bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal Vascular Density on Optical Coherence Tomography Angiography and Age-Related Central and Peripheral Hearing Loss in a Southern Italian Older Population
Authors: Sardone Rodolfo , Sborgia Giancarlo , Niro Alfredo , Giuliani Gianluigi , Pascale Angelo , Puzo Pasquale , Guerra Vito , Castellana Fabio , Lampignano Luisa , Donghia Rossella , Bortone Ilaria , Zupo Roberta , Griseta Chiara , Logroscino Giancarlo , Lozupone Madia , Giannelli Gianluigi , Panza Francesco , Boscia Francesco , Alessio Giovanni , Quaranta Nicola
Published: October 2020

Background

Age-related hearing loss (ARHL) and retinal vessel changes have both been associated to neurodegeneration/dementia, suggesting a possible link between these 2 conditions in older age. We aimed to determine whether superficial and deep vascular density (SVD and DVD) of the capillary plexi of macular vasculature can be associated with peripheral ARHL and age-related central auditory central processing (CAPD).

Method

We analyzed data on 886 older participants (65 years+, age range: 65–92 years) in the cross-sectional population-based Salus in Apulia Study. Optical coherence tomography angiography was used to measure SVD and DVD of the capillary plexi of the macula at the 3-mm circle area centered on the fovea (whole retina), the parafoveal quadrant, and foveal quadrant. Disabling peripheral ARHL was defined as >40 dB hearing level of pure tone average on the frequencies from 0.5, 1, 2, and 4 KHz in the better ear, and age-related CAPD as <50% at the Synthetic Sentence Identification with Ipsilateral Competitive Message test in at least one ear.

Results

DVD at the whole retina and at the parafoveal quadrant were inversely associated only with age-related CAPD (odds ratio [OR]: 0.93, 95% confidence interval [CI]: 0.88–0.96 and OR: 0.94, 95 CI: 0.90–0.99, respectively). No further associations with peripheral ARHL were evident.

Conclusions

Retinal vasculature is associated with central auditory processing pathology, possibly playing an important role in early detection and intervention. The association of retinal vascular density with age-related CAPD may bring us a further step forward in understanding the biological mechanisms underlying the links between neurodegeneration/dementia and ARHL.
The Indonesian Mental Health Act: psychiatrists’ views on the act and its implementation
Authors: Bikker Annemieke P , Lesmana Cokorda Bagus Jaya , Tiliopoulos Niko
Published: October 2020

In 2014, the Indonesian government passed the Mental Health Act (MHA) to address the country’s complex mental health situation. The implementation of the MHA has been slow, and little is known about how the MHA is perceived by mental healthcare providers within local settings. This study aimed to obtain insight into psychiatrists’ views on the MHA, including on how it affected their clinical practice and on challenges of translating the MHA into practice. The study was conducted in Bali, and 27 psychiatrists (15 men and 12 women) participated in a semi-structured interview. Thematic analysis indicated four overarching themes: raising the profile of mental health, developing a shared understanding of mental illness, integrating psychiatric practice with other services and views on implementation of the MHA into practice. Overall, the psychiatrists viewed the MHA as a step in the right direction to improve mental health services and to create awareness at local and national levels. However, there was consensus that the meaning of the MHA’s concepts of mental problems and disorders were not compatible with psychiatric everyday practice or their patients’ understandings. As a result, many assumed that the MHA was targeted at government and policy officials. Furthermore, there was a perceived lack of clarity on issues relating to collaborating with other services and unequal access to resources among regencies that impacted on their clinical practice in a negative way. Moreover, a few psychiatrists raised concerns that local beliefs and practices were not acknowledged in the MHA. According to the participants, mental health remained a highly political issue and without national support, mental health would remain a low priority. In conclusion, insights into providers’ perspectives contribute to developing an evidence-base that can inform the implementation process of the MHA in Indonesia, and possibly elsewhere, into local level guidelines and regulations.
Intragenic complementation of amino and carboxy terminal SMN missense mutations can rescue Smn null mice
Authors: McGovern Vicki L , Kray Kaitlyn M , Arnold W David , Duque Sandra I , Iyer Chitra C , Massoni-Laporte Aurélie , Workman Eileen , Patel Aalapi , Battle Daniel J , Burghes Arthur H M
Published: October 2020

Spinal muscular atrophy is caused by reduced levels of SMN resulting from the loss of SMN1 and reliance on SMN2 for the production of SMN. Loss of SMN entirely is embryonic lethal in mammals. There are several SMN missense mutations found in humans. These alleles do not show partial function in the absence of wild-type SMN and cannot rescue a null Smn allele in mice. However, these human SMN missense allele transgenes can rescue a null Smn allele when SMN2 is present. We find that the N- and C-terminal regions constitute two independent domains of SMN that can be separated genetically and undergo intragenic complementation. These SMN protein heteromers restore snRNP assembly of Sm proteins onto snRNA and completely rescue both survival of Smn null mice and motor neuron electrophysiology demonstrating that the essential functional unit of SMN is the oligomer.
Habitat use and movement patterns of tiger sharks (Galeocerdo cuvier) in eastern Australian waters
Authors: Lipscombe Rebecca S , Spaet Julia L Y , Scott Anna , Lam Chi Hin , Brand Craig P , Butcher Paul A
Published: October 2020

Understanding the movement of marine predators is vital for effective conservation and management. Despite being targeted by shark control programs, the tiger shark, Galeocerdo cuvier, is poorly studied off eastern Australia. To investigate the horizontal movement and habitat use in this region, 16 sharks (157–384 cm total length) were tagged with MiniPAT pop-up satellite archival tags in 2018 and 2019. Eleven of these individuals were also fitted with satellite-linked radio transmitting tags. After release, most sharks moved off the continental shelf and headed north, associating with seamounts as they moved towards Queensland. During their time at liberty they transited through temperate, sub-tropical and tropical waters and spent the majority of time in the upper 50 m of the water column and at temperatures between 22 and 25˚C. Horizontal movement was focused in waters off the continental shelf. Increased movement over shelf waters occurred during the austral spring and summer when the East Australian Current is at its strongest and warm waters encroach the continental shelf. Broad latitudinal movement along the east coast of Australia was evident and highlights the connectivity between tropical and warm-temperate regions.
Development and testing of fish-retention devices for pots: transparent triggers significantly increase catch efficiency for Atlantic cod (Gadus morhua)
Authors: Chladek Jérôme , Stepputtis Daniel , Hermann Andreas , Ljungberg Peter , Rodriguez-Tress Paco , Santos Juan , Svendsen Jon Christian
Published: October 2020

Fish pots have lower catch efficiency than gillnets and trawls and, therefore, are rarely used for catching Atlantic cod (Gadus morhua) and similar species. Fish-retention devices (FRDs), non-return devices that permit fish to enter the pot while impeding exit, reduce the pot exit rate and therefore can increase catches. Conventional FRDs, however, also reduce entry rate and may not improve catches. To increase pot-catch efficiency, we developed and tested a new trigger-type FRD, made of transparent acrylic glass, which we named acrylic fingers (AFs). AFs are almost invisible underwater and offer little resistance to entering cod. We compared AFs with Neptune fingers (NFs), a conventional trigger-type FRD with a distinct visual outline, by observing cod entry and exit rates through both trigger types rigged to a pot in a net pen. Both trigger types significantly reduced exit rates compared with a funnel without triggers; however, NFs also reduced entry rates by visually deterring cod. Specifically, AFs have higher entry-to-exit ratios and therefore improve catch efficiency. Combining AFs with funnels further increased catch efficiency. Thus, transparent acrylic triggers present a promising new approach to increasing pot-catch efficiency and may increase the uptake of the cod pot, an environmentally low-impact gear.
Teflon Trump? Shifting Public Perceptions of Donald Trump’s Personality Traits across Four Studies over 18 Months
Authors: Nai Alessandro , Maier Jürgen
Published: October 2020

Democrats and Republicans have divergent views about Trump’s personality. Are these perceptions stable over time? We describe the evolution of Trump’s perceived personality (Big Five and Dark Triad) between November 2018 and May 2020 by comparing four samples of American respondents (Mechanical Turk). Trump’s perceived personality is on average extremely stable. Liberals have a much more critical perception of Trump than conservatives. Yet, strong Republicans have an increasingly more negative perception over the time—perhaps because the scandals that have marred the Trump presidency are at odds with conservative “moral foundations.” We also detected a potential demobilization trend for strong Republicans; the more they perceive the president negatively, the lower their likelihood to turn out. The electoral implications of these trends are important.
Consensus-based antimicrobial resistance and stewardship competencies for UK undergraduate medical students
Authors: McMaster David , Courtenay Molly , Santucci Catherine , Davies Angharad P , Kirby Andrew , Seddon Owen , Price David A , Barlow Gavin , Lim Felicia H , Davies Bethany S , O’Shea Matthew K , Collini Paul , Basarab Marina , Ahmad Afshan , Albur Mahableshwar , Hemsley Carolyn , Brown Nicholas M , O’Gorman Ciaran , Rautemaa-Richardson Riina , Davies Geraint R , Penfold Christopher N , Patel Sanjay ,   Keep Antibiotics Working (KAW) group, Ahmad Afshan , Kirby Andrew , Davies Angharad P , Davies Bethany S , Robertson Brian D , Hemsley Carolyn , Santucci Catherine , Penfold Christopher N , O’Gorman Ciaran , Price David A , McMaster David , Mitcheson Deborah , Hart Elizabeth , Lim Felicia H , Barlow Gavin , Davies Geraint R , Albur Mahableshwar , Basarab Marina , O’Shea Matthew K , Courtenay Molly , Brown Nicholas M , Jones Nicola , Seddon Owen , McGettigan Patricia , Collini Paul , Munthali Peter , Rautemaa-Richardson Riina , Patel Sanjay , Roberts Sophie , Sloan Tim , Paget Timothy
Published: October 2020

Background

In the UK there is limited coverage of antimicrobial stewardship across postgraduate curricula and evidence that final year medical students have insufficient and inconsistent antimicrobial stewardship teaching. A national undergraduate curriculum for antimicrobial resistance and stewardship is required to standardize an adequate level of understanding for all future doctors.

Objectives

To provide a UK national consensus on competencies for antimicrobial resistance and stewardship for undergraduate medical education.

Methods

Using the modified Delphi method over two online survey rounds, an expert panel comprising leads for infection teaching from 25 UK medical schools reviewed competency descriptors for antimicrobial resistance and stewardship education.

Results

There was a response rate of 100% with all 28 experts who agreed to take part completing both survey rounds. Following the first-round survey, of the initial 55 descriptors, 43 reached consensus (78%). The second-round survey included the 12 descriptors from the first round in which agreement had not been reached, four amended descriptors and 12 new descriptors following qualitative feedback from the panel members. Following the second-round survey, a total of 58 consensus-based competency descriptors within six overarching domains were identified.

Conclusions

The consensus-based competency descriptors defined here can be used to inform standards, design curricula, develop assessment tools and direct UK undergraduate medical education.
A phase II Japanese trial of fludarabine, cyclophosphamide and rituximab for previously untreated chronic lymphocytic leukemia
Authors: Izutsu Koji , Kinoshita Tomohiro , Takizawa Jun , Fukuhara Suguru , Yamamoto Go , Ohashi Yasuo , Suzumiya Junji , Tobinai Kensei
Published: October 2020

Objective

Fludarabine, cyclophosphamide and rituximab (FCR) is the standard regimen for fit patients with untreated CD20-positive chronic lymphocytic leukemia (CLL). However, this combination is unavailable in Japan because rituximab is not approved for CLL. We investigated the efficacy and safety of FCR in this single-arm, multicenter study designed as a bridging study to the CLL8 study by the German CLL Study Group.

Methods

The study enrolled previously untreated patients with CLL of Binet stage B or C with active disease. Patients with a Cumulative Illness Rating Scale score of ≤6 and creatinine clearance of ≥70 ml/min were eligible. Patients received 6 cycles of FCR every 28 days and were followed for up to 1 year.

Results

Seven patients were enrolled. The best overall response rate according to the 1996 NCI-WG Guidelines, the primary endpoint of the study, was 71.4% (95% confidence interval, 29.0–96.3%), with one patient achieving complete response. No deaths or progression occurred during follow-up. The main adverse event was hematotoxicity. CD4-positive T-cell count decreased in all patients; most patients showed no reduction in serum immunoglobulin G.

Conclusion

Although the number of patients was limited, FCR appears to be effective with manageable toxicity for treatment-naïve fit Japanese patients with CD20-positive CLL.

Clinical trial number

JapicCTI-132285.
A new living species of degu, genusOctodon(Hystricomorpha: Octodontidae)
Authors: D’Elía Guillermo , Teta Pablo , Verzi Diego H , Cadenillas Richard , Patton James L
Published: October 2020

We combine morphological (qualitative and quantitative data) and genetic (one mitochondrial and one nuclear gene) data from a large set of specimens of Octodon from the four currently recognized living species of the genus. The integration of the results (qualitative assessment, multivariate analysis of cranial measurements, and gene trees) allows us to state that 1) the current taxonomic scheme does not reflect the species diversity of Octodon; 2) in particular, as currently understood O. bridgesii likely is a complex of three species; 3) one of these, encompassing the southern populations of the genus, in the Araucanía Region (Chile) and Neuquén Province (Argentina), is named and described here as a new species; and 4) the mitochondrial gene tree departs from the nuclear gene tree with respect to O. pacificus and the new species here described.
Photobleaching reduction in modulated super-resolution microscopy
Authors: Ghithan Jafar H , Noel Jennifer M , Roussel Thomas J , McCall Maureen A , Alphenaar Bruce W , Mendes Sergio B
Published: October 2020

Important breakthroughs in far-field imaging techniques have been made since the first demonstrations of stimulated emission depletion (STED) microscopy. To date, the most straightforward and widespread deployment of STED microscopy has used continuous wave (CW) laser beams for both the excitation and depletion of fluorescence emission. A major drawback of the CW STED imaging technique has been photobleaching effects due to the high optical power needed in the depletion beam to reach sub-diffraction resolution. To overcome this hurdle, we have applied a synchronous detection approach based on modulating the excitation laser beam, while keeping the depletion beam at CW operation, and frequency filtering the collected signal with a lock-in amplifier to record solely the super-resolved fluorescence emission. We demonstrate here that such approach allows an important reduction in the optical power of both laser beams that leads to measurable decreases in photobleaching effects in STED microscopy. We report super-resolution images with relatively low powers for both the excitation and depletion beams. In addition, typical unwanted scattering effects and background signal generated from the depletion beam, which invariably arises from mismatches in refractive index in the material composing the sample, are largely reduced by using the modulated STED approach. The capability of acquiring super-resolution images with relatively low power is quite relevant for studying a variety of samples, but particularly important for biological species as exemplified in this work.
Clinical Characteristics and Outcomes of COVID-19–Infected Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Zhang Hua , Han Han , He Tianhui , Labbe Kristen E , Hernandez Adrian V , Chen Haiquan , Velcheti Vamsidhar , Stebbing Justin , Wong Kwok-Kin
Published: October 2020

Background

Previous studies have indicated coronavirus disease 2019 (COVID-19) patients with cancer have a high fatality rate.

Methods

We conducted a systematic review of studies that reported fatalities in COVID-19 patients with cancer. A comprehensive meta-analysis that assessed the overall case fatality rate and associated risk factors was performed. Using individual patient data, univariate and multivariable logistic regression analyses were used to estimate odds ratios (OR) for each variable with outcomes.

Results

We included 15 studies with 3019 patients, of which 1628 were men; 41.0% were from the United Kingdom and Europe, followed by the United States and Canada (35.7%), and Asia (China, 23.3%). The overall case fatality rate of COVID-19 patients with cancer measured 22.4% (95% confidence interval [CI] = 17.3% to 28.0%). Univariate analysis revealed age (OR = 3.57, 95% CI = 1.80 to 7.06), male sex (OR = 2.10, 95% CI = 1.07 to 4.13), and comorbidity (OR = 2.00, 95% CI = 1.04 to 3.85) were associated with increased risk of severe events (defined as the individuals being admitted to the intensive care unit, or requiring invasive ventilation, or death). In multivariable analysis, only age greater than 65 years (OR = 3.16, 95% CI = 1.45 to 6.88) and being male (OR = 2.29, 95% CI = 1.07 to 4.87) were associated with increased risk of severe events.

Conclusions

Our analysis demonstrated that COVID-19 patients with cancer have a higher fatality rate compared with that of COVID-19 patients without cancer. Age and sex appear to be risk factors associated with a poorer prognosis.
Visitor Restriction Policy on Pediatric Wards During Novel Coronavirus (COVID-19) Outbreak: A Survey Study Across North America
Authors: Kitano Taito , Piché-Renaud Pierre-Philippe , Groves Helen E , Streitenberger Laurie , Freeman Renee , Science Michelle
Published: October 2020

Visitor restriction policies in pediatric wards during the novel coronavirus (COVID-19) outbreak are variable. Among 36 hospitals that responded to our survey, 97% allowed at least 1 visitor, with 67% restricting to 1 caregiver. Sixty-nine percent required the visitor to wear personal protective equipment and only 19% allowed non-household visitors.
Pu-miR172d regulates stomatal density and water-use efficiency via targetingPuGTL1in poplar
Authors: Liu Quangang , Wang Zhanchao , Yu Sen , Li Wenlong , Zhang Mengqiu , Yang Jia , Li Dandan , Yang Jingli , Li Chenghao
Published: October 2020

miRNAs play essential regulatory roles in many aspects of plant development and in responses to abiotic and biotic stresses. Here, we characterize Pu-miR172d, which acts as a negative regulator of stomatal density by directly repressing the expression of PuGTL1 in Populus ussuriensis. Quantitative real-time PCR and GUS reporter analyses showed that Pu-miR172d was strongly expressed in the guard cells of young leaves. Overexpression of Pu-miR172d significantly decreased stomatal density, resulting in increases in water use efficiency (WUE) and drought tolerance by reducing net photosynthetic rate, stomatal conductance, and transpiration. Molecular analysis showed that PuGTL1 was a major target of Pu-miR172d cleavage. Moreover, PuGTL1-SRDX plants, in which PuGTL1 is suppressed, phenocopied Pu-miR172d-overexpression lines with reduced stomatal density and enhanced WUE. The expression of PuSDD1, a negative regulator of stomatal development, was significantly increased in young leaves of both Pu-miR172d-overexpression and PuGTL1-SRDX plants. RNA-seq analysis of mature leaves indicated that overexpression of Pu-miR172d decreased the expression of many genes related to photosynthesis. Our findings show that the Pu-miR172d/PuGTL1/PuSDD1 module plays an important role in stomatal differentiation, and hence it is a potential target for engineering improved drought tolerance in poplar.
Joint gas and stellar dynamical models of WLM: an isolated dwarf galaxy within a cored, prolate DM halo
Authors: Leung Gigi Y C , Leaman Ryan , Battaglia Giuseppina , van de Ven Glenn , Brooks Alyson M , Peñarrubia Jorge , Venn Kim A
Published: October 2020

We present multitracer dynamical models of the low-mass (M* ∼ 107), isolated dwarf irregular galaxy WLM in order to simultaneously constrain the inner slope of the dark matter (DM) halo density profile (γ) and flattening (qDM), and the stellar orbital anisotropy (βz, βr). For the first time, we show how jointly constraining the mass distribution from the H i gas rotation curve and solving the Jeans equations with discrete stellar kinematics lead to a factor of ∼2 reduction in the uncertainties on γ. The mass-anisotropy degeneracy is also partially broken, leading to reductions on uncertainty by ${\sim} 30{{\ \rm per\ cent}}$ on Mvir (and ${\sim} 70{{\ \rm per\ cent}}$ at the half-light radius) and ${\sim} 25{{\ \rm per\ cent}}$ on anisotropy. Our inferred value of γ = 0.3 ± 0.1 is robust to the halo geometry, and in excellent agreement with predictions of stellar feedback-driven DM core creation. The derived prolate geometry of the DM halo with qDM = 2 ± 1 is consistent with Lambda cold dark matter simulations of dwarf galaxy haloes. While self-interacting DM (SIDM) models with σ/mX ∼ 0.6 can reproduce this cored DM profile, the interaction events may sphericalize the halo. The simultaneously cored and prolate DM halo may therefore present a challenge for SIDM. Finally, we find that the radial profile of stellar anisotropy in WLM (βr) follows a nearly identical trend of increasing tangential anisotropy to the classical dwarf spheroidals, Fornax and Sculptor. Given WLM’s orbital history, this result may call into question whether such anisotropy is a consequence of tidal stripping in only one pericentric passage or if it instead is a feature of the largely self-similar formation and evolutionary pathways for some dwarf galaxies.
Accurate initial conditions for cosmological N-body simulations: minimizing truncation and discreteness errors
Authors: Michaux Michaël , Hahn Oliver , Rampf Cornelius , Angulo Raul E
Published: October 2020

Inaccuracies in the initial conditions for cosmological N-body simulations could easily be the largest source of systematic error in predicting the non-linear large-scale structure. From the theory side, initial conditions are usually provided by using low-order truncations of the displacement field from Lagrangian perturbation theory, with the first- and second-order approximations being the most common ones. Here, we investigate the improvement brought by using initial conditions based on third-order Lagrangian perturbation theory (3LPT). We show that with 3LPT, truncation errors are vastly suppressed, thereby opening the portal to initializing simulations accurately as late as z = 12 (for the resolution we consider). We analyse the competing effects of perturbative truncation and particle discreteness on various summary statistics. Discreteness errors are essentially decaying modes and thus get strongly amplified for earlier initialization times. We show that late starting times with 3LPT provide the most accurate configuration, which we find to coincide with the continuum fluid limit within 1 per cent for the power- and bispectrum at z = 0 up to the particle Nyquist wavenumber of our simulations (k ∼ 3h Mpc−1). In conclusion, to suppress non-fluid artefacts, we recommend initializing simulations as late as possible with 3LPT. We make our 3LPT initial condition generator publicly available.
They do change after all: 25 yr of GONG data reveal variation of p-mode energy supply rates
Authors: Kiefer René , Broomhall Anne-Marie
Published: October 2020

It has been shown over and over again that the parameters of solar p modes vary through the solar activity cycle: frequencies, amplitudes, lifetimes, energies. However, so far, the rates at which energy is supplied to the p modes have not been detected to be sensitive to the level of magnetic activity. We set out to re-inspect their temporal behaviour over the course of the last two Schwabe cycles. For this, we use Global Oscillation Network Group (GONG) p-mode parameter tables. We analyse the energy supply rates for modes of harmonic degrees l = 0–150 and average over the azimuthal orders and, subsequently, over modes in different parameter ranges. This averaging greatly helps in reducing the noise in the data. We find that energy supply rates are anticorrelated with the level of solar activity, for which we use the F10.7 index as a proxy. Modes of different mode frequency and harmonic degrees show varying strengths of anticorrelation with the F10.7 index, reaching as low as r = −0.82 for low frequency modes with l = 101–150. In this first dedicated study of solar p-mode energy supply rates in GONG data, we find that they do indeed vary through the solar cycle. Earlier investigations with data from other instruments were hindered by being limited to low harmonic degrees or by the data sets being too short. We provide tables of time-averaged energy supply rates for individual modes as well as for averages over disjunct frequency bins.
Sperm histone H3 lysine 4 trimethylation is altered in a genetic mouse model of transgenerational epigenetic inheritance
Authors: Lismer Ariane , Siklenka Keith , Lafleur Christine , Dumeaux Vanessa , Kimmins Sarah
Published: October 2020

Advancing the molecular knowledge surrounding fertility and inheritance has become critical given the halving of sperm counts in the last 40 years, and the rise in complex disease which cannot be explained by genetics alone. The connection between both these trends may lie in alterations to the sperm epigenome and occur through environmental exposures. Changes to the sperm epigenome are also associated with health risks across generations such as metabolic disorders and cancer. Thus, it is imperative to identify the epigenetic modifications that escape reprogramming during spermatogenesis and embryogenesis. Here, we aimed to identify the chromatin signature(s) involved in transgenerational phenotypes in our genetic mouse model of epigenetic inheritance that overexpresses the histone demethylase KDM1A in their germ cells. We used sperm-specific chromatin immunoprecipitation followed by in depth sequencing (ChIP-seq), and computational analysis to identify whether differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3), and histone H3 lysine 27 trimethylation (H3K27me3) serve as mechanisms for transgenerational epigenetic inheritance through the paternal germline. Our analysis on the sperm of KDM1A transgenic males revealed specific changes in H3K4me3 enrichment that predominantly occurred independently from bivalent H3K4me3/H3K27me3 regions. Many regions with altered H3K4me3 enrichment in sperm were identified on the paternal allele of the pre-implantation embryo. These findings suggest that sperm H3K4me3 functions in the transmission of non-genetic phenotypes transgenerationally.
Benzo[a]pyrene represses DNA repair through altered E2F1/E2F4 function marking an early event in DNA damage-induced cellular senescence
Authors: Allmann Sebastian , Mayer Laura , Olma Jessika , Kaina Bernd , Hofmann Thomas G , Tomicic Maja T , Christmann Markus
Published: October 2020

Transcriptional regulation of DNA repair is of outmost importance for the restoration of DNA integrity upon genotoxic stress. Here we report that the potent environmental carcinogen benzo[a]pyrene (B[a]P) activates a cellular DNA damage response resulting in transcriptional repression of mismatch repair (MMR) genes (MSH2, MSH6, EXO1) and of RAD51, the central homologous recombination repair (HR) component, ultimately leading to downregulation of MMR and HR. B[a]P-induced gene repression is caused by abrogated E2F1 signalling. This occurs through proteasomal degradation of E2F1 in G2-arrested cells and downregulation of E2F1 mRNA expression in G1-arrested cells. Repression of E2F1-mediated transcription and silencing of repair genes is further mediated by the p21-dependent E2F4/DREAM complex. Notably, repression of DNA repair is also observed following exposure to the active B[a]P metabolite BPDE and upon ionizing radiation and occurs in response to a p53/p21-triggered, irreversible cell cycle arrest marking the onset of cellular senescence. Overall, our results suggest that repression of MMR and HR is an early event during genotoxic-stress induced senescence. We propose that persistent downregulation of DNA repair might play a role in the maintenance of the senescence phenotype, which is associated with an accumulation of unrepairable DNA lesions.
Association between thrombotic microangiopathy and activated alternative complement pathway in malignant nephrosclerosis
Authors: Zhang Ying , Yang Chaona , Zhou Xinjin , Hu Ruimin , Quan Songxia , Zhou Yali , Li Yuan , Xing Guolan
Published: October 2020

Background

Malignant nephrosclerosis, defined as renal microangiopathy in the setting of severe hypertension, remains a critical renal emergency leading to end-stage renal disease despite aggressive anti-hypertensive treatment. Recently, activation of the complement alternative pathway (AP) has been reported to play a prominent role in the pathogenesis of malignant nephrosclerosis. However, subsequent study failed to recapitulate the findings of genetic complement abnormalities in the disease. This study aimed to determine the presence of AP activation and genetic complement defects and establish their correlations to renal microangiopathy lesions, clinical features and prognosis in patients with malignant nephrosclerosis.

Methods

Fifty patients with malignant hypertension and concomitant thrombotic microangiopathy (TMA) proven by renal biopsy were investigated; 25 cases of kidney donors who received zero-hour allograft biopsies were used as normal controls. Various renal TMA lesions in patients with malignant nephrosclerosis were reviewed and evaluated using a semi-quantitative scoring system. Deposition of C5b-9, C3a, C5a, C4d and mannose-binding lectin was assessed by immunohistochemistry. Co-localization of C5b-9 and CD34 was detected by confocal microscopy. Complement factor B (FB), factor P (FP; properdin), factor D (FD), factor H (FH), C3a and C5a levels were quantified by enzyme-linked immonosorbent assay in plasma and urine samples of patients with malignant nephrosclerosis and controls. Genetic abnormalities of complement components were analysed by whole-exome sequencing.

Results

Renal biopsies of malignant nephrosclerosis showed identical histopathological and ultrastructural features to atypical haemolytic uraemic syndrome. C5b-9, C3a and C5a deposits were found along the walls of arteries/arterioles and glomerular capillaries and localized in the endothelial cells. Elevated plasma and urinary levels of FB, FP, FD, C3a and C5a as well as decreased FH levels were observed in patients with malignant nephrosclerosis compared with normal controls. The urinary levels of complement AP components, but not the plasma levels, were correlated with renal functions, prognosis and active TMA lesions except for arteriolar thrombi. Finally, mutations of the MCP, CFB, CFH and CFHR5 genes were identified in 8 of 20 patients with malignant nephrosclerosis.

Conclusions

Aberrant complement AP dysregulation was demonstrated and associated with the activity, severity and renal outcomes of malignant nephrosclerosis. This observation warrants screening for complement defects in patients with malignant nephrosclerosis for the potential use of complement regulators and also highlights the need for further investigation of the precise role of AP in the pathogenesis of the disease.
Massive Fluid Influx beneath the Colorado Plateau (USA) Related to Slab Removal and Diatreme Emplacement: Evidence from Oxygen Isotope Zoning in Eclogite Xenoliths
Authors: Hoover William F , Page F Zeb , Schulze Daniel J , Kitajima Kouki , Valley John W
Published: October 2020

The Colorado Plateau has undergone as much as 1·8 km of uplift over the past 80 Myr, but never underwent the pervasive deformation common in the neighboring tectonic provinces of the western USA. To understand the source, timing and distribution of mantle hydration, and its role in plateau uplift, garnets from four eclogite xenoliths of the Moses Rock diatreme (Navajo Volcanic Field, Utah, USA) were analyzed in situ for δ18O by secondary ion mass spectrometry. These garnets have the largest reported intra-crystalline oxygen isotope zoning to date in mantle-derived xenoliths with core-to-rim variations of as much as 3 ‰. All samples have core δ18O values greater than that of the pristine mantle (∼5·3 ‰, mantle garnet as derived from mantle zircon in earlier work) consistent with an altered upper oceanic crust protolith. Oxygen isotope ratios decrease from core to rim, recording interaction with a low-δ18O fluid at high temperature, probably derived from serpentinite in the foundering Farallon slab. All zoned samples converge at a δ18O value of ∼6 ‰, regardless of core composition, suggesting that fluid infiltration was widely distributed. Constraints on the timing of this fluid influx, relative to diatreme emplacement, can be gained from diffusion modeling of major element zoning in garnet. Modeling using best estimates of peak metamorphic conditions (620 °C, 3·7 GPa) yields durations of <200 kyr, suggesting that fluid influx and diatreme emplacement were temporally linked. These eclogite xenoliths from the Colorado Plateau record extensive fluid influx, pointing to complex hydration–dehydration processes related to flat-slab subduction and foundering of the Farallon plate. Extensive hydration of the lithospheric mantle during this fluid influx may have contributed to buoyancy-driven uplift of the Colorado Plateau and melt-free emplacement of Navajo Volcanic Field diatremes.
Tilting Modules and Dominant Dimension with Respect to Injective Modules
Authors: Adachi Takahide , Tsukamoto Mayu
Published: October 2020

In this paper, we study a relationship between tilting modules with finite projective dimension and dominant dimension with respect to injective modules as a generalization of results of Crawley-Boevey–Sauter, Nguyen–Reiten–Todorov–Zhu and Pressland–Sauter. Moreover, we give characterizations of almost n-Auslander–Gorenstein algebras and almost n-Auslander algebras by the existence of tilting modules. As an application, we describe a sufficient condition for almost 1-Auslander algebras to be strongly quasi-hereditary by comparing such tilting modules and characteristic tilting modules.
RightPath: a model of community-based musculoskeletal care for children
Authors: Smith Nicola , Mercer Victoria , Firth Jill , Jandial Sharmila , Kinsey Katharine , Light Helen , Nye Alan , Rapley Tim , Foster Helen E
Published: October 2020

Objectives

Musculoskeletal (MSK) presentations are common (reported prevalence of one in eight children) and a frequent cause of consultations (6% of 7-year-olds in a cohort study from the UK). Many causes are self-limiting or raised as concerns about normal development (so-called normal variants). We aimed to describe a new model of care to identify children who might be managed in the community by paediatric physiotherapists and/or podiatrists rather than referral to hospital specialist services.

Methods

Using mixed methods, we tested the feasibility, acceptability and transferability of the model in two UK sites. Evaluation included patient flow, referral times, diagnosis and feedback (using questionnaires, focus groups and interviews).

Results

All general practitioner referrals for MSK presentations (in individuals <16 years of age) were triaged by nurses or allied health professionals using a triage guide; ∼25% of all MSK referrals were triaged to be managed by community-based paediatric physiotherapists/podiatrists, and most (67%) had a diagnosis of normal variants. Families reported high satisfaction, with no complaints or requests for onward specialist referral. No children re-presented to the triage service or with serious MSK pathology to hospital specialist services in the subsequent 6 months after triage. Triagers reported paediatric experience to be important in triage decision-making and case-based learning to be the preferred training format.

Conclusion

The triage model is acceptable, feasible and transferable to enable appropriate care in the community for a proportion of children with MSK complaints. This is a multi-professional model of better working together between primary community and specialist providers.
Between Emotional Involvement and Professional Detachment: The Challenges of Nursing in Dutch Mental Institutions (1880–1980)
Authors: Oosterhuis Harry , Aan de Stegge Cecile
Published: October 2020

This article is about the tension and changing balance between emotional involvement and professional detachment in the practice of nursing in Dutch mental institutions between the 1880s and 1990s. We address this issue in relation to institutional and material conditions, power differences between doctors, nurses and patients, different treatments, and the social marginalisation of hospitalised patients. On the basis of various sources (nursing textbooks, chronicles of skills learning by students, personal accounts, questionnaires and interviews), we describe how nurses were supposed to interact with patients and how they dealt with three sensitive issues: the need to use coercion in response to agitated patients, the sexual behaviour of patients and the risk of suicide in psychiatric institutions. We argue that nursing mental patients required a great deal of emotional work and that there was a shift from strict rules of behaviour imposed from above to more flexible self-regulation, guided by self-reflection.
Clinical application and mechanism of traditional Chinese medicine in treatment of lung cancer
Authors: Su Xiao-Lin , Wang Jiang-Wei , Che Hui , Wang Chang-Fu , Jiang Hai , Lei Xia , Zhao Wan , Kuang Hai-Xue , Wang Qiu-Hong
Published: October 2020

Lung cancer is a malignant tumor characterized by a rapid proliferation rate, less survivability, high mortality, and metastatic potential. This review focuses on updated research about the clinical application of traditional Chinese medicine (TCM) as an adjuvant therapy to lung cancer treatment and the mechanisms of TCM effect on lung cancer in vitro and in vivo. We summarized the recent 5 years of different research progress on clinical applications and antitumor mechanisms of TCM in the treatment of lung cancer. As a potent adjuvant therapy, TCM could enhance conventional treatments (chemotherapy, radiation therapy, and epidermal growth factor receptors [EGFRs] tyrosine kinase inhibitors [TKIs]) effects as well as provide synergistic effects, enhance chemotherapy drugs chemosensitivity, reverse drug resistance, reduce adverse reactions and toxicity, relieve patients’ pain and improve quality of life (QOL). After treating with TCM, lung cancer cells will induce apoptosis and/or autophagy, suppress metastasis, impact immune reaction, and therapeutic effect of EGFR-TKIs. Therefore, TCM is a promisingly potent adjuvant therapy in the treatment of lung cancer and its multiple mechanisms are worthy of an in-depth study.
Cross-sectional analysis tracking workforce density in surgery, anesthesia, and obstetrics as an indicator of progress toward improved global surgical access
Authors: Bouchard Megan E. , Justiniano Jeanine , Vervoort Dominique , Gore-Booth Julian , Emmanuel Adupa , Langer Monica
Published: October 2020

Introdution:

Safe surgical care, including anesthesia, obstetrics, and trauma, is an essential component of a functional health system, yet is lacking in much of the world. One indicator of surgical access is the number of specialist surgeons, anesthesiologists, and obstetricians (SAO) per 100,000 population, but global progress reaching threshold SAO density (SAOD) is unknown. This study measured SAOD change/trajectory and highlighted components of workforce expansion.

Methods:

SAOD in 2019 was captured utilizing publicly available medical licensing data for a convenience sample of 21 countries. Projected 2030 SAOD were estimated by extrapolating annual changes since 2015. Ugandan medical students were surveyed regarding postgraduate plans and SAO training availability. Workforce contribution by nonphysician surgical and anesthetic providers was measured in Sierra Leone.

Results:

Three low-income countries (LICs), 4 lower middle-income countries (L-MICs), 7 upper middle-income countries (UMICs), and 7 high-income countries (HICs) were included. Overall SAOD increased since 2015. The average 2019 SAOD was 1.16±0.81 (LICs), 3.19±1.92 (L-MICs), 20.98±12.55 (UMICs), and 44.04±12.41 (HICs). The projected 2030 SAOD in LICs and L-MICs remains below 20. In Uganda, 144 specialist SAO training positions and practice preferences predict an inadequate future workforce. In Sierra Leone, nonphysician providers contributed a 6-fold increase in the surgical workforce, though remains inadequate.

Conclusions:

Despite incremental positive changes since 2015, the current SAOD trajectory is inadequate to realize 2030 access goals. Increased training and retention of specialists and nonphysician providers are necessary to address this critical deficit.
Five-year trend of colorectal cancer incidence in B.P. Koirala Memorial Cancer Hospital of Central Nepal: a cross-sectional study
Authors: Shrestha Gambhir , Khanal Suman , Mulmi Rashmi , Sapkota Ganga
Published: October 2020

Background:

Colorectal cancer (CRC) is one of the most common cancers in the world including Nepal and has become a major public health issue. This study aims to describe the trend of CRC in a national tertiary cancer hospital in Nepal.

Materials and methods:

This was a cross-sectional study with secondary data analysis conducted at B.P. Koirala Memorial Hospital, Chitwan, Nepal. The data was obtained from the hospital cancer registry and included all new CRC cases registered during a period of 5 years from 2014 to 2018. Analysis was done with Statistical Package for Social Sciences version 20.

Results:

A total of 1129 new CRC cases were registered in the study period comprising 4.6% of total cancer cases. Out of which, 644 (57.0%) were males and 485 (43.0%) were females. The most common age group was 45–59 years. About 36% of CRC cases were of age under 45 years. Rectal cancer (50.0%) was the most common CRC with half of the total cases followed by colon (19.1%), and anal cancer (12.6%). There is an increase in the incidence of CRC with an average annual increase of 1.7% in under 45 years and 6.7% in 45 years and above.

Conclusions:

The incidence of CRC is increasing in Nepal with significant burden borne by younger age groups. Implementation of healthy lifestyle measures, awareness programs, along with routine screening should be implemented to control the burden of CRC in Nepal.
Fertility services in the United Kingdom: effect of COVID-19
Authors: Stewart Jane
Published: October 2020

This report highlights the key considerations for fertility services in the UK during the development of the COVID-19 pandemic.
Social connections and hypertension in women and men: a population-based cross-sectional study of the Canadian Longitudinal Study on Aging
Authors: Hosseini Zeinab , Veenstra Gerry , Khan Nadia A. , Conklin Annalijn I.
Published: October 2020

Background:

Associations between social ties and hypertension are poorly understood in women and men. We investigated the association between marital status, living arrangement, social network size and social participation and hypertension by sex/gender.

Methods:

Cross-sectional analysis of 28 238 middle-age and old-age adults (45–85 years) was conducted using the baseline Canadian Longitudinal Study on Aging Comprehensive cohort data. Blood pressure (BP) was measured using the automated BpTRU device and hypertension was defined as BP more than 140/90 mmHg, or more than 130/80 mmHg in participants with diabetes, self-reported history or receiving antihypertensive therapy.

Results:

Being nonpartnered, having limited social participation (≤2 social activities per month) or a small social network size was associated with higher odds of having hypertension in women. Odds of hypertension were higher among widowed women [odds ratio 1.33 (95% confidence interval (CI): 1.16, 1.51)] compared with married women. The largest difference in adjusted mean SBP in women was between widowed [3.06 mmHg (95% CI: 2.01, 4.11)], vs. married women. For men, lone-living (vs. coliving) was linked to a lower odds of hypertension [odds ratio 0.85 (95% CI: 0.75, 0.96)] When considering two social ties simultaneously, the adverse associations between nonpartnership (mainly for singles and divorced) and BP were mitigated with increased social participation, especially among women.

Conclusion:

Social ties appear to be more strongly associated with hypertension in middle and older aged women than men. Women who are nonpartnered or who engage in few social activities and men who are coliving represent at risk groups for having hypertension. Healthcare professionals may need to consider these social factors in addressing risk for hypertension and cardiovascular disease prevention.
Dignity
Authors: Mohammadi Fateme , Bijani Mostafa , Cheraghi Fatemeh , Kyle Hazel
Published: October 2020

One of the most important areas of nursing care delivery is “dignity.” Because of the increase in hospitalized infants in neonatal intensive care units in recent years, this has led to an increased focus on “family care and maternal dignity.” Given the importance of understanding the phenomenon of maternal dignity in order to improve cooperation in the care of their infants and promote family-centered care, this study aims to describe the lived experience of hospitalized mothers of infants within the context of dignity. This is a descriptive phenomenological qualitative research study. Twenty mothers were invited to participate in this study using purposeful sampling. The data were generated through individual, semistructured interviews and field notes were developed during the interviews. Data were analyzed using the Colaizzi method.

Findings of the study were presented in 3 themes: “privacy,” “respecting individual identity,” and “authority,” and 7 additional subthemes. Mothers in this study needed to take care of their infants in an environment where their personal privacy is preserved, their individual identity is respected, and they have sufficient authority in obtaining medical decisions. It is essential that healthcare teams and policy makers of health organizations provide an appropriate supportive environment in terms of promoting mothers' dignity in different dimensions and subsequently improving family-centered care.