bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional gene expression patterns are associated with task-specific brain activation during reward and emotion processing measured with functional MRI
Authors: Komorowski Arkadiusz , Vidal Ramon , Singh Aditya , Murgaš Matej , Pena-Centeno Tonatiuh , Gryglewski Gregor , Kasper Siegfried , Wiltfang Jens , Lanzenberger Rupert , Goya-Maldonado Roberto
Published: June 2020

The spatial relationship between gene expression profiles and neural response patterns known to be altered in neuropsychiatric disorders, e.g. depression, can guide the development of more targeted therapies. Here, we estimated the correlation between human transcriptome data and two different brain activation maps measured with functional magnetic resonance imaging (fMRI) in healthy subjects. Whole-brain activation patterns evoked during an emotional face recognition task were associated with topological mRNA expression of genes involved in cellular transport. In contrast, fMRI activation patterns related to the acceptance of monetary rewards were associated with genes implicated in neuronal development, synapse regulation, and gene transcription. An overlap of these genes with risk genes from major depressive disorder genome-wide associations studies revealed the involvement of the master regulators TCF4 and MEF2C. These results were further validated by means of meta-analytic fMRI data. Overall, the identification of stable relationships between spatial gene expression profiles and fMRI data may reshape the prospects for imaging transcriptomics studies.
Two-Photon Microperimetry: A media opacity-independent retinal function assay
Authors: Wei Ang , Mehta Urmi V. , Palczewska Grazyna , Palma Anton M. , Hussey Vincent M. , Hoffmann Luke E. , Diep Anna , Nguyen Kevin , Le Bryan , Chang Steven Yone-Shun , Browne Andrew W.
Published: June 2020

Humans perceive light in the visible portion of electromagnetic radiation. However, visible light is scattered and attenuated by optical media opacities. Because all conventional visual function tests rely on visible light, test results are reduced in patients with optical media opacities like corneal scars, cataracts, and vitreous hemorrhages. Infrared (IR) light has greater penetrance through tissue than visible light. Two-photon IR visual stimulation, a recently pioneered technology, should enable testing of retinal visual function and produce results that are less susceptible to media opacities. The effects of simulated media opacities on visual performance in young healthy volunteers and the change in visual function in healthy phakic patients of two age ranges (20-40 and 60-80-year-old) were studied using conventional testing and 2-photon infrared visual stimulation. All subjects completed visual function testing using cone contrast threshold (CCT) testing, conventional microperimetry, visible light microperimetry from a novel device (2PM-Vis), and infrared 2-photon microperimetry (2PM-IR). Retinal sensitivity measured by 2PM-IR demonstrated lower variability than all other devices relying on visible spectrum stimuli. Retinal sensitivity decreased proportionally with the transmittance of light through each filter. CCT scores and retinal sensitivity decreased with age in all testing modalities. Visible spectrum testing modalities demonstrated larger test result differences between young and old patient cohorts; this difference was inversely proportional to the wavelength of the visual function test. 2PM-IR mitigates media opacities which may mask small differences in retinal sensitivity when tested with conventional visual function testing devices.

One Sentence Summary

Two photon infrared visual function testing produces results that are less susceptible to media opacities than conventional tests.
Activation of the Crtc2/Creb1 transcriptional network in skeletal muscle enhances weight loss during intermittent fasting
Authors: Bruno Nelson E. , Nwachukwu Jerome C. , Srinivasan Sathish , Hawkins Richard , Sturgill David , Hager Gordon L. , Hurst Stephen , Sheu Shey-Shing , Conkright Michael D. , Nettles Kendall W.
Published: June 2020

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc 2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, supported by maintenance of higher energy expenditure during the fast. ADF downregulated most of the mitochondrial electron transport genes, and other regulators of mitochondrial function, that were substantially reversed by Crtc2-driven transcription. Glucocorticoids acted with AMPK to drive atrophy and mitophagy, which was reversed by Crtc2/Creb1 signaling. Crtc2/Creb1-mediated signaling coordinates metabolic adaptations in skeletal muscle that explain how Crtc2/Creb1 regulates metabolism and weight loss.
Coordinate transcriptional and post-transcriptional repression of pro-differentiation genes maintains intestinal stem cell identity
Authors: Buddika Kasun , Huang Yi-Ting , Ariyapala Ishara S. , Griffith Alex Butrum- , Norrell Sam A. , O’Connor Alex M. , Patel Viraj K. , Rector Samuel A. , Slovan Mark , Sokolowski Mallory , Kato Yasuko , Nakamura Akira , Sokol Nicholas S.
Published: June 2020

The role of Processing bodies (P-bodies), key sites of post-transcriptional control, in adult stem cells remains poorly understood. Here, we report that adult Drosophila intestinal stem cells, but not surrounding differentiated cells such as absorptive Enterocytes (ECs), harbor P-bodies that containDrosophilaorthologs of mammalian P-body components DDX6, EDC3, EDC4 and LSM14A/B. A targeted RNAi screen in intestinal progenitor cells identified 39 previously known and 64 novel P-body regulators, includingPatr-1, a gene necessary for P-body assembly. Loss ofPatr-1-dependent P-bodies leads to a loss of stem cells that is associated with inappropriate translation and expression of EC-fate genenubbin. Transcriptomic analysis of progenitor cells identifies a cadre of such weakly transcribed pro-differentiation transcripts that are elevated after P-body loss. Altogether, this study identifies a coordinated P-body dependent, translational and transcriptional repression program that maintains a defined set ofin vivostem cells in a state primed for differentiation.

Graphical abstract

Highlights

Drosophila intestinal progenitor cells contain constitutive and ultrastructurally organized P-bodies.

A P-body regulatorPatr-1is required for intestinal progenitor cell maintenance.

Enterocyte (EC) genes such asnubbinare weakly transcribed but not translated in intestinal progenitors.

P-bodies repress EC gene translation to promote stem cell maintenance.
Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by Molecular Simulations
Authors: Ghorbani Mahdi , Brooks Bernard R. , Klauda Jeffery B.
Published: June 2020

The novel coronavirus (nCOV-2019) outbreak has put the world on edge, causing millions of cases and hundreds of thousands of deaths all around the world, as of June 2020, let alone the societal and economic impacts of the crisis. The spike protein of nCOV-2019 resides on the virion’s surface mediating coronavirus entry into host cells by binding its receptor binding domain (RBD) to the host cell surface receptor protein, angiotensin converter enzyme (ACE2). Our goal is to provide a detailed structural mechanism of how nCOV-2019 recognizes and establishes contacts with ACE2 and its difference with an earlier coronavirus SARS-COV in 2002 via extensive molecular dynamics (MD) simulations. Numerous mutations have been identified in the RBD of nCOV-2019 strains isolated from humans in different parts of the world. In this study, we investigated the effect of these mutations as well as other Ala-scanning mutations on the stability of RBD/ACE2 complex. It is found that most of the naturally-occurring mutations to the RBD either strengthen or have the same binding affinity to ACE2 as the wild-type nCOV-2019. This may have implications for high human-to-human transmission of coronavirus in regions where these mutations have been found as well as any vaccine design endeavors since these mutations could act as antibody escape mutants. Furthermore, in-silico Ala-scanning and long-timescale MD simulations, highlight the crucial role of the residues at the interface of RBD and ACE2 that may be used as potential pharmacophores for any drug development endeavors. From an evolutional perspective, this study also identifies how the virus has evolved from its predecessor SARS-COV and how it could further evolve to become more infectious.
Full-length isoform transcriptome of developing human brain provides new insights into autism
Authors: Chau Kevin , Zhang Pan , Urresti Jorge , Amar Megha , Pramod Akula Bala , Chen Jiaye , Thomas Amy , Corominas Roser , Lin Guan Ning , Iakoucheva Lilia M.
Published: June 2020

Alternative splicing plays important role in brain development, however its global contribution to human neurodevelopmental diseases (NDD) has not been fully investigated. Here, we examined the relationships between full-length splicing isoforms expression in the brain andde novoloss-of-function mutations identified in the patients with NDDs. We analyzed the full-length isoform transcriptome of the developing human brain and observed differentially expressed isoforms and isoform co-expression modules undetectable by gene-level analyses. These isoforms were enriched in loss-of-function mutations and microexons, co-expressed with a unique set of partners, and had higher prenatal expression. We experimentally tested the impact of splice site mutations in five NDD risk genes, includingSCN2A,DYRK1AandBTRC,and demonstrated exon skipping. Furthermore, our results suggest that the splice site mutation inBTRCreduces translational efficiency, likely impacting Wnt signaling through impaired degradation of β-catenin. We propose that functional effect of mutations associated with human diseases should be investigated at the isoform-rather than the gene-level resolution.

Highlights

Differential isoform expression analysis of the human brain transcriptome reveals neurodevelopmental processes and pathways undetectable by differential gene expression analyses.

Splicing isoforms impacted by neurodevelopmental disease (NDD) risk mutations exhibit higher prenatal expression, are enriched in microexons and are involved in neuronal-related functions.

Isoform co-expression network analysis identifies modules with splicing and synaptic functions that are enriched in NDD mutations.

Splice site mutations impacting NDD risk genes cause exon skipping and produce novel isoforms with altered biological properties.

Functional impact of mutations should be investigated at the full-length isoform-level rather than the gene-level resolution
Quantifying Color Vision Changes Associated with Cataracts Using Cone Contrast Thresholds
Authors: Mehta Urmi , Diep Anna , Nguyen Kevin , Le Bryan , Yuh Clara , Frambach Caroline , Doan John , Wei Ang , Palma Anton M. , Farid Marjan , Garg Sumit , Kedhar Sanjay , Wade Matthew , Marshall Kailey A. , Jameson Kimberly A. , Kenney M. Cristina , Browne Andrew W.
Published: June 2020

Purpose

The cone contrast threshold (CCT) test quantified color vision changes in subjects of all ages and those undergoing cataract surgery.

Methods

Twenty-four healthy volunteers from two cohort studies performed CCT using best corrected visual acuity, filters, mydriasis, and pinhole correction. Retrospective cross-sectional study of patients seen in eye clinics evaluated the relationship between age and color vision, and age and lens status in 355 eyes. Lastly, 25 subjects performed CCT before and after cataract surgery.

Results

CCT scores were most reliable in the non-mydriatic condition without pinhole correction. Progressively dense brown filters produced small but significant reductions in S-cone sensitivity. Linear regression analysis of phakic subjects showed a decline for all cone classes with age. Rate of decline was greater for S-cones (slope (95% CI) = −1.09 (−1.23, 0.94)) than M-cones (slope (95% CI) = −0.80 (−0.95, −0.66)) and L-cones (slope (95% CI) = −0.66 (−0.81, - 0.52)). CCT scores increased for S-cones but reduced for L- and M-cones in pseudophakic subjects compared to phakic patients. CCT scores after cataract surgery increased for S-cones, M-cones, and L-cones by 33.0 (p<0.001), 24.9 (p=0.001), and 22.0 (p=0.008).

Conclusions

CCT assessment allows for clinically practical quantitation of color and contrast vision improvement after cataract surgery and aging patients who note poor vision despite good visual acuity.

Translational Relevance

CCT testing, historically used in research, is now a clinically practical tool to evaluate age and cataract related changes in color and contrast vision and routinely quantify vision beyond black and white visual acuity testing.
H3K27me3 is dispensable for early differentiation but required to maintain differentiated cell identity
Authors: Miller Sara A. , Damle Manashree , Kingston Robert E.
Published: June 2020

Polycomb repressive complex 2 (PRC2) catalyzes trimethylation of histone H3 on lysine 27 and is required for normal development of complex eukaryotes. The requirement for H3K27me3 in various aspects of mammalian differentiation is not clear. Though associated with repressed genes, the modification is not sufficient to induce gene repression, and in some instances is not required. To examine the role of the modification in mammalian differentiation, we blocked trimethylation of H3K27 with both a small molecule inhibitor, GSK343, and by introducing a point mutation into EZH2, the catalytic subunit of PRC2. We found that cells with substantively decreased H3K27 tri-methylation were able to differentiate, which contrasts with EZH2 null cells. Different PRC2 targets had varied requirements for H3K27me3 in repressive regulation with a subset that maintained normal levels of repression in the absence of methylation. The primary cellular phenotype when H3K27 tri-methylation was blocked was an inability of the altered cells to maintain a differentiated state when challenged. This phenotype was determined by H3K27me3 deposition both in embryonic stem cells and in the first four days of differentiation. H3K27 tri-methylation therefore was not necessary for formation of differentiated cell states but was required to maintain a stable differentiated state.
Dynamic extrinsic pacing of theHOXclock in human axial progenitors controls motor neuron subtype specification
Authors: Mouilleau Vincent , Vaslin Célia , Gribaudo Simona , Robert Rémi , Nicolas Nour , Jarrige Margot , Terray Angélique , Lesueur Léa , Mathis Mackenzie W. , Croft Gist , Daynac Mathieu , Rouiller-Fabre Virginie , Wichterle Hynek , Ribes Vanessa , Martinat Cécile , Nedelec Stéphane
Published: June 2020

Rostro-caudal patterning of vertebrates depends on the temporally progressive activation ofHOXgenes within axial stem cells that fuel axial embryo elongation. WhetherHOXgenes sequential activation, the “HOXclock”, is paced by intrinsic chromatin-based timing mechanisms or by temporal changes in extrinsic cues remains unclear. Here, we studiedHOXclock pacing in human pluripotent stem cells differentiating into spinal cord motor neuron subtypes which are progenies of axial progenitors. We show that the progressive activation of caudalHOXgenes in axial progenitors is controlled by a dynamic increase in FGF signaling. Blocking FGF pathway stalled induction ofHOXgenes, while precocious increase in FGF alone, or with GDF11 ligand, accelerated theHOXclock. Cells differentiated under acceleratedHOXinduction generated appropriate posterior motor neuron subtypes found along the human embryonic spinal cord. TheHOXclock is thus dynamically paced by exposure parameters to secreted cues. Its manipulation by extrinsic factors alleviates temporal requirements to provide unprecedented synchronized access to human cells of multiple, defined, rostro-caudal identities for basic and translational applications.
Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis
Authors: Tian Ruilin , Abarientos Anthony , Hong Jason , Hashemi Sayed Hadi , Yan Rui , Dräger Nina , Leng Kun , Nalls Mike A. , Singleton Andrew B. , Xu Ke , Faghri Faraz , Kampmann Martin
Published: June 2020

Single-cell transcriptomics provide a systematic map of gene expression in different human cell types. The next challenge is to systematically understand cell-type specific gene function. The integration of CRISPR-based functional genomics and stem cell technology enables the scalable interrogation of gene function in differentiated human cells. Here, we present the first genomewide CRISPR interference and CRISPR activation screens in human neurons.

We uncover pathways controlling neuronal response to chronic oxidative stress, which is implicated in neurodegenerative diseases. Unexpectedly, knockdown of the lysosomal protein prosaposin strongly sensitizes neurons, but not other cell types, to oxidative stress by triggering the formation of lipofuscin, a hallmark of aging, which traps iron, generating reactive oxygen species and triggering ferroptosis. We also determine transcriptomic changes in neurons following perturbation of genes linked to neurodegenerative diseases. To enable the systematic comparison of gene function across different human cell types, we establish a data commons named CRISPRbrain.
Antifungal activity of 2,3-diphenyl-2,3-dihydro-1,3-thiaza-4-ones againsttwohuman pathogenic fungi
Authors: Liporagi-Lopes Livia , Sobhi Hany F. , Silverberg Lee J. , Cordero Radames J.B. , Casadevall Arturo
Published: June 2020

Invasive fungal diseases are prevalent in immunocompromised individuals in whom current therapies often provide suboptimal results. Additionally, the increased resistance to the available antifungal drugs necessitates a search for new compounds. This study reports the antifungal activity of six 5-, 6-, and 7-membered 2,3-diphenyl-2,3-dihydro-1,3-thiaza-4-ones againstLomentospora prolificansandCryptococcus neoformans. Our data showed that some of the compounds tested had a low MIC and damage on the cell surface of the tested fungal species.
The epidemiology of autoimmune liver disease varies with geographic latitude
Authors: Webb Gwilym J , Ryan Ronan P , Marshall Tom P , Hirschfield Gideon M
Published: June 2020

Background & aims

The epidemiology of autoimmune liver disease (AILD) is challenging to study because of the diseases’ rarity and because of cohort selection bias. Increased incidence further from the Equator is reported for multiple sclerosis, another autoimmune. We assessed the incidence of primary biliary cholangitis (PBC), primary biliary cholangitis (PSC), and autoimmune hepatitis (AIH) in relation to latitude.

Methods

Retrospective cohort study using anonymised UK primary care records 2002-01-01 to 2016-05-10. All adults without a baseline diagnosis of autoimmune liver disease were included and followed until first occurrence of an AILD diagnosis, death, or they left the database. Latitude was measured as registered general practice rounded down to whole degrees.

Results

The cohort included 8 590 421 records with 53.3 107 years follow-up from 694 practices.

There were 1314 incident cases of PBC, 396 of PSC, and 1034 of AIH. Crude incidences (95% confidence interval) was: PBC 2.47 (2.34-2.60), PSC 0.74 (0.67-0.82), and AIH 1.94 (1.83-2.06)/100 000/year. PBC incidence correlated with female sex, smoking, and deprivation; PSC incidence correlated with male sex and not smoking; AIH incidence correlated with female sex and deprivation.

More northerly latitude was strongly associated with incidence of PBC: 2.16 (1.79-2.60) to 4.86 (3.93-6.00) from 50-57°N (p=0.002) and AIH 2.00 (1.65-2.43) to 3.28 (2.53-4.24)(p=0.003), but not PSC 0.82 (0.60-1.11) to 1.02 (0.64-1.61)(p=0.473).

Incidence after adjustment for age, sex, smoking, and deprivation status showed similar positive correlations for PBC and AIH with latitude, but not PSC. Incident AIH cases were younger at greater latitude.

Conclusions

We describe a novel association between increased latitude and the incidence of PBC and AIH that requires both confirmation and explanation.
Evidence of associative blocking during foraging in the social wasp Vespula germanica
Authors: Moreyra Sabrina , D'Adamo Paola , Lozada Mariana
Published: June 2020

While foraging, Vespula germanica usually return to abundant food sites. During this relocation behavior, these wasps learn to identify contextual cues associated with food position. We analyzed associative blocking in this species, that is, how an association with a conditioned stimulus (CS1) blocks subsequent learning when a novel stimulus (CS2) is added on a second foraging visit. Three groups of wasps (A, B, and C; total 74 individual wasps) were observed while collecting meat during one or two consecutive visits. In group A, an environmental cue (CS1) was paired with food placed at a specific site, and on the second visit, a second cue (CS2) was added while food remained in the same position. In a subsequent testing phase, CS1 was removed and the food source displaced nearby. We then recorded the number of hovers performed over the empty dish (previously baited). Group A wasps appeared to ignore the addition of CS2 on their second visit because they performed fewer hovers over the learned site. For group A, the duration of the decision‐making process to finally fly toward the baited dish was shorter than when CS1 and CS2 were presented together on their first visit (group B). This is the first study to demonstrate the occurrence of associative blocking in vespids, confirming that a prior foraging experience influences subsequent food relocation in V. germanica. Our findings reveal that first learning episodes block further associations with novel contextual cues, contributing to understanding of complex cognitive processes involved in V. germanica´s foraging behavior.
Characterisation of bird cherry‐oat aphid (Rhopalosiphum padi L.) behaviour and aphid host preference in relation to partially resistant and susceptible wheat landraces
Authors: Singh Beant , Simon Amma , Halsey Kirstie , Kurup Smita , Clark Suzanne , Aradottir Gudbjorg Inga
Published: June 2020

The bird cherry‐oat aphid (Rhopalosiphum padi L.) is a major pest of wheat (Triticum aestivum L.) and can cause up to 30% yield losses. Heritable plant resistance to aphids is both an economically and ecologically sound method for managing aphids. Here we report how the behaviour and performance of R. padi differs on two resistant, one susceptible wheat landrace and a susceptible elite wheat variety. Feeding behaviour differed among the genotypes, with aphids on resistant lines spending longer in the pathway phase and less time phloem feeding. These behaviours suggest that both inter‐ and intracellular factors encountered during pathway and phloem feeding phases could be linked to the observed aphid resistance. Locomotion and antennal positioning choice tests also revealed a clear preference for susceptible lines. Although feeding studies revealed differences in the first probe indicating that the resistance factors might also be located in the peripheral layers of the plant tissue, scanning electron microscopy revealed no difference in trichrome length and density on the surface of leaves. Aphids are phloem feeders and limiting the nutrient uptake by the aphids may negatively affect their growth and development as shown here in lower weight and survival of nymphs on resistant genotypes and decreased reproductive potential, with lowest mean numbers of nymphs produced by aphids on W064 (54.8) compared to Solstice (71.9). The results indicate that resistant lines markedly alter the behaviour, reproduction and development potential of R. padi and possess both antixenosis and antibiosis type of resistance.
Borderline patients have difficulties describing feelings; bipolar II patients describe difficult feelings. An alexithymia study
Authors: Bøen E. , Hummelen B. , Boye B. , Elvsåshagen T. , Malt U. F.
Published: June 2020

Objective

Apparent similarities between borderline personality disorder (BPD) and bipolar II disorder (BIP‐II) contribute to clinical difficulties in distinguishing between the disorders. Here, we aimed to explore how subjective Difficulties with the Identification and Description of Feelings (DIDF), a major constituent of the alexithymia construct and assessed as a part of the Toronto Alexithymia Scale (TAS), are related to relationship problems and health complaints in these groups.

Methods

Twenty‐two patients with BPD; 22 patients with BIP‐II; and 23 healthy controls (HC) completed TAS. Health complaints, including symptoms associated with mood swings, were assessed with the Giessener Subjective Complaints List (Giessener Beschwerdebogen—GBB), and relationship problems with the Health of the Nation Outcome scale, Relationship item (HoNOSR). Bivariate correlations were run.

Results

Both patient groups had high DIDF and GBB scores. In BPD only, there was a significant positive correlation between DIDF and HoNOSR. In BIP‐II only, there was a significant positive correlation between DIDF and GBB total score. In BIP‐II, DIDF correlated highly with those GBB subscales assessing symptoms typically occurring during bipolar mood swings (cardiovascular and gastrointestinal symptoms, exhaustion).

Conclusion

Our results suggest that in BPD, high DIDF scores represent genuine problems with identifying and describing emotions which are expected to correlate with relationship problems. In BIP‐II, high DIDF scores could potentially represent difficulties with understanding the unpredictable symptoms of bipolar mood swings. The findings suggest that difficulties with identifying and describing feelings in patients should be carefully explored to increase the validity of the diagnostic evaluation.
Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum
Authors: Xiong Wenju , Kong Xiangjun , Jiang Jun , Yang Zhihui , Jiang Rui
Published: June 2020

Background

The number of erectile dysfunction (ED) patients is increasing annually. How to improve the effectiveness of ED treatment is an important issue for the field of andrology.

Objectives

To investigate whether low androgen status impairs the erectile function of rats by regulated endothelial nitric oxide synthase (eNOS) uncoupling.

Materials and methods

Thirty‐six 8‐week‐old male Sprague Dawley (SD) rats were randomly divided into six groups as follows: 4‐week sham‐operated group (4w‐sham), 4‐week castration group (4w‐cast), 4‐week castration + testosterone (T) group (4w‐cast + T), 8‐week sham‐operated group (8w‐sham), 8‐week castration group (8w‐cast), and 8‐week castration + T group (8w‐cast + T). Three mg/kg of T was subcutaneously injected every other day in castration + T groups. The ratio of the maximum intracavernous pressure/the mean arterial pressure (ICPmax/MAP), the level of serum T, dihydrobiopterin(BH2), tetrahydrobiopterin (BH4), nitric oxygen(NO), 3‐nitrotyrosine(3NT), dihydrofolate reductase (DHFR), guanosine triphosphate cyclohydrolase 1 (GTPCH1), nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), and eNOS monomers/dimers in the corpus cavernosum were detected.

Results

The ratio of ICPmax/MAP and BH4/BH2, the level of serum T, NO, and GTPCH1 decreased significantly in castration groups compared with sham‐operated groups and castration + T groups (P < .05) and decreased significantly in 8w‐cast group compared with 4w‐cast group (P < .05). The expression of 3NT and NOX2 and the ratio of eNOS monomers/dimers increased significantly in castration groups compared with sham‐operated groups and castration + T groups (P < .01) and increased significantly in 8w‐cast group compared with 4w‐cast group (P < .01). The expression of DHFR in 4w‐cast group was significantly higher than that in 4w‐sham group and 4w‐cast + T group (P < .01) and in 8w‐cast group was significantly lower than that in 8w‐sham group and 8w‐cast + T group (P < .01).

Discussion and Conclusion

Low androgen status induces eNOS uncoupling by reducing BH4/BH2 and increasing 3NT. Due to the decreased NO production, the erectile function of the rats was impaired.
Comparison of infection in cemented, cementless and hybrid primary total knee arthroplasty: a network meta‐analysis and systematic review of randomized clinical trials
Authors: Onggo James , Onggo Jason , Phan Kevin , Wilson Christopher
Published: June 2020

Background

Prosthetic joint infection (PJI) is a serious complication of joint replacement surgeries. Surgeons often take extra measures to reduce the risk of PJI. Whilst many studies have compared between cemented, cementless and hybrid fixation (femoral cementless, tibial cemented), most focus on survivorship, clinical and function outcome scores as primary endpoints. This meta‐analysis aims to study the association between fixation methods and risk of PJI in primary total knee arthroplasty (TKA).

Methods

A systematic review and network meta‐analysis of randomized controlled trials (RCT) were performed according to Preferred Reporting Items for Systematic reviews and Meta‐Analyses guidelines. Data from studies assessing prevalence of PJI in each fixation type were extracted and analysed.

Results

Twelve RCT comprising a total of 1573 knees were included. Six RCT compared between cemented (n = 486 knees) and cementless (n = 440 knees) fixation, while six RCT compared between hybrid (n = 324 knees) and cementless (n = 323 knees) fixation. Network meta‐analysis did not reveal any fixation type that significantly increased the infection rate in TKA. Rate of all infection was lowest in cemented TKA as compared to cementless (odds ratio (OR) 0.90, 95% confidence interval (CI) 0.35–2.28) and hybrid (OR 0.63, 95%CI 0.13–2.99) TKA. Rate of PJI requiring revision surgery was lowest in cementless TKA as compared to cemented (OR 0.89, 95%CI 0.30–2.41) and hybrid (OR 0.57, 95%CI 0.09–2.71) TKA. Rate of PJI not requiring revision surgery was lowest in cemented TKA as compared to hybrid (OR 0.56, 95%CI 0.06–6.10) and cementless (OR 0.55, 95% 0.14–5.63).

Conclusion

Unlike total hip arthroplasties, fixation method is not a predisposing risk factor for infections in TKA. However, this meta‐analysis may not have sufficient statistical power to show a significant difference between fixation types. It is recommended that prophylactic precautions against other known risk factors for infection should still be clinically practiced. Level of evidence: Level I, meta‐analysis of randomized controlled trials.
Safe surgery during the coronavirus disease 2019 crisis
Authors: Tivey David R. , Davis Sean S. , Kovoor Joshua G. , Babidge Wendy J. , Tan Lorwai , Hugh Thomas J. , Collinson Trevor G. , Hewett Peter J. , Padbury Robert T. A. , Maddern Guy J.
Published: June 2020

Background

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has created a global pandemic. Surgical care has been impacted, with concerns raised around surgical safety, especially in terms of laparoscopic versus open surgery. Due to potential aerosol transmission of SARS‐CoV‐2, precautions during aerosol‐generating procedures and production of surgical plume are paramount for the safety of surgical teams.

Methods

A rapid review methodology was used with evidence sourced from PubMed, Departments of Health, surgical colleges and other health authorities. From this, a working group of expert surgeons developed recommendations for surgical safety in the current environment.

Results

Pre‐operative testing of surgical patients with reverse transcription‐polymerase chain reaction does not guarantee lack of infectivity due to a demonstrated false‐negative rate of up to 30%. All bodily tissues and fluids should therefore be treated as a potential source of COVID‐19 infection during operative management. Caution must be taken, especially when using an energy source that produces surgical plumes, and an appropriate capture device should also be used. Limiting the use of such devices or using lower energy devices is desirable. To reduce perceived risks association with desufflation of pneumoperitoneum during laparoscopic surgery, an appropriate suction irrigator system, attached to a high‐efficiency particulate air filter, should be used. Additionally, appropriate use of personal protective equipment by the surgical team is necessary during high‐risk aerosol‐generating procedures.

Conclusions

As a result of the rapid review, evidence‐based guidance has been produced to support safe surgical practice.
Nuclear microenvironment in cancer: Control through liquid‐liquid phase separation
Authors: Nozawa Ryu‐Suke , Yamamoto Tatsuro , Takahashi Motoko , Tachiwana Hiroaki , Maruyama Reo , Hirota Toru , Saitoh Noriko
Published: June 2020

The eukaryotic nucleus is not a homogenous single‐spaced but a highly compartmentalized organelle, partitioned by various types of membraneless structures, including nucleoli, PML bodies, paraspeckles, DNA damage foci and RNA clouds. Over the past few decades, these nuclear structures have been implicated in biological reactions such as gene regulation and DNA damage response and repair, and are thought to provide “microenvironments,” facilitating these reactions in the nucleus. Notably, an altered morphology of these nuclear structures is found in many cancers, which may relate to so‐called “nuclear atypia” in histological examinations. While the diagnostic significance of nuclear atypia has been established, its nature has remained largely enigmatic and awaits characterization. Here, we review the emerging biophysical principles that govern biomolecular condensate assembly in the nucleus, namely, liquid‐liquid phase separation (LLPS), to investigate the nature of the nuclear microenvironment. In the nucleus, LLPS is typically driven by multivalent interactions between proteins with intrinsically disordered regions, and is also facilitated by protein interaction with nucleic acids, including nuclear non–coding RNAs. Importantly, an altered LLPS leads to dysregulation of nuclear events and epigenetics, and often to tumorigenesis and tumor progression. We further note the possibility that LLPS could represent a new therapeutic target for cancer intervention.
Physically Based Simulation and Rendering of Urban Thermography
Authors: Aguerre José Pedro , García‐Nevado Elena , Acuña Paz y Miño Jairo , Fernández Eduardo , Beckers Benoit
Published: June 2020

Urban thermography is a non‐invasive measurement technique commonly used for building diagnosis and energy efficiency evaluation. The physical interpretation of thermal images is a challenging task because they do not necessarily depict the real temperature of the surfaces, but one estimated from the measured incoming radiation. In this sense, the computational rendering of a thermal image can be useful to understand the results captured in a measurement campaign. The computer graphics community has proposed techniques for light rendering that are used for its thermal counterpart. In this work, a physically based simulation methodology based on a combination of the finite element method (FEM) and ray tracing is presented. The proposed methods were tested using a highly detailed urban geometry. Directional emissivity models, glossy reflectivity functions and importance sampling were used to render thermal images. The simulation results were compared with a set of measured thermograms, showing good agreement between them.
Unification by Fiat: Arrested Development of Predictive Processing
Authors: Litwin Piotr , Miłkowski Marcin
Published: June 2020

Predictive processing (PP) has been repeatedly presented as a unificatory account of perception, action, and cognition. In this paper, we argue that this is premature: As a unifying theory, PP fails to deliver general, simple, homogeneous, and systematic explanations. By examining its current trajectory of development, we conclude that PP remains only loosely connected both to its computational framework and to its hypothetical biological underpinnings, which makes its fundamentals unclear. Instead of offering explanations that refer to the same set of principles, we observe systematic equivocations in PP‐based models, or outright contradictions with its avowed principles. To make matters worse, PP‐based models are seldom empirically validated, and they are frequently offered as mere just‐so stories. The large number of PP‐based models is thus not evidence of theoretical progress in unifying perception, action, and cognition. On the contrary, we maintain that the gap between theory and its biological and computational bases contributes to the arrested development of PP as a unificatory theory. Thus, we urge the defenders of PP to focus on its critical problems instead of offering mere re‐descriptions of known phenomena, and to validate their models against possible alternative explanations that stem from different theoretical assumptions. Otherwise, PP will ultimately fail as a unified theory of cognition.
Acral localized acquired cutis laxa as presenting sign of underlying systemic amyloidosis
Authors: Vork Diana L. , Shah Kabeer K. , Youssef Molly J. , Wieland Carilyn N.
Published: June 2020

Acral localized acquired cutis laxa (ALACL) is a rare variant of acquired cutis laxa, and the clinical appearance is characterized by loose, redundant and wrinkled skin of the distal extremities. By definition, histopathology of affected tissue reveals sparse or fragmented elastic fibers. However, this can be difficult to assess on routine staining, and sometimes requires electron microscopy. The condition has been associated with plasma cell dyscrasias or recurrent inflammatory states. We present a case of a 65‐year‐old man who presented with enlarged and doughy finger pads. Skin biopsy showed diffuse dermal amyloid deposition displacing dermal stroma and reduction of elastic fibers, although these changes were subtle on routine hematoxylin and eosin staining. Mass spectrometry of laser capture microdissected tissue showed AL kappa‐type amyloid and further workup revealed a diagnosis of primary systemic AL‐kappa amyloidosis requiring bone marrow transplantation. This case represents an unusual presentation of acquired cutis laxa and highlights the need for a high index of suspicion when reviewing histopathology of this entity. In addition, the case highlights the importance of investigation into possible systemic associations, such as plasma cell dyscrasias.
Gastrointestinal endoscopy infection control strategy during COVID‐19 pandemic: Experience from a tertiary medical center in China
Authors: Zhang Shengyu , Wu Xi , Pan Hui , Wu Dong , Xu Tao , Shen Ning , Zhang Yizhen , Feng Yunlu , Wang Qiang , Jiang Qingwei , Guo Tao , Wu Dongsheng , Tang Shou‐jiang , Yang Aiming
Published: June 2020

Objectives

Coronavirus disease 2019 (COVID‐19) has spread globally and become a pandemic. The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) not only infects the gastrointestinal (GI) tract and causes GI symptoms, but also increases nosocomial transmission risk during endoscopic procedures for aerosol generation. We hereby share our infection control strategies aiming to minimize COVID‐19 transmission in the endoscopy center.

Methods

We established our infection control strategies based on the guidance of Chinese Society of Digestive Endoscopy and inputs from hospital infection control experts: admission control through the procedure and patient triage, environmental control to reduce possible virus exposure, proper usage of personal protective equipment (PPE), and scope disinfection and room decontamination. All endoscopic procedures accomplished during COVID‐19 outbreak and progress of stepwise resumption of elective endoscopy procedures were retrospectively reviewed.

Results

Only urgent or semi‐urgent procedures were performed during COVID‐19 outbreak. After no local new‐onset COVID‐19 case in Beijing for four weeks, we reopened the endoscopy center for elective procedures and monitored the outbreak continuously while maintaining a sustainable endoscopy service.

Conclusions

It is imperative that all endoscopy centers should establish standard infection control strategies in order to fight COVID‐19 pandemic based on national guidance and academic society guidelines and tailor them to individual resources. These measures and setup can also be reserved for future pandemics.
A novel case of reverse Takotsubo cardiomyopathy following brain biopsy
Authors: Ives Christopher W. , Smith Phillip A. , Atchley Travis J. , Pogwizd Steven M.
Published: June 2020

Reverse Takotsubo cardiomyopathy (rTTC) is a variant of Takotsubo cardiomyopathy (TTC) or stress‐induced cardiomyopathy. TTC is a transient cardiomyopathy resulting in a heart failure syndrome, triggered by emotional and/or physical stressors, that is usually self‐limited. rTTC is characterized by basal wall hypokinesis and apical wall hyperkinesis, the opposite of TTC. rTTC is more commonly associated with neurologic conditions, most notably intracranial hemorrhage. We present the first case in the literature of rTTC specifically following brain biopsy.
Cardiac mechanics in heart failure with preserved ejection fraction
Authors: Seetharam Karthik , Sengupta Partho P. , Bianco Christopher M.
Published: June 2020

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical entity associated with significant morbidity and mortality. Common comorbidities including hypertension, coronary artery disease, diabetes, chronic kidney disease, obesity, and increasing age predispose to preclinical diastolic dysfunction that often progresses to frank HFpEF. Clinical HFpEF is typically associated with some degree of diastolic dysfunction, but can occur in the absence of many conventional diastolic dysfunction indices. The exact biologic links between risk factors, structural changes, and clinical manifestations are not clearly apparent. Innovative approaches including deformation imaging have enabled deeper understanding of HFpEF cardiac mechanics beyond conventional metrics. Furthermore, predictive analytics through data‐driven platforms have allowed for a deeper understanding of HFpEF phenotypes. This review focuses on the changes in cardiac mechanics that occur through preclinical myocardial dysfunction to clinically apparent HFpEF.
Echocardiographic diagnosis and follow‐up for ALCAPA syndrome treated with the Takeuchi procedure
Authors: Arroyo‐Rodríguez Cuitláhuac , Rodríguez Zanella Hugo , Fritche Salazar Juan Francisco , Ruiz‐Esparza Maria Eugenia , Arias‐Godínez José Antonio
Published: June 2020

We present the case of an 18‐year‐old man with aborted sudden cardiac death. His initial echocardiogram suggested an anomalous origin of the left coronary artery from the pulmonary artery. Diagnosis was confirmed with coronary angiography. He underwent Takeuchi procedure and fully recovered. A two‐year follow‐up echocardiogram showed a moderate supravalvular pulmonary stenosis related to the transpulmonary baffle. The presence of extensive collateral circulation should raise suspicion of ALCAPA. Postoperative surveillance in this group of patients needs to be oriented in finding complications such as supravalvular pulmonary stenosis, aortic and pulmonary valve insufficiency, and baffle obstruction and leaks.
Applications of three‐dimensional transesophageal echocardiography in congenital heart disease
Authors: Jone Pei‐Ni
Published: June 2020

Three‐dimensional echocardiography allows for presurgical planning for congenital heart disease, reduces radiation using fusion imaging in catheter interventions, and provides guidance during catheter interventions and lead placements or extractions. The purpose of this review is to detail applications of three‐dimensional transesophageal echocardiography in presurgical planning of congenital heart disease, guidance of catheter interventions such as fusion imaging, and guidance in electrophysiology lead extractions or placements.
Diastolic function of the left and right ventricles of the heart in outpatients with arterial hypertension
Authors: Kirillova Venera , Garganeeva Alla , Sokolova Ludmila
Published: June 2020

Aim

The aim of the study is to investigate the impairment of diastolic function of the left ventricle (LV) and the right ventricle (RV) in arterial hypertension outpatients.

Materials and methods

Arterial hypertension patients (n = 299) and practically healthy people (n = 62) were examined on an outpatient basis. Echocardiographically, diastolic dysfunctions of both ventricles were evaluated.

Results

All the arterial hypertension patients had a pattern of diastolic dysfunction (DD) of the RV of different grades (grade I RVDD and grade II RVDD), regardless of the presence or absence of pulmonary arterial hypertension. Patterns of grade I LVDD and grade I RVDD were detected in 84 patients. Patterns of grade I LVDD and grade II RVDD were detected in 77 patients. Patterns of grade II LVDD and grade II RVDD were detected in 41 patients. A pattern of grade II RVDD with normal left ventricular diastolic function was detected in 97 patients with a short duration of disease (3.92 ± 0.48 years) vs the other groups with more than 15 years of hypertension. One hundred and seventy‐five arterial hypertension patients had grade I or II LVDD only in 18.3% of cases according to the recommendations of the American and European societies of echocardiographers (2016).

Conclusion

The patients with a short period of hypertensive disease have only the pseudonormal pattern of RVDD, which can be an early diagnostic marker of heart failure. Echocardiographic diagnosis of diastolic function made according to various criteria can both increase the number of chronic heart failure patients and significantly decrease it.
FINANCE‐INEQUALITY NEXUS: THE LONG AND THE SHORT OF IT
Authors: Makhlouf Yousef , Kellard Neil M. , Vinogradov Dmitri V.
Published: June 2020

Financial development affects income inequality differently in the short and in the long term. Investigating OECD countries from 1870–2011, we find in the short run, an improvement in financial development tends to reduce inequality, while in the long run, more finance contributes to more inequality. The short‐run effect concurs with theories advocating financial development increases the availability of financial services, primarily for the poor. However, this effect becomes nil within a few years. Results thus imply that policies aimed at reducing inequality through improving access of the poor to finance need to be carefully designed to ensure longevity of impact. (JEL O15, O16, D31, G20, E44)