej Pal , Jena Srikanta
Published: May 2020

Background Characterization of drug resistance mutations and signature pattern in the archived DNA of HIV-1 infected North Indian patients.Methods Blood samples were collected from 9 patients enrolled in ART Centre, S.N. Medical College, Agra, North India from 1 year to = < 7 years. DNA was isolated and amplified for protease and reverse transcriptase genes using nested primers from WHO dried blood spot protocol 2010. The polymerase chain reaction products were sequenced and drug resistance mutation patterns were analysed using the HIV drug resistance database, Stanford University, USA. Various computational tools and websites like Stanford HIV drug resistance database, Viral epidemiological signature pattern analysis (VESPA), Hypermutation, SNAP version 2.1.1, Entropy were utilized for analysis of the sequence data.Results This study enables an analysis of archived DNA samples in patients having lower viral load and where the situation of HIV RNA isolation was negligible. Lamivudine associated drug-resistant mutations such as M184V/M184I, nevirapine associated mutations Y181C and H221Y and efavirenz associated mutations M230I were observed in two patients. No mutations were observed in the remaining seven patients. The signature pattern analysis of 9 protease and reverse transcriptase genes identified the conservation of amino acid sequences as compared to the reference sequence. The signature pattern of nucleotide substitution (synonymous to non-synonymous ratio) of the protease gene was 5.02 and the reverse transcriptase gene was 7.01. No hyper mutation was observed in the protease and reverse transcriptase gene of the archived DNA.Conclusions The analysis of the drug resistance mutation in the protease and reverse transcriptase gene of the archived DNA of HIV-1 subtype C infected patients over 1 to = < 7 years of first-line ART may be helpful in the treatment guideline in North Indian patients. A few signature amino acids were persisted in the reverse transcriptase and protease gene of similar HIV-1 subtype C infected patients over 1 to = < 7 years of first line ART in comparison to the reference sequence. This archived DNA drug resistance mutation testing could be an important tool when RNA testing becomes unsuccessful.
Influence factors of death risk among COVID-19 patients in Wuhan, China: a hospital-based case-cohort study
Authors: Fu Lin , Fei Jun , Xiang Hui-Xian , Xiang Ying , Li Meng-Die , Liu Fang-Fang , Li Ying , Zhao Hui , Xu De-Xiang
Published: May 2020

Background Coronavirus disease 2019 (COVID-19) triggered by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been widely pandemic all over the world. The aim of this study was to analyze the influence factors of death risk among 200 COVID-19 patients.Methods Two hundred patients with confirmed SARS-CoV-2 infection were recruited. Demographic data and clinical characteristics were collected from electronic medical records. Biochemical indexes on admission were measured and patient's prognosis was tracked. The association of demographic data, clinical characteristics and biochemical indexes with death risk was analyzed.Results Of 200 COVID-19 patients, 163 (81.5%) had at least one of comorbidities. Among all patients, critical cases accounted for 26.2%. Severe cases were 29.7%. Besides, common cases accounted for 44.1%. At the end of follow-up, 34 (17%) were died on mean 10.9 day after hospitalization. Stratified analysis revealed that older ages, lower oxygenation index and comorbidities elevated death risk of COVID-19 patients. On admission, 85.5% COVID-19 patients were with at least one of extrapulmonary organ injuries. Univariable logistic regression showed that ALT, TBIL, AST, myoglobin and LDH, AST/ALT ratio, creatinine, urea nitrogen and uric acid were positively associated with death risk of COVID-19 patients. Multivariable logistic regression revealed that AST/ALT ratio, urea nitrogen, TBIL and LDH on admission were positively correlated with death risk of COVID-19 patients.Conclusion Older age, lower oxygenation index and comorbidities on admission elevate death risk of COVID-19 patients. AST/ALT ratio, urea nitrogen, TBIL and LDH on admission may be potential prognostic indicators.
Clinical characteristics of 276 hospitalized patients with coronavirus disease 2019 in Zengdu District, Hubei Province: A single-center descriptive study
Authors: Wei Yiping , Zeng Weibiao , Huang Xiangyun , Li Junyu , Qiu Xingting , Li Huadong , Liu Dinghua , He Zhaofeng , Yao Wenzhong , Huang Ping , Li Chao , Zhu Min , Zhong Chunlan , Jiansheng Liu
Published: May 2020

Background We aimed to report the epidemiological and clinical characteristics of hospitalized patients with coronavirus disease-19 (COVID-19) in Zengdu District, Hubei Province, China.Methods Epidemiological,clinical features, laboratory findings, radiologic manifestations, and clinical outcomes of 276 patients in Zengdu hospital were analyzed. Clinical outcomes were followed up to March 13, 2020.Results All hospitalized COVID-19 patients, 276 (median age: 51.0 years), were enrolled, including 262 non-severe and 14 severe patients. The proportion of patients aged over 60 years was higher in the severe group (78.6%) than in the non-severe group (18.7%, p < 0.01). Some patients had comorbidities (31.9% [88/276]), the proportion was higher in the severe group (85.7%) than in the non-severe group (29.0%, p < 0.01). Common symptoms included fever (82.2% [227/276]) and cough (78.0% [218/276]). Most patients (94.9% [204/276]) were cured and discharged; 3.6% (10/276) deteriorated to a critical condition and were transferred to another hospital. The median COVID-19 treatment duration and hospital stay were 14.0 and 18.0 days, respectively.Conclusions COVID-19 patients in the areas surrounding Wuhan mainly showed mild and typical symptoms, Older patients or those with underlying comorbidities were at higher risk of deteriorating to a critical condition. In addition, we found that it takes about 14 days for nucleic acid test to turn negative in non-severe patients after antiviral treatment.
Concentration Of Survivin In Children With Juvenile Idiopathic Arthritis (JIA): Diagnostic And Prognostic Value – Single Center Study
Authors: Lipinska Joanna , Kaszkowiak Marcin , Swidrowska-Jaros Joanna , Smolewska Elzbieta
Published: May 2020

BACKGROUND: The goal of the study was to assess the diagnostic and prognostic value of survivin in Juvenile Idiopathic Arthritis (JIA). METHODS: Seventy children with JIA – 59 newly diagnosed and 11 biologically treated (46 girls and 17 boys) aged 1.5-18 years and 29 healthy children as a control group, appropriately matched in terms of sex and age, were included into the study. Concentration of survivin was assessed by an ELISA test in serum and also 18 matched synovial fluid samples collected from JIA patients. RESULTS: Children with JIA were divided according to the subtype of the JIA. In 65.7% of patients oligoarthritis was diagnosed. The disease activity was established on the basis of JADAS-27 criteria, distinguishing three levels of inflammatory process activity: low, medium and high. The largest group comprised children of low activity (62.9%) of the disease. The serum concentration of survivin was significantly higher in JIA compared to the controls (p<0.001). Higher concentration of survivin correlated positively with the presence of anti-cyclic citrullinated peptide autoantibodies (ACPA) (p=0.001). In all synovial fluid samples the concentration of survivin was higher than in matched serum (p=0.003). Serum survivin concentration did not statistically significantly change according to radiological damage status or active synovitis assessed by joint ultrasonography. Survivin level was independent of the disease duration time and treatment with TNF-α inhibitors in DMARD’s non-responders. CONCLUSIONS: On the basis of the conducted study, it could be concluded that survivin seem to be an independent biomarker that may be helpful in the diagnosis of JIA. Nevertheless, the higher concentration of survivin is being associated with ACPA positivity, survivin can act as a unique biomarker that identifies an additional group of patients with JIA negative for autoantibodies, even in the early stage of the disease. We have failed to confirm survivin prognostic potential for the active and destructive course of the rheumatoid process, however it is worth to underline that children have better potential for bone regeneration than adults. Survivin measurement should be considered as aiding tool identifying DMARD’s non-responders.
Hsa_circ_0123190 acts as a competitive endogenous RNA to regulate APLNR expression by sponging hsa-miR-483-3p in lupus nephritis
Authors: Zhang Chunyi , Gao Congcong , Di Xueqi , Cui Siwan , Liang Wenfang , Sun Wenbo , Yao Menghui , Liu Shengyun , Zheng Zhaohui
Published: May 2020

Background
Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs(circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN.
Methods
Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining.
Results
159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in renal tissues of patients with LN (P = 0.014). Bio-informatic analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R2 = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-β1 (TGF-β1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018).
Conclusion
Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.
Expansion and persistence of antibiotic-specific resistance genes following antibiotic treatment
Authors: Kang Kang , Imamovic Lejla , Misiakou Maria-Anna , Sørensen Maria Bornakke , Heshiki Yoshitaro , Ni Yueqiong , Zheng Tingting , Li Jun , Ellabaan Mostafa Mostafa Hashim , Colomer-Lluch Marta , Rode Anne A , Bytzer Peter , Panagiotou Gianni , Sommer Morten
Published: May 2020

Background. Oral antibiotics are commonly prescribed to non-hospitalized adults. However, antibiotic-induced changes on the human gut microbiome are often investigated in cohorts with pre-existing health conditions and/or concomitant medication, leaving the effects of antibiotics not completely understood.Results. We used a combination of omic approaches to comprehensively assess the effects of antibiotics on the gut microbiota and particularly the gut resistome of a small cohort of healthy adults. We observed that 3 to 19 species per individual proliferated during antibiotic treatment and Gram-negative species expanded significantly in relative abundance. While the overall relative abundance of antibiotic resistance gene homologues did not significantly change, antibiotic-specific gene homologues with presumed resistance towards the administered antibiotics were common in proliferating species and significantly increased in relative abundance. Virome sequencing and plasmid analysis showed the expansion of antibiotic-specific resistance gene homologues even three months after antibiotic administration, while paired-end read analysis suggested their dissemination among different species.Conclusions. These results suggest that antibiotic treatment can lead to a persistent expansion of antibiotic resistance genes in the human gut microbiota and provide further data in support of good antibiotic stewardship.
Modeling Familial Predictors of Proband Outcomes in Neurogenetic Disorders: Initial Application in XYY Syndrome
Authors: Wilson Kathleen E. , Fish Ari M. , Mankiw Catherine , Xenophontos Anastasia , Warling Allysa , Whitman Ethan , Clasen Liv , Blumenthal Jonathan , Raznahan Armin
Published: May 2020

Background Genomic copy number variations (CNVs) can significantly increase risk for psychopathology, but outcomes vary greatly amongst carriers of any given CNV. One potential path to advance precision medicine for neurogenetic disorders is modeling penetrance in probands relative to observed phenotypes in their non-carrier relatives. Here, we seek to advance this general analytic framework by developing new methods in application to XYY syndrome.Methods We analyzed a range of cognitive and behavioral domains in XYY probands and their non-carrier family members (n = 58 families), including general cognitive ability (FSIQ), as well as continuous measures of traits related to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Proband and relative scores were compared using covariance, regression and cluster analysis. Comparisons were made both within and across traits.Results Proband scores were shifted away from family scores with effect sizes varying between 0.9 and 2.4 across traits. Only FSIQ and vocabulary scores showed a significant positive correlation between probands and their non-carrier relatives across families (R2 ~ 0.4). Variability in family FSIQ also cross-predicted variability in proband ASD trait severity. Cluster analysis across all trait-relative pairings revealed that variability in parental psychopathology was more weakly coupled to their XYY versus their euploid offspring.Conclusions We present a suite of generalizable methods for modeling variable penetrance in CNV carriers using family data. These methods advance precision psychiatry by updating estimates of phenotypic penetrance for XYY and suggesting that the predictive utility of family data is likely both trait- and CNV-specific.Trial registrations:ClinicalTrials.gov NCT00001246, “89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls.” Date of registry: 01/10/1989.
Evidence of increasing demand for musculoskeletal health services in older Australians: a report on Medicare consultation data and the implications for health profession education.
Authors: Orrock Paul , Engel Roger , Vaughan Brett
Published: May 2020

Background

The proportion of people over 65 years of age in Australia is changing at a faster rate than other age groups. As people live longer, the prevalence of chronic disease increases with a corresponding rise in the burden of disease. Musculoskeletal conditions are highly prevalent in the older age groups, and people with these conditions have greater limitations in daily activities and psychological distress than the general population and are found to require focused multidisciplinary care. In 2005, the chronic disease management (CDM) system was introduced by the Australian Government that enabled general practitioners to plan and coordinate multi-disciplinary health care including referrals to physiotherapy, chiropractic and osteopathy. Our aim was to report on recent trends in Australian CDM referrals to these professions and to reflect on the implications this may have on educational curricula in both the pre- and post- professional arenas.
Methods

Data regarding consultation claims were extracted from the Australian Government’s Medicare website.
Results

There was an overall increase in the number of CDM referrals for people 65 years and older between 2009 and 2018. These increases were more than double the rate of population growth for the same age group during this period.
Conclusions

There is currently a lack of professional leadership in ensuring the essential skills and competencies for treating this age group are present in the workforce, with the burden falling on educators to bridge some of the gap. In order to increase proficiency, we recommend the inclusion of a number of content areas in any review of pre- and post-professional curricula related to aged care management of MSK conditions by these professions. These content areas include: changes in structure and function of the musculoskeletal system, how these changes alter the assessment and management of older patients, specific issues regarding manual therapy and exercise interventions, pharmacology and end of life care.
Cerebellar developmental deficits underlie neurodegenerative disorder spinocerebellar ataxia type 23
Authors: Smeets Cleo JLM , Ma Kai Y , Fisher Simon E , Verbeek Dineke S
Published: May 2020

Background

Spinocerebellar ataxia type 23 (SCA23) is a late-onset neurodegenerative disorder characterized by slowly progressive gait and limb ataxia, for which there is no therapy available. It is caused by mutations in PDYN, which encodes the opioid precursor protein prodynorphin (PDYN). PDYN is processed into the opioid peptides α-neoendorphin, and dynorphins (Dyn) A and B; inhibitory neurotransmitters that function in pain signalling, stress-induced responses, and addiction. Mutations causing SCA23 mostly affect Dyn A, leading to loss of secondary structure and increased peptide stability. PDYNR212W mice express human PDYN containing the SCA23 p.R212W mutation. These mice show gait deficits and progressive loss of motor function from 3 months of age. The cerebella of PDYNR212W mice show climbing fibre (CF) deficits from 3 months of age and Purkinje cell (PC) loss from 12 months of age. A mouse model for SCA1 showed similar CF deficits, and a recent study found additional developmental abnormalities, namely hyperproliferation of stem cells leading to increased GABAergic interneuron connectivity and non-cell autonomous disruption of PC function. As SCA23 mice show a similar pathology to SCA1 mice in adulthood, we hypothesized that SCA23 may also follow SCA1 pathology during development.
Methods

In the present study, we examined the cerebella of PDYNR212W mice during cerebellar development, from 2 to 8 weeks of age, using immunohistochemistry, protein, and RNA analysis.
Results

We uncovered developmental deficits from 2 weeks of age, namely a reduced number of GABAergic synapses on PC soma in PDYNR212W mice, possibly leading to the observed delay in early phase CF elimination between 2 and 3 weeks of age. Furthermore, CFs did not reach terminal height leaving proximal PC dendrites open to be occupied by parallel fibres (PFs). The observed increase in vGlut1 protein -a marker for PF-PC synapses- indicates that PFs indeed take over CF territory and have increased connectivity with PCs. Additionally, we detected altered expression of several critical Ca2+ channel subunits, potentially contributing to altered Ca2+ transients in PDYNR212W cerebella.
Conclusions

These findings indicate that developmental abnormalities contribute to the SCA23 pathology and uncover a developmental role for PDYN in the cerebellum.
Phenotype heterogeneity in Late-onset Behçet’s syndrome: A cohort from a referral center in China
Authors: Zou Jun , Luo Jian-feng , Luo Dan , Shen Yan , Guan Jian-long
Published: May 2020

Objectives To elaluate the demographic, clinical and major organ involvement of patients with late-onset Behçet’s syndrome (BS) in a tertiary centre in China.Methods It was a cross-sectional study of consecutive BS patients in Huadong Hospital of Fudan University between September 2012 and January 2020, we identified 152 late-onset BS patients diagnosed after age of 40 years. We compared clinical variables between patients with disease onset age before and after 40 years. The relative risks (RRs) of clinical variables were calculated between two age groups. Moreover, a hierarchical cluster analysis was conducted according to twenty-nine variables to determine homogeneous subgroups of patients.Results Late-onset BS patients had a higher incidence of intestinal ulcer (late-onset : early-onset, RR 1.47), but a lower incidence of ocular involvement (RR 0.54) and folliculitis (RR 0.46). Female was associated with genital ulcer, erythema nodosum, and arthritis. Four clusters (C1–C4) were formed. C1 (n = 71) the largest cluster, defined as mucocutaneous group. C2 (n = 20), the arthritis group, C3 (n = 39), the gastrointestinal type, all patients presented with intestinal lesion, and five cases with esophageal ulcer. In C4 (n = 22), showing a mixture of uveitis and vascular group, fifteen patients presented with uveitis and eight had vascular lesion, and one cases had central nervous system lesions.Conclusion This is the first cluster analysis to be carried out in a cohort of late-onset BS patients in China. The significantly lower prevalence of folliculitis in late onset BS and the overall milder disease course suggest that testosterone status may influence disease activity.
A rare mutation c.1663G>A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients
Authors: Liang Lili , Shuai Ruixue , Yu Yue , Qiu Wenjuan , Shen Linghua , Wu Shengnan , Wei Haiyan , Chen Yongxing , Yang Chiju , Xu Peng , Chen Xigui , Zou Hui , Feng Jizhen , Niu Tingting , Hu Haili , Ye Jun , Zhang Huiwen , Lu Deyun , Gong Zhuwen , Zhan Xia , Ji Wenjun , Yu Yongguo , Gu Xuefan , Han Lianshu
Published: May 2020

Background Methylmalonic acidemia is an inherited organic acid metabolic disease. it involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G > A (p.A555T), is considered to be of an extremely rare type. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype.Methods Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 patients sharing the mutation c.1663G > A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant.Results Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Mental retardation occurred in 4 patients. Vitamin B12 is responsive in 100% of these patients (29/29). The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G > A (p.A555T) carrying patients were much lower than those in non-c.1663G > A (p.A555T) carrying patients.Conclusion Compared to patients with other mutations in the MMUT gene, patients with the c.1663G > A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.
Age and APOE genotype affect the relationship between objectively measured physical activity and power in the alpha band, a marker of brain disease.
Authors: de Frutos-Lucas Jaisalmer , Cuesta Pablo , Ramirez-Toraño Federico , Nebreda Alberto , Cuadrado-Soto Esther , Peral-Suarez África , Lopez-Sanz David , Bruña Ricardo , Pedro Silvia Marcos-de , Delgado-Losada María L , López-Sobaler Ana M , Rodríguez-Rojo Inmaculada C , Barabash Ana , Rodríguez Juan M Serrano , Laws Simon M , Marcos Alberto , Lopez-Higes Ramon , Brown Belinda M , Maestú Fernando
Published: May 2020

BACKGROUND Electrophysiological studies show that reductions in power within the alpha band are associated with the Alzheimer’s disease (AD) continuum. Physical activity (PA) is a protective factor that has proved to reduce AD risk and pathological brain burden. Previous research has confirmed that exercise increases power in the alpha range. However, little is known regarding whether other non-modifiable risk factors for AD, such as increased age or APOE ε4 carriage, alter the association between PA and power in the alpha band.METHODS The relationship between PA and alpha power band was examined in a sample of 113 healthy adults using magnetoencephalography. Additionally, we explored whether ε4 carriage and age modulate this association. The correlations between alpha power and gray matter volumes and cognition were also investigated.RESULTS We detected a parieto-occipital cluster in which PA positively correlated with alpha power. The association between PA and alpha power remained following stratification of the cohort by genotype. Younger and older adults were investigated separately, and younger adults only exhibited a positive relationship between PA and alpha power. Interestingly, when four groups were created based on age (younger-older adult) and APOE (E3/E3-E3/E4), only younger E3/E3 (least predicted risk) and older E3/E4 (greatest predicted risk) had associations between greater alpha power and higher PA. Among older E3/E4, greater alpha power in these regions was associated with improved memory and preserved brain structure.CONCLUSION PA could protect against the slowing of brain activity that characterizes the AD continuum, where it is of benefit for all individuals, especially E3/E4 older adults.
Diagnostic Value of Clusterin Immunostaining in Hepatocellular Carcinoma
Authors: Li Yuan , Liu Fangfang , Zhou Wendi , Zhang Sharon , Chu Peiguo , Lin Fan , Wang Hanlin
Published: May 2020

Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenging. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC.Methods Enhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immunostaining was also performed on tissue microarray sections that contained 74 HCCs (40 of which were also stained for pCEA and CD10), 55 normal liver tissue samples, and 1305 non-hepatocellular tumors from multiple organs.Results Enhanced CLU canalicular staining was observed in 70% (89/128) HCCs but not in regenerative nodules, normal liver tissues or any non-hepatocellular tumors. The sensitivity and specificity for enhanced canalicular staining pattern of CLU in HCCs were 0.70 and 1.00. This enhanced canalicular pattern was observed in only 26% and 23% HCCs for CD10 and pCEA, respectively. These results further demonstrate that the distinctive enhanced canalicular pattern of CLU is unique to HCC.Conclusions CLU is superior to pCEA and CD10 as a diagnostic immunomarker in that it can help distinguish HCC not only from non-HCC malignancies but also from benign hepatocellular mass lesions.
In Vivo Elevation of Mitochondrial Activity and Amyloid Deposition, but Inversely Correlated, in Early-stage Senescence-Accelerated Mice: A Positron Emission Tomography Study
Authors: Yamagishi Satoru , Iga Yurika , Ikegaya Shunsuke , Kakiuchi Takeharu , Ohba Hiroyuki , Nishiyama Shingo , Kanazawa Masakatsu , Tsukada Hideo , Sato Kohji , Ouchi Yasuomi
Published: May 2020

Background: While marked reductions in neural activity and mitochondrial function have been reported in Alzheimer’s disease (AD), the degree of mitochondrial activity in mild cognitive impairment (MCI) or early-stage AD remains unexplored. Here, we used positron emission tomography (PET) to examine the direct relationship between mitochondrial activity (18F-BCPP-EF) and β-amyloid (Aβ) deposition (11C-PiB), followed by immunohistochemistry for ATPB (an ATP synthase on the mitochondrial inner membrane), in the same brains of senescence-accelerated mouse prone 10 (SAMP10) mice, an Aβ-developing neuroinflammatory animal model showing accelerated senescence with deterioration in cognitive functioning similar to that in MCI.Results: The SUVRs of 18F-BCPP-EF and 11C-PiB were significantly higher in the 15-week-old SAMP10 mice than in the control and 5-week-old SAMP10 mice. The two parameters were found to negatively correlate with each other. Consistent with these binding results, the immunohistochemical analysis demonstrated upregulation of ATPB in neurons, astrocytes, and microglia, but not in pericytes, in the 15-week-old SAMP10 mice. Conclusions: The present results provide in vivo evidence of an increase in mitochondrial energy production and amyloid burden at an early stage in SAMP10 mice. The inverse correlation between these two phenomena suggests a concurrent compensatory increase in neuronal energy production and Aβ-induced elevation of neuroinflammatory responses in glial cells, as confirmed immunohistochemically. The combination of PET and immunohistochemistry allowed in vivo evaluation of altered mitochondrial activity during neuropathological processes, including Aβ accumulation, in an animal model of AD spectrum disorder.
The impact of different simulation modalities on target volume delineation in breast-conserving radiotherapy
Authors: Jin Meng , Liu Xia , Ma Jiabin , Sun Xiansong , Zhen Hongnan , Shen Jing , Liu Zhikai , Lian Xin , Miao Zheng , Hou Xiaorong , Hu Ke , Zhang Fuquan
Published: May 2020

Background In the management of breast-conserving radiotherapy, computed tomography (CT) simulation is now commonly used to identify tumor bed while has difficult ies defining precisely. We aimed to evaluate the impact of magnetic resonance (MR) and CT simulation on defining the postoperative tumor bed for breast-conserving radiotherapy in patients without the aid of surgical clips. Methods From August 2018 to March 2019, twenty patients with T 1 - 2 N 0 M 0 breast cancer at our situation were enrolled. All the patients underwent breast-conserving surgery without implantation of surgical clips and were prepared to receive radiotherapy. CT and MR images were acquired on the same day for each patient. Three radiation oncologists independently assigned cavity visualization score (CVS) and delineated the tumor bed based on first the CT then the MR images with a 14-day interval for each patient. Interobserver variability was assessed by volumes, generalized conformity index (CI gen ) and the distance between the centers of mass (dCOM). Differences in mean values for parameters were tested by paired t -test or one-way analysis of variance, as appropriate. Results The median age of the enrolled patients was 48 years old. First, the mean volumes of tumor bed derived from MR were 22%, 27% and 21% smaller than those based on CT images for each observer. Second, the mean CI gen was significantly superior, and dCOM was smaller for MR than for CT images (CI gen : 0.59 vs 0.52, P = 0.008; dCOM: 1.30 cm vs 1.39 cm, P = 0.095). Third, the mean CVS was 3.23±1.34 and 2.43±0.92 for MR and CT images, respectively ( P = 0.035). In the subgroup with a CT-based CVS≥3, the mean dCOM obtained from CT was larger than that from the MR images (1.35 cm vs 1.19 cm, P = 0.048). Last, there was a positive association between the CVS and CI gen for both modalities (CT: r = 0.699, P = 0.001; MR: r = 0.895, P ＜ 0.001). Conclusion Compared to CT, MR can improve the visualization of changes in the postoperative tumor bed. In addition, MR can yield a more precise definition of the tumor bed and improve the consistency of tumor bed contouring in patients without surgical clips.
Bilateral lung nodules resection by image-guided video-assisted thoracoscopic surgery: A case series
Authors: Liang Chu-Chun , Liao Chi-Hao , Cheng Ya-Fu , Hung Wei-Heng , Chen Heng-Chung , Huang Chang-Lun , Wang Bing Yen
Published: May 2020

Background
We demonstrated the safety and feasibility of image-guided video-assisted thoracoscopic surgery (iVATS) of bilateral lung lesions in a hybrid operating room.
Methods
This study was a retrospective analysis of a case series. A total of 7 patients with 15 small lung nodules underwent bilateral iVATS between July 2018 and May 2019. All procedures were completed within a single anesthesia procedure and performed in a hybrid operating room that had a cone-beam computed tomography (CT) apparatus equipped with a laser navigation system. The lesion characteristics, operation methods, and peri-operative clinical outcomes were summarized.
Results
A total of 7 patients with 15 resected lung nodules were analyzed. The most common pathological result of our bilateral iVATS was metastasis. The median length of hospital stay was 5 days (range from 3 to 10 days). The median right chest tube duration was 2 days (range from 1 to 8 days), and the median left chest tube duration was 3 days (range from 2 to 5 days). Only one patient had a complication during his hospitalization period. There was no surgery-related mortality observed.
Conclusions
The bilateral iVATS procedure seems to be a feasible, safe and cost-effective approach for successful resection of bilateral lung lesions.
Increased serum total bile acid is independently associated with non-alcoholic steatohepatitis in non-diabetes population
Authors: Li Hu , Ma Jin , Gu Leilei , Jin Li , Chen Peizhan , Zhang Xinxin , chen li
Published: May 2020

Background and aims Bile acids, which modulate the glycose and lipid metabolism, play an important role in the development of non-alcoholic fatty liver disease (NAFLD). This study aims to explore the association between serum total bile acid (TBA) and non-alcoholic steatohepatitis (NASH) in the general population from a large clinical dataset. Methods NAFLD individuals confirmed by ultrasonography were enrolled in the study. The NASH was defined as the NAFLD individual with abnormal liver function, and non-alcoholic fatty liver (NAFL) was defined as the NAFLD individual with normal liver function. The demographic characters, biochemical results including serum TBA were compared between NASH and NAFL patients. The independently associated factors with NASH were investigated by multivariate logistic regression analysis. Results A total of 6862 individuals were enrolled in the study, of which 23.7% were NASH. The median age was 45 (39-55) years old, and the BMI was 26.9(25.1-28.9) kg/m 2 . The NASH patients showed higher levels of serum TBA compared to the NAFL patients [3.30(2.30-5.0) μmol/L vs. 2.70(1.90-4.20) μmol/L, P <0.001]. The prevalence of NASH tended to increase with the increasing of serum TBA level ( P <0.001). Multivariate logistic regression analysis showed the age, male, serum TBA levels, diabetes mellitus (DM), serum uric acid, total cholesterol and triglyceride were independent risk factors for NASH ( P <0.05). Stratification analysis according to DM status showed that serum TBA was independently associated with NASH in individuals without DM (OR: 1.55, 95% CI: 1.11-2.13, P =0.008), while not in individuals with DM (OR: 1.32, 95% CI: 0.53-2.96, P =0.515). Conclusion Serum TBA level was significantly higher in NASH patients than in NAFL patients, and was independently associated with NASH in non-diabetes population.
Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma
Authors: Zhao Qiangqiang , Sun Xiaoying , Wu Bin , Shang Yinghui , Huang Xueyuan , Dong Hang , Liu Haiting , Chen Wansong , GUI RONG , Li Jian
Published: May 2020

Background Non-Hodgkin's lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibod y targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Results Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, pH response, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis.Conclusions Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma.
Micelles self-assembled by 3-O-β-D-glucopyranosyl latycodigenin enhances cell membrane permeability, promotes antibiotic pulmonary targeting and improves anti-infect efficacy
Authors: Zhang Man , Ye Lili , Huang Hao , Cheng Dandan , Wu Wenbo , Liu Kaixin , Jiang Zhihong , Hou Yuanyuan , Bai Gang
Published: May 2020

Background: Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. It exhibits significant advantages compared to traditional pulmonary drug delivery systems. However, developing a formulation for each drug is a time-consuming and laborious task. Results: The present study designed and constructed a universal lung-targeting nanoparticle. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-D-glucopyranosyl platycodigenin 682 (GP-682), via its specific amphiphilic structure. After optimization, the GP-682 micelles obtained a stable zeta potential with a particle size between 60 to 90 nm, and the CMC value was approximately 42.3 μg/mL. Pre-incubation of GP-682 micelles markedly enhanced the cell membrane permeability, and improved drug uptake in vitro . The results were visualized using fluorescent dye tracing, transmission electron microscopy observation and a lactate dehydrogenase releasing assay. The benefits enhanced the distribution of levofloxacin in mouse lung tissue and reduced the overdosing of antibiotic. Pseudomonas aeruginosa PA 14 strain-induced acute lung injury mice model demonstrated that preinjection of GP-682 micelles followed by antibiotic administration produced a higher survival rate and anti-infection efficacy in vivo , which included a reduction in pulmonary injury, bacterial invasion and the expression of cytokines compared to treatment with levofloxacin alone. Conclusions: GP-682 micelles are another nanoparticle-based pulmonary drug delivery system to increase the use of antibiotic and provide a new option for antibiotic resistance and lung-targeting therapy.
PPAI: a web server for predicting protein-aptamer interactions
Authors: Li Jianwei , Ma Xiaoyu , Li Xichuan , Gu Junhua
Published: May 2020

Background: The interactions between proteins and aptamers are prevalent in organisms and play an important role in various life activities. Thanks to the rapid accumulation of protein-aptamer interaction data, it is necessary and feasible to construct an accurate and effective computational model to predict aptamers binding to certain interested proteins and protein-aptamer interactions, which is beneficial for understanding mechanisms of protein-aptamer interactions and improving aptamer-based therapies. Results: In this study, a novel web server named PPAI is developed to predict aptamers and protein-aptamer interactions with key sequence features of proteins/aptamers and a machine learning framework integrated adaboost and random forest. A new method for extracting several key sequence features of both proteins and aptamers is presented, where the features for proteins are extracted from amino acid composition, pseudo-amino acid composition, grouped amino acid composition, C/T/D composition and sequence-order-coupling number, while the features for aptamers are extracted from nucleotide composition, pseudo-nucleotide composition (PseKNC) and Moreau-Broto autocorrelation coefficient. On the basis of these feature sets and balanced the samples with SMOTE algorithm, we validate the performance of PPAI by the independent test set. The results demonstrate that the Area Under Curve (AUC) is 0.907 for prediction of aptamer, while the AUC reaches 0.871 for prediction of protein-aptamer interactions. Conclusion: These results indicate that PPAI can query aptamers, predict aptamers and predict protein-aptamer interactions in batch mode precisely and efficiently, which would be a novel bioinformatics tool for the research of protein-aptamer interactions. PPAI web-server is freely available at http://39.96.85.9/PPAI.
Perceived Stress and Its Impact on Health Behavior of Chinese Residents during the Epidemic of COVID-19: An Internet Survey
Authors: Li Yuerong , Yao Lili , Luo Yetao , Yuan Feng , Yan Lupei
Published: May 2020

Background An outbreak of 2019 novel coronavirus disease(COVID-19) could cause a severe respiratory illness, which may come from Spray or ordinary contact, then pose a great threat to life. Meanwhile, epidemic may trigger excessive stress and have a terrible impact on mental health even health behaviors, especially some special individuals. So this study paved the way for psychological interventions focused on specific groups during the COVID-19 epidemic. Methods An internet survey was conducted on 2,449 residents in 20 provinces including Chongqing, Sichuan and Gansu et al, in order to collect the data of Chinese residents' perceived stress, COVID-19 awareness and health behaviors. SAS9.4 was used to analyze the relationship between health behaviors and perceived stress, and logistic regression was used to explore the influencing factors of health risk stress. Results The residents' perceived stress score was 22.25±7.2(total score was 56), and the incidence of health risk stress was 39.89% (977/2449). As perceived stress increased, the frequency of health behaviors such as washing hands and wearing a mask decreased in turn. Age, cognition of susceptibility to COVID-19, life-threaten level, cognition of the importance of home isolation, and cognition of the difference between common cold and COVID-19 were related to the occurrence of health risk stress. Conclusions There was a negative correlation between residents' health behaviors and perceived stress during the COVID-19 outbreak. It is of great significance to improve the public's awareness of the COVID-19, to provide good social support and psychological intervention for people with health risk stress and to promote their health behaviors.
On nature of determining displacement from sole knowledge of self interferometric perturbed phase
Authors: Khan Junaid
Published: May 2020

While self mixing interferometry(SMI) has proven to be suitable for displacement measurement and other sensing applications,its characteristic self mixing signal shape is strongly governed by the non-linear phase equation which forms relation between perturbed and unperturbed phase of self mixing laser.Therefore, while it is desirable for robust estimation of displacement of moving target, the algorithms to achieve this must have an objective direction which can be achieved by understanding the characteristic of extracting knowledge of perturbed phase from unperturbed phase. Therefore, this paper tends to deduce results from the self mixing interferometry(SMI) phase equation,by showing the impossibility of analytically deriving perturbed phase as continuous function of unperturbed phase either through finite or infinite substitutions. Therefore we never get exact displacement just by sole knowledge of perturbed phase. Moreover, it has theoretically shown that the action of practically deriving unperturbed phase from perturbed phase becomes a filltering process in spectral domain followed by perturbative or homotopical deformation.
Associations between socio-demographics, nutrition knowledge, nutrition competencies and attitudes in community-dwelling older adults in Singapore: Findings from the SHIELD study
Authors: Ong Rebecca Hui Shan , Chow Wai Leng , Cheong Magdalin , Lim Gladys Huiyun , Xie Weiyi , Baggs Geraldine , Huynh Dieu Thi Thu , Oh Hong Choon , How Choon How , Tan Ngiap-Chuan , Tey Siew Ling , Chew Samuel Teong Huang
Published: May 2020

Background Nutrition literacy refers to an individual’s knowledge, motivation and competencies to access, process, and understand nutrition information to make nutrition-related decisions. It is known to influence dietary habits of older adults. This cross-sectional study was designed to: (1) understand the nutrition knowledge, competencies and attitudes of community-dwelling older adults in Singapore (2) examine the differences between their nutrition knowledge, and socio-demographic factors, competencies and attitudes, and (3) identify factors associated with better nutrition knowledge in community-dwelling older adults in Singapore. Methods 400 (183 males and 217 females) nourished community-dwelling older adults aged 65 years and above took part in this study. Malnutrition Universal Screening Tool (MUST) was used to determine individuals who were at low risk of undernutrition. Nutrition knowledge, competencies, attitudes and sources of nutrition information were measured using a locally developed scale. Nutrition knowledge scores were summed to form the Nutrition Knowledge Index (NKI). Associations between NKI, competencies, attitudes and socio-demographic variables were examined using Chi-square and Fisher’s Exact tests. Factors associated with NKI were determined using a stepwise regression model with resampling based methods for model averaging. Results Bivariate analyses found significant differences in NKI scores for gender, monthly household earnings, type of housing, the self-reported ability to seek and understand nutrition information and having access to help from family/friends. Females had higher NKI scores compared to males ( p < 0.001). Compared to females, more males left food decisions to others ( p < 0.001), and fewer males reported consuming home cooked food ( p = 0.016). Differences in educational level were found for competencies like the self-reported ability to seek ( p < 0.001) and verify nutrition information ( p < 0.001). Stepwise regression analysis showed that being female, Chinese, self-reported ability to understand nutrition information and having access to help from family/friends were associated with higher NKI scores. Conclusions Our study revealed that nutrition knowledge of older males in Singapore was lower than females and more left food decisions to others. Nutrition education programs could be targeted at both the older male and their caregivers. Trial Registration This study was registered on 7 August 2017 at clinicaltrials.gov (ref. NCT03240952).