bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cytochrome c‐Chlorotoxin Hybrid Protein as a Possible Antiglioma Drug
Authors: Delinois Louis J. , Peón Harold , Villalobos‐Santos Juan C. , Ramírez‐Paz Josell , Miller Jennifer , Griebenow Kai H. , Tinoco Arthur D.
Published: September 2020

Malignant gliomas are the most lethal form of primary brain tumors. Despite advances in cancer therapy, the prognosis of glioma patients has remained poor. Cytochrome c (Cytc), an endogenous heme‐based protein, holds tremendous potential to treat gliomas because of its innate capacity to trigger apoptosis. To this end, a hybrid cytochrome c‐chlorotoxin (Cytc‐CTX) protein was biosynthesized to enable cellular uptake of the cell impenetrable Cytc using CTX transporters. A nucleotide sequence containing 1 : 1 Cytc and CTX was constructed and separated by a hexahistidine‐tag and an enterokinase cleavage site. The sequence was cloned into a pBTR1 plasmid, expressed in Escherichia coli, purified via 2‐dimensional chromatography. The identity and size of the protein were determined by Western blot and mass spectrometry. Cytc in this soluble hybrid protein has similar structure and stability as human Cytc and the hybrid protein is endocytosed into a glioma cell line, while displaying potent cytotoxicity and a favorable therapeutic index. Its facile, low‐cost, and high yield synthesis, biocompatibility, and robustness suggest that the hybrid protein is a promising candidate for antiglioma drug evaluation.
Curability of patients with lymph node metastases from extremity soft‐tissue sarcoma
Authors: Basile Georges , Mattei Jean‐Camille , Alshaygy Ibrahim , Griffin Anthony M. , Catton Charles N. , Chung Peter W. , Shultz David B. , Razak Albiruni R. A. , Demicco Elizabeth G. , Ferguson Peter C. , Wunder Jay S.
Published: September 2020

Background

Lymph node metastases (LNM) rarely occur in adult extremity soft‐tissue sarcoma (STS), affecting approximately 5% of patients. To the authors' knowledge, few studies to date have evaluated the prognosis and survival of patients with LNM.

Methods

A retrospective review was performed of a single‐center, prospectively collected STS database. Demographic, treatment, and oncologic data for patients with STS of the extremity with LNM were obtained from clinical and radiographic records.

Results

Of 2689 patients with extremity STS, a total of 120 patients (4.5%) were diagnosed with LNM. LNM occurred most frequently among patients diagnosed with clear cell sarcoma (27.6%), epithelioid sarcoma (21.9%), rhabdomyosarcoma (17.3%), angiosarcoma (14.0%), and extraskeletal myxoid chondrosarcoma (9.3%). A total of 98 patients (81.7%) underwent LNM surgical resection. Patients with isolated LNM had a greater 5‐year overall survival (57.3%) compared with patients with American Joint Committee on Cancer (AJCC) eighth edition stage IV STS with only systemic metastases (14.6%) or both LNM and systemic disease (0%; P < .0001). Patients with isolated LNM had an overall survival rate (52.9%) similar to that of patients with localized AJCC stage III tumors (ie, large, high‐grade tumors) (49.3%) (P = .8). Patients with late, isolated, metachronous LNM had a 5‐year overall survival rate (61.2%) that was similar to that of patients with isolated synchronous LNM at the time of presentation (53.6%) (P = .4).

Conclusions

Many different types of STS develop LNM. Patients with extremity STS with isolated LNM should not be considered as having stage IV disease as they are according to the current AJCC eighth edition classification because they have significantly better survival than those with systemic metastases. Patients with isolated, late, metachronous LNM have a survival similar to that of patients with isolated synchronous LNM at the time of presentation.

Lay Summary

The results of the current study demonstrated that patients diagnosed with isolated lymph node metastases have a prognosis similar to that of patients diagnosed with localized American Joint Committee on Cancer stage III soft‐tissue sarcomas, which also equates to a significantly better overall survival compared with patients with systemic metastases.

Therefore, the authors recommend modifications to the most recent eighth edition of the American Joint Committee on Cancer staging system to clearly distinguish patients with isolated lymph node metastases to acknowledge their better prognosis compared with those with systemic metastases.
Significant reduction of indeterminate (atypical) diagnosis after implementation of The Paris System for Reporting Urinary Cytology: A single‐institution study of more than 27,000 cases
Authors: Tian Wei , Shore Karen T. , Shah Rajal B.
Published: September 2020

Background

Urinary cytology is a noninvasive and cost‐effective diagnostic and surveillance test in the clinical management of urothelial carcinoma (UC). The Paris System for Reporting Urinary Cytology (TPS), published in 2016, introduced definite diagnostic criteria aimed at improving performance in detecting high‐grade UC (HGUC) and decreasing the indeterminate (atypical) diagnosis.

Methods

The authors retrospectively reviewed and compared urinary cytology diagnoses reported between January 2013 and December 2014 (pre‐TPS, 7658 cases) and between May 2016 and April 2018 (post‐TPS, 20,026 cases) to assess the influence of TPS in their practice. The time in between was used as a learning period. Follow‐up information and correlation with the UroVysion fluorescence in situ hybridization test were obtained when available.

Results

Urinary cytology diagnoses pre‐TPS included negative for UC (NUC) (n = 5293; 69.2%), atypical urothelial cells (AUC) (n = 2227; 29%), and suspicious/positive for HGUC (SHGUC/HGUC) (n = 138; 1.8%). Diagnoses post‐TPS included negative for HGUC (NHGUC) (n = 18,507; 92.4%), AUC (n = 1237; 6.2%), and SHGUC/HGUC (n = 282; 1.4%). Comparing the pre‐TPS and post‐TPS periods, AUC diagnoses decreased from 29% to 6.2% (P < .00001), and the specificity and positive predictive value of AUC to detect HGUC significantly improved from 49% to 86% (P < .00001) and from 9% to 39% (P = .002), respectively. The correlation of an AUC diagnosis with a positive UroVysion test improved from 17% to 38% (P < .00001), whereas overall use of the UroVysion test was decreased.

Conclusions

Implementation of TPS resulted in a significant reduction in AUC diagnoses that had a superior correlation with a subsequent biopsy and a UroVysion test, resulting in potential reductions in test use and medical cost.
Topographic gradients define the projection patterns of the claustrum core and shell in mice
Authors: Marriott Brian A. , Do Alison D. , Zahacy Ryan , Jackson Jesse
Published: September 2020

The claustrum is densely connected to the cortex and participates in brain functions such as attention and sleep. Although some studies have reported the widely divergent organization of claustrum projections, others describe parallel claustrocortical connections to different cortical regions. Therefore, the details underlying how claustrum neurons broadcast information to cortical networks remain incompletely understood. Using multicolor retrograde tracing we determined the density, topography, and co‐projection pattern of 14 claustrocortical pathways, in mice. We spatially registered these pathways to a common coordinate space and found that the claustrocortical system is topographically organized as a series of overlapping spatial modules, continuously distributed across the dorsoventral claustrum axis. The claustrum core projects predominantly to frontal‐midline cortical regions, whereas the dorsal and ventral shell project to the cortical motor system and temporal lobe, respectively. Anatomically connected cortical regions receive common input from a subset of claustrum neurons shared by neighboring modules, whereas spatially separated regions of cortex are innervated by different claustrum modules. Therefore, each output module exhibits a unique position within the claustrum and overlaps substantially with other modules projecting to functionally related cortical regions. Claustrum inhibitory cells containing parvalbumin, somatostatin, and neuropeptide Y also show unique topographical distributions, suggesting different output modules are controlled by distinct inhibitory circuit motifs. The topographic organization of excitatory and inhibitory cell types may enable parallel claustrum outputs to independently coordinate distinct cortical networks.
The Interplay of Nanoconfinement and pH from the Perspective of a Dye‐Reporter Molecule
Authors: Brilmayer Robert , Brodrecht Martin , Kaiser Christoph , Breitzke Hergen , Kumari Bharti , Wachtveitl Josef , Buntkowsky Gerd , Andrieu‐Brunsen Annette
Published: September 2020

A novel thiazol‐based ratiometric dye for the detection of local pH values is synthesized, and its properties are characterized by a combination of optical spectroscopy, solid‐state NMR and DNP (dynamic nuclear polarization)‐enhanced solid‐state NMR. This novel dye covers a completely different sensitivity range with its acidic pKa value of 3.5 compared to other established dyes for ratiometric pH detection, such as SNARF. The dye is grafted to the surfaces of mesoporous silica materials, which enables, for the first time, direct in situ measurements of the local pH values in silica mesopores by a simple UV‐vis spectroscopy method. The obtained results, which are in good agreement with previous indirect techniques, indicate a background electrolyte‐dependent pKa shift of at least one pH unit under nanoconfined conditions compared to the pKa of the dye in bulk solution.
Density peaks clustering based on k‐nearest neighbors sharing
Authors: Fan Tanghuai , Yao Zhanfeng , Han Longzhe , Liu Baohong , Lv Li
Published: September 2020

The density peaks clustering (DPC) algorithm is a density‐based clustering algorithm. Its density peak depends on the density‐distance model to determine it. The definition of local density for samples used in DPC algorithm only considers distance between samples, while the environments of samples are neglected. This leads to the result that DPC algorithm performs poorly on complex data sets with large difference in density, flow pattern or cross‐winding. In the meantime, the fault tolerance of allocation strategy for samples is relatively poor. Based on the findings, this article proposes a density peaks clustering based on k‐nearest neighbors sharing (DPC‐KNNS) algorithm, which uses the similarity between shared neighbors and natural neighbors to define the local density of samples and the allocation. Comparison between theoretical analysis and experiments on various synthetic and real data reveal that the algorithm proposed in this article can discover the cluster center of complex data sets with large difference in density, flow pattern or cross‐winding. It can also provide effective clustering.
Flavylium Fluorophores as Near‐Infrared Emitters
Authors: Uranga‐Barandiaran Olatz , Casanova David , Castet Frédéric
Published: September 2020

This theoretical work rationalizes the absorption and fluorescence emission properties of conjugated dyes composed of dimethylamino flavylium heterocycles linked by a polymethine chain, which were recently reported to act as efficient shortwave infrared emitters. Density functional theory is used to characterize the electronic structure of the low‐lying excited states as a function of the polymethine chain length. Decomposition of the computed excitations in terms of diabatic states is also performed to deconvolute the excited states wavefunction into charge‐transfer intramolecular excitations. Based on these results, chemical substitution patterns consisting in enhancing the electron‐withdrawing strength of the polymethine bridge and the electron‐donating ability of the lateral flavylium fragments, are proposed to further redshift the photoluminescence of the fluorophores.
Structural and Photophysical Properties of Various Polypyridyl Ligands: A Combined Experimental and Computational Study
Authors: De Bruecker Liesbeth , Everaert Jonas , Van Der Voort Pascal , Stevens Christian V. , Waroquier Michel , Van Speybroeck Veronique
Published: September 2020

Covalent triazine frameworks (CTFs) with polypyridyl ligands are very promising supports to anchor photocatalytic complexes. Herein, we investigate the photophysical properties of a series of ligands which vary by the extent of the aromatic system, the nitrogen content and their topologies to aid in selecting interesting building blocks for CTFs. Interestingly, some linkers have a rotational degree of freedom, allowing both a trans and cis structure, where only the latter allows anchoring. Therefore, the influence of the dihedral angle on the UV‐Vis spectrum is studied. The photophysical properties are investigated by a combined computational and experimental study. Theoretically, both static and molecular dynamics simulations are performed to deduce ground‐ and excited state properties based on density functional theory (DFT) and time‐dependent DFT. The position of the main absorption peak shifts towards higher wavelengths for an increased size of the π‐system and a higher π‐electron deficiency. We found that the position of the main absorption peak among the different ligands studied in this work can amount to 271 nm; which has a significant impact on the photophysical properties of the ligands. This broad range of shifts allows modulation of the electronic structure by varying the ligands and may help in a rational design of efficient photocatalysts.
Theoretical Insights into Specific Ion Effects and Strong‐Weak Acid‐Base Rules for Ions in Solution: Deriving the Law of Matching Solvent Affinities from First Principles
Authors: Miranda‐Quintana Ramón Alain , Smiatek Jens
Published: September 2020

We present a detailed study of specific ion effects, volcano plots and the law of matching solvent affinities by means of a conceptual density functional theory (DFT) approach. Our results highlight that specific ion effects and the corresponding implications on the solvation energy are mainly due to differences in the electric chemical potentials and chemical hardnesses of the ions and the solvent. Our approach can be further used to identify reliable criteria for the validity of the law of matching solvent affinities. Basic expressions are derived, which allow us to study the limiting conditions for this empirical observation with regard to matching chemical reactivity indices. Moreover, we show that chaotropic and kosmotropic concepts and their implications for the stability of ion pairs are directly related to a generalized strong and weak acids and bases (SWAB) principle for ions in solution, which is also applicable to rationalize the shape of volcano plots for different solvents. In contrast to previous assumptions, all empirical findings can be explained by the properties of local solvent‐ion complexes which dominate the specific global behavior of ion pairs in solution.
Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants
Authors: Holze Friederike , Liechti Matthias E. , Hutten Nadia R.P.W. , Mason Natasha L. , Dolder Patrick C. , Theunissen Eef L. , Duthaler Urs , Feilding Amanda , Ramaekers Johannes G. , Kuypers Kim P.C.
Published: September 2020

“Microdoses” of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokinetic‐pharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 µg) and placebo were administered in a double‐blind, randomized, placebo‐controlled crossover study in 23 healthy participants. Test days were separated by at least 5 days. Plasma levels of LSD and subjective effects were assessed up to 6 hours after administration. Pharmacokinetic parameters were determined using compartmental modeling. Concentration‐subjective effect relationships were described using pharmacokinetic‐pharmacodynamic modeling. Mean (95% confidence interval) maximal LSD concentrations were 151 pg/mL (127–181), 279 pg/mL (243–320), and 500 pg/mL (413–607) after 5, 10, and 20 µg LSD administration, respectively. Maximal concentrations were reached after 1.1 hours. The mean elimination half‐life was 2.7 hours (1.5–6.2). The 5 µg dose of LSD elicited no significant acute subjective effects. The 10 µg dose of LSD significantly increased ratings of “under the influence” and “good drug effect” compared with placebo. These effects began an average of 1.1 hours after 10 µg LSD administration, peaked at 2.5 hours, and ended at 5.1 hours. The 20 µg dose of LSD significantly increased ratings of “under the influence,” “good drug effects,” and “bad drug effects.” LSD concentrations dose‐proportionally increased at doses as low as 5–20 µg and decreased with a half‐life of 3 hours. The threshold dose of LSD base for psychotropic effects was 10 µg.
Fine Needle Aspiration Cytology of Malignant Digestive System Gastrointestinal Neuroectodermal Tumor in a Lymph Node Metastasis from a Previously Diagnosed Liver Primary: A Case Report and Review of Literature
Authors: Gadde Ramya , Linos Konstantinos , Lisovsky Mikhail , Kerrigan Timothy , Loehrer Andrew P. , Kasumova Gyulnara , Kerr Darcy A. , Liu Xiaoying
Published: September 2020

Malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare neoplasm. Immunohistochemically, GNET typically demonstrates neural differentiation but lacks melanocytic differentiation, making it distinct from clear cell sarcoma of the soft tissues (CCS). Herein we report for the first time the cytomorphologic features of lymph node metastasis from presumably liver GNET. A 36‐year‐old female presented with fevers, night sweats, loss of appetite, and a 20‐lbs weight loss. Radiographic imaging showed a 13 cm heterogeneously enhancing mass in the right lobe of the liver and a hypermetabolic 0.9 cm periportal lymph node on positron emission tomography–computed tomography (PET/CT). Initially, a CT‐guided liver biopsy was performed followed by right hepatic lobectomy and portal lymphadenectomy. The liver biopsy and resection showed an S100‐protein and SOX10 positive malignant neoplasm and genomic profiling of liver biopsy revealed EWSR1‐CREB1gene rearrangement. These findings in conjunction with the morphologic and immunohistochemical profile were diagnostic of GNET. Two months later, she presented with recurrent lymphadenopathy in the upper abdomen. Fine needle aspiration of the periportal nodal mass revealed single and clusters of primitive, large to medium‐sized neoplastic cells with round to oval nuclei, high nuclear‐cytoplasmic ratio, vesicular chromatin, and prominent nucleoli. The tumor cells were S100 protein and SOX10 positive, consistent with metastasis of the patient's recently diagnosed malignant digestive system GNET. Palliative chemotherapy was administered but the patient died a few days later, 4 months from the initial diagnosis. Awareness of this entity and judicial use of ancillary studies including molecular testing are essential for achieving accurate diagnosis.
Practitioners' perspectives on ethical issues within the treatment of eating disorders: Results from a concept mapping study
Authors: Walker D. Catherine , Heiss Sydney , Donahue Joseph M. , Brooks Julia M.
Published: September 2020

Objective

Treating patients with eating disorders (EDs) is associated with an array of ethical concerns, including balancing patients' health and autonomy, access to care, and use of harm‐reduction versus recovery‐oriented treatment models. The primary aim of the current study is to gain a better understanding of ethical issues faced by ED practitioners by using a concept mapping, or Q‐sort, approach.

Method

A total of 12 practitioners completed the brainstorming phase and generated statements regarding ethical issues they faced while treating patients with EDs. A subsequent 38 practitioners completed a sorting task, where they created and labeled piles, into which they grouped each statement. Of those 38 participants, 30 rated both the frequency with which they encountered each ethical issue and its impact on patient care.

Results

A total of six clusters emerged: Insufficient Level of Care, Lack of Evidence‐Based Practice, Insurance Barriers, Family Involvement, Patient Autonomy, and Limited Access to Expertise. Lack of Evidence‐Based Practice, Insurance Barriers, and Insufficient Level of Care was the most frequent problem faced by ED practitioners, whereas Insurance Barriers and Patient Autonomy had the greatest impact.

Discussion

Findings outline frequent and impactful areas of ethical concern that arise when treating patients diagnosed with EDs. Practitioners most commonly reported that patient‐ and insurance‐driven factors limited patient access to appropriate care. Regulations supporting the provision of evidence‐based care should be emphasized in public health policy and advocacy efforts, given their impact in limiting the delivery of adequate patient care.
Polyandry provides reproductive and genetic benefits in colonising populations
Authors: Lewis Rebecca C. , Pointer Michael D. , Friend Lucy A. , Vasudeva Ramakrishnan , Bemrose James , Sutter Andreas , Gage Matthew J. G. , Spurgin Lewis G.
Published: September 2020

Polyandry, when females mate with more than one male, is theorised to play an important role in successful colonisation of new habitats. In addition to possible benefits from sexual selection, even mild polyandry could facilitate colonisation by protecting against inbreeding and reducing the costs of mating with incompatible or infertile males. Here, we measure the importance of mild polyandry for population viability and reproductive fitness following experimental founder events into a higher‐temperature regime. Using colonisation experiments with the model beetle Tribolium castaneum, in which females can produce offspring for up to 140 days following a single mating, we founded more than 100 replicate populations using single females that had been given the opportunity to mate with either one or two males and then tracked their subsequent population dynamics. Following population viability and fitness across 10 generations, we found that extinction rates were significantly lower in populations founded by females given polyandrous opportunities to mate with two males (9%) compared to populations founded by monogamous females (34%). In addition, populations founded by females that had been provided with opportunities to store sperm from two different males showed double the median productivity following colonisation compared to monogamous‐founded populations. Notably, we identified short‐term and longer‐term benefits to post‐colonisation populations from double‐mating, with results suggesting that polyandry acts to both protect against mating with incompatible males through the founder event, and reduce inbreeding depression as the colonisation proceeds for 10 generations. Our results therefore show that even mild polyandry provides both reproductive and genetic benefits for colonising populations.
Scavenger community structure along an environmental gradient from boreal forest to alpine tundra in Scandinavia
Authors: Gomo Gjermund , Rød‐Eriksen Lars , Andreassen Harry P. , Mattisson Jenny , Odden Morten , Devineau Olivier , Eide Nina E.
Published: September 2020

Scavengers can have strong impacts on food webs, and awareness of their role in ecosystems has increased during the last decades. In our study, we used baited camera traps to quantify the structure of the winter scavenger community in central Scandinavia across a forest–alpine continuum and assess how climatic conditions affected spatial patterns of species occurrences at baits. Canonical correspondence analysis revealed that the main habitat type (forest or alpine tundra) and snow depth was main determinants of the community structure. According to a joint species distribution model within the HMSC framework, species richness tended to be higher in forest than in alpine tundra habitat, but was only weakly associated with temperature and snow depth. However, we observed stronger and more diverse impacts of these covariates on individual species. Occurrence at baits by habitat generalists (red fox, golden eagle, and common raven) typically increased at low temperatures and high snow depth, probably due to increased energetic demands and lower abundance of natural prey in harsh winter conditions. On the contrary, occurrence at baits by forest specialists (e.g., Eurasian jay) tended to decrease in deep snow, which is possibly a consequence of reduced bait detectability and accessibility. In general, the influence of environmental covariates on species richness and occurrence at baits was lower in alpine tundra than in forests, and habitat generalists dominated the scavenger communities in both forest and alpine tundra. Following forecasted climate change, altered environmental conditions are likely to cause range expansion of boreal species and range contraction of typical alpine species such as the arctic fox. Our results suggest that altered snow conditions will possibly be a main driver of changes in species community structure.
Efficacy and safety of sacubitril‐valsartan in heart failure: a meta‐analysis of randomized controlled trials
Authors: Zhang Hongzhou , Huang Tieqiu , Shen Wen , Xu Xiuxiu , Yang Pingping , Zhu Dan , Fang Haiyang , Wan Hongbing , Wu Tao , Wu Yanqing , Wu Qinghua
Published: September 2020

Aims

Sacubitril‐valsartan has been shown to have superior effects over angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF) and hypertension. The efficacy and safety of sacubitril‐valsartan in patients with HF are controversial. We performed a meta‐analysis of randomized controlled trials to assess and compare the effect and adverse events of sacubitril‐valsartan, valsartan, and enalapril in patients with HF.

Methods and results

We conducted a systematic search using PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. Randomized controlled trials involving the use of sacubitril‐valsartan in patients with HF were included. We assessed the pooled odds ratio (OR) of all‐cause mortality, cardiovascular mortality, and hospitalization for HF in fixed‐effects models and the pooled risk ratio (RR) of symptomatic hypotension, worsening renal function, and hyperkalaemia in fixed‐effects models. Of the 315 identified records, six studies involving 14 959 patients were eligible for inclusion. Sacubitril‐valsartan reduced the endpoints of all‐cause mortality and cardiovascular mortality in patients with HF with reduced ejection fraction (HFrEF) in three trials with pooled ORs of 0.83 (P = 0.0006) and 0.78 (P < 0.0001), respectively. Regarding the composite outcome of hospitalization for HF in five trials, the pooled OR was 0.79 (P < 0.00001). Compared with enalapril or valsartan, sacubitril‐valsartan was associated with a high risk of symptomatic hypotension (RR 1.47, P < 0.00001), low risk of worsening renal function (RR 0.81, P = 0.005), and low rate of serious hyperkalaemia (≥6.0 mmol/L) (RR 0.76, P = 0.0007) in all six trials.

Conclusions

Compared with angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers, sacubitril‐valsartan significantly decreased the risk of death from all causes or cardiovascular causes in HFrEF and hospitalization for HF in both patients with HFrEF and HF with preserved ejection fraction. Sacubitril‐valsartan reduced the risk of renal dysfunction and serious hyperkalaemia but was associated with more symptomatic hypotension.
Cost‐effectiveness of empagliflozin in the UK in an EMPA‐REG OUTCOME subgroup with type 2 diabetes and heart failure
Authors: Reifsnider Odette S. , Kansal Anuraag R. , Franke Jennifer , Lee Joseph , George Jyothis T. , Brueckmann Martina , Kaspers Stefan , Brand Sarah B. , Ustyugova Anastasia , Linden Stephan , Stargardter Matthew , Hau Nikco
Published: September 2020

Aims

Heart failure (HF) and type 2 diabetes (T2D), common co‐morbidities, translate into worse patient prognoses and higher direct costs than for either condition alone. Empagliflozin has been shown to markedly reduce cardiovascular (CV) deaths and HF hospitalizations (HHF) in HF patients with T2D. This study evaluated the lifetime cost‐effectiveness of supplementing standard of care (SoC) with empagliflozin, relative to SoC alone, in HF patients with T2D from the UK payer perspective.

Methods and results

An existing discrete‐event simulation model was adapted for the economic evaluation. Risk equations developed from time‐dependent parametric survival analyses using patient‐level HF subpopulation data from the EMPA‐REG OUTCOME trial were employed to predict CV and renal events. Non‐CV death, utility weights, and costs were drawn from UK sources. Quality‐adjusted life years (QALYs) and costs were discounted at 3.5% per annum. Relative to SoC, empagliflozin with SoC yielded fewer first HHF, recurrent HHF, CV death, and non‐fatal myocardial infarction but more non‐fatal stroke events. Empagliflozin with SoC vs. SoC alone was associated with increased average life expectancy (10.80 vs. 9.59 LYs) and quality of life (6.27 vs. 5.62 QALYs), though at higher lifetime cost (£18 197 vs. £16 829) per person, resulting in an incremental cost‐effectiveness ratio of £2093 per QALY. The probability of empagliflozin being cost‐effective in the HF subpopulation at a £20 000 per QALY willingness‐to‐pay threshold was 91%.

Conclusions

This analysis suggests that adding empagliflozin to SoC in HF patients with T2D constitutes a cost‐effective use of UK healthcare resources and may provide long‐term health benefits to patients.
Tumor‐derived microparticles in tumor immunology and immunotherapy
Authors: Ma Jingwei , Zhang Huafeng , Tang Ke , Huang Bo
Published: September 2020

Microvesicles or microparticles, a type of cytoplasm membrane‐derived extracellular vesicles, can be released by cancer cells or normal cell types. Alteration of F‐actin cytoskeleton by various signals may lead to the cytoplasm membrane encapsulating cellular contents to form microparticles, which contain various messenger molecules, including enzymes, RNAs and even DNA fragments, and are released to extracellular space. The release of microparticles by tumor cells (T‐MPs) is a very common event in tumor microenvironments. As a result, T‐MPs not only influence tumor cell biology but also profoundly forge tumor immunology. Moreover, T‐MPs can act as a natural vehicle that delivers therapeutic drugs to tumor cells and immune cells, thus, remodeling tumor microenvironments and resetting antitumor immune responses, thus, conferring T‐MPs a potential role in tumor immunotherapies and tumor vaccines. In this review, we focus on the double‐edged sword role of T‐MPs in tumor immunology, specifically in TAMs and DCs, and emphasize the application of drug‐packaging T‐MPs in cancer patients. We aim to provide a new angle to understand immuno‐oncology and new strategies for cancer immunotherapy.
Fatty Acids and Sterol Rich Stem Back Extract of Shorea Roxburghii Attenuates Hyperglycemia, Hyperlipidemia, and Oxidative Stress in Diabetic Rats
Authors: Makinde Emmanuel Ayobami , Radenahmad Nisaudah , Zaman Raihan Uz , Olatunji Opeyemi Joshua
Published: September 2020

This study investigates the effect of fatty acid and sterol rich extract from the stem back of S. roxburghii (MESS) on hyperglycemia, hyperlipidemia, and oxidative stress induced by high fat diet/streptozotocin (HFD/STZ) in rats. The results indicate that MESS (100 and 400 mg kg−1) reduces fasting blood glucose (FBG), serum lipids including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL‐C), aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), creatinine, blood urea nitrogen (BUN), and glycated hemoglobin (HbA1c). In addition, MESS significantly elevates antioxidant enzymes activities including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‐Px) and suppressed malondialdehyde (MDA) and myeloperoxidase (MPO) content in the kidney and liver tissues. Furthermore, MESS enhances insulin secretion and ameliorate histological alterations in the pancreas, kidney, and liver treated diabetic rats. These results demonstrate that MESS exerts potent anti‐hyperglycemic, antihyperlipidemic, and antioxidant effects and may have potentials to prevent diabetes.

Practical Applications: The effects of the stem back of S. roxburghii (MESS) on hyperglycemia, hyperlipidemia, and oxidative stress induced by high fat diet/streptozotocin (HFD/STZ) in rats are investigated. The results show that supplementation with MESS counteracted hyperglycemia, hyperlipidemia, and oxidative stress in diabetic rats indicating its ameliorative effect on diabetes and hyperglycemia induced oxidative stress. This research provides a theoretical basis for the development of functional nutraceuticals from MESS diabetic patients.
Photovoltaic Modules Waste Management: Ethical Issues for Developing Nations
Authors: Okoroigwe Florence C. , Okoroigwe Edmund C. , Ajayi Oluwatoyin O. , Agbo Solomon N. , Chukwuma Joseph N.
Published: September 2020

Solar photovoltaic (PV) systems are composed of modules and batteries characterized by depreciable, short lifespans. A survey was carried out to ascertain the level of awareness of the management of used PV modules in developing countries. Even though the respondents are aware of the environmental and health risks of the chemical components of the modules, nothing is being done presently to recycle or plan for the management of the items at end‐of‐life (EoL) period in developing countries. Whereas PV modules at EoL are being reprocessed by recycling in developed countries like the EU, it is not being considered as a health and environmental challenge, as for other electronic wastes in developing countries. Herein, the status and ethical challenges of PV waste generation in developing countries are discussed. Data from a structured survey instrument are obtained, analyzed, and discussed for determining the precursory method to avoid PV wastes in developing countries. It is observed that soon when most installations will be decommissioned, the developing nations will begin to experience a huge collection of PV wastes like other electronic gadgets and be exposed to the dangers of electronic waste pollution if necessary legislative programs are neglected.
Operation optimization and costs analysis of the wet desulfurization system in an ultra‐supercritical coal‐fired power plants
Authors: Wang Weishu , Luo Xiaoyu , Li Quangong , Xu Kai , Liu Jun
Published: September 2020

With the increasingly strict requirements on energy saving and environmental protection, the economical, efficient and environment friendly operation of large coal‐fired units are being more and more critical. In light of the technical problems of massive energy consumption and high cost in the operation of the wet desulfurization system in a 1,000 MW ultra‐supercritical boiler, the effects of slurry circulation pump combination, slurry pH and absorption tower liquid level on desulfurization efficiency under different unit loads were tested, and the total operating costs were calculated. The results showed that the power consumption under different conditions could be greatly reduced by changing the combination of slurry circulation pumps. The power cost increases from 1,059.42 to 1,146.99 yuan/hr as the combination of slurry circulation pump changes from AC pump combination to BD pump combination under 1,000 MW, increased by 7.63%. Considering all factors, the combination of BC circulating pump can effectively reduce the power consumption cost and achieve the optimal economical operation under the load of 1,000 and 750 MW. The desulfurization efficiency is in direct proportion to the increase of slurry pH. The optimal pH of slurry under 1,000 MW is in the range of 5.50–5.60, 4.80–4.90 under 750 MW, and 4.50–4.60 under 500 MW. Besides, the absorption tower liquid level has a significant impact on the energy consumption of desulfurization system. With the decrease of the absorption tower liquid level, the power consumption cost of desulfurization system shows a downward trend. To avoid the frequent adjustment of liquid level which may result in safety accidents, the optimal liquid level of absorption tower is maintained at 8.00–9.00 m under different unit loads. The research results can provide significant guidance for the operation optimization and fine management of the desulfurization system of the same type.
Microwave assisted solvothermal synthesis of quasi cubic F doped TiO2 nanostructures and its performance as dye sensitized solar cell photoanode
Authors: Madurai Ramakrishnan Venkatraman , Natarajan Muthukumarasamy , Pitchaiya Selvakumar , Santhanam Agilan , Velauthapillai Dhayalan , Pugazhendhi Arivalagan
Published: September 2020

By the process of doping in semiconducting nanomaterials, properties of the materials such as electronic, optical and photochemical properties can be effectively tuned. Here fluorine doped TiO2 nanostructures were synthesized by microwave assisted solvothermal technique. The X‐ray diffraction patterns (XRD) and Raman analysis results of the sample exhibits peaks characteristic of anatase TiO2. From the UV‐visible absorption analysis, an increase in visible light absorption with no significant change in the absorption edge was noticed. F doped TiO2 nanostructures were found to possess quasi cubic morphology through the transmission electron microscope images and from the presence of well‐defined ring pattern in selected area electron diffraction patterns the polycrystalline nature of the samples were confirmed. The presence of fluorine in the TiO2 lattice was confirmed through the presence of Ti3+ states using X‐ray photoelectron spectroscopy (XPS) analysis and electron paramagnetic resonance (EPR) analysis respectively. The prepared TiO2, F doped TiO2 nanostructures were coated over fluorine doped tin oxide (FTO) substrates, further they were subjected to dye sensitization and were used as photoanodes in dye sensitized solar cells and their power conversion efficiencies were studied.
Exploring the Concepts of Concentration Addition and Independent Action Using a Linear Low-Effect Mixture Model
Authors: Escher Beate , Braun Georg , Zarfl Christiane
Published: September 2020

Chemicals emitted into the environment are typically present at low concentrations but may act together in mixtures. Concentration–response curves of in vitro bioassays were often linear for effect levels <30%, and the predictions for concentration addition (CA) of similarly acting chemicals and for independent action (IA) of dissimilarly acting chemicals overlapped. We derived a joint CA/IA mixture model for the low-effect level portion of concentration–response curves. In a first case study, we evaluated the cytotoxicity of over 200 mixtures of up to 17 components that were mixed in concentration ratios as they occurred in river water. The predictions of the full IA model were indistinguishable from the predictions of the full CA model up to 10% effect, confirming the applicability of the joint CA/IA mixture model at low effect levels. In a second case study, we evaluated if environmental concentrations trigger effects at levels low enough for the joint CA/IA mixture model to apply. The detected concentrations were scaled by their toxic potencies to estimate the mixture effect of the detected chemicals in a complex mixture. In 86% of 156 samples the effects fell in the validity range of the joint CA/IA mixture model (<10% effect level), confirming the CA assumption for toxic unit summation. The joint CA/IA mixture model is not suitable for testing specific mixture hypotheses and interactions of chemicals in mixtures, where more refined models are required; but it is helpful for the interpretation of effects of complex (multicomponent) environmental mixtures, especially for water samples with relatively low effect level. Environ Toxicol Chem 2020;39:2552–2559. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Complex mixtures of organic chemicals that occur in water samples typically at low concentrations act together by a joint mixture model that integrates concentration addition and independent action.
Large‐scale simulation of shallow water waves via computation only on small staggered patches
Authors: Bunder Judith E. , Divahar Jayaraman , Kevrekidis Ioannis G. , Mattner Trent W. , Roberts Anthony J.
Published: September 2020

A multiscale computational scheme is developed to use given small microscale simulations of complicated physical wave processes to empower macroscale system‐level predictions. By coupling small patches of simulations over unsimulated space, large savings in computational time are realizable. Here, we generalize the patch scheme to the case of wave systems on staggered grids in two‐dimensional (2D) space. Classic macroscale interpolation provides a generic coupling between patches that achieves consistency between the emergent macroscale simulation and the underlying microscale dynamics. Spectral analysis indicates that the resultant scheme empowers feasible computation of large macroscale simulations of wave systems even with complicated underlying physics. As an example of the scheme's application, we use it to simulate some simple scenarios of a given turbulent shallow water model.
Block bootstrap prediction intervals for parsimonious first‐order vector autoregression
Authors: Li Jing
Published: September 2020

This paper attempts to answer the question of whether the principle of parsimony can be applied to interval forecasting for multivariate series. Toward that end, this paper proposes the block bootstrap prediction intervals based on parsimonious first‐order vector autoregression. The new intervals generalize standard bootstrap prediction intervals by allowing for serially correlated prediction errors. The unexplained serial correlation is accounted for by the generalized multivariate block bootstrap, which resamples two‐dimensional arrays of residuals. Different methods of block bootstraps are compared. A Monte Carlo experiment shows that, in most cases, the new intervals from a parsimonious model outperform the standard bootstrap intervals from a complex model. The proposed block bootstrap prediction intervals are illustrated using financial data for interest rates and exchange rates.
Bacteriostatic activity and partial characterization of the bacteriocin produced by L. plantarum sp. isolated from traditional sourdough
Authors: Zangeneh Mina , Khorrami Sadegh , Khaleghi Moj
Published: September 2020

This study was aimed to isolate and partially characterizes the bacteriocin produced by an L. plantarum sp. isolated from traditional sourdough. The bacteriocin was partially purified, and after treating it with different harsh conditions, its antibacterial activity was evaluated against L. monocytogenes as an indicator. Also, the growth phase during which the bacteriocin is produced, and its mode of action, was examined. Finally, the molecular weight of this compound was evaluated by using SDS‐PAGE analysis. According to the results, this bacteriocin had a molecular weight well lower than 10 kDa that was mainly produced at the early stationary phase and reached its highest activity (3,200 AU/ml) at the same stage. It was tolerant toward a wide range of pH (2–10), temperatures (−20 to 120°C), and high concentrations of NaCl. Notably, the bacteriocin‐producing strain had proteolytic activity, while the bacteriocin produced by that showed resistance to proteolytic enzymes (pepsin, trypsin, and proteinase K). Also, it was revealed that the bacteriocin activity is mostly bacteriostatic so that it considerably inhibits pathogens’ growth, particularly S. aureus, E. coli, and L. monocytogenes. These characteristics prove that strain and its bacteriocin can be considered as one of the most promising agents to use in the food industry.
Biomimetic Antigravity Water Transport and Remote Harvesting Powered by Sunlight
Authors: Geng Hongya , Lv Cunjing , Wu Mingmao , Ma Hongyun , Cheng Huhu , Li Chun , Yuan Jiayin , Qu Liangti
Published: September 2020

Antigravity water transport plays important roles in various applications ranging from agriculture, industry, and environmental engineering. In natural trees, ubiquitous water‐flow over 100 m high from roots through the hierarchical xylem to leaves is driven by sunlight‐powered continuous evaporation and the negative pressure. Inspired by natural trees, herein an artificial trunk‐leaf system is built up to structurally mimic natural trees for a continuous antigravity water delivery. The artificial tree consists of directional microchannels for antigravity water transport, and a top leaf‐like hybrid hydrogel that are acts as continuous solar steam evaporator, plus a purposely engineered steam collector. It is found that continuous uniform microchannels of acetylated chitin optimize and enhance capillary rise (≈37 cm at 300 min) and reduce vertical water transport resistance. A remote water harvesting, and purification is performed with a high rate of 1.6 kg m−2 h−1 and 184 cm in height under 1 sun irradiation and the collection efficiency up to 100% by evaporative cooling technique. It is envisioned that the basic design principles underlying the artificial tree can be used to transform solar energy into potential energy.
Late Miocene Yellow River formation in Qingtongxia area, North China: Detrital zircon and heavy mineral analysis at Niushou Mountain, Ningxia
Authors: Bao Guodong , Chen Hong , Zhao Xitao
Published: September 2020

The development and formation times of the Yellow River, the second largest drainage system in China, remain controversial. The Ganhegou Formation, a set of Upper Miocene–Pliocene fluvial facies sediments, developed around Niushou Mountain in the outermost edge of the arcuate structural belt in the northeastern margin of the Tibetan Plateau and has a sediment composition very similar to that of the Yellow River. In this article, the relationship between the deposition of the Ganhegou Formation and the Yellow River is confirmed through the analysis and comparison of sediment composition, detrital zircons, and heavy mineral characteristics of the Ganhegou Formation, a Yellow River terrace, and the modern Yellow River. The sediments of the Ganhegou Formation contain abundant well‐ground and sorted fluvial pebbles that are largely consistent with Yellow River sediments. The analysis of the composition of zircons and heavy minerals shows that the age peaks of all detrital zircons are primarily among 200–300 Ma, 400–500 Ma, and 1,700–2,000 Ma and that all the heavy minerals are generally characterized by the combination of ‘haematite + garnet + zircon + epidote + quartz and altered minerals’. Therefore, the Ganhegou Formation in the Niushou Mountain area of Ningxia is a likely sediment of the ancient Yellow River, which has existed at Qingtongxia since at least the Late Miocene.