bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Study of an 86-Year-Old Pilates Participant After Experiencing an Injury-Causing Fall
Authors: Sunderland Janet
Published: January 2021

A long-term, consistent 86-year-old Pilates participant suffered an injury-inducing fall while on vacation and returned to full function and all former activities after a very short outpatient rehabilitation period. Lifestyle factors, including her Pilates participation, are believed to have potentially played a role in her positive experience postfall.
Gabapentin-Induced Myokymia: A Case Report
Authors: Brown Alexander , Esechie Aimalohi , Gogia Bhanu , Shanina Elena
Published: January 2021

Background

Gabapentin is a commonly used medication for neuropathic pain and epilepsy that is prescribed by a wide range of medical specialties. Adverse effects including asterixis and myoclonus have been described in patients with chronic kidney disease, but myokymia has not been previously reported.

Case Presentation

A 69-year-old man with a history of traumatic brain injury, peripheral neuropathy, amnesia, and posttraumatic stress disorder presented to the hospital after multiple falls attributed to acute onset muscle spasms. He reported taking a total daily dose of 9600 mg of gabapentin, as prescribed. Physical examination demonstrated stimulus-sensitive myoclonus, painful muscle spasms in all extremities, and myokymia in his bilateral calves. Diffuse action tremors, as well as tongue tremors, were also observed.

Initial workup, including basic laboratory investigations, brain imaging, and electroencephalogram, was unrevealing. Gabapentin toxicity was suspected, and a gabapentin holiday was initiated with the improvement of myokymia by hospital day 3. The patient was found to have a high gabapentin level (25.8 μg/mL; reference range, 2.0–20.0 μg/mL) measured the morning after hospital presentation. After restarting on a lower dose of gabapentin with multimodal pain control, the patient continued to improve with diminution of his myoclonus, tremor, and gait instability.

Conclusions

Myokymia is a newly described motor symptom associated with gabapentin toxicity. The mechanism of gabapentin-associated myokymia is currently unknown. A brief medication holiday resulted in the resolution of motor symptoms without significant withdrawal symptoms. Knowledge of this newly reported adverse manifestation can aid physicians in the diagnosis of gabapentin toxicity and prompt treatment, as gabapentin levels are not widely or immediately available.
Thirteen independent genetic loci associated with preserved processing speed in a study of cognitive resilience in 330,097 individuals in the UK Biobank
Authors: Fitzgerald Joan , Fahey Laura , Holleran Laurena , Broin Pilib Ó , Donohoe Gary , Morris Derek W.
Published: January 2021

Cognitive resilience is the ability to withstand the negative effects of stress on cognitive functioning and is important for maintaining quality of life while aging. UK Biobank (UKB) does not have direct measurements of the same cognitive phenotype at distal timepoints. Therefore, we used number of education years (EY) as a proxy phenotype for past cognitive performance. Current cognitive performance was determined based on processing speed. This approach captured an average time span of 40 years between past and current cognitive performance in 330,097 individuals. A confounding factor was that EY is highly polygenic and masked the genetics of resilience. To overcome this, we employed Genomics Structural Equation Modelling (GenomicSEM) to perform a GWAS-by-subtraction using two GWAS, one GWAS of EY and resilience and a second GWAS of EY but not resilience. Subtracting one from the other generated a GWAS ofResilience. Replication of this approach was shown using independent discovery and replication samples within UKB and the full UKB GWAS results show significant genetic correlation with a GWAS of cognitive change in the independent Health and Retirement Study (N=9,526;P=1.5×10−3). We found 13 independent genetic loci forResilience. Functional analyses showed enrichment in several brain regions and involvement of specific cell types, including GABAergic neurons (P=6.59×10−8) and glutamatergic neurons (P=6.98×10−6) in the cortex. Gene-set analyses implicated the biological process “neuron differentiation” (P=9.7×10−7) and the cellular component “synaptic part” (P=2.14×10−6). Mendelian randomization analysis showed a causative effect of white matter volume on cognitive resilience. These results enhance neurobiological understanding of resilience.
Materials in action: The look and feel of soft
Authors: Cavdan Müge , Drewing Knut , Doerschner Katja
Published: January 2021

The softness of objects can be perceived through several senses. For instance, to judge the softness of our cat’s fur, we do not only look at it, we also run our fingers in idiosyncratic ways through its coat. Recently, we have shown that haptically perceived softness covaries with the compliance, viscosity, granularity, and furriness of materials (Dovencioglu et al.,2020). However, it is unknown whether vision can provide similar information about the various aspects of perceived softness. Here, we investigated this question in an experiment with three conditions: in the haptic condition, blindfolded participants explored materials with their hands, in the visual-static condition participants were presented with close-up photographs of the same materials, and in the visual-dynamic condition participants watched videos of the hand-material interactions that were recorded in the haptic condition. After haptically or visually exploring the materials participants rated them on various attributes. Our results show a high overall perceptual correspondence between the three experimental conditions. With a few exceptions, this correspondence tended to be strongest between haptic and visual-dynamic conditions. These results are discussed with respect to information potentially available through the senses, or through prior experience, when judging the softness of materials.
Category-specific item encoding in the medial temporal lobe and beyond: The role of reward
Authors: Schultz Heidrun , Yoo Jungsun , Meshi Dar , Heekeren Hauke R.
Published: January 2021

Forming new memories is a fundamental part of human life, and the medial temporal lobe (MTL) is central to memory formation. Recent research suggests that within MTL, the perirhinal and parahippocampal cortices (PRC, PHC) process object and scene memory, respectively, whereas the hippocampus (HC) is agnostic to stimulus category. It is unclear, however, whether MTL category specificity extends to item encoding. Furthermore, MTL does not act in isolation: Reward-related memories are formed in interplay with the dopaminergic midbrain (substantia nigra/ventral tegmental area, SNVTA) and amygdala (AMY), but it is unclear whether reward modulates neural item encoding in a category-specific way. To address these questions, we had 39 healthy volunteers (27 for all memory-based analyses) undergo functional magnetic resonance imaging while they solved an incidental encoding task, which paired objects or scenes with high or low reward, followed by a next-day surprise recognition test. Behaviourally, high reward preferably enhanced object memory. Importantly, neural activity in PRC and PHC reflected item encoding of objects and scenes, respectively. Moreover, AMY encoding effects were selective for high-reward objects, with a similar pattern in PRC. SNVTA and HC showed no clear evidence of item encoding. The behavioural and neural asymmetry of reward-related encoding effects may be conveyed through an anterior-temporal memory system, including AMY and PRC, potentially in interplay with the ventromedial prefrontal cortex (vmPFC).
Comparative genomics of emerging lineages and mobile resistomes of contemporary broiler strains ofSalmonellaInfantis andE. coli
Authors: Szmolka Ama , Wami Haleluya , Dobrindt Ulrich
Published: January 2021

Introduction

Commensal and pathogenic strains of MDREscherichia coliand non-typhoid strains ofSalmonellarepresent a growing foodborne threat from foods of poultry origin. MDR strains ofS. Infantis andE. coliare frequently isolated from broiler chicks and the simultaneous presence of these two enteric bacterial species would potentially allow the exchange of mobile resistance determinants.

Objectives

In order to understand possible genomic relations and to obtain a first insight into the potential interplay of resistance genes between enteric bacteria, we compared genomic diversity and mobile resistomes ofS. Infantis andE. colifrom broiler sources.

Results

The cgMLST analysis of 56S. Infantis and 90E. colicontemporary strains revealed a high genomic heterogeneity of broilerE. coli. It also allowed the first insight into the genomic diversity of the MDR clone B2 ofS. Infantis, which is endemic in Hungary. We also identified new MDR lineages forS. Infantis (ST7081 and ST7082) and forE. coli(ST8702 and ST10088). Comparative analysis of antibiotic resistance genes and plasmid types revealed a relatively narrow interface between the mobile resistomes ofE. coliandS. Infantis. The mobile resistance genestet(A), aadA1andsul1were identified at an overall high prevalence in both species. This gene association is characteristic to the plasmid pSI54/04 of the epidemic clone B2 ofS. Infantis. Simultaneous presence of these genes and of IncI and IncX plasmids in cohabitant caecal strains ofE. coliandS. Infantis suggests an important role of these plasmids in a possible interplay of resistance genes betweenS. Infantis andE. coliin broilers.

Conclusions

This is the first comparative genomic analysis of contemporary broiler strains ofS. Infantis andE. coli. The diversity of mobile resistomes suggests that commensalE. colicould be potential reservoirs of resistance forS. Infantis, but so far only a few plasmid types and mobile resistance genes could be considered as potentially exchangeable between these two species. Among these, IncI plasmids could make the greatest contribution to the microevolution and genetic interaction betweenE. coliandS. Infantis.
Don't be a Drag, Just be a Priest: The Clothing and Identity of the Galli of Cybele in the Roman Republic and Empire
Authors: Mowat Chris
Published: January 2021

This paper explores the clothing and representation of the galli priests of Cybele in late Republican and early Imperial Rome. The galli were male‐bodied, but practiced self‐castration and wore traditionally feminine clothing and makeup, which the article argues placed them outside any expected gender binary and allowed them to inhabit a non‐binary identity. The article applies contemporary drag theory and the relationship between clothing and identity, particularly in respect of (assumed) incongruity, to explore the ways in which the galli's identity is visible in the Roman world. In the final section, a case study is made of the way the galli are represented in Lucian of Samosata's On the Syrian Goddess.
Addressing the Ongoing Humanitarian and Environmental Consequences of Nuclear Weapons: An Introductory Review
Authors: Bolton Matthew B. , Minor Elizabeth
Published: January 2021

The use and testing of nuclear weapons caused transnational and catastrophic humanitarian and environmental consequences. Legacies of more than 2,000 nuclear detonations in the territories of 15 states persist today, with serious implications for human rights and sustainable development. There is an inadequate global policy architecture for addressing the humanitarian and environmental consequences of nuclear weapons. However, the Treaty on the Prohibition of Nuclear Weapons (TPNW), adopted by 122 states at the UN in 2017, established obligations to assist victims of nuclear weapons and testing and remediate contaminated environments. Other global policymaking bodies have also mandated action on such concerns. In this review article, introducing a Special Section on ‘Addressing the Humanitarian and Environmental Consequences of Nuclear Weapons’, we provide a global overview of the facts about past nuclear weapons activities in different countries and some of the known and potential ongoing consequences of the blast, heat and radioactive energy released by past nuclear weapons detonations. In doing so, we aim to inform the development of policy around the TPNW and the gathering of further relevant information, enabling efforts to develop global humanitarian, human rights and sustainable development policy assisting communities affected by nuclear weapons.
Unlike dietary restriction, rapamycin fails to extend lifespan and reduce transcription stress in progeroid DNA repair‐deficient mice
Authors: Birkisdóttir María B. , Jaarsma Dick , Brandt Renata M. C. , Barnhoorn Sander , van Vliet Nicole , Imholz Sandra , van Oostrom Conny T. , Nagarajah Bhawani , Portilla Fernández Eliana , Roks Anton J. M. , Elgersma Ype , van Steeg Harry , Ferreira José A. , Pennings Jeroen L. A. , Hoeijmakers Jan H. J. , Vermeij Wilbert P. , Dollé Martijn E. T.
Published: January 2021

Dietary restriction (DR) and rapamycin extend healthspan and life span across multiple species. We have recently shown that DR in progeroid DNA repair‐deficient mice dramatically extended healthspan and trippled life span. Here, we show that rapamycin, while significantly lowering mTOR signaling, failed to improve life span nor healthspan of DNA repair‐deficient Ercc1∆/− mice, contrary to DR tested in parallel. Rapamycin interventions focusing on dosage, gender, and timing all were unable to alter life span. Even genetically modifying mTOR signaling failed to increase life span of DNA repair‐deficient mice. The absence of effects by rapamycin on P53 in brain and transcription stress in liver is in sharp contrast with results obtained by DR, and appoints reducing DNA damage and transcription stress as an important mode of action of DR, lacking by rapamycin. Together, this indicates that mTOR inhibition does not mediate the beneficial effects of DR in progeroid mice, revealing that DR and rapamycin strongly differ in their modes of action.
Speed of adjustment towards target leverage: evidence from a quantile regression analysis
Authors: Nguyen Thao , Bai Min , Hou Greg , Truong Cameron
Published: January 2021

Through employing a quantile regression approach and a dataset of 206,046 firm‐year observations over the period 1970–2017 in the United States market, we examine the heterogeneity and asymmetry in the speed of adjustment (SOA) towards target leverage. We document that high‐ and low‐levered firms adjust more quickly towards their target levels than do mid‐levered firms. This holds true when total leverage and long‐term leverage are considered in the analysis. Second, there is a difference in SOA between low‐ and high‐levered firms, which points to SOA skewness. Third, when short‐term leverage is considered in the analysis, the adjustment speed becomes smaller at varying levels of short‐term debts. Finally, empirical evidence from total leverage and long‐term leverage adjustments is consistent with the trade‐off theory, whereas empirical evidence from short‐term debt adjustments supports the pecking order theory.
Alarming evidence of widespread mite extinctions in the shadows of plant, insect and vertebrate extinctions
Authors: Sullivan Gregory T. , Ozman‐Sullivan Sebahat K.
Published: January 2021

This paper, which addresses the issue of the extinction of mite species at the global scale for the first time, highlights mite diversity, assesses the evidence for an extinction process, discusses contributing factors and estimates losses. The ~1 250 000 mite species occupy an enormous variety of terrestrial and freshwater ecosystems from the equator to the polar regions and to high altitudes. Some groups provide essential ecosystem services, including the incorporation of organic matter into the soil. The maintenance of mite diversity is inextricably linked to the continuance of floristic diversity, habitat complexity and insect diversity. The majority of mite species are assumed to be in the tropical rainforests, of which >50% has been destroyed or severely degraded. Most biodiversity hotspots are in tropical forests; endemic phytoseiid mite species are at least 17 times more concentrated in the hotspots than outside. Habitat destruction and degradation continue on an enormous scale, with increasing human population growth and resource consumption the overarching drivers of extinction. Moreover, climate change is likely to be worsening the effects of the other drivers at an increasing rate. The small body of direct evidence and a considerable body of indirect evidence strongly suggest the continuing, widespread extinction of mite species. Based on estimates of overall biodiversity loss, ~15% of mite species were likely to have become extinct by 2000, with losses currently expected to increase by between 0.6% and 6.0% by 2060. More detailed information on both spatial differences in mite assemblages and anthropogenic threats worldwide is crucial because they underpin the total number of species and their vulnerability to extinction, respectively. The rapid expansion of the protected area estate to capture the maximum possible area of ecosystem heterogeneity, especially in the biodiversity hotspots, is essential, as is best practice management of these areas.
Spatiotemporal patterns of taxonomic and functional β‐diversity of dung beetles in native and introduced pastures in the Brazilian Pantanal
Authors: Correa César M.A. , Da Silva Pedro G. , Puker Anderson , Abot Alfredo R.
Published: January 2021

Anthropogenic activity, such as conversion and degradation of habitats, is causing global biodiversity declines. However, our understanding of how local ecological communities are responding to these changes taxonomically and functionally is still limited. The effects of the replacement of native by introduced pastures on biodiversity are some of those examples with limited understanding. Here, we sampled dung beetles in native and introduced pastures using standardised sampling protocols during the dry and rainy seasons in the Brazilian Pantanal. We used multifaceted β‐diversity partitioning of taxonomy‐, abundance‐ and trait‐based approaches to evaluate spatial (i.e. between pasture types) and temporal (i.e. between seasons) patterns of dung beetle changes in composition, abundance and species traits. Spatially, we found no effects of pasture type, season and their interaction on taxonomy‐based β‐diversity and its components. For abundance‐based β‐diversity and its components, pasture type had effects on both Bray‐Curtis dissimilarity and balanced variation in abundance. Higher values of both metrics were found in native pastures. For functional‐based β‐diversity, Sorensen dissimilarity with higher values in the dry season, while pasture type also had an effect on functional nestedness, where higher values of functional nestedness were found in introduced pastures. Seasonally, we also found no effects of pasture type, season and their interaction on taxonomy‐based β‐diversity and its components. However, pasture type had effects on Bray‐Curtis dissimilarity, with higher values found in introduced pastures. No effects on balanced variation in abundance and abundance gradients were found. Pasture type influenced the functional turnover, but not functional dissimilarity or nestedness. Higher values of functional turnover were found in native pastures. In summary, we demonstrate that the type of pastures and climatic seasonality have effects on abundance‐ and functional‐ but not on taxonomy‐based β‐diversity patterns of dung beetles in the Brazilian Pantanal.
Fatty liver index is associated with the risk of testosterone deficiency in aging men without metabolic syndrome
Authors: Liu Chia‐Chu , Huang Shu‐Pin , Hsieh Tusty‐Jiuan , Lee Cheng‐Hsueh , Cheng Kai‐Hung , Huang Tsung‐Yi , Geng Jiun‐Hung , Li Ching‐Chia , Wu Wen‐Jeng , Lee Yung‐Chin
Published: January 2021

Objectives

Non‐alcoholic fatty liver disease (NAFLD) is suggested to be a precursor of metabolic syndrome (MetS) and could influence the risk of testosterone deficiency (TD). Fatty liver index (FLI) is a simple and useful screening tool for NAFLD. We determined the association between the risk of NAFLD assessed by FLI and TD in aging Taiwanese men, especially those without MetS.

Materials and Methods

A free health screening program was conducted for men (age: >40 years) in a medical center in Kaohsiung, Taiwan. All participants underwent a physical examination; answered a questionnaire assessing demographics, medical history, and clinical symptoms of TD; and provided 20‐mL whole blood samples for biochemical, adipocytokine, and hormonal evaluations. The risk of NAFLD was evaluated using FLI. The presence of NAFLD was ruled out if FLI value was <25 and ruled in if FLI value was ≥35.

Results

A total of 552 men (mean age: 54.7 ± 7.7 years) were enrolled. The prevalence rates of TD and MetS were significantly higher among men with NAFLD than those without NAFLD (both p < 0.001). FLI was significantly correlated with total testosterone (TT) and adipocytokines associated with insulin resistance, such as adiponectin, leptin, and retinol‐binding protein‐4 (RBP‐4) levels, respectively (all p < 0.001). Among men without MetS, those at risk of and with NAFLD had a 3.82 and 8.50 times higher risk of TD, respectively, than those without NAFLD after adjusting for potential covariates.

Conclusion

The FLI is associated with the risk of TD in aging Taiwanese men, especially in those without MetS. Our findings also suggest that insulin resistance may be an important link among the inter‐relationships of NAFLD, MetS, and TD.

Further population‐based studies with larger sample sizes of different ethnicities are warranted to confirm these preliminary results.
Trends in the use of neoadjuvant chemotherapy and oncological outcomes for high‐risk upper tract urothelial carcinoma: a multicentre retrospective study
Authors: Hamaya Tomoko , Hatakeyama Shingo , Tanaka Toshikazu , Kubota Yuka , Togashi Kyo , Hosogoe Shogo , Fujita Naoki , Kusaka Ayumu , Tokui Noriko , Okamoto Teppei , Yamamoto Hayato , Yoneyama Tohru , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara
Published: January 2021

Objective

To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC).

Patients and Methods

We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin‐ or carboplatin‐based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence‐free, cancer‐specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models.

Results

Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006–2010), 58% (2011–2015), to 79% (2016–2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW‐adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin‐based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin‐ and carboplatin‐based regimens.

Conclusions

The use of NAC for high‐risk UTUC increased significantly after 2010. Platinum‐based short‐term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.
Development of an optimal protocol for molecular profiling of tumor cells in pleural effusions at single‐cell level
Authors: Nakamura Ikuko Takeda , Ikegami Masachika , Hasegawa Nobuhiko , Hayashi Takuo , Ueno Toshihide , Kawazu Masahito , Yagishita Shigehiro , Goto Yasushi , Shinno Yuki , Kojima Yuki , Takamochi Kazuya , Takahashi Fumiyuki , Takahashi Kazuhisa , Mano Hiroyuki , Kohsaka Shinji
Published: January 2021

Liquid biopsy analyzes the current status of primary tumors and their metastatic regions. We aimed to develop an optimized protocol for single‐cell sequencing of floating tumor cells (FTCs) in pleural effusion as a laboratory test. FTCs were enriched using a negative selection of white blood cells by a magnetic‐activated cell sorting system, and CD45‐negative and cytokeratin‐positive selection using a microfluidic cell separation system with a dielectrophoretic array. The enriched tumor cells were subjected to whole‐genome amplification (WGA) followed by genome sequencing. The FTC analysis detected an EGFR exon 19 deletion in Case 1 (12/19 cells, 63.2%), and EML4‐ALK fusion (17/20 cells, 85%) with an alectinib‐resistant mutation of ALK (p.G1202R) in Case 2. To eliminate WGA‐associated errors and increase the uniformity of the WGA product, the protocol was revised to sequence multiple single FTCs individually. An analytical pipeline, accurate single‐cell mutation detector (ASMD), was developed to identify somatic mutations of FTCs. The large numbers of WGA‐associated errors were cleaned up, and the somatic mutations detected in FTCs by ASMD were concordant with those found in tissue specimens. This protocol is applicable to circulating tumor cells analysis of peripheral blood and expands the possibility of utilizing molecular profiling of cancers.
Radioiodine therapy reduces the frequency of circulating tumour cells in patients with differentiated thyroid cancer
Authors: Schmidt Mathias , Antke Christina , Mattes‐György Katalin , Hautzel Hubertus , Allelein Stephanie , Haase Matthias , Dringenberg Till , Schott Matthias , Ehlers Margret
Published: January 2021

Objective

The aim of the study was the quantification of circulating tumour cells (CTCs) in differentiated thyroid cancer (DTC) patients before and 6 weeks after radioiodine therapy (RIT).

Context

Circulating tumour cells (CTCs) were described more recently in cancer patients, mostly correlating with poor outcome and advanced metastases.

Design

Peripheral blood for identification and quantification of CTC before RIT or/and 6 weeks after RIT was provided by 55 DTC patients that received RIT for remnant tissue ablation.

Patients

13 follicular thyroid cancer (FTC) patients, 31 papillary thyroid cancer (PTC) patients and 11 patients having the follicular variant PTC (FV‐PTC) were included.

Measurements

Peripheral blood mononuclear cells (PBMCs) were isolated and EpCAM‐positive CTCs were counted by immune fluorescent staining.

Results

A CTC positivity of 31.8% before RIT could be observed. Six weeks after RIT, the CTC positivity was reduced to 13.6%. Paired data at both time points of blood sampling could be gathered for n = 33 DTC patients. These patients had significantly higher CTC numbers before RIT than 6 weeks afterwards (0.27 ± 0.47 vs 0.05 ± 0.15, P = .0215). Additionally, significantly reduced CTC numbers were also demonstrated in pre‐RIT CTC‐positive patients (0.88 ± 0.43 vs 0.05 ± 0.16, P = .0039).

Conclusion

Our results indicate a reducing effect on the number of CTCs by RIT. Therefore, CTC enumeration should be considered as efficient tool for treatment monitoring during RIT.
A review of venous thromboembolism in COVID‐19: A clinical perspective
Authors: Ozsu Savas , Gunay Ersin , Konstantinides Stavros V.
Published: January 2021

Coronavirus disease‐19 (COVID‐19) started in Wuhan, China in December 2019 and spread to all around the world in a short period of time. Hospitalized patients with COVID‐19 mostly could suffer from an abnormal coagulation activation risk with increased venous thrombosis events and a poor clinical course. The reported incidence rates of thrombotic complications in hospitalized COVID‐19 patients vary between 2.6 and 85% (both in non‐critically ill and critically ill patients). The risk of venous thromboembolism is not known in non‐hospitalized patients with COVID‐19. There are numerous studies and guidelines for administration of thromboprophylaxis for COVID‐19 cases. All hospitalized COVID‐19 patients should take pharmacological thromboprophylaxis if there is no contraindication. However, there is no consensus on this issue. In this review, we discussed all these approaches in a critical perspective.
COVID‐19 infection in former living kidney donors
Authors: Doshi Mona D. , Tsapepas Demetra , Prashar Rohini , Mohan Sumit , Edusei Emmanuel , Aull Meredith J. , Sherman Eric , Dadhania Darshana M.
Published: January 2021

The COVID‐19 pandemic brought living donor kidney transplant programs across the United States to a near halt in March 2020. As programs have begun to reopen, potential donor candidates often inquire about their risk of a COVID‐19 infection and its potential impact on kidney function after donation. To address their concerns, we surveyed 1740 former live kidney donors at four transplant centers located in New York and Michigan. Of these, 839 (48.2%) donors responded, their mean age was 46 ± 12.5 years, 543 (65%) were females, and 611 (73%) were white. Ninety‐two donors (11%) had symptoms suggestive of a COVID‐19 infection with fever (48%) and fatigue (43%) being the most common. Among those with symptoms, 42 donors underwent testing and 16 tested positive. Testing was more common among donors with private insurance, and a positive test result was more common among young black donors. Only one donor surveyed required hospitalization and none required dialysis. Fourteen donors have recovered completely and two partially. Our survey highlights that a COVID‐19 infection in former donors results in a mild disease with good recovery. These data will be useful for transplant programs to counsel living donors who are considering kidney donation during this pandemic.
Rapid development of perceptual gaze control in hearing native signing Infants and children
Authors: Bosworth Rain G. , Stone Adam
Published: January 2021

Children's gaze behavior reflects emergent linguistic knowledge and real‐time language processing of speech, but little is known about naturalistic gaze behaviors while watching signed narratives. Measuring gaze patterns in signing children could uncover how they master perceptual gaze control during a time of active language learning. Gaze patterns were recorded using a Tobii X120 eye tracker, in 31 non‐signing and 30 signing hearing infants (5–14 months) and children (2–8 years) as they watched signed narratives on video. Intelligibility of the signed narratives was manipulated by presenting them naturally and in video‐reversed (“low intelligibility”) conditions. This video manipulation was used because it distorts semantic content, while preserving most surface phonological features. We examined where participants looked, using linear mixed models with Language Group (non‐signing vs. signing) and Video Condition (Forward vs. Reversed), controlling for trial order. Non‐signing infants and children showed a preference to look at the face as well as areas below the face, possibly because their gaze was drawn to the moving articulators in signing space. Native signing infants and children demonstrated resilient, face‐focused gaze behavior. Moreover, their gaze behavior was unchanged for video‐reversed signed narratives, similar to what was seen for adult native signers, possibly because they already have efficient highly focused gaze behavior. The present study demonstrates that human perceptual gaze control is sensitive to visual language experience over the first year of life and emerges early, by 6 months of age. Results have implications for the critical importance of early visual language exposure for deaf infants. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=2ahWUluFAAg.
All contexts are not created equal: Social stimuli win the competition for organizing reinforcement learning in 9‐month‐old infants
Authors: Werchan Denise M. , Amso Dima
Published: January 2021

Previous work has shown that infants as young as 8 months of age can use certain features of the environment, such as the shape or color of visual stimuli, as cues to organize simple inputs into hierarchical rule structures, a robust form of reinforcement learning that supports generalization of prior learning to new contexts. However, especially in cluttered naturalistic environments, there are an abundance of potential cues that can be used to structure learning into hierarchical rule structures. It is unclear how infants determine what features constitute a higher‐order context to organize inputs into hierarchical rule structures. Here, we examine whether 9‐month‐old infants are biased to use social stimuli, relative to non‐social stimuli, as a higher‐order context to organize learning of simple visuospatial inputs into hierarchical rule sets. Infants were presented with four face/color‐target location pairings, which could be learned most simply as individual associations. Alternatively, infants could use the faces or colorful backgrounds as a higher‐order context to organize the inputs into simpler color‐location or face‐location rules, respectively. Infants were then given a generalization test designed to probehowthey learned the initial pairings. The results indicated that infants appeared to use the faces as a higher‐order context to organize simpler color‐location rules, which then supported generalization of learning to new face contexts. These findings provide new evidence that infants are biased to organize reinforcement learning around social stimuli.
Evidence of subtle left ventricular systolic dysfunction in cryptogenic stroke in the young
Authors: Pirinen Jani , Kuusisto Jouni , Martinez‐Majander Nicolas , Sinisalo Juha , Pöyhönen Pauli , Putaala Jukka , Järvinen Vesa
Published: January 2021

Introduction

Ischemic stroke in young patients often remains cryptogenic, that is, no underlying reason can be found. Some of these strokes may originate in the heart. Left ventricular (LV) dynamic volumetry and strain analysis are relatively new and promising methods for evaluating LV function.

Methods

In this pilot study, we recruited 30 young (18‐50 years) patients with cryptogenic ischemic stroke and 30 age‐ and sex‐matched controls from the SECRETO study (NCT01934725). The LV systolic function was assessed by LV volumetry (ejection fraction, peak emptying rate, and time to peak emptying rate). The longitudinal systolic function was assessed by speckle tracking strain and strain rate imaging, and by tissue velocity imaging derived MAD (mitral annular displacement) and septal S’.

Results

Stroke patients had less vigorous global longitudinal strain (median −18.9, interquartile range 3.3), compared to healthy controls (median −20.0, interquartile range 2.8), P = .010. There was no statistically significant differences in septal S’, MAD, global longitudinal strain rate, or dynamic volumetry‐derived parameters between the two groups.

Conclusions

Young cryptogenic stroke patients have subtly altered systolic function compared to healthy controls, found merely with longitudinal strain analysis. This infers that the heart may play a role in the pathogenesis of cryptogenic ischemic stroke.
Value of 3D mapping‐guided endomyocardial biopsy in cardiac sarcoidosis
Authors: Haanschoten Danielle M. , Adiyaman Ahmet , ‘t Hart Nils A. , Jager Piet L. , Elvan Arif
Published: January 2021

Aim

Integration of endomyocardial biopsy (EMB) in the diagnostic workup of cardiac sarcoidosis (CS) is under‐recognized in current clinical practice, since capturing focal granulomas is challenging. Our aim was to describe our experience with electro‐anatomic mapping (EAM)‐guided EMB and provide a comprehensive review of the literature.

Methods and results

Five patients (age 49.4 ± 11.4) with suspected CS underwent EAM‐guided EMB in Isala Heart Center (Zwolle, the Netherlands) between 2017 and 2019. In all patients, a 3D bipolar voltage map (<0.5‐1.5 mV) and unipolar voltage map (LV < 8.3 mV, RV < 5.5 mV) was created using a high‐density mapping catheter. The bioptome was connected to the mapping system to guide targeted EMB. Biopsy samples (2‐9 samples) were taken from both LV and RV sites, guided by EAM and areas with abnormal electrograms, without complications. CS diagnosis was based on EMB in 2/5 patients. A granuloma was captured in one patient at the LV basal septum with normal bipolar and abnormal unipolar voltage. All patients with delayed enhancement on cardiac magnetic resonance, revealed fibrosis in the biopsy sample. In one patient with suspected isolated cardiac sarcoidosis, diagnosis could not be confirmed by histopathology analysis, while unipolar voltage mapping was abnormal and diastolic potentials were present. Literature search revealed 7 reports (18 patients) describing EAM‐guided EMB in CS patients, with 100% of the EMB taken form the RV.

Conclusion

Unipolar voltage mapping may be superior to target active inflamed tissue and should be evaluated in future research regarding EAM‐guided EMB in CS.
Blue‐stain fungi isolated from freshly felled Scots pine logs in Poland, including Leptographium sosnaicola sp. nov
Authors: Jankowiak Robert , Szewczyk Grzegorz , Bilański Piotr , Jazłowiecka Dominika , Harabin Beata , Linnakoski Riikka
Published: January 2021

Wounds on felled tree stems provide entrance to inner wood for many fungi, including blue‐staining fungi, which cause permanent discoloration of wood. The aim of work presented here was to explore the diversity of blue‐stain fungi and assess the influence of the felling method and storage time/sampling period on their abundance and species diversity. Scots pines (Pinus sylvestris) grown in Poland were cut in April and July 2016, and fungal isolations from 20 stained logs that were obtained by mechanized harvesting and chainsaw harvesting, were carried out 3, 6, 9 and 12 weeks after felling. In total, eight fungal taxa were identified, including seven known and one novel species. Among the blue‐staining fungi detected, seven taxa belonged to Ophiostomatales, and one was identified as Sphaeropsis sapinea. The most frequently isolated fungi were S. sapinea, Ophiostoma minus and Ophiostoma ips. Additionally, Graphilbum acuminatum, Leptographium sosnaicola sp. nov., O. floccosum, O. piliferum and Sporothrix eucastaneae were found. More fungal isolates were obtained from summer‐harvested logs than spring‐harvested logs and from chainsaw‐harvested logs than mechanically harvested logs.
Neural signatures of temporal regularity and recurring patterns in random tonal sound sequences
Authors: Hodapp Alice , Grimm Sabine
Published: January 2021

The auditory system is highly sensitive to recurring patterns in the acoustic input – even in otherwise unstructured material, such as white noise or random tonal sequences. Electroencephalography (EEG) research revealed a characteristic negative potential to periodically recurring auditory patterns ‐ a response, which has been interpreted as memory trace‐related and specific, rather than as a sign of periodicity‐driven entrainment. Here, we aim to disentangle these two possible contributions by investigating the influence of a periodic sound sequence's inherent temporal regularity on event‐related potentials. Participants were presented continuous sequences of short tones of random pitch, with some sequences containing a recurring pattern, and asked to indicate whether they heard a repetition. Patterns were either spaced equally across the random sequence (isochronous condition) or with a temporal jitter (jittered condition), which enabled us to differentiate between event‐related potentials (and thus processing operations associated with a memory trace for a repeated pattern) and the periodic nature of the repetitions. A negative recurrence‐related component could be observed independently of temporal regularity, was pattern‐specific, and modulated by across trial repetition of the pattern. Critically, isochronous pattern repetition induced an additional early periodicity‐related positive component, which started to build up already before the pattern onset and which was elicited undampedly even when the repeated pattern was occasionally not presented. This positive component likely reflects a sensory driven entrainment process that could be the foundation of a behavioural benefit in detecting temporally regular repetitions.
Elevated expression of endogenous glial cell line‐derived neurotrophic factor impairs spatial memory performance and raises inhibitory tone in the hippocampus
Authors: Marshall Pepin , Garton Daniel R. , Taira Tomi , Võikar Vootele , Vilenius Carolina , Kulesskaya Natalia , Rivera Claudio , Andressoo Jaan‐Olle
Published: January 2021

Parvalbumin‐positive interneurons (PV+) are a key component of inhibitory networks in the brain and are known to modulate memory and learning by shaping network activity. The mechanisms of PV+ neuron generation and maintenance are not fully understood, yet current evidence suggests that signalling via the glial cell line‐derived neurotrophic factor (GDNF) receptor GFRα1 positively modulates the migration and differentiation of PV+ interneurons in the cortex. Whether GDNF also regulates PV+ cells in the hippocampus is currently unknown. In this study, we utilized a Gdnf “hypermorph” mouse model where GDNF is overexpressed from the native gene locus, providing greatly increased spatial and temporal specificity of protein expression over established models of ectopic expression. Gdnfwt/hyper mice demonstrated impairments in long‐term memory performance in the Morris water maze test and an increase in inhibitory tone in the hippocampus measured electrophysiologically in acute brain slice preparations. Increased PV+ cell number was confirmed immunohistochemically in the hippocampus and in discrete cortical areas and an increase in epileptic seizure threshold was observed in vivo. The data consolidate prior evidence for the actions of GDNF as a regulator of PV+ cell development in the cortex and demonstrate functional effects upon network excitability via modulation of functional GABAergic signalling and under epileptic challenge.
Osteosarcoma in the femur of a horse
Authors: Pfeifle R. L. , Beasley E. M. , Crabtree N. E. , Fraser C. , Elbert J. A. , Ducker E. , Nagata K. , Garner B. C. , Sakamoto K.
Published: January 2021

A 27‐year‐old Arabian pony gelding presented for evaluation of weight loss, intermittent sheath oedema, persistent neutropenia and thrombocytopenia, and acute left hindlimb swelling and gait abnormality. Clinical findings included swelling, heat and sensitivity localised over the left greater trochanter, mild to moderate ventral and sheath oedema, a left hindlimb post‐legged gait, and off‐loading of weight from the left hindlimb at rest. Initially, neutropenia and thrombocytopenia were confirmed on bloodwork, but neutrophilia and thrombocytopenia persisted as the case progressed. Diagnostic imaging (radiography and percutaneous ultrasonography) of the left hindquarters revealed an aggressive, mixed proliferative and lytic bony lesion of the proximal left femur as well as associated muscle fibre disruption and a soft tissue mass. A percutaneous core biopsy of the lesion led to the diagnosis of osteoblastic osteosarcoma on histopathology. Pain and inflammation associated with the lesion was medically managed in the hospital with mild improvement. Additionally, palliative radiation was performed under general anaesthesia. Unfortunately, before a response to palliative radiation could be assessed, the patient was subjected to euthanasia due to development of acute neurological signs.
A multi‐label cascaded neural network classification algorithm for automatic training and evolution of deep cascaded architecture
Authors: Pakrashi Arjun , Mac Namee Brian
Published: January 2021

Multi‐label classification algorithms deal with classification problems where a single datapoint can be classified (or labelled) with more than one class (or label) at the same time. Early multi‐label approaches like binary relevance consider each label individually and train individual binary classifier models for each label. State‐of‐the‐art algorithms like RAkEL, classifier chains, calibrated label ranking, IBLR‐ML+, and BPMLL also consider the associations between labels for improved performance. Like most machine learning algorithms, however, these approaches require careful hyper‐parameter tuning, a computationally expensive optimisation problem. There is a scarcity of multi‐label classification algorithms that require minimal hyper‐parameter tuning. This paper addresses this gap in the literature by proposing CascadeML, a multi‐label classification method based on the existing cascaded neural network architecture, which also takes label associations into consideration. CascadeML grows a neural network architecture incrementally (deep as well as wide) in a two‐phase process as it learns network weights using an adaptive first‐order gradient descent algorithm. This omits the requirement of preselecting the number of hidden layers, nodes, activation functions, and learning rate. The performance of the CascadeML algorithm was evaluated using 13 multi‐label datasets and compared with nine existing multi‐label algorithms. The results show that CascadeML achieved the best average rank over the datasets, performed better than BPMLL (one of the earliest well known multi‐label specific neural network algorithms), and was similar to the state‐of‐the‐art classifier chains and RAkEL algorithms.
The contributions of metabolomics in the discovery of new therapeutic targets in Alzheimer's disease
Authors: Altiné‐Samey Rayhanatou , Antier Daniel , Mavel Sylvie , Dufour‐Rainfray Diane , Balageas Anna‐Chloé , Beaufils Emilie , Emond Patrick , Foucault‐Fruchard Laura , Chalon Sylvie
Published: January 2021

Alzheimer's disease (AD) leads to the progressive loss of memory and other cognitive functions. It is the most common form of dementia in the elderly and has become a major public health problem due to the increase in life expectancy. Although the detection of AD is based on several neuropsychological tests, imaging, and biological analyses, none of these biomarkers allows a clear understanding of the pathophysiological mechanisms involved in the disease, and no efficient treatment is currently available. Metabolomics, which allows the study of biochemical alterations underlying pathological processes, could help to identify these mechanisms, to discover new therapeutic targets, and to monitor the therapeutic response and disease progression. In this review, we have summarized and analyzed the results from a number of studies on metabolomics analyses performed in biological samples originated from the central nervous system, in AD subjects, and in animal models of this disease. This synthesis revealed modified expression of specific metabolites in pathological conditions which allowed the identification of significantly impacted metabolic pathways both in animals and humans, such as the arginine biosynthesis and the alanine, aspartate, and glutamate metabolism. We discuss the potential biochemical mechanisms involved, the extent to which they could impact the specific hallmarks of AD, and the therapeutic approaches which could be proposed as a result.