bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic profiling of Italian patients identified methylation sites associated with hereditary transthyretin amyloidosis
Authors: De Lillo Antonella , Pathak Gita A. , De Angelis Flavio , Di Girolamo Marco , Luigetti Marco , Sabatelli Mario , Perfetto Federico , Frusconi Sabrina , Manfellotto Dario , Fuciarelli Maria , Polimanti Renato 
Published: November 2020

AbstractHereditary transthyretin (TTR) amyloidosis (hATTR) is a rare life-threatening disorder caused by amyloidogenic coding mutations located inTTRgene. To understand the high phenotypic variability observed among carriers ofTTRdisease-causing mutations, we conducted an epigenome-wide association study (EWAS) assessing more than 700,000 methylation sites and testing epigenetic difference ofTTRcoding mutation carriersvs. non-carriers. We observed a significant methylation change at cg09097335 site located inBeta-secretase 2(BACE2) gene (standardized regression coefficient = −0.60,p = 6.26 × 10–8). This gene is involved in a protein interaction network enriched for biological processes and molecular pathways related to amyloid-beta metabolism (Gene Ontology: 0050435,q = 0.007), amyloid fiber formation (Reactome HSA-977225,q = 0.008), and Alzheimer’s disease (KEGG hsa05010,q = 2.2 × 10–4). Additionally,TTRandBACE2share APP (amyloid-beta precursor protein) as a validated protein interactor. WithinTTRgene region, we observed that Val30Met disrupts a methylation site, cg13139646, causing a drastic hypomethylation in carriers of this amyloidogenic mutation (standardized regression coefficient = −2.18,p = 3.34 × 10–11). Cg13139646 showed co-methylation with cg19203115 (Pearson’sr2 = 0.32), which showed significant epigenetic differences between symptomatic and asymptomatic carriers of amyloidogenic mutations (standardized regression coefficient = −0.56,p = 8.6 × 10–4). In conclusion, we provide novel insights related to the molecular mechanisms involved in the complex heterogeneity of hATTR, highlighting the role of epigenetic regulation in this rare disorder.
Assessment of MGMT methylation status using high-performance liquid chromatography in newly diagnosed glioblastoma
Authors: Hanihara Mitsuto , Miyake Kunio , Watanabe Atsushi , Yamada Yuriko , Oishi Naoki , Kawataki Tomoyuki , Inukai Takeshi , Kondo Tetsuo , Kinouchi Hiroyuki 
Published: November 2020

Abstract
Background
The utility of O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation status as a prognostic marker in patients with glioblastoma (GBM) has been established. However, the number of CpG sites that must be methylated to cause transcriptional silencing remains unclear, and no significant consensus exists on the optimal method of assessing MGMT methylation. We developed a new high-performance liquid chromatography (HPLC) method that enables accurate analysis of DNA methylation levels using long PCR products. In the present study, we analyzed the MGMT methylation status of 28 isocitrate dehydrogenase–wild-type GBMs treated with temozolomide using ion-exchange HPLC and set the optimal cutoff values.

Results
We designed three primers for separate regions (regions 1–3) that had 21 to 38 CpGs for PCR and validated the MGMT promoter methylation status using frozen samples. There was a strong correlation between HPLC and bisulfite sequencing results (R = 0.794). The optimal cutoff values for MGMT methylation in HPLC were determined to allow differentiation of patient prognosis by receiver operating characteristic curve analysis. The cutoff values were 34.15% for region 1, 8.84% for region 2, and 36.72% for region 3. Kaplan–Meyer curve analysis estimated that the most differentiated prognosis was enabled in the setting of 8.84% methylation of MGMT in region 2. Progression-free survival and overall survival were significantly longer for patients in this setting of region 2 methylation (p = 0.00365 and p = 0.00258, respectively).

Conclusions
The combination of our HPLC method and the original primer setting provides a new standard method for determination of MGMT methylation status in patients with GBM and is useful for refining MGMT-based drug selection.
Prevalence and risk factors for lung involvement on low-dose chest CT (LDCT) in a paucisymptomatic population of 247 patients affected by COVID-19
Authors: Castelli Maxime , Maurin Arnaud , Bartoli Axel , Dassa Michael , Marchi Baptiste , Finance Julie , Lagier Jean-Christophe , Million Matthieu , Parola Philippe , Brouqui Philippe , Raoult Didier , Cortaredona Sebastien , Jacquier Alexis , Gaubert Jean-Yves , Habert Paul 
Published: November 2020

Abstract
Background
Low-dose chest CT (LDCT) showed high sensitivity and ability to quantify lung involvement of COVID-19 pneumopathy. The aim of this study was to describe the prevalence and risk factors for lung involvement in 247 patients with a visual score and assess the prevalence of incidental findings.

Methods
For 12 days in March 2020, 250 patients with RT-PCR positive tests and who underwent LDCT were retrospectively included. Clinical and imaging findings were recorded. The extent of lung involvement was quantified using a score ranging from 0 to 40. A logistic regression model was used to explore factors associated with a score ≥ 10.

Results
A total of 247 patients were analyzed; 138 (54%) showed lung involvement. The mean score was 4.5 ± 6.5, and the mean score for patients with lung involvement was 8.1 ± 6.8 [1–31]. The mean age was 43 ± 15 years, with 121 males (48%) and 17 asymptomatic patients (7%). Multivariate analysis showed that age > 54 years (odds ratio 4.4[2.0–9.6] p < 0.001) and diabetes (4.7[1.0–22.1] p = 0.049) were risk factors for a score ≥ 10. Multivariate analysis including symptoms showed that only age > 54 years (4.1[1.7–10.0] p = 0.002) was a risk factor for a score ≥ 10. Rhinitis (0.3[0.1–0.7] p = 0.005) and anosmia (0.3[0.1–0.9] p = 0.043) were protective against lung involvement. Incidental imaging findings were found in 19% of patients, with a need for follow-up in 0.6%.

Conclusion
The prevalence of lung involvement was 54% in a predominantly paucisymptomatic population. Age ≥ 55 years and diabetes were risk factors for significant parenchymal lung involvement. Rhinitis and anosmia were protective against LDCT abnormalities.
AiZynthFinder: a fast, robust and flexible open-source software for retrosynthetic planning
Authors: Genheden Samuel , Thakkar Amol , Chadimová Veronika , Reymond Jean-Louis , Engkvist Ola , Bjerrum Esben 
Published: November 2020

AbstractWe present the open-source AiZynthFinder software that can be readily used in retrosynthetic planning. The algorithm is based on a Monte Carlo tree search that recursively breaks down a molecule to purchasable precursors. The tree search is guided by an artificial neural network policy that suggests possible precursors by utilizing a library of known reaction templates. The software is fast and can typically find a solution in less than 10 s and perform a complete search in less than 1 min. Moreover, the development of the code was guided by a range of software engineering principles such as automatic testing, system design and continuous integration leading to robust software with high maintainability. Finally, the software is well documented to make it suitable for beginners. The software is available at http://www.github.com/MolecularAI/aizynthfinder.
Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina modulates the functions of chicken dendritic cells to boost Th1 type immune response and stimulates autologous CD4+ T cells differentiation in-vitro
Authors: Lakho Shakeel Ahmed , Haseeb Muhammad , Huang Jianmei , Yang Zhang , Hasan Muhammad Waqqas , Aleem Muhammad Tahir , Naqvi Muhammad Ali-ul-Husnain , Memon Muhammad Ali , Song XiaoKai , Yan RuoFeng , Xu Lixin , Li XiangRui 
Published: November 2020

AbstractDendritic cells (DCs) play a pivotal role to amplify antigen-specific immune responses. Antigens that sensitize T cells via antigen-presentation by DCs could enhance the capacity of host immunity to fight infections. In this study, we tested the immunogenic profiles of chicken DCs towards Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina (EaGAPDH). Immunoblot analysis showed that recombinant EaGAPDH (rEaGAPDH) protein was successfully recognized by rat sera generated against rEaGAPDH. Interaction and internalisation of rEaGAPDH by chicken splenic-derived DCs (chSPDCs) was confirmed by immunofluorescence analysis. Flow cytometry revealed that chSPDCs upregulated MHCII, CD1.1, CD11c, CD80, and CD86 cell-surface markers. Moreover, mRNA expressions of DC maturation biomarkers (CCL5, CCR7, and CD83) and TLR signalling genes (TLR15 and MyD88) were also upregulated whereas those of Wnt signalling were non-significant compared to negative controls. rEaGAPDH treatment induced IL-12 and IFN-γ secretion in chSPDCs but had no effect on IL-10 and TGF-β. Likewise, DC-T cell co-culture promoted IFN-γ secretion and the level of IL-4 was unaffected. Proliferation of T cells and their differentiation into CD3+/CD4+ T cells were triggered in chSPDCs-T cells co-culture system. Taken together, rEaGAPDH could promote Th1 polarization by activating both host DCs and T cells and sheds new light on the role of this important molecule which might contribute to the development of new DCs-based immunotherapeutic strategies against coccidiosis.
Causes of stress and conflict in the veterinary professional workplace – a perspective from Poland
Authors: Wojtacka Joanna , Grudzień Wojciech , Wysok Beata , Szarek Józef 
Published: November 2020

Abstract
Background
The problems of burnout and the moral and ethical distress resulting from various kinds of conflict have been raised in the veterinary profession. However, their sources and inter-relationships have not been thoroughly recognized mainly due to the multidimensional nature of human interactions related to animal breeding, farming, welfare, prophylaxis and therapy. For the first time in Poland, an analysis of conflict and conflict-causing factors in veterinary practice has been conducted with the participation of veterinarians of various specialties and the owners of different animal species.

Results
Conflict in the course of work is most often experienced by young veterinarians. The problems associated with communication between veterinarians and animal owners and unforeseen random situations are the general causes of conflict. Approved Veterinarians were identified by animal owners as the most common professional group associated with the conflict experienced .

Conclusions
There is a lack of professional preparation by veterinary surgeons to cope with unpredicted stressful situations at work, resulting from an absence of appropriate educational input in this area. The animal owners do not understand the role and duties of Approved Veterinarians.
Smooth adversarial examples
Authors: Zhang Hanwei , Avrithis Yannis , Furon Teddy , Amsaleg Laurent 
Published: November 2020

AbstractThis paper investigates the visual quality of the adversarial examples. Recent papers propose to smooth the perturbations to get rid of high frequency artifacts. In this work, smoothing has a different meaning as it perceptually shapes the perturbation according to the visual content of the image to be attacked. The perturbation becomes locally smooth on the flat areas of the input image, but it may be noisy on its textured areas and sharp across its edges.This operation relies on Laplacian smoothing, well-known in graph signal processing, which we integrate in the attack pipeline. We benchmark several attacks with and without smoothing under a white box scenario and evaluate their transferability. Despite the additional constraint of smoothness, our attack has the same probability of success at lower distortion.
The gender gap and healthcare: associations between gender roles and factors affecting healthcare access in Central Malawi, June–August 2017
Authors: Azad Amee D. , Charles Anthony G. , Ding Qian , Trickey Amber W. , Wren Sherry M. 
Published: November 2020

Abstract
Background
Women in low and middle-income countries (LMICs) do not have equal access to resources, such as education, employment, or healthcare compared to men. We sought to explore health disparities and associations between gender prioritization, sociocultural factors, and household decision-making in Central Malawi.

Methods
From June–August 2017, a cross-sectional study with 200 participants was conducted in Central Malawi. We evaluated respondents’ access to care, prioritization within households, decision-making power, and gender equity which was measured using the Gender-Equitable Men (GEM) scale. Relationships between these outcomes and sociodemographic factors were analyzed using multivariable mixed-effect logistic regression.

Results
We found that women were less likely than men to secure community-sourced healthcare financial aid (68.6% vs. 88.8%, p < 0.001) and more likely to underutilize necessary healthcare (37.2% vs. 22.4%, p = 0.02). Both men and women revealed low GEM scores, indicating adherence to traditional gender norms, though women were significantly less equitable (W:16.77 vs. M:17.65, p = 0.03). Being a woman (Odds Ratio (OR) 0.41, 95% confidence interval (CI) 0.21–0.78) and prioritizing a woman as a decision-maker for large purchases (OR 0.38, CI 0.15–0.93) were independently associated with a lower likelihood of prioritizing women for medical treatment and being a member of the Chewa tribal group (OR 3.87, CI 1.83–8.18) and prioritizing women for education (OR 4.13, CI 2.13–8.01) was associated with a higher odds.

Conclusion
Women report greater barriers to healthcare and adhere to more traditional gender roles than men in this Central Malawian population. Women contribute to their own gender’s barriers to care and economic empowerment alone is not enough to correct for these socially constructed roles. We found that education and matriarchal societies may protect against gender disparities. Overall, internal and external gender discrimination contribute to a woman’s disproportionate lack of access to care.
Psychological interventions for depression in children and young people with an intellectual disability and/or autism: systematic review
Authors: Cameron Lauren A. , Phillips Katelyn , Melvin Glenn A. , Hastings Richard P. , Gray Kylie M. 
Published: November 2020

BackgroundChildren and young people with intellectual disability and/or Autism Spectrum Disorder (autism) experience higher rates of mental health problems, including depression, than their typically developing peers. Although international guidelines suggest psychological therapies as first-line intervention for children and young people, there is limited evidence for psychological therapy for depression in children and young people with intellectual disability and/or autism.AimsTo evaluate the current evidence base for psychological interventions for depression in children and young people with intellectual disability and/or autism, and examine the experiences of children and young people with intellectual disability and/or autism, their families and therapists, in receiving and delivering psychological treatment for depression.MethodDatabases were searched up to 30 April 2020 using pre-defined search terms and criteria. Articles were independently screened and assessed for risk of bias. Data were synthesised and reported in a narrative review format.ResultsA total of 10 studies met the inclusion criteria. Four identified studies were clinical case reports and six were quasi-experimental or experimental studies. All studies were assessed as being of moderate or high risk of bias. Participants with intellectual disability were included in four studies. There was limited data on the experiences of young people, their families or therapists in receiving or delivering psychological treatment for depression.ConclusionsWell-designed, randomised controlled trials are critical to develop an evidence base for psychological treatment for young people with intellectual disability and/or autism with depression. Future research should evaluate the treatment experiences of young people, their families and therapists.
Delays Experienced by Patients With Pediatric Cancer During the Health Facility Referral Process: A Study in Northern Tanzania
Authors: Maillie Luke , Masalu Nestory , Mafwimbo Judy , Maxmilian Mastidia , Schroeder Kristin 
Published: November 2020

PURPOSE It is estimated that 50%-80% of patients with pediatric cancer in sub-Saharan Africa present at an advanced stage. Delays can occur at any time during the care-seeking process from symptom onset to treatment initiation. Referral delay, the time from first presentation at a health facility to oncologist evaluation, is a key component of total delay that has not been evaluated in sub-Saharan Africa. METHODS Over a 3-month period, caregivers of children diagnosed with cancer at a regional cancer center (Bugando Medical Centre [BMC]) in Tanzania were consecutively surveyed to determine the number and type of health facilities visited before presentation, interventions received, and transportation used to reach each facility. RESULTS Forty-nine caregivers were consented and included in the review. A total of 124 facilities were visited before BMC, with 31% of visits (n = 38) resulting in a referral. The median referral delay was 89 days (mean, 122 days), with a median of two facilities (mean, 2.5 facilities) visited before presentation to BMC. Visiting a traditional healer first significantly increased the time taken to reach BMC compared with starting at a health center/dispensary (103 v 236 days; P = .02). Facility visits in which a patient received a referral to a higher-level facility led to significantly decreased time to reach BMC ( P < .0001). Only 36% of visits to district hospitals and 20.6% of visits to health centers/dispensaries yielded a referral, however. CONCLUSION The majority of patients were delayed during the referral process, but receipt of a referral to a higher-level facility significantly shortened delay time. Referral delay for pediatric patients with cancer could be decreased by raising awareness of cancer and strengthening the referral process from lower-level to higher-level facilities.
Accessory proteins of the zDHHC family of S-acylation enzymes
Authors: Salaun Christine , Locatelli Carolina , Zmuda Filip , Cabrera González Juan , Chamberlain Luke H. 
Published: November 2020

ABSTRACT
Almost two decades have passed since seminal work in Saccharomyces cerevisiae identified zinc finger DHHC domain-containing (zDHHC) enzymes as S-acyltransferases. These enzymes are ubiquitous in the eukarya domain, with 23 distinct zDHHC-encoding genes in the human genome. zDHHC enzymes mediate the bulk of S-acylation (also known as palmitoylation) reactions in cells, transferring acyl chains to cysteine thiolates, and in so-doing affecting the stability, localisation and function of several thousand proteins. Studies using purified components have shown that the minimal requirements for S-acylation are an appropriate zDHHC enzyme–substrate pair and fatty acyl-CoA. However, additional proteins including GCP16 (also known as Golga7), Golga7b, huntingtin and selenoprotein K, have been suggested to regulate the activity, stability and trafficking of certain zDHHC enzymes. In this Review, we discuss the role of these accessory proteins as essential components of the cellular S-acylation system.
MRI for the display of autologous onlay bone grafts during early healing—an experimental study
Authors: Flügge Tabea , Ludwig Ute , Amrein Philipp , Kernen Florian , Vach Kirstin , Maier Johannes , Nelson Katja 
Published: November 2020

Objectives: Autologous bone grafts are the gold standard to augment deficient alveolar bone. Dimensional graft alterations during healing are not known as they are not accessible to radiography. Therefore, MRI was used to display autologous onlay bone grafts in vivo during early healing. Methods and materials: Ten patients with alveolar bone atrophy and autologous onlay grafts were included. MRI was performed with a clinical MR system and an intraoral coil preoperatively (t0), 1 week (t1), 6 weeks (t2) and 12 weeks (t3) postoperatively, respectively. The graft volumes were assessed in MRI by manual segmentation by three examiners. Graft volumes for each time point were calculated and dimensional alteration was documented. Cortical and cancellous proportions of bone grafts were assessed. The intraobserver and interobserver variability were calculated. Statistical analysis was performed using a mixed linear regression model. Results: Autologous onlay bone grafts with cortical and cancellous properties were displayed in vivo in eight patients over 12 weeks. The fixation screws were visible as signal voids with a thin hyperintense fringe. The calculated volumes were between 0.12–0.74 cm3 (t1), 0.15–0.73 cm3 (t2), and 0.17–0.64 cm3 (t3). Median changes of bone graft volumes of −15% were observed. There was no significant difference between the examiners (p = 0.3). Conclusions: MRI is eligible for the display and longitudinal observation of autologous onlay bone grafts. Image artifacts caused measurements deviations in some cases and minimized the precise assessment of graft volume. To the knowledge of the authors, this is the first study that used MRI for the longitudinal observation of autologous onlay bone grafts.
Healthcare Resource Utilization Following a Discharge Against Medical Advice: An Analysis of Commercially Insured Adults
Authors: Gandhi Aakash Bipin , Onukwugha Eberechukwu , McRae Jacquelyn , Alfandre David 
Published: November 2020

BACKGROUNDA discharge against medical advice (DAMA) is associated with adverse health outcomes. Its association with postdischarge healthcare resource utilization (HcRU) outside an inpatient setting is unknown. This information can help us understand how a DAMA may affect healthcare‐seeking behavior following a hospital stay. We evaluated the relationship between a DAMA and 30‐day postdischarge HcRU.METHODSThis retrospective cohort study uses a 10% random sample of enrollees in the IQVIA PharMetrics® Plus database. We included individuals aged 18 to 64 years with an inpatient admission during 2007‐2015 and continuous insurance coverage. We defined comparison groups as DAMA and routine discharge. Both groups were matched on baseline covariates. We quantified the association between a DAMA and 30‐day HcRU, as well as 90‐day for sensitivity analysis, with use of generalized linear models for binary outcomes (inpatient readmissions, emergency department [ED] visits) and count outcomes (physician office visits, nonphysician outpatient encounters, prescription drug fills).RESULTSOf the 457,530 individuals in the unmatched sample, 2,245 (0.5%) had a DAMA. In the matched sample, a DAMA was positively associated with an ED visit (adjusted odds ratio, 2.28; 95% confidence interval, 1.90‐2.72) but not with an inpatient readmission. There were no differences between groups based on the count outcomes. A DAMA was positively associated with 90‐day HcRU (ie, inpatient readmission, ED visit, and prescription drug fills).CONCLUSIONThe relationship between a DAMA and HcRU varied with the HcRU category and postdischarge time interval. This examination of HcRU in the inpatient and outpatient settings provides important information about outcomes following a DAMA.