bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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&gt;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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.