bluuebunny/crossref_metadata_2025_split huggingface dataset:
4-hydroxytamoxifen does not deteriorate cardiac function in cardiomyocyte-specific MerCreMer transgenic mice
Authors: Heinen Andre , Gödecke Stefanie , Flögel Ulrich , Miklos Dominika , Bottermann Katharina , Spychala André , Gödecke Axel 
Published: February 2021

AbstractConditional, cell-type-specific transgenic mouse lines are of high value in cardiovascular research. A standard tool for cardiomyocyte-restricted DNA editing is the αMHC-MerCreMer/loxP system. However, there is an ongoing debate on the occurrence of cardiac side effects caused by unspecific Cre activity or related to tamoxifen/oil overload. Here, we investigated potential adverse effects of DNA editing by the αMHC-MerCreMer/loxP system in combination with a low-dose treatment protocol with the tamoxifen metabolite 4-hydroxytamoxifen (OH-Txf). αMHC-MerCreMer mice received intraperitoneally OH-Txf (20 mg/kg) for 5 or 10 days. These treatment protocols were highly efficient to induce DNA editing in adult mouse hearts. Multi-parametric magnetic resonance imaging revealed neither transient nor permanent effects on cardiac function during or up to 19 days after 5 day OH-Txf treatment. Furthermore, OH-Txf did not affect cardiac phosphocreatine/ATP ratios assessed by in vivo 31P MR spectroscopy, indicating no Cre-mediated side effects on cardiac energy status. No MRI-based indication for the development of cardiac fibrosis was found as mean T1 relaxation time was unchanged. Histological analysis of myocardial collagen III content after OH-Txf confirmed this result. Last, mean T2 relaxation time was not altered after Txf treatment suggesting no pronounced cardiac lipid accumulation or tissue oedema. In additional experiments, cardiac function was assessed for up to 42 days to investigate potential delayed side effects of OH-Txf treatment. Neither 5- nor 10-day treatment resulted in a depression of cardiac function. Efficient cardiomyocyte-restricted DNA editing that is free of unwanted side effects on cardiac function, energetics or fibrosis can be achieved in adult mice when the αMHC-MerCreMer/loxP system is activated by the tamoxifen metabolite OH-Txf.
Virtual morphometric method using seven cervical vertebrae for sex estimation on the Turkish population
Authors: Ekizoglu Oguzhan , Hocaoglu Elif , Inci Ercan , Karaman Gokce , Garcia-Donas Julieta , Kranioti Elena , Moghaddam Negahnaz , Grabherr Silke 
Published: February 2021

AbstractSex estimation from skeletal remains is crucial for the estimation of the biological profile of an individual. Although the most commonly used bones for means of sex estimation are the pelvis and the skull, research has shown that acceptable accuracy rates might be achieved by using other skeletal elements such as vertebrae. This study aims to contribute to the development of sex estimation standards from a Turkish population through the examination of CT scans from the seven cervical vertebrae. A total of 294 individuals were included in this study. The CT scans were obtained from patients attending the Bakirkoy Training and Research Hospital (Turkey) and the data was collected retrospectively by virtually taking measurements from each cervical vertebrae. The full database was divided into a training set (N = 210) and a validation set (N = 84) to test the fit of the models. Observer error was assessed through technical error of measurement and sex differences were explored using parametric and non-parametric approaches. Logistic regression was applied in order to explore different combinations of vertebral parameters. The results showed low intra- and inter-observer errors. All parameters presented statistically significant differences between the sexes and a total of 15 univariate and multivariate models were generated producing accuracies ranging from a minimum of 83.30% to a maximum of 91.40% for a model including three parameters collected from four vertebrae. This study presents a virtual method using cervical vertebrae for sex estimation on the Turkish population providing error rates comparable to other metric studies conducted on the postcranial skeleton. The presented results contribute not only to the development of population-specific standards but also to the generation of virtual methods that can be tested, validated, and further examined in future forensic cases.
Oncological outcome after local treatment for early stage rectal cancer
Authors: Witjes Caroline D. M. , Patel Abhilashaben S. , Shenoy Aniruddh , Boyce Stephen , East James E. , Cunningham Christopher 
Published: February 2021

Abstract
Background
Treatment of early rectal cancer is evolving towards organ-preserving therapy which includes endoscopic resection and transanal approaches. We aimed to explore the role of local treatments such as endoscopic polypectomy (Endoscopic Mucosal Resection (EMR) or Endoscopic submucosal dissection (ESD)) and transanal endoscopic microsurgery/ transanal minimal invasive surgery (TEM/TAMIS) in patients who had early rectal cancer. We considered these outcomes alongside conventional major surgery using total mesorectal excision (TME) for early stage disease.

Methods
All patients identified at MDT with early stage rectal cancer at our institution between 2010 and 2019 were included. Long-term outcomes in terms of local recurrence, survival and procedure-specific morbidity were analysed.

Results
In total, 536 patients with rectal cancer were identified, of which 112 were included based on their pre-operative identification at the MDT on the basis that they had node-negative early rectal cancer. Among these, 30 patients (27%) had the lesion excised by flexible endoscopic polypectomy techniques (EMR/ESD), 67 (60%) underwent TEM/TAMIS and 15 (13%) had major surgery. There were no differences in patient demographics between the three groups except for TEM/TAMIS patients being more likely to be referred from another hospital (p < 0.001) and they were less active (WHO performance status p = 0.04). There were no significant differences in overall survival rates and cancer-specific survival between the three treatment groups. The 5-year overall survival rate for endoscopic polypectomy, TEM/TAMIS or major resection was 96% versus 90% and 88%, respectively (p = 0.89). The 5- year cancer-specific survival rate was 96%, versus 96% and 100%, respectively (p = 0.74).

Conclusion
Endoscopic polypectomy by EMR/ESD is an appropriate local treatment for early stage rectal cancer in selected patients. It is possible to achieve good oncological outcomes with a polypectomy similar to TEM/TAMIS and major surgery; however, a multidisciplinary approach is necessary enabling close surveillance and the use of adjuvant radiotherapy.
Feasibility and suitability of a graded exercise test in patients with aggressive hemato-oncological disease
Authors: Großek Anja , Elter Thomas , Oberste Max , Wolf Florian , Joisten Niklas , Hartig Philipp , Walzik David , Rosenberger Friederike , Kiesl David , Wahl Patrick , Bloch Wilhelm , Zimmer Philipp 
Published: February 2021

Abstract
Purpose
Physical activity promises to reduce disease-related symptoms and therapy-related side effects in patients suffering from aggressive lymphoma (L) or acute leukemia (AL). For an efficient training program, determination of patients’ physical capacity with a purposive exercise test is crucial. Here, we evaluated the feasibility and suitability of a graded exercise test (GXT) frequently applied in patients suffering from solid tumors by assessing whether patients achieved criteria for maximal exercise testing according to the American College of Sports Medicine (ACSM).

Methods
The GXT was performed by 51 patients with an aggressive L or AL prior to the start or in the earliest possible phase of high-dose chemotherapy, following a recommended protocol for cancer patients, starting at 20 Watts (W), with an increase of 10 W/min until volitional exhaustion. Subsequently, we investigated whether the following ACSM criteria were fulfilled: (1) failure of heart rate to increase despite increasing workload, (2) post-exercise capillary lactate concentration ≥ 8.0 mmol L−1, (3) rating of perceived exertion at exercise cessation > 17 on the 6–20 Borg Scale.

Results
Out of 51 patients, two, six, and 35 participants met the first, second, and third criterion, respectively. No relevant relationships between the completion of the criteria and patients’ characteristics (e.g., gender, age) were found.

Conclusion
Although results of this study suggest a general feasibility of the applied GXT, the ACSM criteria were not met by the majority of the participants. Therefore, this study raises doubts about the suitability of the GXT protocol and the ACSM criteria for this group of patients.
The Asp1 pyrophosphatase from S. pombe hosts a [2Fe-2S]2+ cluster in vivo
Authors: Rosenbach Hannah , Walla Eva , Cutsail George E. , Birrell James A. , Pascual-Ortiz Marina , DeBeer Serena , Fleig Ursula , Span Ingrid 
Published: February 2021

AbstractTheSchizosaccharomyces pombeAsp1 protein is a bifunctional kinase/pyrophosphatase that belongs to the highly conserved eukaryotic diphosphoinositol pentakisphosphate kinase PPIP5K/Vip1 family. The N-terminal Asp1 kinase domain generates specific high-energy inositol pyrophosphate (IPP) molecules, which are hydrolyzed by the C-terminal Asp1 pyrophosphatase domain (Asp1365−920). Thus, Asp1 activities regulate the intracellular level of a specific class of IPP molecules, which control a wide number of biological processes ranging from cell morphogenesis to chromosome transmission. Recently, it was shown that chemical reconstitution of Asp1371−920leads to the formation of a [2Fe-2S] cluster; however, the biological relevance of the cofactor remained under debate. In this study, we provide evidence for the presence of the Fe–S cluster in Asp1365−920inside the cell. However, we show that the Fe–S cluster does not influence Asp1 pyrophosphatase activity in vitro or in vivo. Characterization of the as-isolated protein by electronic absorption spectroscopy, mass spectrometry, and X-ray absorption spectroscopy is consistent with the presence of a [2Fe-2S]2+cluster in the enzyme. Furthermore, we have identified the cysteine ligands of the cluster. Overall, our work reveals that Asp1 contains an Fe–S cluster in vivo that is not involved in its pyrophosphatase activity.
Duration of the pubertal growth spurt in patients with increased craniofacial growth component in sagittal and vertical planes—retrospective and cross-sectional study
Authors: Szemraj-Folmer Agnieszka , Wojtaszek-Słomińska Anna , Racka-Pilszak Bogna , Kuc-Michalska Małgorzata 
Published: February 2021

Abstract
Objectives
The aim of the study is to assess the skeletal age at the onset and end of the pubertal growth spurt and determine its duration in four growth type groups: (1) normodivergent skeletal Class I (I N), (2) normodivergent skeletal Class III (III N), (3) high-angle skeletal Class III (III H) and (4) high-angle skeletal Class I (I H).

Materials and methods
Two hundred thirteen subjects were selected from 2163 examined files. The cervical vertebral maturation stage was recorded by means of Baccetti’s method. The sagittal and vertical skeletal relations were evaluated according to Steiner analysis with Kaminek’s modification. The duration of the pubertal growth spurt was calculated from the difference between the means of the chronological age related to CS3 and CS4 maturation stages.

Results
The shortest lasting pubertal growth spurt was observed in group I N (1.1), followed by group III N (1.6). Major differences between arithmetic means CS4-CS3 were seen in groups I H and III H (2.3 and 2.7, respectively).

Conclusions
The following tendency was observed in the duration of the pubertal growth spurt: I N < III N < I H < III H. This tendency has statistical significance only in high-angle patients in comparison with normodivergent skeletal Class I.

Clinical relevance
Knowledge on the longer pubertal growth spurt in high-angle patients compared to patients with normal anteroposterior and vertical relationships can be useful in the selection of an appropriate therapeutic method and a treatment time.
A scalable framework for large time series prediction
Authors: Hmamouche Youssef , Lakhal Lotfi , Casali Alain 
Published: February 2021

AbstractKnowledge discovery systems are nowadays supposed to store and process very large data. When working with big time series, multivariate prediction becomes more and more complicated because the use of all the variables does not allow to have the most accurate predictions and poses certain problems for classical prediction models. In this article, we present a scalable prediction process for large time series prediction, including a new algorithm for identifying time series predictors, which analyses the dependencies between time series using the mutual reinforcement principle between Hubs and Authorities of the Hits (Hyperlink-Induced Topic Search) algorithm. The proposed framework is evaluated on 3 real datasets. The results show that the best predictions are obtained using a very small number of predictors compared to the initial number of variables. The proposed feature selection algorithm shows promising results compared to widely known algorithms, such as the classic and the kernel principle component analysis, factor analysis, and the fast correlation-based filter method, and improves the prediction accuracy of many time series of the used datasets.
One Step at a Time: The Origins of Sequential Simulation and Beyond
Authors: Gómez-Hernández J. Jaime , Srivastava R. Mohan 
Published: February 2021

AbstractIn the mid-1980s, still in his young 40s, André Journel was already recognized as one of the giants of geostatistics. Many of the contributions from his new research program at Stanford University had centered around the indicator methods that he developed: indicator kriging and multiple indicator kriging. But when his second crop of graduate students arrived at Stanford, indicator methods still lacked an approach to conditional simulation that was not tainted by what André called the ‘Gaussian disease’; early indicator simulations went through the tortuous path of converting all indicators to Gaussian variables, running a turning bands simulation, and truncating the resulting multi-Gaussian realizations. When he conceived of sequential indicator simulation (SIS), even André likely did not recognize the generality of an approach to simulation that tackled the simulation task one step at a time. The early enthusiasm for SIS was its ability, in its multiple-indicator form, to cure the Gaussian disease and to build realizations in which spatial continuity did not deteriorate in the extreme values. Much of Stanford’s work in the 1980s focused on petroleum geostatistics, where extreme values (the high-permeability fracture zones and the low-permeability shale barriers) have much stronger anisotropy, and much longer ranges of correlation in the maximum continuity direction, than mid-range values. With multi-Gaussian simulations necessarily imparting weaker continuity to the extremes, SIS was an important breakthrough. The generality of the sequential approach was soon recognized, first through its analogy with multi-variate unconditional simulation achieved using the lower triangular matrix of an LU decomposition of the covariance matrix as the multiplier of random normal deviates. Modifying LU simulation so that it became conditional gave rise to sequential Gaussian simulation (SGS), an algorithm that shared much in common with SIS. With nagging implementation details like the sequential path and the search neighborhood being common to both methods, improvements in either SIS or SGS often became improvements to the other. Almost half of the contributors to this Special Issue became students of André in the classes of 1984–1988, and several are the pioneers of SIS and SGS. Others who studied later with André explored and developed the first multipoint statistics simulation procedures, which are based on the same concept that underlies sequential simulation. Among his many significant intellectual accomplishments, one of the cornerstones of André Journel’s legacy was sequential simulation, built one step at a time.
Quest for a summary measure of biological age: the health and retirement study
Authors: Crimmins Eileen M. , Thyagarajan Bharat , Kim Jung Ki , Weir David , Faul Jessica 
Published: February 2021

AbstractMeasures of biological age and its components have been shown to provide important information about individual health and prospective change in health as there is clear value in being able to assess whether someone is experiencing accelerated or decelerated aging. However, how to best assess biological age remains a question. We compare prediction of health outcomes using existing summary measures of biological age with a measure created by adding novel biomarkers related to aging to measures based on more conventional clinical chemistry and exam measures. We also compare the explanatory power of summary biological age measures compared to the individual biomarkers used to construct the measures. To accomplish this, we examine how well biological age, phenotypic age, and expanded biological age and five sets of individual biomarkers explain variability in four major health outcomes linked to aging in a large, nationally representative cohort of older Americans. We conclude that different summary measures of accelerated aging do better at explaining different health outcomes, and that chronological age has greater explanatory power for both cognitive dysfunction and mortality than the summary measures. In addition, we find that there is reduction in the variance explained in health outcomes when indicators are combined into summary measures, and that combining clinical indicators with more novel markers related to aging does best at explaining health outcomes. Finally, it is hard to define a set of assays that parsimoniously explains the greatest amount of variance across the range of health outcomes studied here. All of the individual markers considered were related to at least one of the health outcomes.
Surgical reconstruction of the anterolateral acromion with a tricortical iliac crest bone graft after extensive acromioplasty
Authors: Tross Anna-K. , Nolte Philip-C. , Loew Markus , Schnetzke Marc , Lichtenberg Sven 
Published: February 2021

AbstractSubacromial decompression is one of the most frequently performed procedures in the setting of arthroscopic shoulder surgery and typically includes acromioplasty. However, the indication for acromioplasty remains a subject of debate. Possible complications involve deltoid muscle insufficiency due to an excessive removal of the anterior acromion. This case report is intended to draw attention to this particular complication and its management.
Hypercalcemia during pregnancy: management and outcomes for mother and child
Authors: Appelman-Dijkstra Natasha M. , Ertl Diana- Alexandra , Zillikens M. C. , Rjenmark Lars , Winter Elizabeth M. 
Published: February 2021

AbstractDiagnosing and treating hypercalcemia during pregnancy can be challenging due to both the physiological changes in calcium homeostasis and the underlying cause for the hypercalcemia. During pregnancy and lactation there is increased mobilization of calcium in the mother to meet the fetus’ calcium requirements. Here we discuss the diagnostic challenges, management, and patient perspective of hypercalcemia during pregnancy in two particular cases and in other rare conditions causing hypercalcemia.
Cerebellar rTMS in PSP: a Double-Blind Sham-Controlled Study Using Mobile Health Technology
Authors: Pilotto Andrea , Rizzetti Maria Cristina , Lombardi Alberto , Hansen Clint , Biggi Michele , Verzeroli Giacomo , Martinelli Antonella , Romijnders Robbin , Borroni Barbara , Maetzler Walter , Padovani Alessandro 
Published: February 2021

AbstractThere are no effective treatments in progressive supranuclear palsy (PSP). The aim of this study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty PSP patients underwent a session of sham or real cerebellar rTMS in a crossover design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-s trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with increase in time without falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005), acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, in a double-blind design. These results should motivate larger and longer trials using non-invasive brain stimulation for PSP patients.
MicroRNA signature in classical Hodgkin lymphoma
Authors: Paczkowska Julia , Giefing Maciej 
Published: February 2021

AbstractClassical Hodgkin lymphoma (cHL) is one of the most prevalent lymphomas with a unique cell composition compared to other lymphoma entities. Rare, malignant Hodgkin and Reed-Sternberg (HRS) cells embedded with an extensive but ineffective immune infiltration were previously characterized by a large number of genetic and epigenetic alterations. Recently, microRNA profiling studies highlighted the importance of small non-coding RNA in cHL. This review summarizes available literature data and provides a detailed comparison of four studies where cHL cell lines and microdissected HRS cells were used. Several microRNAs were found to be consistently up- (let-7-f, mir-9, mir-21, mir-23a, mir-27a, mir-155, and mir-196a) or downregulated (mir-138 and mir-150) in cHL. These deregulated microRNAs are involved in the processes crucial for cHL pathogenesis, such as impaired B cell development (mir-9, mir-150, and mir-155), NFκB hyperactivation (mir-155 and mir-196a), and immune evasion (mir-138). Therefore, the deregulation of microRNA expression can be considered a complementary mechanism to genetic alterations promoting lymphomagenesis. Moreover, the expression of let-7f, mir-9 and mir-27a is specific for cHL and can serve as a biomarker to distinguish this lymphoma from other B cell lymphomas. However, additional in-depth and high throughput analysis of microRNA expression in HRS cells is necessary to decipher the complete picture of microRNA in cHL.
Correction to: Exploring the potential of black gram (Vigna mungo) flour as a fat replacer in biscuits with improved physicochemical, microstructure, phytochemicals, nutritional and sensory attributes
Authors: Saeed Syed Muhammad Ghufran , Ali Syed Arsalan , Ali Rashida , Sayeed Syed Asad , Mobin Lubna , Ahmed Raheel 
Published: February 2021

The version of Fig. 5 in the initial online publication was incorrect. The original article has been corrected.
Relativistic density functional theory in nuclear physics
Authors: Meng Jie , Zhao Pengwei 
Published: February 2021

AbstractOver the past decades, the relativistic density functional theory has been greatly developed and widely applied to investigate a variety of nuclear phenomena. In this paper, we briefly review the concept of covariant density functional theory in nuclear physics with a few latest applications in describing nuclear ground-state and excitation properties as well as nuclear dynamics. Moreover, attempts to build a microscopic and universal density functional are also discussed in terms of the successful fully self-consistent relativistic Brueckner–Hartree–Fock calculations.