bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth Hormone Stops Excessive Inflammation After Partial Hepatectomy, Allowing Liver Regeneration and Survival Through Induction of H2‐Bl/HLA‐G
Authors: Ishikawa Mayumi , Brooks Andrew J. , Fernández‐Rojo Manuel A. , Medina Johan , Chhabra Yash , Minami Shiro , Tunny Kathryn A. , Parton Robert G. , Vivian Julian P. , Rossjohn Jamie , Chikani Viral , Ramm Grant A. , Ho Ken K.Y. , Waters Michael J. 
Published: April 2020

Background and Aims
Growth hormone (GH) is important for liver regeneration after partial hepatectomy (PHx). We investigated this process in C57BL/6 mice that express different forms of the GH receptor (GHR) with deletions in key signaling domains.

Approach and Results
PHx was performed on C57BL/6 mice lacking GHR (Ghr
−/−), disabled for all GH‐dependent Janus kinase 2 signaling (Box1
−/−), or lacking only GH‐dependent signal transducer and activator of transcription 5 (STAT5) signaling (Ghr391
−/−), and wild‐type littermates. C57BL/6 Ghr
−/−mice showed striking mortality within 48 hours after PHx, whereas Box1
−/− or Ghr391
−/− mice survived with normal liver regeneration. Ghr
−/− mortality was associated with increased apoptosis and elevated natural killer/natural killer T cell and macrophage cell markers. We identified H2‐Bl, a key immunotolerance protein, which is up‐regulated by PHx through a GH‐mediated, Janus kinase 2–independent, SRC family kinase–dependent pathway. GH treatment was confirmed to up‐regulate expression of the human homolog of H2‐Bl (human leukocyte antigen G [HLA‐G]) in primary human hepatocytes and in the serum of GH‐deficient patients. We find that injury‐associated innate immune attack by natural killer/natural killer T cell and macrophage cells are instrumental in the failure of liver regeneration, and this can be overcome in Ghr
−/− mice by adenoviral delivery of H2‐Bl or by infusion of HLA‐G protein. Further, H2‐Bl knockdown in wild‐type C57BL/6 mice showed elevated markers of inflammation after PHx, whereas Ghr
−/− backcrossed on a strain with high endogenous H2‐Bl expression showed a high rate of survival following PHx.

Conclusions
GH induction of H2‐Bl expression is crucial for reducing innate immune‐mediated apoptosis and promoting survival after PHx in C57BL/6 mice. Treatment with HLA‐G may lead to improved clinical outcomes following liver surgery or transplantation.
Toll‐like receptor 4 differentially regulates adult hippocampal neurogenesis in an age‐ and sex‐dependent manner
Authors: Connolly Meghan G. , Yost Oriana L. , Potter Opal V. , Giedraitis Megan E. , Kohman Rachel A. 
Published: April 2020

AbstractToll‐like receptor 4 (TLR4) is primarily responsible for initiating an immune response following pathogen recognition. However, TLR4 is also expressed on neural progenitor cells and has been reported to regulate hippocampal neurogenesis as young male TLR4 knockout mice show increases in cell proliferation and doublecortin positive cells. Whether these effects occur in both sexes and are sustained with normal aging is currently unknown. The present study evaluated whether TLR4 deficiency alters adult hippocampal neurogenesis in young (3–4 months) and aged (18–20 months), male and female, TLR4 deficient (TLR4−/−; B6.B10ScN‐Tlr4lps‐del/JthJ) and wild type (WT) mice. Additionally, neurogenesis within the dorsal and the ventral hippocampal subdivisions was evaluated to determine if TLR4 has differential effects across the hippocampus. Bromodeoxyuridine (BrdU) was administered to quantify new cell survival as well as cell differentiation. Ki‐67 was measured to evaluate cell proliferation. Results show that young TLR4−/− females had higher rates of proliferation and neuronal differentiation in both the dorsal and ventral hippocampus relative to WT females. Young TLR4−/− males show elevated proliferation and neuronal differentiation mainly in the ventral hippocampus. While young TLR4−/− mice show enhanced neurogenesis compared to young WT mice, the increase was not apparent in the aged TLR4−/− mice. Both aged WT and TLR4−/− mice showed a decrease in proliferation, new cell survival, and neuronal differentiation compared to young WT and TLR4−/− mice. The data collectively indicate that TLR4 regulates hippocampal neurogenesis in young adults, but that these effects are region‐specific in males and that females show broader changes in neurogenesis throughout the hippocampus.
Solvent‐based paint and varnish removers: a focused toxicologic review of existing and alternative constituents
Authors: Durrani Timur , Clapp Robert , Harrison Robert , Shusterman Dennis 
Published: April 2020

AbstractPaint and varnish removers constitute a major potential source of organic solvent exposure to contractors and home improvement enthusiasts. Unfortunately, the leading paint remover formulations have traditionally contained, as major ingredients, chemicals classified as probable human carcinogens (eg, methylene chloride) or reproductive toxicants (eg, N‐methylpyrrolidone). In addition, because of its unique toxicology (ie, hepatic conversion to carbon monoxide compounding generic solvent narcosis and arrythmogenesis), high volatility, and rigorous requirements for personal protective equipment, methylene chloride exposures from paint removers have been linked to numerous deaths involving both occupational and consumer usage. The aim of this review is to summarize the known toxicology of solvent‐based paint remover constituents (including those found in substitute formulations) in order to provide health risk information to regulators, chemical formulators, and end‐users of this class of products, and to highlight any data gaps that may exist.
Visualization of Mineral-Targeted Alkaline Phosphatase Binding to Sites of Calcification In Vivo
Authors: Amadeu de Oliveira Flavia , Narisawa Sonoko , Bottini Massimo , Millán José Luis 
Published: April 2020

ABSTRACT
A mineral-targeted form of recombinant tissue-nonspecific alkaline phosphatase (TNAP), asfotase alfa, was approved multinationally as an enzyme replacement therapy for hypophosphatasia in 2015. Two reports to date have shown evidence of binding of this drug to mineralizing tissues using histochemistry and immunohistochemistry. Here, we sought to expand on those earlier studies by directly visualizing the in vivo binding of asfotase alfa conjugated with AnaTag HiLyte Fluor 750 or Alexa Fluor 647 fluorescent dye to sites of skeletal/dental mineralization and ectopic calcification. We utilized 40-day-old Tagln-Cre; HprtALPL/Y mice, a model of severe medial vascular calcification; Tie2-Cre; HprtALPL/Y mice, a model of severe intimal calcification; and sibling WT HprtALPL/Y mice, devoid of soft-tissue calcification. A single dose of 8 mg/kg labeled asfotase alfa was injected via the retro-orbital route. Skeletal tissues and soft organs were imaged ex vivo 2 days after the injection. Strong fluorescence signal was observed in all skeletal tissues (calvaria, vertebra, long bones, jaw, and mandibles) from mutant and WT mice. Fluorescence analysis of histological sections from bones revealed strong binding of asfotase alfa. Asfotase alfa binding to sites of ectopic calcification in the heart, aorta, and renal artery were found in both the Tagln-Cre; HprtALPL/Y and Tie2-Cre; HprtALPL/Y mice but not in WT mice. In addition, asfotase alfa binding was also found in the kidney stroma and brain of the Tie2-Cre; HprtALPL/Y mice. Our results show that fluorescence-labeled asfotase alfa administered in vivo binds not only to sites of skeletal and dental mineralization but also to sites of ectopic calcification in these animal models. © 2020 American Society for Bone and Mineral Research.
Commutability of external quality assessment materials for point‐of‐care glucose testing using the Clinical and Laboratory Standards Institute and International Federation of Clinical Chemistry approaches
Authors: Wang Yan , Plebani Mario , Sciacovelli Laura , Zhang Shunli , Wang Qingtao , Zhou Rui 
Published: April 2020

AbstractObjectivesThe aim of this study was to assess the commutability of three external quality assessment (EQA) materials for point‐of‐care (POC) glucose testing using two approaches, to identify suitable EQA materials to evaluate and monitor the quality of POC testing.MethodsCommercial control materials (CCMs), pooled human serum samples (PHSs), and homemade human whole‐blood samples (HWBs) were measured along with 33 individual clinical samples using five POC instruments and a Hitachi 7600 analyzer. Data were analyzed by Deming regression analysis with a 95% prediction interval as described in Clinical and Laboratory Standards Institute (CLSI) EP30‐A, and by difference in bias analysis as described by the International Federation of Clinical Chemistry (IFCC) Working Group on Commutability.ResultsUsing the CLSI approach, HWBs, CCMs, and PHSs were commutable with five, one, and two instruments, respectively. With the IFCC approach, HWBs were commutable with two instruments, while CCMs and PHSs were largely inconclusive or non‐commutable on five instruments.ConclusionsHWBs were commutable on all instruments by the CLSI approach and may be a suitable EQA material for POC testing. Although some results differed between the IFCC and CLSI approaches, both indicated that HWBs were far superior to CCMs and PHSs in commutability.
The roles of GRP81 as a metabolic sensor and inflammatory mediator
Authors: Hu Jingyun , Cai Ming , Liu Yuran , Liu Beibei , Xue Xiangli , Ji Ruifang , Bian Xuepeng , Lou Shujie 
Published: April 2020

AbstractGPR81 (also named as HCA1) is a member of a subfamily of orphan G‐protein coupled receptors (GPCRs), coupled to Gi‐type G proteins. GPR81 was discovered in 2001 and identified as the only known endogenous receptor of lactate under physiological conditions in 2008, which opened a new field of research on how lactate may act as a signal molecule along with the GPR81 expression in the roles of metabolic process and inflammatory response. Recent studies showed that the physiological functions of GPR81 include lipid metabolism in adipose tissues, metabolic excitability in the brain, cellular development, and inflammatory response modulation. These findings may reveal a novel therapeutic strategy to treat clinical, metabolic, and inflammatory diseases. This article will summarize past research on GPR81, including its characteristics of distribution and expression, functional residues, pharmacological, and physiological agonists, involvement in signal transduction, and pharmacological applications.
Efficacy and safety of renal denervation in addition to pulmonary vein isolation for atrial fibrillation and hypertension—Systematic review and meta‐analysis of randomized controlled trials
Authors: Pranata Raymond , Vania Rachel , Raharjo Sunu Budhi 
Published: April 2020

AbstractIntroductionThis systematic review and meta‐analysis aimed to assess the latest evidence on the use of renal denervation (RDN) + pulmonary vein isolation (PVI) compared to PVI alone for treating atrial fibrillation (AF) with hypertension.MethodsA systematic literature search from several electronic databases was performed up until January 2020. The primary outcome was AF recurrence defined as AF/atrial flutter (AFL)/atrial tachycardia (AT) ≥30 seconds at 12‐month follow‐up and the secondary outcome was procedure‐related complications.ResultsThere were 568 subjects from five studies. AF recurrence was 90/280 (32.1%) in the RDN + PVI group and 142/274 (51.8%) in the PVI group. RDN + PVI was associated with a lower incidence of AF recurrence (RR 0.62 [0.51, 076], P < .001; I2: 0%). Pooled analysis of HR showed that RDN + PVI was associated with reduced AF recurrence (HR 0.51 [0.38, 0.70], P < .001; I2: 0%). Complications were 7/241 (2.9%) in the RDN + PVI group and 8/237 (3.4%) in the PVI group. The rate of complications between the groups was similar (RR 0.87 [0.33, 2.29], P = .77; I2: 0%). In the subgroup analysis of paroxysmal AF, RDN + PVI was shown to reduce AF recurrence (RR 0.64 [0.49, 0.82], P < .001; I2: 0% and HR 0.56 [0.38, 0.82], P = .003; I2: 0%) compared to PVI alone. RDN + PVI has a moderate certainty of evidence in the reducing AF recurrence with an absolute reduction of 197 fewer per 1000 (from 254 fewer to 124 fewer).ConclusionRDN in addition to PVI, is associated with reduced 12‐month AF recurrence and similar procedure‐related complications compared to PVI alone.
Determining the Bio‐Based Carbon Content of Surfactants
Authors: Mudge Stephen M. , Tropsch Juergen , Beaudouin Thierry , Séné Christophe , Hormazabal Horacio 
Published: April 2020

AbstractIn response to a mandate from the European Commission, the European Committee for Standardization (CEN) called on the technical committee CEN/TC 276 to develop a European standard (EN 17035) to define bio‐based surfactants and enable quantification of the bio‐based carbon content of surfactants based on radiocarbon analyses. This analytical approach was tested through directly contracted analyses and through a round robin procedure at commercial facilities in Europe. Initial results were unsatisfactory and further investigation identified issues surrounding the degree of homogenization in the samples. In general, the samples were only homogeneous at the gram level while the maximum quantity of material that could be introduced to the analytical process was at the milligram level. Having identified the root cause of the discrepancies between measured and expected results, new samples were sent to six European laboratories. The results were satisfactory indicating linearity and accuracy across the measurement range.
Effect of the Combination of Different Electrode Spacings and Power on Bipolar Radiofrequency Fat Dissolution: A Computational and Experimental Study
Authors: Zang Lianru , Zhou Yu , Kang Jia , Song ChengLi 
Published: April 2020

Background and ObjectivesThe finite element method was used, and experiments were performed to analyze the effect of different electrode spacings and power combinations on the electrical and thermal aspects of biological tissues during bipolar radiofrequency (RF) fat dissolution. Through these efforts, this study also attempted to develop a reasonable electrode spacing and power combination that can achieve fat dissolution effects, the RF energy of which will not thermally damage the tissue.Study Design/Materials and MethodsCOMSOL was adopted to conduct a finite element analysis for bio‐thermoelectric coupling, and a two‐dimensional time‐domain model of biological tissue was built. A self‐developed single‐channel bipolar RF device was employed to load RF energy on the ex vivo porcine abdominal tissue. The thermal characteristics of the tissue were characterized and analyzed with a thermal imager and thermocouple probes.ResultsUnder a power of 5 W combined with the electrode spacings of 1, 2, and 3 cm, the temperature in the tissue could not reach that required for fat dissolution. Under a power of 15 W combined with the electrode spacings of 1, 2, and 3 cm, the RF energy would thermally damage part of the skin areas. Besides this, the combination of a power of 10 W and the electrode spacing of 1 cm would thermally damage the skin areas. The combination of a power of 10 W and the electrode spacing of 2 or 3 cm made part of the fat layer of the tissue satisfy the requirements of fat dissolution, and the fat dissolution area caused by the former was 118% larger than that of the latter; in the meantime, no heat damage to the skin layer was found.ConclusionDifferent electrode spacings and power combinations significantly affect the electrical and thermal properties of bipolar RF energy loaded on biological tissue, a reasonable electrode spacing and power combination is one of the critical factors leading to the success of bipolar RF fat dissolution. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.
Structural Correlates of the Sensorimotor Cerebellum in Parkinson's Disease and Essential Tremor
Authors: Lopez Alexander M. , Trujillo Paula , Hernandez Adreanna B. , Lin Ya‐Chen , Kang Hakmook , Landman Bennett A. , Englot Dario J. , Dawant Benoit M. , Konrad Peter E. , Claassen Daniel O. 
Published: April 2020

AbstractBackgroundParkinson's disease (PD) and essential tremor (ET) are commonly encountered movement disorders. Pathophysiologic processes that localize to the cerebellum are described in both. There are limited studies investigating cerebellar structural changes in these conditions, largely because of inherent challenges in the efficiency of segmentation.MethodsWe applied a novel multiatlas cerebellar segmentation method to T1‐weighted images in 282 PD and 111 essential tremor patients to define 26 cerebellar lobule volumes. The severity of postural and resting tremor in both populations and gait and postural instability in PD patients were defined using subscores of the UPDRS and Washington Heights‐Inwood Genetic Study motor scales. These clinical measurements were related to lobule volume size. Multiple comparisons were controlled using a false discovery rate method.ResultsGroup differences were identified between ET and PD patients, with reductions in deep cerebellar nucleus volume in ET versus reduced lobule VI volume in PD. In ET patients, lobule VIII was negatively correlated with the severity of postural tremor. In PD patients, lobule IV was positively correlated with resting tremor and total tremor severity. We observed differences in cerebellar structure that localized to sensorimotor lobules of the cerebellum. Lobule volumes appeared to differentially relate to clinical symptoms, suggesting important clinicopathologic distinctions between these conditions. These results emphasize the role of the cerebellum in tremor symptoms and should foster future clinical and pathologic investigations of the sensorimotor lobules of the cerebellum. © 2020 International Parkinson and Movement Disorder Society
An improved target detection method based on multiscale features fusion
Authors: Lu Liping , Li Hanshan , Ding Zhe , Guo Quanmin 
Published: April 2020

AbstractA pedestrian‐target detection method based on multiscale convolution features is proposed to solve the problem of the existing target detection algorithms based on convolutional neural networks that cannot effectively adapt to the target scale change, its deformation, and the complex environment. This article analyzes the characteristics of small target, establishes the a three‐layer pyramid network structure based on horizontal connection fusion, and makes full use of shallow convolution features with lower semantics to improve the accuracy of small target detection; From the angle of the cross ratio, quantitative analysis is made on the effect of eliminating redundant bounding box by nonmaximum suppression based on center point when the window with the cross ratio is less than 0.7, solves the problem of missing detection of overlap and small target, and improves the target detection accuracy and the generalization ability of the target detection model. Through the experimental results on VOC2007 and VOC2012 public data sets, the proposed method of this article has higher detection accuracy and stability for small and incomplete targets, multiscale target detection, and target classification under the complex environment.
Combining Antidepressants with β‐Blockers: Evidence of a Clinically Significant CYP2D6 Drug Interaction
Authors: Shin Jaekyu , Hills Nancy K. , Finley Patrick R. 
Published: April 2020

BackgroundThe β‐blockers and antidepressants are two of the most commonly prescribed drug classes in the United States. Several antidepressants are potent inhibitors of cytochrome P450 2D6 liver enzymes (CYP2D6) and can increase the plasma concentrations of certain β‐blockers when administered concomitantly, potentially leading to serious medical consequences such as hypotension, bradycardia, and falls.ObjectiveThe primary objective of this investigation was to determine whether initiating an antidepressant in patients receiving β‐blockers increased the risk of hemodynamic adverse events. Our primary outcome was time to hospital admissions or emergency department (ED) visits for an International Classification of Diseases‐9 diagnosis suggestive of excessive β‐blockade.MethodsWe conducted a survival analysis for adults continuously enrolled in the California Medicaid system (Medi‐Cal) between 2004 and 2012. Eligible patients were required to be receiving β‐blocker medications that are primarily CYP2D6 substrates (e.g., metoprolol, propranolol, or carvedilol). Univariate and multivariable analyses were performed for patients who concurrently received antidepressants with β‐blockers. An additional multivariable analysis analyzed the association of this combination upon hospitalizations or ED visits for all causes.ResultsA total of 21,292 beneficiaries met the inclusion criteria, and 4.3% of patients required hospitalization or ED visits within 30 days of co‐medication. In multivariable analysis, patients receiving antidepressants with moderate to strong CYP2D6 inhibitory potential (fluoxetine, paroxetine, duloxetine, or bupropion) had a greater risk for hospitalization or ED visits for hemodynamic events than those initiated on antidepressants with weak CYP2D6 inhibition for 30 days or less when each was compared with patients receiving no antidepressants (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.03–2.81; p=0.04 vs HR 1.24; 95% CI 0.82–1.88; p=0.30). Other demographic variables associated with increased morbidity included advanced age, male sex, higher β‐blocker doses, and African American race or Hispanic ethnicity.ConclusionsResults of this analysis suggest that initiation of certain antidepressants was associated with an increased risk for serious medical sequelae among patients concurrently receiving β‐blockers. Greater risk was observed with antidepressants that potently inhibit the CYP2D6 enzyme, implying that increased morbidity may be mediated by a metabolic drug interaction.
On the design of control charts with guaranteed conditional performance under estimated parameters
Authors: Does Ronald J.M.M. , Goedhart Rob , Woodall William H. 
Published: April 2020

AbstractWhen designing control charts the in‐control parameters are unknown, so the control limits have to be estimated using a Phase I reference sample. To evaluate the in‐control performance of control charts in the monitoring phase (Phase II), two performance indicators are most commonly used: the average run length (ARL) or the false alarm rate (FAR). However, these quantities will vary across practitioners due to the use of different reference samples in Phase I. This variation is small only for very large amounts of Phase I data, even when the actual distribution of the data is known. In practice, we do not know the distribution of the data, and it has to be estimated, along with its parameters. This means that we have to deal with model error when parametric models are used and stochastic error because we have to estimate the parameters. With these issues in mind, choices have to be made in order to control the performance of control charts. In this paper, we discuss some results with respect to the in‐control guaranteed conditional performance of control charts with estimated parameters for parametric and nonparametric methods. We focus on Shewhart, exponentially weighted moving average (EWMA), and cumulative sum (CUSUM) control charts for monitoring the mean when parameters are estimated.