bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidentate Pyridyl‐Aminophosphinite and Pyridyl‐Phosphoramidite Ruthenium(II) Complexes: Synthesis, Structure and Application as Levulinic Acid Hydrogenation Pre‐Catalysts
Authors: Amenuvor Gershon , Rono Charles K. , Darkwa James , Makhubela Banothile C. E.
Published: August 2019

Novel multidentate pyridyl‐aminophosphinite (L1) and pyridyl‐phosphoramidite (L2) ligands of N^P^P^N‐donor system have been synthesized via a series of simple steps. The ligands are symmetrical and as a result, their reactions with [Ru(p‐cymene)Cl2]2 and [Ru(benzene)Cl2]2 lead to the formation of four monodentate bimetallic complexes (1–4) that retain the symmetry of the ligands. Meso and racemic mixtures (rac) of bidentate bimetallic complexes 5–8 were formed from the monodentate complexes through coordination of the pyridine nitrogen atoms to the two metal centers. The isomerism occurs at each metal center, which was evidenced by 31P{1H}, 1H NMR spectroscopy and single‐crystal X‐ray diffraction. The complexes were active towards hydrogenation of levulinic acid (LA) to γ‐valerolactone (GVL) using formic acid as the hydrogen source. The complexes are active at relatively low temperatures and are able to perform the hydrogenation in the absence of any additional solvent apart from the reagents to give high TON of 3 600. The catalysts are recyclable up to the fourth cycle, following which 20 % loss of activity is seen.
Stress and the brain: Perceived stress mediates the impact of the superior frontal gyrus spontaneous activity on depressive symptoms in late adolescence
Authors: Wang Song , Zhao Yajun , Zhang Lei , Wang Xu , Wang Xiuli , Cheng Bochao , Luo Kui , Gong Qiyong
Published: August 2019

Identifying factors for the prediction of depression is a long‐standing research topic in psychiatry and psychology. Perceived stress, which reflects the tendency to appraise one's life situations as stressful and overwhelming, has emerged as a stable predictor for depressive symptoms. However, the neurobiological bases of perceived stress and how perceived stress influences depressive symptoms in the healthy brain remain largely unknown. Here, we investigated these issues in 217 healthy adolescents by estimating the fractional amplitude of low‐frequency fluctuations (fALFFs) via resting‐state functional magnetic resonance imaging. A whole‐brain correlation analysis showed that higher levels of perceived stress were associated with greater fALFF in the left superior frontal gyrus (SFG), which is a core brain region for cognitive control and emotion regulation‐related processes. Mediation analysis further indicated that perceived stress mediated the link between the fALFF in the left SFG and depressive symptoms. Importantly, our results remained significant even when excluding the influences of head motion, anxiety, SFG gray matter structure, and school environment. Altogether, our findings suggested that the fALFF in the left SFG is a neurofunctional marker of perceived stress in adolescents and revealed a potential indirect effect of perceived stress on the association between the SFG spontaneous activity and depressive symptoms.
Metal Olefin Complexes: Revisiting theDewar−Chatt−DuncansonModel and Deriving Reactivity Patterns from Carbon‐13 NMR Chemical Shift
Authors: Gordon Christopher P. , Andersen Richard A. , Copéret Christophe
Published: August 2019

Metal olefin complexes that are ubiquitous intermediates in catalysis are investigated by a detailed analysis of their13C‐NMR chemical shift tensors. This analysis allows evidencing specific electronic features, namely the olefin‐to‐metalσ‐donation and the metal‐to‐olefinπ‐backdonation as proposed in theDewar−Chatt−Duncansonmodel. Apart from these interactions, the chemical shift tensor analysis reveals an additional ligand‐to‐metalπ‐donation of the olefinσ(C=C) orbital in systems with suitably oriented vacant d‐orbitals. This interaction which is not accounted for in theDewar−Chatt−Duncansonmodel explains the reactivity of this type of metal olefin complexes towards oxidative cyclization (olefin insertion) and protonolysis.
Applying lean management to reduce radiology turnaround times for emergency department
Authors: Verbano Chiara , Crema Maria
Published: August 2019

Given the high impact of emergency department (ED) on the quality of care delivered by an hospital, and the many challenges it is facing (eg, overcrowding, excessive waiting time, cost containment, and increasing demand from patients), innovative managerial approaches should be adopted in order to develop safer and more efficient healthcare in this setting.

The current study focuses on an application of lean thinking to reduce radiology turnaround times for ED, with the final aim to highlight the key factors enabling the adoption of lean thinking in this context. A research framework has been developed in the literature to analyse lean projects in healthcare and it has been adapted to study the case selected in an Italian hospital. In particular, organizational aspects, phases, and activities of the applied methodology, tools and procedures, and the achieved outcomes have been analysed.

The study reports how radiology turnaround times for ED can be significantly reduced applying lean management principles and techniques. The achieved results contribute not only to comply with the regulation, but also to enhance the quality of care delivered to the patient; moreover, staff communication, involvement, and process awareness are favoured by the realization of similar projects promoting the diffusion of a lean culture.
Oxidative phosphorylation as a potential therapeutic target for cancer therapy
Authors: Sica Valentina , Bravo‐San Pedro José Manuel , Stoll Gautier , Kroemer Guido
Published: August 2019

In contrast to prior belief, cancer cells require oxidative phosphorylation (OXPHOS) to strive, and exacerbated OXPHOS dependency frequently characterizes cancer stem cells, as well as primary or acquired resistance against chemotherapy or tyrosine kinase inhibitors. A growing arsenal of therapeutic agents is being designed to suppress the transfer of mitochondria from stromal to malignant cells, to interfere with mitochondrial biogenesis, to directly inhibit respiratory chain complexes, or to disrupt mitochondrial function in other ways. For the experimental treatment of cancers, OXPHOS inhibitors can be advantageously combined with tyrosine kinase inhibitors, as well as with other strategies to inhibit glycolysis, thereby causing a lethal energy crisis. Unfortunately, most of the preclinical data arguing in favor of OXPHOS inhibition have been obtained in xenograft models, in which human cancer cells are implanted in immunodeficient mice. Future studies on OXPHOS inhibitors should elaborate optimal treatment schedules and combination regimens that stimulate—or at least are compatible with—anticancer immune responses for long‐term tumor control.
Group divisible designs with block size four and type gum1—III
Authors: Forbes A. D.
Published: August 2019

We deal with group divisible designs (GDDs) that have block size four and group type , where or 4 (mod 6). We show that the necessary conditions for the existence of a 4‐GDD of type are sufficient when  = 14, 20, 22, 26, 28, 32, 34, 38, 40, 44, 46, 50, 52, 58, 62, 68, 76, 88, 92, 100, 104, 116, 124, 136, 152, 160, 176, 184, 200, 208, 224, 232, 248, 272, 304, 320, 368, 400, 448, 464 and 496. Using these results we go on to show that the necessary conditions are sufficient for ,  = 19, 23, 25, 29, 31, , , as well as for ,  = 2, 5, 7, 11, 13, 17, , with possible exceptions , and for a few large values of .
CytoMatrix for a reliable and simple characterization of lung cancer stem cells from malignant pleural effusions
Authors: Bruschini Sara , di Martino Simona , Pisanu Maria Elena , Fattore Luigi , De Vitis Claudia , Laquintana Valentina , Buglioni Simonetta , Tabbì Eugenio , Cerri Andrea , Visca Paolo , Alessandrini Gabriele , Facciolo Francesco , Napoli Christian , Trombetta Marcella , Santoro Antonio , Crescenzi Anna , Ciliberto Gennaro , Mancini Rita
Published: August 2019

Cancer stem cells (CSCs) are a subpopulation with the properties of extensive self‐renewal, capability to generate differentiated cancer cells and resistance to therapies. We have previously shown that malignant pleural effusions (MPEs) from patients with non‐small‐cell lung cancer (NSCLC) represent a valuable source of cancer cells that can be grown as three‐dimensional (3D) spheroids enriched for stem‐like features, which depend on the activation of the Yes‐associated protein‐transcriptional coactivator with PDZ‐binding motif (YAP‐TAZ)/Wnt‐βcatenin/stearoyl‐CoA desaturase 1 (SCD1) axis. Here, we describe a novel support, called CytoMatrix, for the characterization of limited amounts of cancer cells isolated from MPEs of patients with NSCLC. Our results show that this synthetic matrix allows an easy and fast characterization of several epithelial cellular markers. The use of CytoMatrix to study CSCs subpopulation confirms that SCD1 protein expression is enhanced in 3D spheroids when compared with 2D adherent cell cultures. YAP/TAZ nuclear‐cytoplasmic distribution analysed by CytoMatrix in 3D spheroids is highly heterogeneous and faithfully reproduces what is observed in tumour biopsies. Our results confirm and extend the robustness of our workflow for the isolation and phenotypic characterization of primary cancer cells derived from the lung MPEs and underscore the role of SCD1.
Weight loss in heart failure is associated with increased mortality only in non‐obese patients without diabetes
Authors: Niedziela Jacek T. , Hudzik Bartosz , Strojek Krzysztof , Poloński Lech , Gąsior Mariusz , Rozentryt Piotr
Published: August 2019

Background

Weight loss (WL) is an independent predictor of mortality in patients with heart failure (HF). Moderate WL is recommended for overweight or obese patients with type 2 diabetes mellitus (DM). The aim of this study was to assess the prognostic impact of body weight reduction on survival in patients with both HF with reduced ejection fraction (HFrEF) and DM.

Methods

The study comprised patients with HFrEF at the outpatient clinic. WL was defined as a body weight reduction of at least 7.5% during at least 6 months. Clinical features and 1 year mortality were analysed in WL and DM groups. Multivariate regression model was chosen to assess the predictive role of WL in HF patients with and without DM. The analysis regarding obesity before HF was also performed.

Results

The study comprised 777 patients with HFrEF. Mean age was 53.2 ± 9.2, 12.0% were women, mean EF was 23.7 ± 6.0 %, and New York Heart Association III or IV class, DM, and WL were found in 60.5%, 33.3%, and 47.1% patients, respectively. WL was more prevalent in diabetic patients, comparing with those without DM (53.7% vs. 43.8%, respectively, 0.01), and was associated with higher 1 year mortality only in non‐diabetic group (17.6% for WL vs. 8.2% for non‐WL, log‐rank 0.001). In the multivariate analysis, WL was associated with a higher risk of 1 year mortality in non‐diabetic patients: HR 1.76 (1.05–2.95), 0.03 and only in the subgroup without obesity: HR 2.35 (1.28–4.32), 0.006. In non‐diabetic patients with obesity and in diabetic patients regardless of weight status, WL was not associated with worse prognosis (thereof, WL was excluded from the multivariate models).

Conclusions

Overall, WL in HFrEF has emerged as a predictor of unfavourable outcomes only in non‐obese patients without DM. More importantly, this study has identified that the presence of DM (irrespective of weight status) or the presence of obesity in non‐diabetic patients abolished the unfavourable impact of WL on long‐term outcomes.
Efficacy and safety of telbivudine to prevent mother‐to‐child transmission of hepatitis B virus in middle‐ and late‐stage pregnancy with high viral loads
Authors: Xu Jing , Tao Lin lin , Ma Li xian
Published: August 2019

Objective

To observe the efficacy and safety of telbivudine on mother‐infant blockade in pregnant women with hepatitis B virus (HBV) DNA.

Methods

A total of 141 pregnant women between 24 and 28 weeks of gestation and chronic HBV carriers with HBV DNA ≥106 copies/mL were enrolled, 105 in the treatment group and 36 in the control group. The treatment group was given telbivudine 600 mg/d oral, and the control group did not use antiviral drugs. Hepatitis B immunoglobulin 200 IU intramuscular injection and hepatitis B vaccine (HBVac) 10 μg subcutaneous injection were given to the infants in both groups within 12 hours after birth, and 10 μg of HBVac was subcutaneously injected when the infants were 1‐month and 6‐month old. Safety endpoints including HBV DNA quantification, liver function, CK were observed before treatment, 4 weeks after treatment, before delivery, and 24 weeks after delivery.

Results

There was no difference in HBV DNA levels between the two groups before treatment and 6 months after delivery (P > .05). The HBV DNA level in the treatment group was significantly lower than that in the control group before delivery (P < .05). Between the two groups, the HBV positive rate was statistically different between the two groups (P < .05), and the difference of serum HBsAg of infants had statistical significance (P < .05), but the safety of the telbivudine group was not significantly different from that of the control group (P > .05).

Conclusion

The application of telbivudine antiviral therapy in the middle and late stage of pregnancy of HBV high‐load pregnant women can significantly reduce the HBV DNA level before delivery, reduce the mother‐to‐child transmission rate of HBV, and have excellent security.
Raman spectroscopic evidence of impurity‐induced structural distortion in SmB6
Authors: Nguyen Thi Huyen , Nguyen Thi Minh Hien , Kang Boyoun , Cho Beongki , Han Mancheon , Choi Hyoung Joon , Kong Mihye , Lee Yongjae , Yang In‐Sang
Published: August 2019

Impurity‐induced structural distortion in SmB6 is suggested by Raman spectroscopy study on impurity‐controlled samples. Significant differences in the Raman spectra of single crystals SmB6(6N), synthesized with 99.9999%‐pure boron, and SmB6(3N), synthesized with 99.9%‐pure boron, are detected. While no noticeable differences are detected in the X‐ray diffraction of SmB6(3N) and SmB6(6N), all the Raman phonon modes of the T2g, Eg, and A1g of SmB6(3N) are clearly broader and shift to higher wavenumbers than those of SmB6(6N), and the T2g and Eg modes of SmB6(3N) show doublet features. Based on the high‐pressure Raman measurements and phonon calculation in uniaxial compression model, we argue that small amount of impurities in SmB6(3N) is enough to induce anisotropic distortion in the B6 octahedra, leading to peculiar behaviors in Raman spectrum of SmB6(3N). Our results may present a clue for understanding the current puzzles about SmB6 of various origins with different impurities.
Raman spectroscopy of zinc oxide nanoplatelets modified with ruthenium (II) complexes
Authors: Ristić‐Djurović Jasna L. , Fernández‐Izquierdo Leunam , Hadžić Branka , Jiménez‐Hernández Linnavel , Díaz‐García Alicia M. , Mitrić Jelena , Babić Biljana , Romčević Maja , Ćirković Saša , Romčević Nebojša
Published: August 2019

We analyzed and compared the unmodified and three modified zinc oxide nanoplatelet materials. The three components used in zinc oxide modification were the 4,4apos;‐bipyridine and two ruthenium (II) complexes, namely, the trans‐[Ru (bpy)(bpyCOO)Cl2]2– and cis‐[Ru (bpy)(bpyCOO)Cl2]2–. The obtained results revealed that after modification, ZnO nanoplatelets became smaller and embedded in the materials used for the modification. When ZnO was modified with either of the two ruthenium (II) complexes, the interaction between them led to a higher activity of ZnO. The metal‐to‐ligand charge transfer that was also detected in the two cases of ZnO nanoplatelets modified with the ruthenium (II) complexes caused significant alteration of the Raman spectrum and consequent changes of the optical properties. Various forms of ruthenium (II) complexes were used in several published studies related to dye‐sensitized solar cells and biomedicine. The biomedical applications include, for example, the ATP (adenosine‐5apos;‐triphosphate) detection, interaction with human serum albumin, DNA analysis, and cancer detection and treatment. The properties of the ZnO nanoplatelets modified with the two ruthenium (II) complexes presented here indicate that it may be worth exploring if the studied materials are applicable in the dye sensitized solar cells and biomedicine. Possible advantage of our results is that they were obtained at room temperature.
Characterizing and evaluating the impacts of national land restoration initiatives on ecosystem services in Ethiopia
Authors: Abera Wuletawu , Tamene Lulseged , Tibebe Degefie , Adimassu Zenebe , Kassa Habtemariam , Hailu Habtamu , Mekonnen Kindu , Desta Gizaw , Sommer Rolf , Verchot Louis
Published: August 2019

Land restoration is considered to be the remedy for 21st century global challenges of land degradation. As a result, various land restoration and conservation efforts are underway at different scales. Ethiopia is one of the countries with huge investments in land restoration. Tremendous land management practices have been implemented across the country since the 1970s. However, the spatial distribution of the interventions has not been documented, and there is no systematic, quantitative evidence on whether land restoration efforts have achieved the restoration of desired ecosystem services. Therefore, we carried out a meta‐analysis of peer‐reviewed scientific literature related to land restoration efforts and their impacts in Ethiopia. Results show that most of the large‐scale projects have been implemented in the highlands, specifically in Tigray and Amhara regions covering about 24 agroecological zones, and land restoration impact studies are mostly focused in the highlands but restricted in about 11 agroecological zones. The highest mean effect on agricultural productivity is obtained from the combination of bunds and biological interventions followed by conservation agriculture practices with 170% and 18% increases, respectively. However, bunds alone, biological intervention alone, and terracing (fanya juu) reveal negative effects on productivity. The mean effect of all land restoration interventions on soil organic carbon is positive, the highest effect being from “bunds + biological” (139%) followed by exclosure (90%). Reduced soil erosion and runoff are the dominant impacts of all interventions. The results can be used to improve existing guidelines to better match land restoration options with specific desired ecosystem functions and services. Although the focus of this study was on the evaluation of the impacts of land restoration efforts on selected ecosystem services, impacts on livelihood and national socioeconomy have not been examined. Thus, strengthening socioeconomic studies at national scale to assess the sustainability of land restoration initiatives is an essential next step.
Assessment of biomass utilization potential of Caragana korshinskii and its effect on carbon sequestration on the Northern Shaanxi Loess Plateau, China
Authors: Liu Weiguo , Yu Zhen , Zhu Qiuan , Zhou Xiaolu , Peng Changhui
Published: August 2019

Biomass has been promoted as a promising energy resource to mitigate global climate change. To evaluate the contribution of biomass utilization to climate change mitigation under the “Grain for Green” program in Northern Shaanxi, China, a soil carbon dynamic model and a life cycle assessment model were integrated to examine the benefits of using Caragana korshinskii Kom. as an energy crop. We found that the annual dry biomass output is maintained at 0.7 Tg during the simulation period (2020–2097). Due to the compensatory effect of biomass regrowth, the global warming potential of biomass‐derived CO2 emissions is approximately 0.045; therefore, the total annual biogenic CO2 emission is 57,211 ± 6,168 Mg CO2 eq. The total annual life cycle CO2 emissions approach 867,072 Mg CO2 eq yr−1. Under the scenario of no biomass removal, final carbon storage ranges from 15.7 to 19.3 TgC, and the highest carbon sequestration rate is 0.47 TgC yr−1. In comparison with the no biomass removal scenario, the carbon sequestration rate (close to 0 MgC yr−1) in the biomass utilization scenario indicates a carbon loss; however, a portion of the carbon loss (31.39–62.09%) can be offset by carbon emission reductions from the substitution of fossil fuels.
Downregulation of CPA4 inhibits non small–cell lung cancer growth by suppressing the AKT/c‐MYC pathway
Authors: Fu Yangyang , Su Lihuang , Cai Mengsi , Yao Boyang , Xiao Sisi , He Qinlian , Xu Le , Yang Lehe , Zhao Chengguang , Wan Tingting , Shao Lianyou , Wang Liangxing , Huang Xiaoying
Published: August 2019

Carboxypeptidase A4 (CPA4) is a member of the metallocarboxypeptidase family. A previous study indicated that CPA4 may participate in the modulation of peptide hormone activity and hormone‐regulated tissue growth and differentiation. However, the role of CPA4 in lung tumorigenesis remains unclear. Our study revealed that CPA4 expression was higher in both lung cancer cells and tumor tissues. We performed 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assays, colony‐formation assays, and Cellomics ArrayScan Infinity analysis to demonstrate that CPA4 knockdown inhibited non small–cell lung cancer (NSCLC) cell proliferation. Conversely, ectopic expression of CPA4 enhanced lung cancer cell proliferation. Consistent with these observations, we generated xenograft tumor models to confirm that CPA4 downregulation suppressed NSCLC cell growth. Mechanistically, we revealed that CPA4 downregulation may induce apoptosis and G1‐S arrest by suppressing the protein kinase B/c‐MYC pathway. These results suggest that CPA4 has an oncogenic effect on lung cancer growth. Taken together, we identified a novel gene in lung cancer that might provide a basis for new therapeutic targets.
Inhibition of mutant Kras and p53‐driven pancreatic carcinogenesis by atorvastatin: Mainly via targeting of the farnesylated DNAJA1 in chaperoning mutant p53
Authors: Xu Dandan , Tong Xin , Sun Leyu , Li Haonan , Jones Ryan D. , Liao Jie , Yang Guang‐Yu
Published: August 2019

Recent studies have indicated that using statins to inhibit the mevalonate pathway induces mutant p53 degradation by impairing the interaction of mutant p53 with DnaJ subfamily A member 1 (DNAJA1). However, the role of the C‐terminus of DNAJA1 with a CAAX box for farnesylation in the binding, folding, and translocation of client proteins such as mutant p53 is not known. In the present study, we used a genetically engineered mouse model of pancreatic carcinoma and showed that atorvastatin significantly increased animal survival and inhibited pancreatic carcinogenesis. There was a dramatic decrease in mutant p53 protein accumulation in the pancreatic acini, pancreas intraepithelial neoplasia lesions, and adenocarcinoma. Supplementation with farnesyl pyrophosphate, a substrate for protein farnesylation, rescued atorvastatin‐induced mutant p53 degradation in pancreatic cancer cells. Tipifarnib, a farnesyltransferase inhibitor, mirrored atorvastatin's effects on mutant p53, degraded mutant p53 in a dose‐dependent manner, and converted farnesylated DNAJA1 into unfarnesylated DNAJA1. Farnesyltransferase gene knockdown also significantly promoted mutant p53 degradation. Coimmunoprecipitation either by an anti‐DNAJA1 or p53 antibody confirmed the direct interaction of mutant p53 and DNAJA1 and higher doses of atorvastatin treatments converted more farnesylated DNAJA1 into unfarnesylated DNAJA1 with much less mutant p53 pulled down by DNAJA1. Strikingly, C394S mutant DNAJA1, in which the cysteine of the CAAX box was mutated to serine, was no longer able to be farnesylated and lost the ability to maintain mutant p53 stabilization. Our results show that farnesylated DNAJA1 is a crucial chaperone in maintaining mutant p53 stabilization and targeting farnesylated DNAJA1 by atorvastatin will be critical for inhibiting p53 mutant cancer.
Clinical implications of sarcomere and nonsarcomere gene variants in patients with left ventricular noncompaction cardiomyopathy
Authors: Li Shijie , Zhang Ce , Liu Nana , Bai Hui , Hou Cuihong , Pu Jielin
Published: August 2019

Background

Robust data regarding genotype–phenotype correlations in left ventricular noncompaction cardiomyopathy (LVNC) are lacking.

Methods

About 72 cardiomyopathy‐related genes were comprehensively screened in a cohort of LVNC patients using targeted sequencing. Baseline and follow‐up data were collected. The primary endpoint was a composite of death and heart transplantation.

Results

A total of 83 unrelated adult patients were included in analyses. Following stringent classification according to the American College of Medical Genetics and Genomics (ACMG) guidelines, 36 pathogenic variants of 14 genes were detected in 32 patients. Among them, 12 patients carried at least one nonsarcomere variant (NSV). At baseline, NSV carriers had a higher frequency of atrial fibrillation, but lower left ventricular ejection fraction, than did noncarriers. During a median follow‐up of 4.2 years, NSV carriers experienced a higher rate of the primary endpoint compared with noncarriers. There was no significant difference in the rate between carriers of sarcomere variant (SV) and noncarriers, as well as between carriers of SV and NSV. The presence of NSV was associated with an increased risk of the primary endpoint independent of age, sex, and cardiac function (hazard ratio: 3.61, 95% confidence interval: 1.42–9.19, p = .002).

Conclusion

NSV may act as a genetic modifier and worsen the clinical phenotype in patients with LVNC.
Novel IFT140 variants cause spermatogenic dysfunction in humans
Authors: Wang Xiong , Sha Yan‐wei , Wang Wen‐ting , Cui Yuan‐qing , Chen Jie , Yan Wei , Hou Xiao‐tao , Mei Li‐bin , Yu Cui‐cui , Wang Jiahui
Published: August 2019

Background

The intraflagellar transport protein 140 homolog (IFT140) is involved in the process of intraflagellar transport (IFT), a process that is essential for the formation and maintenance of most eukaryotic cilia and flagella. Variants IFT140 have been reported to account for ciliopathy but association with male fertility has never been described in humans. Here we report the identification of two novel variants of IFT140 which caused spermatogenic dysfunction and male infertility.

Methods

Whole‐exome sequencing was performed in a 27‐year‐old infertile man presented with severe oligozoospermia, asthenozoospermia, and teratozoospermia (OAT) without other physical abnormality. Sanger sequencing was used to verify gene variants in the patient, his healthy brother, and their parents. Morphology and protein expression in the patient's sperm were examined by transmission electron microscopy (TEM) and immunofluorescence staining. Function of gene variants was predicted by online databases.

Results

Compound heterozygous variants of IFT140: exon16: c.1837G > A: p.Asp613Asn and exon31: c.4247G > A: p.Ser1416Asn were identified in the patient, both of which showed autosomal recessive inheritance in his family, and had extremely low allele frequency in the population. Morphological abnormalities of the head, nucleus, and tails and the absence of IFT140 from the neck and mid‐piece of the patient's spermatozoa were observed. Mutation Taster database predicted a high probability of damage‐causing by both variations.

Conclusion

This study for the first time reported IFT140 variants that cause infertility in humans.
Novel SZT2 mutations in three patients with developmental and epileptic encephalopathies
Authors: Sun Xiaomin , Zhong Xuefei , Li Tingsong
Published: August 2019

Background

The seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that lowers seizure threshold and may also enhance epileptogenesis. In this study, three patients diagnosed with SZT2‐related developmental and epileptic encephalopathies (DEEs) were reviewed aiming to expand knowledge of the genotype and phenotype of SZT2 mutations.

Methods

Targeted next‐generation sequencing was performed to identify pathogenic mutations in 205 cases with DEEs of unknown etiology. Detailed clinical and genetic data were collected from SZT2‐associated patients.

Results

Four novel mutations were found (c.1626 + 1G>A, c.5772dupA, c.4209C > A, c.7307_7308insG) in three patients. All the variants were inherited from their parents. Two patients were siblings and harbored the same mutations and presented developmental delay prior to the onset of seizures. All the individuals were diagnosed as DEEs, drug refractory epilepsy, and experienced status epilepticus (SE); one patient died of SE. One subject showed subependymal nodules as similar as those of tuberous sclerosis complex (TSC) in cranial magnetic resonance imaging (MRI).

Conclusion

Our results expand the genotype and phenotypes of SZT2‐related DEEs, suggesting that SZT2 mutations play a role in developmental delay and epileptic encephalopathy, with high susceptibility to SE and relatively specific MRI findings.
Radiographic patterns of muscle involvement in the idiopathic inflammatory myopathies
Authors: Day Jessica A. , Bajic Nicholas , Gentili Sheridan , Patel Sandy , Limaye Vidya
Published: August 2019

Introduction

This study assesses the burden, distribution, and evolution of muscle inflammation and damage on MRI among subtypes of idiopathic inflammatory myopathy (IIM).

Methods

Musculoskeletal MRIs performed in 66 patients with IIM and 10 patients with non‐IIM between 2009 and 2016 were retrospectively graded for muscle edema, fatty replacement (FR), and atrophy.

Results

Immune‐mediated necrotizing myopathy (IMNM) patients had severe and extensive lower limb muscle edema, FR, and atrophy. The pelvic muscles and adductors were significantly more affected than in patients with dermatomyositis and polymyositis. Inclusion body myositis (IBM) was characterized by marked anterior thigh involvement, which stabilized or progressed at follow‐up imaging. Atrophy and FR grades improved over time in some non‐IBM IIM patients.

Discussion

Patients with IMNM and IBM have characteristic patterns of muscle MRI abnormalities that may allow them to be differentiated radiologically from other IIM subtypes. Muscle damage in non‐IBM IIM may be reversible.
Real‐world experience using hydroxyurea in children with sickle cell disease in Lilongwe, Malawi
Authors: Mvalo Tisungane , Topazian Hillary M. , Kamthunzi Portia , Chen Jane S. , Kambalame Isobel , Mafunga Pilirani , Mumba Noel , Chiume Msandeni , Paseli Khadija , Tegha Gerald , Kumwenda Wiza , Heimlich J. Brett , Ellis Graham , Key Nigel , Gopal Satish , Hoffman Irving , Ataga Kenneth I. , Westmoreland Kate D.
Published: August 2019

Introduction

Sickle cell disease (SCD) is among the most common inherited hematologic diseases in sub‐Saharan Africa (SSA). Historically, hydroxyurea administration in SSA has been restricted due to limited region‐specific evidence for safety and efficacy.

Methods

We conducted a prospective observational cohort study of pediatric patients with SCD in Malawi. From January 2015 to November 2017, hydroxyurea at doses of 10–20 mg/kg/day was administered to children with clinically severe disease (targeted use policy). From December 2017 to July 2018, hydroxyurea was prescribed to all patients (universal use policy).

Results

Of 187 patients with SCD, seven (3.7%) died and 23 (12.3%) were lost to follow‐up. The majority (135, 72.2%) were prescribed hydroxyurea, 59 (43.7%) under the targeted use policy and 76 (56.3%) under the universal use policy. There were no documented severe toxicities. Under the targeted use policy, children with SCD demonstrated absolute decreases in the rates of hospitalization (−4.1 per 1000 person‐days; −7.2, −1.0; P = .004), fevers (−4.2 per 1000 person‐days; −7.2, −1.1; P = .002), transfusions (−2.3 per 1000 person‐days; 95% confidence interval: −4.9, 0.3; P = .06), and annual school absenteeism (−51.2 per person‐year; −60.1, −42.3; P < .0001) within 6 months of hydroxyurea commencement.

Conclusion

We successfully implemented universal administration of hydroxyurea to children with SCD at a tertiary hospital in Malawi. Similar to recently reported trials, hydroxyurea was safe and effective during routine programmatic experience, with clinical benefits particularly among high‐risk children. This highlights the importance of continued widespread scale‐up of hydroxyurea within SCD programs across SSA.
Treatment patterns of prostate cancer with bone metastasis in Beijing: A real‐world study using data from an administrative claims database
Authors: Cheng Yinchu , Zhuo Lin , Pan Yuting , Wang Shengfeng , Zong Jihong , Sun Wentao , Gao Shuangqing , Lu Jian , Zhan Siyan
Published: August 2019

Purpose

To explore treatment patterns among patients with prostate cancer and bone metastasis and to compare clinical outcomes following use of different hormone therapies including combined androgen blockade (CAB), nonsteroidal antiandrogen (NSAA) monotherapy, and castration monotherapy.

Methods

We conducted a population‐based cohort study using data from the Urban Employee Basic Medical Insurance database (2011‐2014) in Beijing. We identified 475 patients with newly diagnosed bone metastatic prostate cancer with at least one prescription for hormone therapy and described their treatment patterns over a median follow‐up of 20.7 months. Cox proportional hazards model was used to compare time to chemotherapy initiation between patients starting on different hormone therapies.

Results

Hormone therapy and/or bisphosphonate therapy with zoledronic acid were the initial treatments in the majority of patients (87.8%); chemotherapy, radiotherapy, and surgery were usually given later in the treatment pathway. CAB was the most common hormone treatment (73.7%). For time to chemotherapy initiation, hazard ratios (95% confidence intervals) were 2.43 (1.08‐5.44) for NSAA alone vs CAB and 1.29 (0.78‐2.13) for castration alone vs CAB.

Conclusions

Our findings show that while a wide range of therapies are used to treat patients with prostate cancer and bone metastasis in Beijing, hormone therapy and bisphosphonate therapy are the most commonly prescribed, and use of CAB was seen to be advantageous in delaying time to chemotherapy initiation over NSAA monotherapy. Future studies should explore longer‐term treatment patterns, including use of newly approved treatments.
Long‐term effects of the intratracheal administration of corticosteroids for the prevention of bronchopulmonary dysplasia: A meta‐analysis
Authors: Zheng Yirong , Xiu Wenlong , Lin Yunfeng , Ren Yanli , Zhang Baoquan , Yang Changyi
Published: August 2019

Background

Bronchopulmonary dysplasia (BPD) is one of the most common complications in premature infants. Since inflammation plays a crucial role in the pathogenesis of BPD, anti‐inflammatory drugs, such as corticosteroids, have long been the focus of prevention research. In this meta‐analysis, we aim to explore the long‐term effects of the intratracheal administration of corticosteroids (IAC) in preventing BPD.

Methods

EMBASE, MEDLINE, the Cochrane Library, Web of Science, CINAHL, Clinicaltrials.gov, the ISRCTN registry, and gray literature were searched to identify randomized controlled trials (RCTs) that evaluated the long‐term effects of IAC for the prevention of BPD in premature infants.

Results

Five RCTs (n = 1515) were eligible for further analysis. The meta‐analysis revealed that the incidence of neurodevelopmental impairment (NDI) did not significantly differ between the IAC group and the control group (relative risk [RR] 0.9, 95% confidence interval [CI] 0.79 to 1.03, P = .14). There was no significant reduction in long‐term mortality (RR, 1.13; 95% CI, 0.9 to 1.41; P = .3) or the incidence of rehospitalization (RR, 0.99; 95% CI, 0.89 to 1.09, P = .82). No significant differences were observed between the IAC group and the control group with regard to height, weight and head circumference at the age of 18 to 36 months of postmenstrual age (PMA) (mean difference [MD], 0.14; 95% CI, −0.26 to 0.54, P = .48).

Conclusions

Our study suggests that IAC in preterm infants does not have significant long‐term benefits or adverse outcomes. However, before routine use, well‐designed studies and studies involving large sample sizes are needed to confirm the pharmacokinetics and long‐term effects of IAC.
Co‐expression Network Analysis Identified Key Proteins in Association With Hepatic Metastatic Colorectal Cancer
Authors: Yang Wang , Shi Jian , Zhou Yan , Liu Tongjun , Li Jiannan , Hong Feng , Zhang Kai , Liu Ning
Published: August 2019

Purpose

Intense efforts have been made in colorectal cancer (CRC) treatment in recent decades. However, the mechanism of development and metastasis of CRC has not been fully cleared. This study is designed to identify key proteins involved in stage III and hepatic metastatic CRC.

Experiment design

Protein expression profiles of paired tumor and benign tissue samples from stage III and hepatic metastatic CRC patients are characterized by using a label‐free proteomics approach. Key proteins relevant to hepatic metastatic CRC are revealed by weighted gene correlation network analysis (WGCNA) and other bioinformatics tools.

Results

WGCNA reveals three hub modules: CRC without specific stage (turquoise), stage III CRC (blue), and hepatic metastatic CRC (green). Nine key proteins (heat shock protein family D member 1 (HSPD1), eukaryotic translation elongation factor 1 gamma, heterogeneous nuclear ribonucleoprotein A2/B1, fibrinogen beta chain (FGB), Talin 1, adaptor related protein complex 2 subunit alpha 2, serrate RNA effector molecule homolog, apolipoprotein C3, phosphoglucomutase 5) are identified. Moreover, upregulation of HSPD1 is validated in CRC tissue by the immunohistochemistry. Upregulation of fibrinogen is validated in metastatic CRC by plasma fibrinogen assay.

Conclusion and clinical relevance

This study provides the proteomic analysis of stage III and hepatic metastatic CRC to identify key proteins of CRC. FGB plays a key role to serve as diagnostic and therapeutic biomarkers for hepatic metastatic CRC.
Identification of carbonylated proteins in a bactericidal process induced by curcumin with blue light irradiation on imipenem‐resistant Acinetobacter baumannii
Authors: Chang Kai‐Chih , Cheng Ya‐Yun , Lai Meng‐Jiun , Hu Anren
Published: August 2019

Rationale

Antimicrobial photodynamic treatment is potentially an alternative to antibiotics and is also effective against viruses, fungi and some cancers. Our previous studies have shown that blue light combined with curcumin, a chemical from the turmeric plant, exerted effective antimicrobial activity via photodynamic treatment. The study reported in this paper investigates which target proteins are affected after the treatment.

Methods

We treated imipenem‐resistant Acinetobacter baumannii with blue light and curcumin and used protein carbonylation as a marker for oxidative damage. After treatment, the bacterial proteins were extracted and the protein carbonyls marked using dinitrophenylhydrazide. After enzyme digestion, we used liquid chromatography/nano‐electrospray ionization (LC/nano‐ESI) ion trap mass spectrometry to identify bacterial peptides from a customized database. The functional enrichment analyses of the identified proteins were performed using gene ontology annotation and the STRING protein–protein interaction network.

Results

The application of curcumin with blue light showed good antibacterial activity against imipenem‐resistant A. baumannii. Using a shotgun proteomics approach, the carbonylated proteins in A. baumannii caused by the photolytic curcumin were identified. The results showed that the proteins related to membrane structures, translation and response to oxidative stress were preferentially modified.

Conclusions

The photolytic curcumin treatment could be a potential alternative to antibiotics for bacterial infection. In this study, the shotgun proteomics strategy allows us to explore the possible bactericidal mechanisms under this oxidative stress. The result provides a reference for future studies on the enhancement of the action of photolytic curcumin.
Coping styles in individuals with hypertension of varying severity
Authors: Casagrande Maria , Boncompagni Ilaria , Mingarelli Alessandro , Favieri Francesca , Forte Giuseppe , Germanò Rosanna , Germanò Giuseppe , Guarino Angela
Published: August 2019

The strategies that people usually use to cope with stressful events, that is, their coping style, may affect blood pressure and cardiovascular functioning. Generally, hypertension is positively associated with emotion‐oriented, maladaptive coping strategies and negatively related to task‐focused coping styles, but no study has investigated the relationship between coping strategies and the severity of hypertension. This study aimed to assess whether the severity of cardiovascular disorders was associated with specific coping strategies. Participants were selected from the Policlinico Umberto I of the University of Rome “Sapienza.” The sample was divided into five groups: (a) healthy people (n = 190); (b) people with untreated hypertension (n = 232); (c) people using antihypertensive medication (n = 158); (d) people using antihypertensive medication with uncontrolled hypertension (n = 179); and (e) people suffering from both hypertension and heart diseases (N = 192). Coping strategies were evaluated with the Coping Inventory for Stressful Situations. One‐way ANCOVAs, considering Group as the independent variable and the coping strategies (task‐focused, emotion‐oriented and avoidance‐oriented coping) as dependent variables, showed that individuals affected by both hypertension and heart diseases made less use of task‐focused coping strategies than the other groups. These findings confirm the relationship between coping style and hypertension and highlight that patients with hypertension and heart diseases make less use of appropriate coping strategies.
On the post‐buckling rotational capacity of square hollow sections in uniform bending
Authors: Müller Andreas , Taras Andreas
Published: August 2019

Nominated for the Bernt Johansson Outstanding Paper Awards at Nordic Steel 2019

The growing popularity of high‐strength steel grades leads to the need for more accurate design specifications, with the aim of fully exploiting the material benefits and creating economic advantages. According to Eurocode 3, the maximum rotational capacity of a section is limited and linked to the definition of cross‐sectional classes. For class 1, the rotational limit θ is assumed to be ”infinite“, whereas it drops significantly for classes 2 and 3 to a maximum rotation of φpl and φel, respectively. In reality, despite their lower hardening capacity and ultimate strains, high‐strength steel sections exhibit a non‐negligible rotational capacity that exceeds these code predictions, which were developed for mild steel and with a level of analysis in mind that is suitable for hand calculations. In order to achieve greater use of high‐strength steel sections, it is thus very important to understand and be able to predict a section's deformation and rotational capacity more accurately, with the aim of implementing the findings in tools for advanced, FEM‐based design by analysis (DbA) approaches. As an initial step in this direction, this paper shows the results from numerical calculations of the rotational capacity of HSS rectangular hollow sections. The numerical results were calibrated against laboratory tests. Consequently, different rectangular cross‐section dimensions and variations of the steel grade and thickness were chosen and analysed in the ABAQUS finite element software.
Systems‐theoretic security requirements modeling for cyber‐physical systems
Authors: Carter Bryan T. , Bakirtzis Georgios , Elks Carl R. , Fleming Cody H.
Published: August 2019

Cyber‐physical systems (CPS) present a unique modeling challenge due to their numerous heterogeneous components, complex physical interactions, and disjoint communication networks. Modeling CPS to aid security analysis further adds to these challenges, because securing CPS requires not only understanding of the system architecture, but also the system's role within its broader expected service. This is due to the infeasibility of completely securing every single component, network, and part within a CPS. As such it is necessary to be cognizant of the system's expected service, or mission, so that the effects of an exploit can be mitigated and the system can perform its mission at least in a partially degraded manner—in other words, a mission‐aware approach to security. As such, a security analysis methodology based on this philosophy is greatly aided by the creation of a model that combines system architecture information, its admissible behaviors, and its mission context. This paper presents a technique for creating such a model using the Systems Modeling Language.
Low secondary risks for captive coyotes from a sodium nitrite toxic bait for invasive wild pigs
Authors: Snow Nathan P. , Horak Katherine E. , Humphrys Simon T. , Staples Linton D. , Hewitt David G. , VerCauteren Kurt C.
Published: August 2019

An acute toxic bait is being developed to deliver micro‐encapsulated sodium nitrite (SN) to stimulate severe methemoglobinemia and humane death for invasive wild pigs (Sus scrofa), thereby providing a new tool for reducing their populations. During April 2016, we evaluated sensitivity to SN and outcomes of secondary consumption in the ubiquitous mammalian scavenger, coyote (Canis latrans), to determine secondary risks of consuming carcasses of wild pigs that died from consuming the SN toxic bait. At the National Wildlife Research Center in Fort Collins, Colorado, USA, we first evaluated whether coyotes fed carcasses of domestic pigs killed by consumption of SN bait showed signs of SN intoxication. Second, we conducted chemical analysis of residual SN in the coyotes for evidence of SN passing from pigs to coyotes. Last, we conducted an acute oral toxicity test (LD50) with SN for coyotes by feeding them meatballs containing capsules of SN. We found no evidence that captive coyotes experienced SN intoxication from consuming on carcasses that had been freshly poisoned with SN, despite consuming   = 1.6 kg of tissues/coyote within 24 hours. None of the captive coyotes consumed digestive tracts or stomach contents from poisoned carcasses, which contained the highest levels of residual SN. Chemical analysis indicated that only ≤34.14 mg/kg of residual SN were passed from the tissues of the pigs into the coyotes, confirming that SN does not bioaccumulate. All coyotes quickly vomited various doses of SN during the LD50 test and fully recovered, suggesting a natural defense against secondary poisoning from SN. Testing with captive coyotes indicates that the risks of secondary poisoning for free‐ranging coyotes are likely low, although field‐testing should be used to confirm. © 2019 The Wildlife Society.
Seeley-DeWitt coefficients in $$ \mathcal{N} $$ = 2 Einstein-Maxwell supergravity theory and logarithmic corrections to $$ \mathcal{N} $$ = 2 extremal black hole entropy
Authors: Karan Sudip , Banerjee Gourav , Panda Binata
Published: August 2019

Abstract

We investigate the heat kernel method for one-loop effective action following the Seeley-DeWitt expansion technique of heat kernel with Seeley-DeWitt coefficients. We also review a general approach of computing the Seeley-DeWitt coefficients in terms of background or geometric invariants. We, then consider the Einstein-Maxwell theory em-bedded in minimal

$$ \mathcal{N} $$

N

= 2 supergravity in four dimensions and compute the first three Seeley-DeWitt coefficients of the kinetic operator of the bosonic and the fermionic fields in an arbitrary background field configuration. We find the applications of these results in the computation of logarithmic corrections to Bekenstein-Hawking entropy of the extremal Kerr-Newman, Kerr and Reissner-Nordström black holes in minimal

$$ \mathcal{N} $$

N

= 2 Einstein-Maxwell supergravity theory following the quantum entropy function formalism.