bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Lower Respiratory Tract Sample Cultures on Outcomes in Community-Acquired Pneumonia: A Propensity Score–Matched Cohort Study
Authors: Fally Markus , Bastrup Israelsen Simone , Benfield Thomas , Tarp Britta , Kolte Lilian , Ravn Pernille ,   the Optimising Treatment of Community-Acquired Pneumonia (optiCAP) Study Group, Clausen Lise Notander , Anhøj Jacob , Hellesøe Anne-Marie Blok , Diernæs Emma , Molzen Line , Seerup Regitze , Nielsen Susanne , Rasmussen Susanne , Hansen Gunhild Agnete , Nielsen Lea Normand , Lindhardt Magnus Søltoft , Schmücker Malte
Published: December 2024

Background

This study aimed to determine whether collecting a lower respiratory tract sample (LRTS) for bacterial microscopy, culture, and resistance (MCR) testing affects outcomes in patients with community-acquired pneumonia (CAP).

Methods

This was a cohort study including adults admitted to hospital with CAP. The primary outcome was the duration of narrow-spectrum antibiotic treatment. Secondary outcomes included intravenous and total antibiotic durations, time to discharge, and 90-day mortality. Propensity score matching (PSM) balanced covariates between those who did and did not have an LRTS taken. Subgroup analyses focused on CAP due to Streptococcus pneumoniae or Haemophilus influenzae.

Results

After PSM, the cohort consisted of 1434 patients. LRTS collection did not impact narrow-spectrum antibiotic use but was associated with longer intravenous (0.6 days longer, P = .001) and total antibiotic treatments (10.4 vs 9.9 days, P = .036). Time-to-event analysis showed lower probability of early discharge for those with an LRTS (hazard ratio [HR], 0.88 [95% confidence interval {CI}:, .79–.98]) and higher probability for those with CAP due to S. pneumoniae or H. influenzae (HR, 1.44 [95% CI: 1.22–1.71]). Survival analysis showed lower 90-day mortality for patients with an LRTS (HR, 0.78 [95% CI: .61–.99]) and for those with CAP due to S. pneumoniae or H. influenzae (HR, 0.38 [95% CI: .24–.62]).

Conclusions

LRTS collection did not directly affect the use of narrow-spectrum antibiotics but was associated with extended antibiotic treatments overall. Additionally, LRTS collection was linked to longer hospital stays and reduced mortality. Until more sensitive methods for determining CAP etiology become available, LRTS MCR testing should remain a standard investigation for patients admitted with CAP.
Current practices in prevention, screening, and treatment of diabetes in kidney transplant recipients: European survey highlights from the ERA DESCARTES Working Group
Authors: Laghrib Yassine , Hilbrands Luuk , Oniscu Gabriel C , Crespo Marta , Gandolfini Ilaria , Mariat Christophe , Mjøen Geir , Sever Mehmet Sukru , Watschinger Bruno , Velioglu Arzu , Demir Erol , Martinez Eva Gavela , De Weerd Annelies , Dedinska Ivana , Pippias Maria , Massart Annick , Abramowicz Daniel , de Fijter Johan Willem , De Block Christophe , Hellemans Rachel
Published: December 2024

Background

Although post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplantation, there are few data on prevention, optimal screening, and treatment strategies.

Methods

The European Renal Association's DESCARTES working group distributed a web-based survey to European transplant centres to gather information on risk assessment, screening procedures, and management practices for preventing and treating PTDM in kidney transplant recipients.

Results

Answers were obtained from 121/241 transplant centres (50%) across 15 European countries. Screening practices for diabetes mellitus during the transplant work-up varied, with only 13% of centres using the recommended oral glucose tolerance test (OGTT) and 14% not screening at all. At transplantation, 19% of centres tailored the immunosuppressive regimen based on perceived PTDM risk, using strategies such as cyclosporin use or early steroid withdrawal. Fifty-two percent adopted strict glycaemic control with basal insulin in the first days post-transplant. Sixty-eight percent had defined screening protocols for early PTDM (45 days–6 months), primarily based on fasting glycaemia and/or HbA1c, while only a minority (7%) incorporated an OGTT. Changes in immunosuppression were considered by 41% in cases of early hyperglycaemia (<45 days) and by 58% in established PTDM (>45 days). Besides insulin therapy, dipeptidyl peptidase-4 (DPP4) inhibitors and metformin were most frequently used to manage early hyperglycaemia (<45 days) and PTDM (>45 days). The use of SGLT2 inhibitors and GLP-analogues increased >45 days post-transplantation.

Conclusion

This European survey underscores the significant variation in PTDM prevention, screening, and treatment practices, emphasizing the imperative for more explicit guidance in approaching this complication.
Improving the diagnostic of absorptive hypercalciuria: a comparative analysis of calcium load tests at 2-hour and 4-hour intervals
Authors: Cabezas Lara , Letourneau Pierre , De Mul Aurélie , Bacchetta Justine , Chardon Laurence , Derain Dubourg Laurence , Lemoine Sandrine
Published: December 2024

Introduction

The calcium load test (CLT) was developed by Pak et al. in 1974 to better discriminate hypercalciuria. Absorptive hypercalciuria (AH) is defined by an increase of the difference between urinary calcium/creatinine ratio (ΔUCa/Cr) of more than 0.5 mmol/mmol with a 4-hour CLT. In clinical practice and more recent studies, CLT is a 2-hour test. We hypothesized that the 4 h timepoint is more efficient in AH diagnosis.

Methods

We report a single-centre retrospective study including all patients who underwent CLT because of hypercalciuria or hyperparathyroidism. After a 3-day low-calcium diet and a 12-hour fast, 24-hour urines were collected. Blood and urinary samples were done at arrival and after 2 h and 4 h of oral ingestion of 1 g of calcium. AH was diagnosed by ΔUCa/Cr between baseline and 2 h or 4 h of more than 0.05 mmol/mmol.

Results

We included 328 patients. Baseline UCa/Cr ratio was 0.3 ± 0.2 mmol/mmol and increased significantly after 2 h and 4 h (0.6 ± 0.3 and 0.8 ± 0.4 mmol/mmol, P < 0.001). ΔUCa/Cr was significantly different between baseline and 2 h or 4 h (0.2 ± 0.2 versus 0.5 ± 0.4, P < 0.001). AH was diagnosed in 35 (10.7%) patients after 2 h, 84 (25.6%) more were diagnosed at 4 h (P < 0.001).

Conclusions

The 4 h CLT improves the diagnosis of AH with more than 50% of AH diagnosed within 4 h of calcium ingestion. It seems that there are cases of AH of later diagnosis with a similar clinical and biological profile depending on enteral absorption.
Common correlated effects estimation of nonlinear panel data models
Authors: Chen Liang , Zhang Minyuan
Published: December 2024

This paper focuses on estimating the coefficients and average partial effects of observed regressors in nonlinear panel data models with interactive fixed effects, using the common correlated effects (CCE, hereafter) framework. The proposed two-step estimation method involves applying principal component analysis to estimate the latent factors based on cross-sectional averages of the regressors in the first step, and jointly estimating the coefficients of the regressors and the factor loadings in the second step. The asymptotic distributions of the proposed estimators are derived under general conditions, assuming that the number of time-series observations is comparable to the number of cross-sectional observations. To correct for asymptotic biases of the estimators, we introduce both analytical and split-panel jackknife methods, and confirm their good performance in finite samples using Monte Carlo simulations. Finally, the proposed method is used to study the arbitrage behavior of nonfinancial firms across different security markets.
Hypoxia-inducible factor prolyl hydroxylase inhibitor-induced thrombosis leading to transcatheter aortic valve dysfunction: a case report
Authors: Ikuta Akihiro , Matsushita Syunsuke , Kadota Kazushige , Komiya Tatsuhiko , Fuku Yasushi
Published: December 2024

Background

Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for patients with severe aortic valve stenosis; however, clinical valve thrombosis is a major challenge.

Case summary

A 92-year-old woman underwent TAVR for severe aortic stenosis. One month later, the patient developed acute heart failure. As the progression of anaemia due to renal anaemia seemed to cause acute heart failure exacerbation, we started an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor. After 2 weeks, the patient redeveloped shortness of breath. Transthoracic echocardiography revealed that the mean aortic valve pressure gradient (ΔP) increased from 9 to 54 mmHg, and the aortic valve area decreased from 1.93 to 0.86 cm2. Blood work revealed a markedly elevated haemoglobin level from 8.0 to 13.2 g/dL, and transoesophageal echocardiography revealed markedly decreased left coronary and non-coronary cusp mobility. We diagnosed that the rapid increase in the haemoglobin level caused by the HIF-PH inhibitor was related to valve thrombosis and bioprosthetic dysfunction of the transcatheter aortic valve. The HIF-PH inhibitor was discontinued, and anticoagulation therapy was started. Transthoracic echocardiography at 16 days later revealed that the mean aortic valve ΔP improved by 15 mmHg, and the subjective symptoms resolved.

Discussion

This is the first report on a successful treatment of TAVR thrombosis formation associated with HIF-PH inhibitor use. When treating renal anaemia in patients undergoing TAVR, care should be taken to avoid rapid anaemia resolution and valve thrombosis development.
Left atrial myxoma associated with multivessel coronary embolism confirmed by cardiac magnetic resonance imaging: a case of myocardial infarction with non-obstructive coronary arteries
Authors: Pasquini Annalisa , Caffè Andrea , Filice Monica , Lillo Rosa , Montone Rocco Antonio , Chiariello Giovanni Alfonso , Pavone Natalia , Nesta Marialisa , Grandinetti Maria , Bruno Piergiorgio , Burzotta Francesco , Massetti Massimo
Published: December 2024

Aims

Explore the diagnostic value of multimodal imaging in identifying considerably rare causes of myocardial infarction.

Methods and results

We report a case of myocardial infarction with non-obstructive coronary arteries (MINOCA) probably due to coronary embolism associated with a left atrial myxoma. A 56-year-old male presented with non-ST-elevation myocardial infarction, with coronary angiography showing mild coronary atherosclerosis without significant epicardial stenosis. Transthoracic echocardiography and cardiac magnetic resonance imaging (CMR) revealed a large left atrial mass, suspected to be an atrial myxoma. CMR also showed an ischaemic pattern involving multiple coronary territories, suggesting coronary embolism as the cause of the MINOCA. The patient underwent successful surgical excision of the left atrial mass, and histopathology confirmed the diagnosis of cardiac myxoma.

Conclusions

This case highlights the relevance of CMR in detecting ischaemic patterns in patients with a working diagnosis of MINOCA and underlines the diagnostic value of multimodal imaging in identifying considerably rare causes of myocardial infarction, such as myxoma-associated coronary embolism.
Inflammation alters the expression and activity of the mechanosensitive ion channels in periodontal ligament cells
Authors: Ren Jianhan , Zhan Chaoning , Lin Yifan
Published: December 2024

Background

Periodontal ligament cells (PDLCs) possess mechanotransduction capability, vital in orthodontic tooth movement (OTM) and maintaining periodontal homeostasis. The study aims to elucidate the expression profiles of mechanosensitive ion channel (MIC) families in PDLCs and how the inflammatory mediator alters their expression and function, advancing the understanding of the biological process of OTM.

Methods and methods

Human PDLCs were cultured and exposed to TNF-α. RNA sequencing was conducted to explore the mRNA transcriptome of both normal and TNF-α-treated PDLCs. Differentially expressed MICs were identified and analyzed. The functional expressions of TRPA1 and TRPM8 were further validated by RT-qPCR, Western blot, and calcium influx assays.

Results

All 10 identified MIC families or subfamilies were expressed in PDLCs, with the TRP family being the most abundant. KCNK2, PIEZO1, TMEM87A, and PKD2 were the most expressed ion channels in PDLCs. TNF-α altered the expression of the MIC families, resulting in increased expression of PIEZO, K2P, TRP, TMEM63, and TMEM87 families and decreased expression of ENaC/ASIC, TMC/TMHS/TMIE, TMEM150, TMEM120, and L/T/N-Type calcium channel families. Furthermore, 17 DEMICs were identified (false discovery rate < 0.05), with the top five (fold change ≥ 2), including upregulated TRPA1 and TRPM8. The functional expressions of TRPA1 and TRPM8 were verified, suggesting that TNF-α significantly increased their expression and sensitized their activities.

Conclusions

The study provides comprehensive expression profiles of the MICs in PDLCs and reveals how inflammation alters the expression and activities of the MICs. Treatments targeting these MICs may offer promising strategies for improving OTM and preventing complications in inflammatory environments, ultimately leading to more effective and safer orthodontic practices.
Evidence for a Novel X Chromosome in Termites
Authors: Fraser Roxanne , Moraa Ruth , Djolai Annika , Meisenheimer Nils , Laube Sophie , Vicoso Beatriz , Huylmans Ann Kathrin
Published: December 2024

Termites, together with cockroaches, belong to the Blattodea. They possess an XX/XY sex determination system which has evolved from an XX/X0 system present in other Blattodean species, such as cockroaches and wood roaches. Little is currently known about the sex chromosomes of termites, their gene content, or their evolution. We here investigate the X chromosome of multiple termite species and compare them with the X chromosome of cockroaches using genomic and transcriptomic data. We find that the X chromosome of the termite Macrotermes natalensis is large and differentiated showing hall marks of sex chromosome evolution such as dosage compensation, while this does not seem to be the case in the other two termite species investigated here where sex chromosomes may be evolutionary younger. Furthermore, the X chromosome in M. natalensis is different from the X chromosome found in the cockroach Blattella germanica indicating that sex chromosome turn-over events may have happened during termite evolution.
Chromosome-level Genome Assembly and Annotation of the Arctic Moss Ptychostomum knowltonii
Authors: Ma Changling , Zhou Xuping , Huang Dan , Zhang Li , Yao Yifeng , Liu Yang , Dong Shanshan , Peng Tao
Published: December 2024

The polar regions host a diverse array of moss species that have evolved to thrive in extreme environments. These mosses exhibit remarkable adaptations, including tolerance to freezing temperatures, desiccation, and ultraviolet radiation. Despite their ecological significance, genomic data on these organisms are still limited, impeding our understanding of their evolutionary history and adaptive mechanisms in the context of climate change. In this study, we present the first chromosome-scale genome assembly and annotation of the Arctic moss Ptychostomum knowltonii. The assembled genome is 408.8 Mb in size, anchored to 12 pseudochromosomes, with a scaffold N50 of 32.61 Mb. Repetitive elements account for 56.24% of the genome. The genome contains 28,014 protein-coding genes, with a BUSCO completeness of 96.20%. This genomic resource will enable future comparative genomic studies, enhancing our understanding of how polar mosses may respond to a warming climate and shedding light on their evolutionary trajectories in persistently extreme environments.
Medicare Resource Use Differs by English Reading Proficiency
Authors: Estenson Lilly , Roberts Eric T , Jacobson Mireille
Published: December 2024

Background and Objectives

Medicare coverage decisions are complex. The Centers for Medicare & Medicaid Services (CMS) provides a hotline, handbook, and website to help Medicare beneficiaries understand their benefits and coverage options, yet it is unclear what factors affect beneficiary use of these resources. We examined limited English speaking and English reading proficiency status as predictors of CMS Medicare informational resource use in a nationally representative sample of Medicare beneficiaries.

Research Design and Methods

We used 2016–2018 Medicare Current Beneficiary Survey data and linear probability models to assess whether the likelihood of using CMS Medicare informational resources differed among beneficiaries with limited English proficiency. We adjusted models for demographic, socioeconomic, health, and local market factors and, in sensitivity analyses, health insurance characteristics. Our primary outcome was an indicator of having previously used at least 1 of the 3 CMS resources.

Results

Among noninstitutionalized beneficiaries (n = 20 715), 4.8% had limited English speaking proficiency, 7.0% had limited English reading proficiency, and 67.7% had used at least 1 CMS resource. After regression adjustment, beneficiaries with limited English reading proficiency were 16.3 percentage points less likely to have used a CMS resource compared to beneficiaries who reported English reading proficiency (p < .001). Limited English speaking proficiency was not associated with CMS resource use.

Discussion and Implications

These findings suggest that English reading proficiency may be an underappreciated factor in Medicare beneficiaries’ use of the Medicare handbook, hotline, and website. Alternative approaches to providing and publicizing informational resources may reduce barriers to Medicare resource use among beneficiaries with limited English reading proficiency.
Changes in coverage stability and churning for private, individual insurance under the Affordable Care Act
Authors: Hill Steven C , Jacobs Paul D
Published: December 2024

The Affordable Care Act (ACA) transformed the market for individual insurance. Using the 2-year panels of the Household Component of the Medical Expenditure Panel Survey covering the 2002-2022 period and controlling for the business cycle and other factors, we find the share of nonelderly adults enrolled in individual insurance doubled under the ACA. The percentage of adults covered by individual insurance 1-23 months more than doubled, and the percentage with at least 24 months rose 80% in states that did not expand Medicaid. Nearly all the gain came from adults who were uninsured immediately prior to enrolling. The prevalence of short individual market spells (<5 months) remained low after ACA implementation, and the ACA primarily helped cover individuals for longer spells. Individual insurance has always played a meaningful role in providing coverage for individuals ineligible for public programs and by bridging gaps between other forms of insurance. Because individual insurance is often temporary, more people may rely on individual insurance in their lifetimes than rely on it at a point in time. We document increases in individual coverage that suggest a strengthened role for this market after ACA implementation.
Americans’ support for future pandemic policies: insights from a national survey
Authors: SteelFisher Gillian K , Findling Mary G , Caporello Hannah L , Sutton Jazmyne , Dewhurst Emma , Evans Katherine , Castrucci Brian C
Published: December 2024

The arrival of bird flu (H5N1) is a poignant reminder of the need for public health leaders to understand Americans’ evolving perspectives on pandemic mitigation policies. To guide response efforts, we conducted a nationally representative opinion survey among 1017 U.S. adults in 2024. Majorities said they would be likely to support each of 4 policies in a future pandemic scenario (related to masking requirements, school closures, restaurant closures, and healthcare worker vaccination requirements). About half (49%) were likely to support all 4 policies, while 32% expressed mixed support. Support varied by gender, age, race, ethnicity, income, metropolitan and parental status, political party, and COVID-specific comorbidities. Roughly 80% expressed concern that future pandemic policies would hurt the economy, be based on political or pharmaceutical company/business interests, pander to critics, or further polarize society. Results suggest public support for future pandemic policies may be wider than media reports suggest, though important divisions exist and concerns about design and implementation are widespread. The most appealing policies will explicitly consider economic impacts and target populations at risk during clear time frames, with scope for personal choice. Ensuring that policies are made without undue political or commercial influence will remain a central challenge for public health leaders.
Plasmodium knowlesi Infection Is Associated With Elevated Circulating Biomarkers of Brain Injury and Endothelial Activation
Authors: Bertran-Cobo Cesc , Dumont Elin , Noordin Naqib Rafieqin , Lai Meng-Yee , Stone William , Tetteh Kevin K A , Drakeley Chris , Krishna Sanjeev , Lau Yee-Ling , Wassmer Samuel C
Published: December 2024

Background

Malaria remains a major public health concern with substantial morbidity and mortality worldwide. In Malaysia, the emergence of Plasmodium knowlesi has led to a surge in zoonotic malaria cases and deaths in recent years. Signs of cerebral involvement have been observed in a noncomatose, fatal case of knowlesi infection, but the potential impact of this malaria species on the brain remains unexplored. To address this gap, we investigated circulating levels of brain injury, inflammation, and vascular biomarkers in a cohort of knowlesi-infected patients and controls.

Methods

Archived plasma samples from 19 Malaysian patients with symptomatic knowlesi infection and 19 healthy, age-matched controls were analyzed. Fifty-two biomarkers of brain injury, inflammation, and vascular activation were measured. Wilcoxon tests were used to examine group differences, and biomarker profiles were explored through hierarchical clustering heatmap analysis.

Results

Bonferroni-corrected analyses revealed significantly elevated brain injury biomarker levels in knowlesi-infected patients, including S100B (P < .0001), Tau (P = .0007), UCH-L1 (P < .0001), αSyn (P < .0001), Park7 (P = .0006), NRGN (P = .0022), and TDP-43 (P = .005). Compared to controls, levels were lower in the infected group for BDNF (P < .0001), CaBD (P < .0001), CNTN1 (P < .0001), NCAM-1 (P < .0001), GFAP (P = .0013), and KLK6 (P = .0126). Hierarchical clustering revealed distinct group profiles for brain injury and vascular activation biomarkers.

Conclusions

Our findings highlight for the first time a potential impact of P knowlesi infection on the brain, with specific changes in cerebral injury and endothelial activation biomarker profiles. Further studies are warranted to investigate the pathophysiology and clinical significance of these altered markers, through neuroimaging and long-term neurocognitive assessments.
Viral and Immune Risk Factors of HIV Rebound After Interruption of Antiretroviral Therapy
Authors: Gianella Sara , Yu Tingting , Wang Rui , Ignacio Caroline , Schanz Merle , Kouyos Roger D , Caballero Gemma , Gaitan Noah C , Rawlings Stephen , Kuster Herbert , Metzner Karin J , Gandhi Rajesh T , Li Jonathan Z , Günthard Huldrych F , Smith Davey M , Chaillon Antoine
Published: December 2024

Background

Identifying risk factors for human immunodeficiency virus (HIV) rebound after treatment interruption is crucial for designing effective remission strategies.

Methods

Peripheral blood mononuclear cells from participants in the Zurich HIV Primary Infection Cohort (ZPHI, n = 73) and ACTG study A5345 (n = 44) were analyzed before antiretroviral therapy (ART) interruption. We measured cell-associated HIV RNA, total HIV DNA, and proviral diversity (env gene). Immune phenotyping was conducted by flow cytometry. Cox proportional hazards (PH) models and penalized Cox PH models with an adaptive LASSO penalty identified risk factors for time to rebound (HIV RNA >1000 copies/mL).

Results

Late ART initiation was associated with higher rebound risk (shorter time to rebound) as compared to early ART. Higher pre-ART HIV RNA in plasma, total HIV DNA, and increased cellular HIV transcription at the time of ART interruption were associated with higher rebound risk. Higher proviral diversity was associated with higher rebound risk but only among male participants and those enrolled in the ZPHI cohort. Fewer CD4+ T cells at ART interruption, higher proportions of effector and terminally differentiated T cells, and more activated and exhausted T cells were associated with higher rebound risk, primarily in early-treated participants. No significant immunological risk factors were found in participants treated during chronic HIV. In the combined cohort, total HIV DNA and terminally differentiated CD8+ T cells appeared to be the most relevant risk factors for time to rebound, as indicated by variable selection in multivariable analysis.

Conclusions

These findings underscore the importance of early ART initiation and suggest that tailored interventions based on virologic, immunologic, and demographic factors may help achieve sustained viral suppression.

Clinical Trials Registration. NCT00537966 and NCT03001128.
Tissue-Resident CD8+ T Cells as Mediators of Protective Immunity in Breast Milk Transmission of Human Cytomegalovirus
Authors: Legg Shara B , Moylan David C , Kamau Neema , Latting Misty P , Devdhara Dhruv , Pati Sunil K , Crossman David K , Boppana Suresh B , Kutsch Olaf , Sabbaj Steffanie
Published: December 2024

While the role of breast milk antibodies to protect infants from human cytomegalovirus (HCMV) has been investigated, the role of T-cells has received little attention. We compared the frequency of memory T-cell populations in breast milk between mothers of infants who acquired breast milk HCMV (transmitters) and those with uninfected infants (nontransmitters). Nontransmitter mothers had an increased frequency of CD8+ effector memory T-cells (Tem) in their breast milk. In addition, we describe tissue-resident memory T cells (Trm) in breast milk and demonstrate most were Tem. We present data that nontransmitter mothers have increased frequency of CD8+ Trm in their breast milk when compared to transmitters and that Trm frequency is inversely correlated with breast milk HCMV viral load. Lastly, using scRNA-seq analysis we identified a unique population of T-cells in nontransmitters and demonstrate that these cells comprise CD8+ Trm. These studies suggest that CD8+ Trm may play a role in preventing viral transmission via breast milk to infants.
Validation of the 11+Myco MS-PREP® Method for Determination of Aflatoxins, Fumonisins, Deoxynivalenol, Ochratoxin A, Zearalenone, HT-2, and T-2 Toxins in Cereals, Baby Food, Spices, and Animal Feed by Immunoaffinity Column with LC–MS/MS: AOAC Performance Tested MethodSM 112401
Authors: Leeman Dave , Allan Andrew B , Cameron Helen , Donelly Carol , Tramaseur Adam , Stratton Joanna , MacDonald Susan J
Published: December 2024

Background

The 11+Myco MS-PREP® immunoaffinity column (IAC) contains a gel suspension of monoclonal antibodies specific to the toxins of interest. Following sample extraction, the IAC is used for cleanup and concentration of mycotoxins prior to analysis by LC with tandem mass spectrometry (LC–MS/MS).

Objective

This study evaluated the IAC with LC–MS/MS method for Performance Tested MethodSM certification for simultaneous determination and confirmation of aflatoxins (AF) B1, B2, G1, G2, and M1; deoxynivalenol (DON), fumonisins B1, B2, and B3; ochratoxin A (OTA); T-2; HT-2; and zearalenone (ZON) from corn, wheat, cereal-based baby food (with and without dairy ingredients), paprika, chili powder, and animal feed.

Methods

A single extraction method using acetonitrile-water (1 + 1, by volume) was used for all matrixes. The method developer validated all matrixes and an independent laboratory verified method performance on corn and animal feed. Data were analyzed for recovery, repeatability precision, LOD, LOQ, confirmation of identity, and method selectivity.

Results

Recovery (72–138%) and repeatability (0.46–24%), with the exception of sporadic data points, were within acceptance criteria. LOQ was estimated as AFB1 0.018–0.32 μg/kg, AFB2 0.037–0.28 μg/kg, AFG1 0.019–0.14 μg/kg, AFG2 0.036–0.28 μg/kg, DON 4.0–75 μg/kg, fumonisin B1 4.9–37 μg/kg, fumonisin B2 4.0–32 μg/kg, fumonisin B3 2.0–16 μg/kg, OTA 0.15–4.4 μg/kg, T-2 0.5–7.5 μg/kg, HT-2 0.70–7.5 μg/kg, and ZON 1.3–7.2 μg/kg, depending on matrix. Method performance was verified with reference and QC materials. Selectivity and confirmation of identity were also demonstrated.

Conclusion

The 11+Myco MS-PREP IAC with LC–MS/MS method demonstrated acceptable performance for simultaneous determination of 12 mycotoxins in seven matrixes.

Highlight

The data were reviewed by the AOAC Performance Tested MethodsSM Program and approval was granted for certification of the 11+Myco MS-PREP Method as PTM 112401.
Initial evaluation of 4-palmitoyloxy butyrate in whole blood as potential biomarker after γ-hydroxybutyric acid intake
Authors: Liut Jennifer , Madea Burkhard , Meißner Dirk , Lützen Arne , Javidi Sirous , Hess Cornelius , Krämer Michael
Published: December 2024

The problem of finding a suitable biomarker to widen the detection window of γ-hydroxybutyric acid (GHB) intake remains a challenge in forensic toxicology. Based on previously published results, the present study deals with the evaluation of a fatty acid ester of GHB (4-palmitoyloxy butyrate [GHB-Pal]) in whole blood as a potential biomarker to extend the detection window of GHB use, e.g. in drug-facilitated sexual assaults. A liquid chromatography–mass spectrometry (LC–MS–MS) method for the quantification of GHB-Pal in whole blood was validated. Whole blood samples were collected from subjects involed in police roadside controls (n = 113) and from narcolepsy patients (n = 10) after the controlled administration of Xyrem® (sodium oxybate). Both sample collectives were previously tested for GHB using two different methods: ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS–MS) and gas chromatography–mass spectrometry (GC–MS). In samples from routine police casework, GHB-Pal was detected in 67 out of 113 analysed GHB-positive samples with a mean concentration of 0.8 ng/mL ± 0.5 ng/mL (standard deviation). Among samples that were tested positive for both compounds, no linear correlation was observed between GHB and GHB-Pal concentrations (r = 0.508). In contrast, GHB-Pal was not detected in any of the blood samples analysed from the patients. The absence of GHB and GHB-Pal in the patient cohort may be attributed to the time interval between dose intake and blood collection (approximately 3 and 6 h), during which GHB was eliminated from the body. Furthermore, GHB-Pal was only detectable at a GHB concentration of at least 16 µg/mL, which indicates that endogenous concentrations or low GHB doses may not be sufficient for GHB-Pal formation. Due to missing correlation between both compounds and the lack of GHB-Pal detection several hours after GHB administration, it can be assumed that GHB-Pal in blood is not a suitable biomarker to widen the detection window of GHB.
Two-sided function of osteopontin during osteoblast differentiation
Authors: Mardiyantoro Fredy , Chiba Norika , Seong Chang-Hwan , Tada Ryohei , Ohnishi Tomokazu , Nakamura Norifumi , Matsuguchi Tetsuya
Published: December 2024

Osteopontin (OPN) is expressed in various cell types including osteoblasts. OPN expression level is robustly increased during osteoblast differentiation. Although OPN was initially found as a secretory protein (sOPN), recent reports identified the intracellular isoform of OPN (iOPN). Distinct functions of each OPN isoform in osteoblasts, however, are not well established. Here, using the Tet-On inducible expression system, we examined the role of each OPN isoform during osteoblast differentiation. Induced overexpression of wild type OPN (wtOPN), which includes both sOPN and iOPN, significantly increased matrix mineralization and osteogenic marker gene expression during osteogenic differentiation induced by either ascorbic acid or bone morphogenetic protein (BMP) 9. In contrast, these osteogenic differentiation processes were significantly inhibited by the specific overexpression of iOPN. Furthermore, the addition of recombinant OPN or neutralizing anti-OPN antibody to the culture medium exerted promotive or inhibitory effect on osteoblast differentiation, respectively. These data strongly indicate that iOPN exerts inhibitory effects on osteoblast differentiation, whereas sOPN exerts positive effects. We also found that the secretion process of OPN is positively regulated by c-Jun N-terminal kinase (JNK) activity in osteoblasts.
Improvement of bone properties in children with osteogenesis imperfecta after pamidronate: a bone biopsy study
Authors: Farlay Delphine , Cornier Mathilde , Rizzo Sébastien , Cormier-Daire Valérie , Charpié Maelle , Pinto Graziella , Simonnet Hina , Badoud Isabelle , Gerbaix Maude , Chavassieux Pascale , Chapurlat Roland
Published: December 2024

OI, or bone brittle disease, is characterized by increased mineralization of bone matrix independently of clinical severity. So, a beneficial effect of antiresorptive treatments such as bisphosphonates (BP) is questionable. We aim to compare the bone matrix characteristics before and after BP pamidronate (PAM). Fifty-eight children (9 ± 5 yr-old) with OI (Type I, III, IV, V, VI, XI, or unknown) received intravenous PAM for 2 yr and underwent transiliac bone biopsies before (n = 57) and after (n = 35) treatment. Compared with age-matched controls, untreated OI was characterized by cortical and cancellous rarefaction. Two years of PAM in OI patients significantly decreased bone remodeling activity, increased cortical thickness, improved the maturation of both organic and mineral matrix, and most of the nanomechanical properties, despite further increase in the degree of mineralization. Overall, in addition to a gain in bone mass, our results showed for the first time that PAM is able to increase the maturation of mineral crystals and collagen matrix contributing to its antifracture efficacy in OI patients.
Ensuring Pharmaceutical Accountability for Human Rights and Access to Medicines: The Dutch Duty of Care Standard Applied to Pharmaceutical Companies
Authors: Turkie Rosalind , Perehudoff Katrina , Sellin Jennifer , Sainz Aldo
Published: December 2024

To effectively protect the human right to health, the global accountability gap for pharmaceutical companies regarding access to medicines must be addressed. Pharmaceutical companies have no formal obligations under human rights law; however, they do have responsibilities, and some companies (directly or indirectly) undermine the right to health and equitable access to medicines. We propose that pharmaceutical companies can be held accountable for human rights interferences by means of a provision in Dutch tort law containing an ‘unwritten duty of care’, an interpretation which is supported by the international human rights framework and recent Dutch jurisprudence. We propose a concrete example of how this duty could be applied in Dutch courts, which have previously held a private corporation accountable for contributing to dangerous climate change in the Milieudefensie et al. v Royal Dutch Shell case. To establish whether this duty could be applied to pharmaceutical companies, we use the court’s reasoning in Milieudefensie to assess the existence of a global consensus on the need for a pharmaceutical duty of care. We argue that human rights norms and soft law instruments that pharmaceutical companies themselves have endorsed prove that there is a growing consensus regarding the damage associated with excessively priced medicines, and an urgent need to establish a framework for holding pharmaceutical companies accountable for ensuring equitable access to medicines through legal measures.
Real-world impact of the platinum chemotherapy shortage on US patients with advanced cancer
Authors: Reibel Jacob B , Sun Lova L , Parikh Ravi B , Mahmud Nadim , Martin Lainie P , Hubbard Rebecca A , Mamtani Ronac
Published: December 2024

The recent cisplatin and carboplatin (“platinum”) chemotherapy shortage, first announced on February 10, 2023, has impacted cancer patients nationwide. Here, we quantify the extent to which the shortage affected platinum chemotherapy prescribing and short-term mortality. This cohort study included 11 797 adults with advanced solid cancers who initiated first-line therapy during the 1-year period before (February 1, 2022–February 9, 2023) or during (February 10, 2023–January 31, 2024) the platinum shortage. During the shortage, there was a 2.7% absolute reduction in platinum use (95% CI = −4.4% to −0.9%) compared to the previous year. At the peak of the shortage, there was a 15.1% absolute reduction in platinum prescribing (June 2023: 57.8% [95% CI = 53.6% to 62.0%]) compared to 1 year prior (June 2022: 72.9% [95% CI = 70.7% to 75.2%]). There was no difference in mortality before vs during the shortage (adjusted hazard ratio 1.00; 95% CI = 0.94 to 1.07) with median follow-up time of 7.6 months. Further research is required to study shortage impacts on long-term mortality.
Unraveling the clinical–pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer’s Coordinating Center dataset
Authors: Hiya Satomi , Maldonado-Díaz Carolina , Rohde Susan K , Gonzales Mitzi M , Canbeldek Leyla , Kulumani Mahadevan Lakshmi S , Yokoda Raquel T , Sullivan A Campbell , Parker Alicia S , White Charles L , Daoud Elena V , Flores-Almazan Victoria , Crary John F , Farrell Kurt , Walker Jamie M , Richardson Timothy E
Published: December 2024

Although Alzheimer disease neuropathologic change (ADNC) is the most common pathology underlying clinical dementia, the presence of multiple comorbid neuropathologies is increasingly being recognized as a major contributor to the worldwide dementia burden. We analyzed 1051 subjects with specific combinations of isolated and mixed pathologies and conducted multivariate logistic regression analysis on a cohort of 4624 cases with mixed pathologies to systematically explore the independent cognitive contributions of each pathology. Alzheimer disease neuropathologic change and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) were both associated with a primary clinical diagnosis of Alzheimer disease (AD) and were characterized by an amnestic dementia phenotype, while only ADNC associated with logopenic variant primary progressive aphasia (PPA). In subjects with ADNC and comorbid LATE-NC, Lewy body disease, and/or cerebrovascular disease, the clinical phenotype was usually diagnosed during life as “Probable AD.” Conversely, the combination of ADNC with frontotemporal lobar degeneration with TDP-43, progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD) resulted in a mixed clinical picture, with variable features of amnestic dementia, PPA subtypes, behavioral variant FTD, PSP syndrome, and CBD syndrome. These findings elucidate the cumulative effects of mixed pathologies and provide insights into interactions between neurodegenerative pathologies contributing to a variety of clinical dementia presentations.
Managing Water Consumption in Colonial Hong Kong: Separate Water Metering, c. 1965–1980s
Authors: Lai Siu-hei , Mok Florence
Published: December 2024

Water troubled administrators of the colonial regime and residents in Hong Kong during the first three decades of the post-war period. The colonial regime attempted to remedy water shortages by exploiting additional water supplies and by improving its administration of water usage. Using archival records in Hong Kong and London, as well as unofficial sources such as local newspapers, this article studies an under-explored demand-side maneuver, separate water metering, introduced by the colonial government in Hong Kong in 1965, and its sociohistorical role in managing water usage. With an improved legibility of water consumption for both local households and the government, separate meterage prompted households to use water more wisely and economically. This article demonstrates that separate meterage expanded the state’s capacity to manage household water consumption and strengthened societal efforts in water conservation. The combination of technology, financial incentives and persuasion—a “pragmatic-persuasive” governing strategy—planted “save water” in the minds of residents which involved households in the water administration to a greater extent. Separate meterage transformed public perceptions of water consumption in the long run and fostered the emergence of civic obligation over water conservation in Hong Kong. This article thereby makes an original contribution to the political and social history of Hong Kong, colonial statecraft, and water management.
(153) CAN LARGE-LANGUAGE MODELS ACCURATELY DISCERN AI-GENERATED SEXUAL MEDICINE SCIENTIFIC LITERATURE FROM HUMAN GENERATED?
Authors: Singh D , Greenberg JW , Shkolnik B , Hellstrom W
Published: December 2024

Introduction

Chat-GPT an iteration of Artificial Intelligence (AI) which utilizes Large-Language Model (LLM) to understand and generate text, has been increasingly employed in scientific literature, healthcare, and education since its release in 2022. While these LLMs offer the possibility of increasing the clarity of scientific writing, they have been met with criticism regarding utility, accuracy, legality, and reliability. To combat potential abuse of these powerful tools, academic institutions have used AI tools to help identify text generated by an LLM. However, no study has currently validated the accuracy and utility of AI in this setting.

Objective

To validate if commercially available AI detector tools can identify potentially AI generated text within published sexual medicine articles. Secondary aims included identifying factors that contribute to an article being flagged as AI generated.

Methods

Phrasly.AI was utilized as the primary AI detector tool that cross-referenced scores from other AI detectors named “ContentAtScale”, “GPTZero”, “ZeroGPT”, “OpenAI”, “CopyLeaks”, “TurnItIn”. Top 20 most cited articles published in the Journal of Sexual Medicine were obtained for the following 5 year intervals: 2004-2008, 2009-2013, 2014-2018, 2019-2024. Positive controls of known AI generated articles were also obtained. Each of these articles and controls were analyzed with Phrasly.AI. The following variables were obtained: type of article, sentences analyzed, number of sentences likely to be AI generated, percent of article AI-generated, country of authorship, and a likelihood AI-generated score (1 = Human, 2 = partial AI, 3 = complete AI). Results were analyzed using program R utilizing binominal regression models to determine likelihood of obtaining an AI-Generated score.

Results

A total of 80 articles in total were analyzed with 5 positive controls. All positive control articles were predicted to be AI-generated. 45% (36/80) articles were flagged as likely AI-Generated. All articles analyzed were published prior to 2022 when the first LLM was released. No significant association was found between the likelihood AI-Generated score and the following variables: country of authorship and the year published of the article. We did observe a significant association between type of article and likelihood of being AI-Generated in our regression model showing review articles had an OR 3.10 (95% 1.19-8.55; p = 0.023).

Conclusions

Current AI detector tools often inaccurately discern human-generated scientific writing as AI-Generated as all articles included in this study were published prior to the releast of Chat-GPT. Review Articles are three times as likely to be flagged as AI-generated. Further validity of the utility and accuracy of these tools is needed prior to their widespread adoption in cross-checking for AI utilization in the construction of scientific literature.

Disclosure

No.
(158) UTILITY OF PRIMARY CARE PHYSICIANS IN A UROLOGY MEN’S HEALTH CLINIC
Authors: Jacobs L , Dhillon H , Patel P
Published: December 2024

Introduction

Urology clinics may receive consultation referrals for clinical issues which do not require surgical specialist management. Additionally, with ongoing expansion of therapeutic options in men’s health, referring family medicine physicians may not be aware of all potential treatment modalities. Delayed time from referral to specialist consultation represents a significant issue in Canadian healthcare. Common referrals from general practice for urology assessment includes erectile dysfunction and testosterone deficiency. Multidisciplinary clinics enable access to care for various men’s health concerns where some may not require urologic surgeon specialist intervention.

Objective

We aim to assess whether men’s health trained primary care providers (PCPs) with foundational training in men’s health working within a multidisciplinary clinic can address common urologic referrals and reduce the need for specialist management of urology clinic referrals.

Methods

A retrospective chart review was performed involving all patients referred by personal primary care providers to urology who were screened by a urologist as appropriate for initial consultation by a PCP at a multidisciplinary men’s health clinic from January 2022 to January 2023 in Winnipeg, Canada. Patient demographics, medical concern, management, time from referral to treatment, and need for urologist follow-up was captured. There were no inclusion or exclusion criteria.

Results

A total of 419 patients were identified. Treatment data for all were collected. 331 patients (79%) were managed by an in-house PCP alone and 88 (21%) required urologist consultation following PCP assessment. De novo erectile dysfunction, low testosterone and orchalgia were the most common issues triaged to PCP initial management. Issues managed by PCP also included penile curvature, functional sexual concerns and lower urinary tract symptoms. Male infertility, penile curvature, and orchalgia were the most prevalent conditions requiring subsequent urologist referral. PCPs were able to initiate non-surgical therapies in a majority of patients. In analysis of treatment by primary referral medical concern, 100% of low testosterone, 96% of erectile dysfunction, and 82% of orchalgia were managed at the PCP level alone and did not require urologic surgeon assessment.

Conclusions

PCPs in a multidisciplinary clinic can provide care for a range of urologic issues and reduce need for urologist consultation. This study demonstrates the utility of PCPs in optimization of urologist consultation. Presenting issues may be predictive of the need for urologist referral.

Disclosure

No.