bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Efficacy of First-Generation EGFR-TKI Combined With Brain Radiotherapy as the First-Line Treatment for Lung Adenocarcinoma Patients With Brain Metastases and EGFR Sensitive Mutations: A Retrospective study
Authors: Liu Yuting , Wang Juanjuan , Wu Jingjing , Yang Qifan , Zeng Yulan , Wu Di , Tian Chen , Hu Yue , Gu Feifei , Li Chang , Zhang Kai , Liu Li 
Published: March 2021

Background: It was controversial that whether LUAD patients with brain metastases (BMs) and EGFR sensitive mutations should be conducted using brain radiotherapy when treated with first-generation EGFR-TKI. Herein, a retrospective study was designed to compare the efficacy of first-generation EGFR-TKI combined with brain radiotherapy and EGFR-TKI alone as first-line treatment for these LUAD patients. Patients and Methods: We retrospectively analyzed the status of patients with advanced LUAD carrying EGFR sensitive mutations who received first-generation EGFR-TKI treatment in our center. iPFS was the first time of intracranial progression or death from the diagnosis of BMs, PFS was the time of progression of any site or death from the diagnosis of BMs, and OS was the time of confirmed BMs to death or the last follow-up time. Differences in characteristics between groups were compared using the Chi-square test. The Kaplan-Meier method was used to calculate the iPFS, PFS, and OS. Univariate analysis, multivariate analysis, and subgroup analysis were conducted by Cox regression model. Results: There were 77 patients (77/134, 57.5%) in the TKI + RT group and 57 patients (57/134, 42.5%) in the TKI group. TKI + RT group had a significant higher intracranial ORR and DCR, and the combination therapy was independently significantly associated with a longer iPFS (18.9 vs. 10.5 months, P = 0.0009), systematic PFS (12.5 vs. 8.4 months, P = 0.0071) and OS (30.8 vs. 22.7 months, P = 0.0183). Females, non-smokers, and younger patients benefited more from the combination therapy. Subgroup analysis demonstrated that the combination therapy could improve the iPFS in patients with more than 3 BMs ( P = 0.005); however, it couldn’t improve the OS for these patients. Conclusion: Our study confirmed the effect of the combination of EGFR-TKI and brain radiotherapy as first-line treatment for LUAD patients with BMs and EGFR sensitive mutations.
Treatment of Super-Refractory Status Epilepticus: A Review
Authors: Ochoa Juan G. , Dougherty Michelle , Papanastassiou Alex , Gidal Barry , Mohamed Ismail , Vossler David G. 
Published: March 2021

Purpose: Super-refractory status epilepticus (SRSE) presents management challenges due to the absence of randomized controlled trials and a plethora of potential medical therapies. The literature on treatment options for SRSE reports variable success and quality of evidence. This review is a sequel to the 2020 American Epilepsy Society (AES) comprehensive review of the treatment of convulsive refractory status epilepticus (RSE). Methods: We sought to determine the effectiveness of treatment options for SRSE. We performed a structured literature search (MEDLINE, Embase, CENTRAL, CINAHL) for studies on reported treatments of SRSE. We excluded antiseizure medications (ASMs) covered in the 2016 AES guideline on the treatment of established SE and the convulsive RSE comprehensive review of the 2020 AES. Literature was reviewed on the effectiveness of vagus nerve stimulation, ketogenic diet (KD), lidocaine, inhalation anesthetics, brain surgery, therapeutic hypothermia, perampanel, pregabalin (PGB), and topiramate in the treatment of SRSE. Two authors reviewed each therapeutic intervention. We graded the level of the evidence according to the 2017 classification scheme of the American Academy of Neurology. Results: For SRSE (level U; 39 class IV studies total), insufficient evidence exists to support that perampanel, PGB, lidocaine, or acute vagus nerve stimulation (VNS) is effective. For children and adults with SRSE, insufficient evidence exists to support that the KD is effective (level U; 5 class IV studies). For adults with SRSE, insufficient evidence exists that brain surgery is effective (level U, 7 class IV studies). For adults with SRSE insufficient, evidence exists that therapeutic hypothermia is effective (level C, 1 class II and 4 class IV studies). For neonates with hypoxic-ischemic encephalopathy, insufficient evidence exists that therapeutic hypothermia reduces seizure burden (level U; 1 class IV study). For adults with SRSE, insufficient evidence exists that inhalation anesthetics are effective (level U, 1 class IV study) and that there is a potential risk of neurotoxicity. Conclusion: For patients with SRSE insufficient, evidence exists that any of the ASMs reviewed, inhalational anesthetics, ketogenic diet, acute VNS, brain surgery, and therapeutic hypothermia are effective treatments. Data supporting the use of these treatments for SRSE are scarce and limited mainly to small case series and case reports and are confounded by differences in patients’ population, and comedications, among other factors.
Predictors of return to work among stroke survivors in south-west Nigeria
Authors: Olaoye Olumide Ayoola , Soeker Shaheed Moghammad , Anthea Rhoda 
Published: March 2021

Introduction Stroke is acknowledged globally and among Nigerian rehabilitation researchers as a public health problem that leaves half of its survivors with significant neurological deficits and inability to re-establish pre-existing roles. Consequent to the dearth of country specific data on return to work and its determinants for stroke survivors in Nigeria, this study investigated the predictors of return to work among stroke survivors in south-west Nigeria. Method Two hundred and ten stroke survivors from five tertiary health facilities in Osun state, Nigeria responded to a validated three-section questionnaire assessing return to work rates and its determinants after stroke in this study. Collected data were analysed using descriptive statistics and inferential statistic of chi-square, t-test and multiple logistic regression. Result The mean age of the respondents was 52.90 ± 7.92 years. Over 60% of the respondents returned to work with about half of them in full time employment (32.9%). Majority of the respondents noted that travel to and from work (43.8%) and access at work (43.3%) had an impact on their ability to work. The symptoms of stroke (odds ratio (OR) = 0.87), the environment (OR = 0.83), body function impairments (OR = 0.86) as well as activity and participation problems (OR = 0.80) were the significant predictors of return to work. Hemiplegia or paresis of the non-dominant side of the body was associated with a higher chance of return to work (OR = 7.64). Conclusion Body function impairments, activity and participation problems were independent predictors of return to work after stroke. Similarly, side of hemiplegia plays a prominent role in resumption of the worker role of stroke survivors in south-west Nigeria.
Deep neural network-based detection and segmentation of intracranial aneurysms on 3D rotational DSA
Authors: Liu Xinke , Feng Junqiang , Wu Zhenzhou , Neo Zhonghao , Zhu Chengcheng , Zhang Peifang , Wang Yan , Jiang Yuhua , Mitsouras Dimitrios , Li Youxiang 
Published: March 2021

Objective Accurate diagnosis and measurement of intracranial aneurysms are challenging. This study aimed to develop a 3D convolutional neural network (CNN) model to detect and segment intracranial aneurysms (IA) on 3D rotational DSA (3D-RA) images. Methods 3D-RA images were collected and annotated by 5 neuroradiologists. The annotated images were then divided into three datasets: training, validation, and test. A 3D Dense-UNet-like CNN (3D-Dense-UNet) segmentation algorithm was constructed and trained using the training dataset. Diagnostic performance to detect aneurysms and segmentation accuracy was assessed for the final model on the test dataset using the free-response receiver operating characteristic (FROC). Finally, the CNN-inferred maximum diameter was compared against expert measurements by Pearson’s correlation and Bland-Altman limits of agreement (LOA). Results A total of 451 patients with 3D-RA images were split into n = 347/41/63 training/validation/test datasets, respectively. For aneurysm detection, observed FROC analysis showed that the model managed to attain a sensitivity of 0.710 at 0.159 false positives (FP)/case, and 0.986 at 1.49 FP/case. The proposed method had good agreement with reference manual aneurysmal maximum diameter measurements (8.3 ± 4.3 mm vs. 7.8 ± 4.8 mm), with a correlation coefficient r = 0.77, small bias of 0.24 mm, and LOA of -6.2 to 5.71 mm. 37.0% and 77% of diameter measurements were within ±1 mm and ±2.5 mm of expert measurements. Conclusions A 3D-Dense-UNet model can detect and segment aneurysms with relatively high accuracy using 3D-RA images. The automatically measured maximum diameter has potential clinical application value.
Preliminary image findings of lower limb stress fractures to aid ultrasonographic diagnoses: A systematic review and narrative synthesis
Authors: Schaper Madeleine , Harcus James 
Published: March 2021

Introduction This systematic review investigates which image appearances are most common when diagnosing lower limb stress fractures using ultrasound imaging, with the aim of outlining an image critique guideline for operators to support confident diagnoses. Method A comprehensive literature search of medical databases and handsearching was undertaken to identify relevant studies. All studies were critically examined for quality using the CASP critical appraisal tool. Results from eight studies were combined and interpreted using a narrative synthesis. Findings A clear outline of common stress fracture appearances using ultrasound were identified in a combined total of 119 participants. Each finding was ranked according to its popularity. Periosteal thickening (78/119) and cortical disruption/irregularity (83/119) were noted in all eight studies. Hypervascularity of the periosteum visualised by colour Doppler imaging (66/119) was reported in six of the eight studies. Soft tissue hypervascularity (13/119), bony callus formation (5/119) and cortical break (22/119) were seen in three studies. Conclusions Based on the findings, we offer a guideline of the most significant preliminary image findings to be utilised by operators when examining athletes suspected of having lower limb stress fractures. The results show a gap in research for evaluating changes in appearance depending on the injury severity. Further research into distinguishing stress fractures from pathological involvement may in future reduce reliance on plain film radiography.
Multi-Timescale Rhythmicity of Blood Glucose and Insulin Delivery Reveals Key Advantages of Hybrid Closed Loop Therapy
Authors: Grant Azure D. , Lewis Dana M. , Kriegsfeld Lance J. 
Published: March 2021

Background: Blood glucose and insulin exhibit coordinated daily and hourly rhythms in people without diabetes (nonT1D). Although the presence and stability of these rhythms are associated with euglycemia, it is unknown if they (1) are preserved in individuals with type 1 diabetes (T1D) and (2) vary by therapy type. In particular, Hybrid Closed Loop (HCL) systems improve glycemia in T1D compared to Sensor Augmented Pump (SAP) therapies, but the extent to which either recapitulates coupled glucose and insulin rhythmicity is not well described. In HCL systems, more rapid modulation of glucose via automated insulin delivery may result in greater rhythmic coordination and euglycemia. Such precision may not be possible in SAP systems. We hypothesized that HCL users would exhibit fewer hyperglycemic event, superior rhythmicity, and coordination relative to SAP users. Methods: Wavelet and coherence analyses were used to compare glucose and insulin delivery rate (IDR) within-day and daily rhythms, and their coordination, in 3 datasets: HCL (n = 150), SAP (n = 89), and nonT1D glucose (n = 16). Results: Glycemia, correlation between normalized glucose and IDR, daily coherence of glucose and IDR, and amplitude of glucose oscillations differed significantly between SAP and HCL users. Daily glucose rhythms differed significantly between SAP, but not HCL, users and nonT1D individuals. Conclusions: SAP use is associated with greater hyperglycemia, higher amplitude glucose fluctuations, and a less stably coordinated rhythmic phenotype compared to HCL use. Improvements in glucose and IDR rhythmicity may contribute to the overall effectiveness of HCL systems.
A Comparison of Artificial Intelligence and Human Diabetic Retinal Image Interpretation in an Urban Health System
Authors: Mokhashi Nikita , Grachevskaya Julia , Cheng Lorrie , Yu Daohai , Lu Xiaoning , Zhang Yi , Henderer Jeffrey D. 
Published: March 2021

Introduction: Artificial intelligence (AI) diabetic retinopathy (DR) software has the potential to decrease time spent by clinicians on image interpretation and expand the scope of DR screening. We performed a retrospective review to compare Eyenuk’s EyeArt software (Woodland Hills, CA) to Temple Ophthalmology optometry grading using the International Classification of Diabetic Retinopathy scale. Methods: Two hundred and sixty consecutive diabetic patients from the Temple Faculty Practice Internal Medicine clinic underwent 2-field retinal imaging. Classifications of the images by the software and optometrist were analyzed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and McNemar’s test. Ungradable images were analyzed to identify relationships with HbA1c, age, and ethnicity. Disagreements and a sample of 20% of agreements were adjudicated by a retina specialist. Results: On patient level comparison, sensitivity for the software was 100%, while specificity was 77.78%. PPV was 19.15%, and NPV was 100%. The 38 disagreements between software and optometrist occurred when the optometrist classified a patient’s images as non-referable while the software classified them as referable. Of these disagreements, a retina specialist agreed with the optometrist 57.9% the time (22/38). Of the agreements, the retina specialist agreed with both the program and the optometrist 96.7% of the time (28/29). There was a significant difference in numbers of ungradable photos in older patients (≥60) vs younger patients (<60) (p=0.003). Conclusions: The AI program showed high sensitivity with acceptable specificity for a screening algorithm. The high NPV indicates that the software is unlikely to miss DR but may refer patients unnecessarily.
Physical and mental health of older people with disabilities in residential homes in Switzerland
Authors: Wicki Monika T 
Published: March 2021

Objectives: People with disabilities are underserved in terms of health care and prevention, and special health conditions exist among older people with intellectual disabilities. The Swiss Health Survey only covers people over the age of 15 years living in private households. Therefore, this study aims to assess the health status of older persons living in residential facilities for adults with disabilities. Methods: A cross-sectional survey with written questionnaires was conducted in six cantons in Switzerland to capture context factors and the physical health status of persons aged between 50 and 65 years in residential homes in Switzerland. The survey collected data on physical and mental health from 241 persons aged 50–65 years living in residential homes for people with disabilities. This was compared with data from the 2012 Swiss Health Survey comprising a sample of 2261 persons of the same age with chronic morbidities living in their own apartments. Results: Regarding their health, 94.1% of the survey respondents rated it as being very good, good or moderate. Although higher limitations on activities of daily living, higher levels of psychological distress and lower energy and vitality were reported by all respondents, a lower level of health issues was assessed than in the sample of persons with chronic morbidities living in their own apartment. Conclusion: Low energy and vitality, high limitations on activities of daily living, high psychological distress, high obesity rates and the assessment of health issues and pain should be specifically addressed in residential homes for people with disabilities.
Social, Psychological, and Behavioral Predictors of Salivary Bacteria, Yeast in Caries-Free Children
Authors: Kopycka-Kedzierawski D.T. , Scott-Anne K. , Ragusa P.G. , Cvetanovska M. , Flint K. , Feng C. , Watson G.E. , Wong C.L. , Billings R.J. , Quivey R.J. , O’Connor T.G. 
Published: March 2021

Introduction: Early childhood caries (ECC) is a complex, multifactorial oral disease that is a major public health concern because it is prevalent, profoundly alters a child’s quality of life, is difficult to treat effectively, and has a distressing tendency to recur following treatment. Objectives: The purpose of the study was to examine social, psychological, and behavioral predictors of salivary bacteria and yeast in young children at risk for ECC. Methods: A sample of 189 initially caries-free preschool children was assessed for child stress physiology from salivary cortisol, child and family stress exposure, diet, oral health behaviors, and sociodemographic risks. Multiple logistic regression analysis was implemented to examine the associations between these risk factors and cariogenic microorganisms: mutans streptococci (MS), lactobacilli (LB), and Candida species. Results: Higher baseline salivary cortisol (odds ratio [OR] = 6.26; 95% confidence level [CL], 1.69–23.16) and a blunted response to an acute laboratory stressor (OR = .56; 95% CL, .37–.83) were associated with an increased likelihood of elevated salivary MS (≥105 colony-forming units/mL) in caries-free children. Sociodemographic risk for cariogenic microorganisms was also found. Specifically, lower education attainment of the parent/primary caregiver was associated with children being more likely to carry salivary Candida species and elevated salivary MS; in addition, children from households with an unemployed parent/primary caregiver were more likely (OR = 3.13; 95% CL, 1.2–8.05) to carry salivary Candida species and more likely (OR = 3.03; 95% CL, 1.25–7.33) to carry elevated levels of MS and/or salivary Candida and/or LB. Conclusions: The impact of sociodemographic risk and stress physiology on cariogenic disease processes are evident prior to ECC onset. The findings provide novel data on the early onset of cariogenic processes in children and the importance of considering sociodemographic, psychosocial, and behavioral factors when judging ECC risk. Knowledge Transfer Statement: The findings provide valuable and novel findings that, pre-ECC onset, the caries disease process is explicable from a detailed assessment of behavioral, sociodemographic, and psychosocial stress variables.
IL-17 deficiency aggravates the streptozotocin‐induced diabetic nephropathy through the reduction of autophagosome formation in mice
Authors: Kim Kyung-Hyun , Hong Geum-Lan , Jung Da-Young , Karunasagara Shanika , Jeong Won-Il , Jung Ju-Young 
Published: March 2021

Abstract
Background
Diabetic nephropathy (DN) is one of the most important medical complications of diabetes mellitus. Autophagy is an important mediator of pathological response and plays a critical role in inflammation during the progression of diabetic nephropathy. Interleukin (IL)-17A favorably modulates inflammatory disorders including DN. In this study, we examined whether IL-17A deficiency affected the autophagy process in the kidneys of mice with streptozotocin (STZ)-induced DN.

Methods
The autophagic response of IL-17A to STZ-induced nephrotoxicity was evaluated by analyzing STZ-induced functional and histological renal injury in IL-17A knockout (KO) mice.

Results
IL-17A KO STZ-treated mice developed more severe nephropathy than STZ-treated wild-type (WT) mice, with increased glomerular damage and renal interstitial fibrosis at 12 weeks. IL-17A deficiency also increased the up-regulation of proinflammatory cytokines and fibrotic gene expression after STZ treatment. Meanwhile, autophagy-associated proteins were induced in STZ-treated WT mice. However, IL-17A KO STZ-treated mice displayed a significant decrease in protein expression. Especially, the levels of LC3 and ATG7, which play crucial roles in autophagosome formation, were notably decreased in the IL-17A KO STZ-treated mice compared with their WT counterparts.

Conclusions
IL-17 deficiency aggravates of STZ-induced DN via attenuation of autophagic response. Our study demonstrated that IL-17A mediates STZ-induced renal damage and represents a potential therapeutic target in DN.
E2F1 copy number variations in germline and breast cancer: a retrospective study of 222 Italian women
Authors: Rocca Maria Santa , Benna Clara , Goldin Elena , Di Nisio Andrea , De Toni Luca , Cosci Ilaria , Marchet Alberto , Nitti Donato , Foresta Carlo 
Published: March 2021

Abstract
Background
Breast cancer is the most common neoplasia among women in developed countries. The risk factors of breast cancer can be distinguished in modifiable and unmodifiable factors and, among the latter, genetic factors play a key role. Copy number variations (CNVs) are genetic variants that are classified as rare when present in less than 1% of the healthy population. Since rare CNVs are often cause of diseases, over the last years, their contribution in carcinogenesis has become a relevant matter of study. E2F1 is a transcriptional factor that plays an important role in regulating cell cycle and apoptosis. Its double and conflicting role is the reason why it acts both as oncogene and as tumour suppressor, depending on cell context. Since anomalies in expression or in number of copies of E2F1 have been related to several cancers, we aimed to study number of germline copies of E2F1 in women with breast cancer in order to better elucidate their contribution as predisposing factor to this tumour.

Methods
We performed, hence, a retrospective study on 222 Italian women with breast cancer recruited from October 2002 to December 2007. TaqMan CNV assay and Real-Time PCR were carried out to analyse, respectively, E2F1 CNV and E2F1 expression in the subjects of the study. Chi square test or Fisher’s exact test and Student's t‐test were used to calculate the frequency of CNVs and differences in continuous variables between groups, respectively.

Results
Intriguingly, we found that 10/222 (4.5%) women with breast cancer had more copies than controls (0/200, 0%), furthermore, the number of copies positively correlated with E2F1 gene expression in breast cancer tissue, suggesting that the constitutive gain of the gene could translate into an increased risk of genomic instability. Additionally, we found that altered E2F1 copies were present prevalently in the patients with contralateral breast cancer (20%) and all of them had a positive family history, both typically associated with hereditary cancer.

Conclusions
Our findings suggest that copy number variations of E2F1 might be a susceptibility factor for breast cancer, however, further studies on large cohorts are to be performed in order to better delineate the phenotype linked to the gain of E2F1 copies.