bluuebunny/crossref_metadata_2025_split huggingface dataset:
TransGEM: a molecule generation model based on Transformer with gene expression data
Authors: Liu Yanguang , Yu Hailong , Duan Xinya , Zhang Xiaomin , Cheng Ting , Jiang Feng , Tang Hao , Ruan Yao , Zhang Miao , Zhang Hongyu , Zhang Qingye 
Published: April 2024

Abstract

Motivation
It is difficult to generate new molecules with desirable bioactivity through ligand-based de novo drug design, and receptor-based de novo drug design is constrained by disease target information availability. The combination of artificial intelligence and phenotype-based de novo drug design can generate new bioactive molecules, independent from disease target information. Gene expression profiles can be used to characterize biological phenotypes. The Transformer model can be utilized to capture the associations between gene expression profiles and molecular structures due to its remarkable ability in processing contextual information.

Results
We propose TransGEM (Transformer-based model from gene expression to molecules), which is a phenotype-based de novo drug design model. A specialized gene expression encoder is used to embed gene expression difference values between diseased cell lines and their corresponding normal tissue cells into TransGEM model. The results demonstrate that the TransGEM model can generate molecules with desirable evaluation metrics and property distributions. Case studies illustrate that TransGEM model can generate structurally novel molecules with good binding affinity to disease target proteins. The majority of genes with high attention scores obtained from TransGEM model are associated with the onset of the disease, indicating the potential of these genes as disease targets. Therefore, this study provides a new paradigm for de novo drug design, and it will promote phenotype-based drug discovery.

Availability and implementation
The code is available at https://github.com/hzauzqy/TransGEM.
Peptide set test: a peptide-centric strategy to infer differentially expressed proteins
Authors: Wang Junmin , Novick Steven 
Published: April 2024

Abstract

Motivation
The clinical translation of mass spectrometry-based proteomics has been challenging due to limited statistical power caused by large technical variability and inter-patient heterogeneity. Bottom-up proteomics provides an indirect measurement of proteins through digested peptides. This raises the question whether peptide measurements can be used directly to better distinguish differentially expressed proteins.

Results
We present a novel method called the peptide set test, which detects coordinated changes in the expression of peptides originating from the same protein and compares them to the rest of the peptidome. Applying our method to data from a published spike-in experiment and simulations demonstrates improved sensitivity without compromising precision, compared to aggregation-based approaches. Additionally, applying the peptide set test to compare the tumor proteomes of tamoxifen-sensitive and tamoxifen-resistant breast cancer patients reveals significant alterations in peptide levels of collagen XII, suggesting an association between collagen XII-mediated matrix reassembly and tamoxifen resistance. Our study establishes the peptide set test as a powerful peptide-centric strategy to infer differential expression in proteomics studies.

Availability and implementation
Peptide set test (PepSetTest) is publicly available at https://github.com/JmWangBio/PepSetTest.
wgd v2: a suite of tools to uncover and date ancient polyploidy and whole-genome duplication
Authors: Chen Hengchi , Zwaenepoel Arthur , Van de Peer Yves 
Published: April 2024

Abstract

Motivation
Major improvements in sequencing technologies and genome sequence assembly have led to a huge increase in the number of available genome sequences. In turn, these genome sequences form an invaluable source for evolutionary, ecological, and comparative studies. One kind of analysis that has become routine is the search for traces of ancient polyploidy, particularly for plant genomes, where whole-genome duplication (WGD) is rampant.

Results
Here, we present a major update of a previously developed tool wgd, namely wgd v2, to look for remnants of ancient polyploidy, or WGD. We implemented novel and improved previously developed tools to (a) construct KS age distributions for the whole-paranome (collection of all duplicated genes in a genome), (b) unravel intragenomic and intergenomic collinearity resulting from WGDs, (c) fit mixture models to age distributions of gene duplicates, (d) correct substitution rate variation for phylogenetic placement of WGDs, and (e) date ancient WGDs via phylogenetic dating of WGD-retained gene duplicates. The applicability and feasibility of wgd v2 for the identification and the relative and absolute dating of ancient WGDs is demonstrated using different plant genomes.

Availability and implementation
wgd v2 is open source and available at https://github.com/heche-psb/wgd.
Online Learning and Liminal Spaces: An Example of Innovation in Social Work Field Education
Authors: Saxton Kate , Harris Sera , Clarke Joanne , Barry Jaimie , Said Shannon 
Published: April 2024

Abstract
Amidst the challenges posed by the coronavirus disease 2019 pandemic, universities grappled with adapting to online service delivery, particularly affecting student placements in programmes requiring practicum experiences. Addressing this, four Australian Universities/Colleges collaboratively initiated the Supporting Placement through online Access and Community Engagement (S.P.A.C.E) Project, a twelve-month research endeavour. This study, based on qualitative data from S.P.A.C.E, reveals that the project’s success in delivering quality placement experiences hinged on three key factors: (1) the creation of a liminal (or third) space, (2) a genuine commitment to critical pedagogy and (3) the intentional use of online technology for an authentic learning experience. Significantly, the findings have implications for the field of social work by challenging assumptions about online learning, influencing social work theory through the exploration of a transformative ‘third space’, enhancing practice through critical pedagogy and suggesting policy directions that support flexible and viable online modalities in social work education. This research contributes to a growing body of evidence supporting online learning as a flexible and effective means for authentic and transformational learning experiences.
Left atrial and ventricular deformation: alterations and predictive value of echocardiography parameters in end-stage renal disease patients after kidney transplantation
Authors: Bagheri Abdulhamid , Khani Mohammad , Ghadirzadeh Erfan , Moradi Amir , Bayat Fariba , Salehi Mashhad Sari Seyed Pooria , Paraandavaji Elham , Akbari Tooba , Hermis Alaa Hamza 
Published: April 2024

Abstract

Aims
End-stage renal disease (ESRD) patients are prone to alterations in cardiac haemodynamics specifically on the left ventricle (LV) and left atrial (LA) functions usually due to factors like uraemia, fluid overload, and inflammation. While studies on LV function in ESRD exist, research on LA function is limited. Successful kidney transplant (KTx) is believed to reverse pathological cardiac remodelling, and monitoring changes in cardiac strain before and after transplantation may guide pre- and post-transplant care. This study has two main objectives: to investigate alterations in LA and LV strain and other echocardiographic parameters after KTx and to identify independent factors predicting impaired strain parameters post-KTx.

Methods and results
We conducted a prospective cohort study of 49 ESRD patients who underwent KTx. Echocardiography was performed at baseline and at 3 months after KTx. LV end-diastolic volume, LV end-systolic volume, LV end-diastolic diameter, LV ejection fraction (LVEF), E/e′, maximum LA volume index (LAVi), LV global longitudinal strain (LVGLS), and all LA strain values, including booster (LASb), conduit (LAScd), and reservoir (LASr), improved significantly after KTx (P &lt; 0.05). Regarding independent predictors of impaired LA and LV strains, pre-KTx values of LVEF, LAVi, and NT-proBNP were associated with LVGLS impairment after KTx; pre-KTx values of LAVi and LVEF were associated with LASr impairment after KTx.

Conclusion
The present study provided valuable evidence on the effects of KTx on uraemic cardiomyopathy demonstrated by LA strain and LV strain improvements and indicated pre-KTx LVEF and LAVi as significant independent predictors of LVGLS and LASr impairment after KTx.
Is histological confirmation necessary to avoid futile resections? Comparative of 4 university hospitals
Authors: Aguinagalde Borja , Lizarbe Ion Ander , Rumbero Juan Carlos , Lorenzo Mónica , Sanchez Leire , Sanchez Laura , Fernández-Monge Arantza , Lopez Iker 
Published: April 2024

Abstract

OBJECTIVES
There is no consensus in the literature on preoperative histological analysis for lung cancer. The objective of this study was to assess 4 diagnostic models used in different hospitals with differing practices regarding preoperative histological diagnosis and the consequences in terms of unnecessary surgery and futile major resection.

METHODS
We carried out a retrospective observational study collected from 4 university hospitals in Spain over 3 years (January 2019 to December 2021). We included all patients with a confirmed diagnosis of primary lung cancer and any patients with suspected primary lung cancer who had undergone surgery. All patients underwent computed tomography and positron emission tomography/computed tomography scans. Each multidisciplinary committee was free to choose whether to perform flexible bronchoscopic or transthoracic lung biopsy. Decisions concerning whether to perform intraoperative sample analysis, the surgical approach and the type of resection were left to the surgical team.

RESULTS
We included a total of 1642 patients. The use of flexible endoscopy and its diagnostic performance varied substantially between hospitals (range: 23.8–79.3% and 25–60.7%, respectively); and the same was observed for transthoracic biopsy and its performance (range: 16.9–82.3% and 64.6–97%, respectively). Regarding major resection surgery (lobectomy or more extensive resection), the lowest rate was observed in hospital C (1%) and the highest in hospital B (2.8%), with between-hospital differences not reaching significance (P = 0.173).

CONCLUSIONS
The rate of histological sampling before lung cancer surgery still varies between hospitals. In spite of very diverse multidisciplinary management, the rate of futile lobectomy is not significantly higher in hospitals with lower rates of preoperative histological analysis.
Risk factors influencing postoperative pleural empyema in patients with pleural mesothelioma: a retrospective single-centre analysis
Authors: Henschke Peter , Guglielmetti Laura Chiara , Hillinger Sven , Monsch Gian-Marco , Schneiter Didier , Opitz Isabelle , Lauk Olivia 
Published: April 2024

Abstract

OBJECTIVES
Postoperative empyema is a severe, potentially lethal complication also present, but poorly studied in patients undergoing surgery for pleural mesothelioma. We aimed to analyse which perioperative characteristics might be associated with an increased risk for postoperative empyema.

METHODS
From September 1999 to February 2023 a retrospective analysis of consecutive patients undergoing surgery for pleural mesothelioma at the University Hospital of Zurich was performed. Uni- and multivariable logistic regression was used to identify associated risk factors of postoperative empyema after surgery.

RESULTS
A total of 400 PM patients were included in the analysis, of which n = 50 patients developed empyema after surgery (12.5%). Baseline demographics were comparable between patients with (Eyes) and without empyema (Eno). 39% (n = 156) patients underwent extrapleural pneumonectomy (EPP), of whom 22% (n = 35) developed postoperative pleural empyema; 6% (n = 15) of the remaining 244 patients undergoing pleurectomy and decortication (n = 46), extended pleurectomy and decortication (n = 114), partial pleurectomy (n = 54) or explorative thoracotomy (n = 30) resulted in postoperative empyema. In multivariable logistic regression analysis, EPP (odds ratio 2.8, 95% confidence interval 1.5–5.4, P = 0.002) emerged as the only risk factor associated with postoperative empyema when controlled for smoking status. Median overall survival was significantly worse for Eyes (16 months, interquartile range 5–27 months) than for Eno (18 months, interquartile range 8–35 months).

CONCLUSIONS
Patients undergoing EPP had a significantly higher risk of developing postoperative pleural empyema compared to patients undergoing other surgery types. Survival of patients with empyema was significantly shorter.
Identification and chemical structure elucidation of synthetic cannabinoids samples seized in Kuwait during 2019-2023 using GC-MS and NMR spectroscopy
Authors: Al-Matrouk Abdullah , Orabi Khaled Y 
Published: April 2024

Abstract
Cannabinoids, a class of chemical compounds, interact with cannabinoid receptors and are categorized into endocannabinoids, phytocannabinoids, and synthetic cannabinoids based on their origin. Among these, synthetic cannabinoids constitute the largest and most structurally diverse group of novel psychoactive substances, with around 280 compounds identified globally. They exhibit a high binding affinity to cannabinoid receptors CB1 and CB2, which are distributed throughout the central nervous and immune systems, leading to more potent psychoactive and toxic effects compared to their natural counterparts. Various adverse effects associated with synthetic cannabinoids include hypothermia, analgesia, catalepsy, psychosis, respiratory depression, cardiac arrest, nephrotoxicity, acute cerebral ischemia, seizures, and mortality. In a previous study, we reported the detection of several novel psychoactive substances in Kuwait using GC-MS and LC-MS/MS techniques. However, the identification was tentative, highlighting a limitation of these methods. To address this, the current study aimed to fully identify seventeen seized synthetic cannabinoid samples. Thin-layer chromatography was initially employed to assess the purity of the samples. Twelve pure samples (AKM-1 – AKM-12) underwent NMR analyses, including 1H, 13C, DEPT 45°, 90°, 135°, COSY, HSQC, and HMBC experiments. The identities of five samples (AKM-1, 5, 6, 8, 10) were confirmed as MDMB-4en-PINACA, one sample (AKM-2) as 4F-MDMB-BUTICA, one sample (AKM-3) as MPHP-2201, and three samples (AKM-4, 9, 11) as MMB-022. Additionally, two samples (AKM-7, 12) were identified as FUB-144. This comprehensive approach enhances the accuracy of synthetic cannabinoids identification compared to previous studies, emphasizing the importance of employing NMR alongside other spectral methods for a more robust analysis.
Allylboranes and boron enolates
Authors: Thomas Susan E. 
Published: April 2024

Abstract
This chapter considers allylboranes in organic synthesis. Focusing on the stability of allylboranes, the chapter displays how allyldialkylboranes can be used in further reactions if either they are prepared and used directly at low temperature, or the predominant isomer at equilibrium is the required isomer. The chapter also discusses the reaction of allylboranes with carbonyl compounds. It examines how triallylboranes react with aldehydes and ketones to give, on hydrolysis, homoallylic alcohols. The chapter then investigates the synthesis of homochiral homoallylic alcohols containing one chiral centre, and the synthesis of homoallylic alcohols containing two chiral centres. It ends with a discussion of boron enolates in organic synthesis.
12 Monitoring Monocyte Anisocytosis Changes as a Burn Injury Recovery Marker: Insights from a Clinical Study
Authors: Nazemidashtarjandi Saeed , Supple Matthew D , Boribong Brittany , Rosado Nikki , Karabacak Nezihi Murat , Yonker Lael , Yarmush Martin , Goverman Jeremy , Irimia Daniel 
Published: April 2024

Abstract

Introduction
Severe burn injuries trigger pathological immune responses. However, our ability to monitor these evolving responses is constrained by the intricate confluence of cellular, biochemical, and metabolic alterations that occur concurrently post-injury. Here, we focus on monocytes as integrators of the changes triggered by the burn injury and potential biomarkers for the immune responses after injury.

Methods
We enrolled patients with major burn injuries (15% or more) and collected blood samples twice a week for the duration of the hospital stay. We measured Monocyte Distribution Width (MDW) using a hematology analyzer. We assessed the association between MDW (an FDA-cleared biomarker for sepsis) and pro-inflammatory cytokines levels released in the serum of burn patients. As a reference, we measured the MDW changes in the presence of pro-inflammatory stimuli, e.g., lipopolysaccharide (LPS), as well as lipid mediators of inflammation resolution, e.g., prostaglandin E2 (PGE2), resolvin D1 (RvD1), and resolvin D2 (RvD2).

Results
We enrolled N = 10 patients with major burn injuries, from which we collected and analyzed N = 78 blood samples. We found that the MDW increases during the first week after a major burn injury (MDW = 24.1) above the threshold of healthy individuals of comparable age (MDW = 20.0) and decreases slowly at discharge. In non-surviving patients, MDW increased for ~10 days post-burn injury (MDW=28.7) and remained high until death. We found the strongest correlations between the MDW values and IL-18 cytokine levels in plasma (Two-tailed Student test, P=0.0095, positive Spearman r coefficient=0.9009).
In blood samples from healthy donors, we found that MDW increased upon LPS stimulation (104 EU/mL, MDW= 31.8), at the higher end of values measured in patients. The addition of RvD2 (5 µM) after LPS stimulation decreased MDW significantly (MDW = 20.1, One-way ANOVA, LPS vs. RvD2 +LPS, P = 0.0002), towards values measured in healthy donors.

Conclusions
In patients with major burns, changes in MDW could serve as a biomarker to track inflammation and its resolution throughout the hospitalization. The ability of RvD2 to decrease MDW is novel and deserves further investigation.

Applicability of Research to Practice
MDW values can be useful for monitoring hospitalized burn patients.
21 Untargeted Metabolomics Analysis: A Candidate Biomarker and Prognostic Tool in Burn Injury
Authors: Misganaw Burook , Pinto Desiree , Le Tuan D , Pusateri Anthony , Gautam Arti , Moffatt Lauren T , Shupp Jeffrey W , Hammamieh Rasha 
Published: April 2024

Abstract

Introduction
Untargeted metabolomics, an analysis of the molecular layer comprising many smaller molecular weight biomolecules, has emerged as a tool to diagnose and predict outcomes early in disease courses. Existing studies of metabolic changes following burn injury focus on select targeted metabolites using animal models. This study aims to identify metabolic signatures associated with burn severity and clinical outcomes using untargeted metabolomics analysis in patients.

Methods
Burn patients admitted to a regional center over the span of 4 years were prospectively enrolled in this study. Patient demographics, burn injury characteristics, and blood samples were collected at set timepoints from admission until 4 weeks. Mass spectrometry (MS)-based method was used to measure untargeted metabolomics. Comparison of the MS-based measurements of select metabolites with alternate standard clinical assaying was performed to ensure concordance and reliability. A linear regression model was then used to identify metabolites associated with bun severity (TBSA &lt; 20% and ≥ 20%). Age, gender, BMI, presence of inhalation injury, administration of propofol and supplemental nutrition were added as covariates to control for confounding effects.

Results
Complete metabolome datasets were collected for 58 patients from a total of 115 patients reviewed. The sample had a median TBSA of 18.3%, median age of 38.5 and 27.6% had concomitant inhalation injury. A total of 925 metabolites, including 335 lipids, 183 amino acids, 146 xenobiotics, 24 carbohydrates, and 23 peptides were analyzed. MS-based measurements compared with alternate standard clinical assaying resulted in a high level of concordance (R ~ 0.8). The first two principal components (account for 22% of total variance) show the main drivers of global metabolomics variation are time since admission and severity of injury. At admission, a significant elevation of xenobiotics, amino acids, nucleotide, and lipids related metabolites was observed among severely burned patients (TBSA ≥ 20%). Longitudinal analysis reveal that xenobiotic related metabolites are significantly elevated at admission but are depleted overtime. An abundance of select metabolites at admission showed an excellent ability to predict 30-day mortality (AUROC ~ 90%).

Conclusions
Patterns of metabolic alterations were associated with severe burn injury (TBSA ≥ 20%). Distinct classes of metabolic profiles change in a time dependent manner. Therefore, metabolic profiling has the potential to be used as early indicators of disease severity and progression.

Applicability of Research to Practice
Identifying and utilizing early indicators of disease severity and outcomes before the onset of clinical signs is crucial for burn patients. Metabolomic changes is a prime candidate for the development of these prognostic and biomarker panels.