bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing the 2018 NIA-AA research framework in a retrospective large cohort of patients with cognitive impairment: from biological biomarkers to clinical syndromes
Authors: Carandini Tiziana , Arighi Andrea , Sacchi Luca , Fumagalli Giorgio G. , Pietroboni Anna M. , Ghezzi Laura , Colombi Annalisa , Scarioni Marta , Fenoglio Chiara , De Riz Milena A. , Marotta Giorgio , Scarpini Elio , Galimberti Daniela 
Published: October 2019

AbstractBackgroundAccording to the 2018 NIA-AA research framework, Alzheimer’s disease (AD) is not defined by the clinical consequences of the disease, but by its underlying pathology, measured by biomarkers. Evidence of both amyloid-β (Aβ) and phosphorylated tau protein (p-tau) deposition—assessed interchangeably with amyloid-positron emission tomography (PET) and/or cerebrospinal fluid (CSF) analysis—is needed to diagnose AD in a living person. Our aim was to test the new NIA-AA research framework in a large cohort of cognitively impaired patients to evaluate correspondence between the clinical syndromes and the underlying pathologic process testified by biomarkers.MethodsWe retrospectively analysed 628 subjects referred to our centre in suspicion of dementia, who underwent CSF analysis, together with neuropsychological assessment and neuroimaging, and were diagnosed with different neurodegenerative dementias according to current criteria, or as cognitively unimpaired. Subjects were classified considering CSF biomarkers, and the prevalence of normal, AD-continuum and non-AD profiles in each clinical syndrome was calculated. The positivity threshold of each CSF biomarker was first assessed by receiver operating characteristic analysis, using Aβ-positive/negative status as determined by amyloid-PET visual reads. The agreement between CSF and amyloid-PET data was also evaluated.ResultsAmong patients with a clinical diagnosis of AD, 94.1% were in the AD-continuum, whereas 5.5% were classified as non-AD and 0.4% were normal. The AD-continuum profile was found also in 26.2% of frontotemporal dementia, 48.6% of Lewy body dementia, 25% of atypical parkinsonism and 44.7% of vascular dementia. Biomarkers’ profile did not differ in amnestic and not amnestic mild cognitive impairment. CSF Aβ levels and amyloid-PET tracer binding negatively correlated, and the concordance between the two Aβ biomarkers was 89%.ConclusionsThe examination of the 2018 NIA-AA research framework in our clinical setting revealed a good, but incomplete, correspondence between the clinical syndromes and the underlying pathologic process measured by CSF biomarkers. The AD-continuum profile resulted to be a sensitive, but non-specific biomarker with regard to the clinical AD diagnosis. CSF and PET Aβ biomarkers were found to be not perfectly interchangeable to quantify the Aβ burden, possibly because they measure different aspects of AD pathology.
PSMA expression level predicts differentiated thyroid cancer aggressiveness and patient outcome
Authors: Sollini Martina , di Tommaso Luca , Kirienko Margarita , Piombo Chiara , Erreni Marco , Lania Andrea Gerardo , Erba Paola Anna , Antunovic Lidija , Chiti Arturo 
Published: October 2019

Abstract

Background
Prostate-specific membrane antigen (PSMA) is overexpressed on the endothelial cells of tumor neo-vessels of several solid malignancies, including differentiated thyroid cancer (DTC). We aimed to test the potential role of PSMA as a biomarker for DTC aggressiveness and outcome prediction.
We retrospectively screened all patients who underwent thyroidectomy between 1 January 2010 and 31 December 2017 in our institution. Applying the inclusion (histological diagnosis of thyroid cancer and tissue availability) and exclusion criteria (no clinical or follow-up data or diagnosis of medullary thyroid cancer), a cohort of 59 patients was selected. The monoclonal mouse anti-human PSMA antibody was used to stain tissue sections. A 3-point scale was used to score PSMA positivity: 0–5% expression was considered as negative (score 0), 6–50% as moderately positive (score 1), and 51–100% as highly positive (score 2). A cumulative score (0–10%, 11–79%, and 80–100%) was also explored. Univariate and multivariate logistic regression analyses were performed to predict the presence of distant metastases, chosen as endpoint of aggressiveness. The area under the curve (AUC) was calculated. Cox models were built to predict patient outcome in terms of recurrence, iodine refractoriness, and status at last follow-up, which were calculated using the Kaplan-Meier failure function.

Results
At immunostaining, 12, 25, and 22 patients had scores of 0, 1, and 2, respectively. According to the cumulative score, PSMA expression was ≤ 10% in 17 cases, 11–79% in 31 cases, and ≥ 80% in 11 cases. At multivariate analysis, age, sex, histotype, vascular invasion, T and N parameters, and PSMA positivity were significant predictors of distant metastases. The AUC was 0.92. Recurrence or progression occurred in 19/59 patients. Twelve patients developed radioiodine (RAI) refractoriness, after a median time of 17 months (range 2–32). One patient died of DTC; 46 of the 58 patients alive at last follow-up were disease free. Median DFS was 23 months (range 3–82). The final multivariate model to predict RAI refractoriness included as covariates the stage, high PSMA expression (≥ 80%), and the interaction between moderate PSMA expression (11–79%) and stage.

Conclusions
PSMA, a marker of neovasculature formation expressed by DTC, contributes in the prediction of tumor aggressiveness and patient outcome.
Supraglottic p16+ squamous cell carcinoma during pregnancy: A case report and review of the literature
Authors: Pugi Jakob , Levin Marc , Gupta Michael 
Published: October 2019

Background Head and neck cancer during pregnancy is uncommon. Specifically, laryngeal cancer in pregnancy has only been previously reported 10 times. HPV p16+ supraglottic cancer during pregnancy has never been described in the literature prior to this case report. This case is important to report to understand the most effective and safe diagnostic, treatment and follow-up options available for pregnant patients with laryngeal cancer. Case presentation This report describes a case of a 33-year-old patient who was 24 weeks pregnant presenting with dysphonia and odynophagia. After laryngeal biopsy and MRI she was diagnosed with T3N1M0, stage three p16+ squamous cell carcinoma of the supraglottis. After inter-disciplinary consultation as well as extensive patient discussion, an awake tracheostomy, PEG tube placement and then elective C-section at 28 weeks’ gestation was completed. This was followed by chemoradiotherapy. The patient has remained free from disease with a healthy child at four years post-treatment. Conclusion Supraglottic cancer during pregnancy is rare with only four previous cases reported in the literature. This case report elucidates the importance of including multiple specialities as well as patient preference in the decision-making process regarding treatment for patients with supraglottic cancer during pregnancy. Furthermore, diagnostic and treatment guidelines for pregnant patients with head and neck cancers should be established to promote the best possible oncological, obstetrical and neonatal care.
Development of research integrity in France is on the rise: the introduction of research integrity officers was a progress
Authors: Maisonneuve Hervé 
Published: October 2019

Abstract

Background
Implementing responsible conduct of research and monitoring bad practices requires time and tact. In France, it was in 2015 that the wishes of those in charge of research proposed the appointment of research integrity officers (RIOs) in all universities, national higher education schools, and research institutions. Our objectives were to search for information to describe the RI development and to analyze the RIOs’ profiles.

Methods
The OFIS (Office Français de l’Intégrité Scientifique) website lists all public research institutions and universities (RIUs) and their designated RIOs. During the period between 6 and 14 October 2018, and on 2 May 2019 (updating), we entered two keywords (“plagiat” and “intégrité”) into the search engines on the RIU homepages and retrieved the relevant information (including “research” and “scientific” integrity when “intégrité” was entered). We consulted the governance and downloaded the organigram to determine whether the RIO positions and names were mentioned. We searched for the domains of expertise, sex, and age of the RIOs from their CVs (institutional websites), LinkedIn profiles, and various Google links.

Results
The OFIS website lists 142 RIUs. Searching for the keyword “plagiarism” retrieved 25 RIUs; however, the web information was minimal, and consisted entirely of charters, interviews, and rare training modules. The keyword “integrity” turned up 23 RIUs. Nonetheless, there was little information available beyond notices for seminars, events, and a few training modules. Of the total 142 RIUs, 66.2% (n = 94) had named 96 RIOs. Furthermore, 29.2% RIOs (n = 28) were female and 70.8% (n = 68) were male; 38 RIOs were retired (> 65 years old) 58 were active (< 65 years old), and had a RIO function added to their usual laboratory activities.

Conclusion
There is a lack of information about RI on the websites of French universities and research organizations, which may reflect a lack of information and commitment in the institutions themselves.
Direct torque control of doubly fed induction motor using three-level NPC inverter
Authors: El Ouanjli Najib , Derouich Aziz , El Ghzizal Abdelaziz , Taoussi Mohammed , El Mourabit Youness , Mezioui Khalid , Bossoufi Badre 
Published: October 2019

Abstract
This article presents the direct torque control (DTC) strategy for the doubly fed induction motor (DFIM) connected to two three-level voltage source inverters (3LVSIs) with neutral point clamped (NPC) structure. This control method allows to reduce the torque and flux ripples as well as to optimize the total harmonic distortion (THD) of motor currents. The use of 3LVSI increases the number of generated voltage, which allows improving the quality of its waveform and thus improves the DTC strategy. The system modeling and control are implemented in Matlab/Simulink environment. The analysis of simulation results shows the better performances of this control, especially in terms of torque and flux behavior, compared to conventional DTC.
Effects of parental mental illness on children's physical health: systematic review and meta-analysis
Authors: Pierce Matthias , Hope Holly F. , Kolade Adekeye , Gellatly Judith , Osam Cemre Su , Perchard Reena , Kosidou Kyriaki , Dalman Christina , Morgan Vera , Di Prinzio Patricia , Abel Kathryn M. 
Published: October 2019

BackgroundChildren of parents with mental disorder face multiple challenges.AimsTo summarise evidence about parental mental disorder and child physical health.MethodWe searched seven databases for cohort or case–control studies quantifying associations between parental mental disorders (substance use, psychotic, mood, anxiety, obsessive–compulsive, post-traumatic stress and eating) and offspring physical health. Studies were excluded if: they reported perinatal outcomes only (<28 days) or outcomes after age 18; they measured outcome prior to exposure; or the sample was drawn from diseased children. A meta-analysis was conducted. The protocol was registered on the PROSPERO database (CRD42017072620).ResultsSearches revealed 15 945 non-duplicated studies. Forty-one studies met our inclusion criteria: ten investigated accidents/injuries; eight asthma; three other atopic diseases; ten overweight/obesity; ten studied other illnesses (eight from low-and middle-income countries (LMICs)). Half of the studies investigated maternal perinatal mental health, 17% investigated paternal mental disorder and 87% examined maternal depression. Meta-analysis revealed significantly higher rates of injuries (OR = 1.15, 95% CI 1.04–1.26), asthma (OR = 1.26, 95% CI 1.12–1.41) and outcomes recorded in LMICs (malnutrition: OR = 2.55, 95% CI 1.74–3.73; diarrhoea: OR = 2.16, 95% CI 1.65–2.84). Evidence was inconclusive for obesity and other atopic disorders.ConclusionsChildren of parents with mental disorder have health disadvantages; however, the evidence base is limited to risks for offspring following postnatal depression in mothers and there is little focus on fathers in the literature. Understanding the physical health risks of these vulnerable children is vital to improving lives. Future work should focus on discovering mechanisms linking physical and mental health across generations.Declaration of interestNone.
Ultra-rapid total abdominal FLASH irradiation in a preclinical model of ovarian cancer.
Authors: Levy Karen , Wang Jinghui , Natarajan Suchitra , Casey Keriann , Eggold Joshua Thomas , Rafat Marjan , Loo Billy W. , Rankin Erinn 
Published: October 2019

103 Background:Total abdominal irradiation (TAI) is no longer used in the treatment of ovarian cancer due to abdominopelvic toxicity. FLASH irradiation is known to spare the lung, skin and brain from radiation toxicity in preclinical models. Conventional radiotherapy delivers a dose-rate of 2-4 Gy/minute, while our small animal FLASH system uses a linear accelerator to generate a dose-rate of 200 Gy/second. We have demonstrated that FLASH-TAI produces less gastrointestinal (GI) toxicity and death compared to conventional (CONV) radiation in a murine model. Here we present the first data supporting the potential for both tumor control and GI sparing using FLASH-TAI in a syngeneic orthotopic preclinical model of ovarian cancer. Methods: Normal tissue toxicity was assessed through survival, total body weight, solid stool production, complete blood count and histologic analysis. For the tumor model, ID8 ovarian cancer cells were injected intraperitoneally into female C57BL/6mice. Radiation was delivered 10 days post-ID8 injection. Tumor burden was assessed at the time of morbidity. Flow cytometry was used to profile infiltrating immune cells. Results: At 16 Gy, 100% of CONV treated mice demonstrated lethal GI toxicity while 90% of FLASH treated mice recovered to normal bodyweight by day 14. Histologic analysis at 96 hours after 14 Gy FLASH found 3-fold more surviving small intestinal crypts compared to CONV. In the ID8 mice, 14 Gy FLASH spared GI function with a 2-fold higher solid stool production at 5 days post-TAI. Both modalities extended median overall survival in the ID8 model by 5 days and reduced tumor burden by 50% relative to unirradiated controls. Irradiated cohorts also demonstrated a 2-3 fold increase in the number of proliferating CD8+ and CD4+ T cells present in the ascites. Conclusions: Compared to CONV-TAI, FLASH-TAI spares gastrointestinal function, provides equivalent tumor control, and is associated with improved post-radiation recovery and overall survival in an orthotopic preclinical model of ovarian cancer. Our findings suggest an exciting new opportunity to improve the safety of TAI in the treatment of intra-abdominal tumors.
A signature predictive of early versus late recurrence after radiation (RT) for breast cancer that may inform the biology of early, aggressive recurrences.
Authors: Speers Corey Wayne , Chang S. Laura , Chandler Benjamin , Pesch Andrea , Michmerhuizen Anna , Wilder-Romans Kari , Nyati Shyam , Pierce Lori J. 
Published: October 2019

112 Background: Unmet clinical needs in breast cancer (BC) management include the identification of patients at high risk to fail locally despite standard local therapy and an understanding of the biology of these recurrences. We previously reported a radiation response signature and here extend those studies to identify a signature predictive of timing of recurrence after RT. Methods: 2 independent patient cohorts were used for training (119 pts) and validation (112 pts). All patients received RT after BCS and systemic therapy as appropriate. Spearman’s rank correlation to correlate gene expression to recurrence time was used for feature selection. Significant genes were used to train a linear model which was locked before validation. Cox regression was used for both UVA and MVA. Results: Spearman’s correlation identified 485 genes whose expression was significantly associated with recurrence time (+/-3 yrs). Feature reduction refined the list to 41 genes retained within the signature. In training, the correlation of score to recurrence time was 0.85, p-value < 1.3x10-31; AUC of 0.91. External validation in an independent BC validation set accurately identified patients with early vs. late recurrences (correlation= 0.75, p-value = 0.001, AUC = 0.92, sens.=0.75, spec.= 1.0, PPV = 1.0, NPV = 0.8). Unique associations of breast cancer intrinsic subtype to timing of local recurrence were found. In UVA and MVA the signature remained the most significant factor associated with recurrence. GSEA analysis of the 41 genes retained within the signature identified proliferation and EGFR concepts associated with early recurrences and luminal and ER-signaling pathways associated with late recurrences. Knockdown of genes associated with the early and late recurrences demonstrated novel effects on proliferation and clonogenic survival, respectively. Conclusions: We report a BC gene expression signatures that may be useful in identifying patients unlikely to respond to adjuvant RT and may be used to predict timing of recurrences, with implications for potential treatment intensification and duration of follow-up for women with breast cancer treated with RT.
Risk factors and therapeutic significance for inguinal lymph node metastasis in advanced lower rectal cancer.
Authors: Nozawa Hiroaki , Shiratori Hiroshi , Kawai Kazushige , Hata Keisuke , Tanaka Toshiaki , Nishikawa Takeshi , Shuno Yasutaka , Sasaki Kazuhito , Kaneko Manabu , Emoto Shigenobu , Murono Koji , Sonoda Hirofumi , Ishii Hiroaki , Ishihara Soichiro 
Published: October 2019

120 Background: Which patients with lower rectal cancer are at risk of inguinal lymph node metastasis (ILNM) and how to treat ILNM remain unclear. This study aimed to clarify the predictors of ILNM and clinical significance of treatment for ILNM. Methods: Consecutive patients with rectal adenocarcinoma invading the anal canal who underwent curative surgery between 2003 and 2019 at a single institution were retrospectively reviewed. The pathological nodal involvement in mesorectal, lateral pelvic or inguinal lymph nodes (ILN) at the time of rectal surgery and of later onset were collectively defined as final nodal metastasis (f-LNM) in this study. Factors associated with f-LNM were analyzed. Moreover, the ‘modified therapeutic value index’ defined by the 5-year overall survival rate of patients treated against f-LNM multiplied by their frequency was calculated for each lymph node area. Results: A total of 145 patients were enrolled, among whom16 patients developed ILNM. For predicting f-ILNM, the cutoff 8.5 mm of ILN diameter gave area under the curve of 0.889. Dentate line involvement and ILN larger than a simplified cutoff of 8 mm were independently associated with the development of ILNM (odds ratio: 33.4 and 11.9, respectively). The modified therapeutic value indice of inguinal, lateral pelvic and mesorectal LNs in the entire population were 6.1, 8.2 and 20.3 points, respectively. In patients with dentate line invaded by cancer, they were 11.7, 5.8 and 16.2 points, respectively. Moreover, the index of ILN was 21.1 points when confined to patients with ILN larger than 8 mm. Conclusions: Dentate line involvement and ILN larger than 8 mm were predictive of developing ILNM in patients with rectal cancer invading the anal canal. Treatment of ILNM may be recommended for patients manifesting the above predictors, given the significant therapeutic outcomes.
LINC00184 involved in the regulatory network of ANGPT2 via ceRNA mediated miR-145 inhibition.
Authors: Piao Haiyan 
Published: October 2019

17 Background: Abnormal gene expression is closely related to the development and poor prognosis of gastric cancer (GC). Since gene does not work alone, we are aimed to elucidate the potential networks between mRNA and non-coding RNAs (ncRNAs) in this study. Methods: Based on the TCGA database, we obtained the differentially expressed RNAs and constructed the competing endogenous RNA (ceRNA) regulatory network. Results: We found a regulatory network based on ANGPT2. We observed ANGPT2 is overexpressed in GC cells and tissues and associated with poor prognosis. ANGPT2 promotes proliferation, invasion, and EMT in GC cells, which could be abolished by miR-145. In addition, LINC00184 can be used as a ceRNA to inhibit the expression of miR-145, thus enhancing the carcinogenic effect of ANGPT2. Conclusions: Our results suggested that LINC00184/miR-145/ANGPT2 axis plays an important role in the occurrence and development of GC and may be potential biomarkers and targets for the treatment of GC.
Creating solutions through design thinking.
Authors: Bariani Giovanni M. , Ribeiro Rafael Lopes , Soares Leonardo de Morais , Katz Artur 
Published: October 2019

20 Background: In recent years the impact of technology has marked a major transformation in the way society produces and generates services. Several initiatives have been developed in the health area to face this new reality. A major oncology center in Brazil carried out a project based on Design Thinking with the objective of understanding the current scenario and promoting innovative solutions for the care of cancer patients. Methods: Design Thinking is the set of ideas and insights to address problems related to information acquisition, knowledge analysis and proposal of solutions. This process took place in four stages designated as empathise (approach to the context of the problem and data collection), define (synthesis of collected information, and organization of insights in order to standardize and better understand the problem), ideate (stimulation of creativity and generation of solutions) and prototype (validation of the ideas). Results: A total of 130 interviews were carried out with hospital personnel and 46 with patients and caregivers, as well as workshops to develop the project activities. Twenty-six projects were generated, and the priorities differed according to personnel and patients. Among the projects are financial consultancy; predictability of the total cost of treatment; diversification of payment methods; customization of the food menu offered to patients; promotion of entertainment activities during waiting periods in the practice; increase interactivity of chemotherapy rooms; improvement of services offered to international patients; and development of digital tools that provide reliable information about cancer, promotes patient autonomy and strengthens patient’s relationship with the hospital personnel. Conclusions: There is a growing need to modernize oncology practices creating new products and services. The opinion of hospital personnel and patients diverged about priorities. The former have chosen projects to improve facilities and design new roles for the team while the latter have given their best evaluations to new systems and services. For patients using digital media is not only welcome but also necessary attributes to provide more information and increase their autonomy.