bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bilirubin Distribution in Plants at the Subcellular and Tissue Levels
Authors: Ishikawa Kazuya , Kodama Yutaka 
Published: March 2024

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract
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

Abstract
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

Abstract

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&lt;0.01) improvements in their QOL, and more than one-half (51.2%) had a favorable adherence score of &gt;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

AbstractTipepidine (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

Abstract

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

SUMMARY

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.