bluuebunny/crossref_metadata_2025 huggingface dataset:
Rewiring the yeast cell wall integrity (CWI) pathway through a synthetic positive feedback circuit unveils a novel role for the MAPKKK Ssk2 in CWI pathway activation
Authors: Jiménez‐Gutiérrez Elena , Alegría‐Carrasco Estíbaliz , Alonso‐Rodríguez Esmeralda , Fernández‐Acero Teresa , Molina María , Martín Humberto
Published: March 2020

The cell wall integrity (CWI) pathway mediates the response of Saccharomyces cerevisiae to cell wall alterations. Stress at the cell surface is detected by mechanosensors, which transduce the signal to a protein kinase cascade that involves Pkc1, Bck1, Mkk1/Mkk2, the mitogen‐activated protein kinase (MAPK) Slt2 and the transcription factor Rlm1. We incorporated a positive feedback loop into this pathway by placing a hyperactive MKK1 allele under the control of the Rlm1‐regulated MLP1 promoter. This circuit operates as a signal amplifier and leads to a highly increased Slt2 activation under stimulating conditions. Triggering the CWI pathway in cells engineered with this circuit, which we have named the Integrity Pathway Activation Circuit (IPAC), results in strong growth inhibition. Exploitation of this hypersensitive phenotype allowed the identification of novel proteins that contribute in signalling to Rlm1 in response to cell surface stressing agents such as Congo red, zymolyase and SDS. Among these proteins, the MAPK kinase kinase Ssk2 of the osmoregulatory high‐osmolarity glycerol (HOG) pathway, but not its paralogue Ssk22, proved to be necessary for the SDS‐induced IPAC‐mediated growth inhibition. We found the existence of an Ssk1‐independent Ssk2‐Pbs2‐Hog1‐CWI pathway signalling axis that contributes to Slt2 activation in response to cell surface stress. We also demonstrated that the MAP kinase kinases Mkk1 and Pbs2 and the MAPKs Slt2 and Hog1 of the HOG and CWI pathways interact physically, forming a complex. Our results show how a simple synthetic circuit can be used as a powerful tool for a better understanding of signalling pathways.
‘I’ll never be one of the boys’: Gender harassment of women working as pilots and automotive tradespeople
Authors: Foley Meraiah , Oxenbridge Sarah , Cooper Rae , Baird Marian
Published: March 2020

Significant research has examined sexual harassment in male‐dominated occupations, but gender harassment — harassment that is not necessarily sexual in nature but is targeted at individuals, or a group of individuals, because of their sex or gender — has received relatively less attention. Drawing on in‐depth, semi‐structured interviews, we analyse the lived experience of gender harassment among women working as pilots and automotive tradespeople in Australia. We find that women in these occupations face a daily barrage of belittling jokes and demeaning comments from colleagues, managers and customers, and such behaviours are retribution for encroaching on traditionally male occupational domains. Although women found these behaviours humiliating, intimidating, and offensive, they lacked a comprehensive vocabulary to define or condemn them. This article contributes to an emerging literature arguing that gender harassment needs to be more clearly problematized, organizationally and legally, as a form of sex‐based harassment constituting unlawful sex discrimination.
Synthesis of multifunctional hollow SiO2‐CaO‐Fe2O3 glass‐ceramic nanospheres
Authors: Luo Wenqin , Li Bin , Wang Yongya , Pan Guoxiang , Wu Haiyan
Published: March 2020

Glass ceramics with multifunctions of bioactivity, drug delivery, and magnetic hyperthermia have great potential applications in the field of bioscience. Herein, we design and synthesize a multifunctional hollow SiO2‐CaO‐Fe2O3 (SCF) glass‐ceramic nanosphere (GCNS) by a template‐mediated sol‐gel precipitate method. The magnetite as the main crystal phase was successfully precipitated from the SCF glassy matrixes after heat treated at 800°C. The influence of composition and the Fe3+/Fe2+ precursor ratio on the morphology, crystallization, micropore structure, and magnetic properties were systematically studied. Intact spherical hollow SCF GCNSs were obtained under the heat treatment at 800°C for 2 hours when the Fe2O3 content below 15 wt%. Under certain Fe2O3 content, the coercivity and micropore volume of SCF GCNSs were found to be increased with increasing the mole ratio of FeCl3/FeCl2 precursors. High drug loading capacity of 24.2 wt% and sustained drug release were observed from the methylene blue–loaded SCF GCNSs in simulated body fluid solution. The hollow SCF GCNSs synthesized in this work exhibiting good magnetic properties and sustained drug release performance have great potential applications in the cancer therapy.
STone Episode Prediction: Development and validation of the prediction nomogram for urolithiasis
Authors: Okita Kazutaka , Hatakeyama Shingo , Imai Atsushi , Tanaka Toshikazu , Hamano Itsuto , Okamoto Teppei , Tobisawa Yuki , Yoneyama Tohru , Yamamoto Hayato , Yoneyama Takahiro , Hashimoto Yasuhiro , Nakaji Shigeyuki , Suzuki Tadashi , Ohyama Chikara
Published: March 2020

Objectives

To develop and validate a nomogram predicting the occurrence of a stone episode, given the lack of such predicting risk tools for urolithiasis.

Methods

We retrospectively analyzed 1305 patients with urolithiasis and 2800 community‐dwelling individuals who underwent a comprehensive health survey. The STone Episode Prediction nomogram was created based on data from the medical records of 600 patients with urolithiasis and 1300 controls, and was validated using a different population of 705 patients with urolithiasis and 1500 controls. Logistic regression analysis was used to construct a model to predict the potential candidate for a stone episode. The predictive ability of the model was evaluated using the results of the area under the receiver operating characteristics curve (area under the curve).

Results

Age, sex, diabetes mellitus, renal function, serum albumin, and serum uric acid were found to be significantly associated with urolithiasis in the training set and were included in the STone Episode Prediction nomogram. The optimal cut‐off value for the probability of a stone episode using the nomogram was >28% with a sensitivity of 79%, a specificity of 76%, and area under the curve of 0.860. In the validation test, area under the curve for the detection of urolithiasis was 0.815 with a sensitivity of 81% and specificity of 63%.

Conclusions

Herein, we developed and validated the STone Episode Prediction nomogram that can predict a potential candidate for an episode of urolithiasis. This nomogram might be beneficial for the first step in stone screening in individuals with lifestyle‐related diseases.
PilVax, a novel Lactococcus lactis‐based mucosal vaccine platform, stimulates systemic and mucosal immune responses to Staphylococcus aureus
Authors: Clow Fiona , Peterken Kelly , Pearson Victoria , Proft Thomas , Radcliff Fiona J
Published: March 2020

Most pathogens initiate infection via the mucosa, therefore delivery of vaccines directly to the mucosa is likely to be advantageous for stimulating protective immunity at the site of entry. PilVax is a novel mucosal vaccine platform that harnesses Lactococcus lactis bacteria engineered to stably express multiple copies of vaccine peptide antigens within pili, hair‐like structures which extend from the cell wall. This strategy elicited systemic and mucosal antibody responses to a model antigen after intranasal immunization, but has not been tested for its capacity to stimulate protective mucosal immunity. A well‐characterized linear B‐cell epitope, D3(22–33), from the fibronectin‐binding protein A of Staphylococcus aureus was successfully introduced into PilVax and delivered intranasally to mice. Specific antipeptide immunoglobulin (Ig) G and IgA antibodies were detected in the serum and respiratory mucosa of vaccinated mice. Responses to the major pilus backbone protein Spy0128 were also assessed; robust antibody responses to this antigen were generated both systemically and in the respiratory and intestinal mucosa. Mice were challenged intranasally with the mouse‐adapted S. aureus JSNZ strain and the S. aureus load quantified 7 days after challenge. Unexpectedly, exposure to PilVax, irrespective of the presence of the peptide, resulted in a significant reduction in S. aureus load in both the intestine and nasal mucosa (both P < 0.05) when compared with unvaccinated control mice. The mechanism(s) of protection are unclear, but merit further investigation to determine whether PilVax is a suitable platform for delivery of vaccine candidate antigens to the mucosa.
Clinical and economic burden of wound care in the tropics: a 5‐year institutional population health review
Authors: Lo Zhiwen J. , Lim Xuxin , Eng Diane , Car Josip , Hong Qiantai , Yong Enming , Zhang Li , Chandrasekar Sadhana , Tan Glenn W. L. , Chan Yam M. , Sim Seow C. , Oei Chien W. , Zhang Xiaojin , Dharmawan Ayliana , Ng Yi Z. , Harding Keith , Upton Zee , Yap Chun W. , Heng Bee H.
Published: March 2020

The aim of this study is to evaluate the clinical and economic burden of wound care in the Tropics via a 5‐year institutional population health review. Within our data analysis, wounds are broadly classified into neuro‐ischaemic ulcers (NIUs), venous leg ulcers (VLUs), pressure injuries (PIs), and surgical site infections (SSIs). Between 2013 and 2017, there were a total of 56 583 wound‐related inpatient admissions for 41 461 patients, with a 95.1% increase in wound episodes per 1000 inpatient admissions over this period (142 and 277 wound episodes per 1000 inpatient admissions in 2013 and 2017, respectively). In 2017, the average length of stay for each wound episode was 17.7 days, which was 2.4 times that of an average acute admission at our institution. The average gross charge per wound episode was USD $12 967. Among the 12 218 patients with 16 674 wound episodes in 2017, 71.5% were more than 65 years of age with an average Charlson Comorbidity Index (CCI) of 7.2. Half (51.9%) were moderately or severely frail, while 41.3% had two or more wound‐related admission episodes. In 2017, within our healthcare cluster, the gross healthcare costs for all inpatient wound episodes stand at USD $216 million within hospital care and USD $596 000 within primary care. Most NIU patients (97.2%) had diabetes and they had the most comorbidities (average CCI 8.4) and were the frailest group of patients (44.9% severely frail). The majority of the VLU disease burden was at the specialist outpatient setting, with the average 1‐year VLU recurrence rate at 52.5% and median time between healing and recurrence at 9.5 months. PI patients were the oldest (86.5% more than 65 years‐old), constituted the largest cohort of patients with 3874 patients at an incidence of 64.6 per 1000 admissions in 2017, and have a 1‐year all‐cause mortality rate of 14.3%. For SSI patients, there was a 125% increase of 14.2 SSI wound episodes per 1000 inpatient admissions in 2013 to 32.0 in 2017, and a 413% increase in wound‐related 30‐day re‐admissions, from 40 in 2013 (4.1% of all surgeries) to 205 (8.3% of all surgeries) in 2017. The estimated gross healthcare cost per patient ranges from USD $15789–17 761 across the wound categories. Similar to global data, there is a significant and rising trend in the clinical and economic burden of wound care in Tropics.
Development and validation of a 10‐gene prognostic signature for acute myeloid leukaemia
Authors: Yang Zuyi , Shang Jun , Li Ning , Zhang Liang , Tang Tingting , Tian Guoyan , Chen Xiaohui
Published: March 2020

Acute myeloid leukaemia (AML) is the most common type of adult acute leukaemia and has a poor prognosis. Thus, optimal risk stratification is of greatest importance for reasonable choice of treatment and prognostic evaluation. For our study, a total of 1707 samples of AML patients from three public databases were divided into meta‐training, meta‐testing and validation sets. The meta‐training set was used to build risk prediction model, and the other four data sets were employed for validation. By log‐rank test and univariate COX regression analysis as well as LASSO‐COX, AML patients were divided into high‐risk and low‐risk groups based on AML risk score (AMLRS) which was constituted by 10 survival‐related genes. In meta‐training, meta‐testing and validation sets, the patient in the low‐risk group all had a significantly longer OS (overall survival) than those in the high‐risk group (P < .001), and the area under ROC curve (AUC) by time‐dependent ROC was 0.5854‐0.7905 for 1 year, 0.6652‐0.8066 for 3 years and 0.6622‐0.8034 for 5 years. Multivariate COX regression analysis indicated that AMLRS was an independent prognostic factor in four data sets. Nomogram combining the AMLRS and two clinical parameters performed well in predicting 1‐year, 3‐year and 5‐year OS. Finally, we created a web‐based prognostic model to predict the prognosis of AML patients (https://tcgi.shinyapps.io/amlrs_nomogram/).
Immigration, Race and the Radical Right: Politics and Policy from Colonialism to Brexit
Authors: Givens Terri E.
Published: March 2020

Abstract

I began studying the radical right and immigration policy in Europe in the mid‐1990s and when conducting my research, I have been acutely aware of the impact of my background and personal experiences on my perspectives on these issues. As an African American, first‐generation college graduate, I am unusual in my knowledge of French and German, let alone the fact that I study immigration and radical right parties in Europe. In fact, given that my name is gender neutral and non‐ethnic sounding, many who meet me are surprised that I am the Terri Givens who wrote the classic book, Voting Radical Right in Western Europe. However, I believe that it is important for a diversity of voices to reflect on and conduct research into these topics.
City‐level water withdrawal in China: Accounting methodology and applications
Authors: Zhang Zongyong , Liu Junguo , Cai Bofeng , Shan Yuli , Zheng Heran , Li Xian , Li Xukun , Guan Dabo
Published: March 2020

In the context of the freshwater crisis, accounting for water withdrawal could help planners better regulate water use in different sectors to combat water scarcity. However, the water withdrawal statistics in China are patchy, and the water data across all sectors at the city level appear to be relatively insufficient. Hence, we develop a general framework to, for the first time, estimate the water withdrawal of 58 economic–social–environmental sectors in cities in China. This methodology was applied because only inconsistent water statistics collected from different data sources at the city level are available. We applied it to 18 representative Chinese cities. Different from conventional perceptions that agriculture is usually the largest water user, industrial and household water withdrawal may also occupy the largest percentages in the water‐use structure of some cities. The discrepancy among annual household water use per capita in the urban areas of different cities is relatively small (as is the case for rural areas), but that between urban and rural areas is large. As a result, increased attention should be paid to controlling industrial and urban household water use in particular cities. China should specifically prepare annual water accounts at the city level and establish a timetable to tackle water scarcity, which is a basic step toward efficient and sustainable water crisis mitigation.
TV 3326 for Alzheimer’s dementia: a novel multimodal ChE and MAO inhibitors to mitigate Alzheimer’s-like neuropathology
Authors: Uddin Md Sahab , Kabir Md Tanvir , Rahman Md Motiar , Mathew Bijo , Shah Muhammad Ajmal , Ashraf Ghulam Md
Published: March 2020

Objectives

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders and a well-recognized cause of dementia with ageing. In this review, we have represented the ChE and MAO inhibitory potential of TV 3326 against AD based on current scientific evidence.

Key findings

The aetiology of AD is quite complex and not completely understood. However, it has been observed that AD involves the deposition of abnormal amyloid beta (Aβ), along with hyperphosphorylation of tau, oxidative stress, low acetylcholine (ACh) level and biometal dyshomeostasis. Due to the complex nature of AD aetiology, active research is required in the areas of development of multitarget drugs with 2 or more complementary biological functions, as they might represent significant progress in the AD treatment. Interestingly, it has been found that TV 3326 (i.e. ladostigil) is regarded as a novel therapeutic agent since it has the potential to cause inhibition of monoamine oxidase (MAO) A and B, and acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the brain. Furthermore, it has the capacity to reverse memory impairments, which further suggests the ability of this drug to elevate cholinergic activity in the brain.

TV 3326 can avert oxidative–nitrative stress and gliosis. It has also been confirmed that TV 3326 contains neuroprotective and anti-apoptotic properties. Therefore, this distinctive combined inhibition of ChE and MAO along with its neuroprotective property makes TV 3326 a useful drug in the treatment of AD.
Diversifying the Social Scientific Study of Religion: The Next 70 Years
Authors: Ecklund Elaine Howard
Published: March 2020

Here I argue that we need to diversify the social scientific study of religion and chart a plan for how we are already and will continue to do so. At the time of the 70th anniversary of our association, I reflect on where—as an association—we have come from and where we are going. Our origin story points to an expansive vision for what would become the Society for the Scientific Study of Religion (SSSR), but unfortunately our past has also been marked by an overrepresentation of white male leadership. It was only in 1982 that the society elected its first woman president, Mary Augusta Neal, and only in 2015 that it elected its first person of color, Fenggang Yang. Here, I discuss our hope for a more diverse future: attending to diversity in studies of religion, diversity in the groups of people who are encouraged to study religion, and efforts to translate religion research well to diverse groups of listeners. I share with you pieces of the new SSSR strategic plan, spearheaded in 2018 by Korie Edwards, the first black and woman of color President of the SSSR: particularly the pieces that are most attentive to diversity. I also highlight insights from my own scholarly story about diversity that I have learned through my work with the Religion and Public Life Program at Rice University.
Nutritional training in a humanitarian context: Evidence from a cluster randomized trial
Authors: Kurdi Sikandra , Figueroa Jose Luis , Ibrahim Hosam
Published: March 2020

Behavioural change communication interventions have been shown to be effective at improving infant and young child nutrition knowledge and practices. However, evidence in humanitarian response contexts is scarce. Using data on secondary outcomes of breastfeeding, water treatment, and knowledge from a cluster randomized control trial of the Yemen Cash for Nutrition programme's impact on child nutritional status, this paper shows that the programme significantly improved knowledge and practices for poor women with young children in the pilot districts. The intervention consisted of cash transfers and monthly group nutrition education sessions led by locally recruited community health volunteers. Data are based on self‐reports by participants. Estimating impacts among all 1,945 women in 190 clusters randomly assigned to treatment versus control and controlling for baseline levels and community characteristic and adjusting for noncompliance with randomization, the programme increased the probability of breastfeeding initiation within the first hour after delivery by 15.6% points (p < .05; control = 74.4% and treatment = 83.6%), the probability of exclusive breastfeeding during the first 6 months by 14.4% points (control = 13.5% and treatment = 25.3%), the probability of households treating water consumed by adults by 16.7% points (p < .01; control = 13.9% and treatment = 23.4%), and treating water consumed by children under two by 10.3% points (p < .10; control = 31.2% and treatment = 37.9%). Impacts on knowledge and breastfeeding are similar for both literate and illiterate women, and water treatment impacts are significantly larger for literate women. This study was registered at 3ie (RIDIE‐STUDY‐ID‐5b4eff881b29a) and funded by the Nordic Trust Fund and Consultative Group on International Agricultural Research programme on Policies, Institutions, and Markets.
Unraveling hierarchical genetic structure in a marine metapopulation: A comparison of three high‐throughput genotyping approaches
Authors: D’Aloia Cassidy C. , Andrés Jose A. , Bogdanowicz Steven M. , McCune Amy R. , Harrison Richard G. , Buston Peter M.
Published: March 2020

Marine metapopulations often exhibit subtle population structure that can be difficult to detect. Given recent advances in high‐throughput sequencing, an emerging question is whether various genotyping approaches, in concert with improved sampling designs, will substantially improve our understanding of genetic structure in the sea. To address this question, we explored hierarchical patterns of structure in the coral reef fishElacatinus loriusing a high‐resolution approach with respect to both genetic and geographic sampling. Previously, we identified three putativeE. loripopulations within Belize using traditional genetic markers and sparse geographic sampling: barrier reef and Turneffe Atoll; Glover's Atoll; and Lighthouse Atoll. Here, we systematically sampled individuals at ~10 km intervals throughout these reefs (1,129 individuals from 35 sites) and sequenced all individuals at three sets of markers: 2,418 SNPs; 89 microsatellites; and 57 nonrepetitive nuclear loci. At broad spatial scales, the markers were consistent with each other and with previous findings. At finer spatial scales, there was new evidence of genetic substructure, but our three marker sets differed slightly in their ability to detect these patterns. Specifically, we found subtle structure between the barrier reef and Turneffe Atoll, with SNPs resolving this pattern most effectively. We also documented isolation by distance within the barrier reef. Sensitivity analyses revealed that the number of loci (and alleles) had a strong effect on the detection of structure for all three marker sets, particularly at small spatial scales. Taken together, these results illustrate empirically that high‐throughput genotyping data can elucidate subtle genetic structure at previously‐undetected scales in a dispersive marine fish.
Allopatric divergence and hybridization withinCupressus chengiana(Cupressaceae), a threatened conifer in the northern Hengduan Mountains of western China
Authors: Li Jialiang , Milne Richard I. , Ru Dafu , Miao Jibin , Tao Wenjing , Zhang Lei , Xu Jingjing , Liu Jianquan , Mao Kangshan
Published: March 2020

Having a comprehensive understanding of population structure, genetic differentiation and demographic history is important for the conservation and management of threatened species. High‐throughput sequencing (HTS) provides exciting opportunities to address a wide range of factors for conservation genetics. Here, we generated HTS data and identified 266,884 high‐quality single nucleotide polymorphisms from 82 individuals ofCupressus chengiana, to assess population genomics across the species' full range, comprising the Daduhe River (DDH), Minjiang River (MJR) and Bailongjiang River (BLJ) catchments in western China.admixture, principal components analysis and phylogenetic analyses indicated that each region contains a distinct lineage, with high levels of differentiation between them (DDH, MJR and BLJ lineages). MJR was newly distinguished compared to previous surveys, and evidence including coalescent simulations supported a hybrid origin of MJR during the Quaternary. Each of these three lineages should be recognized as an evolutionarily significant unit (ESU), due to isolation, differing genetic adaptations and different demographic history. Currently, each ESU faces distinct threats, and will require different conservation strategies. Our work shows that population genomic approaches using HTS can reconstruct the complex evolutionary history of threatened species in mountainous regions, and hence inform conservation efforts, and contribute to the understanding of high biodiversity in mountains.
Conditions for linearity of the wage curve
Authors: Bidard Christian
Published: March 2020

For a given technique, the wage‐rate of profit curve is linear in one‐sector models. In multisector models, Wicksell effects appear and some paradoxes in capital theory are linked to the complex shape of the wage curve. We study the conditions ensuring the linearity of the curve for a bisector model and for models satisfying a specific rank condition.
Caregiving, Self-Care, and Contemplation: Resources from Thomas Aquinas
Authors: Dubie Emily
Published: March 2020

In the last decade, the helping professions have increasingly recognized compassion fatigue, burnout, and secondary trauma as hazards integral to care-work, and in response, they have turned to self-care to build caregiver resilience. To examine the theological and ethical assumptions implicit in self-care literature, I turn to Thomas Aquinas's account of the active and contemplative lives in the Summa Theologiae. In correlating the two lives as meeting neighbors’ needs and beholding God, Thomas offers three competing accounts. Rather than synthesizing these differences, I argue that they map a range of interactions possible between one's own wellbeing and another's: care for the neighbor can hinder, prepare for, or be referred to contemplation and its consolations. While affirming self-care's recognition of human limits, my reading of Thomas also offers a correction, insisting that divergent experiences of caregivers are possible. This depends on the particulars, among which include the grace of divine assistance.
Familial dropped head syndrome with extremity muscle weakness
Authors: Tsunoda Keiichiro , Hishikawa Nozomi , Omote Yoshio , Ikegami Ken , Nakano Yumiko , Sato Kota , Takemoto Mami , Ohta Yasuyuki , Yamashita Toru , Abe Koji
Published: March 2020

We report a new case of familial dropped head syndrome (DHS) due to myopathy. The proband is a 63‐year‐old woman, and her younger sister and son also showed DHS. She was not good at sport since elementary school and showed unique muscle weakness in her paraspine and four limbs. A blood test showed a slight increase in creatine kinase (237 IU/mL) and myoglobin (95 ng/mL). An electromyogram showed myogenic change, and computed tomography revealed a normal muscle volume of the neck but paraspinal muscle atrophy. Muscle biopsy of the right femoral muscle found type 2 fiber atrophy. Based on these unique clinical features, this is the first report of familial DHS which probably due to congenital myopathy.
Articular Cartilage Stem Cells Influence the Postoperative Repair of Hip Replacement by Regulating Endoplasmic Reticulum Stress in Chondrocytes via PERK Pathway
Authors: Rong Ke , Xia Qing‐quan , Wu Xu‐hua , Zhou Zhen‐yu , Li Xu‐jun , Fei Teng , Chen Jiong , Huang Zhongyue , Li Jiang , Liu Jiang‐yi , Yin Xiao‐fan
Published: March 2020

Objective

Endoplasmic reticulum stress (ERS) is present in chondrocytes of osteoarthritis, and the intensity of ERS is related to the degree of cartilage degeneration. In vitro intervention strategies can change the status of ERS and induce the inhibition of ERS‐related pathway. Therefore, this study is designed to explore the role and molecular mechanism of cartilage stem cells (ACSCs) of ERS in chondrocytes after hip replacement.

Methods

Human cartilage cell lines C28/I2 were cultured as the control group. The ERS inducer was added into C28/I2 as ERS group. The third ERS + stem cells group was formed by adding cartilage stem cells into ERS group, and further transfection of si‐PERK was defined as si‐PERK + ERS + stem cells group. Cell cycle and apoptosis in the four groups were determined by flow cytometry. The protein expression of GRP78, PERK, ATF4, TMEM119, CDK4, Cyclin D, and BMP6 in chondrocytes in the four groups were investigated by western blot, and the distribution of PERK, TMEM119, and BMP6 in chondrocytes were observed by immunofluorescence assay. In addition, the transcriptional levels of Bcl2, Bax, and Caspase 3 were also determined by RT‐PCR.

Results

In cell cycle assay, ERS increased the accumulation of cells in G0/G1 and G2/M, while cartilage stem cells weakened the effects. The apoptosis rates in control group, ERS, ERS + stem cells, si‐PERK + ERS + stem cells were 0%, 21.3%, 18.9%, and 15.9%, respectively, and the difference of apoptosis rate between the latter three groups and control group was statistically significant (P < 0.01). Stem cells could weaken the ERS‐induced cell apoptosis, especially reducing the number of cells in the late stage of apoptosis from 5.4% to 1.1%. The protein level of GRP78, PERK, ATF4, TMEM119, and BMP6 in the group of ERS, ERS + stem cells, and si‐PERK + ERS + stem cells were all significantly higher than those in control group, and the group of ERS + stem cells was the highest, all of the differences were significant (P < 0.01). However, the protein level of CDK4 and Cyclin D presented an absolutely opposite trend and the difference was still significant (P < 0.05). The group of si‐PERK + ERS + stem cell was lower than those in the group of ERS + stem cell but higher than those in the group of ERS (P < 0.05). The level of Caspase 3 in the latter three groups was significantly higher than those in the control group, and the group of ERS was the highest (P < 0.01). Besides, the relative level of Bcl‐2/Bax in control group was 1, but the group of ERS was about 0.5, and there was significant difference (P < 0.01). The ratio of Bcl‐2/Bax in the group of ERS + stem cells was more than 2 and significantly higher than those of other groups.

Conclusion

ACSCs could reduce ERS‐induced chondrocyte apoptosis by PERK and Bax/Bcl‐2 signaling pathway.
Mobile echodensities on intracardiac device leads: Is it always a cause for concern?
Authors: Robinson James , Wang William Y. S. , Kaye Gerry
Published: March 2020

Background

Patients with cardiac implantable electronic devices (CIEDs) frequently undergo transthoracic echocardiography (TTE). As a result, incidental mobile echodensities (MEDs) attached to device leads are commonly detected. The aim of this study was to estimate the incidence and clinical outcomes of incidental MEDs on CIED leads.

Methods

A retrospective analysis performed between 2011 and 2018 identified 3548 TTE studies performed on 1849 patients with CIEDs.

Results

MEDs were identified in 30 patients (1.6%) without clinical suspicion of infective endocarditis (IE). Patients with incidental MEDs were apyrexial, and those tested demonstrated low inflammatory markers and negative blood cultures (BC). In this group, the majority (83%) of MEDs were in the right atrium and no MEDs were detected near the tricuspid valve. Transesophageal echocardiography (TEE) did not influence clinical outcomes. No patient required long‐term antibiotics or lead extraction and no IE‐related deaths were identified from electronic health records during a mean follow‐up period of 43 months (1‐89). In contrast, nine patients with suspected IE were all pyrexial with elevated inflammatory markers, had positive BC, and had proven IE. In these cases, the majority of MEDs were at the device lead/tricuspid valve interface. MEDs close to the tricuspid valve were strongly associated with IE (P < .0001).

Conclusions

The incidence of MEDs on CIED leads detected on routine TTE was 1.6%. Conservative management of asymptomatic patients with normal inflammatory markers and BC without TEE, antibiotics, or lead extraction did not reveal any signal for long‐term adverse events within the limitations of the study.
Veterans Justice Programs: Assessing Population Risks for Suicide Deaths and Attempts
Authors: Palframan Kristen M. , Blue‐Howells Jessica , Clark Sean C. , McCarthy John F.
Published: March 2020

Objectives

Understanding suicide risks among Veteran subpopulations is a national priority. This study assessed risks of suicide, suicide attempts, and other‐cause mortality among recipients of Veterans Health Administration (VHA) Veterans Justice Program services as compared to other Veteran VHA users.

Methods

Per VHA records, the cohort included 5,401,192 Veterans alive as of January 1, 2013 and with VHA utilization in 2012. Receipt of Veterans Justice Outreach (VJO) or Health Care for Reentry Veterans (HCRV) services in 2012 was assessed using encounter codes. Multivariable proportional hazards regression assessed risks of suicide (per National Death Index search results from the VA/DoD Mortality Data Repository) and attempts (per diagnoses and site reports) in 2013–2016, adjusting for demographic and clinical indicators.

Results

Compared to other patients, Veterans with VJO encounters had greater risk of suicide (unadjusted HR = 2.80, 95% confidence interval [CI] = 2.30–3.40; adjusted HR = 1.25, 95% CI = 1.02–1.53) and attempts (unadjusted HR = 8.88, 95% CI = 8.45–9.35; adjusted HR = 1.06, 95% CI = 1.00–1.11). Veterans with HCRV encounters had elevated risk of suicide attempts (unadjusted HR = 4.56, 95% CI = 4.00–5.20; adjusted HR = 1.42, 95% CI = 1.24–1.62). Risks were also elevated for other external causes of mortality.

Conclusions

Findings document increased risk of suicidal behavior among Veterans Justice Program recipients. These results have informed VHA suicide prevention activities.
Developing clinical performance indicators for pre‐hospital blood transfusion: The Thames Valley Air Ambulance approach
Authors: Raitt James , Curry Nicola , Lewis Pip , Dearman James , Poole Kurtis , Surendra Kumar Dhushy
Published: March 2020

Objective

In this article, we describe how we developed and validated key performance indicators (KPIs) for pre‐hospital blood transfusion and offer suggestions for other organisations wishing to develop performance metrics.

Background

KPIs are metrics that compare actual care against an ideal structure, process or outcome standard. An increasing number of UK‐based pre‐hospital critical care services now carry blood components to enable pre‐hospital blood transfusion.

Methods

A working group of pre‐hospital physicians and paramedics was formed to create and validate performance indicators that reflected a high‐quality pre‐hospital transfusion. This was performed by literature searching and reviewing consensus documents that guide the best practice and then adjusting the indicators as the process evolved.

Results

Throughout the year, the performance against the domains was monitored monthly and outputs communicated within the clinical staff of the organisation; at the end of the year, the domains were amended. The final list of performance indicators was as follows: (a) rationale for transfusion documented in the notes; (b) rationale for transfusion in line with Thames Valley Air Ambulance blood transfusion guideline; (c) aggressive management of hypothermia; (d) tranexamic acid administered within an hour of injury; (e) evidence of bleeding in hospital; (f) monitoring of adverse effects of blood transfusion; (g) overall—was the use of blood justified; and (h) no units wasted this month.

Conclusions

This study has shown that it is feasible to devise and implement clinical performance indicators for pre‐hospital blood transfusion and that their use has increased the focus on this important area.
Family language policy, translingualism, and linguistic boundaries
Authors: Jenks Christopher
Published: March 2020

The use of trans‐ constructs, such as trans‐languaging and translingualism, in current scholarship is party driven by a desire to create equitable learning opportunities for marginalized and minority students. While such efforts are important and must continue, it is also essential to explore the extent to which the theoretical principles emerging from trans‐language research are material for all individuals seeking to acquire multiple language resources. For example, do poststructuralist interpretations of linguistic boundaries, where individuals fluidly mix and move between language resources, provide an adequate lens through which to understand families seeking to maintain their heritage languages? This article addresses this question by reviewing past family language policy research. The review demonstrates that a one person – one language policy at home can be beneficial for some families, and that moving forward, trans‐language scholarship must thus resist the temptation to adopt a one‐size‐fits‐all approach to multilingualism.
Isotropic dry etching of Si selectively to Si0.7Ge0.3 for CMOS sub-10 nm applications
Authors: Rachidi Sana , Campo Alain , Loup Virginie , Vizioz Christian , Hartmann Jean-Michel , Barnola Sébastien , Posseme Nicolas
Published: March 2020

The fabrication of Si0.7Ge0.3 sub-10 nm nanochannels in gate-all-around devices requires a highly selective Si isotropic etching process. The etching of Si selectively to Si0.7Ge0.3 with CF4/N2/O2 downstream plasma has been investigated using various morphological and surface characterization techniques. Conditions such as 400 W microwave power, 700 mTorr pressure, 25 °C chuck temperature, and 22% CF4:22% N2:56% O2 feed gas mixture were found to be optimum for selectivity and etch rates. X-ray photoelectron spectroscopy showed that, during the etching process, a highly reactive 8 nm thick SiOxFy layer is formed on Si. Meanwhile, a 2 nm thick passivation layer is observed on SiGe. The latter is a mixture of SiOxFy and GeOxFy species that protected the alloy from etching. The process selectivity was improved by investigating different wet and dry oxidant treatments prior to etching. The dry oxidant treatment gives the best results in terms of selectivity. These results obtained on blanket wafers have been validated on pattern wafers. Scanning electron microscopy demonstrated that SiGe nanowires were fully released with a high selectivity after dry oxidation followed by the etching process.
Acoustic radiation from an infrasonic ball-valve siren
Authors: Gorhum Justin D. , Muir Thomas G. , Slack Charles M. , Hawkins Timothy W. , Barlett Martin L. , Hamilton Mark F.
Published: March 2020

The concept of a ball-valve siren is developed through experimentation and theoretical modeling. The ball-valve siren is a source transducer developed for the purpose of establishing the concept of infrasound generation through the modulation of compressed air flowing through a rotating ball valve and released into the atmosphere, in the context of a siren. Directivity, frequency response, and propagation experiments were performed for the fundamental frequency component, and the results compare favorably to an empirical model based on monopole and dipole radiation. The results show that a small ball-valve siren can generate useful infrasound radiation with nominal directivity at frequencies in the range 1 to 8 Hz.
Examining the Relationships Among Cognitive Acceptance, Behavioral Commitment, Autonomous Extrinsic Motivation, and Physical Activity
Authors: Jenkins Matthew , Hargreaves Elaine A. , Hodge Ken
Published: March 2020

This study examined the relationships among cognitive acceptance, behavioral commitment, psychological need satisfaction, autonomous extrinsic motivation (EM) for physical activity (PA), and PA behavior. Participants (N = 456, M
age = 40.7 years) completed online measures of these variables, and data were analyzed using structural equation modeling. Results indicated a direct pathway from behavioral commitment to autonomous EM, plus indirect effects via autonomy, competence, and relatedness. There was no direct pathway from cognitive acceptance to autonomous EM, but there were indirect effects via competence and autonomy satisfaction. There was a direct pathway from cognitive acceptance to self-reported PA plus indirect effects via autonomous EM. There was no direct pathway from behavioral commitment to self-reported PA, but there were indirect effects via autonomous EM. Cognitive acceptance and behavioral commitment potentially support the development of autonomous EM for PA. Future research using longitudinal and intervention-based research designs is required to determine the causal relationships among these variables.
Increasing the Pleasure and Enjoyment of Exercise: A Novel Resistance-Training Protocol
Authors: Hutchinson Jasmin C. , Zenko Zachary , Santich Sam , Dalton Paul C.
Published: March 2020

This study was designed to test the effect of an increasing- (UP) or decreasing-intensity (DOWN) resistance-training (RT) protocol on the pleasure and enjoyment of RT. The participants (N = 40; mean age = 35.0 ± 9.2 years) completed two RT sessions comprising 3 × 10 repetitions of six exercises. In the UP condition, load progressively increased from 55% to 75% of 1-repetition maximum, while in the DOWN condition, this pattern was reversed (i.e., 75–55% 1-repetition maximum). The DOWN condition resulted in more overall pleasure compared with UP and a slope of increasing pleasure, while the UP condition resulted in decreasing pleasure. Enjoyment of RT, postexercise pleasure, and remembered pleasure were all significantly greater for DOWN compared with UP (allps > .01). These findings suggest that decreasing RT intensity throughout an exercise bout can elicit a positive slope of pleasure and enhance affective evaluations of exercise.
Vibrio cholerae
Hemagglutinin/Protease Inactivates CTXφ
Authors: Kimsey Harvey H. , Waldor Matthew K.
Published: March 2020

Pathogenic strains of
Vibrio cholerae
are lysogens of the filamentous phage CTXφ, which carries the genes for cholera toxin (
ctxAB
). We found that the titers of infective CTXφ in culture supernatants of El Tor CTXφ lysogens increased rapidly during exponential growth but dropped to undetectable levels late in stationary-phase growth. When CTXφ transducing particles were mixed with stationary-phase culture supernatants of El Tor strains, CTXφ infectivity was destroyed. Our data indicate that this growth phase-regulated factor, designated CDF (CTXφ-destroying factor), is the secreted hemagglutinin/protease (HA/P) of
V. cholerae
. A strain containing a disrupted
hap
gene, which encodes HA/P of
V. cholerae
, did not produce CDF activity in culture supernatants. Introduction of the HA/P-expressing plasmid pCH2 restored CDF activity. Also, CDF activity in culture supernatants of a variety of pathogenic
V. cholerae
isolates varied widely but correlated with the levels of secreted HA/P, as measured by immunoblotting with anti-HA/P antibody. CDF was purified from
V. cholerae
culture supernatants and shown to contain a 45-kDa polypeptide which bound anti-HA/P antibodies and which comigrated with HA/P in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The production of high levels of secreted HA/P by certain
V. cholerae
strains may be a factor in preventing CTXφ reinfection in natural environments and in the human host.
The Contributions of Reactive Oxygen Intermediates and Reactive Nitrogen Intermediates to Listericidal Mechanisms Differ in Macrophages Activated Pre- and Postinfection
Authors: Ohya Satoshi , Tanabe Yoshinari , Makino Masato , Nomura Takamasa , Xiong Huabao , Arakawa Masaaki , Mitsuyama Masao
Published: March 2020

The contribution of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) to the killing ofListeria monocytogenesby macrophages activated by addition of spleen cells from listeria-immune mice plus specific antigen was examined. When macrophages were infected withL. monocytogenesand then spleen cells were added, there was not as big a difference in listericidal activity between macrophages cultured with normal spleen cells and those cultured with immune spleen cells as expected. In this culture system, RNI was mainly involved in the macrophage intracellular killing. In macrophages first activated and then infected, a significant level of enhanced killing was observed. Blockade of ROI production drastically affected the enhanced killing ability, while inhibition of RNI production had a negligible effect. Thus, the contributions of ROI and RNI to listericidal mechanisms of macrophages were different between macrophages activated at pre- and postinfection stages.
Lyme Disease-Causing
Borrelia
Species Encode Multiple Lipoproteins Homologous to Peptide-Binding Proteins of ABC-Type Transporters
Authors: Kornacki Jon A. , Oliver Donald B.
Published: March 2020

To identify cell envelope proteins of Borrelia burgdorferi, the causative agent of Lyme disease, we constructed a library of
B. burgdorferi
genes fused to the Escherichia coli phoA gene, which expresses enzymatically active alkaline phosphatase. One such gene, oppA-1, encodes a predicted polypeptide with significant similarities to various peptide-binding proteins of ABC-type transporters. Immediately downstream of oppA-1 are two genes, oppA-2 and oppA-3, whose predicted polypeptide products show strong similarities in their amino acid sequences to OppA-1, including a sequence that resembles the most highly conserved region in peptide-binding proteins. By labeling with [
3
H]palmitate, OppA-1, OppA-2, and OppA-3 were shown to be lipoproteins. DNA hybridization analysis showed that the oppA-1 oppA-2 oppA-3 region is located on the linear chromosome of
B. burgdorferi
, and the genes are conserved among different Borrelia species that cause Lyme disease (
B. burgdorferi
, B. garinii, and B. afzelli), suggesting that all three homologous genes are important to the maintenance of Lyme disease spirochetes in one or more of their hosts.
SirR, a Novel Iron-Dependent Repressor in
Staphylococcus epidermidis
Authors: Hill Philip J. , Cockayne Alan , Landers Patrick , Morrissey Julie A. , Sims Catriona M. , Williams Paul
Published: March 2020

In
Staphylococcus epidermidis
and
Staphylococcus aureus
, a number of cell wall- and cytoplasmic membrane-associated lipoproteins are induced in response to iron starvation. To gain insights into the molecular basis of iron-dependent gene regulation in the staphylococci, we sequenced the DNA upstream of the 3-kb
S. epidermidis sitABC
operon, which Northern blot analysis indicates is transcriptionally regulated by the growth medium iron content. We identified two DNA sequences which are homologous to elements of the
Corynebacterium diphtheriae
DtxR regulon, which controls, in response to iron stress, for example, production of diphtheria toxin, siderophore, and a heme oxygenase. Upstream of the
sitABC
operon and divergently transcribed lies a 645-bp open reading frame (ORF), which codes for a polypeptide of approximately 25 kDa with homology to the DtxR family of metal-dependent repressor proteins. This ORF has been designated SirR (staphylococcal iron regulator repressor). Within the
sitABC
promoter/operator region, we also located a region of dyad symmetry overlapping the transcriptional start of
sitABC
which shows high homology to the DtxR operator consensus sequence, suggesting that this region, termed the Sir box, is the SirR-binding site. The SirR protein was overexpressed, purified, and used in DNA mobility shift assays; SirR retarded the migration of a synthetic oligonucleotide based on the Sir box in a metal (Fe
2+
or Mn
2+
)-dependent manner, providing confirmatory evidence that this motif is the SirR-binding site. Furthermore, Southern blot analysis of staphylococcal chromosomal DNA with the synthetic Sir box as a probe confirmed that there are at least five Sir boxes in the
S. epidermidis
genome and at least three in the genome of
S. aureus
, suggesting that SirR controls the expression of multiple target genes. Using a monospecific polyclonal antibody raised against SirR to probe Western blots of whole-cell lysates of
S. aureus
,
S. carnosus
,
S. epidermidis
,
S. hominis
,
S. cohnii
,
S. lugdunensis
, and
S. haemolyticus
, we identified an approximately 25-kDa cross-reactive protein in each of the staphylococcal species examined. Taken together, these data suggest that SirR functions as a divalent metal cation-dependent transcriptional repressor which is widespread among the staphylococci.