bluuebunny/crossref_metadata_2025 huggingface dataset:
Contraction patterns of the systemic right ventricle: a three-dimensional echocardiography study
Authors: Surkova Elena , Kovács Attila , Lakatos Bálint Károly , Tokodi Márton , Fábián Alexandra , West Cathy , Senior Roxy , Li Wei
Published: December 2021

Aims

To investigate contraction patterns of the systemic right ventricle (SRV) in patients with transposition of great arteries (TGA) post-atrial switch operation and with congenitally corrected transposition of great arteries (ccTGA).

Methods and results

Right ventricular (RV) volumes and ejection fraction (EF) were measured by three-dimensional echocardiography in 38 patients with the SRV (24 TGA and 14 ccTGA; mean age 45 ± 12 years, 63% male), and in 38 healthy volunteers. The RV contraction was decomposed along the longitudinal, radial, and anteroposterior directions providing longitudinal, radial, and anteroposterior EF (LEF, REF, and AEF, respectively) and their contributions to total right ventricular ejection fraction (LEFi, REFi, and AEFi, respectvely). SRV was significantly larger with lower systolic function compared with healthy controls. SRV EF and four-chamber longitudinal strain strongly correlated with B-type natriuretic peptide (BNP) level (Rho −0.73, P < 0.0001 and 0.70, P < 0.0001, respectively). In patients with TGA, anteroposterior component was significantly higher than longitudinal and radial components (AEF 17 ± 4.5% vs. REF 13 ± 4.9% vs. LEF 10 ± 3.3%, P < 0.0001; AEFi 0.48 ± 0.09 vs. REFi 0.38 ± 0.1 vs. LEFi 0.29 ± 0.08, P < 0.0001). In patients with ccTGA, there was no significant difference between three SRV components. AEFi was significantly higher in TGA subgroup compared with ccTGA (0.48 ± 0.09 vs. 0.36 ± 0.08, P = 0.0002).

Conclusion

Contraction patterns of the SRV are different in TGA and ccTGA. Anteroposterior component is dominant in TGA providing compensation for impaired longitudinal and radial components, while in ccTGA all components contribute equally to the total EF. SRV EF and longitudinal strain demonstrate strong correlation with BNP level and should be a part of routine echocardiographic assessment of the SRV.
Takotsubo syndrome and complete heart block, which came first? A case report
Authors: Nadeem Mohammad Khurram , Walsh Jason Leo , Davies Simon , Behar Jonathan M
Published: December 2021

Background

In 2018, the European Society of Cardiology published two consensus documents on takotsubo syndrome (TTS), which include the current consensus on nomenclature, diagnosis, management, and complications. However, little is mentioned on the association with complete heart block (CHB), except that ‘AV block [occurs in] 2.9% of cases’. Complete heart block is a recognized rare association of TTS, but causation is often unclear. Does CHB trigger TTS or vice-versa? Here, we present a case of TTS associated with CHB.

Case summary

An 89-year-old woman presented with a transient loss of consciousness, acute chest pain, and dyspnoea. A few days prior to this her daughter died suddenly of a myocardial infarction. On presentation, troponin levels were elevated, the electrocardiogram showed CHB with a broad QRS and an echo showed apical akinesis and ballooning. Angiographic investigation excluded significant coronary artery disease. A dual-chamber pacemaker was implanted after a brief period of temporary pacing. Ventricular function normalized during follow-up and her underlying rhythm remained CHB.

Discussion

Takotsubo syndrome may be triggered by both emotional and physical stressors. Complete heart block is recognized association, but causation is often unclear. In our case, a clear emotional trigger was identified suggesting the TTS may have precipitated CHB not vice versa.
Preventing unnecessary imaging in patients suspect of coronary artery disease through machine learning of electronic health records
Authors: Overmars L Malin , van Es Bram , Groepenhoff Floor , De Groot Mark C H , Pasterkamp Gerard , den Ruijter Hester M , van Solinge Wouter W , Hoefer Imo E , Haitjema Saskia
Published: December 2021

Aims

With the ageing European population, the incidence of coronary artery disease (CAD) is expected to rise. This will likely result in an increased imaging use. Symptom recognition can be complicated, as symptoms caused by CAD can be atypical, particularly in women. Early CAD exclusion may help to optimize use of diagnostic resources and thus improve the sustainability of the healthcare system. To develop sex-stratified algorithms, trained on routinely available electronic health records (EHRs), raw electrocardiograms, and haematology data to exclude CAD in patients upfront.

Methods and results

We trained XGBoost algorithms on data from patients from the Utrecht Patient-Oriented Database, who underwent coronary computed tomography angiography (CCTA), and/or stress cardiac magnetic resonance (CMR) imaging, or stress single-photon emission computerized tomography (SPECT) in the UMC Utrecht. Outcomes were extracted from radiology reports. We aimed to maximize negative predictive value (NPV) to minimize the false negative risk with acceptable specificity. Of 6808 CCTA patients (31% female), 1029 females (48%) and 1908 males (45%) had no diagnosis of CAD. Of 3053 CMR/SPECT patients (45% female), 650 females (47%) and 881 males (48%) had no diagnosis of CAD. On the train and test set, the CCTA models achieved NPVs and specificities of 0.95 and 0.19 (females) and 0.96 and 0.09 (males). The CMR/SPECT models achieved NPVs and specificities of 0.75 and 0.041 (females) and 0.92 and 0.026 (males).

Conclusion

Coronary artery disease can be excluded from EHRs with high NPV. Our study demonstrates new possibilities to reduce unnecessary imaging in women and men suspected of CAD.
Sovereign Immunity as Liminal Space
Authors: Stewart David P , Wuerth Ingrid B
Published: December 2021

Questions of foreign state immunity frequently involve the ‘liminal space’ between substance and procedure, between domestic and international law and between the domestic law of the forum states and domestic laws of other states. US courts typically (and rightly) rest their analysis not only upon relevant foreign law and international practice but also upon procedural norms that are not formally part of the Foreign Sovereign Immunities Act. Immunity frequently implicates both the reach and power of domestic courts and the authority, organization and expectations of foreign states. It is unsurprising, therefore, that the domestic procedures of the forum court and the internal laws of both the forum state and the foreign state play significant roles in immunity determinations, although the relative paucity of concrete evidence of state practice can make it very difficult to discern the content of customary international law. ‘Restatements of domestic law’ can play an important role in developing principles of immunity, perhaps especially in the liminal spaces between domestic and foreign, substance and procedure. Hopefully, institutes in other countries will produce works like the Restatement of the Law (Fourth): The Foreign Relations Law of the United States.
Estimating cost-effectiveness thresholds under a managed healthcare system: experiences from Colombia
Authors: Espinosa Oscar , Rodríguez-Lesmes Paul , Orozco Luis , Ávila Diego , Enríquez Hernán , Romano Giancarlo , Ceballos Mateo
Published: December 2021

Like most of the world, low- and middle-income countries have faced a growing demand for new health technologies and higher budget constraints. It is necessary to have technical instruments to make decisions based on real-world evidence that allows maximization of the population’s health with a limited budget. We estimated the supply-based cost-effectiveness elasticity, which was then used to determine the cost-effectiveness threshold for the healthcare system of Colombia, a middle-income country where multiple insurers, paid under capitation rules, manage the compulsory contributions of the citizens and government subsidies. Using administrative data, we explored the variation of health expenditures and outcomes at the insurer, geographical region, diagnosis group and year levels. To deal with endogeneity in a two-way fixed-effects model, we instrumented health expenditures using characteristics of the health system such as drug-price regulation. We estimated the threshold to be US$4487.5 per years of life lost avoided [14.7 million Colombian pesos (COP) at 2019 prices] and US$5180.8 per quality-adjusted life-years gained (17 million COP at 2019 prices), around one times the gross domestic product GDP per capita. To the best of our knowledge, this is the first estimation of the cost-effectiveness threshold elasticity supply-based in a middle-income country with a managed healthcare system.
Impaired cooperation between IFT74/BBS22–IFT81 and IFT25–IFT27/BBS19 causes Bardet-Biedl syndrome
Authors: Zhou Zhuang , Qiu Hantian , Castro-Araya Roiner-Francisco , Takei Ryota , Nakayama Kazuhisa , Katoh Yohei
Published: December 2021

The IFT-B complex mediates ciliary anterograde protein trafficking and membrane protein export together with the BBSome. Bardet-Biedl syndrome (BBS) is caused by mutations in not only all BBSome subunits but also in some IFT-B subunits, including IFT74/BBS22 and IFT27/BBS19, which form heterodimers with IFT81 and IFT25, respectively. We found that the IFT25–IFT27 dimer binds the C-terminal region of the IFT74–IFT81 dimer and that the IFT25–IFT27-binding region encompasses the region deleted in the BBS variants of IFT74. In addition, we found that the missense BBS variants of IFT27 are impaired in IFT74–IFT81 binding and are unable to rescue the BBS-like phenotypes of IFT27-knockout (KO) cells. Furthermore, the BBS variants of IFT74 rescued the ciliogenesis defect of IFT74-KO cells, but the rescued cells demonstrated BBS-like abnormal phenotypes. Taken together, we conclude that the impaired interaction between IFT74–IFT81 and IFT25–IFT27 causes the BBS-associated ciliary defects.
Predicting prey recovery from scats of California sea lions (Zalophus californianus) for novel prey species and sizes
Authors: Curtis K Alexandra , Lowry Mark S , Sweeney Joelle M , Orr Anthony J , Harvey James T
Published: December 2021

Diet studies of marine top predators increasingly inform assessments of prey stocks and ecosystems, as well as predator ecology. Prey hard parts provide quantitative information on diet composition. However, species and size variation in digestion of hard parts, and thus in recovery rates, introduces bias in diet reconstruction. Captive feeding studies estimate species- and size-specific recovery rates of prey hard parts in pinnipeds, but such studies can only include a small subset of prey species and sizes consumed by these commonly generalist predators. We developed a generalized linear mixed effects model that estimates recovery rates of otoliths in California sea lion (Zalophus californianus) scats from otolith morphometrics, based on previously published captive feeding studies. The resulting model explains 85% of the variance in recovery rates among common teleost prey species of California sea lions. We also reestimated cephalopod beak recovery rate in California sea lion scats using an intercept-only mixed effects model. The resulting models can estimate recovery rates—and numerical correction factors—for novel teleost and cephalopod prey species and sizes in California sea lion scats, supporting more accurate reconstruction of diet composition in the wild and suggesting a way forward for other pinniped species.
Bayesian logistic regression for online recalibration and revision of risk prediction models with performance guarantees
Authors: Feng Jean , Gossmann Alexej , Sahiner Berkman , Pirracchio Romain
Published: December 2021

Objective

After deploying a clinical prediction model, subsequently collected data can be used to fine-tune its predictions and adapt to temporal shifts. Because model updating carries risks of over-updating/fitting, we study online methods with performance guarantees.

Materials and Methods

We introduce 2 procedures for continual recalibration or revision of an underlying prediction model: Bayesian logistic regression (BLR) and a Markov variant that explicitly models distribution shifts (MarBLR). We perform empirical evaluation via simulations and a real-world study predicting Chronic Obstructive Pulmonary Disease (COPD) risk. We derive “Type I and II” regret bounds, which guarantee the procedures are noninferior to a static model and competitive with an oracle logistic reviser in terms of the average loss.

Results

Both procedures consistently outperformed the static model and other online logistic revision methods. In simulations, the average estimated calibration index (aECI) of the original model was 0.828 (95%CI, 0.818–0.938). Online recalibration using BLR and MarBLR improved the aECI towards the ideal value of zero, attaining 0.265 (95%CI, 0.230–0.300) and 0.241 (95%CI, 0.216–0.266), respectively. When performing more extensive logistic model revisions, BLR and MarBLR increased the average area under the receiver-operating characteristic curve (aAUC) from 0.767 (95%CI, 0.765–0.769) to 0.800 (95%CI, 0.798–0.802) and 0.799 (95%CI, 0.797–0.801), respectively, in stationary settings and protected against substantial model decay. In the COPD study, BLR and MarBLR dynamically combined the original model with a continually refitted gradient boosted tree to achieve aAUCs of 0.924 (95%CI, 0.913–0.935) and 0.925 (95%CI, 0.914–0.935), compared to the static model’s aAUC of 0.904 (95%CI, 0.892–0.916).

Discussion

Despite its simplicity, BLR is highly competitive with MarBLR. MarBLR outperforms BLR when its prior better reflects the data.

Conclusions

BLR and MarBLR can improve the transportability of clinical prediction models and maintain their performance over time.
The protection and recovery strategy development of dynamic resilience analysis and cost consideration in the infrastructure network
Authors: Su Yi-Zhu , Yeh Wei-Chang
Published: December 2021

Modern life is becoming more and more convenient, all because of the perfect operation of the infrastructure network. However, if these infrastructure networks encounter interference, the operation of the network system will be delayed or even shut down, often causing huge losses in livelihood, economy, and society. Therefore, how to evaluate the resilience of the network system and provide protection and recovery strategies to deal with attacks that interfere with the system are important issues. This study considers a situation with protection, attack, and recovery strategies, proposes the time-related Binary-Addition Tree-based Resilience Assessment to consider more decision variables and parameters, and further includes the costs in the formulation of the protection and recovery strategies. Moreover, a new performance measure oriented to the degree of network reliability recovery to quantify the resilience of the network system is developed.
Molecular characterization and secreted production of basidiomycetous cell-bound β-glycosidases applicable to production of galactooligosaccharides
Authors: Ishikawa Eiji , Ikeda Masakazu , Sotoya Hidetsugu , Anbe Minako , Matsumoto Hoshitaka , Kiwaki Mayumi , Hatano Hiroshi
Published: December 2021

Cell-bound β-glycosidases of basidiomycetous yeasts show promise as biocatalysts in galactooligosaccharide (GOS) production. Using degenerated primers designed from Hamamotoa singularis (Hs) bglA gene, we newly identified three genes that encode cell-bound β-glycosidase from Sirobasidium magnum (Sm), Rhodotorula minuta (Rm), and Sterigmatomyces elviae (Se). These three genes, also named bglA, encoded family 1 glycosyl hydrolases with molecular masses of 67‒77 kDa. The BglA enzymes were approximately 44% identical to the Hs-BglA enzyme and possessed a unique domain at the N-terminus comprising 110 or 210 amino acids. The Sm-, Rm-, and Se-BglA enzymes as well as the Hs-BglA enzyme were successfully produced by recombinant Aspergillus oryzae, and all enzymes were entirely secreted to the supernatants. Furthermore, addition of some nonionic detergents (e.g. 0.4% [v/v] Triton-X) increased the production, especially of the Hs- or Se-BglA enzyme. Out of the BglA enzymes, the Se-BglA enzyme showed remarkable thermostability (∼70°C). Additionally, the Sm- and Se-BglA enzymes had better GOS yields, so there was less residual lactose than in others. Accordingly, the basidiomycetous BglA enzymes produced by recombinant A. oryzae would be applicable to GOS production, and the Se-BglA enzyme appeared to be the most promising enzyme for industrial uses.
Double trouble: synchronous extrahepatic cholangiocarcinoma and gallbladder cancer in a Caucasian woman with no pancreaticobiliary maljunction
Authors: Simpson Fraser Hugh , Auld Michael , Kandpal Harsh , Tran Kayla , Chandrasegaram Manju D
Published: December 2021

Synchronous malignancies of the bile duct and the gallbladder are rare. These cases are often associated with pancreaticobiliary maljunction which is characterized by a long common shared pancreatobiliary channel leading to the Sphincter of Oddi. This predisposes the biliary epithelium to pancreatic enzyme reflux and makes the development of neoplasia more likely. We describe the case of a 64-year-old Caucasian female who presented with new jaundice and severe cholecystitis secondary to an impacted gallstone which was seen on ultrasound. Magnetic resonance cholangiopancreatography was organized with suspicion of a possible Mirizzi syndrome. This revealed a mid-distal bile duct cancer in addition to cholecystitis from an impacted gallstone. She was treated with intravenous antibiotics for her cholecystitis and underwent an urgent endoscopic retrograde cholangiopancreatography procedure for biliary decompression and stenting for her obstructive jaundice. The patient proceeded to pancreaticoduodenectomy with final histopathology revealing a synchronous primary gallbladder malignancy in addition to the known bile duct cancer.
Functional Constraints on Insect Immune System Components Govern Their Evolutionary Trajectories
Authors: Ruzzante Livio , Feron Romain , Reijnders Maarten J M F , Thiébaut Antonin , Waterhouse Robert M
Published: December 2021

Roles of constraints in shaping evolutionary outcomes are often considered in the contexts of developmental biology and population genetics, in terms of capacities to generate new variants and how selection limits or promotes consequent phenotypic changes. Comparative genomics also recognizes the role of constraints, in terms of shaping evolution of gene and genome architectures, sequence evolutionary rates, and gene gains or losses, as well as on molecular phenotypes. Characterizing patterns of genomic change where putative functions and interactions of system components are relatively well described offers opportunities to explore whether genes with similar roles exhibit similar evolutionary trajectories. Using insect immunity as our test case system, we hypothesize that characterizing gene evolutionary histories can define distinct dynamics associated with different functional roles. We develop metrics that quantify gene evolutionary histories, employ these to characterize evolutionary features of immune gene repertoires, and explore relationships between gene family evolutionary profiles and their roles in immunity to understand how different constraints may relate to distinct dynamics. We identified three main axes of evolutionary trajectories characterized by gene duplication and synteny, maintenance/stability and sequence conservation, and loss and sequence divergence, highlighting similar and contrasting patterns across these axes amongst subsets of immune genes. Our results suggest that where and how genes participate in immune responses limit the range of possible evolutionary scenarios they exhibit. The test case study system of insect immunity highlights the potential of applying comparative genomics approaches to characterize how functional constraints on different components of biological systems govern their evolutionary trajectories.
Genome-wide chromosomal association of Upf1 is linked to Pol II transcription in Schizosaccharomyces pombe
Authors: De Sandip , Edwards David M , Dwivedi Vibha , Wang Jianming , Varsally Wazeer , Dixon Hannah L , Singh Anand K , Owuamalam Precious O , Wright Matthew T , Summers Reece P , Hossain Md Nazmul , Price Emily M , Wojewodzic Marcin W , Falciani Francesco , Hodges Nikolas J , Saponaro Marco , Tanaka Kayoko , Azzalin Claus M , Baumann Peter , Hebenstreit Daniel , Brogna Saverio
Published: December 2021

Although the RNA helicase Upf1 has hitherto been examined mostly in relation to its cytoplasmic role in nonsense mediated mRNA decay (NMD), here we report high-throughput ChIP data indicating genome-wide association of Upf1 with active genes in Schizosaccharomyces pombe. This association is RNase sensitive, correlates with Pol II transcription and mRNA expression levels. Changes in Pol II occupancy were detected in a Upf1 deficient (upf1Δ) strain, prevalently at genes showing a high Upf1 relative to Pol II association in wild-type. Additionally, an increased Ser2 Pol II signal was detected at all highly transcribed genes examined by ChIP-qPCR. Furthermore, upf1Δ cells are hypersensitive to the transcription elongation inhibitor 6-azauracil. A significant proportion of the genes associated with Upf1 in wild-type conditions are also mis-regulated in upf1Δ. These data envisage that by operating on the nascent transcript, Upf1 might influence Pol II phosphorylation and transcription.
Statewide Longitudinal Trends in Transmitted HIV-1 Drug Resistance in Rhode Island, USA
Authors: Novitsky Vlad , Steingrimsson Jon , Gillani Fizza S , Howison Mark , Aung Su , Solomon Matthew , Won Cindy Y , Brotherton Amy , Shah Rajeev , Dunn Casey , Fulton John , Bertrand Thomas , Civitarese Anna , Howe Katharine , Marak Theodore , Chan Philip , Bandy Utpala , Alexander-Scott Nicole , Hogan Joseph , Kantor Rami
Published: December 2021

Background

HIV-1 transmitted drug resistance (TDR) remains a global challenge that can impact care, yet its comprehensive assessment is limited and heterogenous. We longitudinally characterized statewide TDR in Rhode Island.

Methods

Demographic and clinical data from treatment-naïve individuals were linked to protease, reverse transcriptase, and integrase sequences routinely obtained over 2004–2020. TDR extent, trends, impact on first-line regimens, and association with transmission networks were assessed using the Stanford Database, Mann-Kendall statistic, and phylogenetic tools.

Results

In 1123 individuals, TDR to any antiretroviral increased from 8% (2004) to 26% (2020), driven by non-nucleotide reverse transcriptase inhibitor (NNRTI; 5%–18%) and, to a lesser extent, nucleotide reverse transcriptase inhibitor (NRTI; 2%–8%) TDR. Dual- and triple-class TDR rates were low, and major integrase strand transfer inhibitor resistance was absent. Predicted intermediate to high resistance was in 77% of those with TDR, with differential suppression patterns. Among all individuals, 34% were in molecular clusters, some only with members with TDR who shared mutations. Among clustered individuals, people with TDR were more likely in small clusters.

Conclusions

In a unique (statewide) assessment over 2004–2020, TDR increased; this was primarily, but not solely, driven by NNRTIs, impacting antiretroviral regimens. Limited TDR to multiclass regimens and pre-exposure prophylaxis are encouraging; however, surveillance and its integration with molecular epidemiology should continue in order to potentially improve care and prevention interventions.
Regioselectivity mechanism of the Thunbergia alata Δ6-16:0-acyl carrier protein desaturase
Authors: Guy Jodie E , Cai Yuanheng , Baer Marcel D , Whittle Edward , Chai Jin , Yu Xiao-Hong , Lindqvist Ylva , Raugei Simone , Shanklin John
Published: December 2021

Plant plastidial acyl–acyl carrier protein (ACP) desaturases are a soluble class of diiron-containing enzymes that are distinct from the diiron-containing integral membrane desaturases found in plants and other organisms. The archetype of this class is the stearoyl-ACP desaturase which converts stearoyl-ACP into oleoyl (18:1Δ9cis)-ACP. Several variants expressing distinct regioselectivity have been described including a Δ6-16:0-ACP desaturase from black-eyed Susan vine (Thunbergia alata). We solved a crystal structure of the T. alata desaturase at 2.05 Å resolution. Using molecular dynamics (MD) simulations, we identified a low-energy complex between 16:0-ACP and the desaturase that would position C6 and C7 of the acyl chain adjacent to the diiron active site. The model complex was used to identify mutant variants that could convert the T. alata Δ6 desaturase to Δ9 regioselectivity. Additional modeling between ACP and the mutant variants confirmed the predicted regioselectivity. To validate the in-silico predictions, we synthesized two variants of the T. alata desaturase and analyzed their reaction products using gas chromatography-coupled mass spectrometry. Assay results confirmed that mutants designed to convert T. alata Δ6 to Δ9 selectivity exhibited the predicted changes. In complementary experiments, variants of the castor desaturase designed to convert Δ9 to Δ6 selectivity lost some of their Δ9 desaturation ability and gained the ability to desaturate at the Δ6 position. The computational workflow for revealing the mechanistic understanding of regioselectivity presented herein lays a foundation for designing acyl-ACP desaturases with novel selectivities to increase the diversity of monoenes available for bioproduct applications.
Iontophoresis of treprostinil promotes wound healing in a murine model of scleroderma-related ulcers
Authors: Kotzki Sylvain , Savina Yann , Bouvet Raphael , Gil Hugo , Blaise Sophie , Cracowski Jean-Luc , Roustit Matthieu
Published: December 2021

Objective

Systemic sclerosis (SSc) is a rare, chronic disease characterized by fibrosis, vascular alterations and digital ulcerations. Few drugs have shown efficacy to enhance wound healing of existing SSc-related ulcers. Local delivery of treprostinil, a prostacyclin analogue, may improve wound healing. The present work aimed first at developing a mouse model of SSc-related ulcerations and second at assessing the effect of iontophoresis of treprostinil on wound healing.

Methods

We used two murine models of SSc: chemically induced with HOCl, and urokinase-type plasminogen activator receptor (uPAR)-deficient. Excisional wounding was performed on the dorsal midline with a biopsy punch. Animals were randomized into three groups: treated with electrostimulation alone, with treprostinil iontophoresis or untreated. We assessed wound healing over time, as well as skin microvascular reactivity, inflammation, microvessel density and collagen distribution, before wounding and after re-epithelialization.

Results

uPAR–/– mice, but not HOCl-treated mice, showed impaired wound healing and decreased microvascular reactivity compared with their controls. Treprostinil iontophoresis improved wound healing and microvascular density and decreased inflammation in uPAR–/– mice, while electro-stimulation did not. However, treprostinil had no effect on microvascular reactivity and collagen distribution.

Conclusion

This study suggests that excisional wounds in uPAR–/– mice are a relevant model of SSc-related ulcers. In addition, treprostinil iontophoresis enhances wound healing in this model. Further work in now needed to show whether this effect translates in humans.
A multidimensional examination of psychopathy traits and gray matter volume in adults
Authors: Miglin Rickie , Rodriguez Samantha , Bounoua Nadia , Sadeh Naomi
Published: December 2021

Uncovering the neurobiological abnormalities that may contribute to the manifestation of psychopathic traits is an important step toward understanding the etiology of this disorder. Although many studies have examined gray matter volume (GMV) in relation to psychopathy, few have examined how dimensions of psychopathic traits interactively relate to GMV, an approach that holds promise for parsing heterogeneity in neurobiological risk factors for this disorder. The aim of this study was to investigate the affective-interpersonal (Factor 1) and impulsive-antisocial (Factor 2) dimensions of psychopathy in relation to cortical surface and subcortical GMV in a mixed-gender, high-risk community sample with significant justice-system involvement (N = 156, 50.0% men). Cortex-wide analysis indicated that (i) the Factor 1 traits correlated negatively with GMV in two cortical clusters, one in the right rostral middle frontal region and one in the occipital lobe, and (ii) the interaction of the affective-interpersonal and impulsive-antisocial traits was negatively associated with GMV bilaterally in the parietal lobe, such that individuals high on both trait dimensions evidenced reduced GMV relative to individuals high on only one psychopathy factor. An interactive effect also emerged for bilateral amygdalar and hippocampal GMV, such that Factor 1 psychopathic traits were significantly negatively associated with GMV only at high (but not low) levels of Factor 2 traits. Results extend prior research by demonstrating the neurobiological correlates of psychopathy differ based on the presentation of Factor 1 and 2 traits.
Anatomy and phylogenetic relationships of Temnodontosaurus zetlandicus (Reptilia: Ichthyosauria)
Authors: Laboury Antoine , Bennion Rebecca F , Thuy Ben , Weis Robert , Fischer Valentin
Published: December 2021

Parvipelvia is a major clade of ichthyosaurians that diversified during the Triassic-Jurassic transition. The interrelationships of early parvipelvians remain unclear and many genera are loosely diagnosed, such as Temnodontosaurus, an ecologically important genus from the Early Jurassic of Western Europe. One taxon concentrates many taxonomic issues: ‘Ichthyosaurus’ acutirostris was previously assigned to Temnodontosaurus and for which ‘Ichthyosaurus’ zetlandicus represents a junior synonym. We redescribe the holotype of ‘Ichthyosaurus’ zetlandicus (CAMSM J35176) and a new specimen probably attributable to this taxon (MNHNL TU885) from the Toarcian of Luxembourg. We find that Temnodontosaurus zetlandicus comb. nov. is a valid species that should be referred to the genus Temnodontosaurus, sharing a number of traits with Temnodontosaurus nuertingensis and Temnodontosaurus trigonodon, despite having a distinct cranial architecture. Our phylogenetic analyses under both implied weighting maximum parsimony and Bayesian inference recover T. zetlandicus as closely related to several species currently assigned to Temnodontosaurus. Species included in Temnodontosaurus form a polyphyletic yet well-clustered group among basal neoichthyosaurians, demonstrating that the monophyly of this genus needs to be thoroughly investigated.
A Beautiful Friendship—and a Lesson about Friends and Colleagues: A Classic Partnership Revisited
Authors: Warner David S. , Todd Michael M.
Published: December 2021

David Warner, M.D., and Michael Todd, M.D., first met in 1985. They began working together at the University of Iowa (Iowa City, Iowa) a year later with a shared interest in both laboratory and clinical neuroscience—and in the operative care of neurosurgical patients. That collaboration has now lasted for 35 yr, resulting in more than 70 joint publications. More importantly, they have had the privilege of working together with close to 1,000 colleagues from around the world, in a dozen medical specialties. Their careers are an example of what can be accomplished by friendship, mutual commitment, persistence, and a willingness to join with others.
Microbial Interspecies Associations in Fracture-Related Infection
Authors: Gitajn Ida , Werth Paul , O'Toole Robert V. , Joshi Mandarin , Jevsevar David , Wise Brent , Rane Ajinya , Horton Steven , McClure Emily A. , Ross Benjamin , Nadell Carey
Published: December 2021

Objectives:

Describe co-occurrence or clustering of microbial taxa in fracture-related infections to inform further exploration of infection-related interactions among them.

Design:

Retrospective review.

Setting:

Level 1 trauma center.

Patients/Participants:

Four hundred twenty-three patients requiring surgical intervention for deep surgical site infection between January 2006 and December 2015.

Intervention:

None.

Main Outcome Measurement:

Connection between microbial taxa.

Results:

Methicillin-resistant Staphylococcus aureus, methicillin-sensitive Staphylococcus aureus, and coagulase-negative Staphylococcus represented the majority of monomicrobial observations (71%). Gram-negative rods, gram-positive rods, and anaerobes presented more frequently in polymicrobial infections. Enterobacter, vancomycin-sensitive Enterococcus, and Pseudomonas are present in polymicrobial infections with the highest frequencies and represent the top 3 most important nodes within the microorganism framework, with the highest network centrality scores.

Conclusions:

The present study indicates that there are common microbial taxa (Enterobacter, Enterococcus, and Pseudomonas) that tend to co-occur with other microbes greater than 75% of the time. These commonly co-occurring microbes have demonstrated interactive relationships in other disease pathologies, suggesting that there may be similar important interactions in fracture-related infections. It is possible that these microbial communities play a role in the persistently high failure rate associated with management of infection after trauma. Future studies are needed to study the intermicrobial interactions that explain the frequency at which taxa co-occur. Understanding and potentially disrupting these intermicrobial relationships could inform improvements in the treatment of established infections and in the prevention of infection in high-risk patients.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Robotic DIEP Patient Selection: Analysis of CT Angiography
Authors: Kurlander David E. , Le-Petross Huong T. , Shuck John W. , Butler Charles E. , Selber Jesse C.
Published: December 2021

Background:

Preoperative CTA is widely used and extensively studied for planning of DIEP flap breast reconstruction. However, its utility in planning robotic DIEP harvest is undescribed.

Methods:

The authors conducted a retrospective study of consecutive patients presenting to the clinics of select plastic surgeons between 2017 and 2021 for abdominally based autologous breast reconstruction. CTA measurements of intramuscular perforator distance and perforator-to-external iliac distance were used as predicted robotic and open fascial incision lengths, respectively. It was documented if the predicted robotic incision would avoid crossing the arcuate line. Operative notes were reviewed for fascial incision length and number of perforators harvested. Predicted and actual robotic fascial incision lengths were compared.

Results:

CTAs were reviewed for 49 patients (98 hemiabdomens). Inadequate or no perforators were identified on CTA in 18% of hemiabdomens. Mean predicted robotic and open DIEP fascial incisions were 3.1 cm and 12.2 cm, respectively, giving robotic approach fascial incision benefit of 9.1 cm (P < 0.001). The predicted robotic incision avoided crossing the arcuate line in 71% of hemiabdomens. Thirteen patients (28%) underwent robotic DIEP harvest. Actual robotic fascial incision length averaged 3.5 cm, which was not significantly different from the mean predicted fascial incision length (P = 0.374). Robotic DIEP flaps had fewer perforators (1.8 versus 2.6, P = 0.058).

Conclusion:

CTA is useful for identifying patients with anatomy favorable for robotic DIEP flap harvest.
Tear Trough Malar Implant Penetrating Lacrimal Sac Causing Lacrimal Obstruction and Epiphora: Case Report and Review
Authors: Okafor Linda O. , Jamison Aaron , Ali Syed , Malhotra Raman
Published: December 2021

Tear trough implantation may be associated with a number of well-reported complications. To our knowledge, penetration of the lacrimal sac has never been reported as a complication of malar or tear trough implants. We report a case of lacrimal sac penetration discovered at the time of endoscopic dacryocystorhinostomy surgery in a patient who developed epiphora soon after the tear trough implant was placed.
Bilateral Paraneoplastic Orbital Myositis Associated With Malignant Melanoma and Multiple Myeloma
Authors: Hunt Samantha V. , Garrott Helen M. , Williams Mandy E. , Ford Rebecca L.
Published: December 2021

Paraneoplastic extraocular muscle enlargement has been reported in a small number of patients with cancers including breast or lymphoma, usually presenting with bilateral multiple muscle involvement. Such myositis may be autoimmune. Furthermore, orbital inflammation is a recognized complication of immune-modulation therapy used to treat melanoma, such as ipilimumab. Extraorbital myositis has been described in myeloma, and polymyositis in melanoma. We present a case of bilateral, asymmetrical extraocular muscle enlargement with spontaneous resolution in a patient with simultaneous new diagnoses of metastatic malignant melanoma and multiple myeloma. A similar episode 7 months before diagnosis also resolved spontaneously. The authors believe this to be the first reported case of paraneoplastic orbital myositis associated with multiple myeloma or untreated malignant melanoma.
Clinical and Psychological Factors Associated With Return to Work Among United States Diplomats Who Sustained a Work-Related Injury While on Assignment in Havana, Cuba
Authors: Green-McKenzie Judith , Shofer Frances S. , Matthei Jarrod , Biester Rosette , Deibler Marla
Published: December 2021

Objective:

To determine factors associated with return to work in US diplomats injured during a work assignment in Cuba.

Methods:

In this case series work ability was determined at each visit. Questionnaires used included the Symptom Score Questionnaire, Beck Anxiety Inventory, Beck Depression Inventory, Quality-of-Life Inventory, and Patient Health Questionnaire.

Results:

Of the 45 employees referred to Occupational Medicine, the mean age was 42.5 years, 60% were men, 68% were never out of work, 22% were out of work for some period, and 15% remain out of work. Vestibular, cognitive, hearing, sleep, and visual symptoms, and a higher initial symptom score were significantly associated with work inability while psychiatric symptoms were not.

Conclusions:

This exposure resulted in prolonged illness with cognitive impairment and other clinical manifestations associated with work inability.
Carpal Tunnel Syndrome and Hand-Arm Vibration
Authors: Vihlborg Per , Pettersson Hans , Makdoumi Karim , Wikström Sverre , Bryngelsson Ing-Liss , Selander Jenny , Graff Pål
Published: December 2021

Objective:

To investigate the increased risk for carpal tunnel syndrome (CTS) in men and women with hand-arm vibration (HAV) exposure.

Design:

Case–control study of CTS where 4396 cases was obtained from National Outpatient Register between 2005 through 2016. Cases were matched to controls and exposure was estimated using a job exposure matrix.

Results:

Exposure to HAV increased the risk of CTS with an OR of 1.61 (95% CI 1.46–1.77). The risk was highest in men <30 years of age and among women <30 years no increased risk was observed. The risk increased with a mean year exposure above 2.5 m/s2 to OR 1.84 (95% CI 1.38–2.46).

Conclusions:

HAV exposure increase the risk of CTS in both genders, with highest risk increase in younger men. This emphasize identification of HAV exposure in patients with CTS.
Effectiveness of Different Physiotherapy Protocols in Children in the Intensive Care Unit: A Randomized Clinical Trial
Authors: Souza Gabrielle Sousa Barros , Novais Mariana Furtado Marques , Lemes Guilherme Euzébio , de Mello Mary Lucy Ferraz Maia Fiuza , de Sales Susan Carolina Diniz , Cunha Katiane da Costa , Rocha Larissa Salgado de Oliveira , Avila Paulo Eduardo Santos , Rocha Rodrigo Santiago Barbosa
Published: December 2021

Purpose:

This study aimed to investigate the effectiveness of different physical therapy protocols on the autonomic modulation of heart rate, time of invasive mechanical ventilation (IMV), and length of hospital stay.

Methods:

This was a randomized clinical study with 20 children on IMV in an intensive care unit (ICU), between July 2018 and September 2019. The control group (n = 10) performed the hospital's physical therapy protocol and the experimental group (n = 10) performed the physical therapy protocol based on physical exercise.

Results:

Higher values of heart rate variability were found in the experimental group, both in individual and intergroup analyses. There was a significant reduction in the time of IMV and ICU stay.

Conclusion:

There was an improvement in heart rate variability, reduced time on mechanical ventilation and length of stay in the ICU in individuals who performed the study protocol.
Effectiveness of Modified Sports for Children and Adolescents With Cerebral Palsy: A Pragmatic Study Protocol
Authors: R. de Sousa Junior Ricardo , R. Camargos Ana Cristina , Clutterbuck Georgina L. , R. Leite Hércules
Published: December 2021

Purpose:

Sports Stars is a modified sports intervention that aims to prepare individuals with cerebral palsy for the transition from usual physical therapy care to community sports participation. This is a pragmatic randomized controlled trial protocol of a Brazilian applicability of this intervention.

Method:

This study will compare the effectiveness of Sports Stars Brazil with standard care. Seventy-six children who walk and adolescents with cerebral palsy will be randomly assigned into an intervention or control group. The intervention group will receive 8 weekly group sessions. Each session will include 1 hour of sports-focused gross motor activity training and teamwork development, centered on popular Brazilian sports. Participation, levels of physical activity and, physical literacy domains will be measured at baseline, postintervention, and at 12-weeks of follow-up.

Discussion:

The investigation of Sports Stars Brazil will provide high-quality evidence regarding the effectiveness of modified sports intervention to support participation in sports in this population.
Utilization of Kotter’s Stages and Statistical Process Control to Implement and Sustain Delirium Screening in PICU
Authors: Kupferschmid Megan , Tripathi Sandeep
Published: December 2021

Introduction:

Delirium is a preventable cause of ICU morbidity and mortality. Prior unstructured efforts to implement delirium screening in our hospital were unsuccessful. This project aimed to improve the delirium screening compliance from baseline 0% to more than 80% within 12 months (07/2019–06/2020).

Methods:

We utilized Kotter’s stages of transformation as guiding blocks for implementing change and undertook simultaneous efforts to decrease delirium rates. In addition, we used statistical process control to monitor screening compliance and delirium rates.

Results:

Education on delirium assessment and prevention created a sense of urgency among nursing and medical staff (Stage #1). Stakeholder analysis and a key driver diagram were presented to leadership to create a guiding coalition (Stage #2). Process mapping and failure mode and effect analysis created a vision and strategy for the project (Stage #3). Multiple methods were utilized to communicate the change vision (Stage #4) and empower broad-based action (Stage #5). We celebrated small incremental achievements or short-term wins (Stage #6) by reporting delirium compliance and rate on a control chart. We completed 5837 delirium screens on 763 patients (6689 opportunities). The median delirium screening compliance rate was 87.2% (13.4% positive screens). Small achievements produced by the project were communicated to staff, propelling future efforts to recognize and prevent delirium. This momentum was a driver for more change (Stage #7) to ensure a long-term cultural change in the unit (Stage #8).

Conclusion:

Kotter’s principle of change management, along with an emphasis on data-driven process control, may result in sustained improvement.
Immunotherapeutic approaches to HIV cure and remission
Authors: Lee Ming J. , Fidler S. , Frater John
Published: December 2021

Purpose of review

Despite improvements in the effectiveness of antiretroviral therapy (ART), there are still unmet needs for people living with HIV which drive the search for a cure for HIV infection. The goal of this review is to discuss the challenges and recent immunotherapeutic advances towards developing a safe, effective and durable cure strategy for HIV.

Recent findings

In recent years, advances have been made in uncovering the mechanisms of persistence of latent HIV and in developing more accurate assays to measure the intact proviral reservoir. Broadly neutralising antibodies and modern techniques to enhance antibody responses have shown promising results. Other strategies including therapeutic vaccination, latency reversal agents, and immunomodulatory agents have shown limited success, but newer interventions including engineered T cells and other immunotherapies may be a potent and flexible strategy for achieving HIV cure.

Although progress with newer cure strategies may be encouraging, challenges remain and it is essential to achieve a high threshold of safety and effectiveness in the era of safe and effective ART. It is likely that to achieve sustained HIV remission or cure, a multipronged approach involving a combination of enhancing both adaptive and innate immunity is required.
Prognostic Value of Interim 18F-DOPA and 18F-FDG PET/CT Findings in Stage 3–4 Pediatric Neuroblastoma
Authors: Ko Kuan-Yin , Yen Ruoh-Fang , Ko Chi-Lun , Chou Shu-Wei , Chang Hsiu-Hao , Yang Yung-Li , Jou Shiann-Tarng , Hsu Wen-Ming , Lu Meng-Yao
Published: December 2021

Purpose

This retrospective study aimed to determine the prognostic value of imaging parameters derived from midtherapy 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-FDG PET in pediatric patients with stage 3–4 neuroblastoma.

Methods

We enrolled 32 stage 3–4 pediatric neuroblastoma patients who underwent 18F-DOPA and 18F-FDG PET/CT scans before and after 3 chemotherapy cycles. We measured metabolic and volumetric parameters and applied a metabolic burden scoring system to evaluate the primary tumor extent and soft tissue metastases and that of bone/bone marrow involvement. The associations between these parameters and clinical outcomes were investigated.

Results

Over a median follow-up period of 47 months (range, 3–137 months), 16 patients experienced disease progression, and 13 died. After adjustment for clinical factors, multivariate Cox proportional hazard models showed that interim tumor FDG/FDOPA SUVmax (hazard ratio [HR], 5.94; 95% confidence interval [CI], 1.10–34.98) and interim FDOPA whole-body metabolic burden scores (WBMB) (HR, 7.30; 95% CI, 1.50–35.50) were significant prognostic factors for overall survival (OS). Only interim FDOPA WBMB scores (HR, 7.05; 95% CI, 1.02–48.7) were predictive of progression-free survival. Based on median cutoff values, prognosis (OS and progression-free survival) was significantly associated with an interim FDOPA WBMB score ≥21.92 (all P < 0.05) and interim tumor FDG/FDOPA (SUVmax) score ≥0.57 with poor OS (P < 0.05).

Conclusions

Our results indicate that midtreatment FDG and FDOPA PET/CT could serve as prognostic markers in stage 3–4 neuroblastoma patients.