bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of humanized anti‐CD19‐CAR‐T therapy following intensive lymphodepleting chemotherapy for refractory/relapsed B acute lymphoblastic leukaemia
Authors: Wang Jia , Mou Nan , Yang Zhenxing , Li Qing , Jiang Yanyu , Meng Juanxia , Liu Xuxiang , Deng Qi
Published: March 2020

We studied the efficacy and safety of humanized CAR‐T therapy following intensive chemotherapy for refractory/relapsed (R/R) acute lymphoblastic leukaemia (B‐ALL). Twenty‐three patients with R/R B‐ALL were pretreated with intensive chemotherapy (fludarabine combined with medium‐dose cytarabine) 12 days before CAR‐T therapy. Adverse events (AEs), curative effects, infection indicators and cytokine release syndrome (CRS) were monitored. Each of the 23 patients received a dose of 1·0 × 106 cells/kg CAR‐T cell infusion on day 0. After 14 days, 19 patients (82·61%) achieved complete response (CR) or CR with incomplete count recovery. No survival benefit was achieved with consolidative haematopoietic stem‐cell transplantation (HSCT), with a median follow‐up of 14·0 months (range, 1·5–21·0 months). The notable AEs were grade 1–2 CRS in 18 patients, while the other five patients were grade 3 CRS. No patients died of CRS. Only one patient died of respiratory failure due to cytomegalovirus infection 24 days after infusion. The proportion of leukaemic cells in bone marrow on infusion day and the peaks of IL‐6, TNF‐α and IL‐8 levels were correlated with CRS levels. A lower disease burden was achieved by intensive lymphodepleting chemotherapy, and the subsequent CAR‐T therapy had a high response and manageable toxicity.

Trial registration: The patients were enrolled in a clinical trial of ChiCTR‐ONN‐16009862, and ChiCTR1800019622.
Emotional Maltreatment and Adolescent Depression: Mediating Mechanisms and Demographic Considerations in a Child Welfare Sample
Authors: McNeil Shiesha L. , Andrews Arthur R. , Cohen Joseph R.
Published: March 2020

Emotional maltreatment is a risk factor for adolescent depression. Yet, it remains unclear whether commissions and omissions of emotional maltreatment (a) confer vulnerability via distinct mechanisms and (b) demonstrate similar risk across adolescent subpopulations. The present, multiwave study examined whether school engagement and peer relationships explain the depressive effects of distinct emotional maltreatment subtypes in an at‐risk child welfare sample (N = 657; ages 11–14, AgeMean = 12.49). The findings indicated that commission subtypes of emotional maltreatment predicted increasing depressive symptoms via increasing peer relationship problems, especially for girls. Meanwhile, decreasing school engagement was a depressogenic risk pathway for Hispanic adolescents reporting omission subtypes of emotional maltreatment. The results emphasize the importance of distinguish between emotional maltreatment subtypes to identify specific risk pathways for adolescent depression.
Perivenous demyelination: Association with anti‐myelin oligodendrocyte glycoprotein antibody
Authors: Misu Tatsuro , Takai Yoshiki , Takahashi Toshiyuki , Nakashima Ichiro , Fujihara Kazuo , Aoki Masashi
Published: March 2020

By the discovery of an antibody to aquaporin 4 (AQP4), the clinical and radiological findings of neuromyelitis optica (NMO) such as diffuse cerebral or longitudinally extended spinal cord lesions had been clarified as distinct features from multiple sclerosis (MS). Pathological studies in NMO demonstrated loss of immunoreactivity to AQP4 and glial fibrillary acidic protein but a relative preservation of myelin basic protein, especially at the lesions with perivascular deposition of immunoglobulins and complements, suggesting autoimmune disease against astrocytes. In recent years, the antibody against myelin oligodendrocyte glycoprotein (MOG) has been studied for its association with acute demyelinating diseases such as acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM), optic neuritis, AQP4 antibody–negative NMOSD, and brainstem or cerebral cortical encephalomyelitis. We could identify the dominance of perivenous inflammatory demyelination like ADEM in our biopsied case series with MOG antibody. In recent brain‐biopsied cases with MOG antibody, the deposition of humoral immunity, perivascular inflammation, and perivenous demyelination were observed especially in atypical cases including cortical encephalitis or disseminated encephalitis. In this review, we focus on MOG antibody–related diseases, which we considered it as a differentiated disease from MS by means of the disease‐specific autoantibody and the distinct pathophysiology.
Anti‐plexin D1 antibody–mediated neuropathic pain
Authors: Fujii Takayuki , Yamasaki Ryo , Miyachi Yukino , Iinuma Kyoko , Kira Jun‐ichi
Published: March 2020

Neuropathic pain (NeP) is an intractable pain caused by a lesion or disease of the somatosensory nervous system. NeP is often challenging to manage because most of the mechanisms remain to be elucidated. Recent investigations in the field of autoimmune neurology have demonstrated that specific autoantibodies against antigens in the somatosensory pathway can cause NeP. Detection of pathogenic autoantibodies in NeP adds to the understanding of the mechanism of pain, which might aid in the development of novel immunotherapies. Therefore, it is necessary to explore novel NeP‐related autoantibodies to improve the management of intractable pain. Recently, we screened serum autoantibodies that bound to pain‐conducting small dorsal root ganglion (DRG) neurons and their nerve terminals in the dorsal horns of NeP patients. We detected a novel autoantibody that bound to unmyelinated C‐fiber–type small DRG neurons. The positive rate in patients with NeP was 10%. We identified plexin D1 as the target antigen. NeP patients with plexin D1‐IgG developed burning pain and thermal hyperalgesia. The main comorbidities were allergy, collagen vascular disease, and cancer. Plasma exchange and intravenous methylprednisolone pulse therapy are effective for NeP in patients with plexin D1‐IgG, indicating that these autoantibodies might be pathogenic in NeP. Indeed, our in vitro study demonstrated that plexin D1‐IgG induced the membrane hyperpermeability of DRG neurons. In this review, we describe the discovery of plexin D1‐IgG and discuss the association between plexin D1 and pain, allergy, and cancer.
Comprehensive intervention during pregnancy based on short message service to prevent or alleviate depression in pregnant women: A quasi‐experimental study
Authors: Gong Meiqian , Zhang Sheng , Xi Chuhao , Luo Min , Wang Tian , Wang Yingxiang , Wang Songbai , Guo Lan , Lu Ciyong
Published: March 2020

Aim

Women have an increased risk for developing depression during pregnancy, and depression has a serious negative impact on the mother and infant. This study explored the effectiveness and feasibility of a comprehensive intervention based on using a short message service (SMS) to reduce depressive symptoms and prevent depression during pregnancy.

Methods

This quasi‐experimental study was conducted in three public hospitals with similar levels of care and maternal origin in Jiangmen City, Guangdong Province. One of the three hospitals was randomly selected as the intervention hospital, and the others were control hospitals. There were 4501 pregnant women who participated in this study. Pregnant women in the intervention group received a comprehensive intervention based on SMS after enrollment. Data were collected using questionnaires from August 2016 to August 2018.

Results

After the intervention, the Edinburgh Postnatal Depression Scale scores of the intervention group were lower than those of the control group (intervention group: 3.9 ± 3.9, control group: 5.2 ± 4.3, P < .001), and the proportion of subjects with positive depression screening results in the intervention group was also significantly lower than that in the control group (intervention group: 9.0%, control group: 16.1%, P < .001). Moreover, compared with women in the intervention group, women in the control group who did not receive the intervention were more likely to be positive for depression in the third trimester (AOR = 2.04, 95% CI = 1.62‐2.58).

Conclusions

The SMS‐based comprehensive intervention used in this study can effectively alleviate depressive symptoms and reduce the risk of depression during pregnancy.
In defence of the hearing? Emerging geographies of publicness, materiality, access and communication in court hearings
Authors: Hynes Jo , Gill Nick , Tomlinson Joe
Published: March 2020

The shift towards dispute resolution taking place outside traditional legal arenas is fundamentally changing the relationship between space and law, presenting legal geography with pressing new research opportunities. This paper explores how the emerging geographies of publicness, materiality, access to justice and communication shed light on the consequences of alternative and online dispute resolution. Crucially, these consequences raise urgent interdisciplinary questions for geography and law. We set out these questions and suggest that legal geography will be best placed to address them by working through some of the practical, applied ramifications of its concepts and perspectives.
Calcareous algae and cyanobacteria
Authors: Leaf Michael C. , Gay Jessica S. A. , Newbould Matthew J. , Hewitt Owen R. , Rogers Steven L.
Published: March 2020

Algae is an informal term used to describe a broad group of simple organisms from the plant kingdom. The organisms included within this grouping are aquatic photosynthetic biota with an extensive range of life habits and forms. These organisms range from micron‐sized unicellular forms to giant seaweeds and kelps, which can grow to several metres long. Both benthic and planktonic modes of life are known and display a wide variety of life cycles.
Comparison of two perioperative antibiotic schedules in patients undergoing surgical reconstruction with dermal matrix after excision of skin cancer
Authors: Fiorentini Chiara , Bedini Andrea , Mandel Victor Desmond , Bacca Erica , Menozzi Marianna , Reggiani Camilla , De Pace Barbara , Meschiari Marianna , Santoro Antonella , Franceschini Erica , Mussini Cristina , Terrenato Irene , Giacomelli Luca , Magnoni Cristina
Published: March 2020

Perioperative antibiotic treatment duration in skin reconstruction with dermal substitutes is not well established. This study compares the incidence of infective complications after two different durations of perioperative antibiotic treatment in patients undergoing surgical reconstruction with skin dermal substitutes (SDS) after excision of skin cancer. Infective complications at the site of SDS were compared in subjects undergoing surgical reconstruction who received either a > 24‐hour (extended protocol) or a ≤ 24‐hour (short protocol) perioperative antibiotic treatment. Of 116 patients undergoing SDS surgical reconstruction, 62 (53.4%) received an extended schedule, and 54 (46.6%) received a short schedule. The two groups were similar for gender, age, comorbidities, American Society of Anesthesiologists score, and type of skin cancer. Overall incidence rate of infection was 20.7% (24/116). No differences in terms of risk of infection were observed between the two groups (OR: 1.04, 95% CI: 0.42‐2.55; P = .937). Patients undergoing SDS reconstruction in the limb/foot had a higher risk of infection in comparison with those undergoing SDS reconstruction in the chest/head (OR: 2.69, 95% CI: 1.06‐6.86; P = .038). The short protocol was demonstrated to be beneficial to patients undergoing surgical reconstruction with SDS. A ≤ 24‐hour perioperative antibiotic schedule did not increase the infection rate, potentially allowing a reduction of antibiotic exposure.
Enhanced photothermal conversion performances with ultra‐broad plasmon absorption of Au in Au/Sm2O3 composites
Authors: Yu Yang , Xu Sai , Gao Yuefeng , Jiang Muhan , Li Xiangping , Zhang Jinsu , Zhang Xizhen , Chen Baojiu
Published: March 2020

Lanthanide oxides are ideal candidates as photothermal conversion agents owing to their larger photon energy and advantages in biomedical applications. However, the small absorption cross section of rare earth is not conducive of absorbing near infrared light, which will affect the photothermal conversion efficiency of lanthanide oxides. Herein, Au particles are successfully introduced into Sm2O3 to form Au/Sm2O3 composites. The investigation of broadband emission and thermal performances in Sm2O3 and Au/Sm2O3 composites confirm the ultra‐broad plasmon absorption of Au induced thermal effect is in favor of the formation of broadband emission, meanwhile, enhances the photothermal conversion capability of Au/Sm2O3 composites. The temperature increases of the Au/Sm2O3 composites are 5.5°C and 19.6°C compared to Sm2O3 particles under the irradiation of near infrared laser with power density of 11.5 and 29.0 mW/mm2, respectively. In additional, the enhanced photothermal conversion effect is confirmed by the alcohol volatilization experiment and visual infrared thermal images. We present here an idea for enhancing the photothermal conversion capabilities of lanthanide oxides and highlight the promise of using this kind of materials for photothermal therapy.
Indexicality and the Indigenization of Politics: Dancer–Pilgrims Protesting Mining Concessions in the Andes
Authors: Salas Carreño Guillermo
Published: March 2020

El santuario de Quyllurit'i, ubicado al pie de un glaciar a setenta kilómetros de la ciudad del Cuzco, es el foco de la peregrinación más grande de los Andes peruanos. Este artículo analiza una protesta organizada por el Consejo de Naciones Peregrinas del Señor de Qoyllurit'i en la ciudad del Cuzco, reclamando la cancelación de concesiones mineras contiguas al santuario. Si bien los danzantes‐peregrinos no reclaman ser indígenas, sus performances en la protesta estuvieron fuertemente cargadas de índices de indigeneidad enmarcados en las ideologías étnico‐raciales regionales. La protesta obtuvo el apoyo de las autoridades regionales a través de una performance obvia pero implícita de indigeneidad, que también supuso desafíos a la política hegemónica que excluye a los no‐humanos. El artículo resalta cómo múltiples formas de indigeneidad, que emergen primariamente a través de la indexicalidad, pueden intervenir notoriamente en política, pero también cómo la influencia política del Consejo de Naciones depende de su abstención en participar activamente en la política formal. [indigeneidad, performance, orden indexical, protesta contra la minería, cosmopolítica]
Investing in Public School Kitchens and Equipment as a Pathway to Healthy Eating and Equitable Access to Healthy Food
Authors: O'Neill Moira , Mujahid Mahasin , Hutson Malo , Fukutome Amanda , Robichaud Raine , Lopez Jaime
Published: March 2020

BACKGROUND

We gathered baseline data about student need of healthy, free school food, and if current school meal programming serves students in need of healthy free school food, in anticipation of the completion of a district‐wide kitchen infrastructure and educational farm project in a high‐poverty urban school district.

METHODS

We used mixed methods to assess student hunger, whether the school meal program met student needs, and to determine associations between presence of a cooking kitchen and perceptions of healthy food. Participants included 72 staff, 143 parents, and 6437 K‐5 students in the qualitative component, and 9078 parents and 1693 staff in the quantitative component.

RESULTS

Staff participants stated packaging and reheating food influenced student consumption. During observations, students at seven of nine high poverty sites with packaged reheated food did not eat school meals, but this was not true at four out of four high‐poverty sites with unpackaged fresh food. Parents (OR = 1.17, 95% CI 1.00‐1.39) and staff (OR = 1.58, 95% CI 1.15‐2.17) from schools with a cooking kitchen were more likely to perceive school lunch as healthy in adjusted models.

CONCLUSIONS

Food preparation and presentation appears to influence student consumption of school food and adult perception of school meal quality.
Oral doxycycline pharmacokinetics: Lambs in comparison with sheep
Authors: Mileva Rositsa , Subev Sasho , Gehring Ronette , Milanova Aneliya
Published: March 2020

The pharmacokinetics of doxycycline was investigated in lactating sheep and lambs after oral administration at a dose of 10 mg/kg. Concentrations in plasma and milk were assayed with HPLC‐PDA analysis. Doxycycline penetrates into the milk, and levels (0.38 ± 0.21 μg/ml) were found 0.5 hr after the treatment. The results suggest that the lambs can be exposed to doxycycline by suckling milk from their treated mothers. Population pharmacokinetic analysis showed a positive relationship between age, which reflects the stage of development of rumen function, and clearance. Possible explanations for the observed differences include the undeveloped rumen in lambs, the differences in the feed and liver function as evidenced by the blood biochemical parameters aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which were significantly lower in lambs (62.67 ± 27.83 U/L and 8.50 ± 6.80 U/L) than in sheep (114.33 ± 20.77 U/L and 18.00 ± 3.16 U/L).
Sequence and transcript expression of the super‐kdr locus of the horn fly, Haematobia irritans
Authors: Domingues L. N. , Solis G. D. , Bendele K. G. , Foil L. D. , Perez de Leon A. A. , Guerrero F. D.
Published: March 2020

In horn flies, Haematobia irritans irritans (Diptera: Muscidae) (Linnaeus, 1758), target site resistance to pyrethroids can be diagnosed by an allele‐specific PCR that genotypes individual flies at both the super‐kdr (skdr) and the knock down resistance (kdr) associated loci. When this technique uses genomic DNA as template, modifications, such as alternative RNA splicing and RNA editing are not specifically detected. Alternative splicing at the skdr locus has been reported in Dipterans; thus, the genomic DNA‐based allele‐specific PCR may not accurately reflect the frequency of the skdr mutation in horn fly field populations. To investigate if alternative splicing occurs at the skdr locus of horn flies, genomic DNA and cDNA sequences isolated from two wild populations and two laboratory‐reared colonies with varying degrees of pyrethroid resistance were compared. There was no indication of alternative splicing at the super‐kdr locus neither in the wild populations nor in the laboratory‐reared colonies.
Histological characterization of interneurons in Alzheimer's disease reveals a loss of somatostatin interneurons in the temporal cortex
Authors: Waller Rachel , Mandeya Memory , Viney Edward , Simpson Julie E. , Wharton Stephen B.
Published: March 2020

Neuronal dysfunction and synaptic loss are major hallmarks of Alzheimer's disease (AD) which correlate with symptom severity. Impairment of the γ‐aminobutyric acid (GABA)ergic inhibitory interneurons, which form around 20% of the total neuronal network, may be an early event contributing to neuronal circuit dysfunction in neurodegenerative diseases. This study examined the expression of two of the main classes of inhibitory interneurons, parvalbumin (PV) and somatostatin (SST) interneurons in the temporal cortex and hippocampus of AD and control cases, using immunohistochemistry. We report a significant regional variation in the number of PV and SST interneurons with a higher number identified per mm2 in the temporal cortex compared to the hippocampus. Fewer SST interneurons, but not PV interneurons, were identified per mm2 in the temporal cortex of AD cases compared to control subjects. Our results support regional neuroanatomical effects on selective interneuron classes in AD, and suggest that impairment of the interneuronal circuit may contribute to neuronal dysfunction and cognitive decline in AD.
Pilot randomized trial of brief school‐based mentoring for middle school students with elevated disruptive behavior
Authors: McQuillin Samuel D. , McDaniel Heather L.
Published: March 2020

We report a pilot study of a brief (i.e., 10 sessions) goal‐focused mentoring program for middle school students with elevated disruptive behavior. Students with high levels of school misconduct (n = 67) were randomly assigned to the program or school as usual. We collected multi‐informant emotional, behavioral, and academic functioning assessments pre‐ and postintervention. Results indicate that the program produced significant positive changes in school behavioral infractions, math grades, students’ report of emotional symptoms, and school problems. Mentors found the curriculum acceptable, understood the material from the manual, found implementing the curriculum feasible, and felt the program was congruent with the school mission. Mentors of less impaired students indicated that they desired additional support implementing the manual, perhaps indicating the program is overengineered for students with higher levels of impairment. The manuscript concludes with a discussion of considerations for future research and implementation, including the importance of integrating mentoring programs into existing support systems (e.g., multitiered systems of support) within the school context.
De‐ubiquitinases on the move: an emerging field in plant biology
Authors: Majumdar P. , Nath U.
Published: March 2020

A balance between the synthesis and degradation of active proteins governs diverse cellular processes in plants, spanning from cell‐cycle progression and circadian rhythm to the outcome of several hormone signalling pathways. Ubiquitin‐mediated post‐translational modification determines the degradative fate of the target proteins, thereby altering the output of cellular processes. An equally important, and perhaps under‐appreciated, aspect of this pathway is the antagonistic process of de‐ubiquitination. De‐ubiquitinases (DUBs), a group of processing enzymes, play an important role in maintaining cellular ubiquitin homeostasis by hydrolyzing ubiquitin poly‐proteins and free poly‐ubiquitin chains into mono‐ubiquitin. Further, DUBs rescue the cellular proteins from 26S proteasome‐mediated degradation to their active form by cleaving the poly‐ubiquitin chain from the target protein. Any perturbation in DUB activity is likely to affect proteostasis and downstream cellular processes. This review illustrates recent findings on the biological significance and mechanisms of action of the DUBs in Arabidopsis thaliana, with an emphasis on ubiquitin‐specific proteases (UBPs), the largest family among the DUBs. We focus on the putative roles of various protein–protein interaction interfaces in DUBs and their generalized function in ubiquitin recycling, along with their pre‐eminent role in plant development.
A Spatially Varying Distributed Lag Model with Application to an Air Pollution and Term Low Birth Weight Study
Authors: Warren Joshua L. , Luben Thomas J. , Chang Howard H.
Published: March 2020

Distributed lag models have been used to identify critical pregnancy periods of exposure (i.e. critical exposure windows) to air pollution in studies of pregnancy outcomes. However, much of the previous work in this area has ignored the possibility of spatial variability in the lagged health effect parameters that may result from exposure characteristics and/or residual confounding. We develop a spatially varying Gaussian process model for critical windows called ‘SpGPCW’ and use it to investigate geographic variability in the association between term low birth weight and average weekly concentrations of ozone and PM2.5 during pregnancy by using birth records from North Carolina. SpGPCW is designed to accommodate areal level spatial correlation between lagged health effect parameters and temporal smoothness in risk estimation across pregnancy. Through simulation and a real data application, we show that the consequences of ignoring spatial variability in the lagged health effect parameters include less reliable inference for the parameters and diminished ability to identify true critical window sets, and we investigate the use of existing Bayesian model comparison techniques as tools for determining the presence of spatial variability. We find that exposure to PM2.5 is associated with elevated term low birth weight risk in selected weeks and counties and that ignoring spatial variability results in null associations during these periods. An R package (SpGPCW) has been developed to implement the new method.
Measuring the Financial Cycle in South Africa
Authors: Farrell Greg , Kemp Esti
Published: March 2020

We measure the financial cycle of South Africa using three different methodologies. The financial cycle is identified using credit, house prices and equity prices as indicators, and estimated using traditional turning‐point analysis, frequency‐based filters and an unobserved components model‐based approach. We then consider the financial cycle’s main characteristics and examine its relationships with the business cycle. We confirm the presence of a financial cycle in South Africa that has a longer duration and a larger amplitude than the traditional business cycle. Developments in measures of credit and house prices are important indicators of the financial cycle, although the case for including equity prices in the measures is less certain. Periods where financial conditions are stressed are associated with peaks in the financial cycle, suggesting that the estimated financial cycle may have similar leading indicator properties to financial conditions or stress indices.
The Limits of Black Politics in the Post–Civil Rights Era
Authors: Sekou Bilal Dabir
Published: March 2020

Pluralist theorists have long contended that to exercise power and influence in the American political system, blacks should come together like any other organized interest group, form coalitions with other like‐minded people (white liberals), and advocate for policy reforms. Beginning during the “Black Power” era, the goal of putting black faces in high places to help address black concerns became a driving force in black politics. The deteriorating social and economic status of many in the black community, however, has not been prevented by either the political incorporation of more than 11,000 black elected officials or even the election of the nation’s first black president. This article will show how the inherent limitations of the pluralist interest‐group strategy and a growing white backlash fueled by an awareness of changing demographics in the country has spawned an economic and political crisis in black America.
Perception, Content, Generality
Authors: Giananti Andrea
Published: March 2020

How does perceptual experience disclose the world to us? According to the content view (CV), visual perceptual consciousness entails representational content. According to pure relationalism, perception is a non‐representational relation between a subject and an object. In this article, I argue that CV‐theorists are implicitly committed to the claim that there is an element of generality in perception, and I show how pure relationalists would emphasize the particularity of perception, instead of its generality. But I also argue that there are good epistemological and phenomenological reasons for thinking that there is generality in perception. In particular, I focus on Brewer's purely relationalist account and I argue that it either fails to satisfy important phenomenological and epistemological requirements, or it introduces generality in a way that makes it collapse into CV. I contend that construing the debate between CV and pure relationalism in light of particularity and generality advances our understanding of how perceptual experience discloses the world to us, as well as strengthening the standing of CV.
Adiabatic Absorption by Absorbent Atomization for Improving Absorption Heat Transformer Performance
Authors: Evron Yigal , Gommed Khaled , Grossman Gershon
Published: March 2020

Absorption heat transformers (AHTs) are a type of absorption heat pumps that are primarily driven by low-grade (typically waste) heat and produce higher temperature (high-grade) heat. Under the Indus3Es project, a 10 kW LiBr-H2O “Lab Scale” absorption heat transformer was built as a first experimental step toward larger scales. The focus was on the high-pressure vessel (HPV) (absorber and evaporator) design. To enhance performance, the aim was to obtain complete adiabatic absorption prior to the main absorption process accompanied by heat transfer. This maximizes the temperature within the absorber. This is particularly beneficial for absorption heat transformers, compared to chillers, because obtaining an elevated temperature is the objective. To obtain adiabatic absorption, atomizing spray nozzles were used as the liquid absorbent distribution system. This method proved successful; complete adiabatic absorption was obtained before the droplets contacted the absorber heat exchange surfaces. However, the spray nozzles must be supplied with pressurized liquid and are potentially more delicate than alternative liquid distribution systems. Therefore, future work may focus on determining the required atomization level to avoid excessive pressures and nozzle requirements.
Comparative Study on Dynamic Characteristics of Double-Pad Inwardly and Outwardly Pumping Water-Lubricated Spiral-Groove Thrust Bearings
Authors: Zhang Shaowen , Jiang Shuyun , Lin Xiaohui
Published: March 2020

The dynamic characteristics of the double-pad inwardly pumping water-lubricated spiral-groove thrust bearing (SGTB) is different from that of the outwardly pumping version, especially under a high-speed condition. However, no literature on this topic can be found up to now. In this study, a comparative study on the dynamic characteristics of the two types of SGTBs is conducted. First, a turbulent lubrication model considering centrifugal and cavitating effects for the double-pad SGTB is developed based on gas–liquid two-phase flow. The steady-state and perturbed Reynolds equations of liquid phase are derived using linear perturbation method. Subsequently, the boundary fitted coordinate system and control volume method are applied to solve the Reynolds equations. Then, the axial stiffness coefficients of high-speed water-lubricated bearings are verified by an experimental study. Finally, the influence of operating conditions and configuration parameters on the dynamic behaviors for the two types of SGTBs is investigated. The results show that the double-pad outwardly pumping bearing is superior to the inwardly pumping version in all the dynamic coefficients when the radius ratio exceeds 0.65. When the tilt angle exceeds 1.2 × 10−4 as well as when the eccentricity ratio exceeds 0.7, the dynamic damping, angular and cross-coupled stiffness coefficients of the outwardly pumping bearing may be larger than those of the inwardly pumping one.
Proteomic Changes of Klebsiella pneumoniae in Response to Colistin Treatment and
crrB
Mutation-Mediated Colistin Resistance
Authors: Sun Lang , Rasmussen Pernille Kronholm , Bai Yinlei , Chen Xiulan , Cai Tanxi , Wang Jifeng , Guo Xiaojing , Xie Zhensheng , Ding Xiang , Niu Lili , Zhu Nali , You Xuefu , Kirpekar Finn , Yang Fuquan
Published: March 2020

Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant Gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually over the past few years. Although studies on polymyxin mechanisms are expanding, systemwide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how
Klebsiella pneumoniae
adapts to colistin (polymyxin E) pressure, we carried out proteomic analysis of a
K. pneumoniae
strain cultured with different concentrations of colistin.
Remodeling of the Core Leads HIV-1 Preintegration Complex into the Nucleus of Human Lymphocytes
Authors: Blanco-Rodriguez Guillermo , Gazi Anastasia , Monel Blandine , Frabetti Stella , Scoca Viviana , Mueller Florian , Schwartz Olivier , Krijnse-Locker Jacomine , Charneau Pierre , Di Nunzio Francesca
Published: March 2020

How the reverse-transcribed genome reaches the host nucleus remains a main open question related to the infectious cycle of HIV-1. The HIV-1 core has a size of ∼100 nm, largely exceeding that of the NPC channel (∼39 nm). Thus, a rearrangement of the viral CA protein organization is required to achieve an effective nuclear translocation. The mechanism of this process remains undefined due to the lack of a technology capable of visualizing potential CA subcomplexes in association with the viral DNA in the nucleus of HIV-1-infected cells. By the means of state-of-the-art technologies (HIV-1 ANCHOR system combined with CLEM), our study shows that remodeled viral complexes retain multiple CA proteins but not an intact core or only a single CA monomer. These viral CA complexes associated with the retrotranscribed DNA can be observed inside the nucleus, and they represent a potential PIC. Thus, our study shed light on critical early steps characterizing HIV-1 infection, thereby revealing novel, therapeutically exploitable points of intervention. Furthermore, we developed and provided a powerful tool enabling direct, specific, and high-resolution visualization of intracellular and intranuclear HIV-1 subviral structures.
Enterotoxigenic Escherichia coli Heat-Stable Toxin Increases the Rate of Zinc Release from Metallothionein and Is a Zinc- and Iron-Binding Peptide
Authors: Kiefer Mallory C. , Motyka Natalya I. , Clements John D. , Bitoun Jacob P.
Published: March 2020

Enterotoxigenic
Escherichia coli
(ETEC) is a major diarrheal pathogen in children in low- to middle-income countries, deployed military personnel, and travelers to regions of endemicity. The heat-stable toxin (ST) is a small nonimmunogenic secreted peptide with 3 disulfide bonds. It has been appreciated that dietary disulfides modulate intestinal redox potential and that ST could be detoxified using exogenous reductants. Using biochemical and spectroscopic approaches, we demonstrated that ST can separately bind iron and zinc under reducing conditions, thereby reducing ST toxicity. Moreover, we demonstrated that ST modulates the glutathione (GSH)/oxidized glutathione (GSSG) ratio and that ST should be considered a toxin oxidant. ST can be detoxified by oxidizing zinc-loaded metallothionine, causing free zinc to be released. These studies help lay a foundation to understand how diarrheal pathogens modulate intestinal redox potential and may impact how we design therapeutics and/or vaccines for the pathogens that produce them.
Transition to quantitative faecal immunochemical testing from guaiac faecal occult blood testing in a fully rolled-out population-based national bowel screening programme
Authors: Clark Gavin , Strachan Judith A , Carey Frank A , Godfrey Thomas , Irvine Audrey , McPherson Alisson , Brand Jess , Anderson Annie S , Fraser Callum G , Steele Robert JC
Published: March 2020

Objective

Faecal immunochemical tests (FIT) are replacing guaiac faecal occult blood tests (FOBT) in colorectal cancer (CRC) screening. Data from the first year of FIT screening were compared with those from FOBT screening and assumptions based on a pilot evaluation of FIT.

Design

Data on uptake, positivity, positive predictive value (PPV) for CRC and higher-risk adenoma from participants in the first year of the FIT-based Scottish Bowel Screening Programme (n=919 665), with a threshold of 80 µg Hb/g faeces, were compared with those from the penultimate year of the FOBT-based programme (n=862 165) and those from the FIT evaluation (n=66 225).

Results

Overall, uptake of FIT was 63.9% compared with 56.4% for FOBT. Positivity was 3.1% and 2.2% with FIT and FOBT; increases were seen in both sexes, and across age range and deprivation. More CRC and adenomas were detected by FIT, but the PPV for CRC was less (5.2% with FIT and 6.4% with FOBT). However, for higher-risk adenoma, PPV was greater with FIT (24.3% with FIT and 19.3% with FOBT). In the previous FIT evaluation, uptake was 58.5% with FIT compared with 54.0% with FOBT; positivity was 2.5% with FIT and 2.0% with FOBT.

Conclusion

Transition to FIT from FOBT produced higher uptake and positivity with lower PPV for CRC and higher PPV for adenoma. The FIT pilot evaluation underestimated uptake and positivity. Introducing FIT at the same threshold as the evaluation caused a 67.2% increase in colonoscopy demand instead of a predicted 10%.
Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP)
Authors: Butzkueven Helmut , Kappos Ludwig , Wiendl Heinz , Trojano Maria , Spelman Tim , Chang Ih , Kasliwal Rachna , Jaitly Seema , Campbell Nolan , Ho Pei-Ran , Licata Stephanie
Published: March 2020

Objective

The Tysabri Observational Programme (TOP), which began >10 years ago, is an open-label, multinational, prospective observational study evaluating the long-term safety and effectiveness of natalizumab in relapsing-remitting multiple sclerosis patients.

Methods

These data provide a 10-year interim analysis of safety and effectiveness in TOP. Annualised relapse rates (ARRs) and disability progression/improvement were analysed using the Poisson model and the Kaplan-Meier method, respectively. Analyses included patients on natalizumab and those who discontinued natalizumab but remained in TOP.

Results

As of November 2017, TOP included 6148 patients. Overall, 829 patients (13.5%) experienced ≥1 serious adverse event (SAE), with infection the most common (4.1%). Fifty-three patients (0.9%) had confirmed progressive multifocal leukoencephalopathy. SAE data were consistent with natalizumab’s known safety profile; no new safety signals were identified. A total of 3210 patients (52.2%) discontinued natalizumab; 2117 (34.4%) withdrew from TOP. Median time on natalizumab was 3.3 (range 0–11.6) years; median follow-up time was 5.2 (range 0–10.8) years. The on-natalizumab ARR was 0.15, a 92.5% reduction from the year before initiation. Ten-year cumulative probabilities of disability worsening and improvement were 27.8% and 33.1%, respectively. On-natalizumab ARRs were similar between patients who discontinued or remained on natalizumab, suggesting limited attrition bias.

Conclusions

Since the TOP 5-year interim analysis (December 2012), cohort size (6148 vs 4821), median exposure (3.3 vs 1.8 years) and median follow-up time (62 vs 26 months) have increased. This 10-year interim analysis further supports the robust real-world effectiveness and well-established safety profile of natalizumab.

Trial registration number

NCT00493298.
Serum homocysteine and risk of dementia in Japan
Authors: Chen Sanmei , Honda Takanori , Ohara Tomoyuki , Hata Jun , Hirakawa Yoichiro , Yoshida Daigo , Shibata Mao , Sakata Satoko , Oishi Emi , Furuta Yoshihiko , Kitazono Takanari , Ninomiya Toshiharu
Published: March 2020

Objective

To examine the association between serum total homocysteine levels (tHcy) and dementia risk.

Methods

A total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012. Cox proportional hazards models and restricted cubic splines were used to estimate the HRs of tHcy levels on the risk of dementia.

Results

During the follow-up, 372 subjects developed all-cause dementia; 247 had Alzheimer’s disease (AD) and 98 had vascular dementia (VaD). Compared with the lowest tHcy quintile (≤6.4 µmol/L), the multivariable-adjusted HRs (95% CI) of the highest quintile (≥11.5 µmol/L) were 2.28 (1.51–3.43) for all-cause dementia, 1.96 (1.19–3.24) for AD and 2.51 (1.14–5.51) for VaD. In restricted cubic splines, the risk of all-cause dementia steadily increased between approximately 8–15 µmol/L and plateaued thereafter, with a similar non-linear shape observed for AD and VaD (all p for non-linearity ≤0.02). In stratified analyses by the most recognised genetic polymorphism affecting tHcy concentrations (methylenetetrahydrofolate reductase C677T), the positive association of tHcy with all-cause dementia persisted in both non-carriers and carriers of the risk allele, and even tended to be stronger in the former (p for heterogeneity=0.07).

Conclusion

High serum tHcy levels are associated with an elevated risk of dementia, AD and VaD in a non-linear manner, such that an exposure-response association is present only within a relatively high range of tHcy levels. Non-genetic factors affecting serum tHcy concentrations may play important roles in tHcy-dementia associations irrespective of the genetic susceptibility for raised tHcy.
Novel electrocardiography parameter for paroxysmal atrial fibrillation in acute ischaemic stroke patients: P wave peak time
Authors: Öz Ahmet , Cinar Tufan , Kızılto Güler Cansu , Efe Süleyman Çağan , Emre Ufuk , Karabağ Turgut , Ayça Burak
Published: March 2020

Introduction

In this study, we aimed to investigate the usefulness of P wave peak time (PWPT), a novel ECG parameter, in patients who were diagnosed with acute ischaemic stroke (IS) and had paroxysmal atrial fibrillation (PAF) on Holter monitoring.

Materials and methods

In this retrospective cohort study, we included 90 consecutive patients with acute IS who were admitted to our hospital between January 2017 and July 2019. PWPT was described as the time from the beginning of the P wave to its peak, and it was measured from leads DII and VI. The PAF diagnosis was confirmed if it was detected on the ECG during palpitation or in rhythm during the Holter recordings.

Results

In this study, 34 (37.7%) patients with acute IS were diagnosed with PAF. In multivariate analyses, the independent predictors of PAF were age, PWPT in lead VI and PWPT in lead DII (OR: 1.34, 95% CI 1.15 to 1.56; p<0.001). A receiver operating curve analysis demonstrated that area under the curve values for PWPT in lead DII for PAF were 0.88 (95% CI 0.81 to 0.95, p<0.001). The cut-off value for PWPT in lead DII in predicting PAF was 68.5 ms with a sensitivity of 82.4% and a specificity of 75.0%.

Conclusion

To the best of our knowledge, this is the first study to demonstrate a significant relationship between PWPT in lead DII and PAF among patients with acute IS.
Are e-cigarettes reviving the popularity of conventional smoking among Taiwanese male adolescents? A time-trend population-based analysis for 2004-2017
Authors: Gao Wayne , Sanna Mattia , Chuluunbaatar Enkhzaya , Tsai Min-Kuang , Levy David T , Wen Chi Pang
Published: March 2020

Introduction

In Taiwan, national tobacco use surveys show that e-cigarette use has increased since 2014 among youth, while, at the same time, conventional cigarette smoking has continuously decreased. The purpose of this study is to examine whether the increased popularity of e-cigarettes has undermined this favourable declining trend for cigarette smoking.

Methods

We examined conventional cigarette and e-cigarette prevalence among male high school students (aged 16–18 years) and adults from 2004 to 2017, using data from cross-sectional nationally representative surveys. Applying interrupted time series analysis, we assessed whether there was a change in trend in 2014, when e-cigarette use started to gain popularity from long-term trends in prior years (2004–2013).

Results

E-cigarette use prevalence increased from 2.5% in 2014 to 6.4% in 2017 among male high school students but was negligible among male adults, declining from 1.4% in 2015 to 0.8% in 2017. The annual relative decline in the cigarette smoking rate after e-cigarettes started to gain popularity was greater (−10%) than the long-term trend (−2%) among high school students. Among adults, the change in trend over time after e-cigarettes started to gain popularity was not significant (ie, not significantly different from 0).

Conclusions

The increased popularity of e-cigarettes since 2014 is associated with a greater decline in youth smoking, compared with previous years. On the contrary, e-cigarette use has remained very low among Taiwanese male adults and no additional impact on the conventional smoking trend is found.
Seed germination of selected crop and graminoid species in response to treatment with sodium chloride and oil-field brine solutions
Authors: Green Aaron W. , Meehan Miranda A. , DeSutter Thomas M.
Published: March 2020

Oil and gas development is often associated with the production of produced water or “brine”, which is a solution of dissolved salts (NaCl ≈ 90%) exhibiting electrical conductivity (EC) upwards of 200 dS m−1. Accidental releases of brine to soils inhibit seed germination through osmotic and ionic stressors. The final germination (FG; %) of four crop species, Hordeum vulgare L. (barley), Helianthus annuus L. (sunflower), Carthamus tinctorius L. (safflower), Beta vulgaris L. (sugar beet); and four graminoid species, Pascopyrum smithii (Rydb.) Barkworth & D.R. Dewey (western wheatgrass), Elymus hoffmannii K.B. Jensen & Asay (AC Saltlander), Leymus triticoides (Buckley) Pilg. (beardless wildrye), and Elymus trachycaulus (Link) Gould ex Shinners (slender wheatgrass), were determined using sodium chloride (NaCl) and brine solutions prepared at EC levels of 0, 4, 8, 16, 24, and 32 dS m−1. No differences (p > 0.05) in FG were found between NaCl and brine solutions across graminoid species or the crop species barley, sunflower, and sugar beet. AC Saltlander had the highest FG (81.9%) at the maximum EC level (32 dS m−1), compared with 47.2% and 0.8% for western wheatgrass and beardless wildrye, respectively. Within crop species, safflower exhibited the highest germination (10%–30%) across both solutions at 32 dS m−1. Barley (0%–2.9%), sugar beet (4.9%–7.7%), and sunflower (0%–1.4%) exhibited low germination at 32 dS m−1. The implications of this experiment are that previously established NaCl tolerance indices may be used to accurately determine the FG of plant species in brine-contaminated soils and that AC Saltlander, as well as western wheatgrass, have the highest FG at 32 dS m−1, indicating these species may have the greatest potential for successfully revegetating brine-contaminated soils.
Gauge dependences of higher-order corrections to NMSSM Higgs boson masses and the charged Higgs Decay $${H^{\pm } \rightarrow W^\pm h_{i}}$$
Authors: Dao Thi Nhung , Fritz Lukas , Krause Marcel , Mühlleitner Margarete , Patel Shruti
Published: March 2020

In this paper we compute the electroweak corrections to the charged Higgs boson decay into a W boson and a neutral Higgs boson in the CP-conserving NMSSM. We calculate the process in a general $$R_\xi $$Rξ gauge and investigate the dependence of the loop-corrected decay width on the gauge parameter $$\xi $$ξ. The gauge dependence arises from the mixing of different loop orders. Phenomenology requires the inclusion of mass and mixing corrections to the external Higgs bosons in order to match the experimentally measured mass values. As a result, we move away from a strict one-loop calculation and consequently mix orders in perturbation theory. Moreover, determination of the loop-corrected masses in an iterative procedure also results in the mixing of different loop orders. Gauge dependence then arises from the mismatch with tree-level Goldstone boson couplings that are applied in the loop calculation, and from the gauge dependence of the loop-corrected masses themselves. We find that the gauge dependence is significant.