bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Intraoperative Indocyanine Green (ICG) and Preoperative 3-Dimensional (3D) Reconstruction in Laparoscopic Adrenalectomy: A Propensity Score-matched Analysis
Authors: Palomba Giuseppe , Dinuzzi Vincenza Paola , Pegoraro Francesca , Troisi Roberto Ivan , Montalti Roberto , De Palma Giovanni Domenico , Aprea Giovanni
Published: December 2022

Background:

Laparoscopic adrenalectomy (LA) is considered the “gold standard” treatment of adrenal lesions that are often coincidentally diagnosed during the radiologic workup of other diseases. This study aims to evaluate the intraoperative role of indocyanine green (ICG) fluorescence associated with preoperative 3-dimensional reconstruction (3DR) in laparoscopic adrenalectomy in terms of perioperative outcomes. To our knowledge, this is the first prospective case-controlled report comparing these techniques.

Materials and Methods:

All consecutive patients aged≥18 and undergoing laparoscopic transperitoneal adrenalectomy for all adrenal masses from January 1, 2019 to January 31, 2022 were prospectively enrolled. Patients undertaking standard LA and those undergoing preoperative 3D reconstruction and intraoperative ICG fluorescence were matched through a one-on-one propensity score matching analysis (PSM) for age, gender, BMI, CCI score, ASA score, lesion histology, tumor side, and lesion diameter. Differences in operative time, blood loss, intraoperative and postoperative complications, conversion rate, and length of stay were analyzed.

Results:

After propensity score matching analysis, we obtained a cohort of 36 patients divided into 2 groups of 18 patients each. The operative time and intraoperative blood loss were shorter in patients of the 3DR group (P=0,004 and P=0,004, respectively). There was no difference in terms of length of stay, conversion rate, and intraoperative and postoperative complications between the 2 groups.

Conclusions:

The use of intraoperative ICG in LA and preoperative planning with 3DR images is a safe and useful addition to surgery. Furthermore, we observed a reduction in terms of operating time and intraoperative blood loss.
Single-balloon Enteroscopy for Evaluation of Small Bowel Crohn Disease Strictures: Peripheral Blood Lymphocytes As a Risk Factor for Strictures
Authors: Zhang Juanjuan , Qian Xiaoli , Yan Wei , Diao Yanqing , Da Binlin , Shen Juanhong , Wang Zhiming , Zhu Weiming
Published: December 2022

Background:

Few reports have focused on single-balloon enteroscopy (SBE) for evaluation of small bowel Crohn disease (CD) strictures. The aim of this study was to analyze the relationships between peripheral blood inflammatory markers and small bowel CD strictures observed by SBE.

Materials and Methods:

CD patients who underwent SBE between January 2016 and December 2020 were enrolled. The clinical characteristics and peripheral blood inflammatory markers were collected and analyzed to screen for predictive factors significantly associated with small bowel CD strictures.

Results:

A total of 221 CD patients underwent SBE. The lymphocyte (LC) counts in peripheral blood were significantly lower in the active group (n=178) than in the inactive group (n=43) according to the simple endoscopic score for CD (SES-CD), P=0.011, and was correlated with the SES-CD (r=−0.134, P=0.047). The LC levels were significantly lower in the stricture group (n=116) than in the nonstricture group (n=105) based on whether small bowel strictures developed, P=0.000, and LC was a risk factor for strictures in the multivariate analysis [hazard ratio (HR), 2.332; 95% CI, 1.102-4.937; P=0.027]. In the subgroup analysis, LC levels notably decreased after stricture aggravation (P=0.000). Forty-seven patients who underwent small bowel resection underwent SBE at 6 to 12 months after surgery. The LC level was significantly lower in the postoperative patients with strictures (P=0.025), and LC (HR, 4.444; 95% CI, 1.265-15.617; P=0.020) was a risk of postoperative strictures by univariate analysis, but the age at diagnosis (HR, 6.462; 95% CI, 1.272-22.560; P=0.022) was an independent risk factor by multivariate analysis.

Conclusion:

Peripheral blood LC levels were correlated with SES-CD and gradually decreased as the intestinal stricture increased in small bowel CD patients. The LC level was also significantly lower in the postoperative CD patients with strictures. The level of LC was a risk factor for small bowel strictures. These results suggest that peripheral blood LC could be a novel marker of small bowel CD strictures to guide CD diagnosis and therapy.
Role of quantum fluctuation in inducing ergodicity in the spin glass phase and its effect in quantum annealing
Authors: Mukherjee Sudip
Published: December 2022

We review the numerical studies on the critical behaviour of the quantum Sherrington–Kirkpatrick (SK) spin glass model, which indicate that a quantum critical behaviour is observed up to a low but non-zero value of temperature. We revisit the numerical investigations on the spin glass order parameter distributions, which identify a low temperature along with high transverse field spin glass phase where the order parameter distribution becomes a delta function in the thermodynamic limit indicating the restoration of replica symmetry and ergodic nature of the system. In the remaining spin glass phase associated with high temperature and low transverse field, the observed distribution is broad akin to the Parisi order parameter distribution. This essentially indicates the non-ergodic behaviour of the system. We further discuss the annealing dynamics studies on the quantum SK model. Such investigations reveal the system size independence of annealing time when the annealing paths go through the ergodic spin glass region. Interestingly, when such dynamics are performed in the non-ergodic spin glass phase the annealing time becomes an increasing function of the system size. Spin autocorrelation shows faster relaxation in the ergodic spin glass region compared with that found in the non-ergodic spin glass region.

This article is part of the theme issue ‘Quantum annealing and computation: challenges and perspectives’.
Quantum adiabatic theorem for unbounded Hamiltonians with a cutoff and its application to superconducting circuits
Authors: Mozgunov Evgeny , Lidar Daniel A.
Published: December 2022

We present a new quantum adiabatic theorem that allows one to rigorously bound the adiabatic timescale for a variety of systems, including those described by originally unbounded Hamiltonians that are made finite-dimensional by a cutoff. Our bound is geared towards the qubit approximation of superconducting circuits and presents a sufficient condition for remaining within the

2
n

-dimensional qubit subspace of a circuit model of

n

qubits. The novelty of this adiabatic theorem is that, unlike previous rigorous results, it does not contain

2
n

as a factor in the adiabatic timescale, and it allows one to obtain an expression for the adiabatic timescale independent of the cutoff of the infinite-dimensional Hilbert space of the circuit Hamiltonian. As an application, we present an explicit dependence of this timescale on circuit parameters for a superconducting flux qubit and demonstrate that leakage out of the qubit subspace is inevitable as the tunnelling barrier is raised towards the end of a quantum anneal. We also discuss a method of obtaining a

2
n

×

2
n

effective Hamiltonian that best approximates the true dynamics induced by slowly changing circuit control parameters.

This article is part of the theme issue ‘Quantum annealing and computation: challenges and perspectives’.
Understanding domain-wall encoding theoretically and experimentally
Authors: Berwald Jesse , Chancellor Nicholas , Dridi Raouf
Published: December 2022

We analyse the method of encoding pairwise interactions of higher-than-binary discrete variables (these models are sometimes referred to as discrete quadratic models) into binary variables based on domain walls on one-dimensional Ising chains. We discuss how this is relevant to quantum annealing, but also many gate model algorithms such as VQE and QAOA. We theoretically show that for problems of practical interest for quantum computing and assuming only quadratic interactions are available between the binary variables, it is not possible to have a more efficient general encoding in terms of number of binary variables per discrete variable. We furthermore use a D-Wave Advantage 1.1 flux qubit quantum annealing computer to show that the dynamics effectively freeze later for a domain-wall encoding compared with a traditional one-hot encoding. This second result could help explain the dramatic performance improvement of domain wall over one-hot, which has been seen in a recent experiment on D-Wave hardware. This is an important result because usually problem encoding and the underlying physics are considered separately, our work suggests that considering them together may be a more useful paradigm. We argue that this experimental result is also likely to carry over to a number of other settings, we discuss how this has implications for gate-model and quantum-inspired algorithms.

This article is part of the theme issue ‘Quantum annealing and computation: challenges and perspectives’.
Development of research network on Quantum Annealing Computation and Information using Google Scholar data
Authors: Sinha Antika
Published: December 2022

We build and analyse the network of 100 top-cited nodes (research papers and books from Google Scholar; the strength or citation of the nodes range from about 44 000 up to 100) starting in early 1980 until last year. These searched publications (papers and books) are based on Quantum Annealing Computation and Information categorized into four different sets: (A) Quantum/Transverse Field Spin Glass Model, (B) Quantum Annealing, (C) Quantum Adiabatic Computation and (D) Quantum Computation Information in the title or abstract of the searched publications. We fitted the growth in the annual number of publication (np) in each of these four categories, A–D, to the formnp∼exp⁡(t/τ),wheretdenotes the time in years. We found the scaling timeτto be of the order of about 10 years for categories A and C, whereasτis of the order of about 5 years for categories B and D.

This article is part of the theme issue ‘Quantum annealing and computation: challenges and perspectives’.
Simulations of frustrated Ising Hamiltonians using quantum approximate optimization
Authors: Lotshaw Phillip C. , Xu Hanjing , Khalid Bilal , Buchs Gilles , Humble Travis S. , Banerjee Arnab
Published: December 2022

Novel magnetic materials are important for future technological advances. Theoretical and numerical calculations of ground-state properties are essential in understanding these materials, however, computational complexity limits conventional methods for studying these states. Here we investigate an alternative approach to preparing materials ground states using the quantum approximate optimization algorithm (QAOA) on near-term quantum computers. We study classical Ising spin models on unit cells of square, Shastry-Sutherland and triangular lattices, with varying field amplitudes and couplings in the material Hamiltonian. We find relationships between the theoretical QAOA success probability and the structure of the ground state, indicating that only a modest number of measurements (

≲
100

) are needed to find the ground state of our nine-spin Hamiltonians, even for parameters leading to frustrated magnetism. We further demonstrate the approach in calculations on a trapped-ion quantum computer and succeed in recovering each ground state of the Shastry-Sutherland unit cell with probabilities close to ideal theoretical values. The results demonstrate the viability of QAOA for materials ground state preparation in the frustrated Ising limit, giving important first steps towards larger sizes and more complex Hamiltonians where quantum computational advantage may prove essential in developing a systematic understanding of novel materials.

This article is part of the theme issue ‘Quantum annealing and computation: challenges and perspectives’.
Genome-wide association studies reveal distinct genetic correlates and increased heritability of antimicrobial resistance in Vibrio cholerae under anaerobic conditions
Authors: Creasy-Marrazzo Ashton , Saber Morteza M. , Kamat Manasi , Bailey Laura S. , Brinkley Lindsey , Cato Emilee , Begum Yasmin , Rashid Md. Mahbubur , Khan Ashraful I. , Qadri Firdausi , Basso Kari B. , Shapiro B. Jesse , Nelson Eric J.
Published: December 2022

The antibiotic formulary is threatened by high rates of antimicrobial resistance (AMR) among enteropathogens. Enteric bacteria are exposed to anaerobic conditions within the gastrointestinal tract, yet little is known about how oxygen exposure influences AMR. The facultative anaerobe

Vibrio cholerae

was chosen as a model to address this knowledge gap. We obtained

V. cholerae

isolates from 66 cholera patients, sequenced their genomes, and grew them under anaerobic and aerobic conditions with and without three clinically relevant antibiotics (ciprofloxacin, azithromycin, doxycycline). For ciprofloxacin and azithromycin, the minimum inhibitory concentration (MIC) increased under anaerobic conditions compared to aerobic conditions. Using standard resistance breakpoints, the odds of classifying isolates as resistant increased over 10 times for ciprofloxacin and 100 times for azithromycin under anaerobic conditions compared to aerobic conditions. For doxycycline, nearly all isolates were sensitive under both conditions. Using genome-wide association studies, we found associations between genetic elements and AMR phenotypes that varied by oxygen exposure and antibiotic concentrations. These AMR phenotypes were more heritable, and the AMR-associated genetic elements were more often discovered, under anaerobic conditions. These AMR-associated genetic elements are promising targets for future mechanistic research. Our findings provide a rationale to determine whether increased MICs under anaerobic conditions are associated with therapeutic failures and/or microbial escape in cholera patients. If so, there may be a need to determine new AMR breakpoints for anaerobic conditions.
Is the Public Ready for a Tobacco-Free Ireland? A National Survey of Public Knowledge and Attitudes to Tobacco Endgame in Ireland
Authors: Cosgrave Ellen , Blake Martina , Murphy Edward , Sheridan Aishling , Doyle Frank , Kavanagh Paul
Published: December 2022

Tobacco-Free Ireland (TFI) policy sets a tobacco endgame goal to reduce smoking prevalence to less than 5% by 2025. However, public opinion on this goal, an important policy lever, is uncharted in Ireland. This study aimed to inform policy planning by measuring public knowledge and attitudes to tobacco endgame.

A telephone-administered cross-sectional survey of 1,000 randomly-dialled members of the general public was conducted. Prevalence of awareness, perceived achievability, and support for the TFI goal and potential tobacco endgame measures was calculated and compared across tobacco/e-cigarette user status. Logistic regression identified factors independently associated with TFI goal support.

Although TFI goal awareness was low (34.0%), support was high (74.6%), albeit most (60.2%) believed it achievable beyond 2025. Goal support was higher among non-tobacco/e-cigarette users (adjusted Odds Ratio (aOR) 2.68, 95%CI 1.83-3.90), women (aOR 1.55, 95%CI 1.13-2.14) and higher social class members (aOR 1.48, 95%CI 1.03-2.12). Product-focused measures were popular while views on user-focused measures were mixed: e.g. 86.1% supported nicotine content reduction while 40.3% supported user licensing. Phasing-out tobacco sales was highly-supported (82.8%); however, for most, this was contingent on support for currently addicted users.

Despite low awareness, there is strong support for tobacco endgame in Ireland and views on achievability are more realistic than the current goal of 2025. Supporting currently addicted tobacco users and engaging groups with lower support will be important policy planning and communication considerations. The Irish public are ready for tobacco endgame. These findings should re-invigorate policy planning to translate endgame ambition into action.
Bucillamine use for rheumatoid arthritis and type 2 diabetes mellitus are associated with neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy
Authors: Tsuji Takahiro , Iwasaki Sari , Makita Keishi , Furukawa Shota , Watanabe-Kusunoki Kanako , Takeda-Otera Sayo , Itoh Takahito , Shimamoto Mamiko , Yamaji Hiroaki , Yoshimura Tomomasa , Yamamoto Junya , Kudo Takashi , Kondo Makoto , Kataoka Hiroshi , Mukai Masaya , Kaga Yukito , Yoshinari Miku , Nishibata Yuka , Masuda Sakiko , Tomaru Utano , Ishizu Akihiro , Fukasawa Yuichiro , Hashimoto Seiji , Nishio Saori
Published: December 2022

Membranous nephropathy (MN) is a disease characterized by deposition of immune complexes on the glomerular basement membrane. More than 10 specific antigens for MN including M-type phospholipase A2 receptor (PLA2R), thrombospondin type-1 domain-containing 7A (THSD7A), exostosin 1/exostosin 2 (EXT1/EXT2) and neural epidermal growth factor-like 1 (NELL1) have so far been identified. Since the clinicopathologic characteristics of each type of MN in Japanese are not well understood, we first examined 107 cases of MN by immunohistochemistry for four antigens (PLA2R, THSD7A, EXT1, and NELL1) (MN-cohort). Of those 107 cases, 40% were PLA2R-positive, 13% were NELL1-positive, 11% were THSD7A-positive, 5% were EXT1-positive, 2% were PLA2R and NELL1-double-positive, and 29% were quadruple-negative. In one case of PLA2R and NELL1-double-positive, the first biopsy showed PLA2R-positive and the second biopsy showed PLA2R and NELL1-double-positive. Of the 16 cases of NELL1-positive, 12.5% had colon cancer, 18.8% had rheumatic diseases treated with bucillamine, and 63% had type 2 diabetes mellitus (T2DM). Next, 34 patients diagnosed with MN who had rheumatoid arthritis (RA) were examined (RA-MN cohort). Of those 34 patients, 79% were NELL1-positive, 6% were PLA2R-positive, and 15% were quadruple-negative. In the RA-MN cohort, 56% had a history of bucillamine use. In conclusion, NELL1-associated MN is a common MN in patients with RA using bucillamine and may also be associated with T2DM.
The vascular geneApold1is dispensable for normal development but controls angiogenesis under pathological conditions
Authors: Fan Zheng , Ardicoglu Raphaela , Batavia Aashil A. , Rust Ruslan , von Ziegler Lukas , Waag Rebecca , Zhang Jing , Desgeorges Thibaut , Sturman Oliver , Dang Hairuo , Weber Rebecca , Moor Andreas E. , Schwab Martin E. , Germain Pierre-Luc , Bohacek Johannes , Bock Katrien De
Published: December 2022

The molecular mechanisms of angiogenesis have been intensely studied, but many genes that control endothelial behavior and fate still need to be described. Here, we characterize the role ofApold1(Apolipoprotein L domain containing 1) in angiogenesisin vivoandin vitro. Single-cell analyses reveal that - across tissues - the expression ofApold1is restricted to the vasculature, and thatApold1expression in endothelial cells (ECs) is highly sensitive to environmental factors. UsingApold1-/-mice, we find thatApold1is dispensable for development and does not affect postnatal retinal angiogenesis nor alters the vascular network in adult brain and muscle. However, when exposed to ischemic conditions following photothrombotic stroke as well as femoral artery ligation,Apold1-/-micedisplay dramatic impairments in recovery and revascularization. We also find that human tumor endothelial cells express strikingly higher levels ofApold1,and thatApold1deletion in mice stunts the growth of subcutaneous B16 melanoma tumors, which have smaller and poorly perfused vessels. Mechanistically,Apold1is activated in ECs upon growth factor stimulation as well as in hypoxia, andApold1intrinsically controls EC proliferation but not migration. Our data demonstrate thatApold1is a key regulator of angiogenesis in pathological settings, whereas it does not affect developmental angiogenesis, thus making it a promising candidate for clinical investigation.
Microbial symbionts are shared between ants and their associated beetles
Authors: Valdivia Catalina , Newton Justin A. , O’Donnell Sean , von Beeren Christoph , Kronauer Daniel J. C. , Russell Jacob A. , Łukasik Piotr
Published: December 2022

The transmission of microbial symbionts across individuals and generations can be critical for animal development and survival. Likewise, the transmission of microbes across closely interacting species could also affect host biology. Army ants (Formicidae: Dorylinae) and their hundreds of closely associated insect species (myrmecophiles) can provide a unique insight into interspecific symbiont sharing. Here, we compared the microbiota of workers and larvae of the army antEciton burchelliiwith those of 13 myrmecophile beetle species using 16S rRNA amplicon sequencing. We found that the previously characterized symbionts of army ant workers (Unclassified Firmicutes and Unclassified Entomoplasmatales) were largely absent from ant larvae and from myrmecophiles, whose microbial communities were usually dominated byRickettsia, Wolbachia, Rickettsiella, and/orWeissella. Strikingly, different species of myrmecophiles and ant larvae often shared identical 16S rRNA genotypes of common bacteria. In particular, army ant larvae, some workers, and several myrmecophile species often hosted identicalWeissella(Lactobacillales), based on 16S rRNA and also protein-coding gene sequences. Also, we found high relatedness between some newly characterizedWeissellaand animal-associated strains from aquatic and marine habitats. Looking more broadly, we foundWeissellaOTUs in 11.6% of samples from nearly all habitats and environments characterized by the Earth Microbiome Project. Together, our data show that unrelated but closely interacting species can share much of their microbiota. The high relatedness of strains found across such disparate hosts as ants, beetles, trout, and whales suggests that some versatile microbes move between hosts and habitats despite few opportunities for direct interaction.
Clinical andIn SituCharacterization of Hepatitis Delta Virus in Sjogren’s Syndrome
Authors: Hesterman Matthew C. , Furrer Summer V. , Fallon Braden S. , Weller Melodie L.
Published: December 2022

Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjogren’s Syndrome (SjS) patients in the absence of an HBV co-infection. HDV antigen expression was previously shown to trigger an SjS-like phenotype in vivo, demonstrating a cause-and-effect association. We hypothesize that if HDV regulates SjS development, then HDV profiles may correlate with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjS MSG between 2014-2021. Analyses of HDV antigen (HDAg) expression, including cell type and subcellular localization,in situhybridization of HDV RNA, and comparative analyses with associated SjS and viral hepatitis clinical features were conducted. HDAg was detected in MSG acinar, ductal, and adipose cells. HDAg localized with nuclei and mitochondria. HDV genomic RNA localized to the nucleus. A significant negative correlation was noted between HDAg intensity and focal lymphocytic inflammation. No significant associations were detected between MSG-localized HDAg and liver enzymes, or an evident HBV co-infection. This study has identified a non-hepatic reservoir for chronic HDV persistence in SjS-affected MSG and a unique mitochondrial localization for HDV antigen. Detection of non-hepatic HDV-mediated disease in the absence of an evident current or past HBV co-infection warrants further investigation.
SARS-CoV-2 infection induces the production of autoantibodies in severe COVID-19 patients in an age-dependent manner
Authors: Fonseca Dennyson Leandro M , Filgueiras Igor Salerno , Marques Alexandre HC , Vojdani Elroy , Halpert Gilad , Ostrinski Yuri , Baiocchi Gabriela Crispim , Plaça Desirée Rodrigues , Freire Paula P. , Pour Shahab Zaki , Moll Guido , Catar Rusan , Lavi Yael Bublil , Silverberg Jonathan I. , Zimmerman Jason , de Miranda Gustavo Cabral , Carvalho Robson F , Khan Taj Ali , Heidecke Harald , Dalmolin Rodrigo JS , Luchessi Andre Ducati , Ochs Hans D. , Schimke Lena F. , Amital Howard , Riemekasten Gabriela , Zyskind Israel , Rosenberg Avi Z , Vojdani Aristo , Shoenfeld Yehuda , Cabral-Marques Otavio
Published: December 2022

Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) outcomes due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, diabetes, chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health & disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 outcomes (with 71 mild, 61 moderate, and 27 severe patients) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multivariate regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid β peptide, β catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe elderly COVID-19 patients. Follow-up analysis using binomial regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies indicated a significantly increased likelihood of developing a severe COVID-19 phenotype, presenting a synergistic effect on worsening COVID-19 outcomes. These findings provide new key insights to explain why elderly patients less favorable outcomes have than young individuals, suggesting new associations of distinct autoantibody levels with disease severity.
Protocol for a Real-Time Electronic Health Record Implementation of a Natural Language Processing and Deep Learning Clinical Decision Support Tool: A Use-Case for an Opioid Misuse Screener in Hospitalized Adults
Authors: Afshar Majid , Adelaine Sabrina , Resnik Felice , Mundt Marlon P. , Long John , Leaf Margaret , Ampian Theodore , Wills Graham J , Schnapp Benjamin , Chao Michael , Brown Randy , Joyce Cara , Sharma Brihat , Dligach Dmitriy , Burnside Elizabeth S. , Mahoney Jane , Churpek Matthew M , Patterson Brian W. , Liao Frank
Published: December 2022

The clinical narrative in the electronic health record (EHR) carries valuable information for predictive analytics, but its free-text form is difficult to mine and analyze for clinical decision support (CDS). Large-scale clinical natural language processing (NLP) pipelines have focused on data warehouse applications for retrospective research efforts. There remains a paucity of evidence for implementing open-source NLP engines to provide interoperable and standardized CDS at the bedside. This clinical protocol describes a reproducible workflow for a cloud service to ingest, process, and store clinical notes as Health Level 7 messages from a major EHR vendor in an elastic cloud computing environment. We apply the NLP CDS infrastructure to a use-case for hospital-wide opioid misuse screening using an open-source deep learning model that leverages clinical notes mapped to standardized medical vocabularies. The resultant NLP and deep learning pipeline can process clinical notes and provide decision support to the bedside within minutes of a provider entering a note into the EHR for all hospitalized patients. The protocol includes a human-centered design and an implementation framework with a cost-effectiveness and patient outcomes analysis plan.
Enhancing the sensitivity of rapid antigen detection test (RADT) of different SARS-CoV-2 variants and lineages using fluorescence-labeled antibodies and a fluorescent meter
Authors: Nasrallah Gheyath K. , Ali Fatma , Younes Salma , Al-Khatib Heba A. , Al-Thani Asmaa A. , Yassine Hadi M.
Published: December 2022

RT-qPCR is considered the gold standard for diagnosis of COVID-19; however, it is laborious, time-consuming, and expensive. RADTs have evolved recently as relatively inexpensive methods to address these shortcomings, but their performance for detecting different SARS-COV-2 variants remains limited. RADT test performance could be enhanced using different antibody labeling and signal detection techniques. Here, we aimed to evaluate the performance of two Wondfo antigen RADTs for detecting different SARS-CoV-2 variants: (i) the conventional colorimetric RADT (Ab-conjugated with gold beads); and (ii) the new Finecare™ RADT (Ab-coated fluorescent beads). Finecare™ is a meter used for the detection of a fluorescent signal. 187 frozen nasopharyngeal swabs collected in Universal transport (UTM) that are RT-qPCR positive for different SARS-CoV-2 variants were selected, including 60 Alpha, 59 multiple Delta, and 108 multiple Omicron variants. 60 flu and 60 RSV-positive samples were included as negative controls (total sample number=349). The conventional RADT showed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 62.4% (95%CI: 54-70), 100% (95%CI: 97-100), 100% (95%CI: 100-100), and 58% (95%CI: 49-67) respectively. These measurements were enhanced using the Finecare™ RADT: sensitivity, specificity, PPV, and NPV were 92.6% (95%CI: 89.08-92.3), 96% (95%CI: 96-99.61), 98% (95%CI: 89-92.3), and 85% (95%CI: 96-99.6) respectively. The sensitivity of both RADTs could be greatly underestimated because nasopharyngeal swab samples collected UTM and stored at −80 °C were used. Despite that, our results indicate that the Finecare™ RADT is appropriate for clinical laboratory and community-based surveillance due to its high sensitivity and specificity.
Optimizing COVID-19 testing strategies on college campuses: evaluation of the health and economic costs
Authors: Johnson Kaitlyn E. , Pasco Remy , Woody Spencer , Lachmann Michael , Johnson-Leon Maureen , Bhavnani Darlene , Klima Jessica , Paltiel A. David , Fox Spencer J. , Meyers Lauren Ancel
Published: December 2022

Colleges and universities in the US struggled to provide safe in-person education throughout the COVID-19 pandemic. Testing coupled with isolation is a nimble intervention strategy that can be tailored to mitigate health and economic costs, as the virus and our arsenal of medical countermeasures continue to evolve. We developed a decision-support tool to aid in the design of university-based testing strategies using a mathematical model of SARS-CoV-2 transmission. Applying this framework to a large public university reopening in the fall of 2021 with a 60% student vaccination rate, we find that the optimal strategy, in terms of health and economic costs, is twice weekly antigen testing of all students. This strategy provides a 95% guarantee that, throughout the fall semester, case counts would not exceed the CDC’s original high transmission threshold of 100 cases per 100k persons over 7 days. As the virus and our medical armament continue to evolve, testing will remain a flexible tool for managing risks and keeping campuses open. We have implemented this model as anonline toolto facilitate the design of testing strategies that adjust for COVID-19 conditions, university-specific parameters, and institutional goals.

Author Summary

As a part of the COVID-19 response team at a large public university in the US, we performed an analysis that considered together, the potential health and economic costs of different testing policies for the student body. University administrators had to weigh the up-front effort needed to implement wide scale testing against the potential costs of responding to high levels of disease on campus in the Fall of 2021, after vaccines were widely available but vaccination rates among college students were uncertain. The results presented here are applied to this specific instance, but theonline toolprovided can be tailored to university specific parameters, the epidemiological conditions, and the goals of the university. As we confront newly emerging variants of COVID-19 or novel pathogens, consideration of both the health and economic costs of proactive testing may serve as a politically tractable and cost-effective disease mitigation strategy.
Prevalence of and risk factors for Tuberculosis among health care workers in Yogyakarta, Indonesia
Authors: Main Stephanie , Triasih Rina , Greig Jane , Hidayat Arif , Brilliandi Immanuel Billy , Khodijah Syarifah , Chan Geoff , Wilks Nova , Elizabeth Parry Amy , Nababan Betty , du Cros Philipp , Dwihardiani Bintari
Published: December 2022

Background

Healthcare workers (HCWs) are at risk of contracting TB, particularly when in high tuberculosis (TB) burden settings. Routine surveillance data and evidence are limited on the burden of TB amongst HCWs in Indonesia.

Objective

To measure the prevalence of TB infection (TBI) and disease among HCWs in four healthcare facilities in Yogyakarta and explore risk factors for TBI.

Methods

A cross-sectional TB screening study targeted all HCWs from four pre-selected facilities (1 hospital, 3 primary care) in Yogyakarta, Indonesia. Voluntary screening included symptom assessment, Chest X-ray (CXR), Xpert MTB/RIF (if indicated) and tuberculin skin test (TST). Analyses were descriptive and included multivariable logistic regression.

Results

Of 792 HCWs, 681 consented (86%) to the screening; 59% (n=401) were female, 62% were medical staff (n=421), 77% worked in the one participating hospital (n=524), and the median time working in the health sector was 13 years (IQR: 6-25 years). Nearly half had provided services for people with TB (46%, n=316) and 9% reported ever having TB (n=60).

Among participants with presumptive TB (15%, n=99/662), none were diagnosed microbiologically or clinically with active TB disease. TBI was detected in 25% (95% CI: 22-30; n=112/441) of eligible HCWs with a TST result. A significant association was found between TB infection and being male (adjusted Odds Ratio (aOR) 2.02 (95%CI: 1.29-3.17)), currently working in the participating hospital compared to primary care (aOR 3.15 (95%CI: 1.75-5.66)), and older age (1.05 OR increase per year of life between 19-73 years (95%CI: 1.02-1.06)).

Conclusion

This study supports prioritisation of HCWs as a high-risk group for TB infection and disease, and the need for comprehensive prevention and control programs in Indonesia. Further, it identifies characteristics of HCWs in Yogyakarta at higher risk of TBI, who could be prioritised in screening programs if universal coverage of prevention and control measures cannot be achieved.
Circular RNA circPLOD2 regulates pericyte function by targeting the transcription factor KLF4
Authors: Glaser Simone Franziska , Brezski Andre , Baumgarten Nina , Klangwart Marius , Heumüller Andreas W. , Maji Ranjan Kumar , Leisegang Matthias S. , Guenther Stefan , Zehendner Christoph M. , John David , Schulz Marcel H. , Zarnack Kathi , Dimmeler Stefanie
Published: December 2022

Circular RNAs (circRNAs) are generated by back-splicing and control cellular signaling and phenotypes. Pericytes stabilize the capillary structure and play an important role in the formation and maintenance of new blood vessels. Here, we characterized hypoxia-regulated circRNAs in human pericytes and showed that circPLOD2 is induced by hypoxia and regulates pericyte function. Silencing of circPLOD2 increased pericyte proliferation, endothelial-pericyte interaction and tube formation. Transcriptional profiling of circPLOD2-depleted cells and epigenomic analyses revealed widespread changes in gene expression and identified the circPLOD2-dependent regulation of the transcription factor KLF4 as a key effector of these changes. Importantly, overexpression ofKLF4was sufficient to reverse the effects on pericyte proliferation and endothelial-pericyte interactions observed after circPLOD2 depletion. Together, these data revealed a novel function of circPLOD2 in the control of pericyte proliferation and capillary formation and showed that circPLOD2-mediated regulation of KLF4 significantly contributes to the transcriptional response to hypoxia.

Highlights

circPLOD2 is upregulated in hypoxia in human vascular pericytes

Selective depletion of circPLOD2, but not linearPLOD2mRNA, changes pericyte migration and endothelial-pericyte interaction

circPLOD2 depletion triggers widespread changes in gene expression that are mirrored in the transcriptional hypoxia response

Epigenomic analyses pinpoint the transcription factor KLF4 as a central player in circPLOD2-mediated expression changes

KLF4overexpression is sufficient to rescue the changes in pericyte function caused by circPLOD2 depletion
Nanoscaled discovery of a shunt rifamycin fromSalinispora arenicolausing a three-colour GFP-taggedStaphylococcus aureusmacrophage infection assay
Authors: Pham Nhan T. , Alves Joana , Sargison Fiona A. , Cullum Reiko , Wildenhain Jan , Fenical William , Butler Mark S. , Mead David A. , Duggan Brendan M. , Fitzgerald J. Ross , La Clair James J. , Auer Manfred
Published: December 2022

Antimicrobial resistance has emerged as an urgent global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent.Staphylococcus aureusis a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival ofS. aureusin macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by GFP-taggedStaphylococcus aureusas a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a novel, active rifamycin analogue. Our findings indicate a promising new approach to the identification of anti-microbial compounds with macrophage intracellular activity. The novel antibiotic identified here may represent a useful addition to our armoury in tackling the silent pandemic of antimicrobial resistance.
Endometrial adhesion G protein-coupled receptors are dynamically expressed across the menstrual cycle and expression is altered by ovarian stimulation
Authors: Kalakota Nischelle , Lemenze Alexander , George Lea , Zhao Qingshi , Wu Tracy , Morelli Sara S. , Douglas Nataki C. , Babwah Andy V.
Published: December 2022

Ovarian stimulation (OS), utilized for the development of multiple ovarian follicles for IVF, induces supraphysiologic levels of E2 and an early rise in P4 that disrupt endometrial differentiation and decreases implantation rates or result in placental insufficiency and pregnancy complications. To improve pregnancy rates and reduce the risk of pregnancy complications associated with IVF, it is crucial to advance our molecular understanding of the molecular regulation of endometrial differentiation. Previous studies from our laboratory suggest G protein-coupled receptors (GPCRs) are important regulators of endometrial differentiation. To investigate this further, using a retrospective dataset, we identified all GPCRs expressed across the proliferative and secretory phase of the menstrual cycle and found that many members of the adhesion G protein-coupled receptor (ADGR) family are dynamically expressed. For each ADGR subfamily exhibiting differentially-expressed genes across the cycle, their expression was investigated by RT-PCR in the non-pregnant mouse uterus and decidua on E7.5 of pregnancy. For those genes expressed in the E7.5 decidua, their expression was further quantified by qPCR across early mouse pregnancy. The RT-PCR screen revealed expression of 13 ADGRs (4 of the 9 subfamilies) in E7.5 decidua and among these genes, many were differentially expressed between E0.5 and E5.5 or 6.5 and between E5.5 and E6.5. The dynamic expression of the ADGRs across the menstrual cycle and in early mouse pregnancy, suggests theseADGRsare E2- and/or P4-regulated genes. We therefore hypothesized that for theseADGRgenes, mRNA expression would be disrupted in an OS cycle. This hypothesis was tested on endometrial biopsies collected in the secretory phase from prospective cohorts of women in natural and OS cycles. Consistent with the retrospective dataset, our data revealed that members of theADGRgene family are expressed in the secretory phase of the natural menstrual cycle and for the first time, we show that their expression is altered by ovarian stimulation.
Risk of Type 1 Diabetes in Children is Not Increased after SARS-CoV-2 Infection: A Nationwide Prospective Study in Denmark
Authors: Noorzae Rohina , Junker Thor Grønborg , Hviid Anders , Wohlfahrt Jan , Olsen Sjurdur F.
Published: December 2022

Structured Abstract

Objective

It has been hypothesized that SARS-CoV-2 infection in children can increase risk of developing type 1 diabetes.

Research Design and Methods

We undertook a prospective analysis based on all children in Denmark where we investigated the association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes, using information from several different national Danish registers. Denmark had one of the highest test-rates per capita in the world during the pandemic.

Results

We did not observe a higher risk of a first time diagnosis of type 1 diabetes in children 30 days or more after a positive SARS-CoV-2 test, compared to children with a history of only negative SARS-CoV-2 tests (Hazard ratio 0.85, 95% CI 0.70, 1.04).

Conclusions

Our data do not support that SARS-CoV-2 infection is associated with type 1 diabetes, or that type 1 diabetes should be a special focus after a SARS-CoV-2 infection in children.

Article Highlights

Why did we undertake this study?

Studies have shown an association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes, supporting the possibility of a viral etiology in type 1 diabetes and adding to concerns regarding adverse health consequences of COVID-19.

What is the specific question(s) we wanted to answer?

Is the risk of new onset type 1 diabetes increased among children in the period after SARS-CoV-2 infection?

What did we find?

We estimated the relative risk of being diagnosed with type 1 diabetes after a positive compared to a negative SARS-CoV-2 test, to 0.85 (95% CI 0.70, 1.04).

What are the implications of our findings?

Our data do not support an association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes among children.

Twitter Summary

A study based on all children in Denmark does not show any association between #SarsCoV2 infection and subsequent risk of #Type1Diabetes among persons < 18 years. #Type1Diabetes should not be a special focus after a #SarsCoV2 infection in children.
Validation of a decision-analytic model for the cost-effectiveness analysis of a risk-stratified National Breast Screening Programme in the United Kingdom
Authors: Wright Stuart J , Gray Ewan , Rogers Gabriel , Donten Anna , Payne Katherine
Published: December 2022

Background

This study follows structured frameworks to assess the internal and external validity of a decision-analytic model-based cost-effectiveness of approaches to implement a risk-stratified national breast screening programme (risk-NBSP) in the United Kingdom (UK).

Methods

A pre-defined set of steps were used to conduct the process of validation of a published decision-analytic model-based cost-effectiveness analysis of a risk-NBSP (UK healthcare perspective; lifetime horizon; costs (£; 2019). Internal validation was assessed in terms of: descriptive validity; technical validity; face validity. External validation was assessed in terms of: operational validation; convergent validity (or corroboration); predictive validity.

Results

The results outline the findings of each step of internal and external validation. The positive aspects of the model in meeting internal validation requirements are shown. The limitations of MANC-RISK-SCREEN are described.

Conclusion

Following a transparent and structured validation process, MANC-RISK-SCREEN has been shown to have good internal validity and satisfactory external validity. We suggest that MANC-RISK-SCREEN provides a robust decision-analytic model to assess the cost-effectiveness of risk-NBSP from the UK perspective.

Key points for decision makers

There are emerging suggested adaptations to national screening programmes, such as the introduction of risk-stratification to the national breast screening programme (risk-NBSP) in the United Kingdom (UK)

There is a key role for the use of decision-analytic model-based analysis of healthcare interventions, such as a risk-NBSP, that are difficult to evaluate in trials due to the large number of participants required and very long follow up period required.

This study follows structured frameworks to assess the internal and external validity of a decision-analytic model-based cost-effectiveness of a potential risk-NBSP. The decision-analytic model is shown to perform to a satisfactory level, with possible limitations described clearly, to inform resource allocation decisions from the perspective of the UK healthcare system.