bluuebunny/crossref_metadata_2025 huggingface dataset:
Flyby encounters between two planetary systems II: exploring the interactions of diverse planetary system architectures
Authors: Li Daohai , Mustill Alexander J , Davies Melvyn B
Published: June 2020

Planetary systems formed in clusters may be subject to stellar encounter flybys. Here, we create a diverse range of representative planetary systems with different orbital scales and planets’ masses and examine encounters between them in a typical open cluster. We first explore the close-in multisuper Earth systems ≲0.1 au. They are resistant to flybys in that only ones inside a few au can destabilize a planet or break the resonance between such planets. But these systems may capture giant planets on to wide orbits from the intruding star during distant flybys. If so, the original close-in small planets’ orbits may be tilted together through Kozai–Lidov mechanism, forming a ‘cold’ system that is significantly inclined against the equator of the central host. Moving to the intermediately placed planets around solar-like stars, we find that the planets’ mass gradient governs the systems’ long-term evolution post-encounter: more massive planets have better chances to survive. Also, a system’s angular momentum deficit, a quantity describing how eccentric/inclined the orbits are, measured immediately after the encounter, closely relates to the longevity of the systems – whether or not and when the systems turn unstable in the ensuing evolution millions of years post-encounter. We compare the orbits of the surviving planets in the unstable systems through (1) the immediate consequence of the stellar fly or (2) internal interplanetary scattering long post-encounter and find that those for the former are systematically colder. Finally, we show that massive wide-orbit multiplanet systems like that of HR 8799 can be easily disrupted and encounters at a few hundreds of au suffice.
Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair
Authors: Kalasova Ilona , Hailstone Richard , Bublitz Janin , Bogantes Jovel , Hofmann Winfried , Leal Alejandro , Hanzlikova Hana , Caldecott Keith W
Published: June 2020

Hereditary mutations in polynucleotide kinase-phosphatase (PNKP) result in a spectrum of neurological pathologies ranging from neurodevelopmental dysfunction in microcephaly with early onset seizures (MCSZ) to neurodegeneration in ataxia oculomotor apraxia-4 (AOA4) and Charcot-Marie-Tooth disease (CMT2B2). Consistent with this, PNKP is implicated in the repair of both DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs); lesions that can trigger neurodegeneration and neurodevelopmental dysfunction, respectively. Surprisingly, however, we did not detect a significant defect in DSB repair (DSBR) in primary fibroblasts from PNKP patients spanning the spectrum of PNKP-mutated pathologies. In contrast, the rate of SSB repair (SSBR) is markedly reduced. Moreover, we show that the restoration of SSBR in patient fibroblasts collectively requires both the DNA kinase and DNA phosphatase activities of PNKP, and the fork-head associated (FHA) domain that interacts with the SSBR protein, XRCC1. Notably, however, the two enzymatic activities of PNKP appear to affect different aspects of disease pathology, with reduced DNA phosphatase activity correlating with neurodevelopmental dysfunction and reduced DNA kinase activity correlating with neurodegeneration. In summary, these data implicate reduced rates of SSBR, not DSBR, as the source of both neurodevelopmental and neurodegenerative pathology in PNKP-mutated disease, and the extent and nature of this reduction as the primary determinant of disease severity.
Antisense oligonucleotide-mediated correction of CFTR splicing improves chloride secretion in cystic fibrosis patient-derived bronchial epithelial cells
Authors: Michaels Wren E , Bridges Robert J , Hastings Michelle L
Published: June 2020

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, encoding an anion channel that conducts chloride and bicarbonate across epithelial membranes. Mutations that disrupt pre-mRNA splicing occur in >15% of CF cases. One common CFTR splicing mutation is CFTR c.3718-2477C>T (3849+10 kb C>T), which creates a new 5′ splice site, resulting in splicing to a cryptic exon with a premature termination codon. Splice-switching antisense oligonucleotides (ASOs) have emerged as an effective therapeutic strategy to block aberrant splicing. We test an ASO targeting the CFTR c.3718-2477C>T mutation and show that it effectively blocks aberrant splicing in primary bronchial epithelial (hBE) cells from CF patients with the mutation. ASO treatment results in long-term improvement in CFTR activity in hBE cells, as demonstrated by a recovery of chloride secretion and apical membrane conductance. We also show that the ASO is more effective at recovering chloride secretion in our assay than ivacaftor, the potentiator treatment currently available to these patients. Our findings demonstrate the utility of ASOs in correcting CFTR expression and channel activity in a manner expected to be therapeutic in patients.
Intrinsic disorder is essential for Cas9 inhibition of anti-CRISPR AcrIIA5
Authors: An So Young , Ka Donghyun , Kim Iktae , Kim Eun-Hee , Kim Nak-Kyoon , Bae Euiyoung , Suh Jeong-Yong
Published: June 2020

Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins provide adaptive immunity to prokaryotes against invading phages and plasmids. As a countermeasure, phages have evolved anti-CRISPR (Acr) proteins that neutralize the CRISPR immunity. AcrIIA5, isolated from a virulent phage of Streptococcus thermophilus, strongly inhibits diverse Cas9 homologs, but the molecular mechanism underlying the Cas9 inhibition remains unknown. Here, we report the solution structure of AcrIIA5, which features a novel α/β fold connected to an N-terminal intrinsically disordered region (IDR). Remarkably, truncation of the N-terminal IDR abrogates the inhibitory activity against Cas9, revealing that the IDR is essential for Cas9 inhibition by AcrIIA5. Progressive truncations and mutations of the IDR illustrate that the disordered region not only modulates the association between AcrIIA5 and Cas9–sgRNA, but also alters the catalytic efficiency of the inhibitory complex. The length of IDR is critical for the Cas9–sgRNA recognition by AcrIIA5, whereas the charge content of IDR dictates the inhibitory activity. Conformational plasticity of IDR may be linked to the broad-spectrum inhibition of Cas9 homologs by AcrIIA5. Identification of the IDR as the main determinant for Cas9 inhibition expands the inventory of phage anti-CRISPR mechanisms.
IncC conjugative plasmids and SXT/R391 elements repair double-strand breaks caused by CRISPR–Cas during conjugation
Authors: Roy David , Huguet Kevin T , Grenier Frédéric , Burrus Vincent
Published: June 2020

Bacteria have evolved defence mechanisms against bacteriophages. Restriction-modification systems provide innate immunity by degrading invading DNAs that lack proper methylation. CRISPR–Cas systems provide adaptive immunity by sampling the genome of past invaders and cutting the DNA of closely related DNA molecules. These barriers also restrict horizontal gene transfer mediated by conjugative plasmids. IncC conjugative plasmids are important contributors to the global dissemination of multidrug resistance among pathogenic bacteria infecting animals and humans. Here, we show that IncC conjugative plasmids are highly resilient to host defence systems during entry into a new host by conjugation. Using a TnSeq strategy, we uncover a conserved operon containing five genes (vcrx089–vcrx093) that confer a novel host defence evasion (hde) phenotype. We show that vcrx089–vcrx090 promote resistance against type I restriction-modification, whereas vcrx091–vcxr093 promote CRISPR–Cas evasion by repairing double-strand DNA breaks via recombination between short sequence repeats. vcrx091, vcrx092 and vcrx093 encode a single-strand binding protein, and a single-strand annealing recombinase and double-strand exonuclease related to Redβ and λExo of bacteriophage λ, respectively. Homologous genes of the integrative and conjugative element R391 also provide CRISPR–Cas evasion. Hence, the conserved hde operon considerably broadens the host range of large families of mobile elements spreading multidrug resistance.
Temperature-dependent Rutile Solubility in Garnet and Clinopyroxene from Mantle Eclogite: Implications for Continental Crust Formation and V-based Oxybarometry
Authors: Aulbach Sonja
Published: June 2020

Despite its accessory mineral status in metabasaltic rocks, rutile controls the whole-rock Ti, Nb and Ta budget. These are key elements used to trace fluid- and melt-mediated mass transfer across the mantle–crust boundary. Rutile also contains significant amounts of the redox-sensitive element V, which is increasingly used to estimate oxygen fugacity. Kimberlite-borne mantle eclogite xenoliths, which are frequently rutile-bearing, have been interpreted as residues from the extraction of silicic partial melt similar in composition to the average continental crust. Published mineral compositions for eclogite xenoliths from various cratons combined with geothermobarometrical calculations show that TiO2 contents in garnet and clinopyroxene increase with increasing temperature of last residence in the lithospheric mantle, whereas apparent clinopyroxene–garnet distribution coefficients decrease. This implies that (1) increasing TiO2 contents in eclogitic garnet or clinopyroxene are not a signature of increasing metasomatism with depth, (2) whole-rock eclogites reconstructed without rutile will increasingly underestimate TiO2, Nb and Ta contents with decreasing temperature, and (3) low-temperature eclogites are more likely to contain free rutile. Only about a third of the ∼250 samples considered here would have whole-rock TiO2 contents (reconstructed with calculated rutile modes) required for rutile saturation during subduction and partial melting. If there is a role for subducting oceanic crust now sampled as mantle eclogite, the characteristic Ti–Nb–Ta depletion in continental crust may require fluid-dominated processes, where these elements are not efficiently mobilised. In garnet, Ti uptake on the octahedral site is accommodated primarily by coupled substitution with Na and subordinately with a divalent metal cation, and there is no evidence for substitution on the tetrahedral site. For samples equilibrated to the conductive geotherm, Ti in addition to Na enrichment may be indicative of equilibration in the diamond stability field. The jadeite component in clinopyroxene as a function of temperature is a good indicator of the geotherm to which the various samples equilibrated, and can be used to reveal samples within each suite that have been affected by isobaric heating. The distribution of V in eclogitic garnet, clinopyroxene and rutile is affected by bulk composition, temperature and oxygen fugacity. In carefully vetted, low-temperature samples with TiO2 contents >0·8 wt%, V-based oxybarometry may monitor redox conditions prevailing during metamorphism of oceanic crust or, at lower TiO2, during (secular) cooling-related exsolution of rutile from garnet or clinopyroxene, whereas in higher-temperature ilmenite-bearing samples metasomatic conditions may be recorded.
Common Biological Modulators of Acute Pain: An Overview Within the AAAPT Project (ACTTION-APS-AAPM Acute Pain Taxonomy)
Authors: Curatolo Michele
Published: June 2020

Objective

The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) project relies on the identification of modulators to improve characterization and classification of acute pain conditions. In the frame of the AAAPT effort, this paper presents an overview of common biological modulators of acute pain.

Methods

Nonsystematic overview.

Results

Females may experience more acute pain than males, but the clinical significance may be modest. Increasing age is associated with decreasing analgesic requirement and decreasing pain intensity after surgery and with higher risk of acute low back pain. Racial and ethnic minorities have worse pain, function, and perceived well-being. Patients with preexisting chronic pain and opioid use are at higher risk of severe acute pain and high opioid consumption. The OPRM1 gene A118G polymorphism is associated with pain severity and opioid consumption, with modest quantitative impact. Most studies have found positive associations between pain sensitivity and intensity of acute clinical pain. However, the strength of the association is unclear. Surgical techniques, approaches, and complications influence postoperative pain.

Conclusions

Sex, age, race, ethnicity, preexisting chronic pain and opioid use, surgical approaches, genetic factors, and pain sensitivity are biological modulators of acute pain. Large studies with multisite replication will quantify accurately the association between modulators and acute pain and establish the value of modulators for characterization and classification of acute pain conditions, as well as their ability to identify patients at risk of uncontrolled pain. The development and validation of quick, bed-side pain sensitivity tests would allow their implementation as clinical screening tools. Acute nonsurgical pain requires more investigation.
Clonal haematopoiesis is increased in early onset in systemic sclerosis
Authors: Ricard Laure , Hirsch Pierre , Largeaud Laëtitia , Deswarte Caroline , Jachiet Vincent , Mohty Mohamad , Rivière Sébastien , Malard Florent , Tenon Maxime , de Vassoigne Frédéric , Fain Olivier , Gaugler Béatrice , Rossignol Julien , Delhommeau François , Mekinian Arsène ,   on behalf MINHEMON (French Network of dysimmune disorders associated with hemopathies)
Published: June 2020

Objectives

SSc is an autoimmune disease characterized by fibrosis, microangiopathy and immune dysfunctions including dysregulation of proinflammatory cytokines. Clonal haematopoiesis of indeterminate potential (CHIP) is defined by the acquisition of somatic mutations in haematopoietic stem cells leading to detectable clones in the blood. Recent data have shown a higher risk of cardiovascular disease in patients with CHIP resulting from increased production of proinflammatory cytokines and accelerated atherosclerosis. Eventual links between CHIP and autoimmune diseases are undetermined. The aim of our study was to evaluate the prevalence of CHIP in SSc patients and its association with clinical phenotype.

Methods

Forty-one genes frequently mutated in myeloid malignancies were sequenced in peripheral blood mononuclear cells from 90 SSc patients and 44 healthy donors.

Results

A total of 15 somatic variants were detected in 13/90 SSc patients (14%) and four somatic variants in 4/44 (9%) healthy donors (HD) (P = 0.58). The prevalence of CHIP was significantly higher in younger SSc patients than in HD: 25% (6/24) vs 4% (1/26) (P = 0.045) under 50 years and 17% (7/42) vs 3% (1/38) (P = 0.065) under 60 years. The prevalence of CHIP in patients over 70 years was similar in SSc patients and healthy donors. The most common mutations occurred in DNMT3A (seven variants). No major clinical differences were observed between SSc patients with or without CHIP.

Conclusion

Whether CHIP increases the risk to develop SSc or is a consequence of a SSc-derived modified bone marrow micro-environment remains to be explored.
Pre-operative withholding of infliximab and the risk of infections after major surgery in patients with rheumatoid arthritis
Authors: Ward Michael M , Dasgupta Abhijit
Published: June 2020

Objectives

Withholding TNF inhibitors (TNFI) before surgery has been recommended due to concern for post-operative infection. We examined the risks of post-operative infections and mortality in patients with RA in relation to the pre-operative timing of infliximab infusion.

Methods

In this population-based retrospective cohort study, we used US Medicare claims data from 2007 to 2015 to identify patients with RA who underwent coronary artery bypass grafting (CABG), aortic or vascular surgery, or bowel resection, and who were treated with infliximab in the 90 days prior to surgery. We examined associations between the timing of infusion and infections and mortality in the 30 days after surgery. We adjusted for the predicted probability of post-operative infection or death, demographic characteristics, use of MTX, post-operative blood transfusion and hospital volume.

Results

We studied 712 patients with CABG, 244 patients with vascular surgery and 862 patients with bowel resections. Post-operative pneumonia occurred in 7.4–11.9%, urinary tract infection in 9.0–15.2%, surgical site infection in 3.2–18.9%, sepsis in 4.2–9.6% and death in 3.5–7.0% among surgery cohorts. There was no association between the time from last infliximab dose to surgery and the risk of post-operative infection or mortality in any surgical cohort. No subgroups were identified that had an increased risk of infection with more proximate use of infliximab.

Conclusion

Among elderly patients with RA, risks of infection and mortality after major surgery were not related to the pre-operative timing of infliximab infusion.
Tracing the Roots of Dementia Praecox: The Emergence of Verrücktheit as a Primary Delusional-Hallucinatory Psychosis in German Psychiatry From 1860 to 1880
Authors: Kendler Kenneth S
Published: June 2020

While the roots of mania and melancholia can be traced to the 18th century and earlier, we have no such long historical narrative for dementia praecox (DP). I, here, provide part of that history, beginning with Kraepelin’s chapter on Verrücktheit for his 1883 first edition textbook, which, over the ensuing 5 editions, evolved into Kraepelin’s mature concepts of paranoia and paranoid DP. That chapter had 5 references published from 1865 to 1879 when delusional-hallucinatory syndromes in Germany were largely understood as secondary syndromes arising from prior episodes of melancholia and mania in the course of a unitary psychosis. Each paper challenged that view supporting a primary Verrücktheit as a disorder that should exist alongside mania and melancholia. The later authors utilized faculty psychology, noting that primary Verrücktheit resulted from a fundamental disorder of thought or cognition. In particular, they argued that, while delusions in mania and melancholia were secondary, arising from primary mood changes, in Verrücktheit, delusions were primary with observed changes in mood resulting from, and not causing, the delusions. In addition to faculty psychology, these nosologic changes were based on the common-sense concept of understandability that permitted clinicians to distinguish individuals in which delusions emerged from mood changes and mood changes from delusions. The rise of primary Verrücktheit in German psychiatry in the 1860–1870s created a nosologic space for primary psychotic illness. From 1883 to 1899, Kraepelin moved into this space filling it with his mature diagnoses of paranoia and paranoid DP, our modern-day paranoid schizophrenia.
Assessing outcomes of genetic selection panels to predict marbling in crossbred beef cattle
Authors: Weber Tanya M , Buseman Brianna J , Nasados James A , Lancaster Jessica M , Van Buren Jessie B , Smart Jaxon H , Bass Phillip D , Murdoch Gordon K , Insausti Kizkitza , Colle Michael J
Published: June 2020

The objective of this study was to evaluate the effectiveness of genetic panel marbling indexes [Igenity (IT) and PredicGEN (PG)] to predict marbling and tenderness of crossbred cattle. Steers (n = 23) were harvested at the University of Idaho Meat Science Laboratory, and blood samples were submitted to Neogen and Zoetis for genetic panel analysis. Forty-eight hours postharvest, one boneless strip loin was collected from each carcass, and six 2.54-cm thick steaks were cut from each strip loin. Steaks were aged for 14 and 21 d and assigned to consumer sensory evaluation or Warner–Bratzler Shear Force (WBSF) analysis. Results were analyzed using the Mixed Model procedure of the Statistical Analysis System (SAS Institute, Inc., Cary, NC). Carcasses were grouped by marbling index score into Low IT (IT indexes 3–6; n = 16; marbling score (MS) = 410), High IT (IT indexes 7–10; n = 7; MS = 496), Low PG (PG index <50; n = 9; MS = 398), or High PG (PG index ≥50; n = 14; MS = 458). Mean MS was observed to be greater in High IT steaks than Low IT (P < 0.01) and greater in High PG steaks than Low PG (P = 0.01). There was a trend observed in WBSF between IT marbling groups (P = 0.06); however, no difference in WBSF was observed between PG marbling groups (P = 0.83). Consumers did not report differences between IT marbling groups in terms of acceptability (P = 0.99) or tenderness (P = 0.24). Additionally, consumers could not detect differences between PG marbling groups in terms of acceptability (P = 0.75) or tenderness (P = 0.40). Consumers consistently preferred Choice steaks over Select steaks in terms of acceptability (P = 0.02) and tenderness (P = 0.02). In conclusion, though consumers were not able to tell the difference between steaks from each of the genetic panels, using genetic panels to predict marbling, in conjunction with proper nutrition and handling practices, could be a beneficial tool to producers making decisions about retaining ownership at the feedlot.
Compassionate Care: Making It a Priority and the Science Behind It
Authors: Goldberg Michael J.
Published: June 2020

Background:

Compassion is the deep feeling that arises when confronted with another’s suffering coupled with a strong desire to alleviate that suffering. Until recently, evidence was lacking as to whether compassion was innate, acquired, or modifiable. Because patients who experience compassionate health care report better clinical outcomes, an understanding of the science behind it may give rise to methods of incorporating compassion into clinical care delivery.

Methods:

A high-level summary of the social and neuroscience research was constructed.

Results:

Functional neuroimaging of empathy and compassion demonstrates neural networks involving the insula, cingulate, and prefrontal cortices suggesting neurological hard wiring for these emotional and cognitive experiences. Neuroscience and social science research evidence supports the presence of cognitive and/or emotional empathy in all individuals studied; that empathy and compassion can be taught; and that both internal and external factors influence their expression.

Conclusions:

Burnout may result when clinicians know what their patients need (thereby activating the empathy/pain neural pathways) but are unable to deliver that care (therefore inactivation of the compassion/reward neural pathways). Understanding the neuroscience underlying empathy and compassion informs practical programs that mitigate burnout and creates a more compassionate workplace.
Building a Culture of Wellness When Systems Do Not Allow for Collaborative Care
Authors: Baden Harris P.
Published: June 2020

Introduction:

Health care is fragmented and frustrating to patients and physicians. The consequences include patient and physician dissatisfaction.

Methods:

The author’s perspective is informed by his research, innovation, and leadership to optimize the experience of care for physicians and patients.

Results:

Understanding and prioritizing the touchpoints between patients and physicians is essential to designing health care delivery that is compassionate to patients and is fulfilling and sustainable for physicians.

Conclusions:

Hospital administrative leaders and physicians must reject the culture of a dichotomy in purpose, and partner to create systems that make the right thing to do, the easy thing to do.

Levels of Evidence:

Level V—expert opinion.
Inadvertent Rupture of a Silicone Breast Implant during Fat Grafting: Surgical and Radiological Findings
Authors: Stewart Christopher N. , Heinrich Cherrie A.
Published: June 2020

Autologous fat grafting is a common, relatively safe procedure for breast augmentation and reconstruction. The most commonly reported complications tend to be fat necrosis and oil cysts. The incidence of rare events, such as breast implant rupture, is likely underreported. Here we present the case of a patient who underwent fat grafting and sustained implant rupture with injection of fat within the silicone implant. She complained of her implant changing shape and magnetic resonance imaging (MRI) showed classic signs of implant rupture (linguini sign). At the time of surgery however, fat was surprisingly found to be within the implant itself. To our knowledge this finding has yet to be reported. Here we review the radiologic and surgical findings of implant rupture following fat grafting and present some suggestions to prevent this occurrence and ensure safe, aesthetically pleasing outcomes.
Chronic Conjunctival Chemosis—A New Ocular Side Effect of Crizotinib
Authors: Das Joyeeta , Das Nibedita
Published: June 2020

Crizotinib, a targeted molecular therapy drug which inhibits tyrosine kinase, is approved for treatment of non-small cell lung carcinoma which has some ocular side effects like photopsia and delayed dark adaptation.This report documents a unique case of persistent conjunctival chemosis likely due to side effects of crizotinib therapy. A 64-year-old gentleman on crizotinib for metastatic adenocarcinoma of the lung presented with conjunctival chemosis in right eye which appeared 1 month after uneventful clear corneal phacoemulsification surgery. The patient was on crizotinib 250 mg twice a day started 2 months before cataract surgery. Clinical examination revealed marked inferior bulbar conjunctival edema of the right eye. Anterior segment optical coherence tomography, slit-lamp photographs, and magnetic resonance imaging orbit and systemic investigation were done to rule out other causes of conjunctival edema. Magnetic resonance imaging shows conjunctival and preseptal edema around both eye and thinning of the optic nerve in the right eye. Anterior segment optical coherence tomography revealed elevated hyper-reflective thickened conjunctival layer with dilated empty thin wall dark spaces of varying caliber. Chemosis was persisted for the next 3 months and not responded to oral acetazolamide, topical steroid and decongestive eyedrops. After 3 months, crizotinib was discontinued by oncologist due to drug intolerance and surprisingly within 1 week, the conjunctival edema was disappeared totally. To the best of the authors' knowledge, this is the first reported case of persistent unilateral non-inflammatory conjunctival chemosis caused by crizotinib. The physicians should be vigilant about these complications.
Involvement of Multiple Trigeminal Nerve Branches in IgG4-Related Orbital Disease
Authors: Elkhamary Sahar M. , Cruz Antonio Augusto V. , Zotin Maria C. , Cintra Murilo , Akaishi Patricia , Galindo-Ferreiro Alicia , Alkatan Hind M. , Chahud Fernando
Published: June 2020

Purpose:

To describe the occurrence of multiple trigeminal nerves (TGNs) enlargement in patients with orbital IgG4-related disease.

Methods:

Retrospective review of MRI findings and medical records of 6 patients (10 orbits) with orbital IgG4-related disease and enlargement of more than 1 TGN. Orbital biopsies were performed in all cases revealing the typical lymphoplasmacytic infiltrate with significant plasma cell positivity for IgG4 (IgG4+/IgG ratio ≥ 40%). Three experienced neuroradiologists reviewed the MRI sequences using a digital imaging viewer system (Horos, https://horosproject.org/).

Results:

Bilateral involvement of at least 2 TGNs divisions was detected in all 6 patients. Enlargement of both V1 and V2 nerves was diagnosed in 5 patients, and in 3 cases, all TGN divisions were involved. V2 nerves were the most affected. In this division, all 12 infraorbital nerves were enlarged, followed by lesser palatines (10/83.3%), superior alveolar (10/83.3%), and zygomatic (6/50%). V1 and V3 nerves were less affected albeit 9 (75%) frontal branches (V1), and 50% of the inferior alveolar (V3) nerves were also enlarged.

Conclusions:

Widespread involvement of the TGN is an important feature of IgG4-related disease.
Tinnitus Affects Speech in Noise Comprehension in Individuals With Hearing Loss
Authors: Oosterloo Berthe C. , Homans Nienke C. , Goedegebure André
Published: June 2020

Background:

Tinnitus is a prevalent auditory disorder that frequently co-occurs with hearing loss. It is suggested that tinnitus might have negative impact on speech perception. However, studies thus far have not been able to disentangle tinnitus, hearing loss, and speech in noise intelligibility. We therefore investigated whether there is an association between tinnitus and speech understanding in noise, independent of hearing loss.

Methods:

Of 4,211 participants from the population-based Rotterdam Study (mean age 67.8 [SD 8.9], 57.3% female) data was available on tinnitus, pure-tone audiometry, and digits in noise test. We compared the speech reception threshold in noise (SRTn) in participants with and without tinnitus for the whole population as well as for subgroups stratified for average hearing threshold in 10-dB strata. Additionally, we regressed tinnitus on SRTn with a multivariable regression model, adjusting for sex, age, highest achieved education, and cognitive function.

Results:

Participants with tinnitus (20.8%) had a higher SRTn (−3.6 dB [SD 3.7] versus −4.6 dB [SD 3.1]). This difference remained only in the subgroups of participants with hearing loss, between 0.6 and 0.8 dB difference in the SRTn for the different subgroups. In the fully adjusted model tinnitus was associated with 0.2 dB (95% CI 0.00, 0.39) SRTn increase.

Conclusion:

We have shown that tinnitus is associated with speech intelligibility in noise, but it is a small effect, only found in people with co-occurring hearing loss.
Serial Clinical Scoring to Assess Transported Pediatric Patients
Authors: Holt Tanya , Parker Kayla , Shaw Adam , Hansen Gregory
Published: June 2020

Objectives

The objective of this study was to evaluate serial Transport Risk Assessment in Pediatrics (TRAP) scoring during pediatric critical care transport as a potential measure for specialized pediatric transport teams (PTTs).

Methods

This was a retrospective study with a provincial PTT from a tertiary hospital pediatric intensive care unit. All acutely ill children who were transported by the PTT between 2018 and 2019 were included in the study. The TRAP scores were measured at time of transport team arrival (TRAP1), time at arrival to tertiary center (TRAP2), and 4 hours postarrival to tertiary center (TRAP3).

Results

A total of 300 transports were included. Patients' mean age was 54 months, with lower respiratory tract infection (40.7%) as the most common diagnosis. There were significant differences between TRAP1-TRAP2 (P < 0.01) and TRAP1-TRAP3 (P < 0.01), but not between TRAP2-TRAP3 (P = 0.67). The most significant improvements of ΔTRAP1-TRAP2 scores were seen in septic shock (mean, 2.0; SD, 1.7).

Conclusions

The TRAP scores improved following the PTTs' arrival to acutely ill children, particularly with sepsis. Serial TRAP scoring may present a system for evaluation of team performance and/or characterize disease states that are positively impacted by PTTs. Future prospective evaluation is needed to validate TRAP for this purpose.
Relationship Between Breast Ultrasound Background Echotexture and Magnetic Resonance Imaging Background Parenchymal Enhancement and the Effect of Hormonal Status Thereon
Authors: Kim Suk Jung , Jung Hyun Kyung , Han Boo-Kyung , Lee Jin Hwa , Oh Kyung Seung , Lee Jung Sun , Lee Yedaun
Published: June 2020

We studied the relationship between breast ultrasound background echotexture (BET) and magnetic resonance imaging (MRI) background parenchymal enhancement (BPE) and whether this relationship varied with hormonal status and amount of fibroglandular tissue (FGT) on MRI. Two hundred eighty-three Korean women (52.1 years; range = 27–79 years) with newly diagnosed primary breast cancer who underwent preoperative breast ultrasound and MRI were retrospectively studied. Background echotexture, BPE, and FGT were classified into 4 categories, and age, menopausal status, menstrual cycle regularity, and menstrual cycle stage at MRI were recorded. Background echotexture and BPE relationship was assessed overall, and in menopausal, FGT, menstrual cycle regularity, and menstrual cycle stage subgroups. Background echotexture and BPE correlated in women overall, and menopausal, FGT, and menstrual cycle subgroups and those in the first half of the cycle (all P < 0.001). Background echotexture reflects BPE, regardless of menopausal status, menstrual cycle regularity, and FGT and may be a biomarker of breast cancer risk.
Fibrin Glue and Its Alternatives in Peripheral Nerve Repair
Authors: Chow Nathan , Miears Hunter , Cox Cameron , MacKay Brendan
Published: June 2020

Over the past century, many advancements have been made in peripheral nerve repair, yet these reconstructions still remain a challenge. Although sutures have historically been used for neurorrhaphy, they sometimes fail to provide optimal outcomes. As a result, multiple adhesive compounds are currently being investigated for their efficacy in nerve repair. Recently, fibrin glue has shown utility in peripheral nerve repair, and the body of evidence supporting its use continues to grow. Fibrin glue has been shown to reduce inflammation, improve axonal regeneration, and provide excellent functional results. This alternative to traditional suture neurorrhaphy could potentially improve outcomes of peripheral nerve reconstruction.
Satisfaction From Plastic Surgery Residency
Authors: Kaufman Tal , Ad-El Dean
Published: June 2020

Background

Plastic surgery residency programs in Israel have undergone several changes over the years, but the perspectives and satisfaction of the residents have not been investigated.

Methods

An anonymous national survey of plastic surgery residents in Israel was performed. Demographic, professional, and education variables were summarized using descriptive statistics, and findings were related to self-reported satisfaction levels using univariate analysis.

Results

The response rate was 75.9%. Response rates to surgery and education-related items were as follows: 60% performed 5 to 15 surgeries/month; 60.3% performed fewer than 5 surgeries/month as the primary surgeon; 57.3% and 77.8%, respectively, received surgical and academic instruction from fewer than half the attending physicians; 33.9% and 32.3%, respectively, had little or no in-hospital exposure to aesthetic surgeries. The average overall satisfaction rate was 3.33/5. Ten variables were significantly associated with increased satisfaction: total number of surgeries performed (P = 0.01); active participation in complex procedures (P = 0.0009); performing preoperative and postoperative management for one's patients (P = 0.016); marking one's patients preoperatively (P = 0.037); managing complications of one's patients (P = 0.0027); receipt of surgical instruction (P = 0.0035); receipt of academic medical instruction (P < 0.0001); sense that the training will provide the proper professional level (P < 0.0001) and independence (P = 0.0002); and subjective correspondence between demands and capabilities (P = 0.0004).

Conclusions

This study identifies several factors associated with plastic surgery resident satisfaction. It highlights factors that warrant changes by plastic surgery departments and faculty to improve resident training and increase their satisfaction. The questionnaire can also serve as a diagnostic and follow-up tool.
Parapseudoflavitalea muciniphila gen. nov., sp. nov., a member of the family Chitinophagaceae isolated from a human peritoneal tumour and reclassification of Pseudobacter ginsenosidimutans as Pseudoflavitalea ginsenosidimutans comb. nov.
Authors: Lawson Paul A. , Patel Nisha B. , Mohammed Ahmed , Moore Edward R. B. , Lo Alexander S. , Sardi Armando , Davis Jeffrey M. , Doyle D. Annie , Hui Yvonne , Testerman Traci
Published: June 2020

A Gram-stain-negative, microaerophilic, non-motile, rod-shaped bacterium strain designated PMP191FT, was isolated from a human peritoneal tumour. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the organism formed a lineage within the familyChitinophagaceaethat was distinct from members of the genusPseudoflavitalea(95.1–95.2 % sequence similarity) andPseudobacter ginsenosidimutans(94.4 % sequence similarity). The average nucleotide identity values between strain PMP191FTandPseudoflavitalea rhizosphaeraeT16R-265TandPseudobacter ginsenosidimutansGsoil 221Twas 68.9 and 62.3% respectively. The only respiratory quinone of strain PMP191FTwas MK-7 and the major fatty acids were iso-C15 : 0, iso-C15 : 1G and summed feature 3 (C16:1ω7cand/or C16:1ω6c). The polar lipids consisted of phosphatidylethanolamine and some unidentified amino and glycolipids. The G+C content of strain PMP191FTcalculated from the genome sequence was 43.4 mol%. Based on phylogenetic, phenotypic and chemotaxonomic evidence, strain PMP191FTrepresents a novel species and genus for which the nameParapseudoflavitalea muciniphilagen. nov., sp. nov. is proposed. The type strain is PMP191FT(=DSM 104999T=ATCC BAA-2857T= CCUG 72691T). The phylogenetic analyses also revealed thatPseudobacter ginsenosidimutansshared over 98 % sequence similarly to members of the genusPseudoflavitalea. However, the average nucleotide identity value betweenPseudoflavitalea rhizosphaeraeT16R-265T, the type species of the genus andPseudobacter ginsenosidimutansGsoil 221Twas 86.8 %. Therefore, we also propose thatPseudobacter ginsenosidimutansbe reclassified asPseudoflavitalea ginsenosidimutanscomb. nov.
Chitinophaga tropicalis sp. nov., isolated from forest soil
Authors: Zhang Xian-Jiao , Feng Guang-Da , Yao Qing , Zhang Jun , Phuong Le Thi Bich , Zhu Honghui
Published: June 2020

A novel bacterial strain, designated ysch24T, was isolated from a forest soil sample collected from the Cat Tien National Park, southern Vietnam. Cells were Gram-stain-negative, aerobic, gliding, filamentous or rod-shaped. The results of 16S rRNA gene analyses revealed that strain ysch24T belongs to the genus

Chitinophaga

, and was most closely related to

Chitinophaga silvisoli

GDMCC 1.1411T (97.4 %), followed by

Chitinophaga oryziterrae

JCM 16595T (97.3 %) and

Chitinophaga sancti

NBRC 15057T (96.9 %). The average nucleotide identity and digital DNA–DNA hybridization values between strain ysch24T and closely related type strains were 72.0–74.0 % and 19.1–19.4 %, respectively. Major fatty acids were iso-C15 : 0, C16 : 1
 ω5c and iso-C17 : 0 3-OH and the predominant respiratory quinone was menaquinone 7. Polar lipids consisted of phosphatidylethanolamine, four unidentified aminophospholipids, two unidentified phospholipids and four unidentified lipids. The genomic DNA G+C content was 45.6 mol%. The study clearly showed that strain ysch24T should represent a novel species of the genus

Chitinophaga

, for which the name Chitinophaga tropicalis sp. nov. is proposed. The type strain is ysch24T (=GDMCC 1.1355T=KACC 21527T).
A recently formed triploidCardamine insuetainherits leaf vivipary and submergence tolerance traits of parents
Authors: Sun Jianqiang , Shimizu-Inatsugi Rie , Hofhuis Hugo , Shimizu Kentaro , Hay Angela , Shimizu Kentaro K. , Sese Jun
Published: June 2020

Contemporary speciation provides a unique opportunity to directly observe the traits and environmental responses of a new species.Cardamine insuetais an allotriploid species that appeared within the past 150 years in a Swiss village, Urnerboden. In contrast to its two progenitor species,C. amaraandC. rivularisthat live in wet and open habitats, respectively,C. insuetais found in-between their habitats with temporal water level fluctuation. This triploid species propagates clonally and serves as a triploid bridge to form higher ploidy species. Although niche separation is observed in field studies, the mechanisms underlying the environmental robustness ofC. insuetaare not clear. To characterize responses to a fluctuating environment, we performed a time-course analysis of homeolog gene expression inC. insuetain response to submergence treatment. For this purpose, the two parental (C. amaraandC. rivularis) genome sequences were assembled with a reference-guided approach, and homeolog-specific gene expression was quantified by using HomeoRoq software. We found thatC. insuetaandC. rivularisinitiated vegetative propagation by forming ectopic meristems on leaves, whileC. amaradid not. We examined homeolog-specific gene expression of three species at nine time points during the treatment. The genome-wide expression ratio of homeolog pairs was 2:1 over the time-course, consistent with the ploidy number. By searching the genes with high coefficient of variation of expression over time-course transcriptome data, we found many known key transcriptional factors related to meristem development and formation upregulated in bothC. rivularisandrivularis-homeolog ofC. insueta, but not inC. amara. Moreover, someamara-homeologs of these genes were also upregulated in the triploid, suggesting trans-regulation. In turn, Gene Ontology analysis suggested that the expression pattern of submergence tolerant genes in the triploid was inherited fromC. amara. These results suggest that the triploidC. insuetacombined advantageous patterns of parental transcriptomes to contribute to its establishment in a new niche along a water-usage gradient.
Information theoretic approaches to deciphering the neural code with functional fluorescence imaging
Authors: Climer Jason R. , Dombeck Daniel A.
Published: June 2020

Information theoretic metrics have proven useful in quantifying the relationship between behaviorally relevant parameters and neuronal activity with relatively few assumptions. However, these metrics are typically applied to action potential recordings and were not designed for the slow timescales and variable amplitudes typical of functional fluorescence recordings (e.g. calcium imaging). The lack of research guidelines on how to apply and interpret these metrics with fluorescence traces means the neuroscience community has yet to realize the power of information theoretic metrics. Here, we used computational methods to create mock action potential traces with known amounts of information. From these, we generated fluorescence traces and examined the ability of different information metrics to recover the known information values. We provide guidelines for how to use information metrics when applying them to functional fluorescence and demonstrate their appropriate application to GCaMP6f population recordings from mouse hippocampal neurons imaged during virtual navigation.
Genetic and species-level biodiversity patterns are linked by demography and ecological opportunity
Authors: Schmidt Chloé , Dray Stéphane , Garroway Colin J.
Published: June 2020

The processes that give rise to species richness gradients are not well understood, but may be linked to resource-based limits on the number of species a region can support. Ecological limits placed on regional species richness would also limit population sizes, suggesting that these processes could also generate genetic diversity gradients. If true, we might better understand how broad-scale biodiversity patterns are formed by identifying the common causes of genetic diversity and species richness. We develop a hypothetical framework based on the consequences of regional variation in ecological limits to simultaneously explain spatial patterns of species richness and neutral genetic diversity. Repurposing raw genotypic data spanning 38 mammal species sampled across 801 sites in North America, we show that estimates of genome-wide genetic diversity and species richness share spatial structure. Notably, species richness hotspots tend to harbor lower levels of within-species genetic variation. A structural equation model encompassing eco-evolutionary processes related to resource availability, habitat heterogeneity, and human disturbance explained 78% of variation in genetic diversity and 74% of the variation in species richness. These results suggest we can infer broad-scale patterns of species and genetic diversity using two simple environmental measures of resource availability and ecological opportunity.
Efflux pump antibiotic binding site mutations are associated with azithromycin nonsusceptibility in clinicalNeisseria gonorrhoeaeisolates
Authors: Ma Kevin C , Mortimer Tatum D , Grad Yonatan H
Published: June 2020

Lyu and Moseng et al. used cryo-electron microscopy to characterize key residues involved in drug binding by mosaic-like MtrD efflux pump alleles inNeisseria gonorrhoeae(1). Isogenic experiments introducing key MtrD substitutions R714G and K823E increased macrolide MICs, leading the authors to predict that non-mosaic MtrD “gonococcal strains bearing both themtrRpromoter and amino acid changes at MtrD positions 714 or 823 could lead to clinically significant levels of Azi nonsusceptibility resistance”. We tested this hypothesis by analyzing a global meta-analysis collection of 4852N. gonorrhoeaegenomes (2). In support of their prediction, we identified clinical isolates with novel non-mosaic MtrD drug binding site substitutions across multiple genetic backgrounds associated with elevated azithromycin MICs (Table).
Tomato fruit susceptibility to fungal disease can be uncoupled from ripening by suppressing susceptibility factors
Authors: Silva Christian J. , van den Abeele Casper , Ortega-Salazar Isabel , Papin Victor , Adaskaveg Jaclyn A. , Wang Duoduo , Casteel Clare L. , Seymour Graham B. , Blanco-Ulate Barbara
Published: June 2020

The increased susceptibility of ripe fruit to fungal pathogens poses a substantial threat to crop production and marketability. Here, we coupled transcriptomic analyses with mutant studies to uncover critical processes associated with defenses and susceptibility in tomato (Solanum lycopersicum) fruit. Using unripe and ripe fruit inoculated with three fungal pathogens, we identified common pathogen responses reliant on chitinases, WRKY transcription factors, and reactive oxygen species detoxification. We established that the magnitude and diversity of defense responses do not significantly impact the interaction outcome, as susceptible ripe fruit mounted a strong defense response to pathogen infection. Then, to distinguish features of ripening that may be responsible for susceptibility, we utilized non-ripening tomato mutants that displayed different susceptibility patterns to fungal infection. Based on transcriptional and hormone profiling, susceptible tomato genotypes had losses in the maintenance of cellular redox homeostasis, while jasmonic acid accumulation and signaling coincided with defense activation in resistant fruit. We identified and validated a susceptibility factor, pectate lyase (PL). CRISPR-based knockouts ofPL, but not polygalacturonase (PG2a), reduced susceptibility of ripe fruit by >50%. This study suggests that targeting specific genes that drive susceptibility is a viable strategy to improve the resistance of tomato fruit against fungal disease.

Highlight

Increased susceptibility to fungal disease during tomato ripening is driven by the accumulation of susceptibility factors and not the lack of defense responses.
Enhancing Colorimetric LAMP Amplification Speed and Sensitivity with Guanidine Chloride
Authors: Zhang Yinhua , Ren Guoping , Buss Jackson , Barry Andrew J. , Patton Gregory C. , Tanner Nathan A.
Published: June 2020

Loop-mediated isothermal amplification (LAMP) is a versatile technique for detection of target DNA and RNA, enabling rapid molecular diagnostic assays with minimal equipment. The global SARS-CoV-2 pandemic has presented an urgent need for new and better diagnostic methods, with colorimetric LAMP utilized in numerous studies for SARS-CoV-2 detection. However, the sensitivity of colorimetric LAMP in early reports has been below that of the standard RT-qPCR tests, and we sought to improve performance. Here we report the use of guanidine hydrochloride and combined primer sets to increase speed and sensitivity in colorimetric LAMP, bringing this simple method up to the standards of sophisticated technique and enabling accurate and high-throughput diagnostics.