bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between comprehensive geriatric assessment and amyloid PET in older persons with MCI
Authors: Lauretani Fulvio , Ruffini Livia , Scarlattei Maura , Maggio Marcello 
Published: May 2020

Abstract
Background. The association between amyloid deposition and cognitive, behavioral and physical performance in mild cognitive impairment (MCI) due to Alzheimer's disease (AD) has been poorly investigated, especially in older persons. Methods. We studied the in vivo correlation between the amyloid deposition at Positron Emission Tomography (amyloid-PET) and the presence of memory loss, reduced executive function, physical performance and neuropsychiatric symptoms in older persons with MCI. Amyloid-PET was performed with 18F-flutemetamol and quantitatively analyzed. Results. We evaluated 48 subjects, 21 men and 27 women. We performed in each patient a comprehensive geriatric assessment (CGA) including Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), Activity Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Neuropsychiatric inventory (NPI) questionnaire, 15 Geriatric Depression Scale (GDS), Short Physical Performance Battery (SPPB) and Hand Grip strength. Then, each patient underwent amyloid-PET. Mean age of the enrolled subjects was 74.6 ± 7.8 years. All of these subjects showed preserved cognitive function at MMSE > 24, while 29 of 48 subjects (61.0 %) had altered CDT. Mean NPI score was 6.9 ± 5.9. The mean value of SPPB score was 9.0 ± 2.6, while the average muscle strength of the upper extremities measured by hand grip was 25.6±7.7 Kg. CT/MRI images showed cortical atrophic changes in 26 of the 48 examined subjects (54.0 %), while cerebrovascular modifications were present in 31 subjects (64.5 %). Pathological burden of amyloid deposits was detected in 25 of 48 (52.0 %) patients with a mean value of global z-score of 2.8 (subjects defined as MCI due to AD). After stratifying subjects in subclasses of clinical alterations, more probability of pathological amyloid deposition was found in subjects with impaired CDT and higher NPI score (O.R.= 3.45 [1.01-11.2], p=0.04), with both impaired CDT and low physical performance (O.R.= 5.80 [1.04-32.2], p=0.04), with altered CDT and high NPI score (O.R.=7.98 [1.38-46.0], p=0.02), and finally in those subjects with altered CDT, high NPI and low physical performance (O.R.= 5.80 [1.05-32.2], p=0.04). Conclusion. Our findings support the recent hypothesis that amyloid deposition could be associated with multiple cerebral dysfunction, mainly affecting executive, behavioral and motor abilities.
Clinical and molecular spectrum of 46, XY disorders of sex development that harbour MAMLD1 variations: Case series and review of literature
Authors: Lele Li , Fan Lijun , Gao Fenqi , Wu Di , Gong Chunxiu 
Published: May 2020

Abstract
Background Mastermind-like domain-containing 1 (MAMLD1) has previously been identified as a causative gene for "46, XY Disorders of Sex Development (DSD)". Recently, there has been some controversy regarding the causative role of MAMLD1 variations in DSDs. Here we describe a clinical series and review the reported cases to evaluate the role of MAMLD1 variants in children with 46, XY DSD. Cases of 46, XY DSD harbouring MAMLD1 variants from unrelated families were recruited from the Beijing Children’s Hospital in China (N = 10) or identified through a literature search (N = 26). The clinical manifestations and genetic variants of all the patients were evaluated.Results Hypospadias was the most prevalent phenotype among our 10 cases (8 out of 10 cases) and in all the previously reported ones. Central precocious puberty and isolated micropenis were observed for the first time. Among the 10 cases, nine variants were identified, including three nonsense (p.A356X, p.G152X, and p.G124X) and six missense (p.P334S, p.S662A, p.A421P,p.T992I, p.P542S, and p.A927L) variants. In silico analysis showed that the variants p.P334S, p.P542S, p.S662A, and p.A927Lmight lead to drastic changes in the interaction force of the amino acid chain and the flexibility of the spatial structure, and such changes may affect protein function.Conclusion Patients with 46, XY DSD harbouring MAMLD1variants manifest a broad spectrum of phenotypes and mostly present with hypospadias. The six novel variants reported here enrich the mutation database and contribute to our understanding of the pathogenesis of 46, XY DSD.
Proteomic analysis of Rickettsia akari proposes a 44 kDa-OMP as a potential biomarker for Rickettsialpox diagnosis
Authors: Csicsay František , Flores-Ramirez Gabriela , Zuñiga-Navarrete Fernando , Bartošová Mária , Fučíková Alena , Pajer Petr , Dresler Jiří , Škultéty Ľudovít , Quevedo-Diaz Marco Antonio 
Published: May 2020

Abstract
Background: Rickettsialpox is a febrile illness caused by the mite-borne pathogen Rickettsia akari. Several cases of this disease are reported worldwide. Nevertheless, the relationship between the immunogenicity of R. akari and the disease development remains poorly understood. Therefore, misdiagnosis is frequent. Our study is aimed to identify immunogenic proteins that may improve disease recognition and enhance subsequent treatment. To achieve this goal, two proteomics methodologies were applied, followed by immunoblot confirmation. Results: Three hundred and sixteen unique proteins were identified in the whole-cell extract of R. akari. The most represented protein groups were found to be those involved in translation, post-translational modifications, energy production, and cell wall development. A significant number of proteins belonged to amino acid transport and intracellular trafficking. Also, some proteins affecting the virulence were detected. In silico analysis of membrane enriched proteins revealed 25 putative outer membrane proteins containing beta-barrel structure and 11 proteins having a secretion signal peptide sequence. Using rabbit and patient sera, various immunoreactive proteins were identified from which the 44 kDa uncharacterized protein (A8GP63) has demonstrated a unique detection capability. It positively distinguished the sera of patients with Rickettsialpox from other rickettsia positive patient sera. Conclusion: Our proteomic analysis certainly contributed to the knowledge of the pathogenesis of R. akari. The result obtained may also serve as a guideline for a more accurate diagnosis of rickettsial diseases. Identified R. akari antigenic protein can be design as a unique marker of rickettsialpox and used as a target for the development of more effective treatment.
Erenumab in highly therapy-refractory migraine patients: First German Real-world evidence
Authors: Scheffler Armin , Messel Olga , Wurthmann Sebastian , Nsaka Michael , Kleinschnitz Christoph , Glas Martin , Naegel Steffen , Holle-Lee Dagny 
Published: May 2020

Abstract
Background Calcitonin gene related peptide (CGRP) monoclonal antibodies (mAB) are the first specific migraine prophylactic medication. Erenumab is the only CGRP mAB targeting the CGRP receptor. Clinical data regarding efficacy and tolerability of erenumab in highly therapy-refractory patients are not available, yet, although many patients treated with CGRP mAB under real world conditions can be considered as highly therapy-refractory. Methods Clinical routine data of highly therapy-refractory migraine patients treated with erenumab 70mg for three months between November 2018 and December 2019 in the West German Headache Center, University Hospital Essen, Germany, were analysed. Monthly migraine days (MMD), monthly headache days (MHD) and days of acute medication intake (AMD) were assessed. Statistical analysis was performed using the Wilcoxon test. Descriptive statistics were performed to evaluate changes of vegetative symptoms, acute medication response, side effects, as well as treatment satisfaction. Results Complete clinical data were available for 26 episodic (EM) and 74 chronic (CM) migraineurs. Sixty-six % (n=49) of CM patients had an additional medication overuse headache (MOH). After three months 57.7% of EM patients and 41.9% of CM patients had a 50% or greater reduction of MMD. The mean number of MMD was reduced by 3.43 (SE 1.26) in EM, and by 4.72 (SE 0.87) in CM. Thirty-nine patients (52.7%) returned from chronic to episodic course of migraine. After three months, 23 patients (46.9%) were not suffering from a MOH anymore. Conclusions Erenumab seems to be a promising therapeutic option in highly therapy-refractory migraine patients.
Range and niche expansion through multiple interspecific hybridization - a Genotyping by Sequencing analysis of Cherleria (Caryophyllaceae)
Authors: Moore Abigail Jane , Messick Jennifer A. , Kadereit Joachim W. 
Published: May 2020

Abstract
Background
Cherleria (Caryophyllaceae) is a circumboreal genus that also occurs in the high mountains of the northern hemisphere. In this study, we focus on a clade that diversified in the European High Mountains, which was identified using nuclear ribosomal (nrDNA) sequence data in a previous study. With the nrDNA data, all but one species was monophyletic, with little sequence variation within most species. Here, we use genotyping by sequencing (GBS) data to determine whether the nrDNA data showed the full picture of the evolution in the genomes of these species.
Results
The overall relationships found with the GBS data were congruent with those from the nrDNA study. Most of the species were still monophyletic and many of the same subclades were recovered, including a clade of three narrow endemic species from Greece and a clade of largely calcifuge species. The GBS data provided additional resolution within the two species with the best sampling, C. langii and C. laricifolia, with structure that was congruent with geography. In addition, the GBS data showed significant hybridization between several species, including species whose ranges did not currently overlap.
Conclusions
The hybridization led us to hypothesize that lineages came in contact on the Balkan Peninsula after they diverged, even when those lineages are no longer present on the Balkan Peninsula. Hybridization may also have helped lineages expand their niches to colonize new substrates and different areas. Not only do genome-wide data provide increased phylogenetic resolution of difficult nodes, they also give evidence for a more complex evolutionary history than what can be depicted by a simple, branching phylogeny.
Preliminary result of carbon-ion radiotherapy using the spot scanning method for prostate cancer
Authors: Takakusagi Yosuke , Kato Hiroyuki , Kano Kio , Anno Wataru , Tsuchida Keisuke , Mizoguchi Nobutaka , Serizawa Itsuko , Yoshida Daisaku , Kamada Tadashi 
Published: May 2020

Abstract
Background: Carbon-ion radiotherapy (CIRT) for prostate cancer was initiated at Kanagawa Cancer Center in 2015. The present study analyzed the preliminary clinical outcomes of CIRT for prostate cancer. Methods: The clinical outcomes of 253 patients with prostate cancer who were treated with CIRT delivered using the spot scanning method between December 2015 and December 2017 were retrospectively analyzed. The irradiation dose was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. Biochemical relapse was defined using the Phoenix definition. Toxicities were assessed according to CTCAE version 4.0. Results: The median patient age was 70 (47–86) years. The median follow-up duration was 35.3 (4.1–52.9) months. According to the D’Amico classification system, 8, 88, and 157 patients were classified as having low, intermediate, and high risks, respectively. Androgen deprivation therapy was administered in 244 patients. The biochemical relapse-free rate in the low-, intermediate-, and high-risk groups at 3 years was 87.5%, 88.0%, and 97.5%, respectively (P = 0.036). Grade 2 acute urinary toxicity was observed in 12 (4.7%) patients. Grade 2 acute rectal toxicity was not observed. Grade 2 late urinary toxicity and grade 2 late rectal toxicity were observed in 17 (6.7%) and 3 patients (1.2%), respectively. Previous transurethral resection of the prostate was significantly associated with late grade 2 toxicity in univariate analysis. The predictive factor for late rectal toxicity was not detected.Conclusion: The present study demonstrated that CIRT using the spot scanning method for prostate cancer produces favorable outcomes.
The Association between dietary total antioxidant capacity with the risk of helicobacter pylori infection among adult: a case–control study
Authors: Sohouli Mohammadhassan , Haghshenas Niloufar , Fatahi Somaye 
Published: May 2020

Abstract
Background Dietary total antioxidant capacity (DTAC) has been assumed as a useful tool to assess the relationship between the cumulative antioxidant food capacity and several chronic disorders. The aim of this study was to evaluate the association between DTAC and risk of Helicobacter pylori in a case-control study.Methods This case-control study was carried out among 150 patients with Helicobacter pylori and 302 healthy subjects aged 18–55 years. Dietary data were collected using a validated 168- items quantitative food frequency questionnaire. DTAC was calculated based on the ferric reducing-antioxidant power (FRAP) values that reported by US Department of Agriculture. Results The mean age and BMI of the study participants were 38.70 years and 25.86, respectively. Compared with control subjects, participants with H pylori significantly were older and had higher BMI and smoking use. Patients with H pylori compared with control individuals had also lower intake of total fiber, vitamin E, vitamin C, vitamin D, total dairy, whole grain and vegetables. Compared with participants in the lowest tertile of DTAC, those in the highest terrtile had a significantly lower OR for H pylori after further adjustment for potential confounders (Model 2: OR, 0.20; 95% CI, 0.10 – 0.40; P for trend, < 0.001).Conclusions Our findings showed that a high DTAC was associated with a reduced risk of Helicobacter pylori in adult, which reflects the increased intake of natural dietary antioxidants to prevent the progression of Helicobacter pylori. However, further studies are needed to investigate the t relation between DTAC and risk of Helicobacter pylori.
Detection of Speaker De-identification Disguise Based on Dense Convolutional Network
Authors: Wang Yong , Su Zhuoyi , Zhu Zhengyu 
Published: May 2020

Abstract
Nowadays, speaker disguise is a common operation that presents a great challenge to social security. Therefore, it is important to recognize the authenticity of speech. Most of the current researches focus on speech spoofing, which simulates a target speaker to break through the state-of-art ASV systems by increasing false acceptance rate. Meanwhile, there is another type of disguise, i.e. de-identification, which transforms a speech signal without a target to increase the false rejection rate in order not to be recognized. It has received far less attention. Therefore, in this paper, we investigate the de-identification model and propose a method to detect de-identification speeches from genuine speeches by using a very deep dense convolutional network with 135 layers. The experimental results show that the average accuracy of the proposed method outperforms the reported state-of-the-art methods.
DNMT1 facilitates proliferation and metastasis of breast cancer cells by promoting MEG3 promoter methylation in MEG3/miR-494-3p/OTUD4 regulatory axis
Authors: Zhu Xiaotao , Lv Lin , Wang Mingzheng , Fan Chen , Lu Xiaofeng , Jin Miaomiao , Li Shuguang , Wang Fan 
Published: May 2020

Abstract
Background

To explore the mechanism of DNMT1 facilitating proliferation and metastasis of breast cancer cells by promoting MEG3 promoter methylation in MEG3/miR-494-3p/OTUD4 regulatory axis.
Methods

Human breast cancer cell lines (MCF-7, MDA-MB-231, SKBR3) and human breast epithelial cell line MCF10A were selected for the experiments. The expressions of DNMT1, MEG3, miR-494-3p and OTUD4 were detected by qRT-PCR. Western blot was used to detect the protein expressions of DNMT1 and OTUD4. ChIP assay verified the binding relationship of DNMT1 and MEG3 promoter region. MEG3 methylation and its level were test by MethPrimer software and MSP, respectively. The targeted binding sites of miR-494-3p and MEG3/OTUD4 were predicted by bioinformatics. RIP and dual-luciferase reporter gene assays verified the combination of miR-494-3p and MEG3/OTUD4. Cell proliferation, migration and invasion abilities were detected by CCK-8, wound healing and Transwell assays.
Results

DNMT1 was highly expressed while MEG3 was poorly expressed in breast cancer cells. Silencing DNMT1 inhibited the proliferation, migration and invasion of breast cancer cells by promoting the expression of lncRNA MEG3 through demethylation. MEG3 as a ceRNA regulated the expression of miR-494-3p in breast cancer. In addition, miR-494-3p could bind to the 3’-UTR of OTUD4, thus negatively regulating the expression of OTUD4 and forming the MEG3/miR-494-3p/OTUD4 regulatory axis that affected the proliferation, invasion and migration of breast cancer. Overexpression of MEG3 could inhibit breast cancer tumor growth in vivo.
Conclusion

Silencing DNMT1 promoted the expression of MEG3 through demethylation, which inhibited the expression of miR-494-3p to promote the expression of downstream target OTUD4, thus inhibiting the proliferation, migration and invasion abilities of breast cancer cells.
Sleep states detection using halfwave and Franklin transformation
Authors: Paul Yash , Fridli S. 
Published: May 2020

Abstract
Sleep is a physiological phenomenon and a sufficient amount of sleep is mandatory for a human for his/her health. Three biomedical signals namely Blood, EEG and Nasal are used to identify various sleep stages. The discrete version of these signals is piecewise linear function and applied two piecewise linear data reduction techniques namely a new Halfwave method in time domain and Franklin transformation in frequency domain on the discrete versions of these selected signals. As a result we obtained two piecewise linear functions with low complexity that still preserve the characteristics of the stages of the sleep in the signals. The components of the feature vector are generated from the parameters of the two reduced piece wise linear functions. Algorithm is tested on MIT-BIH Polysomnographic Database having more than 70 hours long term EEG, Blood and Nasal signals with six different sleep classes. Proposed method shows better performance so far on such long duration data in terms of Sensitivity, Specificity, Accuracy and False Alarm Rate/hour. Algorithm achieved an average sensitivity, specificity accuracy and false alarm rate of 98.35% and 97.32%, 96.96%, 0.029 respectively for two classes, 96.62% and 97.10%, 93.94%, 0.030 for 4 classes, 96.13% and 98.33%, 93.84%, 0.016 for all (six) classes.
Toward developing a metastatic or neoadjuvant breast cancer treatment strategy that incorporates history of response to previous treatments
Authors: Olow Aleksandra K. , Veer Laura J. van't , Wolf Denise M. 
Published: May 2020

Abstract
Background: Information regarding response to past treatments may provide clues concerning the classes of drugs most or least likely to work for a particular metastatic or neoadjuvant early stage breast cancer patient. However, currently there is no systematized knowledge base that would support clinical treatment decision-making that takes response history into account.Methods: To model history-dependent response data we leveraged a published in vitro breast cancer viability dataset (84 cell lines, 90 therapeutic compounds) to calculate the odds ratios (log(OR)) of responding to each drug given knowledge of (intrinsic/prior) response to all other agents. This OR matrix is assuming (1) response is based on intrinsic rather than acquired characteristics, and (2) intrinsic sensitivity remains unchanged at the time of the next decision point. Fisher’s exact test is used to identify predictive pairs and groups of agents (BH p<0.05). Recommendation systems are used to make further drug recommendations based on past ‘history’ of response.Results: Of the 90 compounds, 57 have sensitivity profiles significantly associated with those of at least one other agent, mostly targeted drugs. Nearly all associations are positive, with (intrinsic/prior) sensitivity to one agent predicting sensitivity to others in the same or a related class (OR>1). In vitro conditional response patterns clustered compounds into five predictive classes: (1) DNA damaging agents, (2) Aurora A kinase and cell cycle checkpoint inhibitors; (3) microtubule poisons; (4) HER2/EGFR inhibitors; and (5) PIK3C catalytic subunit inhibitors. The apriori algorithm implementation made further predictions including a directional association between resistance to HER2 inhibition and sensitivity to proteasome inhibitors.Conclusions: Investigating drug sensitivity conditioned on observed sensitivity or resistance to prior drugs may be pivotal in informing clinicians deciding on the next line of breast cancer treatments for patients who have progressed on their current treatment. This study supports a strategy of treating patients with different agents in the same class where sensitivity was previously observed.
Community midwifery model’s effect on availability, utilization and outcomes of maternal and newborn health services in hard-to-reach communities of Busia Kenya: a Quasi-experimental study
Authors: Shikuku Duncan Ndombi , Tanui Geofrey , Wabomba Mercy , Wanjala Dennis , Friday Josephine , Peru Taphroze , Atamba Evelyne , Sisimwo Kenneth 
Published: May 2020

Abstract
Background
Globally, poor women in hard-to-reach areas are least likely to receive healthcare and carry the burden of maternal and neonatal mortality related to complications of childbirth. Midwifery can avert 83% of all maternal & neonatal deaths and stillbirths. This study evaluated the effect of an enhanced community midwifery model (CMM) on skilled attendance during pregnancy and childbirth and maternal and perinatal outcomes against the background of protracted healthcare workers' strikes in rural Kenya.
Methods
A quasi-experimental (one-group pretest-posttest) designed. Six-months pretest period: December’2016-May’2017. Between Dec’2016-Feb’2017 (period 1) - a doctors’ strike and March-May’2017 (period 2), normal healthcare services resumed. An enhanced CMM (using 10 CMs linked to 6 health facilities) was implemented in the proceeding 5-months posttest period (period 3) – June-October’2017 during the national nurses/midwives’ strike. Differences in performance means for MNH variables of interest between the three periods were computed by ANOVA. Two-groups test of proportions for before and during/after the enhanced CMM computed.
Results
There were differences in mean monthly attendance for community midwifery services for the three periods: 1st ANC (1.8-2.3-9.9, P = 0.0087), 4th ANC (1.4-1.0-7.1, P = 0.0212), skilled births (1.5-1.7-13.1, P < 0.0001). Mean attendance at facility were: 1st ANC (55.7-70.8-4.0), 4th ANC (29.6-38.1-1.2) and skilled births (63.1-87.4-5.6), P ≤ 0.05. No differences in attendance between the doctors’ strike and normalcy period for both CMs and health facilities’ MNH services (P ≥ 0.05). However, significant increases for CMs MNH services during the nurses/midwives strike and significant reductions at the facility level during the same period (P ≤ 0.05). An increase of 68%, 74.5%, 67.8% and 33.3% in the proportion of 1st and 4th ANC, skilled births and PNC conducted by CMs during/after the CMM respectively (P ≤ 0.0001). A double and triple reduction in macerated stillbirths (0.70%-0.36%) and neonatal deaths (0.54%-0.18%) respectively and an increase in babies discharged alive (98.05%-100%) with no change in maternal deaths during/post intervention.
Conclusions
There was improvement in access/utilization of pregnancy and childbirth services from CMs. There is a golden opportunity to integrate the CMs to primary health care system to improve uptake of MNH care services through an enhanced CMM strategy in hard-to-reach communities.