bluuebunny/crossref_metadata_2025 huggingface dataset:
Cationic Tungsten Alkylidyne N‐Heterocyclic Carbene Complexes: Synthesis and Reactivity in Alkyne Metathesis
Authors: Hauser Philipp M. , van der Ende Melita , Groos Jonas , Frey Wolfgang , Wang Dongren , Buchmeiser Michael R.
Published: May 2020

The first cationic and neutral tungsten alkylidyne N‐heterocyclic carbene (NHC) complexes bearing one triflate ligand were synthesized and tested for their reactivity in alkyne metathesis. Both types of tungsten alkylidyne complexes display a higher productivity in alkyne metathesis than the analogous neutral tungsten alkylidyne NHC trisalkoxide complexes. Reaction of W(≡CC6H4OMe)(1,3‐bis(1‐hydroxy‐1,1‐trifluoromethylethyl)‐imidazol‐2‐ylidene)Cl (W18) with AgB(ArF)4 (ArF = 3,5‐bis(trifluoromethyl)phenyl) resulted in the unexpected formation of, to the best of our knowledge, the first cationic ditungstatetrahedrane W2(1,3‐bis(1‐hydroxy‐1,1‐trifluoromethyl‐ethyl)‐imidazol‐2‐ylidene)2(MeCN)(µ‐((Ar)CC(Ar)))+ (B(ArF)4)– (W19, Ar = C6H4OMe), which suggests bimolecular decomposition as a possible decomposition pathway of cationic tungsten alkylidyne NHC complexes. Reaction of the cationic tungsten alkylidyne NHC complex W(≡CC6H4OMe)(1,3‐diisopropylimidazol‐2‐ylidene)(OC(CF3)2Me)2(NCtBu)+ (B(ArF)4)– (W7) with 1‐phenyl‐1‐propyne allowed for the isolation of a cationic tungstacyclobutadiene W(C3(Ph)(Me)(C6H4OMe))(1,3‐diisopropylimidazol‐2‐ylidene)(OC(CF3)2Me)2(NCtBu)+ (B(ArF)4)– (W20). Its formation strongly supports a cationic active species in the alkyne metathesis with tungsten alkylidyne NHC complexes.
Erythritol‐Based Medium‐Chain Sugar Amphiphile: Synthesis and Gelling Capability in Edible Oils
Authors: Pang Min , Lei Zheng , Zheng Donglei , Shi Zhaojuan , Ge Yuanfei , Cheng Jieshun , Jiang Shaotong , Cao Lili
Published: May 2020

The production of organogels from vegetable oils requires low‐molecular‐weight gelators. Herein, a novel small‐molecule sugar ester gelator is synthesized from erythritol and octanoic acid. The purified reaction product is identified as erythritol 1,6‐dioctanoate by high performance liquid chromatography (HPLC) with evaporative light‐scattering detection and nuclear magnetic resonance (NMR). This low‐molecular‐weight erythritol ester exhibits self‐assembly behavior in vegetable oils with a minimum gelation concentration of 4 wt%. Microscopy reveals needle‐like crystals that became slender as the gelator concentration increases. X‐Ray Diffraction (XRD) analyses indicate that the organogels are semicrystalline with both crystalline and amorphous domains. Fourier Transform Infrared (FTIR) spectroscopy reveals that the gel structure is maintained by non‐hydrogen‐bonding interactions. Furthermore, rheological tests show that the mechanical strength of the gel is poor, but as the gelator concentration is increased, the mechanical strength and hardness of the gel also increases. Thus, this erythritol ester effectively promotes the gelation of edible vegetable oils and increases the variety of available organogelators.

Practical Applications: The synthesized erythritol ester is successfully applied as a gelator to produce organogels from a variety of vegetable oils, and are expected to advance the development of effective organogelators for edible oils.
Iodine‐Catalyzed Ring Opening of 1,1‐Diacylcyclopropanes for Synthesis of Fully Substituted Pyrazole Derivatives
Authors: Yang Xiuqin , Zhu Jin , Bao Yishu , Ding Ziyu , Yang Fulai , Zhou Qingfa , Chen Ming
Published: May 2020

An iodine‐catalyzed [3+2] cycloaddition/ring opening reaction of 1,1‐diacylcyclopropanes with sulfonyl hydrazides has been reported. In the presence of 20 mol‐% iodine, a range of structurally diverse fully substituted pyrazoles with a hydroxy functional group are obtained in moderate to excellent yields with extremely high regioselectivity.
Palladium‐Catalyzed Oxidative C–H Alkoxycarbonylation of Arenes with Alkylcarbazates Directed by N‐Heterocyclic Substituents
Authors: Yogesh Kumar Gujjenahalli Ramalingaiah , Begum Noor Shahina
Published: May 2020

With alkyl carbazates as the green ester source, a novel palladium‐catalyzed oxidative free radical carbonylative transformation of the C–H bond on aromatic rings to produce esters has been developed. Good yields of the corresponding products have been obtained with wide functional group tolerance and excellent regioselectivity. A variety of alkyl carbazates are found to be suitable reactants for the ortho‐alkoxycarbonylation on the aromatic ring.
Concentration effects on capture rate and translocation configuration of nanopore‐based DNA detection
Authors: Zhang Yin , Zhao Jiabin , Kan Yajing , Ji Rui , Pan Jianqiang , Huang Weichi , Xu Zheng , Si Wei , Sha Jingjie
Published: May 2020

Nanopore is a kind of powerful tool to detect single molecules and investigate fundamental biological processes. In biological cells or real detection systems, concentration of DNA molecules is various. Here, we report an experimental study of the effects of DNA concentration on capture rate and translocation configuration with different sized nanopores and applied voltages. Three classes of DNA translocation configurations have been observed including linear translocation, folded translocation, and cotranslocation. In the case of relatively large sized nanopore or high applied voltage, considerable cotranslocation events have been detected. The percentage of cotranslocation events also increases with DNA concentration, which leads to the relationship between capture rate and DNA concentration deviates from linearity. Therefore, in order to reflect the number of translocation molecules accurately, the capture rate should be corrected by double‐counting cotranslocation events. These results will provide a valuable reference for the design of nanopore sensors.
The High‐Performance Bifunctional Catalyst Pd/Ti3C2Tx–Carbon Nanotube for Oxygen Reduction Reaction and Hydrogen Evolution Reaction in Alkaline Medium
Authors: Zhang Peng , Wang Ranran , Xiao Tao , Chang Zhou , Fang Zhongwei , Zhu Zuolei , Xu Chenxi , Wang Lianchao , Cheng Jigui
Published: May 2020

The metal–support interaction offers electronic, compositional, and geometric effects that can enhance the catalytic activity and stability. Herein, a performance‐enhanced electrocatalyst of Pd nanoparticles loaded on a hybrid catalytic support comprised of MXene (Ti3C2Tx) and carbon nanotube (CNT) is demonstrated. Such a hybrid catalyst enhances durability and improves both oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER) activities compared with the Pd/C catalysts. The mass specific activity and specific activity of the Pd/Ti3C2Tx–CNT catalyst are 4.4 and 3.3 times that of Pd/C for ORR, respectively. The peak power density of a alkaline anion exchange membrane fuel cell (AAEMFC) based on the Pd/Ti3C2Tx–CNT (1:2) cathode achieves 48 mW cm−2 at 60 °C. Furthermore, Pd/Ti3C2Tx–CNT also exhibits rapid HER kinetics with a low overpotential of 158 mV at 10 mA cm−2 and a Tafel slope of 50 mV dec−1. Pd/Ti3C2Tx–CNT also provides good stability after 1000 cycles. These remarkable catalytic performances are attributed to the role of Ti3C2Tx and CNT by enhancing the catalytic activity surface area and rapid mass/charge transfer due to the synergistic effect between Pd and Ti3C2Tx–CNT.
On modeling positive continuous data with spatiotemporal dependence
Authors: Bevilacqua Moreno , Caamaño‐Carrillo Christian , Gaetan Carlo
Published: May 2020

In this article, we concentrate on an alternative modeling strategy for positive data that exhibit spatial or spatiotemporal dependence. Specifically, we propose to consider stochastic processes obtained through a monotone transformation of scaled version of χ2 random processes. The latter is well known in the specialized literature and originates by summing independent copies of a squared Gaussian process. However, their use as stochastic models and related inference has not been much considered. Motivated by a spatiotemporal analysis of wind speed data from a network of meteorological stations in the Netherlands, we exemplify our modeling strategy by means of a nonstationary process with Weibull marginal distributions. For the proposed Weibull process we study the second‐order and geometrical properties and we provide analytic expressions for the bivariate distribution. Since the likelihood is intractable, even for a relatively small data set, we suggest adopting the pairwise likelihood as a tool for inference. Moreover, we tackle the prediction problem and we propose to use a linear prediction. The effectiveness of our modeling strategy is illustrated by analyzing the aforementioned Netherland wind speed data that we integrate with a simulation study. The proposed method is implemented in the R package GeoModels.
Defeating the Austerians of the warfare state: French arms policy through the lens of the Programmatic Action Framework
Authors: Faure Samuel B. H.
Published: May 2020

This article contributes to the development of the Programmatic Action Framework (PAF) based on the case study of the procurement of the French Rafale fighter jet rather than the American F‐18 by the French government in the 1980s. This decision making dilemma is explained by revealing the competition between two “programmatic cliques.” The “sovereignist” programmatic clique that defends the French option embodies the Custodians of the nation state. The “liberal” programmatic clique that supports the American alternative represents the Austerians of the nation state. The defeat of the Austerians of the French nation warfare state is explained by the ties weakness available to the liberal programmatic clique at the political level of decision making. To this end, 89 semi‐structured interviews were conducted with the political‐military and industrial arms actors.
Preserving quantifiable ethnographic records of disappearing human lifeways
Authors: Kraft Thomas S. , Venkataraman Vivek V. , Endicott Karen L. , Endicott Kirk M.
Published: May 2020

The human evolutionary sciences place high value on quantitative data from traditional small‐scale societies that are rapidly modernizing. These data often stem from the sustained ethnographic work of anthropologists who are today nearing the end of their careers. Yet many quantitative ethnographic data are preserved only in summary formats that do not reflect the rich and variable ethnographic reality often described in unpublished field notes, nor the deep knowledge of their collectors. In raw disaggregated formats, such data have tremendous scientific value when used in conjunction with modern statistical techniques and as part of comparative analyses. Through a personal example of longitudinal research with Batek hunter‐gatherers that involved collaboration across generations of researchers, we argue that quantifiable ethnographic records, just like material artifacts, deserve high‐priority preservation efforts. We discuss the benefits, challenges, and possible avenues forward for digitizing, preserving, and archiving ethnographic data before it is too late.
Multifarious roles of mTOR signaling in cognitive aging and cerebrovascular dysfunction of Alzheimer's disease
Authors: Uddin Md. Sahab , Rahman Md. Ataur , Kabir Md. Tanvir , Behl Tapan , Mathew Bijo , Perveen Asma , Barreto George E. , Bin‐Jumah May N. , Abdel‐Daim Mohamed M. , Ashraf Ghulam Md
Published: May 2020

Age‐related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood–brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.
Collagen ultrastructural symmetry and its malignant alterations in human breast cancer revealed by polarization‐resolved second‐harmonic generation microscopy
Authors: Mercatelli Raffaella , Triulzi Tiziana , Pavone Francesco Saverio , Orlandi Rosaria , Cicchi Riccardo
Published: May 2020

Several specific alterations of the extracellular matrix can be considered a distinctive hallmark of cancer. In particular, a different morphology of the collagen scaffold is frequently found within the peritumoural environment. In this study, we report about a significant difference in the ultrastructural organization of collagen at the supra‐molecular level between the perilesional scaffold and the tumour area in human breast carcinoma samples. In particular, we demonstrated that polarization‐resolved second‐harmonic generation (P‐SHG) microscopy is able to link the altered collagen architecture at the ultrastructural level found in perilesional tissue with a different organization of collagen fibrils at the molecular level.
Neuropilin1 silencing impairs the proliferation and migration of cells in pancreatic cancer
Authors: He Li‐Hong , He Yong‐Lin , Zuo Wen‐Hang , Kang Yue , Xue Huan , Wang Ling‐Yun , Zhang Yun‐Liang , Meng Yong
Published: May 2020

Background

Neuropilin1 (NRP1) participates in cancer cell proliferation, migration, and metastasis as a multifunctional co‐receptor by interacting with multiple signal pathways, but few studies have addressed the precise function of NRP1 in pancreatic cancer (PACA) cells. We aimed to study whether NRP1 gene silencing involved in the proliferation and migration of PACA cells in vitro.

Methods

A lentiviral vector expressing NRP1 shRNA was constructed and transfected into human PACA cells (CFPAC‐1 and PANC‐1). The expression of NRP1 protein and mRNA was detected by Western blot and quantitative real‐time polymerase chain reaction (qRT‐PCR) assay, respectively. CCK‐8 assay, wound healing assay, and transwell assay were conducted to examine the effect of NRP1 silencing on cells proliferation and migration capability.

Results

Results of qRT‐PCR and Western blot showed successfully established, stably transfected shRNA‐NRP1 cells in PACA cells. The proliferation capacity of PACA cells in NRP1 shRNA group was lower significantly than that in the negative control (NC) group (P < .05). The invasion and migration capability of PACA cells in NRP1 shRNA group was lower significantly than that in the NC group (P < .01).

Conclusions

NRP1‐shRNA lentiviral interference vectors can effectively decrease NRP1 gene expression in PACA cells, thereby inhibiting cells proliferation and migration, which provides a basis for finding a valuable therapeutic target for PACA therapy.
A newly isolated strain, Lactobacillus paracasei subsp. paracasei 2, produces l‐lactic acid from pilot‐scale fermentation of food waste under sterile and nonsterile conditions
Authors: Gao Ming , Ma Xiaoyu , Song Na , Wang Qunhui , Wu Chuanfu
Published: May 2020

BACKGROUND

Lactic acid (LA) is a valuable industrial chemical with wide applications. Presently, the demand for optically pure l‐LA has grown considerably as a result of its applications in the food and pharmaceutical industries, and biodegradable polylactic acid production. The production of l‐LA from food waste (FW) has been discussed in some studies; however, most fermentation is performed under sterile conditions and with the addition of specific lactic acid bacteria. Completely autoclaving organic solid wastes is difficult and economically unfeasible. The aim of this work was to investigate pilot‐scale LA production from FW under sterile and nonsterile conditions.

RESULTS

When FW was fermented without sterilization and inoculation, the maximum yield of LA was 0.43 g LA g–1 total solid (TS) and the proportion of l‐LA was only ≈50%. A newly isolated strain, Lactobacillus paracasei subsp. paracasei 2, which was isolated and identified from FW, was used to improve the proportion of l‐LA in total LA. When nonsterile FW was inoculated with this strain, the proportion of l‐LA increased to 72.3%. After FW was sterilized and inoculated with this strain, the proportion of l‐LA was 98.6% and 98.8% under intermittent and real‐time regulation of pH level, respectively. The maximum LA yield could increase to 0.55 g LA g–1TS.

CONCLUSION

Pilot‐scale LA production from FW was determined by comparing the isomer purity of l‐LA between sterilization and nonsterilization and between inoculation and noninoculation, which provided an important strain and fermentation type for production of high concentration of l‐LA. © 2020 Society of Chemical Industry
Protective effects of Coenzyme Q10 against sevoflurane‐induced cognitive impairment through regulating apolipoprotein E and phosphorylated Tau expression in young mice
Authors: Yang Man , Tan Hong , Zhang Kai , Lian Naqi , Yu Yang , Yu Yonghao
Published: May 2020

Children with multiple exposures to anesthesia and surgery may be more likely to develop the learning disability. Coenzyme Q10 (CoQ10) was reported to reduce the multiple sevoflurane treatment‐induced cognitive deficiency in 6‐day‐old young mice. However, its specific mechanisms have not yet been found. This research aimed to reveal the role of ApoE in the pathogenesis of cognitive deficiency caused by sevoflurane anesthesia and the protective mechanism of CoQ10 in a multiple sevoflurane treatment model of young mice. The mice were randomly divided into four groups: Control + corn oil, Sevoflurane + corn oil, Control + CoQ10, and Sevoflurane + CoQ10. Sevoflurane group mice were anesthetized with 3% sevoflurane and 60% oxygen 2 hr a day for 3 days, while control group mice received only 60% oxygen. Mice received an intraperitoneal injection of 50 mg/kg CoQ10 or the same volume of corn oil 30 min before the inhalation of oxygen or sevoflurane for 3 days. Mice received sevoflurane anesthesia or control treatment from the 6th to 8th day after birth. The cortex and hippocampus were harvested on the 8th day. The ATP, MMP, ApoE mRNA, total ApoE, ApoE fragments, Aβ1‐40, Aβ1‐42, Tau5, AT8, and PHF levels were detected. The Morris water maze (MWM) tests were performed from P30 to p36 after anesthesia or control treatment. The results indicated that the injection of CoQ10 ahead of sevoflurane treatment could reverse the anesthesia‐induced energy deficiency, mitochondrial dysfunction, ApoE, and its fragments expression, Aβ1‐42 generation, Tau phosphorylation, and cognitive impairment in young mice. These data reveal that the ApoE and its fragments enhancement may play an important role in the pathogenesis of cognitive deficiency caused by sevoflurane anesthesia. CoQ10 could reduce ApoE expression by improving energy replenishment and mitochondrial functions, thereby alleviating sevoflurane‐induced brain damage and cognitive impairment.
The effect of different pollutants exposure on the pigment content of pigmented macrophage aggregates in the spleen of Vardar chub (Squalius vardarensis Karaman, 1928)
Authors: Ivanova Lozenka , Rebok Katerina , Jordanova Maja , Dragun Zrinka , Kostov Vasil , Ramani Sheriban , Valić Damir , Krasnići Nesrete , Filipović Marijić Vlatka , Kapetanović Damir
Published: May 2020

Pigmented macrophage aggregates (MAs) are known to change under influence of various factors, such as aging, season, starvation, and/or pollution. In this study, changes in the pigment content of the MAs in the spleen of Vardar chub (Squalius vardarensis, Karaman) (n = 129) collected in spring and autumn, from three rivers with different pollution impact was examined: Zletovska River (metals), Kriva River (metals and municipal wastewater), and Bregalnica River (municipal wastewater). Collected data revealed increased relative volume and number of MAs containing hemosiderin under the influence of metals, significant in autumn (p < .05). In chub exposed to metals combined with municipal wastewater, significant increase of lipochrome accumulation in MAs in autumn, melanin in MAs in fish captured in the spring season, and number of splenic MAs containing combination of melanin and lipochrome was noted. Volumes and number of MAs containing combination of hemosiderin and lipochrome increased in spleen of fish captured in autumn from both Zletovska River and Kriva River, most likely due to the contribution of hemosiderin and lipochrome, respectively. Values measured for the various pigments in splenic MAs in fish captured from Bregalnica River, were overall closer to the values measured for fish captured from Kriva River. Notably, melanin and lipochrome are more likely to be found in fish from waters influenced by municipal wastewater (organic pollution) and hemosiderin in fish spleen from water influenced by mining activity (heavy metals pollution).
Genetic counseling graduate training to address religion and spirituality in clinical practice: A qualitative exploration of programs in North America
Authors: Murray Alise , Warren Nancy Steinberg , Bosanko Katherine , Williamson Dean Lori
Published: May 2020

Patients receiving clinical genetics services often navigate emotionally difficult situations and may utilize their faith as a source of support, an aid in decision‐making, or a core coping strategy. Although patients have expressed interest in discussing their religious or spiritual (R/S) beliefs with their genetic counselor (GC), GCs may avoid such conversations because they feel they do not have the necessary skills to discuss R/S beliefs (Reis, Baumiller, Scrivener, Yager, & Warren, 2007). This qualitative study explored how GC programs in North America currently prepare their students to discuss R/S matters with their patients. The aims of this study were to identify (1) the R/S topics genetic counseling programs currently cover in the curriculum, (2) how genetic counseling programs evaluate their students within the R/S topics and activities that are included in the curriculum, and (3) the value or importance placed on R/S training by genetic counseling program directors. Leaders of 12 (36%) of the 33 eligible GC programs at the time of the study participated in a semi‐structured phone interview. Their responses were coded using open and axial coding techniques and analyzed using grounded theory. Results revealed that R/S issues are often covered during the psychosocial portions of the curriculum through writing assignments, in class exercises, and role plays. Almost all participating programs include information on pastoral care services, but have little to no training about specific R/S beliefs or the use of spiritual surveys. While participating program directors emphasized that it is critical for students to be prepared to hold conversations about patients' R/S beliefs, the strategies used to prepare students are inconsistent and often not evaluated. We provide suggestions for enriching the R/S training in genetic counseling graduate programs in order to prepare students to facilitate discussions around patients' religion and/or spirituality in genetic counseling sessions.
Cyclization of thiosemicarbazide derivative: As a source of novel synthesis of some azoles and azines
Authors: Abd El‐Azim Mohamed H. M. , Assy Mohamed G. , Khalil Mohammed I. , Selim Yasser A.
Published: May 2020

In our study, we aimed to synthesize novel, some biologically active compounds, Azoles and Azines derivatives, that to be nitrogen‐containing heterocycles, and have their diverse therapeutic values. Thiosemicarbazide, 2, was obtained from the attack of nitrogen of hydrazine to the carbon of heteroallene function of compound 1. Triazolotriazole derivative, 4, was obtained from the reaction of 2 with diethyl malonate. Cyclization of thiourea unit of compound 2 with heteroallene, 1, gave trazine, 6. Benzolyation of 2 using benzoyl chloride formed triazole derivative, 8. Reaction of 2 and maleic anhydride gave furothiadazine, 10. Cyclohexanopyrimidinthione, 12, was obtained from cyclocondensation of cyclohexanone with 2. Triazole, 14, was obtained from 2 and ammonium isothiocynate under thermal condition. Reaction of 2 with ethyl bromoacetate gave thiazole derivative, 16. [2+3] Cyclocondensation of acetyl acetone with 2 provided pyrazole, 18. Triazolotriazole, 20, was obtained from formalin and 2. Compound 2 suffers intramolecular base mediated cyclization affording pyrazole, 21. Keeping 2 and propinaldehyde under reflux provided triazolotriazole, 24. Acylation of 2 by succinic acid formed pyridazine derivative, 27.
Seroprevalence of group B Coxsackieviruses: Retrospective study in an Italian population
Authors: Sciandra Ilaria , Falasca Francesca , Maida Paola , Tranquilli Giulia , Di Carlo Daniele , Mazzuti Laura , Melengu Taulant , Giannelli Gianluigi , Antonelli Guido , Turriziani Ombretta
Published: May 2020

Group B Coxsackieviruses (CVB) include six serotypes (B1‐6) responsible for a wide range of clinical diseases. Since no recent seroepidemiologic data are available in Italy, the study aim was to investigate CVB seroprevalence in a wide Italian population. The study retrospectively included 2459 subjects referring to a large academic hospital in Rome (Italy) in the period 2004‐2016. Seroprevalence rates and neutralizing antibodies (nAb) titers were evaluated in relation to years of observation and subjects’ characteristics. Positivity for at least one serotype was detected in 69.1% of individuals. Overall, the prevalent serotype was B4, followed by B3 (33.3%), B5 (26.2%), B1 (12.7%), B2 (11.0%), and B6 (1.7%). For B2, a significant decrease in seroprevalence over years was observed. Positivity to at least one virus was 25.2% in children aged 0 to 2 years, but significantly increased in preschool (3‐5 years) (50.3%) and school (6‐10 years) children (70.4%). Higher nAb responses for B3 and B4 were observed in children aged 3 to 5 years. A high overall CVB prevalence was found. Type‐specific variations in prevalence over time probably reflect the fluctuations in circulation typical of Enteroviruses. Children are at greater risk for CVB infection given the high number of seronegative subjects aged 0 to 10 years.
SARS‐CoV‐2 coinfections: Could influenza and the common cold be beneficial?
Authors: Pinky Lubna , Dobrovolny Hana M.
Published: May 2020

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has rapidly spread around the world, causing serious illness and death and creating a heavy burden on the healthcare systems of many countries. Since the virus first emerged in late November 2019, its spread has coincided with peak circulation of several seasonal respiratory viruses, yet some studies have noted limited coinfections between SARS‐CoV‐2 and other viruses. We use a mathematical model of viral coinfection to study SARS‐CoV‐2 coinfections, finding that SARS‐CoV‐2 replication is easily suppressed by many common respiratory viruses. According to our model, this suppression is because SARS‐CoV‐2 has a lower growth rate (1.8/d) than the other viruses examined in this study. The suppression of SARS‐CoV‐2 by other pathogens could have implications for the timing and severity of a second wave.
The long‐standing history ofCorynebacterium parvum, immunity, and viruses
Authors: Palmieri Beniamino , Vadalà Maria , Roncati Luca , Garelli Andrea , Scandone Francesco , Bondi Moreno , Cermelli Claudio
Published: May 2020

We report a review of all the experimental and clinical studies performed in the last 60 years on the antiviral activity of inactivatedCorynebacterium parvum (Cutibacterium acnes). This bacterium has been originally investigated and used for its oncolytic properties linked to immunomodulating activity, but the interest to successfully prevent and treat bacterial, fungal, and viral infections and lethality, uprising the innate immunity barriers produced many experimental models and very few clinical studies. The dramatic defenseless situation due to impending CoViD‐19 pandemic claims to exhume and highlight this aspecific strategy in preventive and therapeutic settings; as a matter of fact, no new or mutated virus can potentially escape to this strong innate immune surveillance strengthened by adequateC. parvumprotocols.
Correlation between human papillomavirus infection and histopathological diagnosis of women in Northeast Brazil
Authors: Miranda Paulo José Cunha , Chagas Bárbara Simas , Coêlho Maria Rosângela Cunha Duarte , Silva Neto Jacinto da Costa
Published: May 2020

Cervical carcinoma is the fourth leading cause of death among women worldwide. Epidemiological studies claim that human papillomavirus (HPV) infection is a necessary condition for cervical cancer development. Knowledge of the geographic distribution of HPV is important in guiding the introduction of prophylactic vaccines. This study analyzed the prevalence of HPV infection in cervical samples obtained from women with abnormal cervical histopathological diagnosis in Northeast Brazil. The study included an analysis of 211 women whose diagnosis was confirmed for cervical intraepithelial neoplasia type 1 (CIN‐1), cervical intraepithelial neoplasia type 2 (CIN‐2), cervical intraepithelial neoplasia type 3 (CIN‐3), and cancer. The identification of the HPV genotypes was based on the polymerase chain reaction–restriction fragment length polymorphism technique. A total of 42.7% of the samples showed a single HPV infection, while 57.3% showed multiple infections. The most common genotypes detected were HPV‐16, HPV‐18, and HPV‐31. HPV‐16, HPV‐31, HPV‐35, and HPV‐18 were the most common types in CIN‐1 with a single infection. HPV‐16 and HPV‐18 were the most often found in CIN‐2 with a single infection. HPV‐16, HPV‐18, and HPV‐31 were the most detected in CIN‐3 with a single infection. HPV‐16 and HPV‐31 were the most frequent in cancer with a single infection. Multiple infection with HPV‐16 shows a 2.7 times greater risk of CIN‐3 (P = .04). Multiple infections for HPV with HPV‐16 and excluding the HPV18/31 types, were associated with CIN‐3 (P = .01). The results allowed the detection and genotyping of HPV types circulating in the population studied. These findings must be taken into account when devising vaccination strategies against HPV.
Moisture sources of extreme precipitation events in arid Central Asia and their relationship with atmospheric circulation
Authors: Xie Tingting , Huang Wei , Chang Shiqiao , Zheng Fei , Chen Jianhui , Chen Jie , Chen Fahu
Published: May 2020

Although moisture is an important factor affecting precipitation in arid Central Asia (ACA), the water vapour sources and their influencing factors are unclear. This study investigates the moisture sources of extreme precipitation events in summer over Northern ACA and in winter over Southern ACA. The results show that in summer over Northern ACA, the water vapour at low and upper atmospheric levels is mainly transported from the North Atlantic and the Arctic Ocean. In addition, the water vapour in winter over Southern ACA is mainly transported from the North Atlantic and the Northern Indian Ocean. Among these sources, anomalous moisture from the North Atlantic is transported to Northern and Southern ACA along the Mediterranean pressure ridge and the Aral Sea pressure trough. In addition, anomalous moisture in Northern ACA from the Arctic Ocean is closely associated with the negative height anomaly near ACA and with the positive height anomaly in the Mediterranean extending northward to the Arctic Ocean; this results in the high‐latitude moisture transporting along the western edge of the cyclone in Northern ACA. In Southern ACA, low‐latitude water vapour from the Northern Indian Ocean is affected by negative and positive height anomalies in Northwest and Southeast ACA. In addition, significant ascending motion occurs in the study area which provides the necessary dynamic conditions for precipitation. The precipitation variations in Northern and Southern ACA are also related to sea‐surface temperature variations, mainly in the North Atlantic, Arctic Ocean, Mediterranean Sea, and Northern Indian Ocean. Therefore, moisture from the North Atlantic, Arctic Ocean, and the Indian Ocean converge and together influence precipitation development during summer over Northern ACA and in winter over Southern ACA.

Highlights

Arctic Ocean and North Atlantic moisture together influence summer and autumn precipitation in northern arid Central Asia.

Indian Ocean and North Atlantic moisture together influence spring and winter precipitation in southern arid Central Asia.

Sea‐surface temperatures in the North Atlantic, Arctic Ocean, Mediterranean Sea, and Northern Indian Ocean have positive or negative effects on precipitation in arid Central Asia.
Washing fresh tea leaves before picking decreases pesticide residues in tea
Authors: Gao Wanjun , Guo Jiagang , Xie Liang , Peng Chuanyi , He Lili , Wan Xiaochun , Hou Ruyan
Published: May 2020

BACKGROUND

The use of pesticides during tea plant cultivation helps agricultural production and prevents and controls pests, diseases and weeds. It is of the utmost importance to balance pesticide application with tea quality, safety and consumer health. The uptake of pesticides into plants may lead to the presence of residues that are hazardous to human health, especially for some foliar‐applied insecticides. The movability or penetration behavior of a pesticide remains unknown after it has been sprayed on a tea leaf.

RESULTS

Two organophosphate (acephate, trichlorfon) and three neonicotinoid pesticides (imidacloprid, thiamethoxam and acetamiprid) were confirmed with respect to their removal from the treated fresh leaves of tea saplings via washing in a phytotron. Four of the targets have little penetrative ability into tea leaves, mainly existing (> 92%) on the tea leaf surface, except for trichlorfon (> 70%), for 30 days. With higher vapor pressures, trichlorfon and acetamiprid had relatively higher penetration ratios of 8.63–29.60% and 0.28–8.03% respectively. Two organophosphate insecticides were found to degrade more quickly, with lower final amounts of residues on and in the whole leaf compared to the neonicotinoid pesticides. In a field test, these residues could be reduced by 45–72% after a pre‐harvest interval of 3 days, and by 16–89% after 7 days, when the fresh tea shoots were sprayed with 2 or 4 L m−2 water.

CONCLUSION

Pesticides with different structures have different penetration abilities on the tea leaf surface, and some pesticides in commercial tea can be reduced by spraying with water before fresh leaves are picked. © 2020 Society of Chemical Industry
Fast cropping method for proper input size of convolutional neural networks in underwater photography
Authors: Park Jin‐Hyun , Choi Young‐Kiu , Kang Changgu
Published: May 2020

The convolutional neural network (CNN) is widely used in object detection and classification and shows promising results. However, CNN has the limitation of fixed input size. If the input image size of the CNN is different from the image size of the system to which the CNN is applied, additional processes, such as cropping, warping, or padding, are necessary. They take additional time to process these processes, and fast cutting methods are required for systems that require real‐time processing. The purpose of our system to which the CNN model will be applied is to classify fish species in real time, using cameras installed in a shallow stream. Therefore, in this paper, we propose a straightforward real‐time image cropping method for fast cutting to the proper input size of CNN. In the experiments, we evaluate the proposed method using CNNs (AlexNet, Vgg 16, Vgg 9, and GoogLeNet).
Usability of the Experience Sampling Method in Parkinson's Disease on a Group and Individual Level
Authors: Mulders Anne E.P. , van der Velden Rachel M.J. , Drukker Marjan , Broen Martijn P.G. , Kuijf Mark L. , Leentjens Albert F.G.
Published: May 2020

Background

Around 50% of PD patients experience motor fluctuations, which are often accompanied by mood fluctuations. The nature of the relationship between motor and mood fluctuations remains unknown. It is suggested that the experience sampling method can reveal such associations on both a group and individual level. Revealing group patterns may enhance our understanding of symptom interactions and lead to more general treatment recommendations, whereas analyses in individual patients can be used to establish a personalized treatment plan.

Objectives

To explore the usability of routinely collected experience sampling method data over a brief period of time to detect associations between motor fluctuations, affective state, and contextual factors in PD patients with motor fluctuations on a group level and on an individual level.

Methods

Eleven patients with motor fluctuations collected data at 10 semirandom moments over the day for 5 consecutive days.

Results

On a group level, multilevel analyses showed significant associations between all motor symptoms and positive affect. Being at home was associated with increased balance problems and rigidity. Analyses on an individual level revealed much less significant associations that mostly, but not always, were in line with the results on a group level.

Conclusion

This exploratory study showed significant associations between affective state, motor symptoms, and contextual factors in a group of PD patients with motor fluctuations, but less so in individual patients. Given that the ultimate aim is to use the experience sampling method as an aid to personalize treatments, the sensitivity of the approach needs to be increased. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
DNAJC6 Mutations Disrupt Dopamine Homeostasis in Juvenile Parkinsonism‐Dystonia
Authors: Ng Joanne , Cortès‐Saladelafont Elisenda , Abela Lucia , Termsarasab Pichet , Mankad Kshitij , Sudhakar Sniya , Gorman Kathleen M. , Heales Simon J.R. , Pope Simon , Biassoni Lorenzo , Csányi Barbara , Cain John , Rakshi Karl , Coutts Helen , Jayawant Sandeep , Jefferson Rosalind , Hughes Deborah , García‐Cazorla Àngels , Grozeva Detelina , Raymond F. Lucy , Pérez‐Dueñas Belén , De Goede Christian , Pearson Toni S. , Meyer Esther , Kurian Manju A.
Published: May 2020

Background

Juvenile forms of parkinsonism are rare conditions with onset of bradykinesia, tremor and rigidity before the age of 21 years. These atypical presentations commonly have a genetic aetiology, highlighting important insights into underlying pathophysiology. Genetic defects may affect key proteins of the endocytic pathway and clathrin‐mediated endocytosis (CME), as in DNAJC6‐related juvenile parkinsonism.

Objective

To report on a new patient cohort with juvenile‐onset DNAJC6 parkinsonism‐dystonia and determine the functional consequences on auxilin and dopamine homeostasis.

Methods

Twenty‐five children with juvenile parkinsonism were identified from a research cohort of patients with undiagnosed pediatric movement disorders. Molecular genetic investigations included autozygosity mapping studies and whole‐exome sequencing. Patient fibroblasts and CSF were analyzed for auxilin, cyclin G–associated kinase and synaptic proteins.

Results

We identified 6 patients harboring previously unreported, homozygous nonsense DNAJC6 mutations. All presented with neurodevelopmental delay in infancy, progressive parkinsonism, and neurological regression in childhood. 123I‐FP‐CIT SPECT (DaTScan) was performed in 3 patients and demonstrated reduced or absent tracer uptake in the basal ganglia. CSF neurotransmitter analysis revealed an isolated reduction of homovanillic acid. Auxilin levels were significantly reduced in both patient fibroblasts and CSF. Cyclin G–associated kinase levels in CSF were significantly increased, whereas a number of presynaptic dopaminergic proteins were reduced.

Conclusions

DNAJC6 is an emerging cause of recessive juvenile parkinsonism‐dystonia. DNAJC6 encodes the cochaperone protein auxilin, involved in CME of synaptic vesicles. The observed dopamine dyshomeostasis in patients is likely to be multifactorial, secondary to auxilin deficiency and/or neurodegeneration. Increased patient CSF cyclin G–associated kinase, in tandem with reduced auxilin levels, suggests a possible compensatory role of cyclin G–associated kinase, as observed in the auxilin knockout mouse. DNAJC6 parkinsonism‐dystonia should be considered as a differential diagnosis for pediatric neurotransmitter disorders associated with low homovanillic acid levels. Future research in elucidating disease pathogenesis will aid the development of better treatments for this pharmacoresistant disorder. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Knowledge‐based isocenter selection in radiosurgery planning
Authors: Berdyshev A. , Cevik M. , Aleman D. , Nordstrom H. , Riad S. , Lee Y. , Sahgal A. , Ruschin M.
Published: May 2020

Purpose

We present a new method for knowledge‐based isocenter selection for treatment planning in radiosurgery. Our objective is to develop a prediction model that can learn from past manually designed treatment plans. We leverage recent advances in deep learning to predict isocenter locations in treatment plans in order to provide a decision support tool.

Methods

The proposed method adapts a geometric approach using orthogonal moment expansions as a feature vector for describing the shape of the tumor. Our approach accounts primarily for tumor shape and OAR proximity, the two factors that are known to greatly affect the isocenter placement. We solve the prediction problem by training a residual neural network with skip connections on the formed shape descriptors. Our network was trained on 533 patient cases and was validated on a set of out‐of‐sample cases.

Results

Our method generates heatmap predictions for isocenter locations that are in most cases comparable to the experienced human planners, which shows that the method can be used in treatment planning to guide the users for determining the isocenters.

Conclusions

Our numerical experiments indicate a positive predictive value on an independent validation set when compared against a test dataset that was not seen by the model during training.
Sex‐opposed inflammatory effects of 27‐hydroxycholesterol are mediated via differences in estrogen signaling
Authors: Houben Tom , Bitorina Albert V , Oligschlaeger Yvonne , Jeurissen Mike LJ , Rensen Sander , Köhler S Eleonore , Westerterp Marit , Lütjohann Dieter , Theys Jan , Romano Andrea , Plat Jogchum , Shiri‐Sverdlov Ronit
Published: May 2020

Despite the increased awareness of differences in the inflammatory response between men and women, only limited research has focused on the biological factors underlying these sex differences. The cholesterol derivative 27‐hydroxycholesterol (27HC) has been shown to have opposite inflammatory effects in independent experiments using mouse models of atherosclerosis and non‐alcoholic steatohepatitis (NASH), pathologies characterized by cholesterol‐induced inflammation. As the sex of mice in these in vivo models differed, we hypothesized that 27HC exerts opposite inflammatory effects in males compared to females. To explore whether the sex‐opposed inflammatory effects of 27HC translated to humans, plasma 27HC levels were measured and correlated with hepatic inflammatory parameters in obese individuals. To investigate whether 27HC exerts sex‐opposed effects on inflammation, we injected 27HC into female and male Niemann–Pick disease type C1 mice (Npc1nih) that were used as an extreme model of cholesterol‐induced inflammation. Finally, the involvement of estrogen signaling in this mechanism was studied in bone marrow‐derived macrophages (BMDMs) that were treated with 27HC and 17β‐estradiol (E2). Plasma 27HC levels showed opposite correlations with hepatic inflammatory indicators between female and male obese individuals. Likewise, hepatic 27HC levels oppositely correlated between female and male Npc1nih mice. Twenty‐seven hydroxycholesterol injections reduced hepatic inflammation in female Npc1nih mice in contrast to male Npc1nih mice, which showed increased hepatic inflammation after 27HC injections. Furthermore, 27HC administration also oppositely affected inflammation in female and male BMDMs cultured in E2‐enriched medium. Remarkably, female BMDMs showed higher ERα expression compared to male BMDMs. Our findings identify that the sex‐opposed inflammatory effects of 27HC are E2‐dependent and are potentially related to differences in ERα expression between females and males. Hence, the individual’s sex needs to be taken into account when 27HC is employed as a therapeutic tool as well as in macrophage estrogen research in general. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Gremlin 1 — small protein, big impact: the multiorgan consequences of disrupted BMP antagonism†
Authors: Gooding Sarah , Leedham Simon J
Published: May 2020

Highly conserved, complex and interacting morphogen signalling pathways regulate adult stem cells and control cell fate determination across numerous different organs. In homeostasis, the bone morphogenetic protein (BMP) pathway predominantly promotes cell differentiation. Localised expression of ligand sequestering BMP antagonists, such as Gremlin 1 (Grem1), necessarily restricts BMP activity within the stem cell niche and facilitate stemness and self‐renewal. In a new paper, Rowan, Jahns et al show that acute deletion of Grem1 in adult mice, using a ubiquitous ROSA26‐Cre recombinase, induced not only severe intestinal enteropathy but also hypocellular bone marrow failure suggestive of stem cell niche collapse in both tissues. Grem1 has an increasingly recognised pleiotrophic role in a number of organ systems and is implicated across a wide range of disease states. Although the importance of Grem1 in intestinal stem cell regulation has been well described, a putative function in haematopoietic niche maintenance is novel and requires further exploration. Moreover, the complex and context‐specific regulation of Grem1, among a host of functionally convergent but structurally disparate BMP antagonists, warrants further research as we learn more about the pathogenic consequences of deranged expression of this small, but important, protein. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Position paper: Challenges and specific strategies for constitutional mismatch repair deficiency syndrome in low‐resource settings
Authors: Kebudi Rejin , Amayiri Nisreen , Abedalthagafi Malak , Rana Asım Noor , Kirmani Salman , Musthaq Naureen , Lamki Zakiya Al , Houdzi Jamila El , Yazici Hulya , El‐Naggar Shahenda , Edwards Melissa , Bianchi Vanessa J. , Durno Carol , Tabori Uri , Bouffet Eric ,   for the International RRD Consortium on Low‐Resource Settings Panel
Published: May 2020

Germline biallelic mutations in one of the mismatch repair genes, mutS homolog 2, mutS homolog 6, mutL homolog 1, or postmeiotic segregation increased 2, result in one of the most aggressive cancer syndromes in humans termed as constitutional mismatch repair deficiency (CMMRD). Individuals with CMMRD are affected with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood without specific interventions. The most common tumors observed are central nervous system, hematological, and gastrointestinal malignancies. The incidence of CMMRD is expected to be high in low‐resource settings due to a high rate of consanguinity in these regions, and it is thought to be underrecognized and consequently underdiagnosed. This position paper is therefore important to provide a summary of the current situation, and to highlight the necessity of increasing awareness, diagnostic criteria, and surveillance to improve survival for patients and family members.