bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient determination of the Hamiltonian and electronic properties using graph neural network with complete local coordinates
Authors: Su Mao , Yang Ji-Hui , Xiang Hong-Jun , Gong Xin-Gao
Published: April 2023

Despite the successes of machine learning methods in physical sciences, the prediction of the Hamiltonian, and thus the electronic properties, is still unsatisfactory. Based on graph neural network (NN) architecture, we present an extendable NN model to determine the Hamiltonian from ab initio data, with only local atomic structures as inputs. The rotational equivariance of the Hamiltonian is achieved by our complete local coordinates (LCs). The LC information, encoded using a convolutional NN and designed to preserve Hermitian symmetry, is used to map hopping parameters onto local structures. We demonstrate the performance of our model using graphene and SiGe random alloys as examples. We show that our NN model, although trained using small-size systems, can predict the Hamiltonian, as well as electronic properties such as band structures and densities of states for large-size systems within the ab initio accuracy, justifying its extensibility. In combination with the high efficiency of our model, which takes only seconds to get the Hamiltonian of a 1728-atom system, the present work provides a general framework to predict electronic properties efficiently and accurately, which provides new insights into computational physics and will accelerate the research for large-scale materials.
The Birch and Swinnerton-Dyer Conjecture: A brief survey
Authors: Burungale Ashay , Skinner Christopher , Tian Ye
Published: April 2023

The celebrated Birch and Swinnerton-Dyer (BSD) conjecture connects the structure of the rational points on an elliptic curve defined over the rationals to the analytic properties of its associated Hasse–Weil

L
L

-function. In this paper we recall the BSD conjecture (and its various parts) and survey some of the known results towards it, especially recent work.
ClusterX: a novel representation learning-based deep clustering framework for accurate visual inspection in virtual screening
Authors: Chen Sikang , Gao Jian , Chen Jiexuan , Xie Yufeng , Shen Zheyuan , Xu Lei , Che Jinxin , Wu Jian , Dong Xiaowu
Published: April 2023

Molecular clustering analysis has been developed to facilitate visual inspection in the process of structure-based virtual screening. However, traditional methods based on molecular fingerprints or molecular descriptors limit the accuracy of selecting active hit compounds, which may be attributed to the lack of representations of receptor structural and protein–ligand interaction during the clustering. Here, a novel deep clustering framework named ClusterX is proposed to learn molecular representations of protein–ligand complexes and cluster the ligands. In ClusterX, the graph was used to represent the protein–ligand complex, and the joint optimisation can be used efficiently for learning the cluster-friendly features. Experiments on the KLIFs database show that the model can distinguish well between the binding modes of different kinase inhibitors. To validate the effectiveness of the model, the clustering results on the virtual screening dataset further demonstrated that ClusterX achieved better or more competitive performance against traditional methods, such as SIFt and extended connectivity fingerprints. This framework may provide a unique tool for clustering analysis and prove to assist computational medicinal chemists in visual decision-making.
Modular response analysis reformulated as a multilinear regression problem
Authors: Borg Jean-Pierre , Colinge Jacques , Ravel Patrice
Published: April 2023

Motivation

Modular response analysis (MRA) is a well-established method to infer biological networks from perturbation data. Classically, MRA requires the solution of a linear system, and results are sensitive to noise in the data and perturbation intensities. Due to noise propagation, applications to networks of 10 nodes or more are difficult.

Results

We propose a new formulation of MRA as a multilinear regression problem. This enables to integrate all the replicates and potential additional perturbations in a larger, over-determined, and more stable system of equations. More relevant confidence intervals on network parameters can be obtained, and we show competitive performance for networks of size up to 1000. Prior knowledge integration in the form of known null edges further improves these results.

Availability and implementation

The R code used to obtain the presented results is available from GitHub: https://github.com/J-P-Borg/BioInformatics
MARSY: a multitask deep-learning framework for prediction of drug combination synergy scores
Authors: El Khili Mohamed Reda , Memon Safyan Aman , Emad Amin
Published: April 2023

Motivation

Combination therapies have emerged as a treatment strategy for cancers to reduce the probability of drug resistance and to improve outcomes. Large databases curating the results of many drug screening studies on preclinical cancer cell lines have been developed, capturing the synergistic and antagonistic effects of combination of drugs in different cell lines. However, due to the high cost of drug screening experiments and the sheer size of possible drug combinations, these databases are quite sparse. This necessitates the development of transductive computational models to accurately impute these missing values.

Results

Here, we developed MARSY, a deep-learning multitask model that incorporates information on the gene expression profile of cancer cell lines, as well as the differential expression signature induced by each drug to predict drug-pair synergy scores. By utilizing two encoders to capture the interplay between the drug pairs, as well as the drug pairs and cell lines, and by adding auxiliary tasks in the predictor, MARSY learns latent embeddings that improve the prediction performance compared to state-of-the-art and traditional machine-learning models. Using MARSY, we then predicted the synergy scores of 133 722 new drug-pair cell line combinations, which we have made available to the community as part of this study. Moreover, we validated various insights obtained from these novel predictions using independent studies, confirming the ability of MARSY in making accurate novel predictions.

Availability and implementation

An implementation of the algorithms in Python and cleaned input datasets are provided in https://github.com/Emad-COMBINE-lab/MARSY.
SpliceAI-10k calculator for the prediction of pseudoexonization, intron retention, and exon deletion
Authors: Canson Daffodil M , Davidson Aimee L , de la Hoya Miguel , Parsons Michael T , Glubb Dylan M , Kondrashova Olga , Spurdle Amanda B
Published: April 2023

SpliceAI is a widely used splicing prediction tool and its most common application relies on the maximum delta score to assign variant impact on splicing. We developed the SpliceAI-10k calculator (SAI-10k-calc) to extend use of this tool to predict: the splicing aberration type including pseudoexonization, intron retention, partial exon deletion, and (multi)exon skipping using a 10 kb analysis window; the size of inserted or deleted sequence; the effect on reading frame; and the altered amino acid sequence. SAI-10k-calc has 95% sensitivity and 96% specificity for predicting variants that impact splicing, computed from a control dataset of 1212 single-nucleotide variants (SNVs) with curated splicing assay results. Notably, it has high performance (≥84% accuracy) for predicting pseudoexon and partial intron retention. The automated amino acid sequence prediction allows for efficient identification of variants that are expected to result in mRNA nonsense-mediated decay or translation of truncated proteins.

Availability and implementation

SAI-10k-calc is implemented in R (https://github.com/adavi4/SAI-10k-calc) and also available as a Microsoft Excel spreadsheet. Users can adjust the default thresholds to suit their target performance values.
Polyethylene glycol-coated haemostatic patch for prevention of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy: randomized clinical trial
Authors: Serradilla-Martín Mario , Paterna-López Sandra , Palomares-Cano Ana , Cantalejo-Díaz Miguel , Abadía-Forcén Teresa , Gutiérrez-Díez Marta L , Artigas-Marco Consuelo , Serrablo-Requejo Alejandro
Published: April 2023

Background

The potential of haemostatic patches to reduce the rate of postoperative pancreatic fistula remains unclear. The aim of this trial was to evaluate the impact of a polyethylene glycol-coated haemostatic patch on the incidence of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy.

Methods

In this randomized, single-centre, clinical trial, patients undergoing pancreatoduodenectomy were randomized 1 : 1 to receive pancreatojejunostomy reinforced with two polyethylene glycol-coated haemostatic patches (patch group) or without any reinforcement (control group). The primary outcome was clinically relevant postoperative pancreatic fistula, defined as grade B/C according to International Study Group of Pancreatic Surgery criteria, within 90 days. Key secondary outcomes were length of hospital stay, total rate of postoperative pancreatic fistula, and overall complication rate.

Results

From 15 May 2018 to 22 June 2020, 72 patients were randomized, and 64 were included in the analyses (31 in the patch group and 33 in the control group). The risk of clinically relevant postoperative pancreatic fistula was reduced by 90 per cent (OR 0.10, 95 per cent c.i. 0.01 to 0.89, P = 0.039). Moreover, the use of the polyethylene glycol-coated patch retained its protective effect on clinically relevant postoperative pancreatic fistula in a multivariable regression model, significantly reducing the risk of clinically relevant postoperative pancreatic fistula by 93 per cent (OR 0.07, 95 per cent c.i. 0.01 to 0.67, P = 0.021), regardless of patient age, sex, or fistula risk score. The incidence of secondary outcomes did not significantly differ between the groups. One patient died within 90 days in the patch group versus three patients in the control group.

Conclusions

A polyethylene glycol-coated haemostatic patch reduced the incidence of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy.

Registration number

NCT03419676 (http://www.clinicaltrials.gov).
Altered nucleus accumbens functional connectivity precedes apathy in Parkinson’s disease
Authors: Morris Lee-Anne , Harrison Samuel J , Melzer Tracy R , Dalrymple-Alford John C , Anderson Tim J , MacAskill Michael R , Le Heron Campbell J
Published: April 2023

Work in animal and human neuroscience has identified neural regions forming a network involved in the production of motivated, goal-directed behaviour. In particular, the nucleus accumbens and anterior cingulate cortex are recognized as key network nodes underlying decisions of whether to exert effort for reward, to drive behaviour. Previous work has convincingly shown that this cognitive mechanism, known as effort-based decision making, is altered in people with Parkinson’s disease with a syndrome of reduced goal-directed behaviour—apathy. Building on this work, we investigated whether the neural regions implementing effort-based decision-making were associated with apathy in Parkinson’s disease, and more importantly, whether changes to these regions were evident prior to apathy development.

We performed a large, multimodal neuroimaging analysis in a cohort of people with Parkinson’s disease (n = 199) with and without apathy at baseline. All participants had ∼2-year follow-up apathy scores, enabling examination of brain structure and function specifically in those with normal motivation who converted to apathy by ∼2-year follow-up. In addition, of the people with normal motivation, a subset (n = 56) had follow-up neuroimaging data, allowing for examination of the ‘rate of change’ in key nodes over time in those who did, and did not, convert to apathy. Healthy control (n = 54) data were also included to aid interpretation of findings.

Functional connectivity between the nucleus accumbens and dorsal anterior cingulate cortex was higher in people with normal motivation who later converted to apathy compared to those who did not, whereas no structural differences were evident between these groups. In contrast, grey matter volume in these regions was reduced in the group with existing apathy. Furthermore, of those with normal motivation who had undergone longitudinal neuroimaging, converters to apathy showed a higher rate of change in grey matter volume within the nucleus accumbens.

Overall, we show that changes in functional connectivity between nucleus accumbens and anterior cingulate cortex precedes apathy in people with Parkinson’s disease, with conversion to apathy associated with higher rate of grey matter volume loss in nucleus accumbens, despite no baseline differences. These findings significantly add to an accumulating body of transdiagnostic evidence that apathy arises from disruption to key nodes within a network in which normal goal-directed behaviour is instantiated, and raise the possibility of identifying those at risk for developing apathy before overt motivational deficits have arisen.
The U-shaped curve predicting cognitive vulnerability to delirium severity
Authors: Lennertz Richard C , Sanders Robert D
Published: April 2023

This scientific commentary refers to ‘Extremes of baseline cognitive function determine the severity of delirium: a population study’ by Tsui et al. (https://doi.org/10.1093/brain/awad062).
Lowering levels of reelin in entorhinal cortex layer II-neurons results in lowered levels of intracellular amyloid-β
Authors: Kobro-Flatmoen Asgeir , Battistin Claudia , Nair Rajeevkumar Raveendran , Bjorkli Christiana , Skender Belma , Kentros Cliff , Gouras Gunnar , Witter Menno P
Published: April 2023

Projection neurons in the anteriolateral part of entorhinal cortex layer II are the predominant cortical site for hyper-phosphorylation of tau and formation of neurofibrillary tangles in prodromal Alzheimer’s disease. A majority of layer II projection neurons in anteriolateral entorhinal cortex are unique among cortical excitatory neurons by expressing the protein reelin. In prodromal Alzheimer’s disease, these reelin-expressing neurons are prone to accumulate intracellular amyloid-β, which is mimicked in a rat model that replicates the spatio-temporal cascade of the disease. Two important findings in relation to this are that reelin-signalling downregulates tau phosphorylation, and that oligomeric amyloid-β interferes with reelin-signalling. Taking advantage of this rat model, we used proximity ligation assay to assess whether reelin and intracellular amyloid-β directly interact during early, pre-plaque stages in anteriolateral entorhinal cortex layer II reelin-expressing neurons. We next made a viral vector delivering micro-RNA against reelin, along with a control vector, and infected reelin-expressing anteriolateral entorhinal cortex layer II-neurons to test whether reelin levels affect levels of intracellular amyloid-β and/or amyloid precursor protein. We analysed 25.548 neurons from 24 animals, which results in three important findings. First, in reelin-expressing anteriolateral entorhinal cortex layer II-neurons, reelin and intracellular amyloid-β engage in a direct protein–protein interaction. Second, injecting micro-RNA against reelin lowers reelin levels in these neurons, amounting to an effect size of 1.3–4.5 (Bayesian estimation of Cohen’s d effect size, 95% credible interval). This causes a concomitant reduction of intracellular amyloid-β ranging across three levels of aggregation, including a reduction of Aβ42 monomers/dimers amounting to an effect size of 0.5–3.1, a reduction of Aβ prefibrils amounting to an effect size of 1.1–3.5 and a reduction of protofibrils amounting to an effect size of 0.05–2.1. Analysing these data using Bayesian estimation of mutual information furthermore reveals that levels of amyloid-β are dependent on levels of reelin. Third, the reduction of intracellular amyloid-β occurs without any substantial associated changes in levels of amyloid precursor protein. We conclude that reelin and amyloid-β directly interact at the intracellular level in the uniquely reelin-expressing projection neurons in anteriolateral entorhinal cortex layer II, where levels of amyloid-β are dependent on levels of reelin. Since amyloid-β is known to impair reelin-signalling causing upregulated phosphorylation of tau, our findings are likely relevant to the vulnerability for neurofibrillary tangle-formation of this entorhinal neuronal population.
Targeted Mass Azithromycin Distribution for Trachoma: A Community-Randomized Trial (TANA II)
Authors: Mahmud Hamidah , Haile Berhan A , Tadesse Zerihun , Gebresillasie Sintayehu , Shiferaw Ayalew , Zerihun Mulat , Liu Zijun , Callahan E Kelly , Cotter Sun Y , Varnado Nicole E , Oldenburg Catherine E , Porco Travis C , Lietman Thomas M , Keenan Jeremy D
Published: April 2023

Background

Current guidelines recommend annual community-wide mass administration of azithromycin for trachoma. Targeting treatments to those most likely to be infected could reduce the amount of unnecessary antibiotics distributed.

Methods

In a cluster-randomized trial conducted from 1 November 2010 through 8 November 2013, 48 Ethiopian communities previously treated with annual mass azithromycin distributions for trachoma were randomized in equal numbers to (1) annual azithromycin distributions targeted to children aged 0–5 years, (2) annual azithromycin distributions targeted to households with a child aged 0–5 years found to have clinically active trachoma, (3) continued annual mass azithromycin distributions to the entire community, or (4) cessation of treatment. The primary outcome was the community prevalence of ocular chlamydia infection among children aged 0–9 years at month 36. Laboratory personnel were masked to treatment allocation.

Results

The prevalence of ocular chlamydia infection among children aged 0–9 years increased from 4.3% (95% confidence interval [CI], .9%–8.6%) at baseline to 8.7% (95% CI, 4.2%–13.9%) at month 36 in the age-targeted arm, and from 2.8% (95% CI, .8%–5.3%) at baseline to 6.3% (95% CI, 2.9%–10.6%) at month 36 in the household-targeted arm. After adjusting for baseline chlamydia prevalence, the 36-month prevalence of ocular chlamydia was 2.4 percentage points greater in the age-targeted group (95% CI, −4.8% to 9.6%; P = .50; prespecified primary analysis). No adverse events were reported.

Conclusions

Targeting azithromycin treatment to preschool children was no different than targeting azithromycin to households with a child with clinically active trachoma. Neither approach reduced ocular chlamydia over the 3-year study.

Clinical Trials Registration

NCT01202331.
Intravascular ultrasound-guided dissection recanalization in a patient with ST-segment elevation myocardial infarction: a case report
Authors: Sangen Hideto , Wakita Masaki , Toguchi Riku , Tanaka Kunio
Published: April 2023

Background

In primary percutaneous coronary intervention (PCI) for acute myocardial infarction, we occasionally experience challenging cases where conventional guidewires cannot pass through the lesion. In such cases, if the use of a tapered guidewire or polymer jacket guidewire is also unsuccessful, coronary artery bypass surgery becomes inevitable. Therefore, other methods to enable revascularization in a reliable and timely manner are desirable.

Case summary

We present the first case of intravenous ultrasound (IVUS)-guided tip detection (TD)-antegrade dissection re-entry (ADR) in a 73-year-old man who suffered ST-segment elevation myocardial infarction (STEMI). The patient had a total thrombotic occlusion of the right coronary artery and stenotic lesion of the left anterior descending artery. Primary PCI was unsuccessful and IVUS-guided rewiring using a chronic total occlusion (CTO) wire failed due to thrombus attenuation. However, IVUS imaging revealed the presence of intimal and subintimal space, which led us to perform IVUS-guided TD-ADR using Conquest Pro 12 ST (Asahi Intecc). Using the TD method, we were successful in swiftly puncturing the true lumen wall, and a stent was implanted following successful re-entry. Final angiography showed the establishment of Thrombolysis in Myocardial Infraction-3 flow and resolution of ST-segment elevation.

Discussion

IVUS-guided TD enables accurate puncture in an ADR procedure, enabling successful recanalization in a relatively short time. Thus, IVUS-guided TD-ADR is a reliable option for revascularization in STEMI cases wherein the guidewire fails to pass the occlusion using conventional techniques.
Primary cardiac lymphoma: a case report
Authors: Ellen Saghie , Emma Higgisson
Published: April 2023

Background

Primary cardiac lymphoma is an extremely rare malignancy involving the heart and pericardium. It is a disease that most commonly effects the right atrium and right ventricle. Left untreated it carries a very poor prognosis. Recent advancements in therapy including early recognition and initiation of chemotherapy has led to improved survival.

Case summary

A 78 year old female presented with weight loss, abdominal pain and distension. An ultrasound abdomen pre admission showed abdominal ascites. An echocardiogram performed during admission showed a large pericardial effusion with asymmetrical increase in left ventricular wall thickness and a new left atrial mass. Pericardial fluid analysis led to the diagnosis of diffuse large B cell non-Hodgkin's lymphoma. Positron Emission Tomography CT (PET-CT) shows avid fluorodeoxyglucose (FDG) uptake in cardiac muscle. Prompt treatment was initiated with a chemotherapy regimen involving Rituximab, Cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). An echocardiogram 3 months post initiation of treatment showed resolution of the pericardial effusion and left atrial mass as well as an improvement in left ventricular wall thickness. A PET-CT following completion of treatment showed complete metabolic response.

Discussion

The diagnosis of primary cardiac lymphoma is uncommon and the presence of left rather than right heart involvement is rarer still. Multimodality imaging is key in diagnosis. Early recognition and treatment is vital in improving associated morbidity and mortality.
Genetic variant in the BRAF gene compatible with Noonan spectrum disorders in an adult Fontan patient with refractory protein losing enteropathy: a follow-up report
Authors: Nederend Marieke , Stoger J Lauran , Egorova Anastasia D , Barge-Schaapveld Daniela Q C M , Jongbloed Monique R M
Published: April 2023

Background

Patients with a univentricular heart form a morphological heterogenous group of patients at the most severe end of the congenital heart disease (CHD) spectrum. Over the past decades, more awareness and knowledge has been raised on the genetic contributions to CHD. To date, only a limited number of genes have been identified in the hypoplastic heart, mainly in left-sided hypoplasia. There is still much more to be elucidated in this field.

Case summary

Here, we present a follow-up report of a case of an adult patient after Fontan palliation, born with a.o. tricuspid atresia with hypoplastic right ventricle and pulmonary stenosis. This patient encountered a myriad of late sequalae involving multiple organ systems during the course of his young adult life, including refractory protein losing enteropathy (PLE). Concomitant extracardiac anomalies, in addition to the complex CHD and its complications, prompted for genetic evaluation. Whole exome sequencing showed a variant of uncertain significance in the BRAF gene [NM_004333.4:c.1897T > C p.(Tyr633His)], associated with Noonan spectrum disorders, that is also infamous for lymphoedema and PLE. The variant regards an evolutionarily highly conserved amino acid and is assumed pathogenic according to all prediction programmes. The mutation was most likely de novo.

Discussion

Genetic screening can provide new insights in the complex and varied phenotype of the (adult) Fontan patient and in the myriad of complications encountered. Adult CHD cardiologists should be aware of genetic syndromes underlying a CHD, concomitant extracardiac anomalies, and a complex clinical course with a broad spectrum of late sequelae.
Precision Medicine in Pancreatitis: The Future of Acute Pancreatitis Care
Authors: Garami Andras , Hegyi Peter
Published: April 2023

Acute pancreatitis (AP) continues to present a substantial burden to patients and healthcare personnel. Despite its occasionally severe progression and high mortality rate, there is no specific therapy that could be routinely applied in patients with AP. Here, we review treatment possibilities in AP, describe how the treatment approaches have changed in pancreatic cancer as an analogy, and point out potential causes for the failure of clinical trials on AP. We highlight that instead of attempting to discover generalized treatment options that could be used in any AP patient, it is time for a paradigm shift in the treatment of AP, which would help to focus more on individual patients or specific patient subpopulations when designing clinical trials and therapeutic approaches (similarly as in pancreatic cancer). Since the recruitment of specific patient subpopulations with AP could take excessive time if clinical centers work separately, the development of precision medicine in AP would require to establish an expert committee, eg, Pancreatitis Precision Medicine Interest Group, which could organize and coordinate the activities of the joined centers. With the joined forces of expert clinicians and leading centers, a new era could start in the treatment of AP, in which personalized treatment options could be discovered and introduced to efficiently reduce the burden of the disease on patients and healthcare workers.
The sweet side of sex as a biological variable
Authors: Hunter Carmanah D , Morris Kaylee M , Derksen Tahlia , Willis Lisa M
Published: April 2023

Glycobiology as a field holds enormous potential for understanding human health and disease. However, few glycobiology studies adequately address the issue of sex differences in biology, which severely limits the conclusions that can be drawn. Numerous CAZymes, lectins, and other carbohydrate-associated molecules have the potential to be differentially expressed and regulated with sex, leading to differences in O-GlcNAc, N-glycan branching, fucosylation, sialylation, and proteoglycan structure, among others. Expression of proteins involved in glycosylation is influenced through hormones, miRNA, and gene dosage effects. In this review, we discuss the benefits of incorporating sex-based analysis in glycobiology research and the potential drivers of sex differences. We highlight examples of where incorporation of sex-based analysis has led to insights into glycobiology. Finally, we offer suggestions for how to proceed moving forward, even if the experiments are already complete. Properly incorporating sex based analyses into projects will substantially improve the accuracy and reproducibility of studies as well as accelerate the rate of discovery in the glycosciences.
Fertility preservation in women with benign gynaecological conditions
Authors: Santulli Pietro , Blockeel Christophe , Bourdon Mathilde , Coticchio Giovanni , Campbell Alison , De Vos Michel , Macklon Kirsten Tryde , Pinborg Anja , Garcia-Velasco Juan A
Published: April 2023

Although a wealth of data has been published regarding fertility preservation (FP) in women with malignant diseases who receive gonadotoxic treatment, the role of FP in non-malignant conditions has been studied to a much lesser extent. These include benign haematological, autoimmune, and genetic disorders, as well as a multitude of benign gynaecological conditions (BGCs) that may compromise ovarian reserve and/or reproductive potential due to pathogenic mechanisms or as a result of medical or surgical treatments. Alongside accumulating data that document the reproductive potential of cryopreserved oocytes and ovarian tissue, there is potential interest in FP for women with BGCs at risk of infertility; however, there are currently insufficient data about FP in women with BGCs to develop guidelines for clinical practice. The purpose of this article is to appraise the available evidence regarding FP for BGC and discuss potential strategies for FP based on estimated ovarian impairment and on short-term and long-term reproductive goals of patients. Cost-effectiveness considerations and patients’ perspectives will also be discussed.
Can Increasing Awareness of Gender Gaps in International Relations Help Close Them? Evidence from a Scholar Ranking Experiment
Authors: Jackson Emily B , Maliniak Daniel , Parajon Eric , Peterson Susan , Powers Ryan , Tierney Michael J
Published: April 2023

We report the results of a survey of international relations (IR) scholars on the use of an increasingly common policy designed to close recognition gaps in IR: gender balance in citation (GBC) statements. GBC statements remind and encourage authors submitting work to peer-reviewed outlets to consider the gender balance among the works they cite. We find that these policies enjoyed wide support among IR scholars in our sample countries soon after journals began instituting the policies, but women were more supportive than men of the policies. We also report the results of a question-order experiment that allows us to study how raising awareness of gender gaps in the IR discipline affects the proportion of women that scholars list among the most influential IR scholars in the last 20 years. The effects of exposure to the gender treatment vary, however, by respondents’ gender and whether respondents teach in the United States. The treatment effects were much larger for women than for men in the United States, but the reverse was true outside the United States.
T2Candida assay: diagnostic performance and impact on antifungal prescribing
Authors: Patrocínio de Jesus Rita , Houston Hamish , Schutte Annemiek H J , Morris-Jones Stephen , Stone Neil , Gorton Rebecca , Pollara Gabriele
Published: April 2023

Objectives

To assess the performance of T2Candida for the diagnosis of invasive candidiasis (IC) against gold standards of candidaemia or consensus IC definitions, and to evaluate the impact of T2Candida on antifungal drug prescribing.

Methods

A retrospective review was undertaken of all T2Candida (T2MR technology, T2 Biosystems) performed from October 2020 to February 2022. T2Candida performance was evaluated against confirmed candidaemia or against proven/probable IC within 48 hours of T2Candida, and its impact on antifungal drug prescriptions.

Results

T2Candida was performed in 61 patients, with 6 (9.8%) positive results. Diagnostic performance of T2Candida against candidaemia had a specificity of 85.7% and negative predictive value (NPV) of 96.8%. When comparing T2Candida results with consensus definitions of IC, the specificity and NPV of T2Candida was respectively 90% (54/60) and 98.2% (54/55) for proven IC, and 91.4% (53/58) and 96.4% (53/55) for proven/probable IC. Antifungals were initiated in three of six patients (50%) with a positive T2Candida result. Thirty-three patients were receiving empirical antifungals at the time of T2Candida testing, and a negative result prompted cessation of antifungals in 11 (33%) patients, compared with 6 (25%) antifungal prescriptions stopped following negative beta-d-glucan (BDG) testing in a control population (n = 24).

Conclusions

T2Candida shows high specificity and NPV compared with evidence of Candida bloodstream infection or consensus definitions for invasive Candida infection, and may play an adjunctive role as a stewardship tool to limit unnecessary antifungal prescriptions.
Association between piperacillin/tazobactam MIC and survival among hospitalized patients with Enterobacterales infections: retrospective cohort analysis of electronic health records from 161 US hospitals
Authors: Strich Jeffrey R , Lawandi Alexander , Warner Sarah , Demirkale Cumhur Y , Sarzynski Sadia , Babiker Ahmed , Dekker John P , Kadri Sameer S
Published: April 2023

Introduction

A recent randomized trial has suggested an increased risk of mortality for ceftriaxone-non-susceptible Enterobacterales infections treated with piperacillin/tazobactam compared with meropenem despite MICs within the susceptible range.

Methods

We conducted a retrospective cohort study of clinical encounters within the Cerner Health Facts database to identify all encounters between 2001 and 2017 in which Enterobacterales infections were treated empirically with piperacillin/tazobactam and for which MICs to the drug were available. Multivariate regression analysis was performed to enable partitioning of MICs into discrete strata based on statistically significant difference in mortality risk.

Results

During the study period, 10 101 inpatient encounters were identified meeting inclusion criteria. The crude in-hospital mortality for the entire cohort was 16.5%. Partitioning analysis identified a breakpoint of ≤16/4 mg/L that dichotomized encounters into lower versus higher mortality risk strata in the primary cohort of overall infections. This finding persisted in sequentially granular subsets where specific MICs ≤8/4 mg/L were reported (in lieu of ranges) as well as in the high-reliability subset with bloodstream infections. A higher clinical breakpoint of ≥128/4 mg/L dichotomized encounters with respiratory tract infection. No breakpoint was identified when restricting to encounters with urinary tract infections, ICU admits or upon restricting analysis to encounters with ceftriaxone-resistant isolates.

Conclusions

Clinical data suggest improved outcomes when piperacillin/tazobactam is prescribed for Enterobacterales infections with an MIC of ≤16/4 mg/L compared with ≥32/4 mg/L.
A Review of Regulations, Terminology, and Practical Approaches to Reportable Range Verification
Authors: Xiao Yi , Chambliss Allison B
Published: April 2023

Background

In the United States, federal regulations under CLIA ‘88 require reportable range verification of quantitative assays used for clinical purposes. Some accreditation agencies and other standards development organizations have their own additional requirements, recommendations, and/or terminologies relating to reportable range verification, leading to varying practices among clinical laboratories.

Content

Requirements and recommendations related to reportable range or analytical measurement range verification from different organizations are reviewed and compared. Optimal approaches to materials selection, data analysis, and troubleshooting are collated.

This review clarifies key concepts and outlines various practical approaches to reportable range verification.
Evaluation of an approach to clinical decision support for preventing inpatient falls: a pragmatic trial
Authors: Cho Insook , Kim MiSoon , Song Mi Ra , Dykes Patricia C
Published: April 2023

Objectives

To assess whether a fall-prevention clinical decision support (CDS) approach using electronic analytics that stimulates risk-targeted interventions is associated with reduced rates of falls and injurious falls.

Materials and Methods

The CDS intervention included a machine-learning prediction algorithm, individual risk-factor identification, and guideline-based prevention recommendations. After a 5-month plan-do-study-act quality improvement initiative, the CDS intervention was implemented at an academic tertiary hospital and compared with the usual care using a pretest (lasting 24 months and involving 23 498 patients) and posttest (lasting 13 months and involving 17 341 patients) design in six nursing units. Primary and secondary outcomes were the rates of falls and injurious falls per 1000 hospital days, respectively. Outcome measurements were tested using a priori Poisson regression and adjusted with patient-level covariates. Subgroup analyses were conducted according to age.

Results

The age distribution, sex, hospital and unit lengths of stay, number of secondary diagnoses, fall history, condition at admission, and overall fall rate per 1000 hospital days did not differ significantly between the intervention and control periods before (1.88 vs 2.05, respectively, P = .1764) or after adjusting for demographics. The injurious-falls rate per 1000 hospital days decreased significantly before (0.68 vs 0.45, P = .0171) and after (rate difference = –0.64, P = .0212) adjusting for demographics. The differences in injury rates were greater among patients aged at least 65 years.

Conclusions

This study suggests that a well-designed CDS intervention employing electronic analytics was associated with a decrease in fall-related injuries. The benefits from this intervention were greater in elderly patients aged at least 65 years.

Trial Registration

This study was conducted as part of a more extensive study registered with the Clinical Research Information Service (CRIS) (KCT0005378).
Relocation Issues of Released and Acquitted at International Criminal Courts and Tribunals
Authors: Lecolle Cécile
Published: April 2023

The study of the treatment of released and acquitted persons by international courts and tribunals (ICTs) has been one of the most neglected aspects of international criminal justice. The system rests on the cooperation of states with the ICTs. However, this cooperation when it exists, often ceases when the trial has ended. Regarding the objective of delivering justice, states appear to have either forgotten or refused to accept that both acquittals and the eventual release of convicted individuals are part of the process of criminal justice. Even states committed to international justice have denied protection against extradition to unsafe countries for acquitted and released persons, or declined to become host countries, grant asylum requests or take any steps to offer these former defendants and convicted persons a dignified life. This article explores the international legal frameworks applicable to the relocation of persons released or acquitted by ICTs. It specifically looks into the cases of the ad hoc tribunals and the International Criminal Court (ICC), the states parties’ general obligation under the statutes and rules to cooperate with the ICTs, and relevant principles of refugee law. The article explores some of the most recent issues relating to relocation that have shaken international criminal justice. At the International Criminal Tribunal for Rwanda, the recent striking failure to obtain the relocation of nine acquitted and released persons is examined as an emblematic and appalling example of the violation of these persons’ fundamental human rights, and the refusal of the international community to pursue justice in all its aspects. At the ICC, important issues of relocation have already arisen for acquitted and released persons, and the Court will urgently need agreements in this area. Importantly, it is necessary to recognize that, to protect the rights of these former defendants, the practical work of defence lawyers continues long after their clients’ release.
Time-to-positivity in bloodstream infection for Candida species as a prognostic marker for mortality
Authors: Keighley Caitlin , Pope Alun L , Marriott Debbie , Chen Sharon C-A , Slavin Monica A ,   Australia and New Zealand Mycoses Interest Group, Arthur Ian , Baird Rob , Bak Narin , Blyth Christopher , Botes Jeannie , Chapman Belinda , Cheong Elaine , Cooley Louise , Daveson Kathryn , George Rob , Goeman Emma , Hajkowicz Krispin , Halliday Catriona , Heath Christopher H , Hofmeyr Ann , Kalukottege Pankaja , Kesson Alison , Kennedy Karina , Kidd Sarah , Korman Tony M , Leung Michael , Liu Eunice , Macesic Nenad , McDonald Kyle , McMullan Brendan , Morrissey Orla , Pendle Stella , Robson Jenny , Sorrell Tania , Underwood Neil , van Hal Sebastian , Weeks Kerry , Wilson Heather
Published: April 2023

Time-to-positivity (TTP) may assist in predicting the outcome of candidaemia. We analysed a candidaemia dataset collected prospectively in Australia over 1 year (2014–2015). TTP was defined as the period from blood culture sampling to the blood culture flagging positive. Of 415 candidaemia episodes, overall, 30-day mortality was 29% (120/415); mortality with Candida albicans was 35% (59/169), C. glabrata complex, 37% (43/115), C. tropicalis, 43% (10/23), Pichia kudriavzevii 25% (3/12), and C. parapsilosis complex 7% (5/71). Each day of increased TTP multiplied the odds ratio (OR) of survival at 30 days by a factor of 1.32 [95% confidence interval (CI) 1.06–1.69]. Shorter TTP was associated with increased mortality, with 1-day TTP associated with 30-day mortality 37% (41/112) (95%CI: 28%–46%) and 5-day TTP 11% (2/18) (95%CI: 2%–36%).
Capture of stars into gaseous discs around massive black holes: alignment, circularization, and growth
Authors: Generozov A , Perets H B
Published: April 2023

The majority of massive black holes (MBHs) likely hosted gas discs during their lifetimes. These could either be long-lived active galactic nuclei (AGN) discs, or shorter-lived discs formed following singular gas infall events, as was likely the case in our own Galactic Centre. Stars and compact objects in such environments are therefore expected to interact with the gaseous disc as they go through it, and potentially become aligned and fully embedded within it. The interactions of embedded stars with the gas could give rise to a plethora of physical processes affecting the stars, including growth through accretion of gas, migration in the disc, stellar captures, and mergers with other stars. The impact of such processes strongly depends on the population of stars that eventually align with the disc and become embedded in it. Here we make use of analytic tools to analyze the alignment process, accounting for both geometric drag and gas dynamical friction. We find that up to $\sim \! 50~{{\ \rm per\ cent}}$ of main sequence stars and stellar mass black holes in the central 0.1 pc can align with AGN disc in the Galactic Centre and similar galactic nuclei. The orbits of aligned stars are typically circularized and are prograde with respect to the AGN disc. Furthermore, alignment and accretion are intimately linked, and the capture of stars by an AGN disc can potentially explain the origin of the young stellar disc in the Galactic Centre with a top-heavy mass function, even without the need for a star-formation event.
RBBP4 is an epigenetic barrier for the induced transition of pluripotent stem cells into totipotent 2C-like cells
Authors: Ping Wangfang , Sheng Yingliang , Hu Gongcheng , Zhong Hongxin , Li Yaoyi , Liu YanJiang , Luo Wei , Yan Chenghong , Wen Yulin , Wang Xinxiu , Li Qing , Guo Rong , Zhang Jie , Liu Ake , Pan Guangjin , Yao Hongjie
Published: April 2023

Cellular totipotency is critical for whole-organism generation, yet how totipotency is established remains poorly illustrated. Abundant transposable elements (TEs) are activated in totipotent cells, which is critical for embryonic totipotency. Here, we show that the histone chaperone RBBP4, but not its homolog RBBP7, is indispensable for maintaining the identity of mouse embryonic stem cells (mESCs). Auxin-induced degradation of RBBP4, but not RBBP7, reprograms mESCs to the totipotent 2C-like cells. Also, loss of RBBP4 enhances transition from mESCs to trophoblast cells. Mechanistically, RBBP4 binds to the endogenous retroviruses (ERVs) and functions as an upstream regulator by recruiting G9a to deposit H3K9me2 on ERVL elements, and recruiting KAP1 to deposit H3K9me3 on ERV1/ERVK elements, respectively. Moreover, RBBP4 facilitates the maintenance of nucleosome occupancy at the ERVK and ERVL sites within heterochromatin regions through the chromatin remodeler CHD4. RBBP4 depletion leads to the loss of the heterochromatin marks and activation of TEs and 2C genes. Together, our findings illustrate that RBBP4 is required for heterochromatin assembly and is a critical barrier for inducing cell fate transition from pluripotency to totipotency.
Dual functions of TET1 in germ layer lineage bifurcation distinguished by genomic context and dependence on 5-methylcytosine oxidation
Authors: van der Veer Bernard K , Chen Lehua , Custers Colin , Athanasouli Paraskevi , Schroiff Mariana , Cornelis Riet , Chui Jonathan Sai-Hong , Finnell Richard H , Lluis Frederic , Koh Kian Peng
Published: April 2023

Gastrulation begins when the epiblast forms the primitive streak or becomes definitive ectoderm. During this lineage bifurcation, the DNA dioxygenase TET1 has bipartite functions in transcriptional activation and repression, but the mechanisms remain unclear. By converting mouse embryonic stem cells (ESCs) into neuroprogenitors, we defined how Tet1–/– cells switch from neuroectoderm fate to form mesoderm and endoderm. We identified the Wnt repressor Tcf7l1 as a TET1 target that suppresses Wnt/β-catenin and Nodal signalling. ESCs expressing catalytic dead TET1 retain neural potential but activate Nodal and subsequently Wnt/β-catenin pathways to generate also mesoderm and endoderm. At CpG-poor distal enhancers, TET1 maintains accessible chromatin at neuroectodermal loci independently of DNA demethylation. At CpG-rich promoters, DNA demethylation by TET1 affects the expression of bivalent genes. In ESCs, a non-catalytic TET1 cooperation with Polycomb represses primitive streak genes; post-lineage priming, the interaction becomes antagonistic at neuronal genes, when TET1’s catalytic activity is further involved by repressing Wnt signalling. The convergence of repressive DNA and histone methylation does not inhibit neural induction in Tet1-deficient cells, but some DNA hypermethylated loci persist at genes with brain-specific functions. Our results reveal versatile switching of non-catalytic and catalytic TET1 activities based on genomic context, lineage and developmental stage.
Prediction of intradialytic hypotension using pre-dialysis features—a deep learning–based artificial intelligence model
Authors: Lee Hanbi , Moon Sung Joon , Kim Sung Woo , Min Ji Won , Park Hoon Suk , Yoon Hye Eun , Kim Young Soo , Kim Hyung Wook , Yang Chul Woo , Chung Sungjin , Koh Eun Sil , Chung Byung Ha
Published: April 2023

Background

Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) that is associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning–based artificial intelligence (AI) model to predict IDH using pre-dialysis features.

Methods

Data from 2007 patients with 943 220 HD sessions at seven university hospitals were used. The performance of the deep learning model was compared with three machine learning models (logistic regression, random forest and XGBoost).

Results

IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared with non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared with non-IDH sessions. Matthews correlation coefficient and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session.

Conclusions

Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.