bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pediatric Tibial Spine Fractures: Exploring Case Burden by Age and Sex
Authors: DeFrancesco Christopher J. , Wilson Lauren , Lebrun Drake G. , Memtsoudis Stavros G. , Fabricant Peter D. 
Published: September 2021

Background: Pediatric tibial spine fractures (TSFs) are a well-known clinical entity, but the epidemiology of these injuries is not fully understood. Further, there are limited data on outcomes after TSF treatment, specifically the proportion of patients requiring subsequent anterior cruciate ligament (ACL) reconstruction. Purpose: To describe the distribution of TSF case burden by age and sex and to determine the proportion of patients undergoing subsequent ACL reconstruction or developing ACL insufficiency. Study Design: Descriptive epidemiology study. Methods: The Truven Health MarketScan database was queried to identify patients aged 7 to 18 years with TSFs between 2016 and 2018. Diagnosis and initial treatment (surgical vs nonoperative) were recorded based on database coding. Case burden by age and sex was calculated. The database, which includes longitudinal data, was then queried for subsequent diagnoses of ACL insufficiency as well as subsequent ACL reconstruction procedures performed among the patients. Results: We found 876 cases of TSF, 71.3% of which were treated nonoperatively. The male to female ratio for case burden was 2.2:1. Cases peaked at age 13 to 14 years for boys and age 11 to 12 years for girls. Of all cases identified, 3.7% also had either a diagnosis code for ACL laxity entered in a delayed fashion into the database or a later procedure code for ACL reconstruction (considered together to represent “subsequent ACL insufficiency”). Only 15 subsequent ACL reconstructions (1.7% of cases) were found, all of which were among boys and 9 of which were among boys aged 13 to 14 years. Conclusion: This longitudinal study is the largest epidemiological analysis of pediatric TSFs to date. We found low rates of subsequent ACL insufficiency and ACL reconstruction, with boys aged 13 to 14 years accounting for most of those cases. Rates of subsequent ACL reconstruction were lower than previously reported. Boys accounted for more than two times as many TSF cases as girls.
An Analytical Cross-Sectional Study to Assess the Effects of Smoking on Common Carotid Intima-Media Thickness and Resistivity Index Among Current Smokers
Authors: Kaur Harmeet , Tiwari Punit , Sharma Sanjeev , Verma Madhur 
Published: September 2021

Objective: The aim was to assess the structural and hemodynamic effects of smoking on the common carotid arteries (CCAs) in current smokers from Himachal Pradesh. In addition, it was important to determine any association between smoking duration, frequency, pack-years, and the occurrence of common carotid atherosclerosis. Materials and Methods: The study evaluated 50 current smokers for common carotid intima-media thickness (CIMT), plaque presence, and resistive index (RI) with sonography. The findings were compared with 50 healthy control patients, who had never smoked. Results: A positive association was observed between smoking and an increase in CIMT ( P = .001) and occurrence of plaques ( P = .007), with substantially higher mean CIMT values in smokers above 45 years ( P < .05) in both genders ( P < .05). No difference in overall RI was seen in both groups taken as a whole, while higher RI values ( P < .05) were noticed in smokers exclusively above 60 years. A positive association was noted between smoking frequency, pack-years, and an increase in CIMT, RI, and occurrence of plaques. For every unit increase in the number of pack-years and smoking duration, there was a 0.01 unit increase in CIMT among the current smokers. Conclusion: This research provides evidence that smoking has a structural impact on CIMT while its hemodynamic effect is still unclear.
How I treat chronic-phase chronic myelogenous leukemia
Authors: Berman Ellin 
Published: September 2021

Abstract
When imatinib, the first tyrosine kinase inhibitor (TKI) developed for use in chronic myelogenous leukemia (CML), was approved in 2001, the treatment of this disease was forever changed. Significant reductions in the molecular burden of disease were seen with the first-generation TKI imatinib and, with the addition of dasatinib (2006), nilotinib (2007), bosutinib (2012), and ponatinib (2013), deeper and more rapid reductions were noted. Physicians could begin to tailor TKI therapy to individual patients, and patients who did not respond to or could not tolerate first-line therapy now had options. Importantly, the number of patients who developed accelerated or blast phase disease decreased dramatically. Research in CML continues to evolve; by presenting illustrative cases, this article reviews some of the newer aspects of clinical care in this disease. Updated information regarding bosutinib and asciminib, the latter currently in clinical trials, will be presented; bosutinib is of particular interest as the drug’s transit through the United States Food and Drug Administration highlights the question of what is considered optimal response to TKI therapy. The challenge of understanding the cardiac safety data of ponatinib and the unique dosing schedule based on individual response will be discussed. Lastly, two cases will focus on features of TKI treatment that, remarkably, have become part of the treatment algorithm: family planning for women with CML and stopping therapy after meeting a specific treatment milestone.
PKM2 promotes neutrophil activation and cerebral thromboinflammation: therapeutic implications for ischemic stroke
Authors: Dhanesha Nirav , Patel Rakesh B. , Doddapattar Prakash , Ghatge Madankumar , Flora Gagan D. , Jain Manish , Thedens Daniel , Olalde Heena , Kumskova Mariia , Leira Enrique C. , Chauhan Anil K. 
Published: September 2021

Abstract
There is a critical need for cerebro-protective interventions to improve the suboptimal outcomes of patients with ischemic stroke who have been treated with reperfusion strategies. We found that nuclear pyruvate kinase muscle 2 (PKM2), a modulator of systemic inflammation, was upregulated in neutrophils after the onset of ischemic stroke in both humans and mice. Therefore, we determined the role of PKM2 in stroke pathogenesis by using murine models with preexisting comorbidities. We generated novel myeloid cell–specific PKM2−/− mice on wild-type (PKM2fl/flLysMCre+) and hyperlipidemic background (PKM2fl/flLysMCre+Apoe−/−). Controls were littermate PKM2fl/flLysMCre– or PKM2fl/flLysMCre–Apoe−/− mice. Genetic deletion of PKM2 in myeloid cells limited inflammatory response in peripheral neutrophils and reduced neutrophil extracellular traps after cerebral ischemia and reperfusion, suggesting that PKM2 promotes neutrophil hyperactivation in the setting of stroke. In the filament and autologous clot and recombinant tissue plasminogen activator stroke models, irrespective of sex, deletion of PKM2 in myeloid cells in either wild-type or hyperlipidemic mice reduced infarcts and enhanced long-term sensorimotor recovery. Laser speckle imaging revealed improved regional cerebral blood flow in myeloid cell–specific PKM2-deficient mice that was concomitant with reduced post-ischemic cerebral thrombo-inflammation (intracerebral fibrinogen, platelet [CD41+] deposition, neutrophil infiltration, and inflammatory cytokines). Mechanistically, PKM2 regulates post-ischemic inflammation in peripheral neutrophils by promoting STAT3 phosphorylation. To enhance the translational significance, we inhibited PKM2 nuclear translocation using a small molecule and found significantly reduced neutrophil hyperactivation and improved short-term and long-term functional outcomes after stroke. Collectively, these findings identify PKM2 as a novel therapeutic target to improve brain salvage and recovery after reperfusion.
PARP1 as a therapeutic target in acute myeloid leukemia and myelodysplastic syndrome
Authors: Kontandreopoulou Christina-Nefeli , Diamantopoulos Panagiotis T. , Tiblalexi Despina , Giannakopoulou Nefeli , Viniou Nora-Athina 
Published: September 2021

Abstract
Poly(ADP-ribose) polymerase 1 (PARP1) is a key mediator of various forms of DNA damage repair and plays an important role in the progression of several cancer types. The enzyme is activated by binding to DNA single-strand and double-strand breaks. Its contribution to chromatin remodeling makes PARP1 crucial for gene expression regulation. Inhibition of its activity with small molecules leads to the synthetic lethal effect by impeding DNA repair in the treatment of cancer cells. At first, PARP1 inhibitors (PARPis) were developed to target breast cancer mutated cancer cells. Currently, PARPis are being studied to be used in a broader variety of patients either as single agents or in combination with chemotherapy, antiangiogenic agents, ionizing radiation, and immune checkpoint inhibitors. Ongoing clinical trials on olaparib, rucaparib, niraparib, veliparib, and the recent talazoparib show the advantage of these agents in overcoming PARPi resistance and underline their efficacy in targeted treatment of several hematologic malignancies. In this review, focusing on the crucial role of PARP1 in physiological and pathological effects in myelodysplastic syndrome and acute myeloid leukemia, we give an outline of the enzyme’s mechanisms of action and its role in the pathophysiology and prognosis of myelodysplastic syndrome/acute myeloid leukemia and we analyze the available data on the use of PARPis, highlighting their promising advances in clinical application.
Excellent response to very-low-dose radiation (4 Gy) for indolent B-cell lymphomas: is 4 Gy suitable for curable patients?
Authors: Imber Brandon S. , Chau Karen W. , Lee Jasme , Lee Jisun , Casey Dana L. , Yang Joanna C. , Wijentunga N. Ari , Shepherd Annemarie , Hajj Carla , Qi Shunan , Chelius Monica R. , Hamlin Paul A. , Palomba M. Lia , Joffe Erel , Zhang Zhigang , Zelenetz Andrew D. , Salles Gilles A. , Yahalom Joachim 
Published: September 2021

Abstract
Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas, such as follicular lymphoma and marginal zone lymphoma. Although the standard of care for localized indolent non-Hodgkin lymphomas remains 24 Gy, de-escalation to very-low-dose radiotherapy (VLDRT) of 4 Gy further reduces toxicities and duration of treatment. Use of VLDRT outside palliative indications remains controversial; however, we hypothesize that it may be sufficient for most lesions. We present the largest single-institution VLDRT experience of adult patients with follicular lymphoma or marginal zone lymphoma treated between 2005 and 2018 (299 lesions; 250 patients) using modern principles including positron emission tomography staging and involved site radiotherapy. Outcomes include best clinical or radiographic response between 1.5 and 6 months after VLDRT and cumulative incidence of local progression (LP) with death as the only competing risk. After VLDRT, the overall response rate was 90% for all treated sites, with 68% achieving complete response (CR). With a median follow-up of 2.4 years, the 2-year cumulative incidence of LP was 25% for the entire cohort and 9% after first-line treatment with VLDRT for potentially curable, localized disease. Lesion size &gt;6 cm was associated with lower odds of attaining a CR and greater risk of LP. There was no suggestion of inferior outcomes for potentially curable lesions. Given the clinical versatility of VLDRT, we propose to implement a novel, incremental, adaptive involved site radiotherapy strategy in which patients will be treated initially with VLDRT, reserving full-dose treatment for those who are unable to attain a CR.
Longitudinal analysis of cardiac abnormalities in pediatric patients with sickle cell anemia and effect of hydroxyurea therapy
Authors: Dhar Arushi , Leung Tung Ming , Appiah-Kubi Abena , Gruber Dorota , Aygun Banu , Serigano Olivia , Mitchell Elizabeth 
Published: September 2021

Abstract
Cardiac abnormalities such as left ventricular hypertrophy, left ventricular dilation, and pulmonary hypertension in sickle cell anemia have been previously described. Hydroxyurea, a disease-modifying therapy for sickle cell anemia, has been used for several decades. Longitudinal assessment of echocardiographic abnormalities in children and young adults with sickle cell anemia receiving hydroxyurea therapy is lacking. The goal of this retrospective study was to determine the prevalence of echocardiographic abnormalities in children and young adults with sickle cell anemia and to examine the effects of hydroxyurea on reverse cardiac remodeling. We reviewed the records of patients with sickle cell anemia who underwent routine cardiac screening at Cohen Children’s Medical Center between 2010 and 2017, followed by retrospective longitudinal analysis of echocardiograms performed on patients receiving treatment with hydroxyurea. Data on a total of 100 patients with sickle cell anemia were analyzed; 60 (60%) were being treated with hydroxyurea. Twenty-five (41.6%) of the patients on hydroxyurea had been treated for &lt;1 year; these patients had a significantly greater prevalence of left ventricular dilation compared with those who had been on treatment for &gt;1 year. Serial echocardiograms of patients receiving hydroxyurea were then analyzed. Left ventricular dilation and hypertrophy improved significantly with hydroxyurea treatment. In addition, the left ventricular volume and mass correlated negatively with duration of treatment with hydroxyurea. Our study provides evidence that prolonged hydroxyurea therapy may lead to reverse cardiac remodeling. Future studies should attempt to follow up this patient cohort for a longer duration.
Poor neutralizing antibody responses in 106 patients with WM after vaccination against SARS-CoV-2: a prospective study
Authors: Gavriatopoulou Maria , Terpos Evangelos , Ntanasis-Stathopoulos Ioannis , Briasoulis Alexandros , Gumeni Sentiljana , Malandrakis Panagiotis , Fotiou Despina , Migkou Magdalini , Theodorakakou Foteini , Eleutherakis-Papaiakovou Evangelos , Kanellias Nikolaos , Kastritis Efstathios , Trougakos Ioannis P. , Dimopoulos Meletios A. 
Published: September 2021

Abstract
Immunocompromised patients with hematologic malignancies are more susceptible to COVID-19 and at higher risk of severe complications and worse outcomes compared with the general population. In this context, we evaluated the humoral response by determining the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with Waldenström macroglobulinemia (WM) after vaccination with the BNT162b2 or AZD1222 vaccine. A US Food and Drug Administration–approved enzyme-linked immunosorbent assay–based methodology was implemented to evaluate NAbs on the day of the first vaccine shot, as well as on days 22 and 50 afterward. A total of 106 patients with WM (43% men; median age, 73 years) and 212 healthy controls (46% men; median age, 66 years) who were vaccinated during the same period at the same center were enrolled in the study (which is registered at www.clinicaltrials.gov as #NCT04743388). Our data indicate that vaccination with either 2 doses of the BNT162b2 or 1 dose of the AZD1222 vaccine leads to lower production of NAbs against SARS-CoV-2 in patients with WM compared with controls on days 22 and 50 (P &lt; .001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with either rituximab or Bruton’s tyrosine kinase inhibitors was proven as an independent prognostic factor for suboptimal antibody response after vaccination. In conclusion, patients with WM have low humoral response after COVID-19 vaccination, which underlines the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.
Health service utilisation associated with chronic breathlessness: random population sample
Authors: Currow David C. , Chang Sungwon , Ekström Magnus , Hutchinson Ann , Luckett Tim , Kochovska Slavica , Hay Phillipa , Touyz Stephen , Dal Grande Eleonora , Johnson Miriam J. 
Published: September 2021

BackgroundMost health service utilisation studies are of people with specific diagnoses or demographic characteristics, and rarely of specific chronic symptoms. The aim of this study was to establish whether population-level health service utilisation increases in people with chronic breathlessness.MethodsA cross-sectional analysis was carried out of the South Australian Health Omnibus Survey 2017, a multi-stage, clustered area, systematic sampling survey of adults where questions are administered face-to-face in respondents’ homes. Self-report of health service utilisation in the previous 3 months (medical consultations, emergency department, hospital admission), chronic breathlessness (severity, duration, modified Medical Research Council (mMRC) breathlessness scale) and demographic data were used to predict self-reported health service utilisation.ResultsA total of 2898 people were included (49.0% male; median age 48.0 years (IQR 32.0–63.0); 64.1% educated beyond school; 55.4% in work; 73.5% had outpatient contact; 6.3% had a hospital admission in the previous 3 months). Chronic breathlessness (mMRC ≥1) was reported by 8.8% of respondents. In bivariable analyses, people with greater contact with health services were older, and a higher proportion were overweight/obese and had more severe chronic breathlessness. In multivariable analyses, chronic breathlessness and older age were positively associated with outpatient care and inpatient care, and people with chronic breathlessness were hospitalised for longer (incidence rate ratio 2.5; 95% CI 1.4–4.5).ConclusionThere is a significant association between worse chronic breathlessness and increased health service utilisation. There is a need for greater understanding of factors that initiate contact with health services.
Multicolor Emission from Ultraviolet GaN-Based Photonic Quasicrystal Nanopyramid Structure with Semipolar InxGa1−xN/GaN Multiple Quantum Wells
Authors: Chen Cheng-Chang , Lin Hsiang-Ting , Chang Shih-Pang , Kuo Hao-Chung , Hung Hsiao-Wen , Chien Kuo-Hsiang , Chang Yu-Choung , Shih M. H. 
Published: September 2021

AbstractIn this study, we demonstrated large-area high-quality multi-color emission from the 12-fold symmetric GaN photonic quasicrystal nanorod device which was fabricated using the nanoimprint lithography technology and multiple quantum wells regrowth procedure. High-efficiency blue and green color emission wavelengths of 460 and 520 nm from the regrown InxGa1−xN/GaN multiple quantum wells were observed under optical pumping conditions. To confirm the strong coupling between the quantum well emissions and the photonic crystal band-edge resonant modes, the finite-element method was applied to perform a simulation of the 12-fold symmetry photonic quasicrystal lattices.
Gold Nanobiosensor Based on the Localized Surface Plasmon Resonance is Able to Diagnose Human Brucellosis, Introducing a Rapid and Affordable Method
Authors: Vakili Sina , Samare-Najaf Mohammad , Dehghanian Amirreza , Tajbakhsh Amir , Askari Hassan , Tabrizi Reza , Iravani Saadi Mahdiyar , Movahedpour Ahmad , Alizadeh Marzieh , Samareh Ali , Taghizadeh Saeed , Noroozi Saam 
Published: September 2021

AbstractBrucellosis is considered as the most common bacterial zoonosis in the world. Although the laboratory findings are the most reliable diagnosis today, the current laboratory methods have many limitations. This research aimed to design and evaluate the performance of a novel technique based on the localized surface plasmon resonance (LSPR) to eliminate or reduce existing shortcomings. For this purpose, smooth lipopolysaccharides were extracted from Brucella melitensis and Brucella abortus and fixed on the surface of the gold nanoparticles through covalent interactions. After some optimizing processes, dynamic light scattering was used to characterize the probe. The detection of captured anti-Brucella antibody was performed by measuring the redshift on LSPR peak followed by the determination of cutoff value, which indicated a significant difference between controls and true positive patients (P value < 0.01). Furthermore, 40 sera from true negative samples and positive patients were used to evaluate the performance of this method by comparing its outcomes with the gold standard (culture), standard tube agglutination test, and anti-brucellosis IgM and IgG levels (ELISA). The sensitivity, specificity, positive predictive value, and negative predictive value showed an appropriate performance of the LSPR-based method (85%, 100%, 100%, and 86%, respectively). The current research results provide a promising fast, convenient, and inexpensive method for detecting the anti-Brucella antibodies in human sera, which can be widely used in medical laboratories to diagnose brucellosis quickly and effectively.
Multimodal imaging supporting the pathophysiology of white dot syndromes
Authors: Testi Ilaria , Modugno Rocco Luigi , Pavesio Carlos 
Published: September 2021

AbstractWhite dot syndromes (WDS) represent a heterogeneous group of inflammatory diseases, primarily affecting the outer retina, choriocapillaris and choroid. Recent advances in the field of ocular imaging and development of new technologies, including optical coherence tomography angiography (OCT-A), have allowed a better characterization of the morphology of these conditions. This review will analyse the WDS from an imaging-based perspective, providing a better understanding of the pathophysiology underlying these disorders.
Randomized boosting with multivariable base-learners for high-dimensional variable selection and prediction
Authors: Staerk Christian , Mayr Andreas 
Published: September 2021

AbstractBackgroundStatistical boosting is a computational approach to select and estimate interpretable prediction models for high-dimensional biomedical data, leading to implicit regularization and variable selection when combined with early stopping. Traditionally, the set of base-learners is fixed for all iterations and consists of simple regression learners including only one predictor variable at a time. Furthermore, the number of iterations is typically tuned by optimizing the predictive performance, leading to models which often include unnecessarily large numbers of noise variables.ResultsWe propose three consecutive extensions of classical component-wise gradient boosting. In the first extension, called Subspace Boosting (SubBoost), base-learners can consist of several variables, allowing for multivariable updates in a single iteration. To compensate for the larger flexibility, the ultimate selection of base-learners is based on information criteria leading to an automatic stopping of the algorithm. As the second extension, Random Subspace Boosting (RSubBoost) additionally includes a random preselection of base-learners in each iteration, enabling the scalability to high-dimensional data. In a third extension, called Adaptive Subspace Boosting (AdaSubBoost), an adaptive random preselection of base-learners is considered, focusing on base-learners which have proven to be predictive in previous iterations. Simulation results show that the multivariable updates in the three subspace algorithms are particularly beneficial in cases of high correlations among signal covariates. In several biomedical applications the proposed algorithms tend to yield sparser models than classical statistical boosting, while showing a very competitive predictive performance also compared to penalized regression approaches like the (relaxed) lasso and the elastic net.ConclusionsThe proposed randomized boosting approaches with multivariable base-learners are promising extensions of statistical boosting, particularly suited for highly-correlated and sparse high-dimensional settings. The incorporated selection of base-learners via information criteria induces automatic stopping of the algorithms, promoting sparser and more interpretable prediction models.