bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon-dependent growth, community structure and methane oxidation performance of a soil-derived methanotrophic mixed culture
Authors: Praeg Nadine , Schachner Iris , Schuster Lisa , Illmer Paul
Published: December 2020

Soil-borne methane-oxidizing microorganisms act as a terrestrial methane (CH4) sink and are potentially useful in decreasing global CH4 emissions. Understanding the ecophysiology of methanotrophs is crucial for a thorough description of global carbon cycling. Here, we report the in situ balance of soils from abandoned landfills, meadows and wetlands, their capacities to produce and oxidize CH4 at laboratory-scale and the isolation of a soil-borne methanotrophic-heterotrophic mixed culture that was used for carbon (C1 and C2) feeding experiments. We showed that even with similar soil properties, the in situ CH4 balance depends on land-use. Different soils had different potentials to adapt to increased CH4 availability, leading to the highest CH4 oxidation capacities for landfill and wetland soils. The most efficient mixed culture isolated from the landfill was dominated by the methanotrophs Methylobacter sp. and Methylosinus sp., which were accompanied by Variovorax sp. and Pseudomonas sp. and remained active in oxidizing CH4 when supplied with additional C-sources. The ratios between type I and type II methanotrophs and between methanotrophic and heterotrophic bacteria changed when C-sources were altered. A significant effect of the application of the mixed culture on the CH4 oxidation of soils was established but the extent varied depending on soil type.
The within-host evolution of antimicrobial resistance in Mycobacterium tuberculosis
Authors: Castro Rhastin A D , Borrell Sonia , Gagneux Sebastien
Published: December 2020

Tuberculosis (TB) has been responsible for the greatest number of human deaths due to an infectious disease in general, and due to antimicrobial resistance (AMR) in particular. The etiological agents of human TB are a closely-related group of human-adapted bacteria that belong to the Mycobacterium tuberculosis complex (MTBC). Understanding how MTBC populations evolve within-host may allow for improved TB treatment and control strategies. In this review, we highlight recent works that have shed light on how AMR evolves in MTBC populations within individual patients. We discuss the role of heteroresistance in AMR evolution, and review the bacterial, patient and environmental factors that likely modulate the magnitude of heteroresistance within-host. We further highlight recent works on the dynamics of MTBC genetic diversity within-host, and discuss how spatial substructures in patients’ lungs, spatiotemporal heterogeneity in antimicrobial concentrations and phenotypic drug tolerance likely modulates the dynamics of MTBC genetic diversity in patients during treatment. We note the general characteristics that are shared between how the MTBC and other bacterial pathogens evolve in humans, and highlight the characteristics unique to the MTBC.
Evolutionary Plasticity of Mating-Type Determination Mechanisms inParamecium aureliaSibling Species
Authors: Sawka-Gądek Natalia , Potekhin Alexey , Singh Deepankar Pratap , Grevtseva Inessa , Arnaiz Olivier , Penel Simon , Sperling Linda , Tarcz Sebastian , Duret Laurent , Nekrasova Irina , Meyer Eric
Published: December 2020

The Paramecium aurelia complex, a group of morphologically similar but sexually incompatible sibling species, is a unique example of the evolutionary plasticity of mating-type systems. Each species has two mating types, O (Odd) and E (Even). Although O and E types are homologous in all species, three different modes of determination and inheritance have been described: genetic determination by Mendelian alleles, stochastic developmental determination, and maternally inherited developmental determination. Previous work in three species of the latter kind has revealed the key roles of the E-specific transmembrane protein mtA and its highly specific transcription factor mtB: type O clones are produced by maternally inherited genome rearrangements that inactivate either mtA or mtB during development. Here we show, through transcriptome analyses in five additional species representing the three determination systems, that mtA expression specifies type E in all cases. We further show that the Mendelian system depends on functional and nonfunctional mtA alleles, and identify novel developmental rearrangements in mtA and mtB which now explain all cases of maternally inherited mating-type determination. Epistasis between these genes likely evolved from less specific interactions between paralogs in the P. aurelia common ancestor, after a whole-genome duplication, but the mtB gene was subsequently lost in three P. aurelia species which appear to have returned to an ancestral regulation mechanism. These results suggest a model accounting for evolutionary transitions between determination systems, and highlight the diversity of molecular solutions explored among sibling species to maintain an essential mating-type polymorphism in cell populations.
Relationships Between Cognitive and Driving Self-awareness in Older Drivers
Authors: Paire-Ficout Laurence , Lafont Sylviane , Hay Marion , Coquillat Amandine , Fabrigoule Colette , Chavoix Chantal
Published: December 2020

Objectives

Many older drivers incorrectly estimate their driving ability. The present study aimed to determine whether, and if so, to what extent unawareness of cognitive abilities affects self-awareness of driving ability.

Method

Two successive studies were conducted in older drivers. A cohort study investigated cognitive self-awareness and an experimental study examined driving self-awareness. In each one, self-awareness was assessed by cross-analyzing objective (respectively Trail-Making Tests A and B and the Digit Symbol Substitution Test and driving performance of on-road assessment) and subjective data (responses about everyday cognitive skills and driving ability). Older drivers were then classified as being over-, correct, or underestimators. The 3 cognitive and driving self-awareness profiles were then cross-analyzed.

Results

In the cohort study, 1,190 drivers aged 70 years or older were included. The results showed that 42.7% of older drivers overestimated their cognitive ability, 42.2% estimated it correctly, and 15.1% underestimated it. The experimental study included 145 participants from the cohort. The results showed that 34% of participants overestimated, 45% correctly estimated, and 21% underestimated their driving ability. There was a significant relationship between cognitive and driving self-awareness profiles (p = .02). This overlap was more marked in overestimators.

Discussion

Significant overlap between cognitive and driving self-awareness provides useful and new knowledge about driving in the aging population. Misestimation of cognitive ability could hamper self-awareness of driving ability, and consequently self-regulation of driving. It is now crucial to develop measures that promote self-awareness of ability.
The Use of International Human Rights Law in the Universal Periodic Review
Authors: Shah Sangeeta , Sivakumaran Sandesh
Published: December 2020

Universal Periodic Review provides a unique insight into states’ perceptions of IHRL. States issue recommendations on fulfilling human rights obligations and commitments. HRC Resolution 5/1 sets out the bases of the reviews: the UN Charter, the UDHR, human rights instruments to which the state is party and voluntary pledges and commitments. Relevant IHL is ‘take[n] into account’. Analysing the identification of these bases of review and how they have been used in the 57,685 recommendations from the first two cycles of UPR, we demonstrate states’ understanding of the term ‘human rights’ and their preferences for certain sources of law. States have not limited themselves to the bases of review in Resolution 5/1. They have used additional materials and rejected distinctions between ‘hard’ and ‘soft’ law. They have interpreted the notion of ‘human rights’ expansively but largely ignored regional human rights instruments. A body of generalised, non-specific IHRL has been recognised.
Genetic stock identification of sea trout (Salmo trutta L.) along the British North Sea Coast shows prevalent long-distance migration
Authors: Bekkevold Dorte , Piper Adam , Campbell Ronald , Rippon Philip , Wright Ros M , Crundwell Charles , Wysujack Klaus , Stevens Jamie R , King R Andrew , Aarestrup Kim , Maltby Alistair
Published: December 2020

Knowledge of migration behaviour and spatio-temporal habitat use is important for management and conservation, not least for diadromous species where population dynamics are affected by processes occurring in both freshwater and marine habitats. Sampling from a commercial capture fishery for the ecologically and economically important salmonid Salmo trutta L. we genotyped 189 single nucleotide polymorphisms and carried out genetic assignment of origin for 916 migratory sea trout sampled along ∼500 km of Britain’s North Sea coast. Population contributions to stocks showed strong geographical differences. Trout from rivers in the northern part of this coast (Tweed, Aln, Coquet, and Tyne) contributed the majority of migrants, irrespective of location, but fish from local rivers contributed to catches in most locations. Almost all (99%) trout assigned to native British populations and a large proportion (34%) of the sampled catches originated in rivers more than 100 km from capture sites, suggesting long-distance migration to be a common trait, confirming and enlarging historical trends from tagging data. Repeated sampling across years indicated short-term stability in migration patterns. Findings illustrate the scope for genetic stock identification to identify marine habitat use and monitor population-specific migration behaviours in species where stock assessment has not traditionally incorporated marine phase dynamics.
Increased Prevalence of Liver Fibrosis in People Living With Human Immunodeficiency Virus Without Viral Hepatitis Compared to Population Controls
Authors: Kirkegaard-Klitbo Ditte Marie , Bendtsen Flemming , Lundgren Jens , de Knegt Robert J , Kofoed Klaus Fuglsang , Nielsen Susanne Dam , Benfield Thomas
Published: December 2020

Background

Liver fibrosis is associated with poor liver-related outcomes and mortality. People with human immunodeficiency virus (PWH) may be at increased risk. We aimed to estimate the prevalence and factors associated with liver fibrosis in PWH compared to population controls.

Methods

This was a cross-sectional cohort study comparing 342 PWH with 2190 population controls aged 50–70 years.

Transient elastography was performed and elevated liver stiffness measurement (LSM) defined as 7.6 kPa as a proxy for significant liver fibrosis. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were computed by logistic regression.

Results

The prevalence of elevated LSM was higher in PWH than in uninfected controls (12% vs 7%; P < .01). Human immunodeficiency virus (HIV) infection was independently associated with elevated LSM. In multivariate analysis, elevated LSM was associated with HIV (aOR, 1.84 [95% CI, 1.17–2.88]; P < .01); higher age (per decade: aOR, 3.34 [95% CI, 1.81–6.18]; P < .01); alanine aminotransferase (ALT) (per 10 IU/L: aOR, 1.25 [95% CI, 1.05–1.49]; P < .01); body mass index (BMI) (per 1 kg/m2: aOR, 1.17 [95% CI, 1.05–1.29]; P < .01), and previous exposure to didanosine (per year: aOR, 2.26 [95% CI, 1.01–5.06]; P = .04).

Conclusions

The prevalence of elevated LSM was higher in PWH compared to population controls. Higher age, BMI, ALT, previous exposure to didanosine, and positive HIV status were independently associated with higher odds of elevated LSM.
Modelling seasonal pasture growth and botanical composition at the paddock scale with satellite imagery
Authors: Ara Iffat , Harrison Matthew Tom , Whitehead Jason , Waldner François , Bridle Kerry , Gilfedder Louise , Marques da Silva José , Marques Francisco , Rawnsley Richard
Published: December 2020

Seasonal pasture monitoring can increase the efficiency of pasture utilization in livestock grazing enterprises. However, manual monitoring of pasture over large areas is often infeasible due to time and financial constraints. Here, we monitor changes in botanical composition in Tasmania, Australia, through application of supervised learning using satellite imagery (Sentinel-2). In the field, we measured ground cover and botanical composition over a 12-month period to develop a supervised classification approach used to identify pasture classes. Across seasons and paddocks, the approach predicted pasture classes with 75–81 % accuracy. Botanical composition varied seasonally in response to biophysical factors (primarily climate) and grazing behaviour, with seasonal highs in spring and troughs in autumn. Overall, we demonstrated that 10-m multispectral imagery can be reliably used to distinguish between pasture species as well as seasonal changes in botanical composition. Our results suggest that farmers and land managers should aim to quantify within-paddock variability rather than paddock average cover, because the extent and duration of very low ground cover puts the paddock/field at risk of adverse grazing outcomes, such as soil erosion and loss of pasture biomass, soil carbon and biodiversity. Our results indicate that satellite imagery can be used to support grazing management decisions for the benefit of pasture production and the improvement of environmental sustainability.
Pharmacokinetic/pharmacodynamic analysis of romidepsin used as an HIV latency reversing agent
Authors: Moltó José , Rosás-Umbert Miriam , Miranda Cristina , Manzardo Christian , Puertas Maria C , Ruiz-Riol Marta , López Miriam , Miró Jose M , Martinez-Picado Javier , Clotet Bonaventura , Brander Christian , Mothe Beatriz , Valle Marta
Published: December 2020

Objectives

To develop a population pharmacokinetic model for romidepsin given as an HIV latency reversing agent (LRA) and to explore the relationship between romidepsin exposure and its in vivo effects on viral gene expression and antiviral immunity.

Methods

A population pharmacokinetic analysis was performed in 15 HIV-1-infected patients who received three weekly infusions of romidepsin (5 mg/m2) within the BCN02 clinical trial. A full pharmacokinetic profile was obtained for each participant at the first dose, and additional samples thereafter. A population pharmacokinetic model was developed. Bayesian estimates of the individual pharmacokinetic parameters of romidepsin were used to simulate individual time–concentration curves on each occasion. The relationship between romidepsin AUC0–∞ and its in vivo effects was assessed.

Results

Romidepsin pharmacokinetics were best described by a three-compartment model with linear kinetics. Body weight influenced romidepsin disposition. A significant relationship was observed between romidepsin AUC0–∞ and increases in expression of exhaustion markers by CD4+ and CD8+ T cells and apoptosis markers in CD4+, but not with histone acetylation levels or HIV-1 cell-associated RNA in CD4+ T cells. For each increase of 100 ng·h/mL in romidepsin AUC0–∞, CD4+ counts decreased by a mean (95% CI) of 74 (42–94) cells/mm3 after dosing.

Conclusions

A population model describing the pharmacokinetics of romidepsin as an HIV LRA was developed. Higher exposure to romidepsin resulted in higher expression of apoptosis markers and declines in CD4+ count but did not increase viral reactivation levels. These observations have important implications for the optimization of effective kick-and-kill strategies for an HIV-1 cure.
Use of 3-nitrooxypropanol in a commercial feedlot to decrease enteric methane emissions from cattle fed a corn-based finishing diet
Authors: Alemu Aklilu W , Shreck Adam L , Booker Calvin W , McGinn Sean M , Pekrul Liana K D , Kindermann Maik , Beauchemin Karen A
Published: December 2020

The present study evaluated enteric CH4 production, dry matter (DM) intake (DMI), and rumen fermentation in feedlot cattle supplemented with increasing concentrations of 3-nitrooxypropanol (3-NOP). A total of 100 crossbred steers (body weight, 421 ± 11 kg) was randomly assigned to one of four treatments (n = 25/treatment): control (no 3-NOP) or low (100 mg/kg DM), medium (125 mg/kg DM), and high (150 mg/kg DM) doses of 3-NOP. The study was comprised of 28 d of adaptation followed by three 28-d periods, with CH4 measured for 7 d per period and cattle remaining on their respective diets throughout the 112-d study. Each treatment group was assigned to a pen, with the cattle and diets rotated among pens weekly to allow the animals to access the GreenFeed emission monitoring (GEM) system stationed in one of the pens for CH4 measurement. Measured concentration (mg/kg DM) of 3-NOP in the total diet consumed (basal diet + GEM pellet) was 85.6 for low, 107.6 for medium, and 124.5 for high doses of 3-NOP. There was a treatment × period interaction (P < 0.001) for DMI; compared with control, the DMI was less for the low and high doses in period 1, with no differences thereafter. Compared with control (10.78 g/kg DMI), CH4 yield (g/kg DMI) was decreased (P < 0.001) by 52%, 76%, and 63% for low, medium, and high doses of 3-NOP, respectively. A treatment × period effect (P = 0.048) for CH4 yield indicated that the low dose decreased in efficacy from 59% decrease in periods 1 and 2 to 37% decrease in period 3, while the efficacy of the medium and high doses remained consistent over time. Irrespective of dose, hydrogen emissions increased by 4.9-fold (P < 0.001), and acetate:propionate ratio in rumen fluid decreased (P = 0.045) with 3-NOP supplementation, confirming that other hydrogen-utilizing pathways become more important in the CH4-inhibited rumen. The study indicates that supplementation of corn-based finishing diets with 3-NOP using a medium dose is an effective CH4 mitigation strategy for commercial beef feedlots with a 76% decrease in CH4 yield. Further research is needed to determine the effects of 3-NOP dose on weight gain, feed conversion efficiency, and carcass characteristics of feedlot cattle at a commercial scale.
Nuclear grade and comedo necrosis of ductal carcinoma in situ as histopathological eligible criteria for the Japan Clinical Oncology Group 1505 trial: an interobserver agreement study
Authors: Tsuda Hitoshi , Yoshida Masayuki , Akiyama Futoshi , Ohi Yasuyo , Kinowaki Keiichi , Kumaki Nobue , Kondo Yuzuru , Saito Akihisa , Sasaki Eiichi , Nishimura Rieko , Fujii Satoshi , Homma Keiichi , Horii Rie , Murata Yuya , Itami Makiko , Kajita Sabine , Kato Hiroyuki , Kurosumi Masafumi , Sakatani Takashi , Shimizu Shigeki , Taniguchi Kohei , Tamiya Sadafumi , Nakamura Harumi , Kanbayashi Chizuko , Shien Tadahiko , Iwata Hiroji
Published: December 2020

Objective

The Japan Clinical Oncology Group 1505 trial is a single-arm multicentre prospective study that examined the possibility of non-surgical follow-up with endocrine therapy for patients with low-grade ductal carcinoma in situ. In that study, the eligible criteria included histopathological findings comprising low to intermediate nuclear grade and absence of comedo necrosis, and cases were entered according to the local histopathological diagnosis. Nuclear grade is largely based on the Consensus Conference criteria (1997), whereas comedo necrosis is judged according to the Rosen’s criteria (2017). The purpose of this study was to standardize and examine the interobserver agreement levels of these histopathological criteria amongst the participating pathologists.

Methods

We held slide conferences, where photomicrographs of haematoxylin–eosin-stained slides from 68 patients with ductal carcinoma in situ were presented using PowerPoint. The nuclear grade and comedo necrosis statuses individually judged by the pathologists were analysed using κ statistics.

Results

In the first and second sessions, where 22 cases each were presented, the interobserver agreement levels of nuclear grade whether low/intermediate grade or high grade were moderate amongst 29 and 24 participating pathologists, respectively (κ = 0.595 and 0.519, respectively). In the third session where 24 cases were presented, interobserver agreement levels of comedo necrosis or non-comedo necrosis were substantial amongst 25 participating pathologists (κ = 0.753).

Conclusion

Although the concordance rates in nuclear grade or comedo necrosis were not high in a few of the cases, we believe that these results could provide a rationale for employing the present criteria of nuclear grade and comedo necrosis in the clinical study of ductal carcinoma in situ.
Observation of an α-synuclein liquid droplet state and its maturation into Lewy body-like assemblies
Authors: Hardenberg Maarten C , Sinnige Tessa , Casford Sam , Dada Samuel , Poudel Chetan , Robinson Elizabeth A , Fuxreiter Monika , Kaminksi Clemens , Kaminski-Schierle Gabriele S , Nollen Ellen A A , Dobson Christopher M , Vendruscolo Michele
Published: December 2020

Misfolded α-synuclein is a major component of Lewy bodies, which are a hallmark of Parkinson’s disease. A large body of evidence shows that α-synuclein can aggregate into amyloid fibrils, but the relationship between α-synuclein self-assembly and Lewy body formation remains unclear. Here we show, both in vitro and in a Caenorhabditis elegans model of Parkinson’s disease, that α-synuclein undergoes liquid‒liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel with Lewy-body-like properties. This maturation process towards the amyloid state is delayed in the presence of model synaptic vesicles in vitro. Taken together, these results suggest that the formation of Lewy bodies may be linked to the arrested maturation of α-synuclein condensates in the presence of lipids and other cellular components.
Discovery and Surveillance of Tick-Borne Pathogens
Authors: Tokarz Rafal , Lipkin W Ian
Published: December 2020

Within the past 30 yr molecular assays have largely supplanted classical methods for detection of tick-borne agents. Enhancements provided by molecular assays, including speed, throughput, sensitivity, and specificity, have resulted in a rapid increase in the number of newly characterized tick-borne agents. The use of unbiased high throughput sequencing has enabled the prompt identification of new pathogens and the examination of tick microbiomes. These efforts have led to the identification of hundreds of new tick-borne agents in the last decade alone. However, little is currently known about the majority of these agents beyond their phylogenetic classification. Our article outlines the primary methods involved in tick-borne agent discovery and the current status of our understanding of tick-borne agent diversity.
Religious Accommodation in Bioethics and the Practice of Medicine
Authors: Smith William R , Audi Robert
Published: December 2020

Debates about the ethics of health care and medical research in contemporary pluralistic democracies often arise partly from competing religious and secular values. Such disagreements raise challenges of balancing claims of religious liberty with claims to equal treatment in health care. This paper proposes several mid-level principles to help in framing sound policies for resolving such disputes. We develop and illustrate these principles, exploring their application to conscientious objection by religious providers and religious institutions, accommodation of religious priorities in biomedical research, and treatment of patients’ religious views in doctor–patient encounters. Given that no sound set of guiding principles yields precise solutions for every policy dispute, we explore how morally sound democracies might deliberatively resolve such policy issues, following our proposed principles. Taken together and carefully interpreted, these principles may help in guiding difficult decision making in the indefinitely large realm where government, medical providers, and patients encounter problems concerning religion and medicine.
Effect of Personalized Breast Cancer Risk Tool on Chemoprevention and Breast Imaging: ENGAGED-2 Trial
Authors: Wernli Karen J , Knerr Sarah , Li Tengfei , Leppig Kathleen , Ehrlich Kelly , Farrell David , Gao Hongyuan , Bowles Erin J A , Graham Amanda L , Luta George , Jayasekera Jinani , Mandelblatt Jeanne S , Schwartz Marc D , O’Neill Suzanne C
Published: December 2020

Background

Limited evidence exists about how to communicate breast density-informed breast cancer risk to women at elevated risk to motivate cancer prevention.

Methods

We conducted a randomized controlled trial evaluating a web-based intervention incorporating personalized breast cancer risk, information on chemoprevention, and values clarification on chemoprevention uptake vs active control. Eligible women aged 40-69 years with normal mammograms and elevated 5-year breast cancer risk were recruited from Kaiser Permanente Washington from February 2017 to May 2018. Chemoprevention uptake was measured as any prescription for raloxifene or tamoxifen within 12 months from baseline in electronic health record pharmacy data. Secondary outcomes included breast magnetic resonance imaging (MRI), mammography use, self-reported distress, and communication with providers. We calculated unadjusted odds ratios (ORs) using logistic regression models and mean differences using analysis of covariance models with 95% confidence intervals (CIs) with generalized estimating equations.

Results

We randomly assigned 995 women to the intervention arm (n = 492) or control arm (n = 503). The intervention (vs control) had no effect on chemoprevention uptake (OR = 1.04, 95% CI = 0.07 to 16.62). The intervention increased breast MRI use (OR = 5.65, 95% CI = 1.61 to 19.74) while maintaining annual mammography (OR = 0.98, 95% CI = 0.75 to 1.28). Women in the intervention (vs control) arm had 5.67-times higher odds of having discussed chemoprevention or breast MRI with provider by 6 weeks (OR = 5.67, 95% CI = 2.47 to 13.03) and 2.36-times higher odds by 12 months (OR = 2.36, 95% CI = 1.65 to 3.37). No measurable differences in distress were detected.

Conclusions

A web-based, patient-level intervention activated women at elevated 5-year breast cancer risk to engage in clinical discussions about chemoprevention, but uptake remained low.
Chylous ascites following elective abdominal aortic aneurysm repair
Authors: Bowden Sylvie , Firdouse Mohammed , Roche-Nagle Graham
Published: December 2020

Postoperative chylous ascites is a rare complication of abdominal surgery. Chyle depletion results in nutritional, immunologic and metabolic deficiencies, making it a serious and potentially life-threatening condition for which prompt diagnosis and management is imperative. A 72-year-old male was referred for open repair of a 62 cm juxtarenal abdominal aortic aneurysm (AAA). Following resumption of diet, he developed abdominal distention. Therapeutic paracenteses confirmed chylous ascites. Failed conservative management and lymphatic embolization lead to surgical sealance of lymphatic leak using glue. Postoperatively, a full diet was tolerated with no further ascites. Paracentesis is the diagnostic modality of choice in evaluating patients with ascites. Management is challenging and should be multifaceted and tailored to individual patient needs. Cornerstones of therapy include correction of the underlying etiology and conservative measures. When conservative measures fail, other interventions can be considered, such as somatostatin analogs, surgical ligation or glue embolization.
Bilateral traumatic distal femoral transphyseal fracture in a 9-year-old male
Authors: Davis Timothy P , Mehta Rujuta , Agrawal Arpit
Published: December 2020

A case of bilateral traumatic distal femoral Salter-Harris Type I fracture presented to our emergency department. History was of a 9-year-old male playing at a building site when a concrete block fell from height on to his knees, which were extended in a sitting position. Management was with analgesia and transfer to theatre followed by closed reduction and internal fixation—position was assessed under mobile X-ray. The patient made a full clinical recovery within 18 weeks and was followed-up over 5 years. There was no clinical effect on final adult length of femur and no deficit in range of movement. The foot-drop observed at presentation resolved over a period of 12 weeks. This case highlights the importance of performing a thorough neurovascular examination of the patient at presentation, followed by a careful closed reduction and internal fixation under anaesthesia, being careful not to damage the distal femoral growth plates.
Access-based intuitionistic knowledge
Authors: Lewitzka Steffen
Published: December 2020

We introduce the concept of $\textit{access-based}$ intuitionistic knowledge which relies on the intuition that agent $i$ knows $\varphi$ if $i$ has found $\textit{access to a proof}$ of $\varphi$. Basic principles are distribution and factivity of knowledge as well as $\square\varphi\rightarrow K_i\varphi$ and $K_i(\varphi\vee\psi) \rightarrow (K_i\varphi\vee K_i\psi)$, where $\square\varphi$ reads $`\varphi$ is proved'. The formalization extends a family of classical modal logics (Lewitzka, 2017, Journal of Logic and Computation, 27, 201--212) designed as combinations of $\mathit{IPC}$ and $\mathit{CPC}$ and as systems for the reasoning about proof, i.e. intuitionistic truth. We adopt a formalization of common knowledge from (Lewitzka, 2011, Studia Logica, 97, 233--264) and interpret it here as access-based common knowledge. We compare our proposal with recent approaches to intuitionistic knowledge (Artemov and Protopopescu, 2016, The Review of Symbolic Logic, 9, 266--298; Lewitzka, 2019, Annals of Pure and Applied Logic, 170, 218--250) and bring together these different concepts in a unifying semantic framework based on Heyting algebra expansions.
Congenital atrioventricular block: clinical presentation, clinical evaluation, and management
Authors: Fabrizio Drago , Irma Battipaglia
Published: December 2020

Congenital atrioventricular block (CAVB) is a cardiac conduction disorder that is diagnosed in utero, at birth, or within the first month of life. When it is diagnosed between the first month and the 18th year of life, it is defined as childhood atrioventricular (AV) block. CAVB may occur in association with concomitant congenital heart disease, or be isolated, in a structurally normal heart (e.g. immune-mediated, inherited, or idiopathic CAVB). The majority of isolated CAVB is an immune-mediated AV block, due to transplacental passage of maternal autoantibodies, damaging the fetal cardiac conduction system. Only in a third of infants with immune-mediated CAVB is a well-defined autoimmune disease known in the mother. During fetal life, fetal echocardiography still represents the gold standard for the diagnosis of CAVB. Two major negative prognostic markers are low ventricular rate and the appearance of foetal hydrops. As regards prognosis, a risk for heart failure, syncope, and sudden death is present both during fetal and postnatal life. Dilated cardiomyopathy represents another complication in CAVB history, with different possible aetiologies (right ventricular permanent pacing, reactivation of autoimmune myocarditis). The indications for pacemaker implantation in patients with CAVB are similar to those for acquired heart disease, with some special technical considerations due to young age (epicardial versus endocardial systems, pacing site, etc.). As a future perspective, leadless cardiac stimulation in children with CAVB may represent a definitive solution and an answer to many questions.
Mitral regurgitation
Authors: Rosenhek Raphael , De Bonis Michele
Published: December 2020

Mitral regurgitation is the second most frequent indication for valve surgery in Europe. Echocardiography is essential to assess the aetiology of mitral regurgitation, as well as valve anatomy and function. An integrative approach is needed to assess the severity of mitral regurgitation. Indication for intervention in primary mitral regurgitation is guided by symptoms and risk stratification that includes the assessment of ventricular function and size, atrial fibrillation, systolic pulmonary pressure, and LA size. Surgical mitral valve repair is the preferred method of treatment, particularly in degenerative mitral regurgitation due to its excellent early and late results. However outcomes depend on surgeon experience and centre-related volume. In secondary mitral regurgitation, there is no conclusive evidence for a survival benefit after mitral valve intervention. Mitral surgery is recommended concomitantly in patients with an indication for coronary surgery. Percutaneous edge-to-edge repair may be considered in patients at high surgical risk, avoiding futility.
Greater Severity and Functional Impact of Post-traumatic Headache in Veterans With Comorbid Neck Pain Following Traumatic Brain Injury
Authors: Shahidi Bahar , Bursch Robyn W , Carmel Jennifer S , Carranza Ashleigh C , Cooper Kelsey M , Lee Jayme V , O’Connor Colleen N , Sorg Scott F , Maluf Katrina S , Schiehser Dawn M
Published: December 2020

Background

Post-traumatic headache (PTH) is a commonly experienced symptom after mild traumatic brain injury (mTBI). Blast injury– or blunt injury–related mechanisms for mTBI in veterans can also affect musculoskeletal structures in the neck, resulting in comorbid neck pain (NP). However, it is unknown whether the presence of comorbid NP may be associated with a different pattern of headache symptoms, physical functioning, or emotional functioning compared to those without comorbid NP. The purpose of this study is to examine the role of comorbid NP in veterans with mTBI and PTH.

Design and Methods

This was a cross-sectional investigation of an existing dataset that included 33 veterans who met inclusion criteria for PTH after mTBI. Standardized measures of headache severity and frequency, insomnia, fatigue, mood disorders, and physical and emotional role function were compared between groups with and without comorbid NP.

Results

The majority of participants with PTH reported comorbid NP (n = 22/33, 67%). Those with comorbid NP experienced more headache symptoms that were severe or incapacitating, as compared to mild or moderate for those without NP (φ = 0.343, P = .049); however, no differences in headache frequency (φ = 0.231, P = .231) or duration (φ = 0.129, P = .712) were observed. Participants with comorbid NP also reported greater insomnia (d = 1.16, P = .003) and fatigue (d = 0.868, P = .040) as well as lower physical functioning (d = 0.802, P = .036) and greater bodily pain (d = 0.762, P = .012). There were no differences in anxiety, depression, mental health, emotional role limitations, vitality, or social functioning between those with and without comorbid NP (d ≤ 0.656, P ≥ .079).

Conclusions

A majority of veterans with mTBI and PTH in our sample reported comorbid NP that was associated with greater headache symptom severity and physical limitations, but not with mood or emotional limitations. Preliminary findings from this small convenience sample indicate that routine assessment of comorbid NP and associated physical limitations should be considered in veterans with mTBI and PTH.
Exploring the link between C iv outflow kinematics and sublimation-temperature dust in quasars
Authors: Temple Matthew J , Banerji Manda , Hewett Paul C , Rankine Amy L , Richards Gordon T
Published: December 2020

Using data from SDSS, UKIDSS, and WISE, we investigate the properties of the high-frequency cutoff to the infrared emission in ≃5000 carefully selected luminous (Lbol ∼ 1047) type 1 quasars. The strength of ≃2 μm emission, corresponding to emission from the hottest ($T\gt 1200\rm \, K$) dust in the sublimation zone surrounding the central continuum source, is observed to correlate with the blueshift of the C iv λ1550 emission line. We therefore find that objects with stronger signatures of nuclear outflows tend to have a larger covering fraction of sublimation-temperature dust. When controlling for the observed outflow strength, the hot dust covering fraction does not vary significantly across our sample as a function of luminosity, black hole mass, or Eddington fraction. The correlation between the hot dust and the C iv line blueshifts, together with the lack of correlation between the hot dust and other parameters, therefore provides evidence of a link between the properties of the broad emission line region and the infrared-emitting dusty regions in quasars.
A homogeneous measurement of the delay between the onsets of gas stripping and star formation quenching in satellite galaxies of groups and clusters
Authors: Oman Kyle A , Bahé Yannick M , Healy Julia , Hess Kelley M , Hudson Michael J , Verheijen Marc A W
Published: December 2020

We combine orbital information from N-body simulations with an analytic model for star formation quenching and SDSS observations to infer the differential effect of the group/cluster environment on star formation in satellite galaxies. We also consider a model for gas stripping, using the same input supplemented with H i fluxes from the ALFALFA survey. The models are motivated by and tested on the Hydrangea cosmological hydrodynamical simulation suite. We recover the characteristic times when satellite galaxies are stripped and quenched. Stripping in massive ($M_{\rm vir}\sim 10^{14.5}\, {\rm M}_\odot$) clusters typically occurs at or just before the first pericentric passage. Lower mass ($\sim 10^{13.5}\, {\rm M}_\odot$) groups strip their satellites on a significantly longer (by $\sim 3\, {\rm Gyr}$) time-scale. Quenching occurs later: Balmer emission lines typically fade $\sim 3.5\, {\rm Gyr}$ ($5.5\, {\rm Gyr}$) after first pericentre in clusters (groups), followed a few hundred Myr later by reddenning in (g − r) colour. These ‘delay time-scales’ are remarkably constant across the entire satellite stellar mass range probed (∼109.5–$10^{11}\, {\rm M}_\odot$), a feature closely tied to our treatment of ‘group pre-processing’. The lowest mass groups in our sample ($\sim 10^{12.5}\, {\rm M}_\odot$) strip and quench their satellites extremely inefficiently: typical time-scales may approach the age of the Universe. Our measurements are qualitatively consistent with the ‘delayed-then-rapid’ quenching scenario advocated for by several other studies, but we find significantly longer delay times. Our combination of a homogeneous analysis and input catalogues yields new insight into the sequence of events leading to quenching across wide intervals in host and satellite mass.
The role of Wnt signaling in male reproductive physiology and pathology
Authors: Xue Ruizhi , Lin Wenfeng , Sun Jingkai , Watanabe Masami , Xu Abai , Araki Motoo , Nasu Yasutomo , Tang Zhengyan , Huang Peng
Published: December 2020

Accumulating evidence has shown that Wnt signaling is deeply involved in male reproductive physiology, and malfunction of the signal path can cause pathological changes in genital organs and sperm cells. These abnormalities are diverse in manifestation and have been constantly found in the knockout models of Wnt studies. Nevertheless, most of the research solely focused on a certain factor in the Wnt pathway, and there are few reports on the overall relation between Wnt signals and male reproductive physiology. In our review, Wnt findings relating to the reproductive system were sought and summarized in terms of Wnt ligands, Wnt receptors, Wnt intracellular signals and Wnt regulators. By sorting out and integrating relevant functions, as well as underlining the controversies among different reports, our review aims to offer an overview of Wnt signaling in male reproductive physiology and pathology for further mechanistic studies.
NOPCHAP1 is a PAQosome cofactor that helps loading NOP58 on RUVBL1/2 during box C/D snoRNP biogenesis
Authors: Abel Yoann , Paiva Ana C F , Bizarro Jonathan , Chagot Marie-Eve , Santo Paulo E , Robert Marie-Cécile , Quinternet Marc , Vandermoere Franck , Sousa Pedro M F , Fort Philippe , Charpentier Bruno , Manival Xavier , Bandeiras Tiago M , Bertrand Edouard , Verheggen Céline
Published: December 2020

The PAQosome is a large complex composed of the HSP90/R2TP chaperone and a prefoldin-like module. It promotes the biogenesis of cellular machineries but it is unclear how it discriminates closely related client proteins. Among the main PAQosome clients are C/D snoRNPs and in particular their core protein NOP58. Using NOP58 mutants and proteomic experiments, we identify different assembly intermediates and show that C12ORF45, which we rename NOPCHAP1, acts as a bridge between NOP58 and PAQosome. NOPCHAP1 makes direct physical interactions with the CC-NOP domain of NOP58 and domain II of RUVBL1/2 AAA+ ATPases. Interestingly, NOPCHAP1 interaction with RUVBL1/2 is disrupted upon ATP binding. Moreover, while it robustly binds both yeast and human NOP58, it makes little interactions with NOP56 and PRPF31, two other closely related CC-NOP proteins. Expression of NOP58, but not NOP56 or PRPF31, is decreased in NOPCHAP1 KO cells. We propose that NOPCHAP1 is a client-loading PAQosome cofactor that selects NOP58 to promote box C/D snoRNP assembly.
Analyzing genomic data using tensor-based orthogonal polynomials with application to synthetic RNAs
Authors: Nafees Saba , Rice Sean H , Wakeman Catherine A
Published: December 2020

An important goal in molecular biology is to quantify both the patterns across a genomic sequence and the relationship between phenotype and underlying sequence. We propose a multivariate tensor-based orthogonal polynomial approach to characterize nucleotides or amino acids in a given sequence and map corresponding phenotypes onto the sequence space. We have applied this method to a previously published case of small transcription activating RNAs. Covariance patterns along the sequence showcased strong correlations between nucleotides at the ends of the sequence. However, when the phenotype is projected onto the sequence space, this pattern does not emerge. When doing second order analysis and quantifying the functional relationship between the phenotype and pairs of sites along the sequence, we identified sites with high regressions spread across the sequence, indicating potential intramolecular binding. In addition to quantifying interactions between different parts of a sequence, the method quantifies sequence–phenotype interactions at first and higher order levels. We discuss the strengths and constraints of the method and compare it to computational methods such as machine learning approaches. An accompanying command line tool to compute these polynomials is provided. We show proof of concept of this approach and demonstrate its potential application to other biological systems.
Unique challenges for glioblastoma immunotherapy—discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank
Authors: Chuntova Pavlina , Chow Frances , Watchmaker Payal B , Galvez Mildred , Heimberger Amy B , Newell Evan W , Diaz Aaron , DePinho Ronald A , Li Ming O , Wherry E John , Mitchell Duane , Terabe Masaki , Wainwright Derek A , Berzofsky Jay A , Herold-Mende Christel , Heath James R , Lim Michael , Margolin Kim A , Chiocca E Antonio , Kasahara Noriyuki , Ellingson Benjamin M , Brown Christine E , Chen Yvonne , Fecci Peter E , Reardon David A , Dunn Gavin P , Liau Linda M , Costello Joseph F , Wick Wolfgang , Cloughesy Timothy , Timmer William C , Wen Patrick Y , Prins Robert M , Platten Michael , Okada Hideho
Published: December 2020

Cancer immunotherapy has made remarkable advances with over 50 separate Food and Drug Administration (FDA) approvals as first- or second-line indications since 2015. These include immune checkpoint blocking antibodies, chimeric antigen receptor-transduced T cells, and bispecific T-cell–engaging antibodies. While multiple cancer types now benefit from these immunotherapies, notable exceptions thus far include brain tumors, such as glioblastoma. As such, it seems critical to gain a better understanding of unique mechanistic challenges underlying the resistance of malignant gliomas to immunotherapy, as well as to acquire insights into the development of future strategies. An Immuno-Oncology Think Tank Meeting was held during the 2019 Annual Society for Neuro-Oncology Scientific Conference. Discussants in the fields of neuro-oncology, neurosurgery, neuro-imaging, medical oncology, and cancer immunology participated in the meeting. Sessions focused on topics such as the tumor microenvironment, myeloid cells, T-cell dysfunction, cellular engineering, and translational aspects that are critical and unique challenges inherent with primary brain tumors. In this review, we summarize the discussions and the key messages from the meeting, which may potentially serve as a basis for advancing the field of immune neuro-oncology in a collaborative manner.
Direct observation and manipulation of hot electrons at room temperature
Authors: Wang Hailu , Wang Fang , Xia Hui , Wang Peng , Li Tianxin , Li Juzhu , Wang Zhen , Sun Jiamin , Wu Peisong , Ye Jiafu , Zhuang Qiandong , Yang Zaixing , Fu Lan , Hu Weida , Chen Xiaoshuang , Lu Wei
Published: December 2020

In modern electronics and optoelectronics, hot electron behaviors are highly concerned, as they determine the performance limit of a device or system, like the associated thermal or power constraint of chips and the Shockley-Queisser limit for solar cell efficiency. To date, however, the manipulation of hot electrons has been mostly based on conceptual interpretations rather than a direct observation. The problem arises from a fundamental fact that energy-differential electrons are mixed up in real-space, making it hard to distinguish them from each other by standard measurements. Here we demonstrate a distinct approach to artificially (spatially) separate hot electrons from cold ones in semiconductor nanowire transistors, which thus offers a unique opportunity to observe and modulate electron occupied state, energy, mobility and even path. Such a process is accomplished through the scanning-photocurrent-microscopy measurements by activating the intervalley-scattering events and 1D charge-neutrality rule. Findings here may provide a new degree of freedom in manipulating non-equilibrium electrons for both electronic and optoelectronic applications.