bluuebunny/crossref_metadata_2025 huggingface dataset:
Digest: Liolaemus lizards as an emerging model system to study hybridization as a driver of rapid radiations
Authors: Olave Melisa
Published: March 2024

Recent perspectives on speciation genomics emphasize the pivotal role of hybridization in driving rapid radiations. The Liolaemus lizard genus displays impressive species richness with around 290 species widely distributed across southern South America. Sánchez et al. conducted a comprehensive study on the 5-million-year-old Liolaemus kingii group, which includes 14 species. The research provides new key insights to enhance our understanding of this rapid radiation, including its diversification in space and time and the consequences of hybridization in its morphological evolution and taxonomy.
Prospective external validation of the FluScore risk score for influenza in outpatients
Authors: Ebell Mark H , Dale Ariella , Merenstein Dan J , Barrett Bruce , Hulme Cassie , Walters Sarah , Sabry Alea , Bentivegna Michelle
Published: March 2024

Background

Testing for influenza in patients with acute lower respiratory tract infection (LRTI) is common and in some cases is performed for all patients with LRTI. A more selective approach to testing could be more efficient.

Methods

We used data from two prospective studies in the US primary and urgent care settings that enrolled patients with acute LRTI or influenza-like illness. Data were collected in the 2016, 2019, 2021, and 2022 flu seasons. All patients underwent polymerase chain reaction (PCR) testing for influenza and the FluScore was calculated based on patient-reported symptoms at their initial visit. The probability of influenza in each risk group was reported, as well as stratum-specific likelihood ratios (SSLRs) for each risk level.

Results

The prevalence of influenza within risk groups varied based on overall differences in flu seasons and populations. However, the FluScore exhibited consistent performance across various seasons and populations based on the SSLRs. The FluScore had a consistent SSLR range of 0.20 to 0.23 for the low-risk group, 0.63 to 0.99 for the moderate-risk group, and 1.46 to 1.67 for the high-risk group. The diagnostic odds ratio based on the midpoints of these ranges was 7.25.

Conclusions

The FluScore could streamline patient categorization, identifying patients who could be exempted from testing, while identifying candidates for rapid influenza tests. This has the potential to be more efficient than a “one size fits all” test strategy, as it strategically targets the use of tests on patients most likely to benefit. It is potentially usable in a telehealth setting.
Computation of prediction intervals for forest aboveground biomass predictions using generalized linear models in a large-extent boreal forest region
Authors: Mukhopadhyay Ritwika , Ekström Magnus , Lindberg Eva , Persson Henrik J , Saarela Svetlana , Nilsson Mats
Published: March 2024

Remotely sensed data have an important application for estimation of forest variables, e.g. height, volume, and aboveground biomass (AGB). The increased use of remotely sensed data implemented along with model-based inference has shown improved efficiency in prediction and mapping of such forest variables. In this study, plot-level airborne laser scanning data and Swedish National Forest Inventory field reference data were used to predict AGB using generalized linear models (GLMs) assuming Gamma and Tweedie distributions for the field observed AGB. The GLMs were selected considering the convenience of not correcting transformation bias as it is required in other regression models with transformed response variable. To overcome the challenge in providing reliable uncertainty estimates for the estimated forest variable map products at individual pixel-scale, we focused on computing 95% prediction intervals (PIs) for Gamma and Tweedie GLMs with a square root link function. The relative uncertainties were computed as the ratio between the half-width of the PIs and the predicted AGBs. The AGB-airborne laser scanning models were developed with root mean square error values of 22.6 Mgha−1 (26%) and 21.7 Mgha−1 (25%), respectively, for the Gamma and Tweedie GLMs. Two methods were applied to compute PIs for the Gamma GLM, one using the R package ‘ciTools’ and another derived through asymptotic theory. It was found that the 95% PIs computed using ‘ciTools’ had the most accurate coverage probability in comparison to the other method. An extended version of these PIs was also utilized for the Tweedie GLMs. The range of PIs associated with the prediction of AGB were narrower for lower predicted AGB values compared with the length of higher predicted AGB values. Comparing the two fitted models, the Gamma GLM showed lower relative uncertainties for the lower range of predicted AGBs, whereas the Tweedie GLM showed lower relative uncertainties for the higher range of predicted AGBs. Overall, the Tweedie GLM provided a better model fit for AGB predictions.
Unraveling betalain suppression in pitaya: insights from co-activator HuMYB9 binding at HuCYP76AD1-1, HuADH1, and HuDODA1 super-enhancers
Authors: Xie Fangfang , Shah Kamran , Chen Canbin , Sabir Irfan Ali , Chen Jiayi , Chen Jiaxuan , Chen Jianye , Qin Yonghua
Published: March 2024

Objectives

Myeloblastosis (MYB) proteins, recognized as crucial transcriptional regulators, play an integral role in orchestrating the range of plant colors.

Materials and Methods

Pitaya (Hylocereus spp.), a distinctive commercially cultivated fruit, stands apart due to its unique betalains, water-soluble nitrogen-enriched pigments that confer its vibrant hues. Although betalain biosynthesis has been extensively explored, the potential influence of co-activators that might disrupt pigment production remains relatively unexplored.

Results

In this study, we found that HuMYB9, an R2R3-MYB repressor, exhibited a remarkable decreasing during pitaya maturation. Sequence alignment analyses showed conserved R2 and R3 domains within the C-terminal of HuMYB9. HuMYB9’s regulatory activities were found to be nuclear localized and it interacted with specific elements within the promoters of HuDODA1, HuADH1, and HuCYP76AD1-1, thus influencing the transcriptional activities in vitro. HuMYB9 transiently downregulated the expression of key betalain biosynthetic genes with a corresponding effect on the levels of pitaya pulp betalains.

Conclusions

Our results suggest that HuMYB9 operates as a suppressor, specifically downregulating the expression of HuCYP76AD1-1, HuDODA1, and HuADH, thereby modulating betalain biosynthesis in pitaya. Collectively, our findings provide invaluable insights into the regulation of betalain accumulation in pitaya.
Desecration, Secularization, Restoration: Cologne’s Churches during the French Revolutionary and Napoleonic Wars, 1792–1815
Authors: Rowe Michael
Published: March 2024

The Napoleonic era was transformative for Cologne’s churches. The wars that characterized this period brought destruction and upheaval. The invading French army that occupied the city in 1794 was an agent of the new Republic, a polity then at war with Catholicism. Most spectacularly, this resulted in the desacralization of Cologne’s churches, some of which were turned into storage depots for the army or made into temples for the new republican cult. However, once Napoleon seized control of the Republic in 1799, a new French policy was enforced in the city and surrounding region. It restored many aspects of the old familiar religious order, but at the same time created new institutions of church management and preservation that survived the end of French rule in 1814.
The highest-cost Medicaid enrollees with sickle cell disease had annual health care expenditures nearing $200 000
Authors: Speller Junelle , Rayel Sarah , Hayashi Kristen , Kirby Michaela , Munevar Dianne , Hartzman Alex , Dietz Kevin
Published: March 2024

Sickle cell disease (SCD) is a painful chronic blood disorder that causes serious complications and comorbidities, often leading to premature death. SCD impacts millions of people worldwide, including an estimated 100 000 in the United States, most of whom are Black or Latino. We analyzed Medicaid enrollment, claims, and encounter data via the Transformed Medicaid Statistical Information System (T-MSIS) to examine the 2021 health care utilization and spending of Medicaid enrollees with SCD. Our analysis found that Medicaid enrollees with SCD have high annual medical and pharmacy expenditures that are not evenly distributed across the population. Among the most severe enrollees with genotypes eligible for clinical trials, those in the top 5% of health care spending incurred, on average, nearly $200 000 per year for this chronic condition.
Student evaluation of an instructional video on how to use a national medicines information resource
Authors: Tait Kirsty , Gandhi Jimit , Ward Michael , Calabretto Jean-Pierre , Rossi Simone
Published: March 2024

Objectives

The objective of this project was to obtain students’ perception of an educational companion video designed to increase the understanding of a national medicines information resource.

Methods

An instructional video was developed to guide students in utilizing the online version of the Australian Medicines Handbook (AMH). All students enrolled in the Bachelor of Pharmacy program during 2021 were given access to this video. A cross-sectional electronic survey was administered to evaluate the video’s effectiveness and its impact on students’ confidence. The survey results were analysed using both descriptive and inferential statistics, in addition to qualitative analysis to identify common themes. Ethics approval was obtained prior to conducting the study.

Key findings

Most students (78%; n = 72/92) reported that watching the video increased their understanding. The most growth in confidence was seen by students in their first or second year of study. Fifty-four percent (n = 48/89) of students was very likely or extremely likely to recommend the video to others, and 37% (n = 33/89) of students were somewhat likely. Students found the instructional video to be useful and expressed a desire for similar content to be integrated into other facets of teaching. The audio–visual mode of delivery was regarded as effective for this context. Constructive feedback included suggestions of incorporating more advanced educational features such as how to interpret comparative medication charts and interaction checkers.

Conclusions

The ‘How to use the AMH’ video is a good introductory resource for undergraduate Australian healthcare students. Our results indicate that this video would be best suited to complement the teaching of students early on in their studies.
Trust your source: quantifying source condition elements for variational regularisation methods
Authors: Benning Martin , Bubba Tatiana A , Ratti Luca , Riccio Danilo
Published: March 2024

Source conditions are a key tool in regularisation theory that are needed to derive error estimates and convergence rates for ill-posed inverse problems. In this paper, we provide a recipe to practically compute source condition elements as the solution of convex minimisation problems that can be solved with first-order algorithms. We demonstrate the validity of our approach by testing it on two inverse problem case studies in machine learning and image processing: sparse coefficient estimation of a polynomial via LASSO regression and recovering an image from a subset of the coefficients of its discrete Fourier transform. We further demonstrate that the proposed approach can easily be modified to solve the machine learning task of identifying the optimal sampling pattern in the Fourier domain for a given image and variational regularisation method, which has applications in the context of sparsity promoting reconstruction from magnetic resonance imaging data.
Effect of Pneumococcal Conjugate Vaccines on Viral Respiratory Infections: A Systematic Literature Review
Authors: Sepúlveda-Pachón Ingrid T , Dunne Eileen M , Hanquet Germaine , Baay Marc , Menon Sonia , Jodar Luis , Gessner Bradford D , Theilacker Christian
Published: March 2024

Background

In addition to preventing pneumococcal disease, emerging evidence indicates that pneumococcal conjugate vaccines (PCVs) might indirectly reduce viral respiratory tract infections (RTIs) by affecting pneumococcal-viral interactions.

Methods

We performed a systematic review of interventional and observational studies published during 2000–2022 on vaccine efficacy/adjusted effectiveness (VE) and overall effect of PCV7, PCV9, PCV10, or PCV13 against viral RTIs.

Results

Sixteen of 1671 records identified were included. Thirteen publications described effects of PCVs against viral RTIs in children. VE against influenza ranged between 41% and 86% (n = 4), except for the 2010–2011 influenza season. In a randomized controlled trial, PCV9 displayed efficacy against any viral RTI, human seasonal coronavirus, parainfluenza, and human metapneumovirus. Data in adults were limited (n = 3). PCV13 VE was 4%–25% against viral lower RTI, 32%–35% against coronavirus disease 2019 outcomes, 24%–51% against human seasonal coronavirus, and 13%–36% against influenza A lower RTI, with some 95% confidence intervals spanning zero. No protection was found against adenovirus or rhinovirus in children or adults.

Conclusions

PCVs were associated with protection against some viral RTI, with the strongest evidence for influenza in children. Limited evidence for adults was generally consistent with pediatric data. Restricting public health evaluations to confirmed pneumococcal outcomes may underestimate the full impact of PCVs.
Impact of Low-Frequency Human Immunodeficiency Virus Type 1 Drug Resistance Mutations on Antiretroviral Therapy Outcomes
Authors: Burdorf Rachel M , Zhou Shuntai , Amon Claire , Long Nathan , Hill Collin S , Adams Lily , Tegha Gerald , Chagomerana Maganizo B , Jumbe Allan , Maliwichi Madalitso , Wallie Shaphil , Li Yijia , Swanstrom Ronald , Hosseinipour Mina C
Published: March 2024

Background

The association between low-frequency human immunodeficiency virus type 1 (HIV-1) drug resistance mutations (DRMs) and treatment failure (TF) is controversial. We explore this association using next-generation sequencing (NGS) methods that accurately sample low-frequency DRMs.

Methods

We enrolled women with HIV-1 in Malawi who were either antiretroviral therapy (ART) naive (cohort A), had ART failure (cohort B), or had discontinued ART (cohort C). At entry, cohorts A and C began a nonnucleoside reverse transcriptase inhibitor–based regimen and cohort B started a protease inhibitor–based regimen. We used Primer ID MiSeq to identify regimen-relevant DRMs in entry and TF plasma samples, and a Cox proportional hazards model to calculate hazard ratios (HRs) for entry DRMs. Low-frequency DRMs were defined as ≤20%.

Results

We sequenced 360 participants. Cohort B and C participants were more likely to have TF than cohort A participants. The presence of K103N at entry significantly increased TF risk among A and C participants at both high and low frequency, with HRs of 3.12 (95% confidence interval [CI], 1.58–6.18) and 2.38 (95% CI, 1.00–5.67), respectively. At TF, 45% of participants showed selection of DRMs while in the remaining participants there was an apparent lack of selective pressure from ART.

Conclusions

Using accurate NGS for DRM detection may benefit an additional 10% of patients by identifying low-frequency K103N mutations.
Religio-erotic Experience and Transoceanic Becoming at the Shoreline in Audre Lorde’s Zami
Authors: Coleman Taylor Ashley
Published: March 2024

In her biomythographical work Zami: A New Spelling of My Name, Audre Lorde’s lover Afrekete appears as a Black queer femme who alters her sense of self and her being through religio-erotic experience. After tracing the spirit who inspired Lorde’s Afrekete throughout the Americas, I propose a theory of the shoreline as a site of transoceanic becoming, or the experience of self-identification required to navigate the Western world as an African diaspora being. I focus primarily on the ontologies of Black trans and queer femmes and the unconscious yet necessary process of becoming at the intersections of existence.
Environmental surveillance reveals co-circulation of distinctive lineages of enteroviruses in southwest China’s border cities, 2020–2022
Authors: Tang Jingjing , Zhang Xiaodie , Zhang Jie , Zhao Zhixian , Ding Zhengrong
Published: March 2024

Aims

Enteroviruses are significant human pathogens associated with a range of mild to severe diseases. This study aims to understand the diversity and genetic characterization of enteroviruses circulated in southwest China’s border cities by using environmental surveillance.

Methods and results

A total of 96 sewage samples were collected in three border cities and a port located in Yunnan Province, China from July 2020 to June 2022. After cell culture and VP1 sequencing, a total of 590 enterovirus isolates were identified, belonging to 21 types. All PV strains were Sabin-like with ≤6 nucleotide mutations in the VP1 coding region. Echovirus 6, echovirus 21 (a rare serotype in previous studies), and coxsackievirus B5 were the predominant serotypes, which accounted for 21.19%, 18.31%, and 13.39% of the total isolates, respectively. The prevalence of the common serotypes varied across different border cities and periods. Phylogenetic analysis revealed the presence of multiple evolutionary lineages for E21, E6, and E30, some of which formed distinct branches.

Conclusions

High diversity of enteroviruses and distinct lineages of predominant serotypes circulated in southwest China’s border cities.
Perforated small bowel lymphoma: a rare presentation of Crohn’s disease
Authors: Herbawi Abdalrahman N , Hroub Osama , Salloum Omar H , Ibraheem Kareem , Alsalah Qusai A , Hammouri Ahmad G , Salhab Rafiq
Published: March 2024

Adenocarcinoma and lymphoma, potential complications of Crohn's disease (CD), may result in small intestinal perforations, particularly in those on immunosuppressive therapy. The ileum is typically the site of small intestinal perforations in CD, and the link between CD and lymphoma remains uncertain. This case report explores a long-term CD patient on immunosuppressive therapy who presented with acute abdominal pain. Imaging revealed signs of intestinal perforation, successfully managed with surgery. The final pathology report confirms the diagnosis of diffuse large B-cell lymphoma. This report sheds light on the complicated nature of gastrointestinal lymphoma in CD patients.
Plant ammonium sensitivity is associated with external pH adaptation, repertoire of nitrogen transporters, and nitrogen requirement
Authors: Rivero-Marcos Mikel , Lasa Berta , Neves Tomé , Zamarreño Ángel M , García-Mina José M , García-Olaverri Carmen , Aparicio-Tejo Pedro M , Cruz Cristina , Ariz Idoia
Published: March 2024

Modern crops exhibit diverse sensitivities to ammonium as the primary nitrogen source, influenced by environmental factors such as external pH and nutrient availability. Despite its significance, there is currently no systematic classification of plant species based on their ammonium sensitivity. We conducted a meta-analysis of 50 plant species and present a new classification method based on the comparison of fresh biomass obtained under ammonium and nitrate nutrition. The classification uses the natural logarithm of the biomass ratio as the size effect indicator of ammonium sensitivity. This numerical parameter is associated with critical factors for nitrogen demand and form preference, such as Ellenberg indicators and the repertoire of nitrogen transporters for ammonium and nitrate uptake. Finally, a comparative analysis of the developmental and metabolic responses, including hormonal balance, is conducted in two species with divergent ammonium sensitivity values in the classification. Results indicate that nitrate has a key role in counteracting ammonium toxicity in species with a higher abundance of genes encoding NRT2-type proteins and fewer of those encoding the AMT2-type proteins. Additionally, the study demonstrates the reliability of the phytohormone balance and methylglyoxal content as indicators for anticipating ammonium toxicity.
High energy gamma-ray sources in the VVV survey - II. The AGN counterparts
Authors: Donoso Laura G , Pichel Ana , Baravalle Laura D , Alonso M Victoria , Schmidt Eduardo O , Minniti Dante , Masetti Nicola , Smith Leigh C , Lucas Philip W , Villalon Carolina , Rovero Adrián C , Coldwell Georgina
Published: March 2024

We identified Active Galactic Nuclei (AGN) candidates as counterparts to unidentified gamma-ray sources (UGS) from the Fermi-LAT Fourth Source Catalogue at lower Galactic latitudes. Our methodology is based on the use of near- and mid-infrared photometric data from the VISTA Variables in the Vía Láctea (VVV) and Wide-field Infrared Survey Explorer (WISE) surveys. The AGN candidates associated with the UGS occupy very different regions from the stars and extragalactic sources in the colour space defined by the VVV and WISE infrared colours. We found 27 near-infrared AGN candidates possibly associated with 14 Fermi-LAT sources using the VVV survey. We also found 2 blazar candidates in the regions of 2 Fermi-LAT sources using WISE data. There is no match between VVV and WISE candidates. We have also examined the Ks light curves of the VVV candidates and applied the fractional variability amplitude (σrms) and the slope of variation in the Ks passband to characterise the near-infrared variability. This analysis shows that more than 85 per cent of the candidates have slopes in the Ks passband >10−4 mag/day and present σrms values consistent with a moderate variability. This is in good agreement with typical results seen from type-1 AGN. The combination of YJHKs colours and Ks variability criteria was useful for AGN selection, including its use in identifying counterparts to Fermi γ-ray sources.
Bilirubin Distribution in Plants at the Subcellular and Tissue Levels
Authors: Ishikawa Kazuya , Kodama Yutaka
Published: March 2024

In heterotrophs, heme degradation produces bilirubin, a tetrapyrrole compound that has antioxidant activity. In plants, heme is degraded in plastids and is believed to be converted to phytochromobilin rather than bilirubin. Recently, we used the bilirubin-inducible fluorescent protein UnaG to reveal that plants produce bilirubin via a non-enzymatic reaction with NADPH. In the present study, we used an UnaG-based live imaging system to visualize bilirubin accumulation in Arabidopsis thaliana and Nicotiana benthamiana at the organelle and tissue levels. In chloroplasts, bilirubin preferentially accumulated in the stroma, and the stromal bilirubin level increased upon dark treatment. Investigation of intracellular bilirubin distribution in leaves and roots showed that it accumulated mostly in plastids, with low levels detected in the cytosol and other organelles, such as peroxisomes, mitochondria and the endoplasmic reticulum. A treatment that increased bilirubin production in chloroplasts decreased the bilirubin level in peroxisomes, implying that a bilirubin precursor is transported between the two organelles. At the cell and tissue levels, bilirubin showed substantial accumulation in the root elongation region but little or none in the root cap and guard cells. Intermediate bilirubin accumulation was observed in other shoot and root tissues, with lower levels in shoot tissues. Our data revealed the distribution of bilirubin in plants, which has implications for the transport and physiological function of tetrapyrroles.
Glutamine induces lateral root initiation, stress responses, and disease resistance in Arabidopsis
Authors: Liao Hong-Sheng , Lee Kim-Teng , Chung Yi-Hsin , Chen Soon-Ziet , Hung Yi-Jie , Hsieh Ming-Hsiun
Published: March 2024

The production of glutamine (Gln) from NO3− and NH4+ requires ATP, reducing power, and carbon skeletons. Plants may redirect these resources to other physiological processes using Gln directly. However, feeding Gln as the sole nitrogen (N) source has complex effects on plants. Under optimal concentrations, Arabidopsis (Arabidopsis thaliana) seedlings grown on Gln have similar primary root lengths, more lateral roots, smaller leaves, and higher amounts of amino acids and proteins compared to those grown on NH4NO3. While high levels of Gln accumulate in Arabidopsis seedlings grown on Gln, the expression of GLUTAMINE SYNTHETASE1;1 (GLN1;1), GLN1;2, and GLN1;3 encoding cytosolic GS1 increases and expression of GLN2 encoding chloroplastic GS2 decreases. These results suggest that Gln has distinct effects on regulating GLN1 and GLN2 gene expression. Notably, Arabidopsis seedlings grown on Gln have an unexpected gene expression profile. Compared with NH4NO3, which activates growth-promoting genes, Gln preferentially induces stress- and defense-responsive genes. Consistent with the gene expression data, exogenous treatment with Gln enhances disease resistance in Arabidopsis. The induction of Gln-responsive genes, including PATHOGENESIS-RELATED1, SYSTEMIC ACQUIRED RESISTANCE DEFICIENT1, WRKY54, and WALL ASSOCIATED KINASE1, is compromised in salicylic acid (SA) biosynthetic and signaling mutants under Gln treatments. Together, these results suggest that Gln may partly interact with the SA pathway to trigger plant immunity.
Too Domestic to Fail: Liquidity Provision and National Champions
Authors: Farhi Emmanuel , Tirole Jean
Published: March 2024

Authorities’ support policies shape the location and continuation of industrial and banking activity on their soil. Firms’ locus of activity depends on their prospect of receiving financial assistance in distress and therefore on factors such as countries’ relative resilience. We predict that global firms are global in life and national in death; and that they become less global when competition is more intense, times are turbulent, and international risk sharing (say, through swap lines) weak. We analyse the competitive benefits of industrial and banking policies as well as their limitations, such as currency appreciation.
Transcriptomic profiling of osteoarthritis synovial macrophages reveals a tolerized phenotype compounded by a weak corticosteroid response
Authors: Wang Cheng , De Francesco Ruben , Lamers Lieke A , Rinzema Sybren , Frölich Siebren , van Lent Peter L E M , Logie Colin , van den Bosch Martijn H J
Published: March 2024

Objectives

It is well-known that long-term osteoarthritis prognosis is not improved by corticosteroid treatments. Here we investigate what could underlie this phenomenon by measuring the short term corticosteroid response of osteoarthritic joint synovial macrophages (OA-Mf).

Methods

We determined the genome-wide transcriptomic response to corticosteroids of end-stage OA-Mf. This was compared with lipopolysaccharide-tolerized and β-glucan-trained circulating blood monocyte-derived macrophage models.

Results

Upon corticosteroid stimulation, the trained and tolerized macrophages significantly altered the abundance of 201 and 257 RNA transcripts, respectively. By contrast, by the same criteria, OA-Mf had a very restricted corticosteroid response of only 12 RNA transcripts. Furthermore, while metalloproteinases 1, 2, 3 and 10 expression clearly distinguish OA-Mf from both the tolerized and trained macrophage models, OA-Mf IL-1, chemokine (CXCL) and cytokine (CCL) family member profiles resembled the tolerized macrophage model, with the exception that OA-Mf showed high levels of CCL20.

Conclusion

Terminal osteoarthritis joints harbour macrophages with an inflammatory state that closely resembles the tolerized macrophage state, and this is compounded by a weak corticosteroid response capacity that may explain the lack of positive long-term effects of corticosteroid treatment for osteoarthritis patients.
A fast correction method of the scattering contributions in the area gamma dosemeter calibration field
Authors: Qian Yi-kun , Zhang Song , Mao Ben-jiang , Liu Yi-xin
Published: March 2024

In the calibration procedure of area gamma dosemeters, how to accurately evaluate and correct the scattering contribution from the complex environmental factors to the point of test is the key problem to ensure the calibration accuracy. This paper proposed a fast correction method of the scattering contributions in the area gamma dosemeter calibration field. First, Monte Carlo method is employed to simulate the influence of scattering caused by different environmental factors in the calibration field, which is named as semi-panoramic reference radiation field. Then, a prediction model of the relationship between environmental factors and environmental scattering contribution is constructed based on the simulation data through the least squares support vector machine. With the model, the scattering contribution from the environmental factors can be fast estimated to correct the calibration results of the area gamma dosemeters, which will improve the accuracy of the calibration.
DKK1 Activates the PI3K/AKT Pathway via CKAP4 to Balance the Inhibitory Effect on Wnt/β-Catenin Signaling and Regulates Wnt3a-Induced MSC Migration
Authors: Chen Huanhuan , Hu Ya’nan , Xu Xiaojing , Dai Yan , Qian Hongxiang , Yang Xinyu , Liu Jinming , He Qisheng , Zhang Huanxiang
Published: March 2024

Wnt/β-catenin signaling plays a crucial role in the migration of mesenchymal stem cells (MSCs). However, our study has revealed an intriguing phenomenon where Dickkopf-1 (DKK1), an inhibitor of Wnt/β-catenin signaling, promotes MSC migration at certain concentrations ranging from 25 to 100 ng/mL while inhibiting Wnt3a-induced MSC migration at a higher concentration (400 ng/mL). Interestingly, DKK1 consistently inhibited Wnt3a-induced phosphorylation of LRP6 at all concentrations. We further identified cytoskeleton-associated protein 4 (CKAP4), another DKK1 receptor, to be localized on the cell membrane of MSCs. Overexpressing the CRD2 deletion mutant of DKK1 (ΔCRD2), which selectively binds to CKAP4, promoted the accumulation of active β-catenin (ABC), the phosphorylation of AKT (Ser473) and the migration of MSCs, suggesting that DKK1 may activate Wnt/β-catenin signaling via the CKAP4/PI3K/AKT cascade. We also investigated the effect of the CKAP4 intracellular domain mutant (CKAP4-P/A) that failed to activate the PI3K/AKT pathway and found that CKAP4-P/A suppressed DKK1 (100 ng/mL)-induced AKT activation, ABC accumulation, and MSC migration. Moreover, CKAP4-P/A significantly weakened the inhibitory effects of DKK1 (400 ng/mL) on Wnt3a-induced MSC migration and Wnt/β-catenin signaling. Based on these findings, we propose that DKK1 may activate the PI3K/AKT pathway via CKAP4 to balance the inhibitory effect on Wnt/β-catenin signaling and thus regulate Wnt3a-induced migration of MSCs. Our study reveals a previously unrecognized role of DKK1 in regulating MSC migration, highlighting the importance of CKAP4 and PI3K/AKT pathways in this process.
‘We no longer experience the same pain’: a cross-sectional study assessing the impact of Heart and Sole Africa's podoconiosis prevention education program
Authors: Gebreselassie Agazi Fitsum , Shimelash Natnael , Kallon Ahamed , Mkondo George , Huston Tonya , Schurer Janna M
Published: March 2024

Background

Podoconiosis is a non-infectious neglected tropical disease caused by long-term exposure to irritant volcanic soils. It results in severe physical, psychological and financial consequences. Heart and Sole Africa (HASA) is a non-governmental, community-based organization providing management to podoconiosis patients in Rwanda. We sought to analyze the impact of their program on the lives of patients.

Methods

Quantitative surveys recorded the participants’ demographics, adherence to HASA's management recommendations and changes in quality of life (QOL). Qualitative questions were used to gather respondent perspectives on HASA programming.

Results

We interviewed 127 patients from HASA's Musanze (n=47) and Burera (n=80) clinics. Almost all participants (98.4%) reported statistically significant (p<0.01) improvements in their QOL, and more than one-half (51.2%) had a favorable adherence score of >80%. Qualitative feedback identified specific challenges to adherence and recognition of program success in symptom management.

Conclusions

Our study demonstrated the value of community-based podoconiosis programming in improving the lives of patients. Practices such as regular feet washing, emollient application, shoe wearing and limb raising can result in a marked reduction of morbidity. Our findings support the argument for scaling up these management practices across Rwanda.
Tipepidine activates AMPK and improves adipose tissue fibrosis and glucose intolerance in high‐fat diet‐induced obese mice
Authors: Sawamoto Atsushi , Okada Madoka , Matsuoka Nanako , Okuyama Satoshi , Nakajima Mitsunari
Published: March 2024

Tipepidine (3‐[di‐2‐thienylmethylene]‐1‐methylpiperidine) (TP) is a non‐narcotic antitussive used in Japan. Recently, the potential application of TP in the treatment of neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder, has been suggested; however, its functions in energy metabolism are unknown. Here, we demonstrate that TP exhibits a metabolism‐improving action. The administration of TP reduced high‐fat diet‐induced body weight gain in mice and lipid accumulation in the liver and increased the weight of epididymal white adipose tissue (eWAT) in diet‐induced obese (DIO) mice. Furthermore, TP inhibited obesity‐induced fibrosis in the eWAT. We also found that TP induced AMP‐activated protein kinase (AMPK) activation in the eWAT of DIO mice and 3T3‐L1 cells. TP‐induced AMPK activation was abrogated by the transfection of liver kinase B1 siRNA in 3T3‐L1 cells. The metabolic effects of TP were almost equivalent to those of metformin, an AMPK activator that is used as a first‐line antidiabetic drug. In summary, TP is a potent AMPK activator, suggesting its novel role as an antidiabetic drug owing to its antifibrotic effect on adipose tissues.
Racial and Ethnic Bias in Letters of Recommendation in Academic Medicine: A Systematic Review
Authors: Deshpande Saarang R. , Lepore Gina , Wieland Lily , Kogan Jennifer R.
Published: March 2024

Purpose

Letters of recommendations (LORs) are key components of academic medicine applications. Given that bias against students and trainees underrepresented in medicine (UIM) has been demonstrated across assessment, achievement, and advancement domains, the authors reviewed studies on LORs to assess racial, ethnic, and UIM differences in LORs. Standardized LORs (SLORs), an increasingly common form of LORs, were also assessed for racial and ethnic differences.

Method

A systematic review was conducted for English-language studies that assessed racial or ethnic differences in LORs in academic medicine published from database inception to July 16, 2023. Studies evaluating SLORs underwent data abstraction to evaluate their impact on the given race or ethnicity comparison and outcome variables.

Results

Twenty-three studies describing 19,012 applicants and 41,925 LORs were included. Nineteen studies (82.6%) assessed LORs for residency, 4 (17.4%) assessed LORs for fellowship, and none evaluated employment or promotion. Fifteen of 17 studies (88.2%) assessing linguistic differences reported a significant difference in a particular race or ethnicity comparison. Of the 7 studies assessing agentic language (e.g., “strong,” “confident”), 1 study found fewer agentic terms used for Black and Latinx applicants, and 1 study reported higher agency scores for Asian applicants and applicants of races other than White. There were mixed results for the use of communal and grindstone language in UIM and non-UIM comparisons. Among 6 studies, 4 (66.7%) reported that standout language (e.g., “exceptional,” “outstanding”) was less likely to be ascribed to UIM applicants. Doubt-raising language was more frequently used for UIM trainees. When SLORs and unstructured LORs were compared, fewer linguistic differences were found in SLORs.

Conclusions

There is a moderate bias against UIM candidates in the domains of linguistic differences, doubt-raising language, and topics discussed in LORs, which has implications for perceptions of competence and ability in the high-stakes residency and fellowship application process.
High rate of undetected infections in failed osteosynthesis of pertrochanteric fractures
Authors: Coelho Alexandre , Alier Albert , Martínez-Diaz Santos , Puig-Verdié Lluis , Gómez-Junyent Joan , García-Bernedo Carlos , Pérez-Prieto Daniel
Published: March 2024

OBJECTIVE:

The objective of this study was to assess the incidence of infection in patients with cut-out after PFF osteosynthesis.

METHODS:

Design: Retrospective cohort study.

Setting:

Third-level trauma center.

Patient selection criteria:

Patients presenting with a cut-out following proximal femur fracture (PFF) (OTA/AO 31A) osteosynthesis, between January 2007 to December 2020.

Outcome Measurements:

The primary outcome was infection according to EBJIS criteria.

RESULTS:

Sixty-seven patients presenting with a cut-out were included, with mean age of 83.3 years (range 63-96) and 51 (76.1%) were women. Of all cases, 16 (24.7%) presented a concomitant infection. The presence of concomitant infection was suspected preoperatively in only 3 of the cases. A subgroup analysis was performed between the cases with infection and those without infection, the groups being comparable in terms of demographic data and postoperative radiological criteria. Patients with underlying infection had a higher rate of surgical wound complication (56.3% vs 22%, p = 0.014) and higher rates of leukocytosis (11.560 vs 7.890, p = 0.023).

Conclusion:

Faced with a cut-out after osteosynthesis of a proximal femur fracture, underlying infection should be considered as a possible etiological factor.

Level of evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Diagnostic evaluation of PanBio, and standard Q COVID-19 rapid antigen tests for the detection of SARS-CoV-2: a cross-sectional study from Nepal
Authors: Yadav Gopal K. , Karki Praju , Raut Amar , Subedi Prativa , Aryal Saurav , Tamrakar Rama , Paudel Binod , Bastola Ambika D. K. , Pradhananga Smeena , Rohita Dipesh K. , Kafle Pramod , Shrestha Aayush , Oli Milan P. , Yadav Ajay K. , Sharma Sanjeev K.
Published: March 2024

Introduction:

The diagnosis of COVID-19 infection was time-consuming and costly, contributing to rampant transmission, particularly in developing countries like Nepal. This study aimed to compare the diagnostic performance of two rapid antigen diagnostic tests (RDTs, PanBio and Standard Q) against real-time reverse transcriptase PCR (rRT-PCR).

Methods:

This retrospective cross-sectional study was conducted among 1171 suspected COVID-19 patients at a provincial hospital in Nepal. Each participant provided two nasopharyngeal swabs, one for RDT and the other for rRT-PCR, spanning a total duration of four months. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of each RDT, as well as the combined antigen-RDT, were determined in reference to the rRT-PCR status.

Results:

The sensitivity and specificity of PanBio were 60.87% (95% CI: 55.84–65.74) and 98.43% (95% CI: 96.80–99.37), respectively, while that of Standard Q was 59.83% (95% CI: 53.16–66.23) and 96.15% (95% CI: 90.44–98.94), respectively. Positive and negative predictive values of PanBio were 97.14 and 74.20%, respectively, and that of Standard Q were 97.16 and 52.08%. The positive likelihood ratio was higher for PanBio (38.87, 95% CI: 18.56–81.41) than for Standard Q (15.55, 95% CI: 5.92–40.90). Meanwhile, the negative likelihood ratio was more than 0.40 for both RDTs. The accuracy for PanBio, Standard Q, and combined RDTs were 80.91% (95% CI: 78.08–83.52), 71.17% (95% CI: 65.98–75.98), and 78.14% (95% CI: 75.66–80.48), respectively.

Conclusion:

RDTs exhibited unsatisfactory sensitivity and positive predictive value, rendering them ineffective as a screening tool. Nonetheless, they demonstrated excellent specificity and negative predictive value. Hence, a negative test result almost entirely excludes the possibility of infection.
Clinical Trials That Have Changed Obstetric Practice: The Chronic Hypertension and Pregnancy (CHAP) Trial
Authors: Sanusi Ayodeji A. , Sinkey Rachel G. , Tita Alan T.N.
Published: March 2024

We describe the evolution of treatment recommendations for chronic hypertension (CHTN) in pregnancy, the CHTN and pregnancy (CHAP) trial, and its impact on obstetric practice. The US multicenter CHAP trial showed that antihypertensive treatment for mild CHTN in pregnancy [blood pressures (BP)<160/105 mm Hg] to goal<140/90 mm Hg, primarily with labetalol or nifedipine compared with no treatment unless BP were severe reduced the composite risk of superimposed severe preeclampsia, indicated preterm birth <35 weeks, placental abruption, and fetal/neonatal death. As a result of this trial, professional societies in the United States recommended treatment of patients with CHTN in pregnancy to BP goal<140/90 mm Hg.
[18F]AlF-ND-bisFAPI PET imaging of fibroblast activation protein as a biomarker to monitor the progression of liver fibrosis
Authors: Li Hongsheng , Dai Ruoxue , Huang Yueqi , Zhong Jiawei , Yan Qingsong , Yang Jiaqi , Hu Kongzhen , Zhong Yuhua
Published: March 2024

Background:

Hepatic fibrosis is a progressive disease, which is reversible in the early stages. The current monitoring methods have notable limitations that pose a challenge to early detection. In this study, we evaluated the utility of [18F]AlF-ND-bisFAPI positron emission tomography imaging of fibroblast activation protein (FAP) to monitor the progression of liver fibrosis.

Methods:

Two mouse models of liver fibrosis were established by bile duct ligation and carbon tetrachloride administration, respectively. Positron emission tomography imaging was performed with the FAP-specific radiotracer [18F]AlF-ND-bisFAPI for the evaluation of rat HSCs and mouse models of fibrosis and combined with histopathology, immunohistochemical staining, and immunoblotting to elucidate the relationships among radioactivity uptake, FAP levels, and liver fibrosis progression. Furthermore, [18F]AlF-ND-bisFAPI autoradiography was performed to assess tracer binding in liver sections from patients with varying degrees of liver fibrosis.

Results:

Cell experiments demonstrated that [18F]AlF-ND-bisFAPI uptake was specific in activated HSCs. Compared with control mice, [18F]AlF-ND-bisFAPI uptake in livers increased in the early stages of fibrosis and increased significantly further with disease progression. Immunohistochemistry and western blot analyses demonstrated that FAP expression increased with fibrosis severity. In accordance with the findings in animal models, ex vivo autoradiography on human fibrotic liver sections showed that radioactivity increased as fibrosis progressed from mild to severe.

Conclusions:

[18F]AlF-ND-bisFAPI positron emission tomography imaging is a promising noninvasive method for monitoring the progression of liver fibrosis.
Sprint Team Approach Yields Rapid Improvement in Leapfrog Quality Indicators
Authors: Sharieff Ghazala Q. , Uejo Craig
Published: March 2024

Goal:

Patient safety and quality care are two critical areas that every healthcare organization strives to grow and improve upon. At Scripps Health, specific efforts reviewed for this article were implemented to reduce hospital-acquired conditions and hospital readmissions that are components of Centers for Medicare & Medicaid Services programs and Leapfrog Hospital Survey scores.

Methods:

Sprint teams, a novel approach to rapidly develop a checklist for lower-performing care improvement areas, were implemented after an internal review of existing tools and an evidence-based literature review. These areas included catheter-associated urinary tract infections (CAUTIs), central-line associated bloodstream infections (CLABSIs), Clostridioides difficile (C. diff.) and methicillin-resistant Staphylococcus aureus (MRSA) infections, chronic obstructive pulmonary disease (COPD) and heart failure readmissions, surgical site infections and handwashing, bar coding, and the computerized physician order entry components of Leapfrog scoring. The checklist for each area served as a teaching tool for staff and a guideline for case review to ensure that standard work was routinely performed.

Principal Findings:

The sprint teams showed dramatic results in the initial focus areas. From a baseline standardized infection ratio (SIR) of 1.141 for CLABSIs, the sprint team reduced the SIR to 0.885 in Year 1 of the program and to 0.687 in Year 2. For CAUTIs, the SIR decreased from a baseline of 1.391 in Year 1 to 0.720 in Year 2. C. diff. infections fell from 0.422 to 0.315 in Year 1 and to 0.260 in Year 2. While the MRSA SIR did not improve during the first year, the MRSA reduction sprint team showed success in Year 2 with a decrease in the SIR from 0.537 to 0.245. Readmission reduction sprint teams focused on heart failure, COPD, and total hip and knee complications. The teams also achieved positive results in reducing readmissions by following checklists and reviewing each readmission case for justification.

Practical Applications:

Rapid change can be safely and effectively implemented with multidisciplinary sprint teams. Developed with an evidence-based, case review approach, sprint team checklists can help to standardize processes for the review of any infections or readmissions that occur in the inpatient arena.
Validation of the Meditech ABPM-06 24-hour blood pressure monitoring system in a pediatric population according to International Organization for Standardization Protocol 81060-2:2018
Authors: Jakab Andrea E. , Horváth Edit , Molnár Dorottya , Bukva Mátyás , Bereczki Csaba
Published: March 2024

Objective

Ambulatory blood pressure monitoring (ABPM) devices play a crucial role in diagnosing hypertension, not only in adults but also in pediatric patients. ABPM-06, the latest oscillometric device from Meditech Ltd. (Budapest, Hungary), is the focus of this study. The objective was to validate the ABPM-06 device using the International Organization for Standardization (ISO) 81060-2 : 2018 standard.

Methods

A total of 86 healthy patients, consisting of 34 males and 52 females, aged between 3 and 17 years, were enrolled in this study. During the ambulatory phase, a total of 50 patients were enrolled, with 35 patients falling within the 3- to 12-year-old age range and 15 patients aged between 12 and 17 years. Additionally, for the dynamic test, 36 patients were selected, comprising of 10 individuals aged 3–12 years and 26 patients aged 12–17 years. These patients were recruited from the outpatient clinics of the Department of Pediatrics at Albert Szent-Györgyi University in Szeged, Hungary. The validation process involved utilizing the same-arm sequence protocol, both in resting positions and during stress testing.

Results

The ABPM-06 performed well in both clinical and ambulatory validations. In terms of validation criterion 1, the mean ± SD of the differences between the test device and reference blood pressure readings was −1.3 ± 3.5  mmHg for systolic and −0.1  ± 2.3 mmHg for diastolic, in children under the age of 12 years. For those over the age of 12 years, the mean ± SD of the differences was −2.8 ± 4.6 mmHg for systolic and −0.5 ± 2.7 mmHg for diastolic. Regarding the ambulatory validation, for children under 12 years old, the mean ± SD of the differences was −1.3  ± 3.5  mmHg for systolic and −0.1  ± 2.3  mmHg for diastolic. In the age group above 12 years, the mean ± SD of the differences was −2.8 ± 4.6 mmHg for systolic and −0.5 ± 2.7 mmHg for diastolic. Both tests successfully met the established criteria regarding the mean and SD values of the differences between the device readings and the observed SBP and DBP measurements.

Conclusion

The ABPM-06 oscillometric device fully adheres to the ISO 81060-2 : 2018 standard requirements for ABPM determination in the pediatric population (ages 3–17 years). Consequently, this ABPM device proves to be suitable for effectively managing hypertension in children and adolescents.