bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delirium‐associated medication in people at risk: A systematic update review, meta‐analyses, and GRADE‐profiles
Authors: Reisinger Michael , Reininghaus Eva Z. , Biasi Johanna De , Fellendorf Frederike T. , Schoberer Daniela 
Published: September 2022

AbstractBackgroundDrug‐associated delirium is a common but potentially preventable neuropsychiatric syndrome associated with detrimental outcomes. Empirical evidence for delirium‐associated medication is uncertain due to a lack of high‐quality studies. We aimed to further investigate the body of evidence for drugs suspected to trigger delirium.MethodsA systematic update review and meta‐analyses of prospective studies presenting drug associations with incident delirium in adult study populations was conducted. Two authors independently searched MEDLINE, PsycINFO, Embase, and Google Scholar dated from October 1, 2009 to June 23, 2020, after screening a previous review published in 2011. The most reliable results on drug‐delirium associations were pooled in meta‐analyses using the random‐effects model. Quality of evidence was assessed using the GRADE‐approach. This study is preregistered with OSF (DOI https://doi.org.10.17605/OSF.IO/4PUHY).ResultsThe 31 eligible studies, presenting results for 24 medication classes were identified. Meta‐analyses and GRADE level of evidence ratings show no increased delirium risk for Haloperidol (OR: 0.96, 95% CI 0.72–1.28; high‐quality evidence), Olanzapine (OR: 0.25, 95% CI 0.15–0.40), Ketamine (OR: 0.72, 95% CI 0.35–1.46) or corticosteroids (OR: 0.69, 95% CI 0.32–1.50; moderate quality evidence, respectively). Low‐level evidence suggests a three‐fold increased risk for anticholinergics (OR: 3.11, 95% CI 1.04–9.26). Opioids, benzodiazepines, H1‐antihistamines, and antidepressants did not reach reliable evidence levels in our analyses.ConclusionWe investigated the retrievable body of evidence for delirium‐associated medication. The results of this systematic review were then interpreted in conjunction with other evidence‐based works and guidelines providing conclusions for clinical decision‐making.
PC‐DOT: Improving genomic prediction ability of principal component regression by DOT product
Authors: Sun Hao , Wei Meng , Xu Zhong , Bai Chunyan , Sun Boxing 
Published: September 2022

AbstractPrincipal component regression (PC regression) is a useful method developed for prediction based on a dimension‐reducing strategy. Generally, the principal components (PCs) are added to the regression model one by one based on the eigenvalue (PC‐Eigen). Considering that some PCs with large eigenvalues may be poorly associated with the response variable, the PC‐Eigen may not be the best framework. Researchers previously tried to add PCs to the model based on their contribution to the sum of squares of the regression (PC‐SS) and they found that the performance of PC‐SS is generally lower than that of the PC‐Eigen. A standard approach for selecting the optimal set of PCs remains a challenge. Here, from the cosine similarity theory, we postulated that we could rank the PCs by dot product, and this framework (we called PC‐DOT) could help to preferentially extract PCs that are highly correlated with the response variable and meanwhile have a large eigenvalue. Based on one simulated and three real genomic datasets (a total of 15 traits), we tested the prediction ability of different frameworks. In general, the PC‐DOT method showed a better performance than both PC‐Eigen and PC‐SS. To facilitate the application of PC, we attached a series of R codes for different frameworks (https://github.com/SUNHAO‐JLU/Genome_Prediction‐PC_DOT). In addition, the HAT matrix was used to reduce the compute complex in reference data during the cross‐validation process. Our work may help researchers to better understand and carry out the PC regression model.
Ustekinumab during pregnancy in patients with inflammatory bowel disease: a prospective multicentre cohort study
Authors: Avni‐Biron Irit , Mishael Tali , Zittan Eran , Livne‐Margolin Moran , Zinger Adar , Tzadok Roie , Goldenberg Rosie , Kopylov Uri , Ron Yulia , Hadar Eran , Helman Sarit , Granovsky Sorina Grisaru , Ollech Jacob E. , Arazi Ayelet , Farkash Rivka , Pauker Maor H. , Yanai Henit , Dotan Iris , Shitrit Ariella Bar‐Gil 
Published: September 2022

SummaryBackgroundWomen with inflammatory bowel diseases (IBD) often receive biologics to maintain remission during pregnancy.AimsTo assess maternal and neonatal outcomes in patients with IBD treated with ustekinumab (UST) during pregnancyMethodsIn a multicentre, prospective cohort study, we recruited women with IBD treated with UST during pregnancy between 2019 and 2021. Outcomes were compared among patients treated with UST, anti‐tumour necrosis factor α, (anti‐TNF) and non‐UST, non‐anti‐TNF therapies. UST‐treated patients were matched 1:2 to controls according to age, body mass index and parity. Newborns were followed up to 12 months.ResultsWe recruited 129 pregnant patients: UST 27; anti‐TNF 52; non‐UST, non‐anti‐TNF 50 (thiopurine or mesalazine 30, no therapy 20); Crohn's disease 25 (96.9%). Overall, pregnancy, neonatal and newborn outcomes were satisfactory, with no significant differences among patients treated with UST, anti‐TNF and non‐UST non‐anti‐TNF agents for obstetrical maternal complications [UST 3 (11.5%), anti TNF 12 (23.1%), non UST, non‐anti‐TNF 4 (8.2%), p = 0.095], pre‐term delivery [1 (4.3%), 9 (18.4%), 4 (5.7%), p = 0.133], low birth weight [1 (4.2%), 5 (10.2%), 4 (8.3%), p = 0.679], or first year newborn hospitalisation [2 (9.1%), 4 (8.2%), 3 (6.1%), p = 0.885].ConclusionPregnant patients with IBD treated with UST demonstrated favourable pregnancy and neonatal outcomes that were comparable with those in patients treated with anti‐TNF or other therapy. Data are reassuring for patients with IBD and their physicians when considering UST during pregnancy.
Abemaciclib plus fulvestrant in East Asian women with HR+, HER2− advanced breast cancer: Overall survival from MONARCH 2
Authors: Toi Masakazu , Huang Chiun‐Sheng , Im Young‐Hyuck , Sohn Joohyuk , Zhang Wei , Sakaguchi Sachi , Haddad Nadine , van Hal Gertjan , Sledge George W. 
Published: September 2022

AbstractMONARCH 2 is a global, randomized, double‐blind, phase 3 study of abemaciclib/placebo + fulvestrant in patients with hormone receptor positive, human epidermal growth factor receptor 2‐negative advanced breast cancer. The East Asian population comprised 212 (31.7%) of the 669 intent‐to‐treat population in the MONARCH 2 trial. Consistent with the primary analysis, this subpopulation analysis of East Asian patients indicated progression‐free survival benefit in the abemaciclib arm. The median overall survival was not reached in the abemaciclib arm and was 48.9 months in the placebo arm (hazard ratio 0.80; 95% confidence interval 0.52–1.24; p = 0.377). In addition, other efficacy endpoints, including time to chemotherapy, chemotherapy free survival, and time to second disease progression, indicated benefit in the abemaciclib arm. This analysis found no new safety concerns with longer follow‐up. These findings support the positive benefit–risk balance of the MONARCH 2 regimen in East Asian patients with hormone receptor positive, human epidermal growth factor receptor 2‐negative advanced breast cancer.
Evaluating near‐infrared photoimmunotherapy for targeting fibroblast activation protein‐α expressing cells in vitro and in vivo
Authors: Jin Jiefu , Barnett James D. , Krishnamachary Balaji , Mironchik Yelena , Luo Catherine K. , Kobayashi Hisataka , Bhujwalla Zaver M. 
Published: September 2022

AbstractPhotoimmunotherapy (PIT), carried out using an Ab conjugated to the near infrared dye IRDye700DX, is achieving significant success in target‐specific elimination of cells. Fibroblast activation protein alpha (FAP‐α) is an important target in cancer because of its expression by cancer‐associated fibroblasts (CAFs) as well as by some cancer cells. Cancer‐associated fibroblasts that express FAP‐α have protumorigenic and immune suppressive functions. Using immunohistochemistry of human breast cancer tissue microarrays, we identified an increase of FAP‐α+ CAFs in invasive breast cancer tissue compared to adjacent normal tissue. We found FAP‐α expression increased in fibroblasts cocultured with cancer cells. In proof‐of‐principle studies, we engineered human FAP‐α overexpressing MDA‐MB‐231 and HT‐1080 cancer cells and murine FAP‐α overexpressing NIH‐3T3 fibroblasts to evaluate several anti‐FAP‐α Abs and selected AF3715 based on its high binding affinity with both human and mouse FAP‐α. After conjugation of AF3715 with the phthalocyanine dye IR700, the resultant Ab conjugate, FAP‐α‐IR700, was evaluated in cells and tumors for its specificity and effectiveness in eliminating FAP‐α expressing cell populations with PIT. Fibroblast activation protein‐α‐IR700‐PIT resulted in effective FAP‐α‐specific cell killing in the engineered cancer cells and in two patient‐derived CAFs in a dose‐dependent manner. Following an intravenous injection, FAP‐α‐IR700 retention was three‐fold higher than IgG‐IR700 in FAP‐α overexpressing tumors, and two‐fold higher compared to WT tumors. Fibroblast activation protein‐α‐IR700‐PIT resulted in significant growth inhibition of tumors derived from FAP‐α overexpressing human cancer cells. A reduction of endogenous FAP‐α+ murine CAFs was identified at 7 days after FAP‐α‐IR700‐PIT. Fibroblast activation protein‐α‐targeted near infrared PIT presents a promising strategy to eliminate FAP‐α+ CAFs.
High levels of AXL expression in untreated EGFR‐mutated non‐small cell lung cancer negatively impacts the use of osimertinib
Authors: Yoshimura Akihiro , Yamada Tadaaki , Serizawa Masakuni , Uehara Hisanori , Tanimura Keiko , Okuma Yusuke , Fukuda Akito , Watanabe Satoshi , Nishioka Naoya , Takeda Takayuki , Chihara Yusuke , Takemoto Shinnosuke , Harada Taishi , Hiranuma Osamu , Shirai Yukina , Shukuya Takehito , Nishiyama Akihiro , Goto Yasuhiro , Shiotsu Shinsuke , Kunimasa Kei , Morimoto Kenji , Katayama Yuki , Suda Kenichi , Mitsudomi Tetsuya , Yano Seiji , Kenmotsu Hirotsugu , Takahashi Toshiaki , Takayama Koichi 
Published: September 2022

AbstractFor non‐small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, the initial therapeutic interventions will have crucial impacts on their clinical outcomes. Drug tolerant factors reportedly have an impact on EGFR‐tyrosine kinase inhibitor sensitivity. This prospective study investigated the impacts of drug tolerant‐related protein expression in tumors based on the efficacy of osimertinib in the first‐setting of EGFR‐mutated advanced NSCLC patients. A total of 92 patients with EGFR‐mutated advanced or postoperative recurrent NSCLC were analyzed and treated with osimertinib at 14 institutions in Japan. AXL, p53, and programmed death‐ligand 1 (PD‐L1) expression in patient tumors was determined using immunohistochemistry. The AXL signaling pathway was investigated using a cell line‐based assay and AXL‐related gene expression in The Cancer Genome Atlas (TCGA) database. High levels of AXL and positive‐p53 expression were detected in 26.1% and 53.3% of the pretreatment EGFR‐mutated NSCLC tumors, respectively. High AXL expression levels were significantly associated with a shorter progression‐free survival compared with low AXL expression levels, irrespective of the EGFR activating mutation status (p = 0.026). Cell line‐based assays indicated that the overexpression of AXL protein accelerated PD‐L1 expression, which induced insensitivity to osimertinib. In the TCGA database, AXL RNA levels were positively correlated with PD‐L1 expression in the lung adenocarcinoma cohort. The results show that high AXL expression levels in tumors impact clinical predictions when using osimertinib to treat EGFR‐mutated NSCLC patients. Trial Registration: UMIN000043942.
GAN‐C: A generative adversarial network with a classifier for effective event prediction
Authors: Rajita B. S. A. S. , Halani Vrutik , Shah Dhruvil , Panda Subhrakanta 
Published: September 2022

AbstractEvent prediction is essential in social network (SN) analysis to study the SN's evolutionary patterns (communities). Machine learning (ML) models are often used to predict events in SN communities. The ML algorithms manifest the results with biasness for the same dataset. Hence, the performance of an ML model requires validation for the unseen data to avoid biasness in learning. Generally, researchers use the generative adversarial network (GAN) model for generating realistic sample data to enhance the prediction of events. It is challenging for the discriminator to learn features using a single layer with similar weights in a conventional GAN technique. Therefore, this article proposes an improved version of the GAN model named generative adversarial network classifier (GAN‐C). The proposed GAN‐C model contains an additional layer, called classifier, that generates different feature maps. Wherein weights are adjusted dynamically based on the conditions to predict the events. To be precise, conditioning the weights in a classifier layer using entropy values of the features is a simple and effective way to minimize the classifier loss function (categorical cross‐entropy). GAN‐C model results in 16% loss up to 10 batches, and after that, the loss becomes negligible and can generate non‐overlapping events. The gaps between such non‐overlapping events are analyzed using the Jensen–Shannon divergence technique. The experimental results show that the existing single‐GAN and multi‐GAN methods predict events with 79.34% and 82.17% accuracy, respectively. While the proposed GAN‐C comparatively predicts events with improved accuracy of 88.56% on the same dataset. The data generated by the GAN‐C model are also approximately 55.85% and 80.59% more realistic than multi‐GAN and single‐GAN, respectively, based on root mean square error and inception score comparisons. GAN‐C is also approximately 68.01% faster than other GAN models. Thus, this article's theoretical and experimental analysis justifies that GAN‐C works suitably for predicting events in a massive dataset.
Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID‐19 pneumonia: An open‐label randomised trial
Authors: Corral‐Gudino Luis , Cusacovich Ivan , Martín‐González Jose Ignacio , Muela‐Molinero Alberto , Abadía‐Otero Jésica , González‐Fuentes Roberto , Ruíz‐de‐Temiño Ángela , Tapia‐Moral Elena , Cuadrado‐Medina Francisca , Martín‐Asenjo Miguel , Miramontes‐González Pablo , Delgado‐González Jose Luis , Ines Sandra , Abad‐Manteca Laura , Usategui‐Martín Iciar , Ruiz‐Albi Tomás , Miranda‐Riaño Sara , Rodríguez‐Fortúnez Patricia , Rodríguez‐Jiménez Consuelo , López‐Franco Esperanza , Marcos Miguel ,   MP3 pulses COVID‐19 collaborative group
Published: September 2022

AbstractBackgroundThe efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID‐19 has shown mixed outcomes in controlled trials and observational studies. We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID‐19.MethodsA randomised, open‐label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days.ResultsOf the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, −8.8 to 9.1%]; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non‐invasive respiratory or high‐flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, −18.9% [95% CI, −31.8 to ‐ 5.6%]; p = 0.007).ConclusionsAmong severe but not critical patients with COVID‐19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation.
Effect of the presence of predatory cues and hunger on cannibalistic behaviour of ladybird beetle,Menochilus sexmaculatusFabricius (Coleoptera: Coccinellidae)
Authors: Yadav Tripti , Omkar  , Mishra Geetanjali 
Published: September 2022

AbstractCannibalism and its role in population dynamics, along with various factors influencing the rate of cannibalism, have been widely studied across taxa.The effects of predatory cue concentrations and starvation on cannibalistic tendencies and other life‐history traits in cannibalistic and non‐cannibalistic adults ofMenochilus sexmaculatuswere investigated.Egg cannibalism increased with increasing predatory cue concentration and was maximum in high predatory cue treatment; increased with starvation irrespective of their diet history.Latency to cannibalise eggs was shorter for cannibalistic adults as compared to non‐cannibalistic adults irrespective of their hunger status and concentration of conspecific cues.Non‐cannibalistic females have higher fecundity than cannibalistic females.In conclusion, both cannibalistic and non‐cannibalistic individuals respond differently to intrinsic (hunger) and extrinsic cues (predatory cue concentrations). Cannibalistic individuals cannibalise more than non‐cannibalistic ones at low levels of starvation and predatory cues.Our finding suggests that cannibalistic individuals are better at assessing the risk and removing future competitors, which might favour these individuals over non‐cannibalistic ones in adverse conditions and increased competition.
Multiple sclerosis risk variants influence the peripheral B‐cell compartment early in life in the general population
Authors: de Mol Casper L. , van Luijn Marvin M. , Kreft Karim L. , Looman Kirsten I. M. , van Zelm Menno C. , White Tonya , Moll Henriette A. , Smolders Joost , Neuteboom Rinze F. 
Published: September 2022

AbstractBackground and purposeMultiple sclerosis (MS) is associated with abnormal B‐cell function, and MS genetic risk alleles affect multiple genes that are expressed in B cells. However, how these genetic variants impact the B‐cell compartment in early childhood is unclear. In the current study, we aim to assess whether polygenic risk scores (PRSs) for MS are associated with changes in the blood B‐cell compartment in children from the general population.MethodsSix‐year‐old children from the population‐based Generation R Study were included. Genotype data were used to calculate MS‐PRSs and B‐cell subset‐enriched MS‐PRSs, established by designating risk loci based on expression and function. Analyses of variance were performed to examine the effect of MS‐PRSs on total B‐cell numbers (n = 1261) as well as naive and memory subsets (n = 675).ResultsAfter correction for multiple testing, no significant associations were observed between MS‐PRSs and total B‐cell numbers and frequencies of subsets therein. A naive B‐cell‐MS‐PRS (n = 26 variants) was significantly associated with lower relative, but not absolute, naive B‐cell numbers (p = 1.03 × 10−4 and p = 0.82, respectively), and higher frequencies and absolute numbers of CD27+ memory B cells (p = 8.83 × 10−4 and p = 4.89 × 10−3, respectively). These associations remained significant after adjustment for Epstein–Barr virus seropositivity and the HLA‐DRB1*15:01 genotype.ConclusionsThe composition of the blood B‐cell compartment is associated with specific naive B‐cell‐associated MS risk variants during childhood, possibly contributing to MS pathophysiology later in life. Cell subset‐specific PRSs may offer a more sensitive tool to define the impact of genetic risk on the immune system in diseases such as MS.
Youth participation in environmental action in Vietnam: Learning citizenship in liminal spaces
Authors: Beckwith Laura , Smith Matt Baillie , Hensengerth Oliver , Nguyen Hue , Greru Chamithri , Warrington Siobhan , Nguyen Tanh , Smith Graham , Minh Thuy Mai Thi , Nguyen Lan , Woolner Pamela 
Published: September 2022

AbstractYouth participation has become an important element of environmental governance and is also a way that young people learn about the expectations of citizenship. In the global South, young people are confronted with multiple understandings of citizenship as international development organisations may introduce citizenship in a liberal, democratic framing which may differ from national citizenship norms. In Vietnam, state agencies have a history of supporting youth participation linked to nation building and community service. These activities create an imaginary which highlights citizenship as a status and the national scale as being central. More recently, liberalisation policies have opened the door for activities of international organisations which extend imaginaries of citizenship to the global scale and beyond status to a process centred on creating a sense of belonging. Other forms of participation are also flourishing, thanks to the increasing reach of social media. This paper explores how the diversity of this landscape creates liminal spaces of citizenship which young people navigate, working within and between different scales and imaginaries.
Incidence and predictors of sternal surgical wound infection in cardiac surgery: A prospective study
Authors: Arribas‐Leal José María , Rivera‐Caravaca José Miguel , Hernández‐Torres Alicia , Jiménez‐Aceituna Antonio , Moral‐Escudero Encarnación , Pérez‐Andreu Joaquín , García‐Vázquez Elisa , Gutiérrez‐García Francisco , García‐Puente Julio J. , Marín Francisco , Cánovas‐López Sergio J. , Herrero‐Martínez José Antonio 
Published: September 2022

AbstractSternal surgical wound infection (SSWI) in cardiac surgery is associated with increased morbidity. We investigated the incidence of SSWI, the main germs implicated and predictors of SSWI. Prospective study including patients undergoing full median sternotomy between January 2017 and December 2019. Patients were followed‐up for 3 months after hospital discharge. All sternal wound infections up to 90 days after discharge were considered SSWI. 1004 patients were included. During follow‐up, 68 (6.8%) patients presented SSWI. Patients with SSWI had a higher incidence of postoperative renal failure (29.4% vs 17.1%, P = .007), a higher incidence of early postoperative reoperation for non‐infectious causes (42.6% vs 9.1%, P < .001), longer ICU stay (3 [2–9] days vs 2 [2–4] days, P = .006), and longer hospital stay (24.5 [14.8–38.3] days vs 10 [7–18] days, P < .001). Gram‐positive germs were presented in 49% of the cultures, and gram‐negative bacteria in 35%. Early reoperation for non‐infectious causes (OR 4.90, 95% CI 1.03–23.7), and a longer ICU stay (OR 1.37 95% CI 1.10–1.72) were independent predictors of SSWI. SSWI is rare but leads to more postoperative complications. The need for early reoperation because of non‐infectious cause and a longer ICU stay were independently associated with SSWI.