bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward a genetic system in the marine cyanobacteriumProchlorococcus
Authors: Laurenceau Raphaël , Bliem Christina , Osburne Marcia S. , Becker Jamie W. , Biller Steven J. , Cubillos-Ruiz Andres , Chisholm Sallie W.
Published: October 2019

As the smallest and most abundant primary producer in the oceans, the cyanobacteriumProchlorococcusis of interest to diverse branches of science. For the past 30 years, research on this minimal phototroph has led to a growing understanding of biological organization across multiple scales, from the genome to the global ocean ecosystem. Progress in understanding drivers of its diversity and ecology, as well as molecular mechanisms underpinning its streamlined simplicity, has been hampered by the inability to manipulate these cells genetically.

Multiple attempts have been made to develop an efficient genetic transformation method forProchlorococcusover the years; all have been unsuccessful to date, despite some success with their close relative,Synechococcus. To avoid the pursuit of unproductive paths, we report here what has not worked in our hands, as well as our progress developing a method to screen the most efficient electroporation parameters for optimal DNA delivery intoProchlorococcuscells. We also report a novel protocol for obtaining axenic colonies and a new method for differentiating live and dead cells. The electroporation method can be used to optimize DNA delivery into any bacterium, making it a useful tool for advancing transformation systems in other genetically recalcitrant microorganisms.
A conserved enzyme found in diverse human gut bacteria interferes with anticancer drug efficacy
Authors: Spanogiannopoulos Peter , Kyaw Than S. , Guthrie Ben G. H. , Bradley Patrick H. , Lee Joyce V. , Melamed Jonathan , Malig Ysabella Noelle Amora , Lam Kathy N. , Gempis Daryll , Sandy Moriah , Kidder Wes , Van Blarigan Erin L. , Atreya Chloe E. , Venook Alan , Gerona Roy R. , Goga Andrei , Pollard Katherine S. , Turnbaugh Peter J.
Published: October 2019

Pharmaceuticals are the top predictor of inter-individual variations in gut microbial community structure1, consistent with in vitro evidence that host-targeted drugs inhibit gut bacterial growth2 and are extensively metabolized by the gut microbiome3,4. In oncology, bacterial metabolism has been implicated in both drug efficacy5,6 and toxicity7,8; however, the degree to which bacterial drug sensitivity and metabolism can be driven by conserved pathways also found in mammalian cells remains poorly understood. Here, we show that anticancer fluoropyrimidine drugs inhibit the growth of diverse gut bacterial strains by disrupting pyrimidine metabolism, as in mammalian cells. Select bacteria metabolized 5-fluorouracil (5-FU) to its inactive metabolite dihydrofluorouracil (DHFU), mimicking the major host pathway for drug clearance. The preTA operon was necessary and sufficient for 5-FU inactivation in Escherichia coli, exhibited high catalytic efficiency for the reductive reaction, decreased the bioavailability and efficacy of oral fluoropyrimidine treatment in mice, and was prevalent in the gut microbiomes of colorectal cancer patients prior to and during treatment. The observed conservation of both the targets and pathways for metabolism of therapeutics across domains highlights the need to distinguish the relative contributions of human and microbial cells to drug disposition9, efficacy, and side effect profiles.
Methionyl-tRNA synthetase inhibitor has potentin vivoactivity in a novelGiardia lamblialuciferase murine infection model
Authors: Michaels Samantha A. , Shih Han-Wei , Zhang Bailin , Navaluna Edelmar D. , Zhang Zhongsheng , Ranade Ranae M. , Gillespie J. Robert , Merritt Ethan A. , Fan Erkang , Buckner Frederick S. , Paredez Alexander R. , Ojo Kayode K.
Published: October 2019

Objectives

Methionyl-tRNA synthetase (MetRS) inhibitors are under investigation for the treatment of intestinal infections caused byGiardia lamblia. To properly analyze the therapeutic potential of the MetRS inhibitor1717, experimental tools including a robust cell-based assay and a murine model of infection were developed based on novel strains ofG. lambliathat employ luciferase reporter systems to quantify viable parasites.

Methods

Systematic screening of Giardia-specific promoters and luciferase variants led to the development of a strain expressing the click beetle green luciferase. Further modifying this strain to express NanoLuc created a dual reporter strain capable of quantifying parasites in both the trophozoite and cyst stages. These strains were used to develop a high throughput cell assay and a mouse infection model. A library of MetRS inhibitors was screened in the cell assay and1717was tested for efficacy in the mouse infection model.

Results

Cell viability inin vitrocompound screens was quantified via bioluminescence readouts while infection loads in mice were monitored with noninvasive whole-animal imaging and fecal analysis. Compound1717was effective in clearing mice ofGiardiainfection in 3 days at varying doses, which is supported by data from enzymatic and phenotypic cell assays.

Conclusions

The newin vitroandin vivoassays based on luciferase expression by engineeredG. lambliastrains are useful for the discovery and development of new therapeutics for giardiasis. MetRS inhibitors, as validated by1717, have promising anti-giardiasis properties that merit further study as alternative therapeutics.
End lateral extension path strategy for intersection in wire and arc additive manufactured 2319 aluminum alloy
Authors: Li Runsheng , Zhang Haiou , Dai Fusheng , Huang Cheng , Wang Guilan
Published: October 2019

Purpose

Large-scale aircraft parts usually with many frame features, which consist of intersections. Profile and tensile properties of junctions in wire and arc additive manufacturing (WAAM) are significantly affected by path strategies. The purpose of this paper is to propose a novel path strategy for intersections in WAAM and compare it with commonly used ones.

Design/methodology/approach

Three typical intersections including T crossing (TC), square crossing (SC) and arbitrary-angle crossing (AAC) were built up with two commonly used path strategies (parallel and oscillation) and a proposed method named end lateral extension (ELE) which extends the weld track along the crossed direction. A robotic system and cold metal transfer (CMT) process were used to deposit Al-6.3Cu (2319) alloy. The profile of the bead was scanned by laser vision sensor. Tightened ratio (r), inter-layer height increment (Δh) and deviation to the fitting plane (df) are calculated based on the point cloud. Tensile tests were done for all built intersections.

Findings

Comparison to the commonly used path strategies, the proposed ELE method eliminated the tightened defects at the intersection, achieved a more stable inter-layer height increment (Δh) and improved the profile quality with a lower deviation to the fitting plane (df). Tensile tests show that the proposed strategy has exhibited favorable tensile properties.

Originality/value

In this paper, a novel path strategy named ELE is proposed, which provides a new path choice for fabricating intersections by WAAM.
A priori models and inversion of gravity gradient data in hilly terrain
Authors: Pedersen Laust B. , Kamm Jochen , Bastani Mehrdad
Published: October 2019

The increased popularity of airborne measurements of the gravity gradient tensor for resource studies and geological mapping has resulted in a new awareness of the importance of terrain effects. In these measurements, the terrain effect often overwhelms that of the underlying crust and it becomes important to formulate a strategy for taking it into account when presenting the data and when inverting the data into density models. Using newly acquired data from Northern Sweden, we first attempted to estimate a variable terrain density model by inverting the data using a terrain model with a laterally varying density. Using data weights related to the topography variations, we find the best estimate of the lateral variation of the terrain density. We translate this model into a full three‐dimensional model such that all columns have the same vertical centre of mass as estimated from inspecting the radially averaged power spectrum of the area. This then defines a reference model for subsequent three‐dimensional inversion of the gravity gradient tensor dataset. We tested this approach first on synthetic data calculated from the measured topography including two density anomalies before we applied it to the measured data. The result is a model in which the surface density variations are propagated downwards in a systematic manner now in better agreement with measured densities of rock samples in the area.
Incorporation of Propionibacterium shermanii subsp. freudenreichii in probiotic dairy drink production: physicochemical, rheological, microbiological and sensorial properties
Authors: Yerlikaya Oktay , Akpinar Asli , Saygili Derya , Karagozlu Nural
Published: October 2019

The aim of this study was to investigate the use of Propionibacterium shermanii subsp. freudenreichii as a combined culture with Lactobacillus acidophilus (AP), Bifidobacterium animalis subsp. lactis (BP), Lactobacillus casei (CP) and Lactobacillus rhamnosus (RP) in probiotic dairy drink production. Although Propionibacterium spp. is used for many purposes including biopreservative and adjunct culture, in this study, probiotic dairy drinks containing P. freudenreichii were evaluated in terms of their physicochemical, rheological, microbiological and sensory properties. The results of the study showed that P. freudenreichii can also be suitable for the production of probiotic drinks and that there are no adverse effects on the product characteristics.
“Whiteness” and natural resource management: let's talk about race baby, let's talk about sovereignty!
Authors: Searle Tania , Muller Samantha
Published: October 2019

Issues of race and sovereignty are embedded in every cross‐cultural collaboration in natural resource management (NRM). This article aims to bring these issues to the forefront by incorporating the term whiteness. Whiteness enables a critique of the privileging of Western sovereignty and the so‐called objective and universal value of Western science. By reversing the gaze away from the colonised Other and onto systems descended from colonial authority and its inheritors, whiteness identifies how race privilege works. A critical whiteness lens provides an analytical and practical tool for decolonising NRM. We provide a case study of the South Australian Department of Environment and Water to consider how NRM professionals reproduce and deconstruct whiteness in nuanced ways, where (a) participants are defeated by Western sovereignty when whiteness is seen as normal or as the only way; (b) the privilege of Western sovereignty begins to be unsettled; and (c) the gaze is reversed. Thus,Western sovereignty is problematized, and solutions to persistent problems are found in collaboration. We argue that reversing the gaze is a process that opens spaces to co‐develop context specific solutions with Indigenous nations that decolonise cross‐cultural engagement in NRM and respect Indigenous sovereignty.
Contextual characteristics of adults’ drinking occasions and their association with levels of alcohol consumption and acute alcohol‐related harm: a mapping review
Authors: Stevely Abigail K. , Holmes John , Meier Petra S.
Published: October 2019

Background and Aims

There is a growing literature using event‐level methods to estimate associations between contextual characteristics of drinking occasions, consumption levels and acute harms. This literature spans many research traditions and has not been brought together as a whole. This mapping review aimed to identify and describe the theoretical approaches to conceptualizing drinking occasions, study designs, predictors and outcome measures used in existing research with a view to identifying dominant approaches, research gaps and areas for further synthesis.

Methods

Eligible papers studied adults’ drinking occasions using quantitative event‐level methods and considered one or more contextual characteristics (e.g. venue, timing or company) and at least one event‐level consumption or acute alcohol‐related harm outcome. We systematically searched Ovid MEDLINE, PsycInfo and the Web of Science Social Sciences Citation Index, extracting data on studies’ theoretical approach, data collection methods, settings, populations, drinking occasion characteristics and outcome measures.

Results

Searches identified 278 eligible papers (from 1975 to 2019), predominantly published after 2010 (n = 181; 65.1%). Most papers reported research conducted in the United States (n = 170; 61.2%) and half used student participants (n = 133; 47.8%). Papers typically lacked a stated theoretical approach (n = 203; 73.0%). Consistent with this, only 53 (19.1%) papers studied three or more occasion characteristics and most used methods that assume occasion characteristics do not change during an occasion (n = 189; 68.0%). The most common outcome type considered was consumption (n = 224; 80.6%) and only a few papers studied specific acute harm outcomes such as unprotected sex (n = 24; 8.6%), drink driving (n = 14; 5.0%) or sexual violence (n = 9; 3.2%).

Conclusions

Studies from 1975 to 2019 using event‐level methods to estimate associations between contextual characteristics of drinking occasions, consumption levels and acute harms were largely focused on students and consumption outcomes, and most have considered a limited range of contextual characteristics.
Physical and behavioural factors, negative emotion and cognitive function among near‐centenarians and centenarians in China
Authors: Zhang Yuting , Xu Yi , Si Guanglin , Ran Li , Xie Yaofei , Yang Jinru , Tan Xiaodong
Published: October 2019

Objective

To investigate the association among demographic, physical, behavioural parameters, psychosocial and cognitive function in near‐centenarians and centenarians.

Methods

The present study data originated from the 2014 wave of the largest nationwide longitudinal survey of the population aged 95 and above in China (N = 175). The aim of this study was to systematically identify the relationship among physical and behavioural variables, negative emotions and cognitive function. Cognitive function was evaluated by the modified Mini‐Mental State Examination (mMMSE) Chinese version. Structured responses were obtained for the analysis of physical and behavioural factors and negative emotions.

Results

The average age of the sample was 98.78 years (SD = 4.00, range: 95‐112 years). The average score of the mMMSE was 20.71 (SD = 3.48), average activities of daily living (ADL) total score was 17.21 (SD = 1.72), average instrumental activities of daily living (IADL) total score was 17.90 (SD = 5.57), and average negative emotion score was 8.77 (SD = 2.69). In the combined multiple linear regression model, the quality of sleep, IADL and negative emotion of centenarians were significantly associated with cognitive function (P < 0.05).

Conclusion

The cognitive function of centenarians was significantly associated with the quality of sleep, IADL and negative emotion. Improving physical functioning and social resources can help emotional health and improve the overall cognition of centenarians.
Redox status assessment in infertile patients with non‐obstructive azoospermia undergoing testicular sperm extraction: A prospective study
Authors: Cito Gianmartin , Becatti Matteo , Natali Alessandro , Fucci Rossella , Picone Rita , Cocci Andrea , Falcone Patrizia , Criscuoli Luciana , Mannucci Amanda , Argento Flavia R. , Bertocci Francesco , Serni Sergio , Carini Marco , Fiorillo Claudia , Coccia Maria E.
Published: October 2019

Background

Oxidative stress (OS) is one of the most prevalent causes of sperm damage, through the toxic effects of endogenously generated hydrogen peroxide, superoxide anion, and hydroxyl radicals. Peripheral leukocytes represent a feasible model for studying the pathophysiology of OS‐mediated homeostasis, which can be responsible for cell dysfunction and cell injury.

Objective

To evaluate the redox status in patients with non‐obstructive azoospermia (NOA), establishing the potential role exerted by reactive oxygen species (ROS) in the genesis of testicular secretory injury.

Material and methods

From May 2018 to March 2019, 39 patients were enrolled in this prospective single‐center cohort study and divided into two groups. Group 1 included 19 patients with NOA, and Group 2 included 20 normozoospermic men, partners of women with infertility tubal factor. All patients underwent serum blood tests. NOA underwent testicular sperm extraction (TeSE). ROS production (in lymphocytes, monocytes, and granulocytes) was assessed by fluorescence‐activated cell sorting (FACS) analysis. Plasma oxidative stress was evaluated by lipid peroxidation markers (MDA) and total antioxidant capacity (TAC) both assessed by fluorometric techniques.

Results

Mean lymphocyte ROS production resulted 967.0 ± 224.5 vs 728.0 ± 98.0 (NOA vs Controls, P < .001), monocyte ROS resulted 2102.5 ± 517.5 vs 1253 ± 171 (P < .001), and granulocyte ROS were 2366.5 ± 595.4 vs 1751.0 ± 213.0 (P < .001). Significant increases plasma lipid peroxidation markers were found in NOA patients compared with controls (2.7 ± 0.8 vs 0.37 ± 0.2 nmol/mL, P < .001). Significant decreased TAC was evident in NOA compared with controls (13.4 ± 3.9 vs 3.0 ± 0.2 µmol/mL Trolox equivalents, P < .001). No significant differences were found in blood leukocyte subpopulations ROS production, plasma lipid peroxidation, and TAC comparing groups (positive vs negative sperm retrieval, P > .05).

Conclusion

ROS production can be directly related to disorders of spermatogenesis, leading to severe conditions of male infertility, including azoospermia.
Influence of cataract light scatters on retinal vessel oxygen saturation
Authors: della Volpe Waizel Maria , Türksever Cengiz , Todorova Margarita G.
Published: October 2019

Background

The aim of our study was to compare metabolic (oxygen saturation; %) and anatomical parameters (retinal vessel diameter; μm) of retinal vessel oximetry (RO) in patients with cataract formation against those of healthy controls with clear lenses.

Methods

A total of 96 eyes of 62 subjects were examined: 51 eyes from 33 cataract patients (mean age: 64.8y) were compared to 45 eyes from 29 controls with clear lenses (mean age: 61.5y). RO was performed with the oxygen saturation measurement tool from the RVA (IMEDOS Systems UG). The oxygen saturation in all major peripapillary retinal arterioles (A‐SO2) and venules (V‐SO2) was measured, and their difference (A‐V SO2) was calculated. In addition, the corresponding diameter in retinal arterioles (D‐A) and venules (D‐V) was evaluated. Cataract formation was graded according to the Lens Opacities Classification System III (LOCS III). Oximetry data were compared with the grade of cataract formation within both groups. For statistical evaluation, anova‐based linear mixed‐effects models were calculated (spss®, pairwise comparisons: Bonferroni‐corrected; p < 0.05).

Results

Cataract eyes showed significantly lower A‐SO2 and A‐V SO2 values (mean ± SD 92.52 ± 9.80% and 28.56 ± 9.80%), when compared to healthy controls (95.47 ± 4.48% and 34.8 ± 7.08%; p = 0.046 and p = 0.001). Within the cataract group, cortical opacities showed significant interactions with the A‐SO2, V‐SO2 and the A‐V SO2 parameters (p = 0.027; p = 0.002; and p = 0.026, respectively).

Conclusions

These data indicate that the cataract‐induced light scatter influences optical retinal oxygen measurements. Cortical opacities showed the highest influence on RO measurement when compared to nuclear opacification, nuclear colour and posterior cataract formation.
Ganglion cell layer thickening in well‐controlled patients with type 1 diabetes: an early sign for diabetic retinopathy?
Authors: Gerendas Bianca S. , Hatz Katja , Kaider Alexandra , Zulewski Henryk , Lehmann Roger , Montuoro Alessio , Schmidt‐Erfurth Ursula , Pruente Christian
Published: October 2019

Purpose

To evaluate early changes in retinal layers using optical coherence tomography (OCT) in patients with long‐standing type 1 diabetes (DM1) receiving intensified insulin therapy.

Methods

In a cross‐sectional case–control study 150 patients with DM1 and 150 age‐ and sex‐matched healthy control participants underwent OCT imaging. Scans of both eyes were analysed for different layers (NFL, GCL (+IPL), INL, outer layer complex (OLC, including OPL, ONL and ELM) and photoreceptors (PR)) in all subfields of an ETDRS grid. All analyses were performed semi‐automatically using custom software by certified graders of the Vienna Reading Center. ANOVA models were used to compare the mean thickness of the layers between patients and controls.

Results

Six hundred eyes with 512 datapoints in 49 b‐scans in each OCT were analysed. Mean thickness in patients/controls was 31.35 μm/30.65 μm (NFL, p = 0.0347), 76.7 μm/73.15 μm (GCL, p ≤ 0.0001), 36.29 μm/37.13 μm (INL, p = 0.0116), 114.34 μm/112.02 μm (OLC, p < 0.0001) and 44.71 μm/44.69 μm (PR, p = 0.9401). When evaluating the ETDRS subfields separately for clinically meaningful hypotheses, a significant swelling of the GCL in patients could be found uniformly and a central swelling for the OLC, whereas the distribution of NFL and INL thickening suggests that their statistical significance was not clinically relevant.

Conclusion

These preliminary results demonstrate that preclinical retinal changes in patients with long‐standing DM1 can be found by retinal layer evaluation. However, the changes are layer‐specific, with significant thickening of the GCL and less so of the OLC suggesting a role as an early sign for diffuse swelling and the evolution of DME even in well‐controlled diabetes.
Standard cross‐linking protocol versus accelerated and transepithelial cross‐linking protocols for treatment of paediatric keratoconus: a 2‐year comparative study
Authors: Iqbal Mohammed , Elmassry Ahmed , Saad Hisham , AM Gad Ahmed , Ibrahim Ola , Hamed Noha , Saeed Ahmed , S. Khalil Ahmad , Tawfik Mohamed , Said Amr , Amer Ibrahim , Nooreldin Asaad , Said Omar , Reffat Mohamed , Anwar Seif , Badawi Amani
Published: October 2019

Purpose

To compare the efficacy, safety and stability of standard epithelium‐off cross‐linking (SCXL) versus accelerated epithelium‐off cross‐linking (ACXL) and transepithelial epithelium‐on cross‐linking (TCXL) in the treatment of progressive keratoconus (KC) in children.

Methods

This prospective multicentre controlled trial included 271 eyes (136 children) with grade 1–3 progressive KC who were randomized to undergo SCXL (n = 91, as a control group), ACXL (n = 92) or TCXL (n = 88). Uncorrected and corrected distance visual acuity, subjective refraction, pachymetry, keratometry and corneal topography measurements were recorded preoperatively and 6, 12 and 24 months postoperatively.

Results

At 1 year, there was no significant difference in uncorrected distance visual acuity, refractive sphere, cylinder, spherical equivalent or Kmax between the ACXL and SCXL groups; however, during year 2, ACXL regressed while SCXL continued to improve. After 2 years, there were significant differences in all visual, refractive and keratometric components between SCXL and both ACXL and TCXL (p < 0.0001) and between ACXL and TCXL (p < 0.0001). KC progressed in 5.4% of patients who had ACXL and 28.4% of those who had TCXL but in none of those who had SCXL. Vernal keratoconjunctivitis was documented in 43.3% of eyes that progressed postoperatively.

Conclusion

SCXL was more effective for paediatric KC and achieved greater stability than either ACXL or TCXL, and ACXL was superior to TCXL. SCXL also achieved marked improvement in both myopia and spherical equivalent; however, these refractive outcomes were unpredictable and uncontrollable. TCXL had a 28.4% failure rate within 2 years. SCXL is preferable for management of paediatric KC.
Short‐time effect of intravitreal injections on retinal vascular oxygenation and vessel diameter in patients with diabetic macular oedema or neovascular age‐related macular degeneration
Authors: Mitsch Christoph , Pemp Berthold , Pollreisz Andreas , Gleiss Andreas , Karst Sonja , Scholda Christoph , Sacu Stefan , Schmidt‐Erfurth Ursula
Published: October 2019

Purpose

To investigate the short‐time effect of intravitreal injections (IVI) of the vascular endothelial growth factor inhibitors ranibizumab and aflibercept on retinal arterial and venous oxygen saturation (SO2a and SO2v), arteriovenous oxygen saturation difference (AVD) and vessel diameter (VDa and VDv) in patients with diabetic macular oedema (DME) and patients with choroidal neovascularization (CNV) due to age‐related macular degeneration.

Methods

Uncontrolled prospective observational study in 100 eyes. Retinal vessel oxygen saturation and diameters were assessed using a retinal oximeter before and minutes after IVI of ranibizumab or aflibercept.

Results

40 eyes with CNV and 34 eyes with DME were included in the analysis. At baseline, SO2a and SO2v were significantly higher in DME (p = 0.043 and p = 0.009, respectively). After IVI, SO2a significantly decreased in CNV and DME eyes by 2.6% (p = 0.016) and 4.6% (p = 0.002) and SO2v decreased by 14.0% (p = 0.004) and 12.4% (p = 0.017), respectively. However, a significant increase in AVD was only found in CNV (15.7%, p = 0.001). VDa decreased significantly only in DME by 5.7% (p = 0.010). No medication‐specific disease effect was found and vice versa.

Conclusions

The observed changes can be interpreted as signs of increased metabolic demand during the physiological stress after an IVI. The abnormal arterial constriction and the abolished increase in AVD seen only in eyes with DME indicate an impairment of vascular autoregulation and oxygen distribution and a reduced neuroretinal metabolism in the diabetic retina with a significant impact on inner retinal oxygen consumption shortly after IVI.
Risk of falls and injuries requiring hospitalisation after first‐eye cataract surgery in elderly Australians
Authors: Gadzhanova Svetla , Gillam Marianne , Roughead Elizabeth
Published: October 2019

Purpose

To investigate the impact of the type of the intraocular lenses (IOLs) in first‐eye cataract surgery in elderly people on the risk of hospitalisation due to falls and injuries.

Methods

A retrospective cohort study was conducted using the Australian Government Department Veterans’ Affairs claims data. All people aged 65 years and above who had first cataract surgery between January 2007 and July 2017 were identified. Two cohorts were established depending on the type of IOL—monofocal and multifocal. The risk of injuries and falls requiring hospitalisation in the first 3 months post the surgery was assessed using Cox proportional hazard models with age at entry as primary time scale and adjusting for gender, comorbidities and prior history of falls.

Results

There were 45 728 people across the two cohorts with the majority receiving monofocal lenses (97%), followed by multifocal lenses (3%) at the time of first cataract surgery. The risk of injury and falls was lower (but not significant) in the multifocal cohort compared to monofocal cohort (adjusted hazard ratio (aHR) 0.56, 95% CI 0.26–1.17). The risk was also lower (but not significant) when stratifying by age group at the time of the surgery.

Conclusions

Regardless of age, multifocal lenses did not appear to be associated with the higher risk of serious injuries and falls after first‐eye cataract surgery compared to monofocal lenses.
Prevalence of Charles Bonnet syndrome in patients with age‐related macular degeneration: systematic review and meta‐analysis
Authors: Niazi Siar , Krogh Nielsen Marie , Singh Amardeep , Sørensen Torben Lykke , Subhi Yousif
Published: October 2019

Age‐related macular degeneration (AMD) is the most common cause of visual impairment in the developed world. A number of patients experience complex lifelike visual experiences—Charles Bonnet syndrome (CBS). In this systematic review, our aim was to provide an overview of the CBS literature in relation to AMD, to determine the prevalence of CBS in patients with AMD and to provide an overview of associated demographical and clinical aspects. We searched the literature databases PubMed/MEDLINE, EMBASE, Web of Science, the Cochrane Central, and PsycINFO on 22 March 2019 for studies evaluating the prevalence of CBS in patients with AMD. Two independent authors extracted the data and evaluated risk of bias. Studies were reviewed qualitatively in the text and quantitatively in a meta‐analysis including subgroup analyses for differences between demographic and clinical factors. We identified 18 studies with data on >4303 patients with AMD. We found an overall prevalence of CBS of 15.8% (95% confidence interval: 11.0%–21.2%). When looking at consecutively recruited patients with neovascular AMD from the clinic, prevalence of CBS was 7.2% (95% confidence interval: 4.3%–10.6%). Among visitors to visual rehabilitation centres, prevalence of CBS was 31.6% (95% confidence interval: 21.7%–42.3%). Taken together, we find that CBS is rather common in patients with AMD.
Reported proton pump inhibitor side effects: what are physician and patient perspectives and behaviour patterns?
Authors: Ghosh Gaurav , Schnoll‐Sussman Felice , Mathews Steven , Katz Philip O.
Published: October 2019

Background

Proton pump inhibitors (PPI) are among the most commonly prescribed medications and studies are reporting potentially harmful PPI‐related adverse events. While these studies’ findings are controversial, their impact on patients and physicians remains unknown.

Aim

To determine patient and physician awareness of PPI‐related adverse events, source of information, and subsequent effect on patient behaviour and physician practice.

Methods

A 20‐item questionnaire was administered to English speaking adult patients and physicians in primary care and specialty clinics about topics including knowledge of PPI‐related adverse events, change in behaviour of patients on PPIs and physician management of patients on PPIs.

Results

Of 277 patients surveyed, 45% reported knowledge of side effects related to PPIs. Patients were more likely to hear about PPI side effects from non‐physician sources (66%) than physicians (38%). Of patients who had heard about PPI side effects, bone fractures and osteoporosis were the most common concerns, 42% and 44% respectively. Of PPI users, 38% changed their behaviour based upon concerns about PPI‐related adverse events. Change in patient behaviour due to concern about PPI side effects was associated with age ≥ 65 years (odds ratio [OR] 4.07 [1.19‐13.94]; P = 0.03) and concern about long‐term side effects (OR 2.31 [1.03‐5.17]; P = 0.04). Of 83 physicians surveyed, 60% reported concern about PPI‐related adverse events, with bone fractures (46%) and osteoporosis (49%) being the most frequently reported. Overall, 37% of physicians reported changing their practice based upon their concerns.

Conclusions

Nearly half of patients reported knowledge of PPI‐related adverse events, most often from non‐physician sources, and general concern regarding their impact. PPI users are changing their behaviour based upon these concerns, without physician input, and care providers are changing behaviour based on relatively weak evidence.
Decolonial reflections on urban pedagogy in India
Authors: Sundaresan Jayaraj
Published: October 2019

This paper engages with deep and entrenched coloniality of the urban pedagogy, epistemology, and policy in India. After outlining the context, I will discuss my reflections on some relevant pedagogical initiatives that I had an opportunity to be part of as a faculty in a graduate‐level programme in India.
Inference in MCMC step selection models
Authors: Michelot Théo , Blackwell Paul G. , Chamaillé‐Jammes Simon , Matthiopoulos Jason
Published: October 2019

Habitat selection models are used in ecology to link the spatial distribution of animals to environmental covariates and identify preferred habitats. The most widely used models of this type, resource selection functions, aim to capture the steady‐state distribution of space use of the animal, but they assume independence between the observed locations of an animal. This is unrealistic when location data display temporal autocorrelation. The alternative approach of step selection functions embed habitat selection in a model of animal movement, to account for the autocorrelation. However, inferences from step selection functions depend on the underlying movement model, and they do not readily predict steady‐state space use. We suggest an analogy between parameter updates and target distributions in Markov chain Monte Carlo (MCMC) algorithms, and step selection and steady‐state distributions in movement ecology, leading to a step selection model with an explicit steady‐state distribution. In this framework, we explain how maximum likelihood estimation can be used for simultaneous inference about movement and habitat selection. We describe the local Gibbs sampler, a novel rejection‐free MCMC scheme, use it as the basis of a flexible class of animal movement models, and derive its likelihood function for several important special cases. In a simulation study, we verify that maximum likelihood estimation can recover all model parameters. We illustrate the application of the method with data from a zebra.
Weight bias and grading among middle and high school teachers
Authors: Finn Kristin E. , Seymour Clancy M. , Phillips Anna E.
Published: October 2019

Background

Weight bias is a pervasive problem for adolescents in school contexts. Despite evidence of negative attitudes towards students who are overweight, comparatively little research has examined whether teachers provide biased assessments of student work.

Aims

The purpose of this study was to experimentally test whether middle and high school teachers unfairly assess students who are overweight and perceive them to be less competent.

Sample

Participants included 133 teachers from first‐ring suburban middle and high schools (Mteaching experience = 16 years; 38% male).

Methods

Teachers evaluated the quality of a bogus student essay assignment accompanied by photographs that portrayed the student as either not overweight or overweight. Weight bias was assessed by having teachers grade the essay and provide perceptions of student sufficiency (perceived effort, need for tutoring, and overall success in school). Opinions about bias in grading for other teachers and self were also assessed.

Results

Essays for students who were overweight were judged to be similar in structural quality, but were assigned lower grades compared to their healthy weight counterparts. Further, teachers estimated that students who were overweight put forth more effort, needed more remedial assistance, and had lower overall grades in school. Teachers’ beliefs about grading bias showed low levels of supposed bias among other teachers and a significantly lesser degree for themselves.

Conclusions

This study confirms prior research on anti‐fat attitudes and provides new evidence of biased attitudes in school settings.
Why have I failed? Why have I passed? A comparison of students’ causal attributions in second language acquisition (A1–B2 levels)
Authors: Soriano‐Ferrer Manuel , Alonso‐Blanco Elena
Published: October 2019

Background

Previous literature highlights the importance of causal attributions in achievement and motivation. However, the studies about causal attributions in second language acquisition (SLA) are limited and scarce.

Aims

This study was designed to determine the frequency of successful and unsuccessful activities per English level and to compare the causal attributions (explanations of outcomes) on successful and failure authentic tasks undertaken in the context of learning English as a foreign language (EFL) acquisition in an Official School of Languages (OSL).

Sample

To this aim, 407 native Spanish students from levels A1 (n = 111), A2 (n = 113), B1 (n = 98), and B2 (n = 85) in OSL participated in this study.

Method

Participants completed Attribution to Success and Failure Questionnaires (ASQ & AFQ).

Results

Results of ANOVAs and Scheffe post hoc test show main significant differences between A1 and B2 students. Students at A1 level perceive their success in the foreign language (FL) as dependent on some internal but unstable controllable variables, such as effort and strategy, and to some external variables such as teacher influence, task difficulty, and class atmosphere. On the contrary, students at B2 level perceive that their successful outcomes in FL depend on ability, marks, class level, preparation, and enjoyment within the classroom, whereas they perceive that their failure outcomes are dependent on external factors such as luck, teacher influence, and/or task difficulty.

Conclusions

Results provide evidence that students from OSL employ multiple causal attributions to explain their academic success and failure, which may also have educational implications for class teachers.
Inhibition of allergen‐induced dermal eosinophilia by an oxoeicosanoid receptor antagonist in non‐human primates
Authors: Miller Lisa A. , Cossette Chantal , Chourey Shishir , Ye Qiuji , Reddy Chintam Nagendra , Rokach Joshua , Powell William S.
Published: October 2019

Background and Purpose

5‐Oxo‐6,8,11,14‐eicosatetraenoic acid (5‐oxo‐ETE), acting via the OXE receptor, is unique among 5‐lipoxygenase products in its ability to directly induce human eosinophil migration, suggesting its involvement in eosinophilic diseases. To address this hypothesis, we synthesized selective indole‐based OXE receptor antagonists. Because rodents lack an OXE receptor orthologue, we sought to determine whether these antagonists could attenuate allergen‐induced skin eosinophilia in sensitized monkeys.

Experimental Approach

In a pilot study, cynomolgus monkeys with environmentally acquired sensitivity to Ascaris suum were treated orally with the “first‐generation” OXE antagonist 230 prior to intradermal injection of 5‐oxo‐ETE or Ascaris extract. Eosinophils were evaluated in punch biopsy samples taken 6 or 24 hr later. We subsequently treated captive‐bred rhesus monkeys sensitized to house dust mite (HDM) allergen with a more recently developed OXE antagonist, S‐Y048, and evaluated its effects on dermal eosinophilia induced by either 5‐oxo‐ETE or HDM.

Key Results

In a pilot experiment, both 5‐oxo‐ETE and Ascaris extract induced dermal eosinophilia in cynomolgus monkeys, which appeared to be reduced by 230. Subsequently, we found that the related OXE antagonist S‐Y048 is a highly potent inhibitor of 5‐oxo‐ETE‐induced activation of rhesus monkey eosinophils in vitro and has a half‐life in plasma of about 6 hr after oral administration. S‐Y048 significantly inhibited eosinophil infiltration into the skin in response to both intradermally administered 5‐oxo‐ETE and HDM.

Conclusions and Implications

5‐Oxo‐ETE may play an important role in allergen‐induced eosinophilia. Blocking its effects with S‐Y048 may provide a novel therapeutic approach for eosinophilic diseases.
FOXO1 inhibition prevents renal ischemia–reperfusion injury via cAMP‐response element binding protein/PPAR‐γ coactivator‐1α‐mediated mitochondrial biogenesis
Authors: Wang Di , Wang Yanqing , Zou Xiantong , Shi Yundi , Liu Qian , Huyan Tianru , Su Jing , Wang Qi , Zhang Fengxue , Li Xuejun , Tie Lu
Published: October 2019

Background and Purpose

Growing evidence indicates targeting mitochondrial dynamics and biogenesis could accelerate recovery from renal ischemia–reperfusion (I/R) injury, but the underlying mechanisms remain elusive. Transcription factor forkhead box O1 (FOXO1) is a key regulator of mitochondrial homeostasis and plays a pathological role in the progression of renal disease.

Experimental Approach

A mouse model of renal I/R injury and a hypoxia/reoxygenation (H/R) injury model for human renal tubular epithelial cells were used.

Key Results

I/R injury up‐regulated renal expression of FOXO1 and treatment with FOXO1‐selective inhibitor AS1842856 prior to I/R injury decreased serum urea nitrogen, serum creatinine and the tubular damage score after injury. Post‐I/R injury AS1842856 treatment could also ameliorate renal function and improve the survival rate of mice following injury. AS1842856 administration reduced mitochondrial‐mediated apoptosis, suppressed the overproduction of mitochondrial ROS and accelerated recovery of ATP both in vivo and in vitro. Additionally, FOXO1 inhibition improved mitochondrial biogenesis and suppressed mitophagy. Expression of PPAR‐γ coactivator 1α (PGC‐1α), a master regulator of mitochondrial biogenesis, was down‐regulated in both I/R and H/R injury, which could be abrogated by FOXO1 inhibition. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that FOXO1 inhibited PGC‐1α transcription by competing with cAMP‐response element binding protein (CREB) for its binding to transcriptional coactivators CREBBP/EP300 (CBP/P300).

Conclusion and Implications

These findings suggested that FOXO1 was critical to maintain mitochondrial function in renal tubular epithelial cells and FOXO1 may serve as a therapeutic target for pharmacological intervention in renal I/R injury.
Mu and delta opioid receptors play opposite nociceptive and behavioural roles on nerve‐injured mice
Authors: Martínez‐Navarro Miriam , Cabañero David , Wawrzczak‐Bargiela Agnieszka , Robe Anne , Gavériaux‐Ruff Claire , Kieffer Brigitte L. , Przewlocki Ryszard , Baños Josep E. , Maldonado Rafael
Published: October 2019

Background and Purpose

Mu and delta opioid receptors (MOP, DOP) contribution to the manifestations of pathological pain is not understood. We used genetic approaches to investigate the opioid mechanisms modulating neuropathic pain and its comorbid manifestations.

Experimental Approach

We generated conditional knockout mice with MOP or DOP deletion in sensory Nav1.8‐positive neurons (Nav1.8), in GABAergic forebrain neurons (DLX5/6) or constitutively (CMV). Mutant mice and wild‐type littermates were subjected to partial sciatic nerve ligation (PSNL) or sham surgery and their nociception was compared. Anxiety‐, depressive like behaviour and cognitive performance were also measured. Opioid receptor mRNA expression, microgliosis and astrocytosis were assessed in the dorsal root ganglia (DRG) and/or the spinal cord (SC).

Key Results

Constitutive CMV‐MOP knockouts after PSNL displayed reduced mechanical allodynia and enhanced heat hyperalgesia. This phenotype was accompanied by increased DOP expression in DRG and SC, and reduced microgliosis and astrocytosis in deep dorsal horn laminae. Conditional MOP knockouts and control mice developed similar hypersensitivity after PSNL, except for anenhanced heat hyperalgesia by DLX5/6‐MOP male mice. Neuropathic pain‐induced anxiety was aggravated in CMV‐MOP and DLX5/6‐MOP knockouts. Nerve‐injured CMV‐DOP mice showed increased mechanical allodynia, whereas Nav1.8‐DOP and DLX5/8‐DOP mice had partial nociceptive enhancement. CMV‐DOP and DLX5/6‐DOP mutants showed increased depressive‐like behaviour after PSNL.

Conclusions and Implications

MOP activity after nerve injury increased anxiety‐like responses involving forebrain GABAergic neurons and enhanced mechanical pain sensitivity along with repression of DOP expression and spinal cord gliosis. In contrast, DOP shows a protective function limiting nociceptive and affective manifestations of neuropathic pain.
Attention Deficit Hyperactivity Disorder‐Symptoms, Social Media Use Intensity, and Social Media Use Problems in Adolescents: Investigating Directionality
Authors: Boer Maartje , Stevens Gonneke , Finkenauer Catrin , van den Eijnden Regina
Published: October 2019

Cross‐sectional research shows that adolescents’ social media use (SMU) and attention deficit hyperactivity disorder (ADHD)‐symptoms are related, but it is unclear whether this relation is explained by SMU intensity or by addiction‐like SMU problems. Also, due to the lack of longitudinal studies, the direction of this relation remains unknown. This study aims to disentangle which type of SMU is related to ADHD‐symptoms, and in which direction, using a three‐wave longitudinal study among Dutch adolescents aged 11–15 years (n = 543). Findings suggest a unidirectional relation: SMU problems increased ADHD‐symptoms over time, SMU intensity did not. This implies that problematic use, rather than the intensity of use harmfully affects adolescents’ ADHD‐symptoms.
Prognostic role of the lymphocyte‐to‐monocyte ratio for clinical outcomes of patients with progressive radioiodine‐refractory differentiated thyroid carcinoma treated by sorafenib
Authors: Ahn Jonghwa , Song Eyun , Kim Won Gu , Kim Tae Yong , Kim Won Bae , Shong Young Kee , Jeon Min Ji
Published: October 2019

Objectives

The lymphocyte‐to‐monocyte ratio (LMR) reflects the status of tumour‐infiltrating immune cells and host immunity. The LMR has been reported as a prognostic marker in various cancers. The present study evaluated the role of the LMR as a prognostic marker in patients with progressive radioiodine‐refractory (RAIR) differentiated thyroid carcinoma (DTC).

Design

Retrospective cohort study.

Patients

Forty patients with progressive RAIR DTC who were treated by sorafenib with available baseline complete blood cell count data.

Measurements

We assessed the response rate, progression‐free survival (PFS) and overall survival (OS).

Results

The patients were divided into low and high LMR groups based on their baseline LMRs (<4, n = 22, 55% and ≥4, n = 18, 45%, respectively). There were no significant differences in baseline characteristics between the groups. The OS curves differed significantly based on the LMR. The median OS of the low LMR group was 24.3 months and that of the high LMR group was not reached until the end of observation period (P = .015). The PFS curves and median PFS also differed significantly based on the LMR values (P = .019). In multivariate analysis, low LMR was an independent risk factor for all‐cause mortality in patients with progressive RAIR DTC (hazard ratio, 2.64; 95% confidence interval: 1.04‐6.72, P = .041).

Conclusion

A low LMR was associated with poor response rate, PFS and OS in patients with progressive RAIR DTC treated with sorafenib. Thus, LMR could be a simple prognostic biomarker in patients with progressive RAIR DTC.
Loss‐of‐function mutations in centrosomal protein 112 is associated with human acephalic spermatozoa phenotype
Authors: Sha Yanwei , Wang Xiong , Yuan JinTing , Zhu Xingshen , Su Zhiying , Zhang Xuequan , Xu Xiaohui , Wei Xiaoli
Published: October 2019

Acephalic spermatozoa, characterized by the headless sperm in the ejaculate, is a rare type of teratozoospermia. Here, we recruited two infertile patients with an acephalic spermatozoa phenotype to investigate the genetic pathology of acephalic spermatozoa. Whole‐exome sequencing analysis was performed and found mutations in CEP112 in the two patients: homozygous mutation c.496C > T:p.(Arg166X) in exon 5 from P1; and the biallelic mutations c.2074C > T:p.(Arg692Trp) in exon 20 and c.2104C > T:p.(Arg702Cys) in exon 20 from P2. Sanger sequencing confirmed the CEP112 mutations in the two patients. In silico analysis revealed that these CEP112 mutations are deleterious and rare, and all the mutations impact the coiled‐coil domain of CEP112, which may affect the protein function. The c.496C > T:p.Arg166X resulted in a truncated CEP112, which was verified by the mutation expression plasmid. The CEP112 expression was significantly reduced in the P2, suggesting the biallelic mutations c.2074C > T and c.2104C > T may affect the function and stability of CEP112. Therefore, we speculate that the loss‐of‐function mutations in CEP112 may be account for the human acephalic spermatozoa phenotype.