bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombotic microangiopathy associated with anticancer and immune system targeting drugs: New insights from real‐world data using the WHO pharmacovigilance database
Authors: Largeau Bérenger , Thoreau Benjamin , Grangé Steven , Jonville‐Béra Annie‐Pierre , Halimi Jean‐Michel 
Published: August 2023

AbstractBackgroundThe worldwide development of immune system targeting/anticancer drugs has revolutionized immuno‐oncology, but their implication in thrombotic microangiopathy syndromes (TMA) is increasingly suspected. Using real‐world data, the aim of this study was to identify drugs associated with TMA reporting and to describe the evolution of TMA reporting over time with a focus on these drugs.MethodsA global disproportionality study was performed using the individual case safety reports (ICSRs) extracted from the World Health Organization (WHO) pharmacovigilance database (VigiBase) from its inception (1968) to April 30, 2022.ResultsOf the 31,251,040 ICSRs, 6946 cases of suspected drug‐induced TMA were included from 55 countries. The outcome was fatal in 18.2% of cases. A total of 72 immune system targeting/anticancer drugs were associated with significant overreporting, including 17 drugs with a potential new safety concern for TMA. Although the rate of TMA reporting per million of ICSRs has remained fairly stable, an absolute increase in reported cases of suspected drug‐induced TMA has been observed over the last decade. The pattern of drugs reported in TMA has evolved with a substantial increase in the proportion of cases involving immune system‐targeting drugs/anticancer drugs from 47.3% (205/433) in the period 1992–2001 to 80.7% (3819/4730) in the period 2012–2021.ConclusionSeveral recently marketed immune system targeting/anticancer drugs have been identified as potential new drugs associated with TMA, which will require confirmatory studies. The number of drugs associated with TMA reporting markedly increased within the past 10 years, primarily due to innovative anticancer drugs.
Parasite manipulation of host phenotypes inferred from transcriptional analyses in a trematode‐amphipod system
Authors: Rand David M. , Nunez Joaquin C. B. , Williams Shawn , Rong Stephen , Burley John T. , Neil Kimberly B. , Spierer Adam N. , McKerrow Wilson , Johnson David S. , Raynes Yevgeniy , Fayton Thomas J. , Skvir Nicholas , Ferranti David A. , Zeff Maya Greenhill , Lyons Amanda , Okami Naima , Morgan David M. , Kinney Kealohanuiopuna , Brown Bianca R. P. , Giblin Anne E. , Cardon Zoe G. 
Published: August 2023

AbstractManipulation of host phenotypes by parasites is hypothesized to be an adaptive strategy enhancing parasite transmission across hosts and generations. Characterizing the molecular mechanisms of manipulation is important to advance our understanding of host–parasite coevolution. The trematode (Levinseniella byrdi) is known to alter the colour and behaviour of its amphipod host (Orchestia grillus) presumably increasing predation of amphipods which enhances trematode transmission through its life cycle. We sampled 24 infected and 24 uninfected amphipods from a salt marsh in Massachusetts to perform differential gene expression analysis. In addition, we constructed novel genomic tools forO. grillusincluding a de novo genome and transcriptome. We discovered that trematode infection results in upregulation of amphipod transcripts associated with pigmentation and detection of external stimuli, and downregulation of multiple amphipod transcripts implicated in invertebrate immune responses, such as vacuolar ATPase genes. We hypothesize that suppression of immune genes and the altered expression of genes associated with coloration and behaviour may allow the trematode to persist in the amphipod and engage in further biochemical manipulation that promotes transmission. The genomic tools and transcriptomic analyses reported provide new opportunities to discover how parasites alter diverse pathways underlying host phenotypic changes in natural populations.
Clinical characteristics and severity of diabetic ketoacidosis: A cross‐sectional study from a tertiary hospital in Ghana
Authors: Atiase Yacoba , Yorke Ernest , Akpalu Josephine , Reynolds Margaret , Annan Ofoliquaye Allotey , Aryee Robert , Hayfron‐Benjamin Charles , Yawson Alfred 
Published: August 2023

AbstractObjectivesDiabetic ketoacidosis (DKA) is a common, severe and often fatal complication of diabetes. This study aimed to investigate the clinical characteristics and precipitants of DKA, as well as factors associated with DKA severity in Ghanaian patients.MethodsCross‐sectional study of the medical records of all 70 adult patients >18 years managed for DKA in the adult emergency room of Korle‐Bu Teaching Hospital in Ghana from March 2019 to July 2019. DKA diagnosis was based on hyperglycaemia >11.0 mmol/L, ketonuria (more than 2+) plus acidaemia of (pH < 7.3) or bicarbonate (HCO3−) <15.0 mmol/L. However, when serum bicarbonate and pH were not available, clinical signs of acidosis, for example, Kussmaul breathing aided in the diagnosis. DKA severity was assessed based on the Joint British Diabetes Societies (JBDS) guidelines of factors suggestive of severe DKA. Multivariable logistic regression was used to determine the factors associated with DKA severity. Odds ratio and 95% confidence interval for factors associated with DKA severity were determined.ResultsThe mean (±standard deviation) age, diabetes duration and blood sugar at admission were 44.06 (±16.23) years, 7.19 (±6.04) years and 26.37 (±6.70) mmol/L, respectively. Females comprised 51.4% of the study population. The most common presenting symptoms were generalised weakness (30.0%) and fever (14.3%). The major precipitants were infection (70.0%) and non‐compliance (22.9%). Overall, 71.4% of participants had features suggestive of severe DKA. In a multivariable regression model, Type 2 diabetes was associated with over fourfold decreased odds of severe DKA (OR 0.23, 95% CI [0.07–0.76], p = 0.016). Patient education on prevention of DKA was documented for only 18.6% of patients before being discharged.ConclusionIn this study, more than 70% of the study participants had features suggestive of severe DKA, with infection being the most common precipitant of DKA. 51.4% of patients had Type 2 diabetes which was associated with a statistically lower risk of severe DKA. Female sex tended to be positively associated with DKA severity. In a setting where the venous/arterial pH and bicarbonate levels may be inaccessible and/or unaffordable, using clinical features as found in the JBDS guidelines may help categorise patients and escalate care when needed. Indeed it may be useful to validate the use of the JBDS criteria for use in such settings.
Predictors of positive patient-reported outcomes from ‘Early Intervention in Psychosis’: a national cross-sectional study
Authors: Williams Ryan , Morris Aimee , Gupta Veenu , Penington Ed , Cullen Alexis E , Quirk Alan , French Paul , Lennox Belinda , Bottle Alex , Crawford Mike J 
Published: August 2023

BackgroundThe components of care delivered by Early Intervention in Psychosis (EIP) services vary, but the impact on patient experience is unknown.ObjectiveTo investigate associations between components of care provided by EIP services in England and patient-reported outcomes.Methods2374 patients from EIP services in England were surveyed during the National Clinical Audit of Psychosis. Participants were asked about the care they received, and completed the ‘Patient Global Impressions’ Scale (rating whether their mental health had improved), and ‘Friends and Family Test’ (rating whether they would recommend their service). Information about service structure was obtained from service providers. We analysed associations between outcomes and components of care using multilevel regression.FindingsThe majority of participants were likely to recommend the treatment they had received (89.8%), and felt that their mental health had improved (89.0%). Participants from services where care coordinators had larger case loads were less likely to recommend their care. Participants were more likely to recommend their care if they had been offered cognitive behavioural therapy for psychosis, family therapy or targeted interventions for carers. Participants were more likely to report that their mental health had improved if they had been offered cognitive behavioural therapy for psychosis or targeted interventions for carers.ConclusionsSpecific components of EIP care were associated with improved patient reported outcomes. Psychosocial interventions and carer support may be particularly important in optimising outcomes for patients.Clinical implicationsThese findings emphasise the need for small case load sizes and comprehensive packages of treatment in EIP services.
Interstitial lung disease with and without progressive fibrosing phenotype in patients with idiopathic inflammatory myopathies: data from a large multicentric cohort
Authors: Zanatta Elisabetta , Cocconcelli Elisabetta , Castelli Gioele , Giraudo Chiara , Fraia Anna Sara , De Zorzi Elena , Gatto Mariele , Ienna Luana , Treppo Elena , Malandrino Danilo , Cereser Lorenzo , Emmi Giacomo , Giannelli Federico , Bellani Serena , Martini Andrea , Moccaldi Beatrice , Ghirardello Anna , Avouac Jérôme , Quartuccio Luca , Allanore Yannick , Doria Andrea , Spagnolo Paolo , Balestro Elisabetta , Iaccarino Luca 
Published: August 2023

ObjectivesPatients with connective tissue diseases can develop interstitial lung disease (ILD), leading to a progressive fibrosing ILD (PF-ILD) phenotype in some cases. We aimed to investigate the occurrence of PF-ILD in idiopathic inflammatory myopathies (IIMs), and factors potentially predicting this phenotype. Secondary aims were to assess the radiological pattern and factors associated with IIMs-ILD.MethodsPatients with IIMs from our multicentric prospective cohort were retrospectively evaluated. Data were recorded at IIMs and ILD diagnosis, and during follow-up. Patients with ILD were classified according to the predominant high-resolution CT (HRCT) pattern: non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP) and organising pneumonia (OP). PF-ILD was defined according to the 2022 American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS) and Latin American Thoracic Society (ALAT) guidelines. Univariate and multivariate analyses were performed to identify factors associated to ILD and to PF-ILD.ResultsOf 253 patients with IIMs, 125 (49%) had ILD: 99 (78%) at IIMs diagnosis and 26 (22%) during follow-up (21/26 within 5 years). Multivariate analysis identified anti-Jo-1, anti-MDA5, anti-Ro52, high score on manual muscle test, mechanic’s hands and Raynaud’s phenomenon as independently associated with ILD. The predominant HRCT pattern was NSIP (50% of patients), followed by UIP (28%) and OP (22%). At 1-year follow-up, PF-ILD occurred in 18% of IIMs-ILD. PF-ILD was predicted by anti-MDA5, heliotropic rash, xerostomia and xerophthalmia at univariate but not at multivariate analysis.ConclusionPatients with IIM should be carefully screened for ILD at IIMs diagnosis and yearly during follow-up. All patients with IIMs-ILD should be carefully monitored to capture ILD progression since a consistent proportion of them are expected to develop PF-ILD.
Development of a Rare Earth Nanoprobe Enables In Vivo Real-Time Detection of Sentinel Lymph Node Metastasis of Breast Cancer Using NIR-IIb Imaging
Authors: Zhu Yuan-Yuan , Song Liang , Zhang Yong-Qu , Liu Wan-Ling , Chen Wei-Ling , Gao Wen-Liang , Zhang Li-Xin , Wang Jia-Zheng , Ming Zi-He , Zhang Yun , Zhang Guo-Jun 
Published: August 2023

Abstract

Sentinel lymph node (SLN) biopsy plays a critical role in axillary staging of breast cancer. However, traditional SLN mapping does not accurately discern the presence or absence of metastatic disease. Detection of SLN metastasis largely hinges on examination of frozen sections or paraffin-embedded tissues post-SLN biopsy. To improve detection of SLN metastasis, we developed a second near-infrared (NIR-II) in vivo fluorescence imaging system, pairing erbium-based rare-earth nanoparticles (ErNP) with bright down-conversion fluorescence at 1,556 nm. To visualize SLNs bearing breast cancer, ErNPs were modified by balixafortide (ErNPs@POL6326), a peptide antagonist of the chemokine receptor CXCR4. The ErNPs@POL6326 probes readily drained into SLNs when delivered subcutaneously, entering metastatic breast tumor cells specifically via CXCR4-mediated endocytosis. NIR fluorescence signals increased significantly in tumor-positive versus tumor-negative SLNs, enabling accurate determination of SLN breast cancer metastasis. In a syngeneic mouse mammary tumor model and a human breast cancer xenograft model, sensitivity for SLN metastasis detection was 92.86% and 93.33%, respectively, and specificity was 96.15% and 96.08%, respectively. Of note, the probes accurately detected both macrometastases and micrometastases in SLNs. These results overall underscore the potential of ErNPs@POL6326 for real-time visualization of SLNs and in vivo screening for SLN metastasis.

Significance:
NIR-IIb imaging of a rare-earth nanoprobe that is specifically taken up by breast cancer cells can accurately detect breast cancer macrometastases and micrometastases in sentinel lymph nodes.
Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma
Authors: Hatia Rikita I. , Eluri Madhulika , Hawk Ernest T. , Shalaby Akram , Karatas Elif , Shalaby Ahmed , Abdelhakeem Ahmed , Abdel-Wahab Reham , Chang Ping , Rashid Asif , Jalal Prasun K. , Amos Christopher I. , Han Younghun , Armaghany Tannaz , Shroff Rachna T. , Li Donghui , Javle Milind , Hassan Manal M. 
Published: August 2023

Abstract

Background:
It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States.

Methods:
We conducted a case–control study of 121 patients with ECC and 308 patients with ICC treated at MD Anderson Cancer Center between May 2014 and March 2020, compared with 1,061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted OR (AOR) and 95% confidence interval (CI) for each risk factor.

Results:
Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20–40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P &lt; 0.001; 6.1 months for ICC, P = 0.001; 8.2 months for ECC, P = 0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95% CI) were 1.11 (1.06–1.48) and 1.32 (1.01–2.00) for ICC and ECC, respectively.

Conclusions:
In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals.

Impact:
The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.
The Association of Kidney Function and Inflammatory Biomarkers with Epithelial Ovarian Cancer Risk
Authors: Hathaway Cassandra A. , Townsend Mary K. , Sklar Elliot M. , Thomas-Purcell Kamilah B. , Terry Kathryn L. , Trabert Britton , Tworoger Shelley S. 
Published: August 2023

Abstract

Background:
One of the mechanisms of ovarian tumorigenesis is through inflammation. Kidney dysfunction is associated with increased inflammation; thus, we assessed its relationship with ovarian cancer risk.

Methods:
In prospectively collected samples, we evaluated the association of kidney function markers and C-reactive protein (CRP) with ovarian cancer risk in the UK Biobank. We used multivariable-adjusted Cox proportional hazards models to evaluate quartiles of serum and urine markers with ovarian cancer risk overall and by histology. We assessed effect modification by CRP (≤3.0, &gt;3.0 mg/L).

Results:
Among 232,908 women (1,110 ovarian cancer cases diagnosed from 2006–2020), we observed no association between estimated glomerular filtration rate and ovarian cancer risk (Q4 vs. Q1: HR, 1.00; 95% confidence intervals, 0.83–1.22). Potassium was associated with endometrioid (Q4 vs. Q1: 0.33, 0.11–0.98) and clear cell (4.74, 1.39–16.16) tumors. Poor kidney function was associated with a nonsignificant increase in ovarian cancer risk among women with CRP&gt;3.0 mg/L (e.g., uric acid Q4 vs. Q1; 1.23, 0.81–1.86), but not CRP≤3.0 mg/L (0.83, 0.66–1.05). Other associations did not vary across CRP categories.

Conclusions:
Kidney function was not clearly associated with ovarian cancer risk. Larger studies are needed to evaluate possible histology specific associations. Given the suggestive trend for increased ovarian cancer risk in women with poor kidney function and high CRP, future work is needed, particularly in populations with a high prevalence of inflammatory conditions.

Impact:
This study provided the first evaluation of markers of kidney function in relation to ovarian cancer risk.
FBXO24 Suppresses Breast Cancer Tumorigenesis by Targeting LSD1 for Ubiquitination
Authors: Dong Bo , Song Xiang , Wang Xinzhao , Dai Tao , Wang Jianlin , Yu Zhiyong , Deng Jiong , Evers B. Mark , Wu Yadi 
Published: August 2023

Abstract

Lysine-specific demethylase 1 (LSD1), a critical chromatin modulator, functions as an oncogene by demethylation of H3K4me1/2. The stability of LSD1 is governed by a complex and intricate process involving ubiquitination and deubiquitination. Several deubiquitinases preserve LSD1 protein levels. However, the precise mechanism underlying the degradation of LSD1, which could mitigate its oncogenic function, remains unknown. To gain a better understanding of LSD1 degradation, we conducted an unbiased siRNA screening targeting all the human SCF family E3 ligases. Our screening identified FBXO24 as a genuine E3 ligase that ubiquitinates and degrades LSD1. As a result, FBXO24 inhibits LSD1-induced tumorigenesis and functions as a tumor suppressor in breast cancer cells. Moreover, FBXO24 exhibits an inverse correlation with LSD1 and is associated with a favorable prognosis in breast cancer patient samples. Taken together, our study uncovers the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation.

Implications:
Our study provides comprehensive characterization of the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation.
Association Between Prenatal Diagnosis and Age at Surgery for Noncritical and Critical Congenital Heart Defects
Authors: Woo Joyce L. , Laternser Christina , Anderson Brett R. , Grobman William A. , Monge Michael C. , Davis Matthew M. 
Published: August 2023

BACKGROUND:
The relationship between the prenatal diagnosis of congenital heart defects (CHDs) and age at CHD surgery is poorly understood, despite the known relationships between age at surgery and long-term outcomes. The objective of this study was to determine the associations between prenatal diagnosis of CHD and age at surgery, and whether these associations differ for critical and noncritical CHDs.

METHODS:
This is a cohort analysis of patients aged 0 to 9 years who received their initial cardiac surgery at Ann & Robert H. Lurie Children’s Hospital of Chicago between 2015 and 2021 with prenatal diagnosis as the exposure variable. All data were obtained from the locally maintained Society of Thoracic Surgeons Congenital Heart Surgery Database at Lurie Children’s Hospital. We used multivariable fixed effects regression models to estimate the strength of the association of prenatal diagnosis with age at surgery among patients with critical (surgery ≤60 days) and noncritical (surgery >60 days) CHDs.

RESULTS:

Of 1131 individuals who met inclusion criteria, 532 (47%) had a prenatal diagnosis, 428 (38%) had critical CHDs, 533 (47%) were female, and the median age at surgery was 119 days (interquartile range, 11–309 days). After controlling for demographics, comorbidities, and surgical complexity, the mean age at surgery was significantly younger in those with prenatally versus postnatally diagnosed critical CHD (7.1 days sooner,
P
<0.001) and noncritical CHDs (atrial septal defects [12.4 months sooner,
P
=0.037], ventricular septal defects [6.0 months sooner,
P
<0.003], and noncritical coarctation of the aorta [1.8 months sooner,
P
=0.010]).

CONCLUSIONS:
Younger age at CHD surgery, which is associated with postsurgical neurodevelopmental and physical outcomes, is significantly associated with prenatal CHD diagnosis. This relationship was identified for both critical and noncritical CHDs.
Weather-Driven Complementarity between Daily Energy Demand at One Location and Renewable Supply at Another
Authors: Fabry Frédéric , Samuel Joseph , Meunier Véronique 
Published: August 2023

Abstract
In a future world where most of the energy must come from intermittent renewable energy sources such as wind or solar energy, it would be more efficient if, for each demand area, we could determine the locations for which the output of an energy source would naturally match the demand fluctuations from that area. In parallel, meteorological weather systems such as midlatitude cyclones are often organized in a way that naturally shapes where areas of greater energy need (e.g., regions with more cold air) are with respect to windier or sunnier areas, and these are generally not collocated. As a result, the best places to generate renewable energy may not be near consumption sites; these may be determined, however, by common meteorological patterns. Using data from a reanalysis of six decades of past weather, we determined the complementarity between different sources of energy as well as the relationships between renewable supply and demand at daily averaged time scales for several North American cities. In general, demand and solar power tend to be slightly positively correlated at nearby locations away from the Rocky Mountains; however, wind power often must be obtained from greater distances and at altitude for energy production to be better timed with consumption.

Significance Statement
Weather patterns such as high and low pressure systems shape where and when energy is needed for warming or cooling; they also shape how much renewable energy from winds and the sun can be produced. Hence, they determine the regions where more energy is likely to be available in periods of unusually high need for each demand location. Finding where those areas are may result in more timely renewable energy production in the future to help reduce fossil fuel use for energy production.