bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Cadmium a Risk Factor for Breast Cancer – Results from a Nested Case–Control Study Using Data from the Malmö Diet and Cancer Study
Authors: Andersson Eva M. , Sandsveden Malte , Forsgard Niklas , Sallsten Gerd , Manjer Jonas , Engström Gunnar , Barregard Lars 
Published: July 2021

Abstract

Background:
Some studies have shown that cadmium (Cd) is associated with breast cancer risk. One hypothesis is that Cd has estrogen-like properties. This case-control study investigated the association between breast cancer risk and blood Cd (BCd) levels.

Methods:
All breast cancers in the Malmö Diet and Cancer cohort were identified through linkage to the Swedish Cancer Registry, baseline (1991–1996) through 2014. Two controls per case were selected from the same cohort. BCd was analyzed at baseline. Associations were analyzed using logistic regression.

Results:
Mean BCd was 0.51 μg/L among 1,274 cases and 0.46 among 2,572 controls. There was an overall increased risk of breast cancer [OR, 1.18; 95% confidence interval (CI), 1.05–1.36] per μg/L of BCd. An increased risk was, however, only found at high BCd [OR, 1.34 (95% CI, 1.05–1.73)] for BCd more than 1.20 μg/L. The group with the highest BCd was mainly smokers. A spline indicated that at BCd less than 1.0 μg/L, the OR was not increased. The association with BCd was stronger in current smokers and at body mass index (BMI) above 25, while no modification due to receptor status was found.

Conclusions:
The results indicated increased risk of breast cancer only for high Cd exposure, which occurred mainly among smokers. This made it difficult to disentangle the effects of smoking and Cd, despite inclusion of smoking habits in the models.

Impact:
This study provides support for reducing Cd exposure through smoking cessation and dietary choice. On the population level, preventive measures against Cd pollution are warranted.
MicroRNA-21 Controls Circadian Regulation of Apoptosis in Atherosclerotic Lesions
Authors: Schober Andreas , Blay Richard M. , Saboor Maleki Saffiyeh , Zahedi Farima , Winklmaier Anja E. , Kakar Mati Y. , Baatsch Isabelle M. , Zhu Mengyu , Geißler Claudia , Fusco Anja E. , Eberlein Anna , Li Nan , Megens Remco T.A. , Banafsche Ramin , Kumbrink Jörg , Weber Christian , Nazari-Jahantigh Maliheh 
Published: July 2021

Background:
The necrotic core partly formed by ineffective efferocytosis increases the risk of an atherosclerotic plaque rupture. Microribonucleic acids contribute to necrotic core formation by regulating efferocytosis and macrophage apoptosis. Atherosclerotic plaque rupture occurs at increased frequency in the early morning, indicating diurnal changes in plaque vulnerability. Although circadian rhythms play a role in atherosclerosis, the molecular clock output pathways that control plaque composition and rupture susceptibility are unclear.

Methods:

Circadian gene expression, necrotic core size, apoptosis, and efferocytosis in aortic lesions were investigated at different times of the day in
Apoe

–/–

Mir21
+/+

mice and
Apoe

–/–

Mir21

–/–

mice after consumption of a high-fat diet for 12 weeks. Genome-wide gene expression and lesion formation were analyzed in bone marrow–transplanted mice. Diurnal changes in apoptosis and clock gene expression were determined in human atherosclerotic lesions.

Results:

The expression of molecular clock genes, lesional apoptosis, and necrotic core size were diurnally regulated in
Apoe

–/–

mice. Efferocytosis did not match the diurnal increase in apoptosis at the beginning of the active phase. However, in parallel with apoptosis, expression levels of oscillating
Mir21
strands decreased in the mouse atherosclerotic aorta.
Mir21
knockout abolished circadian regulation of apoptosis and reduced necrotic core size but did not affect core clock gene expression. Further,
Mir21
knockout upregulated expression of proapoptotic Xaf1 (XIAP-associated factor 1) in the atherosclerotic aorta, which abolished circadian expression of Xaf1. The antiapoptotic effect of
Mir21
was mediated by noncanonical targeting of
Xaf1
through both
Mir21
strands.
Mir21
knockout in bone marrow cells also reduced atherosclerosis and necrotic core size. Circadian regulation of clock gene expression was confirmed in human atherosclerotic lesions. Apoptosis oscillated diurnally in phase with
XAF1
expression, demonstrating an early morning peak antiphase to that of the
Mir21
strands.

Conclusions:

Our findings suggest that the molecular clock in atherosclerotic lesions induces a diurnal rhythm of apoptosis regulated by circadian
Mir21
expression in macrophages that is not matched by efferocytosis, thus increasing the size of the necrotic core.
Comparing the Prognostic Impact of Age and Baseline National Institutes of Health Stroke Scale in Acute Stroke due to Large Vessel Occlusion
Authors: Ospel Johanna Maria , Brown Scott , Kappelhof Manon , van Zwam Wim , Jovin Tudor , Roy Daniel , Campbell Bruce C.V. , Mitchell Peter , Roos Yvo , Guillemin Francis , Buck Brian , Muir Keith , Bracard Serge , White Phil , du Mesnil de Rochemont Richard , Goyal Mayank ,   for the HERMES Investigators
Published: July 2021

Background and Purpose:
Little is known about the combined effect of age and National Institutes of Health Stroke Scale (NIHSS) in endovascular treatment (EVT) for acute ischemic stroke due to large vessel occlusion, and it is not clear how the effects of baseline age and NIHSS on outcome compare to each other. The previously described Stroke Prognostication Using Age and NIHSS (SPAN) index adds up NIHSS and age to a 1:1 combined prognostic index. We added a weighting factor to the NIHSS/age SPAN index to compare the relative prognostic impact of NIHSS and age and assessed EVT effect based on weighted age and NIHSS.

Methods:
We performed adjusted logistic regression with good outcome (90-day modified Rankin Scale score 0–2) as primary outcome. From this model, the coefficients for NIHSS and age were obtained. The ratio between the NIHSS and age coefficients was calculated to determine a weighted SPAN index. We obtained adjusted effect size estimates for EVT in patient subgroups defined by weighted SPAN increments of 3, to evaluate potential changes in treatment effect.

Results:
We included 1750/1766 patients from the HERMES collaboration (Highly Effective Reperfusion Using Multiple Endovascular Devices) with available age and NIHSS data. Median NIHSS was 17 (interquartile range, 13–21), and median age was 68 (interquartile range, 57–76). Good outcome was achieved by 682/1743 (39%) patients. The NIHSS/age effect coefficient ratio was ([−0.0032]/[−0.111])=3.4, which was rounded to 3, resulting in a weighted SPAN index defined as ([3×NIHSS]+age). Cumulative EVT effect size estimates across weighted SPAN subgroups consistently favored EVT, with a number needed to treat ranging from 5.3 to 8.7.

Conclusions:
The impact on chance of good outcome of a 1-point increase in NIHSS roughly corresponded to a 3-year increase in patient age. EVT was beneficial across all weighted age/NIHSS subgroups.
Acute Stroke Imaging Research Roadmap IV: Imaging Selection and Outcomes in Acute Stroke Clinical Trials and Practice
Authors: Campbell Bruce C.V. , Lansberg Maarten G. , Broderick Joseph P. , Derdeyn Colin P. , Khatri Pooja , Sarraj Amrou , Saver Jeffrey L. , Vagal Achala , Albers Gregory W. ,   on behalf of the STAIR XI Consortium†, Adeoye Opeolu , Ansari Saeed , Boltze Johannes , Buchan Alastair , Chaisinanunkul Napasri , Chen Christopher , Davis Thomas P. , Ermakova Tatiana , Fisher Marc , Haddad Walid , Hill Michael D. , Houser Gary , Jadhav Ashutosh P. , Kimberly W. Taylor , Landen Jaren W. , Liebeskind David S. , Lyden Patrick , Lynch John , Mansi Chris , Mocco J , Nogueira Raul G. , Savitz Sean I. , Schwamm Lee H. , Sheth Kevin N. , Solberg Yoram , Venkatasubramanian Chitra , Warach Steven , Wechsler Lawrence R. , Zhu Bin , Ziogas Nikolaos K. 
Published: July 2021

Background and Purpose:
The Stroke Treatment Academic Industry Roundtable (STAIR) sponsored an imaging session and workshop during the Stroke Treatment Academic Industry Roundtable XI via webinar on October 1 to 2, 2020, to develop consensus recommendations, particularly regarding optimal imaging at primary stroke centers.

Methods:
This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss imaging priorities in the light of developments in reperfusion therapies, particularly in an extended time window, and reinvigorated interest in brain cytoprotection trials.

Results:
The imaging session summarized and compared the imaging components of recent acute stroke trials and debated the optimal imaging strategy at primary stroke centers. The imaging workshop developed consensus recommendations for optimizing the acquisition, analysis, and interpretation of computed tomography and magnetic resonance acute stroke imaging, and also recommendations on imaging strategies for primary stroke centers.

Conclusions:
Recent positive acute stroke clinical trials have extended the treatment window for reperfusion therapies using imaging selection. Achieving rapid and high-quality stroke imaging is therefore critical at both primary and comprehensive stroke centers. Recommendations for enhancing stroke imaging research are provided.
A Comprehensive Intermediate-Term Drought Evaluation System and Evaluation of Climate Data Products over the Conterminous United States
Authors: Xue Zeyu , Ullrich Paul 
Published: July 2021

AbstractClimate models are frequently-used tools for adaptation planning in light of future uncertainty. However, not all climate models are equally trustworthy, and so model biases must be assessed to select models suitable for producing credible projections. Drought is a well-known and high-impact form of extreme weather, and knowledge of its frequency, intensity, and duration key for regional water management plans. Droughts are also difficult to assess in climate datasets, due to the long duration per event, relative to the length of a typical simulation. Therefore, there is a growing need for a standardized suite of metrics addressing how well models capture this phenomenon. In this study, we present a widely applicable set of metrics for evaluating agreement between climate datasets and observations in the context of drought. Two notable advances are made in our evaluation system: First, statistical hypothesis testing is employed for normalization of individual scores against the threshold for statistical significance. And second, within each evaluation region and dataset, principal feature analysis is used to select the most descriptive metrics among 11 metrics that capture essential features of drought. Our metrics package is applied to three characteristically distinct regions in the conterminous US and across several commonly employed climate datasets (CMIP5/6, LOCA and CORDEX). As a result, insights emerge into the underlying drivers of model bias in global climate models, regional climate models, and statistically downscaled models.
Graphic Reading Performance of Students with Visual Impairments and Its Implication for Instruction and Assessment
Authors: Zebehazy Kim T. , Wilton Adam P. 
Published: July 2021

Introduction: The ability of students to engage with graphical materials supports learning in science, technology, engineering, arts, and mathematics areas. For students with visual impairments, understanding the factors that contribute to the effective interpretation of graphics can promote meaningful access to the curricula. Methods: Forty students with visual impairments completed multiple-choice question tasks for five types of graphics presented in their medium of choice and provided difficulty ratings. The teachers of students with visual impairments rated the students on several factors. Statistical analyses investigated the relationship between performance differences and teacher-rated factors. Results: Significant differences in performance between print and tactile graphics users were found for bar graph, map, and total correct responses on all tasks. For some tasks, perceived difficulty by tactile graphic users did not align with actual performance. Teachers’ ratings of students who had Individualized Education Program goals for graphics, independence in using graphics, problem-solving ability, mathematics ability, and frequency of engaging with graphics contributed to significant differences in performance across total correct and most individual graphic results. Discussion: Although medium type was a significant contributor across graphic types, some teacher-rated variables appeared to mitigate the importance of medium on student performance. Depending on the graphic type, experience, content knowledge, skills with graphics, and confidence and motivation can all affect student performance when interpreting graphics. Implications for practitioners: Teachers should provide students with early and frequent opportunities to engage with graphics and support their problem-solving abilities regarding how to engage with different graphic types to enhance their independent use of graphics.
Implementation of a Surgical Intensivist Model Increases Palliative Care Consultation in the Care of Trauma ICU Patients
Authors: Kirkland Kevin D. , Chabanon-Hicks Chloe , Acquista Elizabeth 
Published: July 2021

Objective: This study investigated patient outcomes of care before and after transitioning to a surgical intensivist-led trauma-intensive care unit (ICU) team. The intensivist team provided daily multidisciplinary rounds and continuity of care. Prior to an intensivist model, general surgeons cared for trauma patients admitted to the unit. Methods: Outcomes of 1,078 trauma patients, admitted to the ICU at a Level II trauma center, under care of general surgeons (1/2011-8/2012, n = 449) were retrospectively compared with care managed by a surgical intensivist team (1/2013-5/2015, n = 629) by Pearson Chi-squared and Wilcoxon tests. A multivariable logistic regression technique was used to control for covariates. Demographics and injury severity were analyzed. The primary outcome was ICU mortality. The secondary outcomes were length of stay (LOS), ventilator-free and ICU-free days, and ICU readmission rate. Other data collected included palliative care consultation. Results: There were no statistically significant differences in ICU mortality (P = 0.055), hospital LOS (P = 0.481), ventilator-free days (P = 0.174), or ICU readmission rate (P = 0.587). The surgical intensivist team consulted palliative care more frequently (4.0% vs 13.5%, P < 0.001), while managing more trauma patients who were older than 65 years (P < 0.001) with lower Glasgow Coma Scale (P = 0.048) and higher injury severity (P = 0.025) and abbreviated injury scale (P < 0.001) scores. Discussion: There were no differences in outcomes. However, incorporating palliative care consultation in the ICU is essential in the support of critically ill patients and their families. These data demonstrate that a surgical intensivist team utilized palliative care more often in the management of trauma patients admitted to the ICU.
Staged Head and Neck Reconstruction: Heresy or a Reasoned Approach in a Select Group of Patients?
Authors: Urken Mark. L. , O’Malley Quinn , Sandler Mykayla , Xing Monica H. , Ansari Edward , Mundi Neil , Buchbinder Daniel , Alon Eran , Okay Devin 
Published: July 2021

Study Design: case series. Objective: The restoration of defects in a single procedure with microvascular free flap reconstruction has become a mainstay of head and neck surgery. Yet in patients with complex defects and pre-existing comorbid medical conditions, a staged-reconstructive approach can enhance the safety of the procedure and improve the patient’s outcome. Methods: We present 3 representative case examples of a larger series of patients who underwent reconstruction of major defects and discuss the usefulness of a staged-reconstructive approach in the management of complex patients. Results: All 3 patients, with an existing composite defect in the setting of prior radiation therapy, underwent successful staged-reconstructive surgery using a variety of free tissue and regional flap transfers. Conclusions: A staged approach facilitates the reconstruction of complex composite defects, increases vessel availability, and mitigates the risk of flap failure. Although this approach commits the patient to multiple procedures and a more prolonged plan of care, it is preferable to 1 operation in specific complex situations with adverse, high-risk clinical features.
Quantification of the relative arm use in patients with hemiparesis using inertial measurement units
Authors: David Ann , ReethaJanetSureka StephenSukumaran , Gayathri Sankaralingam , Annamalai Salai Jeyseelan , Samuelkamleshkumar Selvaraj , Kuruvilla Anju , Magimairaj Henry Prakash , Varadhan SKM , Balasubramanian Sivakumar 
Published: July 2021

Introduction Accelerometry-based activity counting for measuring arm use is prone to overestimation due to non-functional movements. In this paper, we used an inertial measurement unit (IMU)-based gross movement (GM) score to quantify arm use. Methods In this two-part study, we first characterized the GM by comparing it to annotated video recordings of 5 hemiparetic patients and 10 control subjects performing a set of activities. In the second part, we tracked the arm use of 5 patients and 5 controls using two wrist-worn IMUs for 7 and 3 days, respectively. The IMU data was used to develop quantitative measures (total and relative arm use) and a visualization method for arm use. Results From the characterization study, we found that GM detects functional activities with 50–60% accuracy and eliminates non-functional activities with >90% accuracy. Continuous monitoring of arm use showed that the arm use was biased towards the dominant limb and less paretic limb for controls and patients, respectively. Conclusions The gross movement score has good specificity but low sensitivity in identifying functional activity. The at-home study showed that it is feasible to use two IMU-watches to monitor relative arm use and provided design considerations for improving the assessment method. Clinical trial registry number: CTRI/2018/09/015648
Dartanan: Prototype evaluations of a serious game to engage children in the calibration of their hearing aid functionalities
Authors: Hallewell Madeline , Salanitri Davide , D’Cruz Mirabelle , Cobb Sue , Picinali Lorenzo , Frost Emily , Tamascelli Stefano , Patel Harshada ,   On behalf of the 3D Tune-In project consortium
Published: July 2021

Introduction It is notoriously difficult to obtain a perfect fitting of hearing aids (HAs) for children as they often struggle to understand their hearing loss well enough to discuss the fitting adequately with their audiologist. Dartanan is an ‘edutainment’ game developed to help children understand the functions of their HA in different sound contexts. Dartanan also has elements of a leisure game for all children, in order to create an inclusive activity. Methods Game prototypes were evaluated during two formative evaluations and a summative evaluation. In total 106 children with and without hearing loss in Italy, Spain and the UK played Dartanan. A built-in virtual HA enabled children with hearing loss to use headphones to play. Results and conclusions: During the formative stages, feedback was discussed during focus groups on factors such as the audiological aspects, the extent to which children learned about HA functions, accessibility and usability, and this feedback was presented to the developers. After redevelopment, a summative evaluation was performed using an online survey. It was concluded that the game had met the goals of helping children understand their HA functionalities and providing an inclusive activity. User-evaluations were crucial in the development of the app into a useful and useable service.
The Use of Split Temporalis Muscle Flap in Maxillofacial Reconstruction
Authors: Marwan Hisham , Hardman Caleb 
Published: July 2021

Study Design: Case Report. Objective: The Temporalis muscle (TM) Flap is a reliable, versatile flap with adequate bulk and flexibility. However, temporal hollowing is the most common postoperative complication after harvesting the flap. We describe a surgical modification for harvesting the split TM flap to prevent postoperative temporal hollowing and report 2 cases with up to 18 months of follow-up. Method: This study discusses the posterior ⅔ split temporalis muscle flap in preventing temporal hollowing. We report 2 well-documented cases with up to 18 months of postoperative follow-up. Also, the authors discuss the key points regarding the technique’s indication and limitation. Results: The posterior ⅔ split temporalis muscle flap is reliable in both benign and malignant disease processes. The results demonstrate the flap’s reliability with minimum donor site morbidity. Conclusion: The use of the posterior ⅔ of the TM flap is a viable technique to prevent the flap’s harvest’s temporal hollowing.
ets1 associates with KMT5A to participate in high glucose-mediated EndMT via upregulation of PFN2 expression in diabetic nephropathy
Authors: Lu Lihong , Zhong Ziwen , Gu Jiahui , Nan Ke , Zhu Minmin , Miao Changhong 
Published: July 2021

AbstractBackgroundDiabetic nephropathy (DN) is currently the leading cause of end-stage renal disease globally. The endothelial-to-mesenchymal transition (EndMT) of glomerular endothelial cells has been reported to play a crucial role in DN. As a specific form of epithelial-to-mesenchymal transition, EndMT and epithelial-to-mesenchymal transition may exhibit mutual modulators. Profilin 2 (PFN2) has been reported to participate in epithelial-to-mesenchymal transition. Moreover, ETS proto-oncogene 1 (ets1) and lysine methyltransferase 5A (KMT5A) have been reported to contribute to high glucose-mediated endothelial injury and epithelial-to-mesenchymal transition. In this study, we hypothesize ets1 associates with KMT5A to modulate PFN2 transcription, thus participating in high glucose-mediated EndMT in glomerular endothelial cells.MethodsImmunohistochemistry (IHC) was performed to detect protein levels in the kidney tissues and/or aorta tissues of human subjects and rats. Western blot, qPCR and immunofluorescence were performed using human umbilical vein endothelial cells (HUVECs). Chromatin immunoprecipitation (ChIP) assays and dual luciferase assays were performed to assess transcriptional activity. The difference between the groups was compared by two-tailed unpaired t-tests or one-way ANOVAs.ResultsOur data indicated that vimentin, αSMA, S100A4 and PFN2 levels were increased, and CD31 levels were reduced in glomerular endothelial cells of DN patients and rats. Our cell experiments showed that high glucose induced EndMT by augmenting PFN2 expression in HUVECs. Moreover, high glucose increased ets1 expression. si-ets1 suppressed high glucose-induced PFN2 levels and EndMT. ets1 overexpression-mediated EndMT was reversed by si-PFN2. Furthermore, ets1 was determined to associate with KMT5A. High glucose attenuated KMT5A levels and histone H4 lysine 20 methylation (H4K20me1), one of the downstream targets of KMT5A. KMT5A upregulation suppressed high glucose-induced PFN2 levels and EndMT. sh-KMT5A-mediated EndMT was counteracted by si-PFN2. Furthermore, H4K20me1 and ets1 occupied the PFN2 promoter region. sh-KMT5A cooperated with ets1 overexpression to activate PFN2 promoter activity. Our in vivo study demonstrated that KMT5A was reduced, while ets1 was augmented, in glomerular endothelial cells of DN patients and rats.ConclusionsThe present study indicated that ets1 cooperated with KMT5A to transcribe PFN2, thus contributing to hyperglycemia-induced EndMT in the glomerular endothelial cells of DN patients and rats.Trial registrationChiCTR, ChiCTR2000029425. 2020/1/31,http://www.chictr.org.cn/showproj.aspx?proj=48548