bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational Modeling of Electrochemomechanics of High-Capacity Composite Electrodes in Li-Ion Batteries
Authors: Shah Sameep Rajubhai , de Vasconcelos Luize Scalco , Zhao Kejie 
Published: June 2022

Abstract
Mechanical failure and its interference with electrochemistry are a roadblock in deploying high-capacity electrodes for Li-ion batteries. Computational prediction of the electrochemomechanical behavior of high-capacity composite electrodes is a significant challenge because of (i) complex interplay between mechanics and electrochemistry in the form of stress-regulated Li transport and interfacial charge transfer, (ii) thermodynamic solution non-ideality, (iii) nonlinear deformation kinematics and material inelasticity, and (iv) evolving material properties over the state of charge. We develop a computational framework that integrates the electrochemical response of batteries modulated by large deformation, mechanical stresses, and dynamic material properties. We use silicon as a model system and construct a microstructurally resolved porous composite electrode model. The model concerns the effect of large deformation of silicon on charge conduction and electrochemical response of the composite electrode, impact of mechanical stress on Li transport and interfacial charge transfer, and asymmetric charging/discharging kinetics. The study captures the rate-dependent, coupled electrochemomechanical behavior of high-capacity composite electrodes that agrees well with experimental results.
Hydride Intercalation of Lithium into Ni3GaTe2
Authors: Buzanov G. A. , Stroganova E. A. , Bykov A. Yu. , Zhizhin K. Yu. , Kuznetsov N. T. 
Published: June 2022

Abstract
In order to expand the methods of lithium intercalation into layered multicomponent matrices, the reaction of lithium hydride with layered telluride Ni3GaTe2 through the stage of formation of mechanocomposites has been studied. Intercalation compounds LixNi3GaTe2 (0 ≤ x ≤ 0.3) have been shown to form when annealing mechanocomposites of the matrix and intercalating agent (LiH) in argon. The channels of hydride ion conversion have been studied and transformations involving the matrix have been described at various temperatures and molar ratios of the matrix and intercalating agent.
Synthesis of MAX Phases in the Ti2AlC–V2AlC System as Precursors of Heterometallic MXenes Ti2 – xVxC
Authors: Simonenko E. P. , Simonenko N. P. , Nagornov I. A. , Simonenko T. L. , Mokrushin A. S. , Sevastyanov V. G. , Kuznetsov N. T. 
Published: June 2022

Abstract
A relatively low-temperature molten salt assisted synthesis is developed to prepare MAX phase solid solutions in the Ti2AlC–V2AlC system, to be used as precursors for the preparation of heterometallic MXenes Ti2 –xVxC. When the synthesis temperature is 1000°С, Ti1V1AlC, Ti0.5V1.5AlC, and Ti0.2V1.8AlC samples (despite the formation of a MAX phase and a systematic shift of reflection (002) in response to progressing vanadium-for-titanium substitution) typically feature appreciable amounts of impurity phases, namely Al2O3 and vanadium (their reflections are partially overlapping). An increase in synthetic temperature to 1100°С appreciably reduces the amount of impurities and, in a Ti1V1AlC sample, decreases the unit cell parameter a, which yet far exceeds the calculated and published values (while the parameter c corresponds with those values). Thermal analysis of Ti2AlC, Ti1V1AlC, and V2AlC samples in the range 20–1000°С shows that the oxidation resistance decreases in the progress of vanadium-for-titanium substitution in a MAX phase. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are used to study the microstructure of the prepared Ti2AlC and V2AlC phases.
Chronic lesion activity and disability progression in secondary progressive multiple sclerosis
Authors: Beynon Vanessa , George Ilena C , Elliott Colm , Arnold Douglas L , Ke Jun , Chen Huaihou , Zhu Li , Ke Chunlei , Giovannoni Gavin , Scaramozza Matthew , Campbell Nolan , Bradley Daniel P , Franchimont Nathalie , Gafson Arie , Belachew Shibeshih 
Published: June 2022

ObjectiveSlowly expanding lesions (SELs), a subgroup of chronic white matter lesions that gradually expand over time, have been shown to predict disability accumulation in primary progressive multiple sclerosis (MS) disease. However, the relationships between SELs, acute lesion activity (ALA), overall chronic lesion activity (CLA) and disability progression are not well understood. In this study, we examined the ASCEND phase III clinical trial, which compared natalizumab with placebo in secondary progressive MS (SPMS).MethodsPatients with complete imaging datasets between baseline and week 108 (N=600) were analysed for SEL prevalence (the number and volume of SELs), disability progression, ALA (assessed by gadolinium-enhancing lesions and new T2-hyperintense lesions) and CLA (assessed by T1-hypointense lesion volume increase within baseline T2-non-enhancing lesions identified as SELs and non-SELs).ResultsCLA in both SELs and non-SELs was greater in patients with SPMS with confirmed disability progression than in those with no progression. In the complete absence of ALA at baseline and on study, SEL prevalence was significantly lower, while CLA within non-SELs remained associated with disability progression. Natalizumab decreased SEL prevalence and CLA in SELs and non-SELs compared with placebo.ConclusionsThis study shows that CLA in patients with SPMS is decreased but persists in the absence of ALA and is associated with disability progression, highlighting the need for therapeutics targeting all mechanisms of CLA, including smouldering inflammation and neurodegeneration.Trial registration numberNCT01416181.
Development trend of primary healthcare after health reform in China: a longitudinal observational study
Authors: Feng Jie , Gong Yanhong , Li Hui , Wu Jianxiong , Lu Zuxun , Zhang Guopeng , Zhou Xuan , Yin Xiaoxv 
Published: June 2022

ObjectivesReconstructing the primary healthcare system is the focus of the new round of Chinese health reform. Nevertheless, there have been few studies focusing on the strengthening of primary healthcare in Chinese health system.DesignThis study was a longitudinal observational study.Primary and secondary outcome measuresThe data of this study came from China Health Statistical Yearbook (2009–2018). We evaluated the development of primary healthcare based on the absolute values of health resources allocation and health service provision and evaluated the status of primary healthcare throughout the health system based on the composition ratios of the indicators across the health system. The Cochran-Armitage trend test and linear trend test were used to identify the indicators’ trends over time.ResultsFrom 2009 to 2018, the amounts of health resources allocation and health service provision of Chinese primary healthcare institutions showed a significant upward trend (p<0.001). However, compared with the indicators in 2009, excepting that the proportion of grants from the government in the whole health system has an upward trend, the proportions of other indicators had an escalating trend in 2018 by 3.66% for practicing (assistant) physicians, by 2.69% for nurses, by 3.99% for total revenues, by 5.87% for beds, by 8.39% for outpatient visits.ConclusionThe primary healthcare system has developed rapidly, but its development speed lagged behind the entire health system, resulting in the weakening of its actual functions, which is not in line with the goal of health reform. The government should be more aware of the importance of primary healthcare at all levels of local governments and ensure adequate financial input.
Standardised protocol for a prospective cross-sectional multicentre clinical utility evaluation of two dual point-of-care tests in non-clinical settings for the screening of HIV and syphilis in men who have sex with men
Authors:   The ProSPeRo Network
Published: June 2022

IntroductionPoint-of-care dual tests (POCTs) for simultaneously detecting antibodies to HIV and syphilis (dual HIV-syphilis POCTs) have been developed recently and show encouraging performance compared with the reference tests in laboratory-based studies. As community-based voluntary, counselling and testing (CBVCT) services are effective providers of HIV and syphilis testing and counselling with high acceptability among men who have sex with men (MSM), the evaluation of the utility of these dual tests in CBVCT services is a high priority. This prospective cross-sectional study will conduct a clinical utility evaluation of two dual POCTs in non-clinical settings for the screening of HIV and syphilis in MSM. This master protocol outlines the overall research approach that will be used in four countries.Methods and analysisMSM presenting at CBVCT services participating in the study for HIV/STI screening will be enrolled. The (WHO preapproved) dual POCTs to be evaluated will be SD Bioline HIV/Syphilis Duo (Abbot) and Dual Path Platform HIV-Syphilis Assay (Chembio). Trained staff will collect a capillary blood sample using finger prick blood to perform both POCTs according the manufacturers’ instructions. An analysis of the feasibility of introducing the dual POCT for the screening of HIV and syphilis in MSM at CBVCT services will be performed, by assessing its acceptability and usability at CBVCT service among MSM users and providers.Ethics and disseminationThis core protocol was independently peer reviewed and approved by the Research Project Review Panel (RP2) of the WHO Department of Sexual and Reproductive Health and Research and by the WHO Ethics Review Committee (ERC). The protocol has been adapted to individual countries and approved by RP2, ERC and institutional review boards at each site. Results will be disseminated through peer-reviewed journals and relevant conferences.
Experimental Study on Gas–Water Relative Permeability Characteristics of Tight Sandstone Reservoir in Ordos Basin
Authors: Ren Xiaoxia , Li Aifen , Memon Asadullah 
Published: June 2022

Accurate measurement of relative permeability curve is the basis for evaluating gas reservoir performance. The unsteady-state method could bring significant measurement error for low-permeability cores. However, it is difficult to control the constant gas flow rate in the traditional steady-state method, which obstacles the experimental operation. In this study, an improved steady-state method was proposed. First, the pressure value obtained from the experiment, when the gas permeability no longer changed with the average pressure on the rock core, was set as the testing pressure. Then, the gas was injected under constant pressure, and the water was injected with a constant flow rate. Finally, the relative permeability values of gas and water phases were calculated based on Darcy’s law. Comparative analysis of the results of the relative permeability curves under formation pressure and pressure with negligible slip effect indicates that the relative permeability curves are the same in gas and water phases, proving the feasibility of the new method. Further, the results were compared with those of the test method at normal pressure, the water-phase relative permeability showed no significant change, the relative permeability of gas phase was larger, the two-phase flow area became wider, and the irreducible water saturation was lower than that at the normal pressure. This result reflects that pressure does not significantly affect the flow of wetting phase but tremendously influences the nonwetted phase under low pressure. The relationship between relative permeability and water saturation is linear in the semilogarithmic coordinate diagram and can be described by using the following relationship:

ln

k

rg

/

k

rw

=
a

S

w

+
ln

b

. With the decrease in the core permeability, relative permeability curve, and isotonic point moved to the right, irreducible water saturation gradually increased, and residual gas saturation decreased, indicating that the smaller permeability induced a lower gas-phase flow capacity.
The discovery of a new structural class of cyclin-dependent kinase inhibitors, aminoimidazo[1,2-a]pyridines
Authors: Hamdouchi Chafiq , Keyser Heather , Collins Elizabeth , Jaramillo Carlos , De Diego Jose Eugenio , Spencer Charles D. , Dempsey Jack Alan , Anderson Bryan D. , Leggett Tillie , Stamm Nancy B. , Schultz Richard M. , Watkins Scott A. , Cocke Kim , Lemke Stephanie , Burke Teresa F. , Beckmann Richard P. , Dixon Jeffrey T. , Gurganus Thomas M. , Rankl Nancy B. , Houck Keith A. , Zhang Faming , Vieth Michal , Espinosa Juan , Timm David E. , Campbell Robert M. , Patel Bharvin K. R. , Brooks Harold B. 
Published: June 2022

Abstract
The protein kinase family represents an enormous opportunity for drug development. However, the current limitation in structural diversity of kinase inhibitors has complicated efforts to identify effective treatments of diseases that involve protein kinase signaling pathways. We have identified a new structural class of protein serine/threonine kinase inhibitors comprising an aminoimidazo[1,2-a]pyridine nucleus. In this report, we describe the first successful use of this class of aza-heterocycles to generate potent inhibitors of cyclin-dependent kinases that compete with ATP for binding to a catalytic subunit of the protein. Co-crystal structures of CDK2 in complex with lead compounds reveal a unique mode of binding. Using this knowledge, a structure-based design approach directed this chemical scaffold toward generating potent and selective CDK2 inhibitors, which selectively inhibited the CDK2-dependent phosphorylation of Rb and induced caspase-3-dependent apoptosis in HCT 116 tumor cells. The discovery of this new class of ATP-site-directed protein kinase inhibitors, aminoimidazo[1,2-a]pyridines, provides the basis for a new medicinal chemistry tool to be used in the search for effective treatments of cancer and other diseases that involve protein kinase signaling pathways.
Roscovitine-induced up-regulation of p53AIP1 protein precedes the onset of apoptosis in human MCF-7 breast cancer cells
Authors: Węsierska-Gądek Józefa , Gueorguieva Marieta , Horky Marcel 
Published: June 2022

Abstract
We reported recently that roscovitine arrested human MCF-7 cancer cells at G2-M phase of the cell cycle and concomitantly induced apoptosis. After roscovitine treatment, the level of wild-type p53 protein strongly increased and p53 was accumulated in the nucleus. Here, we raised the question of which pathway would be involved in roscovitine-induced apoptosis in MCF-7 cells, which are known to be caspase-3-deficient, and whether roscovitine-mediated activation of p53 protein might positively affect the execution of cell death. Roscovitine induced a depolarization of mitochondrial potential beginning at 6 hours posttreatment as evidenced by changes in J-aggregate formation and release of the mitochondrial proteins cytochrome c and apoptosis-inducing factor. Interestingly, roscovitine stimulated a site-specific phosphorylation of wild-type p53 protein in a time-dependent manner. p53 protein was specifically phosphorylated at Ser46. P-Ser46-activated wild-type p53 tumor suppressor up-regulated p53AIP1 protein, its downstream target known to mediate the depolarization of mitochondria. The onset of phosphorylation of p53 at Ser46 preceded the up-regulation of p53AIP1 protein and the depolarization of mitochondrial potential. We compared the kinetics of roscovitine-mediated p53 activation between caspase-3-deficient parental MCF-7 cells and cells reconstituted with caspase-3. The kinetics and the extent of p53 protein activation in caspase-3-proficient cells differed from those observed in caspase-3-deficient parental cells. Remarkably, roscovitine failed to induce phosphorylation at Ser46 in caspase-3-reconstituted MCF-7 cells. Our results indicate that, depending on the status of caspase-3 in MCF-7 cells, different apoptotic pathways were initialized.
BimEL is an important determinant for induction of anoikis sensitivity by mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitors
Authors: Fukazawa Hidesuke , Noguchi Kohji , Masumi Atsuko , Murakami Yuko , Uehara Yoshimasa 
Published: June 2022

Abstract
Loss of contact with substratum triggers apoptosis in many normal cell types, a phenomenon termed anoikis. We reported previously that mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitors induced apoptosis in nonanchored MDA-MB231 and HBC4 human breast cancer cells, whereas anchored cells remained viable. Here, we report that activation of the BH3-only protein BimEL is the major mechanism for induction of anoikis sensitivity by MEK inhibitors in MDA-MB231 and HBC4 cells. On treatment with MEK inhibitors, BimEL in MDA-MB231 and HBC4 cells rapidly increased, irrespective of the state of anchorage. However, it translocated to mitochondria only in nonanchored cells, explaining why attached cells remain viable. MDA-MB231 and HBC4 cells had exceedingly low basal levels of BimEL compared with other breast cancer cells, suggesting that maintenance of low BimEL amount is important for survival of these cells. MEK inhibitors also induced the electrophoretic mobility shift of BimEL, indicative of reduced phosphorylation. In vitro, BimEL was phosphorylated by extracellular signal-regulated kinase on Ser69, which resides in the BimEL-specific insert region. Using phosphospecific antibody against this site, we show that this residue is actually phosphorylated in cells. We also show that phosphorylation of Ser69 promotes ubiquitination of BimEL. We conclude that MEK inhibitors sensitize MDA-MB231 and HBC4 cells to anoikis by blocking phosphorylation and hence degradation of BimEL, a mechanism that these cells depend on to escape anoikis.
Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-XL [(−)-gossypol] against diffuse large cell lymphoma
Authors: Mohammad Ramzi M. , Wang Shaomeng , Aboukameel Amro , Chen Ben , Wu Xihan , Chen Jianyong , Al-Katib Ayad 
Published: June 2022

Abstract
Overexpression of Bcl-2/Bcl-XL protein has been observed in more than 80% of B-cell lymphomas. Diffuse large cell lymphoma (DLCL) is the most common subtype of non-Hodgkin's lymphoma. (−)-Gossypol, a natural product isolated from cottonseeds, was discovered as a potent small-molecule inhibitor of Bcl-2 and Bcl-XL proteins, with a Ki value in the nanomole per liter range for both. In vitro, (−)-gossypol showed significant growth inhibition effect against WSU-DLCL2 lymphoma cell line and fresh cells obtained from a lymphoma patient with no effect on normal peripheral blood lymphocytes. As expected (−)-gossypol induced complete cytochrome c release from mitochondria, increased caspases-3 and -9 activity, and caused apoptotic death without affecting protein levels of Bcl-2, Bcl-XL, Bax, and Bak. The addition of cyclophosphamide-Adriamycin-vincristine-prednisolone (CHOP) regimen to lymphoma cells preexposed to (−)-gossypol enhanced killing significantly. The maximum tolerated dose of (−)-gossypol in severe combined immunodeficient (SCID) mice was 40 mg/kg for three i.v. injections when given alone and 20 mg/kg × 3 when given in combination with CHOP. Using WSU-DLCL2-SCID mouse xenograft model, the tumor growth inhibition, the tumor growth delay, and the log10 kill of mice treated with (−)-gossypol + CHOP were better than CHOP or (−)-gossypol alone. We conclude that adding Bcl-2/Bcl-XL small-molecule inhibitor to standard chemotherapy may prove an effective strategy in lymphoma therapy.
Discovery and mechanism of action of a novel series of apoptosis inducers with potential vascular targeting activity
Authors: Kasibhatla Shailaja , Gourdeau Henriette , Meerovitch Karen , Drewe John , Reddy Sanjeeva , Qiu Ling , Zhang Hong , Bergeron Frederick , Bouffard David , Yang Quan , Herich John , Lamothe Serge , Cai Sui Xiong , Tseng Ben 
Published: June 2022

Abstract
A novel series of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes was identified as apoptosis-inducing agents through our cell-based apoptosis screening assay. Several analogues from this series, MX-58151, MX-58276, MX-76747, MX-116214, MX-126303, and MX-116407, were synthesized and further characterized. MX-116407, a lead compound from this series, induced apoptosis with an EC50 of 50 nmol/L and inhibited cell growth with a GI50 of 37 nmol/L in T47D breast cancer cells. Treatment of cells with these analogues led to G2-M arrest, cleavage of essential proapoptotic caspase substrates, and induction of nuclear fragmentation. We identified these compounds as tubulin destabilizers with binding site at or close to the colchicine binding site. Compounds in this series were also active in drug-resistant cancer cell lines with a GI50 value for one of the analogues (MX-58151) of 2.5 nmol/L in paclitaxel-resistant, multidrug-resistant MES-SA/DX5 tumor cells. This series of compounds displayed high selectivity against proliferating versus resting cells. Interestingly, these compounds were shown to disrupt preformed endothelial cell capillary tubules in vitro and affect functional vasculature to induce tumor necrosis in vivo and are thus likely to work as tumor vasculature targeting agents. Among these compounds, MX-116407 showed capillary tubule disruption activity in vitro at concentrations well below the cytotoxic dose. In a separate study, we further characterized the antitumor efficacy and pharmacokinetic profile of this series of compounds and identified MX-116407 as a potent apoptosis-inducing agent with apparent activity as tumor vasculature targeting agent.
Cyclooxygenase-2-dependent and -independent effects of celecoxib in pancreatic cancer cell lines
Authors: El-Rayes Basil F. , Ali Shadan , Sarkar Fazlul H. , Philip Philip A. 
Published: June 2022

Abstract
Cyclooxygenase-2 (COX-2) is involved in inhibition of apoptosis, potentiation of cell growth, and angiogenesis and as such is a target for drug development. The COX-2 enzyme is frequently overexpressed in pancreatic cancer. The aim of this study was to determine the effects of celecoxib on the growth inhibition and induction of apoptosis by gemcitabine in pancreatic cancer cell lines. Baseline expression of COX-2 enzyme was determined by Western blot analysis in five human pancreatic cancer cell lines. Cells were treated with gemcitabine (100 nmol/L), celecoxib (1, 10, and 50 μmol/L), and the combination. No potentiation in growth inhibition was observed in MIAPaCa cells (low COX-2 expression). However, growth inhibition and apoptosis were significantly increased with celecoxib in the BxPC-3 cells that have a high COX-2 expression. Significant down-regulation of nuclear factor-κB activation was observed in BxPC-3 cells treated with celecoxib and gemcitabine. Moreover, down-regulation of COX-2 mRNA and protein expression was also observed in the BxPC-3 cells treated with the combination as compared with the untreated and the celecoxib-treated and gemcitabine-treated cell lines. We conclude that celecoxib potentiates gemcitabine-induced growth inhibition and apoptosis in pancreatic cell lines. In addition to inhibition of the COX-2 enzyme, the celecoxib and gemcitabine combination down-regulated nuclear factor-κB activation, which in turn may have contributed to the induction of apoptosis and the down-regulation of transcription of the COX-2 enzyme.