bluuebunny/crossref_metadata_2025_split huggingface dataset:
ERANET JTC 2011: Submission and Activation of an International Academic Translational Project in Advanced Breast Cancer. Experience From the ET-FES Study
Authors: Monti Manuela , Degenhardt Tom , Brain Etienne , Wuerstlein Rachel , Argusti Alessandra , Puntoni Matteo , Rollandi Gian Andrea , Corradengo Davide , Boni Luca , Ilhan Harun , Nanni Oriana , Cortes Javier , Piris-Gimenez Alejandro , Piccardo Arnoldo , Iacozzi Massimiliano , Matteucci Federica , Di Iorio Valentina , Alberini Jean Louis , Schröder Carolien , Harbeck Nadia , Gennari Alessandra 
Published: January 2022

Background: Academic research is important to face unmet medical needs. The Oncological community encounters many hurdles in setting up multicenter investigator-driven trials mainly due to administrative complexity. The purpose of a network organization at a multinational level is to facilitate clinical trials through standardization, coordination, and education for drug development and regulatory approval.Methods: The application of an European grant foresees the creation of a consortium which aims at facilitating multi-center academic clinical trials.Results: The ERA-NET TRANSCAN Call 2011 on “Validation of biomarkers for personalized cancer medicine” was released on December 2011. This project included Italian, Spanish, French and German centers. The approval process included Consortium constitution, project submission, Clinical Trial Submission, and activation on a national level. The different timescales for submitting study documents in each Country and the misalignment of objections by each Competent Authority CA, generated several requests for changes to the study documents which meant amendments had to be made; as requested by the 2001/20/EC Directive, the alignment of core documents is mandatory. This procedure impacted significantly on study activation timelines. Time to first patient in was 14, 10, 28, and 31 months from the date of submission in Italy, France, Spain, and Germany, respectively. Accrual was stopped on 22nd January 2021 due to an 18F FES shortage as the primary reason but also for having exceeded the project deadlines with consequent exhaustion of the funds allocated for the project.Conclusions: Pharmaceutical companies might be reluctant to fund research projects aimed at treatment individualization if the approval for a wider indication has already been achieved. Academic trials therefore become fundamental for promoting trials which are not attractive to big pharma. It was very difficult and time consuming to activate an academic clinical trial, for this reason, a study may become “old” as new drugs entered into the market. National institutions should promote the development of clinical research infrastructures and network with competence in regulatory, ethical, and legal skills to speed up academic research.
Molecular Characterization and Clinical Relevance of ALDH2 in Human Cancers
Authors: Ma Bo , Liu Zaoqu , Xu Hui , Liu Long , Huang Tao , Meng Lingfang , Wang Libo , Zhang Yuyuan , Li Lifeng , Han Xinwei 
Published: January 2022

Background: Aldehyde dehydrogenase 2 (ALDH2) is well-known to be a key enzyme in alcohol metabolism. However, a comprehensive understanding of ALDH2 across human cancers is lacking.Methods: A systematic and comprehensive analysis of the molecular alterations and clinical relevance for ALDH2 in more than 10,000 samples from 33 cancer types was performed. qRT-PCR was performed on 60 cancer and 60 paired nontumor tissues.Results: It was observed that ALDH2 was generally downregulated in most cancers, which was mainly driven by DNA hypermethylation rather than mutations or copy number variations. Besides, ALDH2 was closely related to the inhibition and activation of tumor pathways and a variety of potential targeted agents had been discovered in our research. Last but not least, ALDH2 had the best prediction efficacy in assessing immunotherapeutic response compared with PD-L1, PD-1, CTLA4, CD8, and tumor mutation burden (TMB) in cutaneous melanoma. According to the analysis of large-scale public data and 60 pairs of clinical cancer samples, we found the downregulation of ALDH2 expression tends to suggest the malignant phenotypes and adverse prognosis, which might enhance the precise diagnosis and timely intervention of cancer patients.Conclusion: This study advanced the understanding of ALDH2 across cancers, and provided important insight into chemotherapy, immunotherapy and prognosis of patients with cancer.
Serotype Distribution, Antimicrobial Susceptibility, Multilocus Sequencing Type and Virulence of Invasive Streptococcus pneumoniae in China: A Six-Year Multicenter Study
Authors: Zhou Menglan , Wang Ziran , Zhang Li , Kudinha Timothy , An Haoran , Qian Chenyun , Jiang Bin , Wang Yao , Xu Yingchun , Liu Zhengyin , Zhang Hong , Zhang Jingren 
Published: January 2022

Background:Streptococcus pneumoniae is an important human pathogen that can cause severe invasive pneumococcal diseases (IPDs). The aim of this multicenter study was to investigate the serotype and sequence type (ST) distribution, antimicrobial susceptibility, and virulence of S. pneumoniae strains causing IPD in China.Methods: A total of 300 invasive S. pneumoniae isolates were included in this study. The serotype, ST, and antimicrobial susceptibility of the strains, were determined by the Quellung reaction, multi-locus sequence typing (MLST) and broth microdilution method, respectively. The virulence level of the strains in the most prevalent serotypes was evaluated by a mouse sepsis model, and the expression level of well-known virulence genes was measured by RT-PCR.Results: The most common serotypes in this study were 23F, 19A, 19F, 3, and 14. The serotype coverages of PCV7, PCV10, PCV13, and PPV23 vaccines on the strain collection were 42.3, 45.3, 73.3 and 79.3%, respectively. The most common STs were ST320, ST81, ST271, ST876, and ST3173. All strains were susceptible to ertapenem, levofloxacin, moxifloxacin, linezolid, and vancomycin, but a very high proportion (&gt;95%) was resistant to macrolides and clindamycin. Based on the oral, meningitis and non-meningitis breakpoints, penicillin non-susceptible Streptococcus pneumoniae (PNSP) accounted for 67.7, 67.7 and 4.3% of the isolates, respectively. Serotype 3 strains were characterized by high virulence levels and low antimicrobial-resistance rates, while strains of serotypes 23F, 19F, 19A, and 14, exhibited low virulence and high resistance rates to antibiotics. Capsular polysaccharide and non-capsular virulence factors were collectively responsible for the virulence diversity of S. pneumoniae strains.Conclusion: Our study provides a comprehensive insight into the epidemiology and virulence diversity of S. pneumoniae strains causing IPD in China.
Cerebrospinal Fluid Biomarkers, Brain Structural and Cognitive Performances Between Normotensive and Hypertensive Controlled, Uncontrolled and Untreated 70-Year-Old Adults
Authors: Badji Atef , Pereira Joana B. , Shams Sara , Skoog Johan , Marseglia Anna , Poulakis Konstantinos , Rydén Lina , Blennow Kaj , Zetterberg Henrik , Kern Silke , Zettergren Anna , Wahlund Lars-Olof , Girouard Hélène , Skoog Ingmar , Westman Eric 
Published: January 2022

Background:Hypertension is an important risk factor for Alzheimer’s disease (AD). The pathophysiological mechanisms underlying the relationship between AD and hypertension are not fully understood, but they most likely involve microvascular dysfunction and cerebrovascular pathology. Although previous studies have assessed the impact of hypertension on different markers of brain integrity, no study has yet provided a comprehensive comparison of cerebrospinal fluid (CSF) biomarkers and structural brain differences between normotensive and hypertensive groups in a single and large cohort of older adults in relationship to cognitive performances.Objective:The aim of the present work was to investigate the differences in cognitive performances, CSF biomarkers and magnetic resonance imaging (MRI) of brain structure between normotensive, controlled hypertensive, uncontrolled hypertensive, and untreated hypertensive older adults from the Gothenburg H70 Birth Cohort Studies.Methods:As an indicator of vascular brain pathology, we measured white matter hyperintensities (WMHs), lacunes, cerebral microbleeds, enlarged perivascular space (epvs), and fractional anisotropy (FA). To assess markers of AD pathology/neurodegeneration, we measured hippocampal volume, temporal cortical thickness on MRI, and amyloid-β42, phosphorylated tau, and neurofilament light protein (NfL) in cerebrospinal fluid. Various neuropsychological tests were used to assess performances in memory, attention/processing speed, executive function, verbal fluency, and visuospatial abilities.Results:We found more white matter pathology in hypertensive compared to normotensive participants, with the highest vascular burden in uncontrolled participants (e.g., lower FA, more WMHs, and epvs). No significant difference was found in any MRI or CSF markers of AD pathology/neurodegeneration when comparing normotensive and hypertensive participants, nor among hypertensive groups. No significant difference was found in most cognitive functions between groups.Conclusion:Our results suggest that good blood pressure control may help prevent cerebrovascular pathology. In addition, hypertension may contribute to cognitive decline through its effect on cerebrovascular pathology rather than AD-related pathology. These findings suggest that hypertension is associated with MRI markers of vascular pathology in the absence of a significant decline in cognitive functions.
Coronary Artery Disease in Patients Presenting With Acute Ischemic Stroke or Transient Ischemic Attack and Elevated Troponin Levels
Authors: Kruska Mathieu , Kolb Anna , Fastner Christian , Mildenberger Iris , Hetjens Svetlana , Kittel Maximilian , Bail Kathrin , Behnes Michael , Akin Ibrahim , Borggrefe Martin , Szabo Kristina , Baumann Stefan 
Published: January 2022

Background: There is little information concerning the invasive coronary angiography (ICA) findings of patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) with elevated troponin levels and suspected myocardial infarction (MI). This study analyzed patient characteristics associated with ICA outcomes.Methods: A total of 8,322 patients with AIS or TIA, treated between March 2010 and May 2020, were retrospectively screened for elevated serum troponin I at hospital admission. Patients in whom ICA was performed, due to suspected type 1 MI based on symptoms, echocardiography, and ECG, were categorized according to ICA results (non-obstructive coronary artery disease (CAD): ≥1 stenosis ≥50% but no stenosis ≥80%; obstructive CAD: any stenosis ≥80% or hemodynamically relevant stenosis assessed by FFR/iwFR).Results: Elevated troponin levels were detected in 2,205 (22.5%) patients, of whom 123 (5.6%) underwent ICA (mean age 71 ± 12 years; 67% male). CAD was present in 98 (80%) patients, of whom 51 (41%) were diagnosed with obstructive CAD. Thus, ICA findings of obstructive CAD accounted for 2.3% of patients with troponin elevation and 0.6% of all stroke patients. The clinical hallmarks of myocardial ischemia, including angina pectoris (31 vs. 15%, p &lt; 0.05) and regional wall motion abnormalities (49 vs. 32%, p = 0.07), and increased cardiovascular risk indicated obstructive CAD. While there was no association between lesion site or stroke severity and ICA findings, causal large-artery atherosclerosis was significantly more common in patients with obstructive coronary disease (p &lt; 0.05).Conclusion: The rate of obstructive CAD in patients with stroke or TIA and elevated troponin levels with suspected concomitant type I MI is low. The cumulation of several cardiovascular risk factors and clinical signs of MI were predictive. AIS patients with large-artery atherosclerosis and elevated troponin may represent an especially vulnerable subgroup of stroke patients with risk for obstructive CAD.
Endoscopic Submucosal Dissection for Early Gastric Cancer in Elderly vs. Non-Elderly Patients: A Systematic Review and Meta-Analysis
Authors: Zhao Jiting , Sun Zhen , Liang Junwei , Guo Song , Huang Di 
Published: January 2022

ObjectiveThis study aimed to review the applicability and complications rate associated with endoscopic submucosal dissection (ESD) for early gastric cancer in elderly patients.MethodsDatabases of PubMed, Embase, CENTRAL, and ScienceDirect were searched till 15th April 2021. All types of studies comparing ESD in the elderly vs non-elderly were included. Subgroup analysis was conducted for the following groups: ≥80 years vs &lt;80 years, ≥75 years vs &lt; 75 years, and ≥65 years vs &lt;65 years.Results17 studies were included. Meta-analysis indicated no statistically significant difference in the en-bloc resection rates (OR: 0.92 95% CI: 0.68, 1.26 I2 = 8% p=0.62) and histological complete resection rates (OR: 0.93 95% CI: 0.75, 1.15 I2 = 26% p=0.50) between elderly and non-elderly patients. The results were non-significant even on subgroup analysis. Overall, we found a non-significant but a tendency of increased perforation rates in the elderly as compared to non-elderly patients (OR: 1.22 95% CI: 0.99, 1.52 I2 = 0% p=0.06). However, there was a significantly increased risk of perforation in elderly patients aged ≥80 years as compared to patients &lt;80 years (OR: 1.50 95% CI: 1.00, 2.24 I2 = 3% p=0.05). Bleeding rates were not different in the two groups (OR: 1.07 95% CI: 0.87, 1.32 I2 = 19% p=0.52). Pooled analysis indicated a statistically significantly increased risk of pneumonia in elderly patients (OR: 2.52 95% CI: 1.72, 3.70 I2 = 7% p&lt;0.00001). Length of hospital stay was reported only by five studies. Meta-analysis indicated no significant difference between the two study groups (MD: 0.67 95% CI: -0.14, 1.48 I2 = 83% p=0.10).ConclusionEn-bloc and histological complete resection rates do not differ between elderly and non-elderly patients undergoing ESD for early gastric cancer. Elderly patients have a small tendency of increased risk of perforation with significantly increased rates in the super-elderly (≥80 years of age). The risk of pneumonia is significantly higher in elderly patients but the rates of bleeding do not differ. The certainty of evidence is “very low” and there is a need for high-quality studies taking into account confounding factors to enhance the quality of evidence.
Case Report: Locking Plate for Cubitus Varus Correction in a 7-Year-Old Girl With Osteogenesis Imperfecta
Authors: Hong Pan , Liu Ruikang , Rai Saroj , Li Jin 
Published: January 2022

Background: Cubitus varus deformity is a common complication of untreated elbow fractures in children. However, cubitus varus in osteogenesis imperfecta (OI) children is a rare but challenging situation. To the author's knowledge, this is the first study discussing the correction of cubitus varus deformity in patient with OI.Case Presentation: Here we report a case of a 7-year-old OI girl with cubitus varus deformity due to a supracondylar fracture of humerus 3 year ago. The patient's parent gave a history of supracondylar fracture of left humerus in 2015. Without medical intervention, the patient was admitted into our institution for corrective surgery with the diagnosis of osteogenesis imperfecta and cubitus varus deformity in the left arm.Result: Medications including calcium, vitamin D and bisphosphonates were administered before the corrective surgery of cubitus varus, and a single locking plate was used to fixate the osteotomy. After the surgery, the appearance and range of motion (ROM) of the left arm was almost normal. Combined with gradual rehabilitation, the ROM of the left arm was normal without pain during daily use within the 1-year follow up. The hardware was removed as the nailing of the forearm fractures was performed at the same time. In the latest follow-up in September 2021, the appearance and ROM of the left arm was normal.Conclusion: Cubitus varus is a common deformity in children with elbow injuries, but it presents a challenging situation in compound fractures in OI patients. Locking plate combined with meticulous pharmacological intervention provides a good option for corrective surgery of cubitus varus in patients with OI.
Case Report: Is It Premature Ovarian Insufficiency or Swyer Syndrome After Bone Marrow Transplantation?
Authors: Li Hui , Li Jin , Li Xiaohong , Yi Hong , Ren Qixiu , Chen Xiaoyan 
Published: January 2022

Introduction: Iatrogenic factor is one of the recognized causes for premature ovarian insufficiency. The aim of this case report was to present a rare case with premature ovarian insufficiency and 46, XY karyotype after bone marrow transplant (BMT) for thalassaemia major at childhood. We also reviewed some relevant literature in this report.Case Presentation: A 17-year-old girl was presented with primary amenorrhea and premature ovarian insufficiency after receiving chemotherapy and BMT from her brother due to thalassaemia major at childhood. She had poor secondary sex characteristics, assessed as stage I for the development of breasts and external genitalia based on the Tanner scale. Transabdominal ultrasound showed small uterus with visible endometrial lining and small ovaries. Laboratory data showed hypergonadotropic hypogonadism profile with low level of estrogen and high level of follicular-stimulating hormone (FSH). Patient's peripheral lymphocytes karyotype was 46, XY.Conclusions: This case was diagnosed as a chemotherapy induced premature ovarian insufficiency. Patient's peripheral lymphocytes karyotype (46, XY) after she received BMT from a male donor was a misleading finding, and the case could be easily misdiagnosed as Swyer syndrome. A correct diagnosis in such cases should depend not only on the recent clinical findings, but also on the detailed medical history. To prevent premature ovarian insufficiency in similar cases, fertility preservation should be offered to girls before they receive chemotherapy, total body irradiation and BMT.
Deep Learning-Aided Automatic Contouring of Clinical Target Volumes for Radiotherapy in Breast Cancer After Modified Radical Mastectomy
Authors: You Jinqiang , Wang Qingxin , Wang Ruoxi , An Qin , Wang Jing , Yuan Zhiyong , Wang Jun , Chen Haibin , Yan Ziye , Wei Jun , Wang Wei 
Published: January 2022

Purpose: The aim of this study is to develop a practicable automatic clinical target volume (CTV) delineation method for radiotherapy of breast cancer after modified radical mastectomy.Methods: Unlike breast conserving surgery, the radiotherapy CTV for modified radical mastectomy involves several regions, including CTV in the chest wall (CTVcw), supra- and infra-clavicular region (CTVsc), and internal mammary lymphatic region (CTVim). For accurate and efficient segmentation of the CTVs in radiotherapy of breast cancer after modified radical mastectomy, a multi-scale convolutional neural network with an orientation attention mechanism is proposed to capture the corresponding features in different perception fields. A channel-specific local Dice loss, alongside several data augmentation methods, is also designed specifically to stabilize the model training and improve the generalization performance of the model. The segmentation performance is quantitatively evaluated by statistical metrics and qualitatively evaluated by clinicians in terms of consistency and time efficiency.Results: The proposed method is trained and evaluated on the self-collected dataset, which contains 110 computed tomography scans from patients with breast cancer who underwent modified mastectomy. The experimental results show that the proposed segmentation method achieved superior performance in terms of Dice similarity coefficient (DSC), Hausdorff distance (HD) and Average symmetric surface distance (ASSD) compared with baseline approaches.Conclusion: Both quantitative and qualitative evaluation results demonstrated that the specifically designed method is practical and effective in automatic contouring of CTVs for radiotherapy of breast cancer after modified radical mastectomy. Clinicians can significantly save time on manual delineation while obtaining contouring results with high consistency by employing this method.
Family Sense of Coherence Scale: A Confirmatory Factor Analysis in a Portuguese Sample
Authors: Carneiro Francis Anne T. , Salvador Vanessa F. , Costa Pedro A. , Leal Isabel P. 
Published: January 2022

Background: Family sense of coherence (FSOC) can be defined as the cognitive map of a family that enables the family to deal with stress during their lifetime. FSOC is the degree to which a family perceives family life as comprehensible, manageable, and meaningful. To the best of our knowledge, few studies have used this scale, and very few have evaluated FSOC Scale psychometric properties.Objective: This study aimed to evaluate the psychometric properties of the original FSOC Scale in a sample of Portuguese caregivers of children aged between 10 and 15 years.Methods: A total of 329 caregivers completed a sociodemographic questionnaire and the FSOC Scale. Analyses were performed to evaluate the factor structure of the FSOC Scale with 26 items as well as composite reliability, internal consistency, convergent-related validity, and discriminant-related validity of the scale scores.Results: The findings supported a three-factor solution for a 13-item version that maintains the original FSOC Scale structure. The three FSOC dimensions presented a good fit to the data. Cronbach’s alpha, composite reliability, and convergent-related validity were considered very good for the FSOC Scale (α = 0.956; CR = 0.974; AVE = 0.689). No evidence of discriminant-related validity was found for the dimensions of FSOC.Conclusion: The findings support the use of the Portuguese FSOC Scale for research and clinical purposes with Portuguese caregivers. Future research is necessary to further develop a European Portuguese version of the FSOC Scale.Implications: This study provides a psychometric evaluation of FSOC Scale characteristics in a Portuguese sample. The results are helpful for clinicians and family therapists who work with families since it could help them to assess the resources of families and their ability to cope with adversity and enhance their strengths.
The Brain-Derived Neurotrophic Factor Val66Met Polymorphism Is Associated With Female Obsessive-Compulsive Disorder: An Updated Meta-Analysis of 2765 Obsessive-Compulsive Disorder Cases and 5558 Controls
Authors: Shang Yanan , Wang Na , Zhang En , Liu Qian , Li Hengfen , Zhao Xiaofeng 
Published: January 2022

Objective: Accumulated evidence has implicated that brain-derived neurotrophic factor (BDNF) gene polymorphisms play a role in the etiology of obsessive-compulsive disorder (OCD). A single nucleotide polymorphism in the coding exon of the BDNF gene at position 66, Val66Met (rs6265), is found to be associated with OCD in different populations, but results linking Val66Met with OCD have been inconsistent and inconclusive. In our study we performed a meta-analysis to further examine whether rs6265 genetic variants are involved in the etiology of OCD.Methods: By searching databases, relevant case-control studies were retrieved; using established inclusion criteria, we selected eligible studies for analysis.Results: Thirteen studies were identified that examined the association between the rs6265 polymorphism and OCD. After statistical analyses, no significant association was found between the rs6265 polymorphism and OCD (OR = 1.07, 95% CI = 1.00–1.15, P = 0.06 for genotype; OR = 1.06, 95% CI = 0.98–1.15, P = 0.15 for allele). However, in gender-specific analysis, female Val carriers might be a risk factor for OCD (OR = 1.36, 95% CI = 1.03–1.80, P = 0.03 for genotype; OR = 1.15, 95% CI = 1.01–1.32, P = 0.04 for allele).Conclusion: Our updated meta-analysis suggests that female carriers of the Val66Met BDNF polymorphism might be more suspectable to develop OCD.