bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproducibility of a battery of human evoked pain models to detect pharmacological effects of analgesic drugs
Authors: Siebenga Pieter S. , van Amerongen Guido , Okkerse Pieter , Denney William S. , Dua Pinky , Butt Richard P. , Hay Justin L. , Groeneveld Geert J.
Published: February 2019

Background

Although reproducibility is considered essential for any method used in scientific research, it is investigated only rarely; thus, strikingly little has been published regarding the reproducibility of evoked pain models involving human subjects. Here, we studied the reproducibility of a battery of evoked pain models for demonstrating the analgesic effects of two analgesic compounds.

Methods

A total of 81 healthy subjects participated in four studies involving a battery of evoked pain tests in which mechanical, thermal and electrical stimuli were used to measure pain detection and tolerance thresholds. Pharmacodynamic outcome variables were analysed using a mixed model analysis of variance, and a coefficient of variation was calculated by dividing the standard deviation by the least squares means.

Results

A total of 76 subjects completed the studies. After being administered pregabalin, the subjects’ pain tolerance thresholds in the cold pressor and pressure stimulation tests were significantly increased compared to the placebo group. Moreover, the heat pain detection threshold in UVB‐irradiated skin was significantly increased in subjects who were administered ibuprofen compared to the placebo group. Variation among all evoked pain tests ranged from 2.2% to 30.6%.

Conclusions

Four studies using a similar design showed reproducibility with respect to the included evoked pain models. The relatively high consistency and reproducibility of two analgesics at doses known to be effective in treating clinically relevant pain supports the validity of using this pain test battery to investigate the analgesic activity and determine the active dosage of putative analgesic compounds in early clinical development.

Significance

The consistency and reproducibility of measuring the profile of an analgesic at clinically relevant doses illustrates that this pain test battery is a valid tool for demonstrating the analgesic activity of a test compound and for determining the optimal active dose in early clinical drug development.
Co0.5Ni0.5MoO4 Double‐Shelled Hollow Spheres with Enhanced Electrochemical Performance for Supercapacitors and Lithium‐Ion Batteries
Authors: Li Lun , Chen Wei , Luo Wen , Xiao Zhitong , Zhao Yunlong , Owusu Kwadwo Asare , Liu Zhenhui , Zhou Liang , Mai Liqiang
Published: February 2019

Transition metal molybdates represent a promising family of electrode materials for supercapacitors and lithium‐ion batteries (LIBs). Herein, Co0.5Ni0.5MoO4 double‐shelled hollow spheres (DSHSs) are synthesized using a simple and scalable spray‐drying method followed by calcination in air. Benefited from the unique hollow structure as well as the coexistence of Co and Ni, the as‐synthesized Co0.5Ni0.5MoO4 DSHSs exhibit an improved pseudocapacitive property with a specific capacitance of 731 F g−1 at 0.5 A g−1 and a high capacitance retention of 91% (10 A g−1) after 5000 cycles. In addition, the obtained Co0.5Ni0.5MoO4 DSHSs also manifest a high specific capacity (900 mAh g−1 at 0.2 A g−1 after 50 cycles) and an excellent cyclability (756 mAh g−1 at 1 A g−1 after 1000 cycles) for lithium storage. This rational design on both component and structure provides an effective strategy to achieve high‐performance supercapacitors and LIBs.
On the correction of spectra by a displacement reduction factor in direct displacement‐based seismic design and assessment
Authors: Calvi Gian Michele
Published: February 2019

The application of some design and assessment approaches, such as the direct displacement‐based design (DDBD) and the capacity spectrum methods, requires the modification of elastic design spectra by some displacement reduction factor, to account for the appropriate energy dissipation capacity of different structures.

While several equations to correlate dissipation and hysteresis cycles are available, once the displacement reduction factor has been obtained, the correction of the spectra is operated reducing the displacement demand accordingly and conserving the period of vibration at each point.

This procedure is here discussed and proved to be conceptually inappropriate, because the spectral acceleration rather than the period should be kept at each point. The application of this alternative procedure may result in increased shear strength demand in design and in larger required displacement capacity for the same level of strength in assessment, if all other factors are not modified.

However, the calibration of the reduction factors applied in DDBD has been extensive, and the method has proved to be effective in predicting displacement demands consistent with those resulting from refined nonlinear time history analysis; therefore, a possible introduction of the proposed correction will require equally extensive studies and possibly compensating corrections in the calculation of the equivalent damping.

On the contrary, an appropriate calibration of the factors to be used in the application of the “capacity spectrum” method is still being developed, and the consideration of a constant acceleration may facilitate the derivation of effective equations.
Supercritical CO2 adsorption in a simulated deep coal reservoir environment, implications for geological storage of CO2 in deep coals in the southern Qinshui Basin, China
Authors: Han Sijie , Sang Shuxun , Liang Jingjing , Zhang Jinchao
Published: February 2019

CO2 sequestration in deep, unmineable coal seams has been proposed as a method for offsetting increasing anthropogenic CO2 emissions, while increasing natural gas production. Through laboratory experiments on gaseous/supercritical CO2 adsorption using a manometric procedure, we investigated anomalies in supercritical CO2 adsorption and determined CO2 density‐temperature effects on adsorption capacity, which are closely related to the CO2 storage potential in deep coal reservoirs. Results indicate that the revised Dubinin‐Radushkevich (D‐R) model can fit supercritical CO2 adsorption data well, and there is a significant difference between excess and absolute adsorption capacity as CO2 density increases. In the supercritical isochore, a rapid change in CO2 density results in a transition from Langmuir‐like monolayer adsorption to multilayer adsorption, and there is an unsaturated multilayer system during this transition. Above the temperature at the cross point, the increasing of density decreases, and a negative dependence on temperature causes a gradual decrease in adsorption capacity. Coal reservoirs near the boundary between the supercritical isochore stage and fully supercritical CO2 stage should be the prime target for geological storage of CO2. In order to better understand supercritical CO2 adsorption behavior and identify target coal seams, further supercritical CO2 adsorption experiments are needed in the southern Qinshui Basin.
Robust meta‐analysis of biobank‐based genome‐wide association studies with unbalanced binary phenotypes
Authors: Dey Rounak , Nielsen Jonas B. , Fritsche Lars G. , Zhou Wei , Zhu Huanhuan , Willer Cristen J. , Lee Seunggeun
Published: February 2019

With the availability of large‐scale biobanks, genome‐wide scale phenome‐wide association studies are being instrumental in discovering novel genetic variants associated with clinical phenotypes. As increasing number of such association results from different biobanks become available, methods to meta‐analyse those association results is of great interest. Because the binary phenotypes in biobank‐based studies are mostly unbalanced in their case–control ratios, very few methods can provide well‐calibrated tests for associations. For example, traditional Z‐score‐based meta‐analysis often results in conservative or anticonservative Type I error rates in such unbalanced scenarios. We propose two meta‐analysis strategies that can efficiently combine association results from biobank‐based studies with such unbalanced phenotypes, using the saddlepoint approximation‐based score test method. Our first method involves sharing the overall genotype counts from each study, and the second method involves sharing an approximation of the distribution of the score test statistic from each study using cubic Hermite splines. We compare our proposed methods with a traditional Z‐score‐based meta‐analysis strategy using numerical simulations and real data applications, and demonstrate the superior performance of our proposed methods in terms of Type I error control.
Southward subduction of the Mongolia–Okhostk Ocean: Insights from Early–Middle Triassic intrusive rocks from the Jiawula–Tsagenbulagen area in NE China
Authors: Dai Meng , Yan Guangsheng , Liu Cui , Deng Jinfu , Li Yongsheng , Jia Wenbin , Lai Chun‐Kit
Published: February 2019

New zircon U–Pb age data, Hf isotopes, whole‐rock major and trace elements, and Sr–Nd isotopic data for Early–Middle Triassic intrusive rocks from the Jiawula and Tsagenbulagen area in the southern part of the Erguna Massif provide valuable constraints on the southward subduction of the Mongolia–Okhostk Ocean lithosphere. The Jiawula–Tsagenbulagen granitoids mainly consist of granodiorite, quartz monzonite, and biotite granite. These granitoids, long believed to be mainly Late Jurassic–Early Cretaceous (ca. 150–139 Ma) and minor Permian (ca. 278 Ma and 254–253 Ma), are newly found to contain a latest Early Triassic to Middle Triassic generation (zircon U–Pb age: ca. 248–244 Ma). Geochemically, the Early to Middle Triassic granitoids are characterized by high SiO2 (74–77 wt.%) and Al2O3 (12.2–15.95 wt.%), low Mg# values (12.98–37.32), and variable Na2O/K2O ratios (0.62–1.75). They are metaluminous to peraluminous and belong to the high‐K calc‐alkaline series. Moreover, they show enrichment in light rare earth elements and large‐ion lithophile elements and depletion in heavy rare earth elements and high‐field‐strength elements (e.g., Nb, Ta, and Ti). They have an increased amount of SiO2/Al2O3 but lower V/Th ratios and negative correlations between V/Th and SiO2/Al2O3 ratios, indicating that the magmas experienced various degrees of biotite and/or plagioclase fractional crystallization. Their whole‐rock εNd(t) and zircon εHf(t) values ranged from +1.07 to +4.15 and from +0.5 to +2.9, respectively, indicating that the primary magmas were probably generated by partial melting of juvenile crustal material with the help of mantle‐derived mafic magmas. These magmas subsequently underwent fractional crystallization, magma mixing, and a small amount of crustal contamination during their emplacement. The geochemical characteristics of these Early–Middle Triassic intrusive rocks have affinities with intrusive rocks from active continental margin settings. Therefore, we conclude that the Early–Middle Triassic magmatism in the Erguna Massif was generated within an Andean‐type arc setting related to the southwards subduction of the Mongol–Okhotsk oceanic plate beneath the Erguna Massif. We summarized previous age data of the Early to Late Triassic magmatic rocks from Erguna and Central Mongolia and identified arc setting granites and post‐orogenic granites. Thus, a tectonic evolutionary model was proposed for the geological observations in the Erguna and Central Mongolia massifs, involving the Triassic continuous southward subduction in the Erguna Massif and the Late Triassic slab‐rollback and back‐arc basin extension in the south‐eastern Central Mongolia Massif.
Comparison of Bethesda cytopathology classification to surgical pathology across racial‐ethnic groups
Authors: Bresler Amishav , Mehta Vikas , Schiff Bradley A. , Smith Richard V. , Khader Samer , Ramos‐Rivera Gloria , Lin Juan , Libutti Steven K. , Laird Amanda M. , Ow Thomas J.
Published: February 2019

Background

The Bethesda System standardized the reporting of thyroid cytopathology and created categories to provide an estimation of a nodule's risk of malignancy. There are limited data describing their utility in different racial‐ethnic groups.

Methods

A retrospective chart review of thyroid fine‐needle aspirations (FNA) was performed within our health‐care systems. Sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPVs) were calculated for the total cohort, and racial‐ethnic groups.

Results

The sensitivity, specificity, PPV, and NPV of the entire cohort was 93%, 77%, 57%, and 97%. Among patients who underwent surgery, African Americans contained a high number of Bethesda II FNAs (63%) compared to Hispanics (48%) and whites (45%). The sensitivity, specificity, and NPV were comparable among groups, the PPV was lowest for African Americans (43%), followed by Hispanics (60%) and whites (69%).

Conclusions

The Bethesda system's predictive value may differ among racial‐ethnic groups.
Switching between persistent firing and depolarization block in individual rat CA1 pyramidal neurons
Authors: Knauer Beate , Yoshida Motoharu
Published: February 2019

The hippocampal formation plays a role in mnemonic tasks and epileptic discharges in vivo. In vitro, these functions and malfunctions may relate to persistent firing (PF) and depolarization block (DB), respectively. Pyramidal neurons of the CA1 field have previously been reported to engage in either PF or DB during cholinergic stimulation. However, it is unknown whether these cells constitute disparate populations of neurons. Furthermore, it is unclear which cell‐specific peculiarities may mediate their diverse response properties. However, it has not been shown whether individual CA1 pyramidal neurons can switch between PF and DB states. Here, we used whole cell patch clamp in the current clamp mode on in vitro CA1 pyramidal neurons from acutely sliced rat tissue to test various intrinsic properties which may provoke individual cells to switch between PF and DB. We found that individual cells could switch from PF to DB, in a cholinergic agonist concentration dependent manner and depending on the parameters of stimulation. We also demonstrate involvement of TRPC and potassium channels in this switching. Finally, we report that the probability for DB was more pronounced in the proximal than in the distal half of CA1. These findings offer a potential mechanism for the stronger spatial modulation in proximal, compared to distal CA1, as place field formation was shown to be affected by DB. Taken together, our results suggest that PF and DB are not mutually exclusive response properties of individual neurons. Rather, a cell's response mode depends on a variety of intrinsic properties, and modulation of these properties enables switching between PF and DB.
Perspectives of beneficiaries, health service providers, and community members on a maternal and child health conditional cash transfer pilot programme in Nigeria
Authors: Oduenyi Chioma , Ordu Victor , Okoli Ugo
Published: February 2019

Background

Our paper presents experiences and perceptions of beneficiaries, health service providers, and community members about a conditional cash transfer (CCT) programme piloted in Nigeria from April 2013 to May 2015 to boost demand for maternal, newborn, and child health services.

Methods

We conducted a descriptive cross‐sectional retrospective study using both qualitative and quantitative methods. Personal interviews and focus group discussions (FGDs) were conducted between June and July 2015 for 314 CCT beneficiaries, 72 ward development committee (WDC) members, and 60 service providers (midwives, community health extension workers [CHEWs], and village health workers [VHWs]) including 29 officers‐in‐charge as key informants. Content analysis was applied to qualitative findings and grouped into themes of attitude, practices, CCT operations, payout, and perceived impact.

Results

Over 97% of beneficiaries affirmed that the cash incentive was very helpful and almost 70% opined that the free supply‐side services were the real benefit. Majority of service providers applauded the programme though, with complaints about the increased workload. Community members applauded the scheme, with mixed feelings over some operational processes.

Conclusion

Beneficiaries, service providers, and community members expressed deep satisfaction with the CCT programme and opined that antenatal care (ANC) and skilled birth delivery service utilization increased. Insights into some programmatic challenges are provided to enrich future CCT design and implementation.
Modelling PTSD diagnosis using sleep, memory, and adrenergic metabolites: An exploratory machine‐learning study
Authors: Breen Michael S. , Thomas Kevin G.F. , Baldwin David S. , Lipinska Gosia
Published: February 2019

Objective

Features of posttraumatic stress disorder (PTSD) typically include sleep disturbances, impaired declarative memory, and hyperarousal. This study evaluated whether these combined features may accurately delineate pathophysiological changes associated with PTSD.

Method

We recruited a cohort of PTSD‐diagnosed individuals (N = 20), trauma survivors without PTSD (TE; N = 20), and healthy controls (HC; N = 20). Analyses of between‐group differences and support vector machine (SVM)‐learning were applied to participant features.

Results

Analyses of between‐group differences replicated previous findings, indicating that PTSD‐diagnosed individuals self‐reported poorer sleep quality, objectively demonstrated less sleep depth, and evidenced declarative memory deficits in comparison to HC. Integrative SVM‐learning distinguished HC from trauma participants with 80% accuracy using a combination of five features, including subjective and objective sleep, neutral declarative memory, and metabolite variables. PTSD and TE participants could be distinguished with 70% accuracy using a combination of subjective and objective sleep variables but not by metabolite or declarative memory variables.

Conclusion

From among a broad range of sleep, cognitive, and biochemical variables, sleep characteristics were the primary features that could differentiate those with PTSD from those without. Our exploratory SVM‐learning analysis establishes a framework for future sleep‐ and memory‐based PTSD investigations that could drive improvements in diagnostic accuracy and treatment.
A Comprehensive Review on Pronephrium penangianum
Authors: Zhou Qi , Jian Yuqing , Yi Pan , Sun Jing , Zhou Xiaoling , Chen Shenghuang , Wang Wei
Published: February 2019

A fern, Pronephrium penangianum (Hook.) Holtt., is a highly reputable medicinal plant in tujia ethenomedicine. It has good effect on relaxing muscles and tendons to promoting blood circulation, stanching bleeding and relieving pain in tujia system of medicine. In order to evaluate this traditional plant in a modern perspective, the current review presents essential aspects of Pronephrium penangianum including traditional uses, geographical distribution, chemical constituents, pharmacological studies and standardization. The chemical composition of the herb comprised of flavonoids, phenolic acids, lignans, etc. However, so far there has been few concrete published papers that explicate its chemical therapeutic basis according to Sci‐Finder database and its identification and standardization still remains unknown. This review is intended to summarize the published information of this fern and discuss the current problems for the further studies.
The size premium and macrovolatility risks: Evidence from U.S. and U.K. equity markets
Authors: Cho Sungjun
Published: February 2019

The size effect is alive well but visible only when the economy is in high volatility regimes. This paper develops variant conditional asset pricing tests for the size effect with independent business cycle and volatility regimes and shows that the size effect is present conditionally during the high‐volatility regimes. This result is robust across two countries (United States and United Kingdom) with various specifications and the January effect. An economic rationale for the relation between the size premium and macrovolatility risk is provided through the capital‐market‐imperfection hypothesis.
Living‐donor kidney transplantation in an end‐stage renal disease patient with situs inversus totalis: Three case reports
Authors: Ochi Atsuhiko , Unagami Kohei , Akanuma Takafumi , Inoue Takahiro , Okada Daigo , Fan Bo , Suzuki Tomo , Abe Hirokazu , Okumi Masayoshi , Ishida Hideki , Tanabe Kazunari
Published: February 2019

Introduction

Only few cases of renal dysfunction in patients with situs inversus totalis have been reported. Thus, studies on kidney transplantation in patients with this condition are still limited.

Case presentation

We present three cases of end‐stage renal disease patients with situs inversus totalis: a 30‐year‐old man, 21‐year‐old woman, and 31‐year‐old man. Each left living‐donor kidney was transplanted in the right iliac fossa in the usual way. Because of the anatomical reversal and right external iliac vein being deep, the internal iliac vein was cut for venous anastomosis in one patient. Another one patient developed temporary congestive kidney, which was speculated to be due to poor blood flow in the renal vein. All recipients could be weaned off dialysis, with stable allograft function.

Conclusion

Kidney transplantation in patients with situs inversus totalis is the same as anatomical normal cases, except that attention is paid to venous anastomosis.
An open‐source code for Mie extinction extended multiplicative signal correction for infrared microscopy spectra of cells and tissues
Authors: Solheim Johanne H. , Gunko Evgeniy , Petersen Dennis , Großerüschkamp Frederik , Gerwert Klaus , Kohler Achim
Published: February 2019

Infrared spectroscopy of single cells and tissue is affected by Mie scattering. During recent years, several methods have been proposed for retrieving pure absorbance spectra from such measurements, while currently no user‐friendly version of the state‐of‐the‐art algorithm is available. In this work, an open‐source code for correcting highly scatter‐distorted absorbance spectra of cells and tissues is presented, as well as several improvements of the latest version of the Mie correction algorithm based on extended multiplicative signal correction (EMSC) published by Konevskikh et al. In order to test the stability of the code, a set of apparent absorbance spectra was simulated. To this purpose, pure absorbance spectra based on a Matrigel spectrum are simulated. Scattering contributions where obtained by mimicking the scattering features observed in a set of experimentally obtained spectra . It can be concluded that the algorithm is not depending strongly on the reference spectrum used for initializing the algorithm and retrieves well the underlying pure absorbance spectrum. The calculation time of the algorithm is considerably improved with respect to the resonant Mie scattering EMSC algorithm used by the community today.
CERNA2: A predictor for clinical progression and poor prognosis in cervical carcinoma
Authors: Wang Min , Ouyang Jianghua , Li Huali
Published: February 2019

Competing long noncoding RNA 2 (lncRNA 2) for microRNA let‐7b (CERNA2) has emerged as an important regulator of tumorigenesis and cancer progression but the clinical value and regulatory function of CERNA2 is yet to be investigated in cervical carcinoma. In our study, we found the CERNA2 expression was obviously increased in cervical carcinoma tissues compared with adjacent normal cervical tissues. In addition, we observed that metastatic lymph nodes exhibited high levels of CERNA2 expression in contrast to primary cervical carcinoma tissues. Furthermore, high CERNA2 expression was associated with advanced clinical stage, lymph node metastasis, distant metastasis poor histological grade, and short overall survival in cervical carcinoma patients. Moreover, high CERNA2 expression acted as an independent unfavorable predictor for overall survival in cervical carcinoma patients. The cell migration and invasion assays in vitro suggested that knockdown of CERNA2 remarkably inhibited cell migration and invasion in cervical carcinoma. In conclusion, CERNA2 functions as an oncogenic lncRNA and may be as a potential therapeutic target in cervical carcinoma.
Methyl B12 protects PC12 cells against cytotoxicity induced by Aβ25−35
Authors: Wang Mingkai , Xu Tingting
Published: February 2019

Alzheimer's disease (AD) is the most common aging‐associated dementia. The population of AD patients is increasing as the world age grows. Currently, there is no cure for AD. Given that methyl vitamin B12 (methylcobalamin) deficiency is related to AD and Aβ‐induced oxidative damage and that methylcobalamin can scavenge reactive oxygen species (ROS) by direct or indirect ways, we studied the effect of methylcobalamin on the cytotoxicity of Aβ. PC12 cells were chronically exposed (24 hours) to Aβ25‐35 (25 μM) to establish an AD cell model. The cells were pretreated with or without methylcobalamin (1‐100 μM) to investigate the role of methylcobalamin. Cell viability and apoptosis were tested, followed by testing of mitochondrial damage, oxidative stress, and mitochondrial calcium concentration. We observed that methylcobalamin improved the cell viability by decreasing the ratio of apoptosis cells in this AD cell model. Further experiments suggested that methylcobalamin functioned as an antioxidant to scavenge ROS, reducing the endoplasmic reticulum‐mitochondria calcium flux through IP3R, preventing mitochondria dysfunction, ultimately protecting cells against apoptosis and cell death. Taken together, our results presented, for the first time, that methyl vitamin B12 can protect cells from Aβ‐induced cytotoxicity and the mechanism was mainly relevant to the antioxidative function of methyl B12.
Differential roles of VEGF: Relevance to tissue fibrosis
Authors: Zhang Juan , Chu Maolin
Published: February 2019

Excessive extracellular matrix deposition and pathological vascularization are characteristics of fibrosis, which compromises the normal functioning of organs. Although whether angiogenesis can be induced and can occur in parallel with the progression of fibrosis has not been definitely determined, angiogenesis undoubtedly plays a vital role in fibrosis. Since vascular endothelial growth factor (VEGF) is one of the most effective proangiogenic factors, VEGF‐targeting interventions have been a focus for the development of therapeutic strategies against fibrosis. In this review, we will summarize the current knowledge of the role of VEGF and its relevant mechanisms in fibrotic biology. We especially expect to provide a comprehensive overview of the therapeutic potential of VEGF‐targeted therapy strategies to restore vascular function in the organs affected by fibrosis.
A novel copper (II) complex activated both extrinsic and intrinsic apoptotic pathways in liver cancerous cells
Authors: Rezaei Azadeh , Mahmoodi Mehdi , Mohammadizadeh Fatemeh , Mohamadi Maryam , Hajizadeh Mohammad Reza , Mirzaei Mohammad Reza , Khanamani Falahati‐pour Soudeh
Published: February 2019

Recent advances have put fundamental focus on the application of copper (II) (Cu [II]) complexes as agents for fighting against cancer. To determine whether [Cu(L)(2imi)] complex as a novel Cu complex can induce apoptosis in HepG2 as cancerous cells and L929 as normal cells via extrinsic or intrinsic apoptotic pathways, both cell lines were treated for 24 and 48 hours at IC50 concentrations of [Cu(L)(2imi)] complex. Then, the expression of some apoptosis‐related genes including p53, caspase‐8, bcl‐2, and bax were assayed by real‐time polymerase chain reaction. The [Cu(L)(2imi)] complex seems to inhibit the expression of bcl‐2 in complex‐treated HepG2 cancerous cells following the 24‐ and 48‐hour treatment. The complex upregulated the p53, bax, and caspase‐8 genes, therefore treatment of HepG2 cancerous cells with [Cu(L)(2imi)] complex induces programmed cell death via the upregulation of relative bax/bcl‐2 ratio. Finally, this copper complex triggered apoptosis in HepG2 cells via both intrinsic and extrinsic pathway, whereas treatment of normal L929 cells with this complex induce apoptosis only via intrinsic pathway with the upregulation of relative bax/bcl‐2 ratio and does not affect the expression level of caspase‐8 gene and does not trigger the extrinsic pathway. Finally, these results obtained from present study confirm the role of a novel Cu complex on the induction of apoptosis process in HepG2 and L929 cells by overexpression of bax, inhibition of bcl‐2 and increase of the relative bax/bcl‐2 ratio. These results support that the [Cu(L)(2imi)] complex is able to induce apoptosis in cancerous cells, therefore, it has a potential for development as a novel anticancer drug.
Strengthening mentalizing in a depressed mother of an infant with sleep disorders
Authors: Georg Anna , Kress Sandra , Taubner Svenja
Published: February 2019

Parent–infant psychotherapy treats parents to reduce infants’ symptoms and strengthen the quality of the parent–infant relationship. However, little is known about the change processes that are set in place in parent–infant psychotherapy and the therapeutic techniques that are most helpful. The aim of this study was to provide a comprehensive description of the course of one treatment with a depressed mother of an 8 months old infant who received focused parent–infant psychotherapy (fPIP), a brief psychological intervention that aims at fostering mentalizing in the parent. This study also aimed at examining the specific interventions that fostered mentalizing in this case. We assessed therapeutic interventions with the fPIP adherence scale and in‐session mentalizing with the Reflective Functioning Scale, and we analyzed qualitatively the moments in therapy that were relevant for the treatment focus and during which the mother demonstrated an increase in reflective functioning. We discussed the results with regard to the processes in the course of treatment and the strengths and limitations of fPIP.
Cyclin‐dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing
Authors: Amirhosseini Mehdi , Bernhardsson Magnus , Lång Pernilla , Andersson Göran , Flygare Johan , Fahlgren Anna
Published: February 2019

Cyclin‐dependent kinase 8 (CDK8) is a mediator complex‐associated transcriptional regulator that acts depending on context and cell type. While primarily under investigation as potential cancer therapeutics, some inhibitors of CDK8—and its paralog CDK19—have been reported to affect the osteoblast lineage and bone formation. This study investigated the effects of two selective CDK8/19 inhibitors on osteoclastogenesis and osteoblasts in vitro, and further evaluated how local treatment with a CDK8/19 inhibitor affects cancellous bone healing in rats. CDK8/19 inhibitors did not alter the proliferation of neither mouse bone marrow–derived macrophages (BMMs) nor primary mouse osteoblasts. Receptor activator of nuclear factor κΒ (NF‐κB) ligand (RANKL)‐induced osteoclastogenesis from mouse BMMs was suppressed markedly by inhibition of CDK8/19, concomitant with reduced tartrate‐resistant acid phosphatase (TRAP) activity and C‐terminal telopeptide of type I collagen levels. This was accompanied by downregulation of PU.1, RANK, NF‐κB, nuclear factor of activated T‐cells 1 (NFATc1), dendritic cell‐specific transmembrane protein (DC‐STAMP), TRAP, and cathepsin K in RANKL‐stimulated BMMs. Downregulating RANK and its downstream signaling in osteoclast precursors enforce CDK8/19 inhibitors as anticatabolic agents to impede excessive osteoclastogenesis. In mouse primary osteoblasts, CDK8/19 inhibition did not affect differentiation but enhanced osteoblast mineralization by promoting alkaline phosphatase activity and downregulating osteopontin, a negative regulator of mineralization. In rat tibiae, a CDK8/19 inhibitor administered locally promoted cancellous bone regeneration. Our data indicate that inhibitors of CDK8/19 have the potential to develop into therapeutics to restrict osteolysis and enhance bone regeneration.
Resistance to bortezomib in breast cancer cells that downregulate Bim through FOXA1 O‐GlcNAcylation
Authors: Liu Yubo , Wang Xue , Zhu Tong , Zhang Nana , Wang Lingyan , Huang Tianmiao , Cao Yu , Li Wenli , Zhang Jianing
Published: February 2019

Bortezomib (BTZ), a well‐established proteasome inhibitor used in the clinical therapy, leads the modulation of several biological alterations and in turn induces apoptosis. Although clinical trials with BTZ have shown promising results for some types of cancers, but not for some others, including those of the breast. The molecular basis of BTZ resistance in breast cancer remains elusive. In the present study, we found that cellular O‐GlcNAc modification was dramatically elevated by BTZ treatment in intrinsic resistant MCF‐7 and T47D cells, but not in sensitive MDA‐MB‐231 cells. A progressive increase in O‐GlcNAcylation characterized the increased acquired resistance of MDA‐MB‐231‐derived cells. We showed that elevated O‐GlcNAc subsequently modified breast cancer related pioneer factor FOXA1 and reduced its protein stability. Further, we demonstrated that FOXA1 attenuation was involved in transcriptional downregulation of proapoptotic Bim and thus suppressed breast cancer cell apoptosis. Finally, the combination of O‐GlcNAc inhibitor L01 to BTZ sensitized resistant cells. Our results have revealed a new regulatory mechanism that involves O‐GlcNAc elevation mediated Bim deficiency, which plays a key role in the apoptotic dysregulation and BTZ resistance in breast cancer cells.
Irisin ameliorates angiotensin II‐induced cardiomyocyte apoptosis through autophagy
Authors: Li Ruli , Wang Xiaoxiao , Wu Sisi , Wu Yao , Chen Hongying , Xin Juanjuan , Li He , Lan Jie , Xue Kunyue , Li Xue , Zhuo Caili , He Jinhan , Tang Chao‐Shu , Jiang Wei
Published: February 2019

Cardiac hypertrophy is the main cause of heart failure and sudden death in patients. But the pathogenesis is unclear. Angiotensin II may contribute to cardiac hypertrophy in response to pressure overload. In angiotensin II‐treated cardiomyocytes, there is a larger cross‐sectional area, more apoptosis cells, and a reduction of irisin expression. An increase in P62, an autophagy flux index, as well as LC3II, were observed in cardiomyocytes after angiotensin II‐induced injury. Surprisely, irisin supplementation increased LC3II expression and decreased P62 expression, consisted of results of RFP‐GFP‐LC3B adenovirus transfection, and reduced cardiomyocyte apoptosis, meanwhile, the protection of irisin was reversed by the autophagy inhibitor 3‐methyladenine. In animal experiments, overexpression of irisin reduced cardiomyocyte apoptosis and alleviated myocardial hypertrophy caused by pressure overload. The above results indicate that irisin‐induced protective autophagy and alleviated the apoptosis signaling pathway in cardiomyocytes, consequently reducing cardiomyocyte apoptosis after angiotensin II‐induced injury. Hence, increasing irisin expression may be a new way to improve cardiac function and quality of life in patients with cardiac hypertrophy.
Easy surveillance of muscle volume decline in chronic liver disease patients using finger‐circle (yubi‐wakka) test
Authors: Hiraoka Atsushi , Izumoto Hirofumi , Ueki Hidetaro , Yoshino Takeaki , Aibiki Toshihiko , Okudaira Tomonari , Yamago Hiroka , Suga Yoshifumi , Iwasaki Ryuichiro , Tomida Hideomi , Mori Kenichiro , Miyata Hideki , Tsubouchi Eiji , Kishida Masato , Ninomiya Tomoyuki , Hirooka Masashi , Abe Masanori , Matsuura Bunzo , Hiasa Yoichi , Michitaka Kojiro
Published: February 2019

Background

Muscle atrophy (MA) and muscle strength decline are important clinical features in chronic liver disease (CLD) patients. An easy to perform MA screening method without need for special equipment would be helpful. We evaluated the usefulness of the previously reported finger‐circle test as screening for MA in CLD patients.

Methods

We retrospectively enrolled 358 Japanese CLD outpatients (70.8 ± 10.2 years, male/female = 234/124) who had undergone a computed tomography examination from December 2017 to March 2018, of whom 137 had chronic hepatitis, 169 had liver cirrhosis Child–Pugh A, and 52 had liver cirrhosis Child–Pugh B/C. Bilateral psoas muscle area at the middle of the third lumber vertebra (L3) was evaluated with computed tomography findings, which was performed as a screening of hepatocellular carcinoma, using a previously reported parameter for MA [psoas index (PI): total psoas muscle area (cm2)/height (m)2] [mean PI ± standard deviation (SD) of male patients: 6.50 ± 1.13 cm2/m2 and those of female patients: 4.30 ± 0.90 cm2/m2]. We then evaluated the correlation between MA and finger‐circle test results in these patients.

Results

The mean PI values for finger‐circle test results Bigger, Just‐fits, and Smaller were 5.64 ± 1.34, 5.00 ± 1.25, and 4.83 ± 1.46 cm2/m2, respectively, in male patients (P < 0.001) and 4.31 ± 1.06, 3.93 ± 0.97, and 3.42 ± 0.94 cm2/m2, respectively, in female patients (P = 0.001). We found that a finger‐circle test result in male patients other than Bigger (Just‐fits and Smaller) predicted a decline in psoas muscle area of L3 to PI 5.25 cm2/m2 (sensitivity/specificity 0.619/0.667, area under the curve 0.654, 95% confidence interval 0.583–0.724), which was approximately mean minus 1 SD (5.37 cm2/m2). On the other hand, a Smaller test result in female patients predicted a decline in psoas muscle area of L3 to PI 3.33 cm2/m2 (sensitivity/specificity 0.740/0.583, area under the curve 0.698, 95% confidence interval 0.583–0.813), approximately mean minus 1 SD (3.40 cm2/m2).

Conclusions

The finger‐circle test is an easy to perform and effective screening method for predicting earlier stage of MA in CLD patients without the need for special equipment.
Prenatal allometric trajectories and the developmental basis of postcranial phenotypic diversity in bats (Chiroptera)
Authors: López‐Aguirre Camilo , Hand Suzanne J. , Koyabu Daisuke , Son Nguyen Truong , Wilson Laura A. B.
Published: February 2019

Most morphological and physiological adaptations associated with bat flight are concentrated in the postcranium, reflecting strong functional demands for flight performance. Despite an association between locomotory diversity and trophic differentiation, postcranial morphological diversity in bats remains largely unexplored. Evolutionary developmental biology is a novel approach providing a link between the analysis of genotypic and phenotypic variation resulting from selective pressures. To quantify the morphological diversity of the postcranium in bats and to explore its developmental basis, we reconstructed the postcranial allometric trajectories of nine bat species from different prenatal developmental series, representing five families and both suborders. We tested for allometric growth in Chiroptera and also quantified levels of allometric disparity and inter‐trajectory distances. Using a phylogenetic scaffold, we assessed whether ontogenetic differences reflect evolutionary relationships. We found significant allometric growth trajectories in almost all species. Interspecific trajectory distances showed lower variance within Yinpterochiroptera than within Yangochiroptera and between suborders. Each suborder occupied nonoverlapping sections of allometric space, showing changes in the growth rates of specific bones for each suborder. The allometry‐corrected disparity was significantly higher in larger species. Statistically significant phylogenetic signal in our results suggests that there is an ontogenetic basis for the postcranial morphological diversity in modern bats. Ancestral state reconstruction also showed an increase in the amount of change in shape with size in the larger species studied. We hypothesize that differences in allometric patterns among bat taxa may reflect a size‐dependent evolutionary constraint, whereby variability in body size and allometric patterns are associated.
Inflammatory bowel disease and the South Asian diaspora
Authors: Farrukh Affifa , Mayberry John Francis
Published: February 2019

Migration is associated with changes in the incidence of diseases, often linked to new environmental exposures or movement away from such exposures. Studies are complicated by the time and length of migration and also by differences in the experience of second‐ and third‐generation migrants. South Asian people have migrated across the world. In this review, the incidence and prevalence of inflammatory bowel disease in these communities is considered, along with their potential role in future investigative studies of the diseases’ etiology.
Acute kidney injury after hepatectomy can be reasonably predicted after surgery
Authors: Kim Minjae , Kiran Ravi P. , Li Guohua
Published: February 2019

Background

Hepatectomy presents unique challenges potentially heightening acute kidney injury (AKI) risk, but the full spectrum of risk factors has not been identified.

Methods

Data for hepatectomy patients in the 2016 American College of Surgeons National Surgical Quality Improvement Program (n = 3,814) was randomly split into derivation (70%) and validation (30%) cohorts. AKI was defined as an increase in serum creatinine ≥0.3 mg/dl or ≥1.5‐fold above the preoperative value within 30 days of surgery. Multivariable logistic regression assessed preoperative and intraoperative risk factors for AKI.

Results

Of 2,692 patients (derivation cohort), 432 (16%) developed AKI. Risk factors were the following: age (years; adjusted odds ratio [aOR] 1.016 [95% confidence interval 1.006–1.026], female sex (aOR 0.65 [0.51–0.82]), body mass index (kg/m2; aOR 1.043 [1.024–1.062]), diabetes (aOR 1.71 [1.31–2.24]), hypertension (aOR 1.66 [1.30–2.13]), hematocrit (%; aOR 0.944 [0.924–0.966]), operative time (min; aOR 1.004 [1.003–1.004]), planned open procedure (aOR 2.00 [1.47–2.73]), and Pringle maneuver (aOR 1.36 [1.07–1.72]). The areas under the curve of the receiver operating characteristic curves were 0.74 (95% CI 0.71–0.76) and 0.71 (95% CI 0.67–0.75) in the derivation and validation cohorts, respectively.

Conclusions

Postoperative AKI affects one in six hepatectomy patients; preoperative and intraoperative factors can predict the risk of postoperative AKI.
Presence, localization and morphology of TELOCYTES in developmental gonads of fishes
Authors: Mazzoni Talita Sarah , Viadanna Renan Ribeiro , Quagio‐Grassiotto Irani
Published: February 2019

Telocytes are a new defined type of interstitial cells, considered as a stem cell, with very long and thin cytoplasmic extensions. They are present in the vertebrates, and may participate in tissue remodeling. In fish, during gonadal development, the events that culminate with the germinal epithelium formation are well known. However, the interstitial compartment remains poorly explored, although it may have a great contribution to the morpho‐functional changes that occur in the gonad. As in other organisms, in fish, the interstitium consists especially of connective tissue elements. However, until now, there are no reports of the presence and the action of the telocytes in the connective tissue of gonads of fish. Thus, this study aimed to detect the presence, localization and morphology of telocytes during the gonadal development of several species of fish. The gonads were analyzed by light microscopy, transmission electron microscopy and immunohistochemistry for localization of CD34, Vimentin, and metalloproteinases. The presence of two proteins characteristics of mesenchymal cell was detected in cells of the gonads of all species. In addition, they presented a typical morphology of telocytes, showing cellular extensions. Gonadal telocytes also presented positive response to metalloproteinases. In mammals, telocytes can undergo de‐differentiation contributing to the reorganization of the extracellular matrix. This role may be performed by the metalloproteinases detected here. The detection of Vimentin and CD34 in the same cellular type, associated with its morphological characteristics, allows us to conclude that some interstitial cells in Teleostei are considered telocytes, identical to the ones already described in mammals and other vertebrates.
3D‐printed, externally‐implanted, bioresorbable airway splints for severe tracheobronchomalacia
Authors: Les Andrea S. , Ohye Richard G. , Filbrun Amy G. , Ghadimi Mahani Maryam , Flanagan Colleen L. , Daniels Rodney C. , Kidwell Kelley M. , Zopf David A. , Hollister Scott J. , Green Glenn E.
Published: February 2019

Objectives/Hypothesis

To report the clinical safety and efficacy of three‐dimensional (3D)–printed, patient‐specific, bioresorbable airway splints in a cohort of critically ill children with severe tracheobronchomalacia.

Study Design

Case series.

Methods

From 2012 to 2018, 15 subjects received 29 splints on their trachea, right and/or left mainstem bronchi. The median age at implantation was 8 months (range, 3–25 months). Nine children were female. Five subjects had a history of extracorporeal membrane oxygenation (ECMO), and 11 required continuous sedation, six of whom required paralytics to maintain adequate ventilation. Thirteen were chronically hospitalized, unable to be discharged, and seven were hospitalized their entire lives. At the time of splint implantation, one subject required ECMO, one required positive airway pressure, and 13 subjects were tracheostomy and ventilator dependent, requiring a median positive end‐expiratory pressure (PEEP) of 14 cm H2O (range, 6–20 cm H20). Outcomes collected included level of respiratory support, disposition, and splint‐related complications.

Results

At the time of discharge from our institution, at a median of 28 days postimplantation (range, 10–56 days), the subject on ECMO was weaned from extracorporeal support, and the subjects who were ventilated via tracheostomy had a median change in PEEP (discharge–baseline) of −2.5 cm H2O (range, −15 to 2 cm H2O, P = .022). At median follow‐up of 8.5 months (range, 0.3–77 months), all but one of the 12 surviving subjects lives at home. Of the 11 survivors who were tracheostomy dependent preoperatively, one is decannulated, one uses a speaking valve, six use a ventilator exclusively at night, and three remain ventilator dependent.

Conclusions

This case series demonstrates the initial clinical efficacy of the 3D‐printed bioresorbable airway splint device in a cohort of critically ill children with severe tracheobronchomalacia.

Level of Evidence

4

Laryngoscope, 129:1763–1771, 2019
Dirty weekends and personal hygiene products: The embodiment of casual sex in marketing
Authors: Chan Eugene Y.
Published: February 2019

In the current inquiry, we propose that reminders of casual sex might lead individuals to feel physically dirty, and this would then motivate consumers to acquire and like personal hygiene products such as toothpaste, body soap, and face wash. We further test the possibility that our hypothesized effect would arise mainly for those who link casual sex with impurity. In three studies, reminders of casual sex increase liking for personal hygiene products mainly among conservative (Study 1), religious (Study 2), and individuals who see “casual sex” to be “dirty,” “wrong,” or even “immoral” (Study 3). These findings are consistent with embodied cognition, suggesting that abstract representations can effect concrete sensations. We study this possibility in a novel domain in sex and sexuality. Our work is relevant to marketers of personal hygiene products, but we situate our findings in the broader discourse of how mere reminders of casual sex might influence individuals’ choices and behaviors.