bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of predicting allele specific expression from DNA sequencing using machine learning
Authors: Zhang Zhenhua , van Dijk Freerk , de Klein Niek , van Gijn Mariëlle E , Franke Lude H , Sinke Richard J , Swertz Morris A , van der Velde K Joeri 
Published: May 2021

AbstractAllele specific expression (ASE) concerns divergent expression quantity of alternative alleles and is measured by RNA sequencing. Multiple studies show that ASE plays a role in hereditary diseases by modulating penetrance or phenotype severity. However, genome diagnostics is based on DNA sequencing and therefore neglects gene expression regulation such as ASE. To take advantage of ASE in absence of RNA sequencing, it must be predicted using only DNA variation. We have constructed ASE models from BIOS (n = 3432) and GTEx (n = 369) that predict ASE using DNA features. These models are highly reproducible and comprise many different feature types, highlighting the complex regulation that underlies ASE. We applied the BIOS-trained model to population variants in three genes in which ASE plays a clinically relevant role: BRCA2, RET and NF1. This resulted in predicted ASE effects for 27 variants, of which 10 were known pathogenic variants. We demonstrated that ASE can be predicted from DNA features using machine learning. Future efforts may improve sensitivity and translate these models into a new type of genome diagnostic tool that prioritizes candidate pathogenic variants or regulators thereof for follow-up validation by RNA sequencing. All used code and machine learning models are available at GitHub and Zenodo.
Drop homotopic effects of masseter-muscle pain on somatosensory sensitivity in healthy participants
Authors: Hayakawa Hidetoshi , Iida Takashi , Honda-Sakaki Mika , Masuda Manabu , Svensson Peter , Komiyama Osamu 
Published: May 2021

AbstractCurrent pain classifications use 1.0-kg palpation of the masseter muscle to distinguish between “pain patients” and “healthy controls” but a thorough understanding of the normal physiological responses to various somatosensory stimuli is lacking. The aim of this study was to investigate somatosensory function of the skin over the masseter muscle in healthy participants that were divided into a masseter pain prone group (MPP) (n = 22) and non-MPP group (n = 22), according to the response to a 1.0-kg palpation. Quantitative sensory testing (QST) was performed at the skin above the right masseter muscle (homotopic). In an additional experiment, 13 individuals each from MPP and non-MPP received application of 60% topical lidocaine tape to the skin over the masseter muscle for 30 min. Immediately after, mechanical pain sensitivity (MPS), dynamic mechanical allodynia, and pressure pain threshold were tested. Homotopic MPS was significantly higher and PPTs significantly lower in MPP than in N-MPP (P < 0.05). Strikingly, no other differences in QST outcomes were observed between the groups (P > 0.05). After lidocaine application, no significant differences in homotopic MPS were observed between groups. The presence or absence of acute provoked pain in masseter muscle is exclusively associated with differences in homotopic MPS which is decreased following topical anesthesia.
Watching sports and depressive symptoms among older adults: a cross-sectional study from the JAGES 2019 survey
Authors: Tsuji Taishi , Kanamori Satoru , Watanabe Ryota , Yokoyama Meiko , Miyaguni Yasuhiro , Saito Masashige , Kondo Katsunori 
Published: May 2021

AbstractThe current study investigated the relationship between the frequency of watching sports and depressive symptoms among older adults. This study used cross-sectional data from the Japan Gerontological Evaluation Study, a nationwide mail survey of 21,317 older adults. Depressive symptoms were defined as a Geriatric Depression Scale score of ≥ 5. Participants were queried regarding the average frequency at which they watched sports on-site and via TV/Internet over the past year. Among the 21,317 participants, 4559 (21.4%) had depressive symptoms, while 4808 (22.6%) and 16,576 (77.8%) watched sports on-site and via TV/Internet at least once a year, respectively. Older adults who watched sports on-site a few times/year (prevalence ratio, 0.70; 95% confidence interval, 0.65–0.74) or 1–3 times/month (0.66, 0.53–0.82) were less likely to have depressive symptoms compared to non-spectators after adjusting for frequency of playing sports, exercise activities, and other potential confounders. Meanwhile, a dose–response relationship was confirmed for watching via TV/Internet (prevalence ratio of 0.86, 0.79, and 0.71 for a few times/year, 1–3 times/month, and ≥ 1 time/week, respectively). This study suggested that watching sports on-site or via TV/Internet, regardless of whether they regularly engage in sports, may reduce the risk of depressive symptoms among older adults.
Patient-derived tumor xenograft and organoid models established from resected pancreatic, duodenal and biliary cancers
Authors: Pham Nhu-An , Radulovich Nikolina , Ibrahimov Emin , Martins-Filho Sebastiao N. , Li Quan , Pintilie Melania , Weiss Jessica , Raghavan Vibha , Cabanero Michael , Denroche Robert E. , Wilson Julie M. , Metran-Nascente Cristiane , Borgida Ayelet , Hutchinson Shawn , Dodd Anna , Begora Michael , Chadwick Dianne , Serra Stefano , Knox Jennifer J. , Gallinger Steven , Hedley David W. , Muthuswamy Lakshmi , Tsao Ming-Sound 
Published: May 2021

AbstractPatient-derived xenograft (PDX) and their xenograft-derived organoid (XDO) models that recapitulate the genotypic and phenotypic landscape of patient cancers could help to advance research and lead to improved clinical management. PDX models were established from 276 pancreato-duodenal and biliary cancer resections. Initial, passage 0 (P0) engraftment rates were 59% (118/199) for pancreatic, 86% (25/29) for duodenal, and 35% (17/48) for biliary ductal tumors. Pancreatic ductal adenocarcinoma (PDAC), had a P0 engraftment rate of 62% (105/169). KRAS mutant and wild-type PDAC models were molecularly profiled, and XDO models were generated to perform initial drug response evaluations. Subsets of PDAC PDX models showed global copy number variants and gene expression profiles that were retained with serial passaging, and they showed a spectrum of somatic mutations represented in patient tumors. PDAC XDO models were established, with a success rate of 71% (10/14). Pathway activation of KRAS-MAPK in PDXs was independent of KRAS mutational status. Four wild-type KRAS models were characterized by one with EGFR (L747-P753 del), two with BRAF alterations (N486_P490del or V600E), and one with triple negative KRAS/EGFR/BRAF. Model OCIP256, characterized by BRAF (N486-P490 del), had activated phospho-ERK. A combination treatment of a pan-RAF inhibitor (LY3009120) and a MEK inhibitor (trametinib) effectively suppressed phospho-ERK and inhibited growth of OCIP256 XDO and PDX models. PDAC/duodenal adenocarcinoma have high success rates forming PDX/organoid and retaining their phenotypic and genotypic features. These models may be effective tools to evaluate novel drug combination therapies.
Decreased vascular smooth muscle contractility in Hutchinson–Gilford Progeria Syndrome linked to defective smooth muscle myosin heavy chain expression
Authors: von Kleeck Ryan , Castagnino Paola , Roberts Emilia , Talwar Shefali , Ferrari Giovanni , Assoian Richard K. 
Published: May 2021

AbstractChildren with Hutchinson–Gilford Progeria Syndrome (HGPS) suffer from multiple cardiovascular pathologies due to the expression of progerin, a mutant form of the nuclear envelope protein Lamin A. Progerin expression has a dramatic effect on arterial smooth muscle cells (SMCs) and results in decreased viability and increased arterial stiffness. However, very little is known about how progerin affects SMC contractility. Here, we studied the LaminAG609G/G609G mouse model of HGPS and found reduced arterial contractility at an early age that correlates with a decrease in smooth muscle myosin heavy chain (SM-MHC) mRNA and protein expression. Traction force microscopy on isolated SMCs from these mice revealed reduced force generation compared to wild-type controls; this effect was phenocopied by depletion of SM-MHC in WT SMCs and overcome by ectopic expression of SM-MHC in HGPS SMCs. Arterial SM-MHC levels are also reduced with age in wild-type mice and humans, suggesting a common defect in arterial contractility in HGPS and normal aging.
Comparison between selective caudal fixed screw construct and all variable screw construct in anterior cervical discectomy and fusion
Authors: Yang Jae Jun , Park Sehan , Park Seongyun 
Published: May 2021

AbstractThis retrospective comparative study aimed to compare the efficacy of selective caudal fixed screw constructs with all variable screw constructs in anterior cervical discectomy and fusion (ACDF). Thirty-five patients who underwent surgery using selective caudal fixed screw construct (SF group) were compared with 44 patients who underwent surgery using all variable constructs (AV group). The fusion rate, subsidence, adjacent level ossification development (ALOD), adjacent segmental disease (ASD), and plate-adjacent disc space distance were assessed. The one-year fusion rates assessed by computed tomography bone bridging and interspinous motion as well as the significant subsidence rate did not differ significantly between the AV and SF groups. The ALOD and ASD rates and plate-adjacent disc space distances did not significantly differ between the two groups at both the cranial and caudal adjacent levels. The number of operated levels was significantly associated with pseudarthrosis in the logistic regression analysis. The stability provided by the locking mechanism of the fixed screw did not lead to an increased fusion rate at the caudal level. Therefore, the screw type should be selected based on individual patient’s anatomy and surgeon’s experience without concern for increased complications caused by screw type.
Distribution of genetic alterations in high-risk early-stage cervical cancer patients treated with postoperative radiation therapy
Authors: Murakami Naoya , Asami Yuka , Yoshida Hiroshi , Takayanagi Daisuke , Hirose Sou , Kuno Ikumi , Takahashi Kazuaki , Matsuda Maiko , Shimada Yoko , Yamano Shotaro , Sunami Kuniko , Honda Takayuki , Nakahara Tomomi , Watanabe Tomoko , Okuma Kae , Kuroda Takafumi , Kohno Takashi , Kato Tomoyasu , Shiraishi Kouya , Itami Jun 
Published: May 2021

AbstractSomatic genetic alteration analysis was performed for post-hysterectomy high-risk early-stage uterine cervical cancer patients who underwent post-operative radiation therapy. Post-operative radiation therapy was performed for patients with pathological features of pelvic lymph node metastasis, parametrium invasion, or positive vaginal margin, which corresponded to the post-operative high-risk category. DNA was extracted from paraffin-embedded surgical specimens, and 50 somatic hotspot genetic alternations were detected using Ion AmpliSeq Cancer Hotspot Panel. The existence of actionable mutation was assessed based on OncoKB evidence level > 3A. Between January 2008 and November 2019, 89 patients who underwent abdominal radical hysterectomy followed by post-operative radiation therapy were identified. The follow-up period for living patients was 82.3 months (range 9.3–153.9), and the 5-year relapse-free survival and overall survival rates were 72.6% and 85.9%, respectively. The most frequently detected somatic mutation was PIK3CA (26 [29.2%] patients); however, no prognostic somatic genetic alterations were identified. Actionable mutations were detected in 30 (33.7%) patients. Actionable mutations were detected in approximately one-third of patients, suggesting that precision medicine can be offered to patients with post-operative high-risk uterine cervical cancer in the near future.
Prediction of velocity profile of water based copper nanofluid in a heated porous tube using CFD and genetic algorithm
Authors: Ciano Tiziana , Ferrara Massimiliano , Babanezhad Meisam , Khan Afrasyab , Marjani Azam 
Published: May 2021

AbstractThe heat transfer improvements by simultaneous usage of the nanofluids and metallic porous foams are still an attractive research area. The Computational fluid dynamics (CFD) methods are widely used for thermal and hydrodynamic investigations of the nanofluids flow inside the porous media. Almost all studies dedicated to the accurate prediction of the CFD approach. However, there are not sufficient investigations on the CFD approach optimization. The mesh increment in the CFD approach is one of the challenging concepts especially in turbulent flows and complex geometries. This study, for the first time, introduces a type of artificial intelligence algorithm (AIA) as a supplementary tool for helping the CFD. According to the idea of this study, the CFD simulation is done for a case with low mesh density. The artificial intelligence algorithm uses learns the CFD driven data. After the intelligence achievement, the AIA could predict the fluid parameters for the infinite number of nodes or dense mesh without any limitations. So, there is no need to solve the CFD models for further nodes. This study is specifically focused on the genetic algorithm-based fuzzy inference system (GAFIS) to predict the velocity profile of the water-based copper nanofluid turbulent flow in a porous tube. The most intelligent GAFIS could perform the most accurate prediction of the velocity. Hence, the intelligence of GAFIS is tested for different values of cluster influence range (CIR), squash factor(SF), accept ratio (AR) and reject ratio (RR), the population size (PS), and the percentage of crossover (PC). The maximum coefficient of determination (~ 0.97) was related to the PS of 30, the AR of 0.6, the PC of 0.4, CIR of 0.15, the SF 1.15, and the RR of 0.05. The GAFIS prediction of the fluid velocity was in great agreement with the CFD. In the most intelligent condition, the velocity profile predicted by GAFIS was similar to the CFD. The nodes increment from 537 to 7671 was made by the GAFIS. The new predictions of the GAFIS covered all CFD results.
Live-cell imaging of glucose-induced metabolic coupling of β and α cell metabolism in health and type 2 diabetes
Authors: Wang Zhongying , Gurlo Tatyana , Matveyenko Aleksey V. , Elashoff David , Wang Peiyu , Rosenberger Madeline , Junge Jason A. , Stevens Raymond C. , White Kate L. , Fraser Scott E. , Butler Peter C. 
Published: May 2021

AbstractType 2 diabetes is characterized by β and α cell dysfunction. We used phasor-FLIM (Fluorescence Lifetime Imaging Microscopy) to monitor oxidative phosphorylation and glycolysis in living islet cells before and after glucose stimulation. In healthy cells, glucose enhanced oxidative phosphorylation in β cells and suppressed oxidative phosphorylation in α cells. In Type 2 diabetes, glucose increased glycolysis in β cells, and only partially suppressed oxidative phosphorylation in α cells. FLIM uncovers key perturbations in glucose induced metabolism in living islet cells and provides a sensitive tool for drug discovery in diabetes.
CD28 engagement inhibits CD73-mediated regulatory activity of CD8+ T cells
Authors: Lai Yo-Ping , Kuo Lu-Cheng , Lin Been-Ren , Lin Hung-Ju , Lin Chih-Yu , Chen Yi-Ting , Hsiao Pei-Wen , Chang Huan-Tsung , Ko Patrick Chow-In , Chen Hsiao-Chin , Chang Hsiang-Yu , Lu Jean , Ho Hong-Nerng , Wu-Hsieh Betty A. , Kung John T. , Chen Shu-Ching 
Published: May 2021

AbstractCD28 is required for T cell activation as well as the generation of CD4+Foxp3+ Treg. It is unclear, however, how CD28 costimulation affects the development of CD8+ T cell suppressive function. Here, by use of Hepa1.6.gp33 in vitro killing assay and B16.gp33 tumor mouse model we demonstrate that CD28 engagement during TCR ligation prevents CD8+ T cells from becoming suppressive. Interestingly, our results showed that ectonucleotidase CD73 expression on CD8+ T cells is upregulated in the absence of CD28 costimulation. In both murine and human tumor-bearing hosts, CD73 is upregulated on CD28−CD8+ T cells that infiltrate the solid tumor. UPLC-MS/MS analysis revealed that CD8+ T cells activation without CD28 costimulation produces elevated levels of adenosine and that CD73 mediates its production. Adenosine receptor antagonists block CD73-mediated suppression. Our data support the notion that CD28 costimulation inhibits CD73 upregulation and thereby prevents CD8+ T cells from becoming suppressive. This study uncovers a previously unidentified role for CD28 costimulation in CD8+ T cell activation and suggests that the CD28 costimulatory pathway can be a potential target for cancer immunotherapy.
Distinctly different reactivity of bis(silylenyl)-versus phosphanyl-silylenyl-substituted o-dicarborane towards O2, N2O and CO2
Authors: Xiong Yun , Yao Shenglai , Ruzicka Ales , Driess Matthias 
Published: May 2021

While the reactions of carborane-based bis-silylene with O2, N2O, and CO2 yield the same Si2O2 containing product, activations of the latter with phosphanyl-silylenyl carborane affords different products featuring SiO, PO, or CO functionalities.
Magnetic flux structuring of the quiet Sun internetwork
Authors: Faurobert M. , Ricort G. 
Published: May 2021

Context. The small-scale magnetism of the quiet Sun has been investigated by various means in recent decades. It is now well established that the quiet Sun contains in total more magnetic flux than active regions and represents an important reservoir of magnetic energy. But the nature and evolution of these fields remain largely unknown.
Aims. We investigate the solar-cycle and center-to-limb variations of magnetic-flux structures at small scales in internetwork regions of the quiet Sun.
Methods. We used Hinode SOT/SP data from the irradiance program between 2008 and 2016. Maps of the magnetic-flux density are derived from the center-of gravity method applied to the circular polarization profiles in the FeI 630.15 nm and FeI 630.25 nm lines. To correct the maps from the instrumental smearing of the telescope, we applied a deconvolution method based on a principal component analysis of the line profiles and on a Richardson-Lucy deconvolution of their coefficients. We took defocus effects and the diffraction of the SOT telescope into account. We then performed a spectral analysis of the spatial fluctuations of the magnetic-flux density in 10″ × 10″ internetwork regions spanning a wide range of latitudes from ±70° to the equator.
Results. At low and mid latitudes the power spectra normalized by the mean value of the unsigned flux in the regions do not vary significantly with the solar cycle. However at solar maximum for one scan in the activity belt showing an enhanced network, a marginal increase in the power of the magnetic fluctuations is observed at granular and larger scales in the internetwork. At high latitudes, we observe variations at granular and larger scales where the power decreases at solar maximum. At all the latitudes the power of the magnetic fluctuations at scales smaller than 0.5″ remains constant throughout the solar cycle.
Conclusions. At the equator the unsigned flux density is related to the vertical component of the magnetic field, whereas at high latitudes this flux density is mainly related to the horizontal component and probe higher altitudes. Our results favor a small-scale dynamo that operates in the internetwork, but they show that the global dynamo also contributes to the internetwork fields. At solar maximum the high-latitude horizontal internetwork fields seem to be depleted from the structures at granular and larger scales that are seen at solar minimum, whereas the internetwork within enhanced network regions show more structures at those scales than at solar minimum.
The management of displaced intracapsular femoral neck fractures at a Sub-Saharan Academic Hospital
Authors: Mukiibi Winifred , Maharaj Zia , Sekeitto Allan Roy , Mokete Lipalo , Pietrzak Jurek Rafal Tomasz 
Published: May 2021

Background: Femoral neck fractures (FNFs) remain “the unsolved fracture” and optimal management is still controversial. The outcomes of hemiarthroplasty (HA) and total hip arthroplasty (THA) in the treatment of FNFs are inconsistent. As demand for management of FNFs continues to grow globally, evaluation of the appropriateness of treatment remains essential, particularly in resource-constrained settings. Methods: We conducted a retrospective chart review of all patients presenting with isolated low energy intracapsular FNFs to an orthopaedic academic unit in Sub-Saharan Africa from January 2016 to April 2019. The decision regarding HA or THA was largely based upon the Sernbo score and ASA classification. The majority of patients with a Sernbo score of ≥15 and ASA class III or better received THA. Results: There were 117 patients (33 male/84 female) 72 years (33–97 years) with FNFs who underwent 56 THA and 61 HA between January 2016 and April 2019. The mean Sernbo score was 15.99 overall (range 8–20) and was 18.95 (11–20) for THA patients compared to 14.46 (8–20) for HA patients (p = 0.042). Time taken from admission to the theatre was 8–19 days (1–22) and 7–61 days (2–31) for HA and THA respectively. The average length of stay (LOS) was 16.04 days and the main reason for same-day cancellations was the lack of post ICU/High Care beds. The 30-day mortality rates were 1.78% and 4.91% for THA and HA patients, respectively (p = 0.07). The mortality rate for patients with a Sernbo score < 15 was 15.38% overall, 8.93% for THA patients, and 21.31% for HA patients, respectively (p = 0.021). Conclusion: The 30-day mortality rate was comparable with published rates from developed countries. There were significant delays in time to theatre, high rates of same-day surgical cancellations, and increased LOS for both HA and THA. These factors play a cumulative role in inflating costs on a strained healthcare system in a developing country. A multidisciplinary approach including the care provision of a specialized geriatric unit is recommended.
Retrospective Study, Level III evidence
Der Nasen- oder Rachenabstrich in der COVID-19-Pandemie – Aspekte für den HNO-Arzt/die HNO-Ärztin – SARS-CoV-2, Coronavirus, Nasenabstrich, Rachenabstrich, Komplikationen
Authors: Deitmer Thomas , Dietz A. , Chaberny I. F. , Pietsch C. 
Published: May 2021

ZusammenfassungSeit Beginn der SARS-CoV-2-Pandemie werden zunehmend Abstriche oder andere Beprobungen aus dem oberen Aerodigestivtrakt genommen, da hier vor allen Dingen in frühen Erkrankungsstadien hohe Viruslasten bestehen. Als diagnostische Möglichkeiten sind Abstriche aus der vorderen Nase, dem Nasopharynx oder dem Oropharynx sowie die Gewinnung von Rachenspülwasser oder Speichel möglich. Als Labormethoden stehen in einigen Minuten ablesbare Antigentests oder langwierigere RT-PCR-Methoden zur Verfügung. Abstriche werden von ärztlichem Personal, medizinischem Fachpersonal, Laien und im Eigentest, jeweils nach Instruktionen, durchgeführt. Auf die Aussagekraft und die Sensitivität des gesamten diagnostischen Prozesses haben somit viele dieser Faktoren einen Einfluss. Die PCR-Labormethode ist sensitiver als die Antigenmethode; der Abstrich aus dem Nasopharynx wird als der valideste Abstrichort angesehen. Eine korrekte Durchführung eines Tests kann auch bei nicht professionellen Personen mit guten Instruktionen erreicht werden. Komplikationen werden bei solchen Abstrichen, gemessen an der anzunehmenden Anzahl durchgeführter Prozeduren, sehr selten berichtet. Kurzfristiges Nasenbluten bei traumatischen Abstrichen ist anzunehmen, ohne dass darüber Publikationen aufgefunden werden konnten. Abgebrochene Abstrichträger mussten HNO-ärztlich entfernt werden. Verletzungen der Schädelbasis mit Liquorrhö wurden bisher sehr vereinzelt berichtet, davon 2-mal bei Anomalien wie Meningozelen. Die Wahl eines geeigneten diagnostischen Mediums hängt von vielen Parametern, wie Verfügbarkeit, zeitlicher Ablauf bis zum Ergebnis, Abstrich durch kundiges Personal oder Eigentest und etlichen anderen praktischen Erwägungen, ab.