bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease Transmission by Patients With Subclinical Tuberculosis
Authors: Nguyen Hai Viet , Tiemersma Edine , Nguyen Nhung Viet , Nguyen Hoa Binh , Cobelens Frank
Published: January 2023

Background

Subclinical tuberculosis has been increasingly recognized as a separate state in the spectrum of the disease. However, evidence on the transmissibility of subclinical tuberculosis is still inconclusive.

Methods

We re-analyzed the data from the 2007 combined tuberculosis prevalence and tuberculin surveys in Vietnam. Poisson regression with robust standard errors was conducted to assess the effect of clinical presentation of individuals with tuberculosis in the household on tuberculin skin test (TST) positivity among children aged 6–14 years who participated in the tuberculin survey, adjusting for child's age, smear status of the index patient, and other covariates.

Results

In the multivariate analysis, we found significantly increased risks for TST positivity in children living with patients with clinical, smear-positive tuberculosis, compared with those living with individuals without tuberculosis (adjusted risk ratio [aRR]: 3.04; 95% confidence interval [CI]: 2.00–4.63) and with those living with patients with subclinical tuberculosis, adjusting for index smear status (aRR: 2.26; 95% CI: 1.03–4.96). Among children aged 6–10 years, those living with patients with clinical, smear-positive tuberculosis and those living with patients with subclinical, smear-positive tuberculosis had similarly increased risks of TST positivity compared with those living with individuals without tuberculosis (aRRs [95% CI] of 3.56 [1.91–6.62] and 3.11 [1.44–6.72], respectively).

Conclusions

Our findings support the hypothesis that smear-positive subclinical tuberculosis contributes to Mycobacterium tuberculosis transmission. To eliminate tuberculosis in 2035, control strategies need to address subclinical presentations of the disease.
Pulmonary transit time of cardiovascular magnetic resonance perfusion scans for quantification of cardiopulmonary haemodynamics
Authors: Segeroth Martin , Winkel David Jean , Strebel Ivo , Yang Shan , van der Stouwe Jan Gerrit , Formambuh Jude , Badertscher Patrick , Cyriac Joshy , Wasserthal Jakob , Caobelli Federico , Madaffari Antonio , Lopez-Ayala Pedro , Zellweger Michael , Sauter Alexander , Mueller Christian , Bremerich Jens , Haaf Philip
Published: January 2023

Aims

Pulmonary transit time (PTT) is the time blood takes to pass from the right ventricle to the left ventricle via pulmonary circulation. We aimed to quantify PTT in routine cardiovascular magnetic resonance imaging perfusion sequences. PTT may help in the diagnostic assessment and characterization of patients with unclear dyspnoea or heart failure (HF).

Methods and results

We evaluated routine stress perfusion cardiovascular magnetic resonance scans in 352 patients, including an assessment of PTT. Eighty-six of these patients also had simultaneous quantification of N-terminal pro-brain natriuretic peptide (NTproBNP). NT-proBNP is an established blood biomarker for quantifying ventricular filling pressure in patients with presumed HF. Manually assessed PTT demonstrated low inter-rater variability with a correlation between raters >0.98. PTT was obtained automatically and correctly in 266 patients using artificial intelligence. The median PTT of 182 patients with both left and right ventricular ejection fraction >50% amounted to 6.8 s (Pulmonary transit time: 5.9–7.9 s). PTT was significantly higher in patients with reduced left ventricular ejection fraction (<40%; P < 0.001) and right ventricular ejection fraction (<40%; P < 0.0001). The area under the receiver operating characteristics curve (AUC) of PTT for exclusion of HF (NT-proBNP <125 ng/L) was 0.73 (P < 0.001) with a specificity of 77% and sensitivity of 70%. The AUC of PTT for the inclusion of HF (NT-proBNP >600 ng/L) was 0.70 (P < 0.001) with a specificity of 78% and sensitivity of 61%.

Conclusion

PTT as an easily, even automatically obtainable and robust non-invasive biomarker of haemodynamics might help in the evaluation of patients with dyspnoea and HF.
Acute pulmonary embolism with coexisting right heart thrombi in transit—surgical treatment of 20 consecutive patients
Authors: Zieliński Dariusz , Zygier Marcin , Dyk Wojciech , Wojdyga Ryszard , Wróbel Krzysztof , Pirsztuk Ewelina , Szostakiewicz Katarzyna , Szatkowski Piotr , Darocha Szymon , Kurzyna Marcin , Ciurzyński Michał , Machowski Michał , Pruszczyk Piotr , Torbicki Adam , Biederman Andrzej
Published: January 2023

OBJECTIVES

The presence of right heart thrombi in transit (RHTiT) in the setting of acute pulmonary embolism (PE) is associated with high mortality. The optimal management in such cases is inconclusive. We present the results of surgical treatment of 20 consecutive patients diagnosed with high- or intermediate-high-risk PE with coexisting RHTiT.

METHODS

A retrospective analysis was performed of all consecutive patients undergoing surgical treatment in the Medicover Hospital between 2013 and 2021 for acute PE with coexisting thrombi in-transit in right heart cavities. The diagnosis was based on echocardiography, computed tomography pulmonary angiography and laboratory tests. Eligibility criteria for surgical treatment were acute PE with RHTiT, right ventricular overload on imaging studies and significantly elevated levels of cardiac troponin and NTproBNP. All patients were operated on with extracorporeal circulation using deep hypothermia and total circulatory arrest. The primary end point was hospital all-cause mortality; secondary end points were perioperative complications and long-term mortality.

RESULTS

The analysis included 20 patients. There was no in-hospital death. Nearly one-third of patients required temporal hemofiltration for postoperative renal failure, but this did not involve the need for dialysis at discharge. No neurological complications occurred in any patient. The mean follow-up was 46 months (range 13–98). There was 1 death in the long-term follow-up, not related to PE.

CONCLUSIONS

Surgical treatment of patients with acute PE and coexisting RHTiT can provide favourable results.
Between the West and Russia: Explaining Individual Foreign Policy Preferences in the Small States
Authors: Abbasov Namig , Thies Cameron G
Published: January 2023

This paper examines mass public opinion in three small states of the South Caucasus, Armenia, Azerbaijan, and Georgia, to understand why some individuals in these states prefer a pro-Western foreign policy orientation–pursuing membership in North Atlantic Treaty Organization (NATO) and the European Union (EU), while others do not. We draw on social identity theory to hypothesize the potential affinity some individuals feel toward the West. Using public data from the South Caucasus region where Russia has strongly attempted to block Western penetration, the paper demonstrates that the commitment to democratic values is central to the understanding of mass opinion over foreign alliances in small states: individuals who demonstrate pro-democracy attitudes and support democratic values are more likely to approve of pro-Western foreign policy orientation. These findings suggest that the study of foreign policy preferences in small states is important for our understanding of great power politics and alliance competition.
Middle Powers and Soft-Power Rivalry: Egyptian–Israeli Competition in Africa
Authors: Siniver Asaf , Tsourapas Gerasimos
Published: January 2023

Scholars of international relations have long recognized the importance of soft power in great powers’ hegemonic designs. In contrast, we know little of middle powers’ employment of noncoercive strategies of attraction and, in particular, how soft power operates in the context of middle-power antagonism. We suggest that, first, soft power enhances coalition-building strategies for middle powers. Contrary to expectations that states join forces against a shared threat, the use of soft power via development aid produces an “Us” versus “Them” distinction in target states that unites them in the absence of a common enemy. Second, middle states’ soft-power strategies are likely to support coalition maintenance so long as it does not challenge target states’ national interests. Utilizing extensive archival and interview-based data, we examine how soft power featured in Egyptian–Israeli competition across sub-Saharan Africa (SSA) from 1957 to 1974. We demonstrate how soft power operates beyond the context of great power agenda setting, therefore providing novel evidence for the importance of soft power in the interplay between interstate antagonism and noncoercion in world politics.
Dynamic coalescence of yeast Heat Shock Protein genes bypasses the requirement for actin
Authors: Rubio Linda S , Gross David S
Published: January 2023

Nuclear actin has been implicated in dynamic chromatin rearrangements in diverse eukaryotes. In mammalian cells, it is required to reposition double-strand DNA breaks to enable homologous recombination repair and to enhance transcription by facilitating RNA Pol II recruitment to gene promoters. In the yeast Saccharomyces cerevisiae, nuclear actin modulates interphase chromosome dynamics and is required to reposition the induced INO1 gene to the nuclear periphery. Here, we have investigated the role of actin in driving intergenic interactions between Heat Shock Factor 1 (Hsf1)-regulated Heat Shock Protein (HSP) genes in budding yeast. These genes, dispersed on multiple chromosomes, dramatically reposition following exposure of cells to acute thermal stress, leading to their clustering within dynamic biomolecular condensates. Using an auxin-induced degradation strategy, we found that conditional depletion of nucleators of either linear or branched F-actin (Bni1/Bnr1 and Arp2, respectively) had little or no effect on heat shock-induced HSP gene coalescence or transcription. In addition, we found that pretreatment of cells with latrunculin A, an inhibitor of both filamentous and monomeric actin, failed to affect intergenic interactions between activated HSP genes and their heat shock-induced intragenic looping and folding. Moreover, latrunculin A pretreatment had little effect on HSP gene expression at either RNA or protein levels. In notable contrast, we confirmed that repositioning of activated INO1 to the nuclear periphery and its proper expression do require actin. Collectively, our work suggests that transcriptional activation and 3D genome restructuring of thermally induced, Hsf1-regulated genes can occur in the absence of actin.
Early Life Stress in Mice Leads to Impaired Colonic Corticosterone Production and Prolonged Inflammation Following Induction of Colitis
Authors: Muir Rachel Q , Klocke Barbara J , Jennings Melissa S , Molina Patrick A , Hsu Jung-Shan , Kellum Cailin E , Alexander Katie L , Lee Goo , Foote Jeremy B , Lorenz Robin G , Pollock Jennifer S , Maynard Craig L
Published: January 2023

Background

Early life stress (ELS) is an environmental trigger believed to promote increased risk of IBD. Our goal was to identify mechanisms whereby ELS in mice affects susceptibility to and/or severity of gut inflammation.

Methods

We utilized 2 published animal models of ELS. In the first model, newborn mice were separated from the dam daily for 4 to 8 hours starting on postnatal day 2 and then weaned early on postnatal day 17. Control mice were left undisturbed with the dams until weaning on postnatal day 21. In the second model, dams were fed dexamethasone or vehicle ad libitum in drinking water on postpartum days 1 to 14. Plasma and colonic corticosterone were measured in juvenile and adult mice. Colitis was induced in 4-week-old mice via intraperitoneal injection of interleukin (IL)-10 receptor blocking antibody every 5 days for 15 days. Five or 15 days later, colitis scores and transcripts for Tnf, glucocorticoid receptors, and steroidogenic enzymes were measured.

Results

Mice exposed to ELS displayed reduced plasma and colonic corticosterone. Control animals showed improvements in indices of inflammation following cessation of interleukin-10 receptor blockade, whereas ELS-exposed animals maintained high levels of Tnf and histological signs of colitis. In colitic animals, prior exposure to ELS was associated with significantly lower expression of genes associated with corticosterone synthesis and responsiveness. Finally, TNF stimulation of colonic crypt cells from ELS mice led to increased inhibition of corticosterone synthesis.

Conclusions

Our study identifies impaired local glucocorticoid production and responsiveness as a potential mechanism whereby ELS predisposes to chronic colitis in susceptible hosts.
Populism, Competitive Authoritarianism, and Foreign Policy: The Case of Uganda's 2021 Election
Authors: Lacatus Corina
Published: January 2023

Despite populism being a fast-growing field of inquiry, populist discourse in an African setting is understudied. This paper expands our knowledge of populist communication and foreign policy in a competitive authoritarian context, proposing an analysis of two Ugandan politicians—Bobi Wine and Yoweri Museveni—and their communication on Twitter before the January 2021 election. Counter to expectations, I find that thick ideology has a limited effect on the electoral discourses of both candidates in a competitive autocracy such as Uganda, and this applies also to their communication about foreign policy. When it comes to their position on foreign policy, strategic electoral communication is focused on positioning themselves in relation to the West, signaling a commitment to a strong future linkage with the West and democratization in the event of electoral victory. The content analysis of Twitter-based communication finds that the long-standing incumbent, Museveni, uses tried-and-tested populist tropes to reinforce his regime, emphasizing his government's allegedly strong capacity to maintain a linkage to Western donors and to conduct a successful foreign policy focused on receiving foreign aid and advancing its investment in economic development. In his turn, counter-candidate Wine is a contemporary populist who contests the long-standing regime and promises a truthful commitment to democratization and an authentic and corruption-free linkage with the West if successfully elected. This paper aims to broaden our understanding of how political leaders in competitive autocratic countries of the Global South make strategic use of populist communication about foreign policy to advance their political agendas.
Blood and adipose-resident eosinophils are defined by distinct transcriptional profiles
Authors: Shah Manan , Knights Alexander J , Vohralik Emily J , Psaila Annalise M , Quinlan Kate G R
Published: January 2023

Eosinophils are granular leukocytes of the innate immune system that play important functions in host defense. Inappropriate activation of eosinophils can occur in pathologies such as asthma and esophagitis. However, eosinophils also reside within adipose tissue, where they play homeostatic roles and are important in the activation of thermogenic beige fat. Here we performed bulk RNA sequencing in mouse adipose tissue-resident eosinophils isolated from both subcutaneous and gonadal depots, for the first time, and compared gene expression to blood eosinophils. We found a predominantly conserved transcriptional landscape in eosinophils between adipose depots that is distinct from blood eosinophils in circulation. Through exploration of differentially expressed transcription factors and transcription factors with binding sites enriched in adipose-resident eosinophil genes, we identified KLF, CEBP, and Fos/Jun family members that may drive functional specialization of eosinophils in adipose tissue. These findings increase our understanding of tissue-specific eosinophil heterogeneity, with implications for targeting eosinophil function to treat metabolic disorders such as obesity.
Mechanical bacterial lysate enhances antimicrobial barrier mechanisms in human airway epithelial cells
Authors: Sidoti Migliore Giacomo , Campana Stefania , Barberi Chiara , De Pasquale Claudia , Pezzino Gaetana , Cavaliere Riccardo , Orecchia Paola , Ginestra Giovanna , Mandalari Giuseppina , Del Zotto Genny , Bonaccorsi Irene , Carrega Paolo , Mingari Maria Cristina , Ferlazzo Guido
Published: January 2023

Polyvalent mechanical bacterial lysate is effective in the prevention of respiratory tract infections, although its mechanism of action is not entirely elucidated. Because epithelial cells constitute the frontline defense against infections, we investigated the molecular mechanisms of innate response exerted by bronchial epithelial cells in the presence of polyvalent mechanical bacterial lysate. By using primary human bronchial epithelial cells, we observed that polyvalent mechanical bacterial lysate was able to increase the expression of cellular adhesion molecules such as ICAM-1 and E-cadherin, as well as the expression of amphiregulin, a growth factor able to support human bronchial epithelial cell proliferation. Remarkably, polyvalent mechanical bacterial lysate promoted in human bronchial epithelial cells the de novo expression of human β-defensin-2, a major antimicrobial peptide, conferring them a direct antimicrobial activity. Moreover, polyvalent mechanical bacterial lysate–stimulated human bronchial epithelial cells provided signals for increased IL-22 production by innate lymphoid cells via IL-23, which could further contribute to the release of antimicrobial peptides by epithelial cells. In agreement with these in vitro data, the concentration of both IL-23 and antimicrobial peptides (human β-defensin-2 and LL-37) increased in the saliva of healthy volunteers after sublingual administration of polyvalent mechanical bacterial lysate. Altogether, these results indicate that polyvalent mechanical bacterial lysate administration might support mucosal barrier integrity and promote mechanisms of antimicrobial activity in airway epithelial cells.
Atom Probe Tomography for the Observation of Hydrogen in Materials: A Review
Authors: Chen Yi-Sheng , Liu Pang-Yu , Niu Ranming , Devaraj Arun , Yen Hung-Wei , Marceau Ross K W , Cairney Julie M
Published: January 2023

Atom probe tomography (APT) is an emerging microscopy technique that has high sensitivity for hydrogen with sub-nanometre-scale spatial resolution, which makes it a unique method to investigate the atomic-scale distribution of hydrogen at interfaces and defects in materials. This article introduces the basics of APT-based hydrogen analysis, particularly the challenge of distinguishing a hydrogen background signal in APT by using hydrogen isotopes, along with strategies to yield high-quality analysis. This article also reviews several important findings on hydrogen distribution in a range of materials, including both structural alloys and functional materials, enabled by using APT. Limitations and future opportunities for hydrogen analysis by APT are also discussed.
Sample Preparation Biases in Automated Quantitative Mineralogical Analysis of Mine Wastes
Authors: Saberi Nima , Vriens Bas
Published: January 2023

Mineralogical information is becoming increasingly important for the interpretation and prediction of the long-term leaching behavior of mine waste rock and tailings, yet the collection of quantitative mineralogical data for these materials is complicated by biases introduced during sample preparation. Here, we present experiments with synthetic reference materials, soluble mineral (gypsum) and pulverized weathered waste rock samples to investigate potential artifacts that can be introduced during the preparation of granular sample specimen for quantitative mineralogical analysis. Our results show that, during epoxy-molding, particle segregation due to size is more important than that due to density, both of which can be effectively circumvented by cutting molds perpendicular to the orientation of settling. We also determine that sacrificing sample polish to avoid phase alteration need not impede phase attribution as long as surface roughness and slope are calibrated with sample-internal contrast references. Finally, bootstrapping analysis shows that variability in geometric and mineralogical particle parameters due to unresolved sample heterogeneity is small compared with other biases, even at particle numbers <25,000 at sizes >150 µm. Our results demonstrate the importance of quantifying potential sources of error during sample preparation in quantitative mineralogical studies on mine wastes.
A Modular and Automated Serial Section Collection System for Ultramicrotomy and Subsequent Imaging
Authors: Böhm Thomas , Felfer Peter , Thiele Simon
Published: January 2023

Ultramicrotomy with automated section collection enables a reliable collection of sequential sections for 3D imaging. Here, we introduce a system for collecting several hundred ultra-thin sections on tape as a flexible polymeric substrate. The tape is stored within a portable cassette, which can be used as a modular platform for different applications. The motorized cassette with its retractable section collection cantilever is installed in front of an ultramicrotome for section collection. Section collection and imaging of the sections can be conducted without requiring any manual handling of the tape, which reduces the risk of specimen contamination and offers various options for automatization and cross-compatibility. For instance, processing steps such as a plasma glow-discharge of the substrate can be performed on the tape while it is enclosed in the cassette. As a proof of concept, more than 300 sequential sections at a thickness of 150 nm were cut from a polymer blend sample and collected on a metal-coated tape. Finally, a subset of 15 × 15 × 15 µm³ of the original sample volume was successfully imaged by confocal Raman microscopy and reconstructed at submicron resolution. The serial section cassette harbors the potential to standardize, simplify, and automate sample library collection, imaging, and storage.
Integration of an Event-driven Timepix3 Hybrid Pixel Detector into a Cryo-EM Workflow
Authors: van Schayck J Paul , Zhang Yue , Knoops Kèvin , Peters Peter J , Ravelli Raimond B G
Published: January 2023

The development of direct electron detectors has played a key role in low-dose electron microscopy imaging applications. Monolithic active-pixel sensor detectors are currently widely applied for cryogenic electron microscopy (cryo-EM); however, they have best performance at 300 kV, have relatively low read-out speed and only work in imaging mode. Hybrid pixel detectors can operate at any energy, have a higher detective quantum efficiency (DQE) at lower voltage, have unprecedented high time resolution, and can operate in both imaging and diffraction modes. This could make them well-suited for novel low-dose life-science applications, such as cryo-ptychography, iDPC, and liquid cell imaging. Timepix3 is not frame-based, but truly event-based, and can record individual hits with 1.56 ns time resolution. Here, we present the integration of such a detector into a cryo-EM workflow and demonstrate that it can be used for automated data collection on biological specimens. The performance of the detector in terms of modulation transfer function and DQE has been investigated at 200 kV and we studied the effect of deterministic blur. We describe a single-particle analysis structure of 3 Å resolution and compare it with Falcon3 data collected using the same microscope. These studies could pave the way towards more dose-efficient single-particle techniques.
Microstructural Analysis of Collagenous Structures in Relapsed Clubfoot Tissue
Authors: Vondrášek David , Hadraba Daniel , Přibyl Jan , Eckhardt Adam , Ošťádal Martin , Lopot František , Jelen Karel , Doubková Martina , Knitlová Jarmila , Novotný Tomáš , Janáček Jiří
Published: January 2023

Talipes equinovarus congenitus (clubfoot) is frequently defined as a stiff, contracted deformity, but few studies have described the tissue from the point of view of the extracellular matrix, and none have quantified its mechanical properties. Several researchers have observed that clubfoot exhibits signs of fibrosis in the medial side of the deformity that are absent in the lateral side. Our study aims to quantify the differences between the medial and lateral side tissue obtained from relapsed clubfoot during surgery in terms of the morphological and mechanical properties of the tissue. Combining methods of optical and atomic force microscopy, our study revealed that the medial side has a higher Young’s modulus, contains more collagen and less adipose tissue and that the collagen fibers propagate at a higher frequency of the crimp pattern after surgical dissection of the tissue. Our study offers a multi-correlative approach that thoroughly investigates the relapsed clubfoot tissue.
Automated Sarcomere Structure Analysis for Studying Cardiotoxicity in Human Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Cao Lu , Schoenmaker Linde , Ten Den Simone A , Passier Robert , Schwach Verena , Verbeek Fons J
Published: January 2023

Drug-induced cardiotoxicity is one of the main causes of heart failure (HF), a worldwide major and growing public health issue. Extensive research on cardiomyocytes has shown that two crucial features of the mechanisms involved in HF are the disruption of striated sarcomeric organization and myofibril deterioration. However, most studies that worked on extracting these sarcomere features have only focused on animal models rather than the more representative human pluripotent stem cells (hPSCs). Currently, there are limited established image analysis systems to specifically assess and quantify the sarcomeric organization of hPSC-derived cardiomyocytes (hPSC-CMs). Here, we report a fully automated and robust image analysis pipeline to detect z-lines and myofibrils from hPSC-CMs with a high-throughput live-imaging setup. Phenotype measurements were further quantified to evaluate the cardiotoxic effect of the anticancer drug Doxorubicin. Our findings show that this pipeline is able to capture z-lines and myofibrils. The pipeline filters out disrupted sarcomere structures and irrelevant noisy signals, which allows us to perform automated high-throughput imaging for accurate quantification of cardiomyocyte injury.
Modeling Curved Fibers by Fitting R-vine Copulas to their Frenet Representations
Authors: Weber Matthias , Grießer Andreas , Glatt Erik , Wiegmann Andreas , Schmidt Volker
Published: January 2023

In the present paper, we propose a novel single-fiber model which exploits a description of fibers as a sequence of bond and torsion angles. Using the Frenet–Serret formulas, this representation can be translated into three-dimensional (3D) space and vice-versa. While the precise locations of points along a fiber do not directly convey information about the inner material properties of the fiber, the distribution of bond, and torsion angles may be related to various material characteristics and, thus, our model may form a direct link between inner material properties and emerging microstructure properties. More precisely, we model curved fibers in the 3D Euclidean space R3 as polygonal tracks that we represent by their local curvature and torsion at each sampling point. The 2D sequences of curvatures and torsions obtained in this way are then considered as realizations of a Markov chain with finite memory which takes its values in R2. The transition kernel of this Markov chain is given by a family of conditional multivariate probability distributions. They are constructed using so-called R-vine copulas, which are fitted and validated by means of experimental data.
Fine Structure of the Compound Eyes of Male and FemaleHeortia vitessoidesMoore (Lepidoptera: Crambidae)
Authors: Pan Zijian , Wen Chao , Liu Chuanhe , Woodgate Joseph L , Chen Zhiyun , Yang Wenjuan , Li Yizhen , Ma Tao
Published: January 2023

Heortia vitessoides is a destructive pest of the economically important plant Aquilaria sinensis in China. We investigated the external morphology and ultrastructure of H. vitessoides compound eyes using scanning and transmission electron microscopy. We found that H. vitessoides has superposition eyes, made up of a mean of 3,671 and 3,428 ommatidia in males and females, respectively. The mean ommatidial diameter for males and females was 18.87 and 16.81 µm, respectively. Each ommatidium was capped by a convexly curved corneal facet lens of about 13.85 µm thickness. Corneal nipples measuring 226.36 nm in height in males and 295.48 nm in females, covered the surface of the eyes. Heortia vitessoides eyes are eucone, with each ommatidium having a crystalline cone comprising four cone cells, surrounded by two primary pigment cells. The centrally fused rhabdom of each ommatidium was formed by 8–11 of retinal cells, somewhat more than are typically found in Lepidoptera. The relatively large size of the compound eyes, the large number of ommatidia, large number of retinula cells, and high corneal nipples all suggest that H. vitessoides eyes are adapted to optimize visual sensitivity under dim light conditions.
Benchmark Tests of Atom Segmentation Deep Learning Models with a Consistent Dataset
Authors: Wei Jingrui , Blaiszik Ben , Scourtas Aristana , Morgan Dane , Voyles Paul M
Published: January 2023

The information content of atomic-resolution scanning transmission electron microscopy (STEM) images can often be reduced to a handful of parameters describing each atomic column, chief among which is the column position. Neural networks (NNs) are high performance, computationally efficient methods to automatically locate atomic columns in images, which has led to a profusion of NN models and associated training datasets. We have developed a benchmark dataset of simulated and experimental STEM images and used it to evaluate the performance of two sets of recent NN models for atom location in STEM images. Both models exhibit high performance for images of varying quality from several different crystal lattices. However, there are important differences in performance as a function of image quality, and both models perform poorly for images outside the training data, such as interfaces with large difference in background intensity. Both the benchmark dataset and the models are available using the Foundry service for dissemination, discovery, and reuse of machine learning models.
Evaluation of prognostic factors for patients with eosinophilic granulomatosis with polyangiitis recruited at the pneumonological centre and mainly ANCA negativity: A retrospective analysis of a single cohort in Poland
Authors: Fijolek Justyna , Wiatr Elzbieta , Bujnowski Pawel , Piotrowska-Kownacka Dorota , Roszkowski-Sliz Kazimierz
Published: January 2023

Objectives

The aim was to investigate the risk factors for relapse and death in patients with eosinophilic granulomatosis with polyangiitis (EGPA) recruited at the pneumonological centre and mainly antineutrophil cytoplasmic antibody negativity.

Methods

We retrospectively recruited 86 patients. Relapse was defined as the recurrence or appearance of new organ symptoms. The study end-point included the final examination.

Results

Relapses occurred in 34.9% of the patients, while 9.3% died. Immunosuppressive therapy (P = 0.042), prolonged low-dose corticosteroid treatments (mainly for asthma) (P = 0.006), and longer follow-up duration (P = 0.004) were associated with a higher relapse risk, while advanced EGPA severity (P = 0.0015) and activity (P = 0.044), older age of onset (P = 0.030), symptomatic cardiac involvement (P = 0.007), and postinflammatory cardiac fibrosis (P = 0.038) were associated with a higher risk of death. Sinusitis (P = 0.028) and prolonged low-dose corticosteroid treatments (P = 0.025) correlated with a better prognosis. Relapses did not have an impact on the mortality (P = 0.693).

Conclusions

Relapses in EGPA remain frequent, although they do not impact mortality. Cardiac involvement is common, but clinically symptomatic cardiomyopathy is associated with a higher risk of death. Asthma requiring chronic corticosteroid treatments is associated with a lower risk of death, although the risk of EGPA recurrence is significantly higher.
Phylodynamics and migration data help describe HIV transmission dynamics in internally displaced people who inject drugs in Ukraine
Authors: Kovalenko Ganna , Yakovleva Anna , Smyrnov Pavlo , Redlinger Matthew , Tymets Olga , Korobchuk Anna , Kolodiazieva Anna , Podolina Anna , Cherniavska Svitlana , Skaathun Britt , Smith Laramie R , Strathdee Steffanie A , Wertheim Joel O , Friedman Samuel R , Bortz Eric , Goodfellow Ian , Meredith Luke , Vasylyeva Tetyana I
Published: January 2023

Internally displaced persons are often excluded from HIV molecular epidemiology surveillance due to structural, behavioral, and social barriers in access to treatment. We test a field-based molecular epidemiology framework to study HIV transmission dynamics in a hard-to-reach and highly stigmatized group, internally displaced people who inject drugs (IDPWIDs). We inform the framework by Nanopore generated HIV pol sequences and IDPWID migration history. In June–September 2020, we recruited 164 IDPWID in Odesa, Ukraine, and obtained 34 HIV sequences from HIV-infected participants. We aligned them to publicly available sequences (N = 359) from Odesa and IDPWID regions of origin and identified 7 phylogenetic clusters with at least 1 IDPWID. Using times to the most recent common ancestors of the identified clusters and times of IDPWID relocation to Odesa, we infer potential post-displacement transmission window when infections likely to happen to be between 10 and 21 months, not exceeding 4 years. Phylogeographic analysis of the sequence data shows that local people in Odesa disproportionally transmit HIV to the IDPWID community. Rapid transmissions post-displacement in the IDPWID community might be associated with slow progression along the HIV continuum of care: only 63% of IDPWID were aware of their status, 40% of those were in antiviral treatment, and 43% of those were virally suppressed. Such HIV molecular epidemiology investigations are feasible in transient and hard-to-reach communities and can help indicate best times for HIV preventive interventions. Our findings highlight the need to rapidly integrate Ukrainian IDPWID into prevention and treatment services following the dramatic escalation of the war in 2022.
The Impact of Social Determinants of Health on Pressure Injury Progression: A Retrospective Chart and Scoping Review
Authors: Sasson Daniel C. , Duan Kaiti , Patel Seema M. , Junn Alexandra , Hsia Henry C.
Published: January 2023

OBJECTIVE

To understand the effects of nutrition security and social determinants of health (SDOHs) on pressure injury (PI) progression through a scoping review and retrospective review of patients reporting to New England’s largest healthcare system.

METHODS

Authors performed a scoping review for full-text, original articles reporting outcomes data specific to PIs in patients with socially informed nutrition insecurity. Investigators also performed a retrospective review of all patients from 2012 to 2021 to search for patients with PI documentation and International Classification of Diseases, Tenth Revision Z codes related to the SDOHs.

RESULTS

A full-text review of 2,323 articles from 1965 to 2020 failed to locate any eligible studies. Investigators identified 1,044 patients who met the inclusion criteria; 50.7% were men, 74.3% were White, and 13.3% had evidence of detrimental SDOHs. The average PI duration was 12.13 days (interquartile range, 6 days). Multivariate regression analysis revealed that PI duration was longer in men, Black patients, and patients with evidence of detrimental SDOHs compared with their converse counterparts (P < .0001). The presence of detrimental SDOHs independently predicted an increased duration of disease by 13.07 days (95% CI, 8.99–17.15; t = 6.29, P < .0001).

CONCLUSIONS

A patient’s SDOH history has a significant and considerably stronger correlation with disease progression than predictors that are traditionally studied such as sex, race, or body mass index. These findings are novel, as highlighted by the absence of data uncovered in the literature. These data carry relevance for plastic surgeons wishing to prevent early recurrence following operative closure of PI-related wounds.
Impact of Early Tracheostomy Versus Late or No Tracheostomy in Nonneurologically Injured Adult Patients: A Systematic Review and Meta-Analysis*
Authors: Villemure-Poliquin Noémie , Lessard Bonaventure Paule , Costerousse Olivier , Rouleau-Bonenfant Thierry , Zarychanski Ryan , Lauzier François , Audet Nathalie , Moore Lynne , Gagnon Marc-Aurèle , Turgeon Alexis F.
Published: January 2023

OBJECTIVE:

The optimal timing of tracheostomy in nonneurologically injured mechanically ventilated critically ill adult patients is uncertain. We conducted a systematic review of randomized controlled trials to evaluate the effect of early versus late tracheostomy or prolonged intubation in this population.

DATA SOURCES:

We searched MEDLINE, Embase, CENTRAL, CINAHL, and Web of science databases for randomized controlled trials comparing early tracheostomy (<10 d of intubation) with late tracheostomy or prolonged intubation in adults.

DATA SELECTION:

We selected trials comparing early tracheostomy (defined as being performed less than 10 d after intubation) with late tracheostomy (performed on or after the 10th day of intubation) or prolonged intubation and no tracheostomy in nonneurologically injured patients. The primary outcome was overall mortality. Secondary outcomes included ventilator-associated pneumonia, duration of mechanical ventilation, ICU, and hospital length of stay.

DATA EXTRACTION:

Two reviewers screened citations, extracted data, assessed the risk of bias, and classification of Grading of Recommendations, Assessment, Development, and Evaluation independently.

DATA SYNTHESIS:

Our search strategy yielded 8,275 citations, from which nine trials (n = 2,457) were included. We did not observe an effect on the overall mortality of early tracheostomy compared with late tracheostomy or prolonged intubation (risk ratio, 0.91, 95% CI, 0.82–1.01; I
2 = 18%). Our results were consistent in all subgroup analyses. No differences were observed in ICU and hospital length of stay, duration of mechanical ventilation, incidence of ventilator-acquired pneumonia, and complications. Our trial sequential analysis showed that our primary analysis on mortality was likely underpowered.

CONCLUSION:

In our systematic review, we observed that early tracheostomy, as compared with late tracheostomy or prolonged intubation, was not associated with a reduction in overall mortality. However, we cannot exclude a clinically relevant reduction in mortality considering the level of certainty of the evidence. A well-designed trial is needed to answer this important clinical question.
Prospective Real-Time Validation of a Lung Ultrasound Deep Learning Model in the ICU
Authors: Dave Chintan , Wu Derek , Tschirhart Jared , Smith Delaney , VanBerlo Blake , Deglint Jason , Ali Faraz , Chaudhary Rushil , VanBerlo Bennett , Ford Alex , Rahman Marwan A. , McCauley Joseph , Wu Benjamin , Ho Jordan , Li Brian , Arntfield Robert
Published: January 2023

OBJECTIVES:

To evaluate the accuracy of a bedside, real-time deployment of a deep learning (DL) model capable of distinguishing between normal (A line pattern) and abnormal (B line pattern) lung parenchyma on lung ultrasound (LUS) in critically ill patients.

DESIGN:

Prospective, observational study evaluating the performance of a previously trained LUS DL model. Enrolled patients received a LUS examination with simultaneous DL model predictions using a portable device. Clip-level model predictions were analyzed and compared with blinded expert review for A versus B line pattern. Four prediction thresholding approaches were applied to maximize model sensitivity and specificity at bedside.

SETTING:

Academic ICU.

PATIENTS:

One-hundred critically ill patients admitted to ICU, receiving oxygen therapy, and eligible for respiratory imaging were included. Patients who were unstable or could not undergo an LUS examination were excluded.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 100 unique ICU patients (400 clips) were enrolled from two tertiary-care sites. Fifty-six patients were mechanically ventilated. When compared with gold standard expert annotation, the real-time inference yielded an accuracy of 95%, sensitivity of 93%, and specificity of 96% for identification of the B line pattern. Varying prediction thresholds showed that real-time modification of sensitivity and specificity according to clinical priorities is possible.

CONCLUSIONS:

A previously validated DL classification model performs equally well in real-time at the bedside when platformed on a portable device. As the first study to test the feasibility and performance of a DL classification model for LUS in a dedicated ICU environment, our results justify further inquiry into the impact of employing real-time automation of medical imaging into the care of the critically ill.
The Effect of Biomarkers on Clinical Trial Risk in Gastric Cancer
Authors: Dhillon Sumeet , Lopes Gilberto , Parker Jayson L.
Published: January 2023

Objectives:

This study examined clinical trial success rates for new drug developments in gastric cancer since 1998. We also examined the clinical trial design features that may mitigate the risk of clinical trial failure.

Materials and Methods:

Clinical trial data was obtained from clinicaltrials.gov. Drugs were included if they entered testing between January 1, 1998 and January 1, 2022 and were excluded if they did not have a completed phase I trial or treated secondary effects of gastric cancer. Transition probabilities were calculated for each phase and compared with industry averages. Success rates were determined based on biomarker usage, drug target, type of therapy, and drug chemistry.

Results:

Upon screening 1990 trials, 219 drugs met our inclusion criteria. The probability of a drug completing all phases of testing and obtaining FDA approval was 7%, which is below the 11% industry average. The use of biomarkers in clinical development resulted in nearly a 2-fold increase in the cumulative success rate. Biologics also exhibited higher success rates (17%) as opposed to small molecules (1%). This was true even when we compared both drug types that shared the same target. When comparing only receptor-targeted therapies, biologics (62%) continued to outperform small molecules (18%). Similarly, when narrowed down to drugs targeting solely HER2 receptors, biologics continued to prevail (64% vs. 24%).

Conclusions:

Implementing biomarkers, receptor-targeted therapies, and biologics in clinical development improves clinical trial success rates in gastric cancer. Thus, physicians should prioritize the enrollment of gastric cancer patients in clinical trials that incorporate the aforementioned features.
Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury
Authors: Zhong Allen , Short Celia , Xu Jiabo , Fernandez G. Esteban , Malkoff Nicolas , Noriega Nicolas , Yeo Theresa , Wang Larry , Mavila Nirmala , Asahina Kinji , Wang Kasper S.
Published: January 2023

Background and Aims:

Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury.

Approach and Results:

Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly >10-fold dilated peribiliary glands following rhesus rotavirus–mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility.

Conclusions:

We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.
A “What Matters Index” (WMI) for Adolescents
Authors: Wasson John H.
Published: January 2023

A “What Matters Index” (WMI) represents the distillation of many self-reported measures about what matters. The WMI for adults contains only 5 items that efficiently identify important needs, reliably identify people at risk for future problems, and provide guidance for improving health care and well-being. This report uses data from 10 000 respondents to illustrate the value of a 3-item WMI for adolescents built on the model of the Adult WMI.
Analysis of Imaging Results for Semisitting Compared with Supine Positioning in the Retrosigmoid Approach for Resection of Cerebellopontine Angle Vestibular Schwannomas
Authors: Arambula Alexandra M. , Wichova Helena , Lucas Jacob C. , Schelbar Natalie , Harn Nicholas , Ledbetter Luke , Chamoun Roukoz B. , Camarata Paul J. , Lin James , Staecker Hinrich
Published: January 2023

Objective

To compare the completeness of resection of vestibular schwannomas using three-dimensional segmented volumetric analysis of pre- and postoperative magnetic resonance imaging (MRI) of patients undergoing supine and semisitting positioning for the retrosigmoid approach.

Study Design

Retrospective chart review.

Setting

Tertiary medical center.

Patients

Patients with vestibular schwannomas undergoing surgical resection via the retrosigmoid approach.

Intervention(s)

Tumor resection via the retrosigmoid approach with different patient positioning: standard supine versus semisitting.

Main Outcome Measure(s)

Preoperative versus postoperative three-dimensional segmented volumetric MRI analysis of vestibular schwannomas.

Results

A total of 43 patients (15 supine and 28 semisitting) underwent retrosigmoid craniotomy for resection of vestibular schwannomas. For the conventional supine and semisitting positioning, mean preoperative tumor volumes were 12.65 and 8.73 cm3 (p = 0.15), respectively. Postoperative mean tumor volumes for the supine and semisitting positions were 2.09 and 0.48 cm3 (p = 0.13), respectively. There were 11 cases of postoperative sigmoid sinus thrombosis, 3 in the conventional supine group and 8 in the semisitting groups, and there were 6 cases of postoperative cerebrospinal fluid leaks, all in the semisitting group. The mean House–Brackmann scores for the supine and semisitting groups were 2.9 and 2.3, respectively. There was no statistically significant difference between groups in the rates of these or any other postoperative complications.

Conclusions

The semisitting position for the suboccipital retrosigmoid approach for vestibular schwannoma resection does not compromise the ability to adequately resect the tumor as seen by volumetric MRI results. Further studies are needed to establish the safety of this position compared with the traditional supine approach.