bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence–Based Emphysema Quantification in Routine Chest Computed Tomography: Correlation With Spirometry and Visual Emphysema Grading
Authors: Wiedbrauck Damian , Karczewski Maciej , Schoenberg Stefan O. , Fink Christian , Kayed Hany
Published: December 2023

Objective

The aim of the study is to assess the correlation between artificial intelligence (AI)–based low attenuation volume percentage (LAV%) with forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) and visual emphysema grades in routine chest computed tomography (CT). Furthermore, optimal LAV% cutoff values for predicting a FEV1/FVC < 70% or moderate to more extensive visual emphysema grades were calculated.

Methods

In a retrospective study of 298 consecutive patients who underwent routine chest CT and spirometry examinations, LAV% was quantified using an AI-based software with a threshold < −950 HU. The FEV1/FVC was derived from spirometry, with FEV1/FVC < 70% indicating airway obstruction. The mean time interval of CT from spirometry was 3.87 ± 4.78 days. Severity of emphysema was visually graded by an experienced chest radiologist using an established 5-grade ordinal scale (Fleischner Society classification system). Spearman correlation coefficient between LAV% and FEV1/FVC was calculated. Receiver operating characteristic determined the optimal LAV% cutoff values for predicting a FEV1/FVC < 70% or a visual emphysema grade of moderate or higher (Fleischner grade 3–5).

Results

Significant correlation between LAV% and FEV1/FVC was found (ϱ = −0.477, P < 0.001). Increasing LAV% corresponded to higher visual emphysema grades. For patients with absent visual emphysema, mean LAV% was 2.98 ± 3.30, for patients with trace emphysema 3.22 ± 2.75, for patients with mild emphysema 3.90 ± 3.33, for patients with moderate emphysema 6.41 ± 3.46, for patients with confluent emphysema 9.02 ± 5.45, and for patients with destructive emphysema 16.90 ± 8.19. Optimal LAV% cutoff value for predicting a FEV1/FVC < 70 was 6.1 (area under the curve = 0.764, sensitivity = 0.773, specificity = 0.665), while for predicting a visual emphysema grade of moderate or higher, it was 4.7 (area under the curve = 0.802, sensitivity = 0.766, specificity = 0.742). Furthermore, correlation between visual emphysema grading and FEV1/FVC was found. In patients with FEV1/FVC < 70% a high proportion of subjects had emphysema grade 3 (moderate) or higher, whereas in patients with FEV1/FVC ≥ 70%, a larger proportion had emphysema grade 3 (moderate) or lower. The sensitivity for visual emphysema grading predicting a FEV1/FVC < 70% was 56.3% with an optimal cutoff point at a visual grade of 4 (confluent), demonstrating a lower sensitivity compared with LAV% (77.3%).

Conclusions

A significant correlation between AI-based LAV% and FEV1/FVC as well as visual CT emphysema grades can be found in routine chest CT suggesting that AI-based LAV% measurement might be integrated as an add-on functional parameter in the evaluation of chest CT in the future.
Performance of three predictive scores to avoid delayed diagnosis of significant blunt bowel and mesenteric injury. A 12-year retrospective cohort study
Authors: Agri Fabio , Pache Basile , Bourgeat Mylène , Darioli Vincent , Demartines Nicolas , Schmidt Sabine , Zingg Tobias
Published: December 2023

Background

Avoiding missed diagnosis and therapeutic delay for significant blunt bowel and mesenteric injuries (sBBMI) after trauma is still challenging despite the widespread use of computed tomography. Several scoring tools aiming at reducing this risk have been published. The purpose of the present work was to assess the incidence of delayed (>24 h) diagnosis for sBBMI patients and to compare the predictive performance of three previously published scores using clinical, radiological and laboratory findings: the “Bowel Injury Prediction Score” (BIPS) and the scores developed by Raharimanantsoa (RS) and by Faget (FS).

Methods

Population-based retrospective observational cohort study of adult trauma patients after road traffic crashes (RTC) admitted to Lausanne University Hospital, Switzerland, between 2008 and 2019 (n = 1258) with reliable information about sBBMI status (n = 1164) and for whom all items for score calculation were available (n = 917). The three scores were retrospectively applied on all patients to assess their predictive performance.

Results

The incidence of sBBMI after RTC was 3.3% (38/1164) and in 18% (7/38) there was a diagnostic and treatment delay of more than 24 hours. The diagnostic performance of the FS, the RS and the BIPS to predict sBBMI, expressed as the area under the receiver operating characteristic (ROC) curve, were 95.3% (95% CI: 92.7%-97.9%), 89.2% (95% CI: 83.2%-95.3%) and 87.6% (95% CI: 81.8%-93.3%) respectively.

Conclusion

The present study confirms that diagnostic delays for sBBMI still occur despite the widespread use of abdominal CT. When CT findings during the initial assessment are negative or equivocal for sBBMI, using a score may be helpful to select patients for early diagnostic laparoscopy. The FS had the best individual diagnostic performance. However, the BIPS or the RS, relying on clinical and laboratory variables, may be helpful to select patients for early diagnostic laparoscopy when there are unspecific CT signs of bowel or mesenteric injury.

Level of evidence and study type

Level III, Prognostic/Epidemiological
The role of gravity in naturalness versus consistency: strong-
CP
and dark energy
Authors: Dvali Gia
Published: December 2023

There is an ongoing debate on how seriously one should take the naturalness puzzles as the guidelines to new physics. In this debate gravity is often put aside, as an insignificant spectator force. However, this attitude misses the entire essence of the story. Through its

S

-matrix formulation, gravity promotes certain puzzles, such as the cosmological constant and strong-

C
P

problems, into the consistency issues. The respective consistency requirements make the theory highly predictive. In particular, the cosmological vacuum energy must be zero. This has fundamental implications both for strong-

C
P

and for dark energy puzzles. QCD must include an axion as an intrinsic part of the gauge redundancy, without the need of any global symmetry. This gives

ϑ
¯

=
0

to all orders in operator expansion. Applied to cosmology, the

S

-matrix implies that the energy budget of the Universe cannot come from a constant. Correspondingly, the dark energy is an unambiguous signal of new physics around the Hubble scale.

This article is part of the theme issue ‘The particle-gravity frontier’.
Flavour physics as a window to new physics searches
Authors: Križan Peter
Published: December 2023

Flavour physics is one of the essential elements of the Standard Model (SM). Experimental studies of weak decays of

B

and

D

mesons at

B

factories have, together with the discovery of the Higgs boson at LHC, provided the final confirmation of the validity of the SM. The present generation of precision flavour physics experiments is looking for departures from the SM. We discuss studies of anomalies in

b

hadron decays, and studies of rare decays, which are a very promising method for searching for new physics.

This article is part of the theme issue ‘The particle-gravity frontier’.
After the Higgs boson discovery: a turning point in particle physics
Authors: Pokorski Stefan
Published: December 2023

The discovery of the Higgs particle has completed the Standard Model of elementary interactions which is stunningly successful in describing most of the elementary processes observed so far in the laboratories. Nevertheless, it is not the Theory of Everything. Its structure faces some theoretical puzzles and, even more importantly, it leaves unexplained neutrino masses and several fundamental astrophysical observations. Thus, the quest for a deeper theory is at present the main experimental and theoretical challenge in particle physics. However, contrary to the past research characterized by certain continuity and clear goals, we are now in a turning point surfing into totally unknown territory beyond the Standard Model physics. Precision measurements of the Higgs particle properties is one of the promising directions in the search for extensions to the existing theory.

This article is part of the theme issue ‘The particle-gravity frontier’.
Characterization of Multidrug Resistant serogroup 19 Streptococcus pneumoniae isolated from the healthy children below five years of age in Indonesia
Authors: Salsabila Korrie , Winarti Yayah , Paramaiswari Wisiva Tofriska , Tafroji Wisnu , Putri Hanifah Fajri Maharani , Daningrat Wa Ode Dwi , Wulandari I Gusti Ayu Inten , Soebandrio Amin , Safari Dodi
Published: December 2023

We investigated the resistance genes, pilus islet, biofilm formation ability, and sequence types of multidrug-resistant Streptococcus pneumoniae (MDRSP) isolated from the healthy children below 5 years of age in Indonesia. In all, 104 archived MDRSP isolates from previous carriage study in Indonesia in 2016-2019 were screened for the presence of antibiotic resistance genes and the rrgC (pilus islet 1) and pitB (pilus islet 2) genes. Multilocus sequence typing and biofilm formation was determined by PCR-Sequencing and the ability of cells to adhere to the walls, respectively. Results have shown that the mefA, ermB, and tetM genes were found in 93%, 52%, and 100% of MDRSP isolates respectively. The insertion of arginine, proline, and Ile-100-Leu were the most common mutations in the folA and folP genes. Pilus islet 1 and type 2 were discovered in 93% and 82% of MDRSP isolates respectively. The MDRSP isolates showed no biofilm formation ability (64%), and five out of ten strains of MDRSP strains were ST1464. This finding can be used to provide further considerations in implementing and monitoring pneumococcal vaccination in Indonesia.
Cell division cycle fluctuation of Pal concentration in Escherichia coli
Authors: Mertens Laureen , Liu Xinwei , Verheul Jolanda , Egan Alexander J.F. , Vollmer Waldemar , den Blaauwen Tanneke
Published: December 2023

The Tol-Pal proteins stabilise the outer membrane during cell division in many gram-negative bacteria, including Escherichia coli. Pal is an outer membrane lipoprotein that can bind peptidoglycan. It accumulates at the septum during division by a mobilisation-and-capture mechanism. This work further substantiates and extends knowledge of Pal's localisation in E. coli using immunolabeling, this method enables the detection of endogenous proteins. The midcell localisation of Pal and TolB, as seen with fluorescent protein fusions, during cell division, was confirmed. The retention of Pal in newly formed cell poles seemed to persist longer than observed with fluorescent Pal fusions. The concentration of endogenous Pal during the cell division cycle fluctuated: it decreased initially and then increased during the second half of the cell division cycle. We probed for possible regulators and proposed two new putative regulators of Pal. Deleting the periplasmic protease, Prc decreased the total Pal abundance and affected its concentration fluctuation during the cell cycle. This suggests that Prc controls a cell division stage-specific regulator of Pal. Immunolabeling also supported the prediction that the small RNA MicA suppresses Pal expression. However, the regulation by MicA occurred in a cell-cycle-independent manner. All these findings urge further research on the tight regulation of the dividing cell envelope stability.
The population structure of vancomycin-resistant and -susceptible Enterococcus faecium in a low-prevalence antimicrobial resistance setting is highly influenced by circulating global hospital-associated clones
Authors: AL Rubaye Mushtaq , Janice Jessin , Bjørnholt Jørgen Vildershøj , Kacelnik Oliver , Haldorsen Bjørg C. , Nygaard Randi M. , Hegstad Joachim , Sundsfjord Arnfinn , Hegstad Kristin ,   the Norwegian VRE study group
Published: December 2023

Between 2010 and 2015 the incidence of vancomycin-resistant

Enterococcus faecium

(VREfm) in Norway increased dramatically. Hence, we selected (1) a random subset of vancomycin-resistant enterococci (VRE) from the Norwegian Surveillance System for Communicable Diseases (2010–15; n=239) and (2) Norwegian vancomycin-susceptible

E. faecium

(VSEfm) bacteraemia isolates from the national surveillance system for antimicrobial resistance in microbes (2008 and 2014; n=261) for further analysis. Whole-genome sequences were collected for population structure, van gene cluster, mobile genetic element and virulome analysis, as well as antimicrobial susceptibility testing. Comparative genomic and phylogeographical analyses were performed with complete genomes of global

E. faecium

strains from the National Center for Biotechnology Information (NCBI) (1946–2022; n=272). All Norwegian VREfm and most of the VSEfm clustered with global hospital-associated sequence types (STs) in the phylogenetic subclade A1. The vanB2 subtype carried by chromosomal Tn1549 integrative conjugative elements was the dominant van type. The major Norwegian VREfm cluster types (CTs) were in accordance with concurrent European CTs. The dominant vanB-type VREfm CTs, ST192-CT3/26 and ST117-CT24, were mostly linked to a single hospital in Norway where the clones spread after independent chromosomal acquisition of Tn1549. The less prevalent vanA VRE were associated with more diverse CTs and vanA carrying Inc18 or RepA_N plasmids with toxin–antitoxin systems. Only 5 % of the Norwegian VRE were Enterococcus faecalis, all of which contained vanB. The Norwegian VREfm and VSEfm isolates harboured CT-specific virulence factor (VF) profiles supporting biofilm formation and colonization. The dominant VREfm CTs in general hosted more virulence determinants than VSEfm. The phylogenetic clade B VSEfm isolates (n=21), recently classified as

Enterococcus lactis

, harboured fewer VFs than

E. faecium

in general, and particularly subclade A1 isolates. In conclusion, the population structure of Norwegian

E. faecium

isolates mirrors the globally prevalent clones and particularly concurrent European VREfm/VSEfm CTs. Novel chromosomal acquisition of vanB2 on Tn1549 from the gut microbiota, however, formed a single major hospital VREfm outbreak. Dominant VREfm CTs contained more VFs than VSEfm.
Molecular landscapes of oral cancers of unknown etiology
Authors: Deneuve Sophie , Fervers Béatrice , Senkin Sergey , Bouaoun Liacine , Pérol Olivia , Chavanel Bérénice , Lu Lingeng , Coste Isabelle , Renno Toufic , Zavadil Jiri , Virard François
Published: December 2023

The incidence of the mobile tongue cancer in young patients has been rising. This oral cancer (OC) type has no identified risk factors (NIRF), no established molecular markers and is not yet recognized as a distinct clinical entity.

To understand this emerging malignancy, we innovatively analyzed the public head and neck cancer multi-omics data. We identified mutational signatures that successfully stratified 307 OC and 109 laryngeal cancer cases according to their clinico-pathological characteristics. The NIRF OCs exhibited significantly increased activities of endogenous clock-like and APOBEC-associated mutagenesis, alongside specific cancer driver gene mutations, distinct methylome patterns and prominent antimicrobial transcriptomic responses. Furthermore, we show that mutational signature SBS16 in OCs reflects the combined effects of alcohol drinking and tobacco smoking.

Our study characterizes the unique disease histories and molecular programs of the NIRF OCs revealing that this emerging cancer subtype is likely driven by increased endogenous mutagenesis correlated with responses to microbial insults.
Towards routine long-read sequencing for rare disease: a national pilot study on chromosomal rearrangements
Authors: Eisfeldt Jesper , Ameur Adam , Lenner Felix , ten Berk de Boer Esmee , Ek Marlene , Wincent Josephine , Vaz Raquel , Ottosson Jesper , Jonsson Tord , Ivarsson Sofie E , Thunstrom Sofia , Topa Alexandra , Stenberg Simon , Rohlin Anna , Sandestig Anna , Nordling Margareta , Palmebäck Pia , Burstedt Magnus , Nordin Frida , Stattin Eva-Lena , Sobol Maria , Baliakas Panagiotis , Bondeson Marie-Louise , Höijer Ida , Bilgrav Saether Kristine , Lovmar Lovisa , Ehrencrona Hans , Melin Malin , Feuk Lars , Lindstrand Anna
Published: December 2023

Background: Clinical genetic laboratories often require comprehensive analysis of chromosomal rearrangements/structural variants (SVs) which can range from gross chromosomal events, such as translocations and inversions, to supernumerary ring/marker chromosomes, and small deletions or duplications. To fully understand the complexity of a specific event and its associated clinical consequences, it is imperative to locate the breakpoint junctions and to resolve the derivative chromosome structure. This task, however, often surpasses the capabilities of conventional short-read sequencing technologies. In contrast, emerging long-read sequencing techniques present a compelling alternative for clinical diagnostics. Methods: Here, the Genomic Medicine Sweden Rare Diseases (GMS-RD) consortium explored the utility of HiFi Revio long-read whole genome sequencing (lrGS) for clinical digital karyotyping of SVs nationwide. The first 16 samples included in this study were collected from all health care regions in Sweden. We established a national pipeline and a shared variant database for variant calling and filtering. The included validation samples cover a spectrum of simple and complex SVs including inversions, translocations and copy number variants. Results: The results from the lrGS analysis match the reported karyotype for 14/16 individuals and 12 known SVs were mapped at nucleotide resolution. A complex rearrangement on chromosome 15 was identified only through read depth analysis and two chromosome 21 rearrangements remained undetected, one of which was mosaic. The average read length ranged from 8.3-18.8 kb and the coverage was >20x for all samples. De novo assembly resulted in a limited number of contigs per individual (N50 range 6-86 Mb) clearly separating the two alleles in most cases, enabling direct characterization of the chromosomal rearrangements. Conclusions: In a national pilot study, we successfully demonstrated the utility of HiFi Revio lrGS as a clinical analysis of chromosomal rearrangements. Based on our results we propose a five-year plan for the wider implementation of lrGS for rare disease diagnostics in Sweden.
Calling for diversity: improving transfusion safety through high-throughput blood group microarray genotyping
Authors: Wittig Michael , Steiert Tim Alexander , ElAbd Hesham , Degenhardt Frauke , Valenti Luca , Prati Daniele , Ronzoni Luisa , Bujanda Luis , Banales Jesus M. , Blay Natalia , Invernizzi Pietro , Buti Maria , Albillos Agustín , Fernández Javier , Sacchi Nicoletta , Julià Antonio , Latiano Anna , de Cid Rafael , D’Amato Mauro , Asselta Rosanna , Laudes Matthias , Lieb Wolfgang , Juhl David , Gassner Christoph , Franke Andre
Published: December 2023

Blood transfusions, conducted between donors compatible in their red blood cell (RBC) antigens, play a life-saving role in transfusion medicine. Genetic differences at blood group loci between ethnicities result in diversity and altered frequency of RBC antigens that need to be considered in blood transfusion. Consequently, comprehensive, and accurate blood group antigen typing is especially relevant for inter-ethnic blood transfusions and for minorities underrepresented in the donor population. Blood group microarray genotyping is a cost-efficient and scalable method for comprehensive blood group typing. Previously, however, microarray typing has been challenging for the clinically important blood group systems Rh and MNS, as these feature highly paralogous genomic loci leading to mixed signals. We here present an approach for accurately typing blood group systems, including Rh and MNS variations, that we benchmarked in an ethnically diverse cohort. We tested its performance using gold-standard, diagnostic-grade MALDI-TOF data from 1,052-samples, including 334 CEPH diversity samples and applied the approach to 4,999 samples of a COVID-19 genetics study. Overall, we obtained a 99.95% benchmarking concordance and 99.65% call rate. In summary, we provide a highly accurate and cost-efficient high-throughput genotyping method for comprehensive blood group analysis that is also suitable for ethnically diverse sample sets.
Inference of causal and pleiotropic effects with multiple weak genetic instruments: application to effect of adiponectin on type 2 diabetes
Authors: McKeigue Paul M , Iakovliev Andrii , Spiliopoulou Athina , Erabadda Buddhiprabha , Colhoun Helen M
Published: December 2023

Current methods for Mendelian randomization (MR) analyses are restricted to single SNP instruments, and cannot reliably infer causality with instruments that are mostly weak and pleiotropic. We describe methods to overcome these limitations: key innovations are construction of scalar instruments from multiple SNPs, use of a regularized horseshoe prior, and hypothesis tests based on the marginal likelihood of the causal effect parameter. To demonstrate the approach, we constructed genotypic instruments from unlinkedtrans-pQTLs detected in two large GWAS studies of plasma proteins, and tested the top 20 genes for which the aggregated effects of the instruments was associated with type 2 diabetes in the UK Biobank cohort. The only protein with clear evidence of a causal effect on type 2 diabetes was adiponectin, encoded byADIPOQ: standardized log odds ratio -0.34 (95% CI -0.44 to -0.24) using UK Biobank instruments. These results have implications for the design and analysis of Mendelian randomization studies. Where the exposure under study is expression of a gene, restricting the instruments tocis-acting variants is likely to miss causal effects. Tests based on the marginal likelihood should supersede other methods of testing for causality in the presence of pleiotropy.
Disproportionate increase in cannabis use among individuals with serious psychological distress and association with psychiatric hospitalization and outpatient service use in the National Survey on Drug Use and Health 2009-2019
Authors: Hyatt Andrew S , Flores Michael William , Cooke Benjamin Lê
Published: December 2023

Aims

Estimate trends in levels of cannabis use among adults with and without serious psychological distress (SPD) in the United States from 2009-2019, and to ascertain whether cannabis use among individuals with SPD was associated with inpatient psychiatric hospitalization and outpatient mental health care.

Design

Using multivariable logistic regression models and predictive margin methods, we estimated linear time trends in levels of cannabis use by year and SPD status and rates of psychiatric hospitalization and outpatient service use.

Setting

The United States: National Survey on Drug Use and Health (NSDUH), an annual cross-sectional survey, 2009-19 public use files.

Participants

447,228 adults aged ≥ 18 years.

Measurements

In the past year, self-report of any and greater-than-weekly cannabis use, any inpatient psychiatric hospitalization, and any outpatient mental health care.

Findings

Rates of any and weekly-plus cannabis use increased similarly among individuals with SPD compared to those without from 2009-2014 but more rapidly in SPD from 2015-2019 (p<0.001). Among individuals with SPD, probability of psychiatric hospitalization was greater among individuals with less than weekly (5.2%, 95% CI 4.4-5.9%, p=0.011), and weekly-plus cannabis use (5.4%, 95% CI 4.6-6.1, p=0.002) compared to no use (4.1%, 95% CI 3.8-4.4%). For outpatient mental health care, no use was associated with a 27.4% probability (95% CI 26.7-8.1%) of any outpatient care, significantly less than less than weekly use (32.7% probability, 95% CI 31.3-34.1% p<0.001) and weekly-plus use (29.9% probability, 95% CI 28.3-31.5% p=0.006).

Conclusions

Cannabis use is increasing more rapidly among individuals with SPD than the general population, and is associated with increased rates of psychiatric hospitalization as well as increased outpatient service use. These findings can inform policy makers looking to better tailor regulations on advertising for medical and adult use cannabis and develop public health messaging on the use of cannabis in people with mental illness.
The Trend of Ischemic Evaluation, Intervention, and In-Hospital Mortality and Outcomes among Patients with Acute Myocardial Infarction and Atrial Fibrillation
Authors: Baig Mirza Faris Ali
Published: December 2023

Background

Atrial fibrillation (AF) is associated with increased cardiovascular mortality. Data regarding the relationship between coronary artery disease (CAD) and AF is mixed. It is uncertain if AF directly increases the risk for future coronary events and if such patients are appropriately evaluated for CAD.

Methods

This is a cross-sectional study performed on hospitalized patients with AMI and concurrent AF in 2019 using National Inpatient Sample from HCUP. Patients with missing information and type II non-ST elevation myocardial infarction (NSTEMI) were excluded. Using STATA 18, In-hospital mortality, ischemic evaluation, percutaneous treatment, rates of ventricular tachycardiac (VT), ventricular fibrillation (VF), cardiogenic shock, cardiac arrest, average length of stay (LOS), and total hospitalization charges were studied. Regression models were used for data analyses.

Results

A total of 600,645 patients met inclusion criteria (219,660 females [36.5%], 428,755 Caucasian [71%], 65,870 African American [10.9%], 51,155 Hispanic [8.5%]; mean [SD] age, 66.7 [0.5] years), including 166,680 (28%) STEMI and 433,965 (72%) NSTEMI patients. 109,520 (18%) patients with AMI had AF. For patients with AMI and AF, the adjusted odds of mortality increased by 23% (adjusted Odds ratio [aOR], 1.23; CI, 1.15-1.32; p<0.001). AF patients were less likely to undergo ischemic evaluation (aOR, 0.77; CI, 0.74-0.80; p<0.001) and ischemic intervention (aOR, 0.64; CI, 0.62-0.66; p<0.001). AF patients had higher odds of VT (aOR, 1.41; CI, 1.33-1.49; p<0.001), VF (aOR, 1.44; CI, 1.33-1.57; p<0.001), cardiogenic shock (aOR, 1.43; CI, 1.35-1.52; p<0.001), and cardiac arrest (aOR, 1.35; CI, 1.24-1.47; p<0.001). AF patients had longer LOS (mean, 1.39; SCD, 1.29-1.48; p<0.001) and higher total hospital charges (mean $22,188; 19,311-25,064, p<0.001).

Conclusion

AF was independently associated with increased mortality in patients admitted with AMI. AF was associated with higher rates of cardiac complications. Patients with AF were less likely to receive ischemic evaluation or percutaneous intervention and had overall higher healthcare resource utilization. This study encourages AF to be viewed as an independent risk factor for CAD and suggests more efforts to diagnose CAD in such patients.

Clinical Perspective

What is new

Patients with acute myocardial infarction and atrial fibrillation have higher odds of mortality.

AMI patients with AF are subjected to lesser odds of undergoing ischemic evaluation and intervention.

Healthcare resource utilization is higher in this cohort.

What are the clinical implications

AF should be considered as an independent risk factor for increased mortality in AMI.

Early ischemic evaluation should be considered to diagnose coronary artery disease in this cohort.

Increased awareness to recognize all risk factors of coronary artery disease.
Methods for assessing bee foraging preferences: a short review and a new automated apparatus
Authors: Magner Evin T. , Norris Jeff T. , Snell-Rood Emilie C. , Hegeman Adrian D. , Carter Clay J.
Published: December 2023

Bees are essential pollinators for many plant species, but multiple threats exist to both managed and wild bee populations. Their innate foraging behaviors and food preferences are subjects of intense research since bee nutrition is essential for maintaining hive and colony health. Multiple approaches have been developed to assess bee foraging behavior and associated preferences, but they are often labor-intensive and provide data on a limited number of parameters. In this manuscript, we provide a short review of these methods and present the design, build, and implementation of a new, inexpensive, and automated feeding apparatus capable of recording: (1) number of visits, (2) total food consumed, (3) photos and videos of bee behavior while inside of the feeder, and (4) environmental conditions. The efficacy of this apparatus is demonstrated through preference tests with artificial nectars, while also acknowledging the relative strengths and limitations of this approach.
Aging decreases osteocyte lacunar-canalicular turnover in female C57BL/6 mice
Authors: Vahidi Ghazal , Boone John Connor , Hoffman Fawn , Heveran Chelsea M
Published: December 2023

Osteocytes engage in bone resorption and mineralization surrounding their expansive lacunar-canalicular system (LCS) through LCS turnover. However, fundamental questions persist about where, when, and how often osteocytes engage in LCS turnover and how these processes change with aging. Furthermore, whether LCS turnover depends on tissue strain remains unexplored. To address these questions, we utilized confocal scanning microscopy, immunohistochemistry, and scanning electron microscopy to characterize osteocyte LCS turnover in the cortical (mid-diaphysis) and cancellous (metaphysis) femurs from young (5 mo) and early-old-age (22 mo) female C57BL/6JN mice. LCS bone mineralization was measured by the presence of perilacunar fluorochrome labels. LCS bone resorption was measured by immunohistochemical markers of bone resorption. The dynamics of LCS turnover were estimated from serial fluorochrome labeling, where each mouse was administered two labels between 2 days and 16 days before euthanasia. Osteocyte participation in mineralizing their surroundings is highly abundant in both cortical and cancellous bone of young adult mice but significantly decreases with aging. LCS bone resorption also decreases with aging. Aging has a greater impact on LCS turnover dynamics in cancellous bone than in cortical bone. Lacunae with recent LCS turnover have larger lacunae in both age groups. The impacts of aging on LCS turnover also varies with cortical region of interest and intracortical location, suggesting a dependence on tissue strain. The impact of aging on decreasing LCS turnover may have significant implications for bone quality and mechanosensation.
DeepPBS: Geometric deep learning for interpretable prediction of protein–DNA binding specificity
Authors: Mitra Raktim , Li Jinsen , Sagendorf Jared M. , Jiang Yibei , Chiu Tsu-Pei , Rohs Remo
Published: December 2023

Predicting specificity in protein-DNA interactions is a challenging yet essential task for understanding gene regulation. Here, we present Deep Predictor of Binding Specificity (DeepPBS), a geometric deep-learning model designed to predict binding specificity across protein families based on protein-DNA structures. The DeepPBS architecture allows investigation of different family-specific recognition patterns. DeepPBS can be applied to predicted structures, and can aid in the modeling of protein-DNA complexes. DeepPBS is interpretable and can be used to calculate protein heavy atom-level importance scores, demonstrated as a case-study on p53-DNA interface. When aggregated at the protein residue level, these scores conform well with alanine scanning mutagenesis experimental data. The inference time for DeepPBS is sufficiently fast for analyzing simulation trajectories, as demonstrated on a molecular-dynamics simulation of aDrosophilaHox-DNA tertiary complex with its cofactor. DeepPBS and its corresponding data resources offer a foundation for machine-aided protein-DNA interaction studies, guiding experimental choices and complex design, as well as advancing our understanding of molecular interactions.
Epigenetic disruption of the RARγ complex impairs its function to bookmark AR enhancer interactions required for enzalutamide sensitivity in prostate cancer
Authors: Wani Sajad A , Hussain Shahid , Gray Jaimie S , Nayak Debasis , Tang Hancong , Perez Lillian M , Long Mark D , Siddappa Manjunath , McCabe Christopher J , Sucheston-Campbell Lara E , Freeman Michael R , Campbell Moray J
Published: December 2023

The current study in prostate cancer (PCa) focused on the genomic mechanisms at the cross-roads of pro-differentiation signals and the emergence of lineage plasticity. We explored an understudied cistromic mechanism involving RARγ’s ability to govern AR cistrome-transcriptome relationships, including those associated with more aggressive PCa features. The RARγ complex in PCa cell models was enriched for canonical cofactors, as well as proteins involved in RNA processing and bookmarking. Identifying the repertoire of miR-96 bound and regulated gene targets, including those recognition elements marked by m6A, revealed their significant enrichment in the RARγ complex. RARγ significantly enhanced the AR cistrome, particularly in active enhancers and super-enhancers, and overlapped with the binding of bookmarking factors. Furthermore, RARγ expression led to nucleosome-free chromatin enriched with H3K27ac, and significantly enhanced the AR cistrome in G2/M cells. RARγ functions also antagonized the transcriptional actions of the lineage master regulator ONECUT2. Similarly, gene programs regulated by either miR-96 or antagonized by RARγ were enriched in alternative lineages and more aggressive PCa phenotypes. Together these findings reveal an under-investigated role for RARγ, modulated by miR-96, to bookmark enhancer sites during mitosis. These sites are required by the AR to promote transcriptional competence, and emphasize luminal differentiation, while antagonizing ONECUT2.
Neuropeptide Modulation of Bidirectional Internetwork Synapses
Authors: Fahoum Savanna-Rae H , Blitz Dawn M
Published: December 2023

Oscillatory networks underlying rhythmic motor behaviors, and sensory and complex neural processing, are flexible, even in their neuronal composition. Neuromodulatory inputs enable neurons to switch participation between networks, or participate in multiple networks simultaneously. Neuromodulation of internetwork synapses can both recruit and coordinate a switching neuron in a second network. We previously identified an example in which a neuron is recruited into dual-network activity via peptidergic modulation of intrinsic properties. We now ask whether the same neuropeptide also modulates internetwork synapses for internetwork coordination. The crab (Cancer borealis) stomatogastric nervous system contains two well-defined feeding-related networks (pyloric, food filtering, ∼1 Hz; gastric mill, food chewing, ∼0.1 Hz). The projection neuron MCN5 uses the neuropeptide Gly1-SIFamide to recruit the pyloric-only LPG neuron into dual pyloric plus gastric mill-timed bursting via modulation of LPG’s intrinsic properties. Descending input is not required for a coordinated rhythm, thus intra-network synapses between LPG and its second network must underlie coordination among these neurons. However, synapses between LPG and gastric mill neurons have not been documented. Using two-electrode voltage clamp recordings, we found that graded synaptic currents between LPG and gastric mill neurons (LG, IC, DG) were primarily negligible in saline, but were enhanced by Gly1-SIFamide. Further, LPG and gastric mill neurons entrain each other during Gly1-SIFamide application, indicating bidirectional, functional connectivity. Thus, a neuropeptide mediates neuronal switching through parallel actions, modulating intrinsic properties in a switching neuron to recruit it into a second network and as shown here, also modulating bidirectional internetwork synapses for coordination.

New and Noteworthy

Neuromodulation can enable neurons to be simultaneously coordinated with separate networks. Both recruitment into, and coordination with, a second network can occur via modulation of internetwork synapses. Alternatively, recruitment can occur via modulation of intrinsic ionic currents. We find that the same neuropeptide previously determined to modulate intrinsic currents also modulates bidirectional internetwork synapses that are typically ineffective. Thus, complementary modulatory peptide actions enable recruitment and coordination of a neuron into a second network.
Fully Automated Explainable Abdominal CT Contrast Media Phase Classification Using Organ Segmentation and Machine Learning
Authors: Salimi Yazdan , Mansouri Zahra , Hajianfar Ghasem , Sanaat Amirhossein , Shiri Isaac , Zaidi Habib
Published: December 2023

Purpose

To detect contrast media injection phase from CT images by means of organ segmentation and deep learning.

Materials and Methods

A total number of 2509 CT images split into four subsets of non-contrast (class #0), arterial (class #1), venous (class #2), and delayed (class #3) after contrast media injection were collected from two CT scanners. Seven organs including the liver, spleen, heart, kidneys, lungs, urinary bladder, and aorta along with body contour masks were generated by pre-trained deep learning algorithms. Subsequently, five first-order statistical features including average, standard deviation, 10, 50, and 90 percentiles extracted from the above-mentioned masks were fed to machine learning models after feature selection and reduction to classify the CT images in one of four above mentioned classes. A ten-fold data split strategy was followed. The performance of our methodology was evaluated in terms of classification accuracy metrics.

Results

The best performance was achieved by Boruta feature selection and RF model with average area under the curve of more than 0.999 and accuracy of 0.9936 averaged over four classes and ten folds. Boruta feature selection selected all predictor features. The lowest classification was observed for class #2 (0.9888), which is already an excellent result. In the ten-fold strategy, only 33 cases from 2509 cases (∼1.4%) were misclassified.

Conclusion

We developed a fast, accurate, reliable, and explainable methodology to classify contrast media phases which may be useful in data curation and annotation in big online datasets or local datasets with non-standard or no series description.

Key points

The lack of standard series description and information about contrast media phase limits the usability of medical CT data.

We developed a twostep deep learning/machine learning solution with excellent performance.

This fast, automated, reliable and explainable purposed pipeline can tag every CT images with using only image matrices.
Copper-deficiency is associated with impairments in social behavior and oligodendrocyte development via mTOR signaling pathway
Authors: Usui Noriyoshi , Doi Miyuki , Berto Stefano , Matsuoka Kiwamu , Ishida Rio , Irie Koichiro , Nakama Nanako , Miyauchi Hana , Fujiwara Yuuki , Yamauchi Takahira , Hirai Takaharu , Toritsuka Michihiro , Xie Min-Jue , Kayashima Yoshinori , Umeda Naoko , Iwata Keiko , Okumura Kazuki , Harada Taeko , Yoshimura Takeshi , Katayama Taiichi , Tsujii Masatsugu , Matsuzaki Hideo , Makinodan Manabu , Shimada Shoichi
Published: December 2023

Autism spectrum disorder (ASD) is a heterogeneous disorder characterized by impaired social communication and restricted repetitive behaviors, however the biological mechanisms remain unclear. Although trace elements play essential roles in the living body, it is unclear how alterations of trace elements in ASD are involved in pathogenesis. Here we analyzed the plasma metallome and identified the alterations of 11 elements in individuals with ASD. The copper decrease was negatively correlated with ASD symptom scores. A copper-deficient mouse model reflecting the condition showed ASD-like behaviors and impaired oligodendrocyte development. In copper-deficient mice, mechanistic target of rapamycin (mTOR) signaling was reduced, and its activation by agonist improved social impairment and oligodendrocyte developmental defects. Supporting these results, white matter volumes were negatively correlated with social symptoms in individuals with ASD. Our results demonstrate that copper-deficiency contributes to ASD by causing oligodendrocytes impairment via mTOR signaling. Our findings indicate that the effects of copper-deficiency and mTOR imbalance are relevant to the pathogenesis of ASD and are potential therapeutic targets.
Factors influencing referral to maternity models of care in Australian general practice
Authors: Thomas J , Kuliukas L , Frayne J , Bradfield Z
Published: December 2023

Background

In the Australian maternity system, general practitioners play a vital role in advising and directing prospective parents to maternity models of care. Optimising model of care discussions and the decision-making process avoids misaligning women with over or under specialised care, reduces the potential for disruptive care transitions and unnecessary healthcare costs, and is critical in ensuring consumer satisfaction. Current literature overwhelmingly focusses on women’s decision-making around model of care discussions and neglects the gatekeeping role of the General Practitioner (GP). This study aimed to explore and describe the factors influencing Australian GPs decision-making when referring pregnant women to maternity models of care.

Methods

This study used a qualitative descriptive approach. General practitioners (N=12) with experience referring women to maternity models of care in Australia participated in a semi-structured interview. Interviews occurred between October and November 2021 by telephone or videoconference. Reflexive thematic analysis was facilitated by NVivo-12 data management software to codify and interpret themes from the data.

Findings

Two broad themes were interpreted from the data. The first theme entitled ‘GP Factors’, incorporated three associated sub-themes including ‘GPs Previous Model of Care Experience’, ‘Gaps in GP Knowledge’ and ‘GP Perception of Models of Care’. The second theme, entitled ‘Woman’s Factors’, encapsulated two associated sub-themes including the ‘Woman’s Preferences’ and ‘Access to Models’.

Conclusions

This study provides novel evidence regarding general practitioner perspectives of the factors influencing model of care decision-making and referral. The exploration and description of factors influencing model of care decisions provide unique insight into the ways that all stakeholders can experience access to a broader range of models of care including midwifery-led continuity of care models aligned with consumer-demand. In addition, the role of national primary health networks is outlined as a means to achieving this.
The Philosophical Perspective in Transculturizing Instrument Tools to Detect Diabetic Foot Ulcer : A Literature Review
Authors: Awaluddin Sri Wahyuni , Rumambo Pandin Moses Glorino , Nursalam
Published: December 2023

Diabetes foot ulcer (DFU) is one of the main complications of diabetes mellitus (DM) and one of the main causes of death worldwide from non-communicable diseases (NCDs). The development of an instrument tool for the early diagnosis of diabetic foot is crucial since the findings can be used to prioritize clinical examinations for patients who are at risk. This literature review aimed to examine the philosophical viewpoint on transculturalizing instrument instruments to detect DFU from a variety of study reports published in both domestic and foreign journals. The original research publications published between January 2018 and December 2023 were the focus of the literature search. This study used secondary data, which came from 17 credible journal publications obtained from Science Direct, CINAHL, Pubmed, and SCOPUS databases. The PICOS framework was utilized to assess the papers’ suitability after they were selected. Articles meeting the inclusion requirements would be chosen: the studies should show the outcome of DFU detection or intervention for the outcome, and the population should consist of DM patients with or without DFU, with early DFU detection or intervention for Intervention. The studies could use any kind of research design, including descriptive, cross-sectional, observational, quasi-experimental, randomized controlled trials, and mixed methods, and should be written in English. The result of this literature review showed all the newly developed instrument tools to detect DFU have tested the validity and reliability of content, particularly translation to the local language to meet cultural appropriateness. It is important for researchers working on new DFU detection risk tools to consider including transcultural theory in their assessment instruments for DFU early detection.
Cardiac afferent signals can facilitate visual dominance in binocular rivalry
Authors: Veillette John P. , Gao Fan , Nusbaum Howard C.
Published: December 2023

Sensory signals from the body’s visceral organs (e.g. the heart) can robustly influence the perception of exteroceptive sensations. This interoceptive-exteroceptive interaction has been argued to underlie self-awareness by situating one’s perceptual awareness of exteroceptive stimuli in the context of one’s internal state, but studies probing cardiac influences on visual awareness have yielded conflicting findings. In this study, we presented separate grating stimuli to each of subjects’ eyes as in a classic binocular rivalry paradigm – measuring the duration for which each stimulus dominates in perception. However, we caused the gratings to “pulse” at specific times relative to subjects’ real-time electrocardiogram, manipulating whether pulses occurred during cardiac systole, when baroreceptors signal to the brain that the heart has contracted, or in diastole when baroreceptors are silent. The influential “Baroreceptor Hypothesis” predicts the effect of baroreceptive input on visual perception should be uniformly suppressive. In contrast, we observed that dominance durations increased for systole-entrained stimuli, inconsistent with the Baroreceptor Hypothesis. Further, we show that this cardiac-dependent rivalry effect is preserved in subjects who are at-chance discriminating between systole-entrained and diastole-presented stimuli in a separate interoceptive awareness task, suggesting that our results are not dependent on conscious access to heartbeat sensations.
Differential spatial regulation and activation of integrin nanoclusters inside focal adhesions
Authors: Keary Sarah , Mateos Nicolas , Campelo Felix , Garcia-Parajo Maria F.
Published: December 2023

α5β1and αvβ3integrins are core components of focal adhesions (FAs) involved in cell attachment, migration and mechanobiology-dependent processes. Recent works indicate that both integrins organize in nanoclusters inside FAs, with sub-populations of active and inactive β1nanoclusters. However, whether both integrins work in concert or their activities are spatially regulated is not fully understood. Using dual-color super-resolution microscopy we show that integrins α5β1and αvβ3exhibit similar functional nanoscale segregation. Notably, both integrins never mix at the nanoscale indicating that their functions might be spatially regulated. We find a nearly 1:1 stoichiometry between active integrin and adaptor nanoclusters suggesting that coordinated integrin activation occurs via the concurrent engagement of adaptor nanoclusters. Interestingly, α5β1nanoclusters preferentially localize at the FA periphery in close proximity to adaptor nanoclusters, establishing regions of multi-nanocluster enrichment, whereas αvβ3nanoclusters uniformly distribute throughout FAs. Overall, our results show that adhesion proteins arrange as modular nanoscale units that distinctively organize inside FAs to spatially regulate integrin activation and function.