bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of methylphenidate is associated with increased risk of out-of-hospital cardiac arrest in the general population: a nationwide nested case-control study
Authors: Eroglu Talip E , Halili Andrim , Arulmurugananthavadivel Anojhaan , Coronel Ruben , Kessing Lars Vedel , Fosbøl Emil Loldrup , Folke Fredrik , Torp-Pedersen Christian , Gislason Gunnar Hilmar
Published: April 2023

Aim

Methylphenidate, a sympathomimetic drug prescribed to treat attention-deficit/hyperactivity disorder (ADHD), is associated with cardiovascular events, but few studies have explored the risk of out-of-hospital cardiac arrest (OHCA). We investigated whether methylphenidate use is associated with OHCA in the general population.

Methods and results

Using Danish nationwide registries, we conducted a nested case-control study with OHCA cases of presumed cardiac causes and age/sex/OHCA-date-matched non-OHCA controls from the general population. Conditional logistic regression models with adjustments for well-known risk factors of OHCA were employed to estimate the odds ratio (OR) of OHCA by comparing methylphenidate use with no use of methylphenidate.

The study population consisted of 46 578 OHCA cases [median: 72 years (interquartile range: 62–81), 68.8% men] and 232 890 matched controls. Methylphenidate was used by 80 cases and 166 controls, and was associated with an increased OR of OHCA compared with non-users {OR: 1.78 [95% confidence interval (CI): 1.32–2.40]}. The OR was highest in recent starters (OR≤180 days: 2.59, 95% CI: 1.28–5.23). The OR of OHCA associated with methylphenidate use did not vary significantly by age (P-value interaction: 0.37), sex (P-value interaction: 0.94), and pre-existing cardiovascular disease (P-value interaction: 0.27). Furthermore, the ORs remained elevated when we repeated the analyses in individuals without registered hospital-based ADHD (OR: 1.85, 95% CI: 1.34–2.55), without severe psychiatric disorders (OR: 1.98, 95% CI: 1.46–2.67), without depression (OR: 1.93, 95% CI: 1.40–2.65), or in non-users of QT-prolonging drugs (OR: 1.79, 95% CI: 1.27–2.54).

Conclusion

Methylphenidate use is associated with an increased risk of OHCA in the general population. This increased risk applies to both sexes and is independent of age and the presence of cardiovascular disease.
Hybrid breakdown in male reproduction between recently divergedDrosophila melanogasterpopulations has a complex and variable genetic architecture
Authors: Lollar Matthew J , Biewer-Heisler Timothy J , Danen Clarice E , Pool John E
Published: April 2023

Secondary contact between formerly isolated populations may result in hybrid breakdown, in which untested allelic combinations in hybrids are maladaptive and limit genetic exchange. Studying early-stage reproductive isolation may yield key insights into the genetic architectures and evolutionary forces underlying the first steps toward speciation. Here, we leverage the recent worldwide expansion of Drosophila melanogaster to test for hybrid breakdown between populations that diverged within the last 13,000 years. We found clear evidence for hybrid breakdown in male reproduction, but not female reproduction or viability, supporting the prediction that hybrid breakdown affects the heterogametic sex first. The frequency of non-reproducing F2 males varied among different crosses involving the same southern African and European populations, as did the qualitative effect of cross direction, implying a genetically variable basis of hybrid breakdown and a role for uniparentally inherited factors. The levels of breakdown observed in F2 males were not recapitulated in backcrossed individuals, consistent with the existence of incompatibilities with at least three partners. Thus, some of the very first steps toward reproductive isolation could involve incompatibilities with complex and variable genetic architectures. Collectively, our findings emphasize this system’s potential for future studies on the genetic and organismal basis of early-stage reproductive isolation.
Effect of pomegranate peel extract on the reduction of heterocyclic amines and quality characteristics of mutton meatballs
Authors: Chen Jingjing , Shi Xixiong , Zhao Ruina , Tian Zhu , Zhang Li , Yu Qunli , Chen Cheng
Published: April 2023

Pomegranate peel extract (PPE), rich in phenolic compounds, is an undervalued byproduct derived from processing pomegranates. However, there are very few studies on the inhibitory effect of PPE on harmful substances during meat processing. This study was intended to investigate the influence of different concentrations of PPE (0.50%, 1%, and 1.50%) on the generation of heterocyclic amines (HCAs) and some quality attributes in mutton meatballs. All samples with the addition of PPE (0, 0.50%, 1%, and 1.50%) were fried for different lengths of time (2.5 min and 5 min) at 175±5 °C, and the contents of fourteen HCAs, color, thiobarbituric acid reactive substances, and carbonyl values of fried mutton meatballs were evaluated. The results showed that samples fried at 2.5 min had a low HCA content, and the HCA content enhanced significantly when the frying time was increased from 2.5 to 5 min (P<0.05). In comparison with the control group, PPE could significantly inhibit the generation of total HCAs in fried mutton meatballs (P<0.05), and the total HCAs content decreased with increasing PPE concentration. PPE significantly reduced carbonyl and TBARS values in fried mutton meatballs (P<0.05). Moreover, PPE resulted in a significant increase in a* and b* values as well as a decrease in L* values in fried mutton meatballs (P<0.05). In conclusion, PPE could inhibit the formation of HCAs and improve the quality of mutton meatballs, and could be considered as a natural inhibitor of HCAs in fried meat products.
Evidence of two mitochondrial lineages and genetic variability in forensically important Lucilia eximia (Diptera: Calliphoridae) in Colombia
Authors: Pérez-Pérez Juliana , Pulgarín Díaz John Alexander , López-Rubio Andrés , Gómez-Piñerez Luz M , Rúa-Uribe Guillermo , Márquez Edna J
Published: April 2023

Lucilia eximia (Wiedemann, 1819) (Diptera: Calliphoridae) is a blowfly with medical and forensic importance that shows genetic and color variation, however, these variations have not justified the description of new species. But in forensic entomology an accurate identification of species and subpopulations is crucial. We explored the genetic variation of L. eximia from eight localities, in five natural regions in Colombia using two mitochondrial fragments, including the standard locus for insect identification COI and the Cytb-tRNA-Ser-ND1 region. We found significant differentiation at COI and Cytb-tRNA-Ser-ND1 level, characterizing two lineages and revealing a deep and significant genetic split. High values of FST and genetic distances supported the two lineages. The origin of the divergence of L. eximia remains to discover. Examining whether the lineages have diverse ecological and biological behaviors could be a significant impact on the use of L. eximia in forensic and medical science. Our results could have relevant implications for the use of post-mortem interval estimation based on insect evidence, as well as our sequences improve the database used in DNA-based methods for identifying forensically important flies.
The representation of animal communication and language evolution in introductory linguistics textbooks
Authors: Wacewicz Sławomir , Pleyer Michael , Szczepańska Aleksandra , Ewa Poniewierska Aleksandra , Żywiczyński Przemysław
Published: April 2023

The last three decades have brought a wealth of new empirical data and methods that have transformed investigations of language evolution into a fast-growing field of scientific research. In this paper, we investigate how the results of this research are represented in the content of the most popular introductory linguistic textbooks. We carried out a comprehensive computer-assisted qualitative study, in which we inspected eighteen English-language textbooks for all content related to the evolutionary emergence of language and its uniqueness in nature, in order to evaluate its thematic scope, selection of topics, theories covered, researchers cited, structural soundness, currency, and factual accuracy. Overall, we found that the content of interest lacks a defined canonical representation across the textbooks. The coverage of animal communication was relatively broad, with some recurring classic examples, such as vervet monkeys or honeybees; this content was mostly structured around the ‘design features’ approach. In contrast, the coverage of topics related to language origins and evolution was much less extensive and systematic, and tended to include a relatively large the proportion of content of historical value (i.e. creation myths, ‘bow-wow’ theories). We conclude by making recommendations for future editions of textbooks, in particular, a better representation of important frameworks such as signalling theory, and of current research results in this fast-paced field.
A Diagnostic Accuracy Study to Evaluate Standard Rapid Diagnostic Test (RDT) Alone to Safely Rule Out Imported Malaria in Children Presenting to UK Emergency Departments
Authors: Bird Chris , Hayward Gail N , Turner Philip J , Merrick Vanessa , Lyttle Mark D , Mullen Niall , Fanshawe Thomas R ,   for the Paediatric Emergency Research in the UK and Ireland (PERUKI), Amenos Barraza Glenda , Ramlakhan Shammi , Shackley Fiona , Simmerson Mark , Wynne Emma , Tough Emma , Beer Sally , Brown Charlotte , Steensma Jiske , Blakey Sarah , Shone Eleanor , Foster Steve , Jacobs Michelle , Rineesh Mohamed , Palmer Katie , Thakker Manish , Morgan Jeff , Muller Jennifer , McEvoy Sophie , Browning Jen , Malik Kashif , Okoye Jude , Wong Shye-Wei , Diaba Cynthia , Hemraj Sudeepta , Patel Poonam , Lawson George , Knight Katie , McCartney Deborah , Tanto Paul , Fraser Lauren , Al-Rawi Sarah , Ghafoor Kazim , Nezafat Behrouz , Silva Ferreira Ana , Barrett Michael , Sivanenthiran Nilaksa , Jarman Heather , Jamall Erum , Davies Karen , Wasala Desha , Hadfield Sarah , Hartshorn Stuart
Published: April 2023

Background

Microscopy is the gold standard for malaria diagnosis but is dependent on trained personnel. Rapid diagnostic tests (RDTs) form the mainstay of diagnosis in endemic areas without access to high-quality microscopy. We aimed to evaluate whether RDT alone could rule out imported malaria in children presenting to UK emergency departments (EDs).

Methods

UK-based, multi-center, retrospective, diagnostic accuracy study. Included: any child <16 years presenting to ED with history of fever and travel to a malaria-endemic country, between 01/01/2016 and 31/12/2017. Diagnosis: microscopy for malarial parasites (clinical reference standard) and RDT (index test). UK Health Research Authority approval: 20/HRA/1341.

Results

There were 47 cases of malaria out of 1,414 eligible cases (prevalence 3.3%) in a cohort of children whose median age was 4 years (IQR 2–9), of whom 43% were female. Cases of Plasmodium falciparum totaled 36 (77%, prevalence 2.5%). The sensitivity of RDT alone to detect malaria infection due to any Plasmodium species was 93.6% (95% CI 82.5–98.7%), specificity 99.4% (95% CI 98.9–99.7%), positive predictive value 84.6% (95% CI 71.9–93.1%) and negative predictive value 99.8% (95% CI 99.4–100.0%). Sensitivity of RDT to detect P. falciparum infection was 100% (90.3–100%), specificity 98.8% (98.1–99.3%), positive predictive value 69.2% (54.9–81.2%, n = 46/52) and negative predictive value 100% (99.7–100%, n = 1,362/1,362).

Conclusions

RDTs were 100% sensitive in detecting P. falciparum malaria. However, lower sensitivity for other malaria species and the rise of pfhrp2 and pfhrp3 (pfhrp2/3) gene deletions in the P. falciparum parasite mandate the continued use of microscopy for diagnosing malaria.
Schistosomal appendicitis: a rare cause of a common surgical condition
Authors: Li Jia Xi Julian , Fan Howard Shihao
Published: April 2023

Despite the prevalence of schistosomiasis across the world, appendicitis secondary to schistosomiasis is a rarely encountered presentation even in endemic areas, let alone in developed Western countries. We report a case of a 34-year-old male in Australia with acute appendicitis and subsequent histopathology, demonstrating the presence of schistosome ova. The case highlights the difficulties in pre-operative diagnosis of this entity and the importance of its recognition for the practising surgeon, especially in the developed world, where this rare condition may be encountered because of changing global travel and migration patterns.
Internal hernia in the medial inguinal fossa with a concurrent indirect inguinal hernia: a case report
Authors: Shinohara Kentaro , Hattori Masaoki , Aono Keiya , Hirata Akihiro , Ito Ryogo , Yoshihara Motoi
Published: April 2023

A 51-year-old male was presented with abdominal pain and vomiting. Contrast-enhanced computed tomography showed a dilated small intestine with a sac-like appearance in the right lower abdomen. An internal hernia in the inguinal area was found during emergency laparoscopic exploration. The incarcerated small intestine was gently reduced, and the internal hernia sac was located in the right medial inguinal fossa. An indirect inguinal hernia was identified just behind the dissected internal hernia sac. The internal hernia sac was resected, and the indirect inguinal hernia was repaired through a transabdominal preperitoneal approach. The patient had no recurrence of hernia within the 20 months of follow-up after the surgery. This is the first case of an internal hernia in the medial inguinal fossa with a concurrent indirect inguinal hernia. The topographical relationship of these two hernias suggested that an indirect inguinal hernia may cause an internal hernia in the medial inguinal fossa.
Impact of Nonpharmaceutical Interventions During the COVID-19 Pandemic on Medically Attended Acute Respiratory Infection: The U.S. Naval Academy Experience
Authors: Millar Eugene V , Rossi Stephen P , Pollett Simon , Saperstein Adam K , Burgess Timothy H , Modi Jitendrakumar
Published: April 2023

Introduction

Medically attended acute respiratory infections (MAARI) at the U.S. Naval Academy increase during Plebe Summer, a training program for incoming freshmen. Because of COVID-19, extensive nonpharmaceutical interventions (NPI) were implemented during 2020 Plebe Summer.

Methods

We reviewed MAARI counts in weeks 22–45 from 2012 to 2020 and compared counts in pandemic (2020) vs. pre-pandemic (2012–2019) periods.

Results

From 2012 to 2019, an average of 1,642 MAARI cases occurred annually. In 2020, 443 MAARI cases occurred. NPI use was associated with a 77% reduction in MAARI.

Conclusions

During a high-risk military training period, routine NPI use was associated with a major reduction in MAARI.
Evolution of the angles between magnetic moments and rotation axes in radio pulsars
Authors: Ken’ko Z V , Malov I F
Published: April 2023

Distribution of angles β between magnetic moments and rotation axes for radio pulsars with periods in the interval 0.1 s < P < 2 s has been obtained. This distribution is rather wide with a mean value of 23°. For the bulk of pulsars, the inclination of axes is characterized by moderate values of angles β. About 60 per cent of pulsars considered have angles in the interval from 20° to 45°. The useful correlation between kinematic tkin and characteristic ages τ has been detected. The relationship between tkin and τ can be used to make a conversion of catalogue values of τ to more real pulsar ages tkin. It will be important in further pulsar investigations. It is shown that inclination angles for pulsars with 0.1 s < P < 2 s decrease with their ages. This decrease is the best described by the power law. Values of angles β have been calculated for pulsars, which are at the moment in SNRs. These angles are not changed markedly during 105 yr. Their decrease begins much later.
Retrieval study of cool, directly imaged exoplanet 51 Eri b
Authors: Whiteford Niall , Glasse Alistair , Chubb Katy L , Kitzmann Daniel , Ray Shrishmoy , Phillips Mark W , Biller Beth A , Palmer Paul I , Rice Ken , Waldmann Ingo P , Changeat Quentin , Skaf Nour , Wang Jason , Edwards Billy , Al-Refaie Ahmed
Published: April 2023

Retrieval methods are a powerful analysis technique for modelling exoplanetary atmospheres by estimating the bulk physical and chemical properties that combine in a forward model to best fit an observed spectrum, and they are increasingly being applied to observations of directly imaged exoplanets. We have adapted taurex3, the Bayesian retrieval suite, for the analysis of near-infrared spectrophotometry from directly imaged gas giant exoplanets and brown dwarfs. We demonstrate taurex3’s applicability to sub-stellar atmospheres by presenting results for brown dwarf benchmark GJ 570D which are consistent with previous retrieval studies, whilst also exhibiting systematic biases associated with the presence of alkali lines. We also present results for the cool exoplanet 51 Eri b, the first application of a free chemistry retrieval analysis to this object, using spectroscopic observations from GPI and SPHERE. While our retrieval analysis is able to explain spectroscopic and photometric observations without employing cloud extinction, we conclude this may be a result of employing a flexible temperature-pressure profile which is able to mimic the presence of clouds. We present Bayesian evidence for an ammonia detection with a 2.7σ confidence, the first indication of ammonia in a directly imaged exoplanetary atmosphere. This is consistent with this molecule being present in brown dwarfs of a similar spectral type. We demonstrate the chemical similarities between 51 Eri b and GJ 570D in relation to their retrieved molecular abundances. Finally, we show that overall retrieval conclusions for 51 Eri b can vary when employing different spectral data and modelling components, such as temperature–pressure and cloud structures.
Ferrocenoyl-substituted quinolinone and coumarin as organometallic inhibitors of SARS-CoV-2 3CLpro main protease
Authors: Graf Dominic , Farn Nikolas , Klopf Jonas , Hojjati Mahniya , Schatzschneider Ulrich
Published: April 2023

The 3-chymotrypsin-like protease 3CLpro from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a potential target for antiviral drug development. In this work, three organometallic ferrocene-modified quinolinones and coumarins were compared to their benzoic acid ester analogues with regard to inhibition of 3CLpro using an HPLC-based assay with a 15mer model peptide as the substrate. In contrast to FRET-based assays, this allows direct identification of interference of buffer constituents with the inhibitors, as demonstrated by the complete abolishment of ebselen inhibitory activity in the presence of dithiothreitol as a redox protectant. The presence of the organometallic ferrocene moiety significantly increased the stability of the title compounds towards hydrolysis. Among the studied compounds, 4-ferrocenyloxy-1-methyl-quinol-2-one was identified as the most stable and potent inhibitor candidate. IC50 values determined for ebselen and this sandwich complex compound are (0.40 ± 0.07) and (2.32 ± 0.21) μM, respectively.
Interaction of the La-related protein Slf1 with colliding ribosomes maintains translation of oxidative-stress responsive mRNAs
Authors: Jennings Martin D , Srivastava Priya , Kershaw Christopher J , Talavera David , Grant Christopher M , Pavitt Graham D
Published: April 2023

In response to oxidative stress cells reprogram gene expression to enhance levels of antioxidant enzymes and promote survival. In Saccharomyces cerevisiae the polysome-interacting La-related proteins (LARPs) Slf1 and Sro9 aid adaptation of protein synthesis during stress by undetermined means. To gain insight in their mechanisms of action in stress responses, we determined LARP mRNA binding positions in stressed and unstressed cells. Both proteins bind within coding regions of stress-regulated antioxidant enzyme and other highly translated mRNAs in both optimal and stressed conditions. LARP interaction sites are framed and enriched with ribosome footprints suggesting ribosome–LARP–mRNA complexes are identified. Although stress-induced translation of antioxidant enzyme mRNAs is attenuated in slf1Δ, these mRNAs remain on polysomes. Focusing further on Slf1, we find it binds to both monosomes and disomes following RNase treatment. slf1Δ reduces disome enrichment during stress and alters programmed ribosome frameshifting rates. We propose that Slf1 is a ribosome-associated translational modulator that stabilises stalled/collided ribosomes, prevents ribosome frameshifting and so promotes translation of a set of highly-translated mRNAs that together facilitate cell survival and adaptation to stress.
A multidisciplinary approach to the identification of the protein–RNA connectome in double-stranded RNA virus capsids
Authors: Sung Po-yu , Zhou Yiyang , Kao C Cheng , Aburigh Ali A , Routh Andrew , Roy Polly
Published: April 2023

How multi-segmented double-stranded RNA (dsRNA) viruses correctly incorporate their genomes into their capsids remains unclear for many viruses, including Bluetongue virus (BTV), a Reoviridae member, with a genome of 10 segments. To address this, we used an RNA-cross-linking and peptide-fingerprinting assay (RCAP) to identify RNA binding sites of the inner capsid protein VP3, the viral polymerase VP1 and the capping enzyme VP4. Using a combination of mutagenesis, reverse genetics, recombinant proteins and in vitro assembly, we validated the importance of these regions in virus infectivity. Further, to identify which RNA segments and sequences interact with these proteins, we used viral photo-activatable ribonucleoside crosslinking (vPAR-CL) which revealed that the larger RNA segments (S1-S4) and the smallest segment (S10) have more interactions with viral proteins than the other smaller segments. Additionally, using a sequence enrichment analysis we identified an RNA motif of nine bases that is shared by the larger segments. The importance of this motif for virus replication was confirmed by mutagenesis followed by virus recovery. We further demonstrated that these approaches could be applied to a related Reoviridae member, rotavirus (RV), which has human epidemic impact, offering the possibility of novel intervention strategies for a human pathogen.
Sex-lethal regulates back-splicing and generation of the sex-differentially expressed circular RNAs
Authors: Fan Yu-Jie , Ding Zhan , Zhang Yu , Su Ruibao , Yue Jia-Le , Liang An-Min , Huang Qi-Wei , Meng Yan-Ran , Li Muwang , Xue Yuanchao , Xu Yong-Zhen
Published: April 2023

Conversely to canonical splicing, back-splicing connects the upstream 3' splice site (SS) with a downstream 5'SS and generates exonic circular RNAs (circRNAs) that are widely identified and have regulatory functions in eukaryotic gene expression. However, sex-specific back-splicing in Drosophila has not been investigated and its regulation remains unclear. Here, we performed multiple RNA analyses of a variety sex-specific Drosophila samples and identified over ten thousand circular RNAs, in which hundreds are sex-differentially and -specifically back-spliced. Intriguingly, we found that expression of SXL, an RNA-binding protein encoded by Sex-lethal (Sxl), the master Drosophila sex-determination gene that is only spliced into functional proteins in females, promoted back-splicing of many female-differential circRNAs in the male S2 cells, whereas expression of a SXL mutant (SXLRRM) did not promote those events. Using a monoclonal antibody, we further obtained the transcriptome-wide RNA-binding sites of SXL through PAR-CLIP. After splicing assay of mini-genes with mutations in the SXL-binding sites, we revealed that SXL-binding on flanking exons and introns of pre-mRNAs facilitates back-splicing, whereas SXL-binding on the circRNA exons inhibits back-splicing. This study provides strong evidence that SXL has a regulatory role in back-splicing to generate sex-specific and -differential circRNAs, as well as in the initiation of sex-determination cascade through canonical forward-splicing.
Haplogrep 3 - an interactive haplogroup classification and analysis platform
Authors: Schönherr Sebastian , Weissensteiner Hansi , Kronenberg Florian , Forer Lukas
Published: April 2023

Over the last decade, Haplogrep has become a standard tool for haplogroup classification in the field of human mitochondrial DNA and is widely used by medical, forensic, and evolutionary researchers. Haplogrep scales well for thousands of samples, supports many file formats and provides an intuitive graphical web interface. Nevertheless, the currently available version has limitations when applying it to large biobank-scale data. In this paper, we present a major upgrade to the software by adding (a) haplogroup summary statistics and variant annotations from various publicly available genome databases, (b) an interface to connect new phylogenetic trees, (c) a new state-of-the-art web framework managing large scale data, (d) algorithmic adaptions to improve FASTA classification using BWA-specific alignment rules and (e) a pre-classification quality control step for VCF samples. These improvements will give researchers the opportunity to classify thousands of samples as usual but providing additional ways to investigate the dataset directly in the browser. The web service and its documentation can be accessed freely without any registration at https://haplogrep.i-med.ac.at.
MyGeneset.info: an interactive and programmatic platform for community-curated and user-created collections of genes
Authors: Avila Ricardo , Rubinetti Vincent , Zhou Xinghua , Hu Dongbo , Qian Zhongchao , Cano Marco Alvarado , Rodolpho Everaldo , Tsueng Ginger , Greene Casey , Wu Chunlei
Published: April 2023

Gene definitions and identifiers can be painful to manage–more so when trying to include gene function annotations as this can be highly context-dependent. Creating groups of genes or gene sets can help provide such context, but it compounds the issue as each gene within the gene set can map to multiple identifiers and have annotations derived from multiple sources. We developed MyGeneset.info to provide an API for integrated annotations for gene sets suitable for use in analytical pipelines or web servers. Leveraging our previous work with MyGene.info (a server that provides gene-centric annotations and identifiers), MyGeneset.info addresses the challenge of managing gene sets from multiple resources. With our API, users readily have read-only access to gene sets imported from commonly-used resources such as Wikipathways, CTD, Reactome, SMPDB, MSigDB, GO, and DO. In addition to supporting the access and reuse of approximately 180k gene sets from humans, common model organisms (mice, yeast, etc.), and less-common ones (e.g. black cottonwood tree), MyGeneset.info supports user-created gene sets, providing an important means for making gene sets more FAIR. User-created gene sets can serve as a way to store and manage collections for analysis or easy dissemination through a consistent API.
The 2000s Housing Cycle with 2020 Hindsight: A Neo-Kindlebergerian View
Authors: Chodorow-Reich Gabriel , Guren Adam M , McQuade Timothy J
Published: April 2023

With “2020 hindsight,” the 2000s housing cycle is not a boom–bust but a boom–bust–rebound. Using a spatial equilibrium regression in which house prices are determined by income, amenities, urbanization, and supply, we show that long-run city-level fundamentals predict not only 1997–2019 price and rent growth but also the amplitude of the boom–bust–rebound. This evidence motivates our model of a cycle rooted in fundamentals. Households learn about fundamentals by observing “dividends” but become over-optimistic in the boom due to diagnostic expectations. A bust ensues when beliefs start to correct, exacerbated by a price–foreclosure spiral that drives prices below their long-run level. The rebound follows as prices converge to a path commensurate with higher fundamental growth. The estimated model explains the boom–bust–rebound with a single shock and accounts quantitatively for the dynamics of prices, rents, and foreclosures in cities with the largest cycles. We draw implications for asset cycles more generally.
Vaginal dryness in women infected by human T-lymphotropic virus type 1: an exploratory study
Authors: Martins Adenilda Lima Lopes , de Aquino Firmino Alisson , Boa-Sorte Ney , Araújo Jean Paulo Lacerda , Paixão Taiane Silva , Viriato Adriele Ribeiro França , Galvão-Castro Bernardo , Grassi Maria Fernanda Rios
Published: April 2023

Background

Human T-lymphotropic virus type-1 (HTLV-1) causes a variety of sicca symptoms, including xeroderma, xerostomia, and xerophthalmia.

Aim

We sought to evaluate vaginal dryness via the degree of perceived vaginal lubrication, vaginal hormonal cytology, and direct measurements of vaginal wetting.

Methods

The research was designed as a cross-sectional study. Vaginal dryness was assessed by scores in the lubrication domain of the Female Sexual Function Index (FSFI) questionnaire and the Vaginal Maturation Index (VMI) determined by vaginal hormonal cytology, as well as the measurement of vaginal lubrication using Schirmer strips placed at the anterior vaginal wall. Medians (25th-75th percentiles) were calculated for each group and compared using a nonparametric Kruskal-Wallis test and the Dunn-Bonferroni post hoc method.

Outcomes

Outcomes were detection of the presence of vaginal dryness in women who were infected or noninfected with HTLV-1.

Results

HTLV-1–infected women (n = 72, 57 asymptomatic and 15 with HTLV-1–associated myelopathy/tropical spastic paraparesis [HAM/TSP]) and uninfected women (n = 49) were studied. Women with HAM/TSP had significantly lower FSFI lubrication scores than asymptomatic and uninfected women (P = .032). In addition, women with HAM/TSP had significantly lower VMI compared with the asymptomatic and uninfected groups (P = .027 and P = .039, respectively).

Clinical Implications

The results of this study show a reduction in vaginal lubrication in HTLV-1-infected women diagnosed with HAM/TSP compared with asymptomatic and uninfected women.

Strengths and Limitations

The lack of a gold standard test for the diagnosis of vaginal dryness and the fact that no assessment of vaginal pH was performed were limitations of this study. The strength of the study was the comprehensive assessment of vaginal dryness from several perspectives: subjective (perception of vaginal lubrication according to the vaginal lubrication domain of the FSFI), hormonal (vaginal hormonal cytology to assess local hormone status), and the degree of vaginal moisture (direct measurement of vaginal dryness with an instrument, the Schirmer strip, already used to measure the presence of dry eye).

Conclusion

HTLV-1-infected women with HAM/TSP have decreased vaginal lubrication compared with asymptomatic and uninfected women after adjusting for age.
Quantifying the number of US men with erectile dysfunction who are potential candidates for penile prosthesis implantation
Authors: Rojanasarot Sirikan , Williams Abimbola O , Edwards Natalie , Khera Mohit
Published: April 2023

Introduction

Penile prosthesis implantation (PPI) is a treatment option recommended in clinical guidelines for erectile dysfunction (ED). However, a limited number of urologists perform PPI procedures in the United States.

Aim

To quantify the number of insured men with ED in the United States and project the number of potential candidates for PPI in 2022.

Methods

An Excel-based disease impact model was constructed using a top-down estimation approach. The starting US male population consisted of adult men from 2022 US Census data after exclusion of age-specific mortality rates from the National Vital Statistics Reports. Men with health insurance were included in the model based on insurance status data from the US Census database. ED prevalence and ED treatment rates were obtained from administrative claims data analyses—the Merative MarketScan Commercial Database (18-64 years) and the 5% Medicare Standard Analytical Files (≥65 years)—and literature-based estimates of patient-reported ED prevalence.

Outcomes

The number of men with ED in the United States and the number of potential candidates for PPI were estimated.

Results

By utilizing ED prevalence based on administrative claims, an estimated 8.3% of insured men (10,302,540 estimated men [8,882,548 aged 18-64 years and 1,419,992 aged ≥65 years]) had a diagnosis of ED and sought ED care, out of 124,318,519 eligible US men aged ≥18 years in 2022. An estimated 17.1% of men with an ED diagnosis claim could benefit from PPI in 2022 (1,759,248 men aged ≥18 years). Patient self-reported ED prevalence across all ages ranged from 5.1% to 70.2%. Scenario analyses applying the patient self-reported ED prevalence range revealed the number of men in the United States who could benefit from PPI could have been higher than 1.7 million if their ED symptoms were diagnosed by health care providers.

Clinical Implications

Most men with ED in the United States are undertreated, and many could benefit from PPI.

Strengths and Limitations

This analysis is a US population–level estimation. However, given this study utilized a variety of assumptions, the results may vary if different model assumptions are applied.

Conclusions

This disease impact model estimated that approximately 10.3 million men were diagnosed with ED by their health care providers and sought ED care in the United States in 2022. Of those, 1.7 million men could be PPI candidates and benefit from the treatment option.
EptA of Riemerella anatipestifer mediates phenotypes involved in colistin resistance and virulence
Authors: Chen Qiwei , Quan Heng , Yu Yongfeng , Liu Donghui , Li Caiyu , Chu Yuefeng , Gong Xiaowei
Published: April 2023

Colistin (polymyxin E) is a group of cationic antimicrobial cyclic peptides and is recognized as a last‐resort defense against lethal infections with carbapenem‐resistant pathogens. In addition to the plasmid‐borne mobilized phosphoethanolamine (PEA) transferases, the functional expression of lipid A‐modifying enzymes encoded on chromosomes has been attributed to intrinsic bacterial colistin resistance. However, the mechanisms of colistin resistance in Riemerella anatipestifer remain unknown. Herein, the GE296_RS09715 gene‐encoded Lipid A PEA transferases (RaEptA) was identified in R. anatipestifer. Genetic and structural analyses revealed that the amino acid sequence of RaEptA shared 26.6%–33.1% similarities with the family of Lipid A PEA transferases (EptA) and MCR‐like proteins and have defined 12 residues that contribute to the formation of phosphatidylethanolamine (PE)‐recognizable cavities. Comparative analyses of colistin resistance in RA‐LZ01 and RA‐LZ01ΔRaEptA showed the level of colistin has fallen from 96 μg mL−1 down to 24 ~ 32 μg mL−1. Site‐directed mutagenesis assay of the PE‐binding cavity and expression of the mutants reveals that K309‐rRaEptA can remodel the surface of Escherichia coli and rendering it resistant to colistin, suggesting this point‐mutation of P309K is necessary for EptA‐mediated lipid A modification. Moreover, the virulence of RA‐LZ01ΔRaEptA was attenuated compared with RA‐LZ01 both in vivo and vitro. Taken together, the results represent the RaEptA involved in the colistin resistance and pathogenicity, and the P309K mutation might alter bacterial adaptation and increase the spread of colistin resistance from R. anatipestifer to other gram‐negative bacteria. The findings of this study suggest another scenario for the spread of colistin resistance genes and should be considered by a wide audience.
Phenobarbital-Based Protocol for Alcohol Withdrawal Syndrome in a Medical ICU: Pre-Post Implementation Study
Authors: Alwakeel Mahmoud , Alayan Dina , Saleem Talha , Afzal Saira , Immler Ellen , Wang Xiaofeng , Akbik Bassel , Duggal Abhijit
Published: April 2023

OBJECTIVES:

We assessed the efficacy and safety of PB compared with benzodiazepine (BZD)-based protocols in treating AWS in MICU.

DESIGN:

Single-center, pre-post protocol implementation study.

SETTING:

The setting is a forty-bed MICU in a tertiary-level academic medical center.

PATIENTS:

We included all patients admitted to the MICU with a primary diagnosis of AWS.

INTERVENTIONS:

Intravenous PB 260 mg followed by 130-mg doses every 15–30 minutes as needed up to 15 mg/kg of ideal body weight versus escalating doses of BZD, to achieve a Clinical Institute Withdrawal Assessment Alcohol Scale-Revised score less than 10.

MEASUREMENTS AND MAIN RESULTS:

ICU and hospital length of stay (LOS), in addition to safety measures were the main outcomes of the study. A total of 102 patients were included, 51 in the PB arm and 51 in the BZD arm. There were no differences in baseline clinical characteristics. Half the patients in each group were admitted with delirium tremens. The use of PB-based protocol was associated with 35% reduction in median ICU LOS (1.5 d [interquartile range, 1.2–2.4 d] vs 2.3 d [1.4–4.8 d]; p = 0.009) and 50% reduction in hospital LOS (3 d [2.7–4 d] vs 6 d [4–10 d]; p < 0.001). After adjustment for comorbidities and clinical factors, PB protocol decreased ICU LOS days by 40% (95% CI; 25.8–53.5%). PB group required fewer adjunctive medications to control symptoms (0.7 [0.5–1] vs 2.5 [2–3]; p < 0.001), less need for intubation (1/51 [2%] vs 10/10 [19.6%]; p = 0.023) and less need for physical restraint (19/51 [37.3%] vs 29/51 [56.9%]; p = 0.047), compared with the BZD group.

CONCLUSIONS:

A protocol utilizing rapidly escalating doses of PB over a short period is an effective and safe alternative to BZD in treating AWS in MICU.
State-of-the-Art Evaluation of Acute Adult Disorders of Consciousness for the General Intensivist
Authors: Chang Cherylee W. J. , Provencio Jose Javier , Pascual Jose , Heavner Mojdeh S. , Olson DaiWai , Livesay Sarah L. , Kaplan Lewis J.
Published: April 2023

Objectives:

To provide a concise review of knowledge and practice pertaining to the diagnosis and initial management of unanticipated adult patient disorders of consciousness (DoC) by the general intensivist.

Data Sources:

Detailed search strategy using PubMed and OVID Medline for English language articles describing adult patient acute DoC diagnostic evaluation and initial management strategies including indications for transfer.

Study Selection:

Descriptive and interventional studies that address acute adult DoC, their evaluation and initial management, indications for transfer, as well as outcome prognostication.

Data Extraction:

Relevant descriptions or studies were reviewed, and the following aspects of each manuscript were identified, abstracted, and analyzed: setting, study population, aims, methods, results, and relevant implications for adult critical care practice.

Data Synthesis:

Acute adult DoC may be categorized by etiology including structural, functional, infectious, inflammatory, and pharmacologic, the understanding of which drives diagnostic investigation, monitoring, acute therapy, and subsequent specialist care decisions including team-based local care as well as intra- and inter-facility transfer.

Conclusions:

Acute adult DoC may be initially comprehensively addressed by the general intensivist using an etiology-driven and team-based approach. Certain clinical conditions, procedural expertise needs, or resource limitations inform transfer decision-making within a complex care facility or to one with greater complexity. Emerging collaborative science helps improve our current knowledge of acute DoC to better align therapies with underpinning etiologies.
Emerging Modalities for Temporary Mechanical Circulatory Support in Cardiogenic Shock
Authors: Isath Ameesh , Fishkin Tzvi , Spira Yaakov , Frishman William H. , Aronow Wilbert S. , Levine Avi , Gass Alan
Published: April 2023

Cardiogenic shock (CS) is a life-threatening medical condition that requires prompt recognition and treatment. The use of standardized CS criteria, such as the Society for Cardiovascular Angiography and Interventions criteria, can categorize patients and guide therapeutic strategies. Temporary mechanical circulatory support (MCS) devices have become valuable tools in the treatment of CS, as they can provide cardiovascular support as a bridge to recovery, cardiac surgery, or advanced therapies such as cardiac transplant or durable ventricular assist devices. The use of MCS should be tailored to each individual patient, focused on a stepwise escalation of circulatory support to support both end-organ perfusion and myocardial recovery. As newer MCS devices reduce myocardial oxygen demand without increasing ischemia, the possibility of recovery is optimized. In this review, we discuss the different modalities of MCS focusing on the mechanism of support and the advantages and disadvantages of each device.
Early Coronary Angiography in Patients With Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation: A Systematic Review, Meta-Analysis, and Comparative Analysis of Studies
Authors: Gupta Rahul , Behnoush Amir Hossein , Khalaji Amirmohammad , Malik Aaqib H. , Goel Akshay , Sreenivasan Jayakumar , Bandyopadhyay Dhrubajyoti , Agrawal Ankit , Frishman William H. , Aronow Wilbert S. , Vyas Apurva V. , Patel Nainesh C.
Published: April 2023

Out-of-hospital cardiac arrest has a high mortality rate. Unlike ST-elevation myocardial infarction, the results of performing early coronary angiography (CAG) in non-ST-elevation myocardial infarction patients are controversial. This study aimed to compare early and nonearly CAG in this population, in addition to the identification of differences between randomized controlled trials (RCTs) and observational studies conducted in this regard. A systematic search in PubMed, Embase, and Cochrane library was performed to identify the relevant studies. Random-effect meta-analysis was done to calculate the pooled effect size of early versus nonearly CAG outcomes in all studies in addition to each of the RCT and observational subgroups of the studies. The relative risk ratio (RR), along with its 95% confidence interval (CI), was used as a measure of difference. A total of 16 studies including 5234 cases were included in our analyses. Compared with observational cohorts, RCT studies had patients with higher baseline comorbidities (older age, hypertension, diabetes, and coronary artery disease). Random-effect analysis revealed a lower rate of in-hospital mortality in the early-CAG group (RR, 0.79; 95% CI, 0.65–0.97; P = 0.02); however, RCT studies did not find a statistical difference in this outcome (RR, 1.01; 95% CI, 0.83–1.23; P = 0.91). Moreover, mid-term mortality rates were lower in the early-CAG group (RR, 0.87; 95% CI, 0.78–0.98; P = 0.02), mostly due to observational studies. There was no significant difference between the groups in other efficacy and safety outcomes. Although early CAG was associated with lower in-hospital and mid-term mortality in overall analyses, no such difference was confirmed by the results obtained from RCTs. Current evidence from RCTs may not be representative of real-world patients and should be interpreted within its limitation.
Relationship Between Canagliflozin, Sodium Glucose Cotransporter 2 Inhibitor, and Hematopoietic Effects in Patients With Diabetes and Mild Heart Failure: Results From the CANDLE Trial
Authors: Nakatani Daisaku , Dohi Tomoharu , Hikoso Shungo , Tanaka Atsushi , Nanasato Mamoru , Shimizu Wataru , Node Koichi , Sakata Yasushi ,   on behalf of the CANDLE Trial Investigators
Published: April 2023

There were few clinical studies on the relationship between sodium glucose cotransporter 2 inhibitors (SGLT2i) and hematopoiesis in patients with diabetes (DM) and heart failure (HF) with consideration of systemic volume status. A total of 226 DM patients with HF enrolled in the CANDLE trial, a multicenter, prospective, randomized open-label blinded-endpoint trial, were studied. Estimated plasma volume status (ePVS) was calculated based on a weight- and hematocrit-based formula. At baseline, there was no significant difference in hematocrit and hemoglobin between the canagliflozin (n = 109) and glimepiride (n = 116) groups. Hematocrit and hemoglobin at 24 weeks, changes in hematocrit and hemoglobin difference (24 weeks-baseline), and hematocrit and hemoglobin ratio (24 weeks/baseline) were significantly higher in the canagliflozin than in the glimepiride group, respectively. There was no significant difference in ePVS at baseline and 24 weeks between the 2 groups. After adjustment for baseline parameters, canagliflozin correlated positively with changes in hematocrit and hemoglobin difference, and hematocrit and hemoglobin ratio by multivariate linear regression analyses. The difference in hematocrit and hemoglobin between the 2 groups became statistically significant at 3 and 6 months after randomization. There was no heterogeneity between canagliflozin and the characteristics of the patients for hematocrit and hemoglobin difference and ratio. A correlation of the changes in hematocrit and hemoglobin with cardiac and renal improvement was not observed. In conclusion, canagliflozin was associated with an increased hematocrit and hemoglobin in patients with diabetes and HF regardless of their volume status and characteristics.
The Belun sleep platform to diagnose obstructive sleep apnea in patients with hypertension and high cardiovascular risk
Authors: Ou Yi-Hui , Ong Joy , Thant As Tar , Koo Chieh Yang , Leung Lydia , Sia Ching Hui , Chan Siew Pang , Wong Serene , Lee Chi-Hang
Published: April 2023

Study objective:

Current hypertension guidelines recommend that at-risk individuals be screened for obstructive sleep apnea (OSA). The Belun Ring is a wearable OSA diagnostic device worn on the palmar side of the proximal phalanx of the index finger.

Methods:

We recruited 129 participants (age: 60 ± 8 years, male sex: 88%, BMI: 27 ± 4 kg/m2) with hypertension and high cardiovascular risk for a simultaneous polysomnography and Belun Ring monitoring for one night. Epworth Sleepiness Scale score more than 10 was detected in 27 (21.0%) participants.

Results:

In the 127 participants who completed the study, the apnea–hypopnea index (AHI) derived from polysomnography was 18.1 (interquartile range: 33.0) events/h and that derived from the Belun Ring was 19.5 (interquartile range: 23.3) events/h [intraclass correlation coefficient: 0.882, 95% confidence interval (95% CI): 0.837–0.916]. A Bland–Altman plot showed the difference between the Belun Ring and polysomnography AHIs to be -1.3 ± 10.4 events/h. Area under the receiver operating characteristic for the Belun Ring AHI was 0.961 (95% CI: 0.932–0.990, P < 0.001). When the Belun Ring AHI of at least 15 events/h was used to diagnose OSA, the sensitivity, specificity, positive predictive value, and negative predictive value were 95.7, 77.6, 85.3, and 93.8%, respectively. The overall accuracy was 87.4%. The Cohen's kappa agreement was 0.74 ± 0.09 (P < 0.001). Similar results were obtained when the oxygen desaturation index was used to diagnose OSA.

Conclusion:

A high prevalence of OSA was detected in patients with hypertension and high cardiovascular risk. The Belun Ring is a reliable device for OSA diagnosis similar to polysomnography.

Graphical abstract: http://links.lww.com/HJH/C180