bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular machine learning with conformer ensembles
Authors: Axelrod Simon , Gómez-Bombarelli Rafael 
Published: August 2023

Abstract
Virtual screening can accelerate drug discovery by identifying promising candidates for experimental evaluation. Machine learning is a powerful method for screening, as it can learn complex structure–property relationships from experimental data and make rapid predictions over virtual libraries. Molecules inherently exist as a three-dimensional ensemble and their biological action typically occurs through supramolecular recognition. However, most deep learning approaches to molecular property prediction use a 2D graph representation as input, and in some cases a single 3D conformation. Here we investigate how the 3D information of multiple conformers, traditionally known as 4D information in the cheminformatics community, can improve molecular property prediction in deep learning models. We introduce multiple deep learning models that expand upon key architectures such as ChemProp and SchNet, adding elements such as multiple-conformer inputs and conformer attention. We then benchmark the performance trade-offs of these models on 2D, 3D and 4D representations in the prediction of drug activity using a large training set of geometrically resolved molecules. The new architectures perform significantly better than 2D models, but their performance is often just as strong with a single conformer as with many. We also find that 4D deep learning models learn interpretable attention weights for each conformer.
Estimating Gibbs free energies via isobaric-isothermal flows
Authors: Wirnsberger Peter , Ibarz Borja , Papamakarios George 
Published: August 2023

Abstract
We present a machine-learning model based on normalizing flows that is trained to sample from the isobaric-isothermal ensemble. In our approach, we approximate the joint distribution of a fully-flexible triclinic simulation box and particle coordinates to achieve a desired internal pressure. This novel extension of flow-based sampling to the isobaric-isothermal ensemble yields direct estimates of Gibbs free energies. We test our NPT-flow on monatomic water in the cubic and hexagonal ice phases and find excellent agreement of Gibbs free energies and other observables compared with established baselines.
New angles on fast calorimeter shower simulation
Authors: Diefenbacher Sascha , Eren Engin , Gaede Frank , Kasieczka Gregor , Korol Anatolii , Krüger Katja , McKeown Peter , Rustige Lennart 
Published: August 2023

AbstractThe demands placed on computational resources by the simulation requirements of high energy physics experiments motivate the development of novel simulation tools. Machine learning based generative models offer a solution that is both fast and accurate. In this work we extend the Bounded Information Bottleneck Autoencoder (BIB-AE) architecture, designed for the simulation of particle showers in highly granular calorimeters, in two key directions. First, we generalise the model to a multi-parameter conditioning scenario, while retaining a high degree of physics fidelity. In a second step, we perform a detailed study of the effect of applying a state-of-the-art particle flow-based reconstruction procedure to the generated showers. We demonstrate that the performance of the model remains high after reconstruction. These results are an important step towards creating a more general simulation tool, where maintaining physics performance after reconstruction is the ultimate target.
Wet etching of gold on graphene for high-quality resist-free graphene surfaces
Authors: Kunc J , Shestopalov M , Jo J , Park K 
Published: August 2023

Abstract
Wet etching of gold on graphene is challenging due to the weak adhesion of the resist mask to graphene. We report an operating procedure for alkali ion-free wet etching of gold on graphene using a mixture of hydrochloric and nitric acids (aqua regia) with a high lateral resolution down to 100 nm. We investigate the role of positive and negative resists, electron beam lithography (EBL) dose, hard-bake, oxygen etching, aging, and sensitivity to the etch parameters, such as the freshness of dilute aqua regia, etch time, and the order of etched samples. The negative-tone resist provides the best results. The over-dosed EBL exposure can enhance the resist adhesion, as hard-bake below the glass-transition temperature and well-defined wet etch of the resist-residua-free gold surface. We also present a cleaning procedure to avoid bubble formation after the hard bake. Our results demonstrate that wet etching of gold on graphene using aqua regia is a viable method for achieving high-quality resist-free graphene surfaces. This method has potential applications in graphene nanoelectronics and nanophotonics, where high-quality graphene surfaces are essential for device performance.
Less favourable food consumption ratings in the Five-Color Nutri-Score are associated with incident frailty in older adults
Authors: Rey-García Jimena , Donat-Vargas Carolina , Sandoval-Insausti Helena , Banegas José R , Dominguez Ligia J , Rodríguez-Artalejo Fernando , Guallar-Castillón Pilar 
Published: August 2023

Abstract

Background
The Nutri-Score front-of-package labelling classifies food products according to their nutritional quality, so healthier food choices are easier when shopping. This study prospectively assesses the association of a diet rated according to the Nutri-Score system and incident frailty in community-dwelling older adults.

Methods
Cohort study with 1,875 individuals aged ≥60 recruited during 2008–2010 in Spain. At baseline, food consumption was assessed using a validated dietary history. Food was categorised into five Nutri-Score labels (A/green—best quality; B, C, D, E/red—worst quality) utilising an algorithm established in 2017 and currently in use. For each participant, a Five-Color Nutri-Score Dietary Index (5-CNS DI) in grams per day per kilogram was calculated. The 5-CNS DI sums up the grams per day of food consumed times their corresponding nutritional quality value (from A rated as 1 to E rated as 5) and divided by weight in kilograms. From baseline to December 2012, incident frailty was ascertained based on Fried’s criteria. Statistical analyses were performed with logistic regression adjusted for main confounders.

Results
After a mean follow-up of 3.5 years, 136 cases of frailty were identified. The multivariable-adjusted odds ratios (95% confidence interval) of incident frailty across increasing quartiles of the 5-CNS DI were 1, 1.51 (0.86–2.68), 1.56 (0.82–2.98) and 2.32 (1.12–4.79); P-trend = 0.033. The risk of frailty increased by 28% (3–58%) with a 10-unit increment in this dietary index. Similar results were found with the Nutri-Score algorithm modified in 2022.

Conclusions
consumption of a diet with less favourable Nutri-Score ratings doubles the risk of frailty among community-dwelling older adults.
Associations Between Executive Functioning, Behavioral Functioning, and Adaptive Functioning Difficulties in Wiedemann–Steiner Syndrome
Authors: Ng Rowena , Bjornsson Hans Tomas , Fahrner Jill A , Harris Jacqueline 
Published: August 2023

Abstract

Objectives
Wiedemann–Steiner syndrome (WSS) is a neurogenetic disorder caused by heterozygous variants in KMT2A. Recent investigations suggest increased anxiety and behavior regulation challenges among those with WSS although the neurobehavioral phenotype remains largely unknown. This study aims to examine the pattern of and associations between executive functioning (EF) and behavior functioning among those with WSS.

Method
This study involved utilizing caregiver-report inventories (Behavior Rating Inventory of Executive Function 2nd Edition, BRIEF-2; Adaptive Behavior Assessment 3rd Edition, ABAS-3; Strengths and Difficulties Questionnaire, SDQ) to assess day-to-day behavior functioning among those with WSS (N = 24; mean age = 10.68 years, SD = 3.19). Frequency of clinical elevations in daily difficulties in EF, adaptive behaviors, and behavior regulation were reported. Correlations and hierarchical linear regressions were used to determine the relationships between EF with behavior and adaptive functioning.

Results
Out of our sample, 63% met clinical levels of executive functioning difficulties on the BRIEF-2, and 75% with Hyperactivity and 54% with Emotional Problems on the SDQ. In addition, 33% were rated &gt;2 SD below the normative mean in overall adaptive functioning on the ABAS-3. Elevated ratings in BRIEF-2 Shift, reflective of challenges with mental flexibility, predicted more Emotional Problems and accounted for 33.5% of its variance. More difficulties in Emotional Control were related to greater adaptive deficits, accounting for 33.3% of its variance.

Conclusions
Those with WSS are at risk for EF deficits, hyperactivity, and emotional dysregulation. EF correlates with adaptive and affective behaviors, highlighting the promise of behavioral interventions to target cognitive flexibility, emotional awareness, and reactivity in this population.
Secreted arabinogalactan protein from salt-adapted tobacco BY-2 cells appears to be glycosylphosphatidyl inositol-anchored and associated with lipophilic moieties
Authors: Nweke Arinze Boniface , Nagasato Daiki , Matsuoka Ken 
Published: August 2023

ABSTRACT
Arabinogalactan proteins (AGPs) are plant extracellular proteoglycans associated with the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. This moiety is thought to be cleaved by phospholipase for secretion. Salt-adapted tobacco BY-2 cells were reported to secrete large amounts of AGPs into the medium. To investigate this mechanism, we expressed a fusion protein of tobacco sweet potato sporamin and AGP (SPO-AGP) in BY-2 cells and analyzed its fate after salt-adapting the cells. A two-phase separation analysis using Triton X-114 indicated that a significant proportion of SPO-AGP in the medium was recovered in the detergent phase, suggesting that this protein is GPI-anchored. Differential ultracentrifugation and a gradient density fractionation implicated extracellular vesicles or particles with SPO-AGP in the medium. Endogenous AGP secreted from salt-adapted and nontransgenic BY-2 cells behaved similarly to SPO-AGP. These results suggest that a part of the secreted AGPs from salt-adapted tobacco BY-2 cells are GPI-anchored and associated with particles or vesicles.
CMMS-GCL: cross-modality metabolic stability prediction with graph contrastive learning
Authors: Du Bing-Xue , Long Yahui , Li Xiaoli , Wu Min , Shi Jian-Yu 
Published: August 2023

Abstract

Motivation
Metabolic stability plays a crucial role in the early stages of drug discovery and development. Accurately modeling and predicting molecular metabolic stability has great potential for the efficient screening of drug candidates as well as the optimization of lead compounds. Considering wet-lab experiment is time-consuming, laborious, and expensive, in silico prediction of metabolic stability is an alternative choice. However, few computational methods have been developed to address this task. In addition, it remains a significant challenge to explain key functional groups determining metabolic stability.

Results
To address these issues, we develop a novel cross-modality graph contrastive learning model named CMMS-GCL for predicting the metabolic stability of drug candidates. In our framework, we design deep learning methods to extract features for molecules from two modality data, i.e. SMILES sequence and molecule graph. In particular, for the sequence data, we design a multihead attention BiGRU-based encoder to preserve the context of symbols to learn sequence representations of molecules. For the graph data, we propose a graph contrastive learning-based encoder to learn structure representations by effectively capturing the consistencies between local and global structures. We further exploit fully connected neural networks to combine the sequence and structure representations for model training. Extensive experimental results on two datasets demonstrate that our CMMS-GCL consistently outperforms seven state-of-the-art methods. Furthermore, a collection of case studies on sequence data and statistical analyses of the graph structure module strengthens the validation of the interpretability of crucial functional groups recognized by CMMS-GCL. Overall, CMMS-GCL can serve as an effective and interpretable tool for predicting metabolic stability, identifying critical functional groups, and thus facilitating the drug discovery process and lead compound optimization.

Availability and implementation
The code and data underlying this article are freely available at https://github.com/dubingxue/CMMS-GCL.
Comparative Analysis of Practice Research in Australia and the UK: The Shift to Practice-driven Research
Authors: Webber Martin , Joubert Lynette 
Published: August 2023

AbstractAustralia and the UK share many historic connections. These connections have influenced developments in welfare systems, and the bi-directional migration of social work practitioners between Australia and the UK has helped to support the sharing of knowledge in social work education, research and practice. However, developments in practice research in both countries has largely been influenced by local activity rather than cross-national collaboration, though there have been similar growth trajectories. This article uses a comparative case study methodology to analyse the development of practice research in Australia and the UK since the Salisbury Statement on social work practice research. Each case study explores and provides examples of the nature of the relationship between practitioners and academic researchers; how practice questions are generated; how methodologies are selected; how data are collected within social work practice and the impact of practice research on practice in both countries. The comparative analysis provides a unique insight into how local, and often small, projects provide a more significant narrative about the creation of knowledge in social work practice. These insights have the potential to inform and stimulate the development of practice research in other countries which are earlier in the journey towards practice-driven research.
DOT1L deletion impairs the development of cortical parvalbumin-expressing interneurons
Authors: Cheffer Arquimedes , Garcia-Miralles Marta , Maier Esther , Akol Ipek , Franz Henriette , Srinivasan Vandana Shree Vedartham , Vogel Tanja 
Published: August 2023

Abstract
The cortical plate (CP) is composed of excitatory and inhibitory neurons, the latter of which originate in the ganglionic eminences. From their origin in the ventral telencephalon, maturing postmitotic interneurons migrate during embryonic development over some distance to reach their final destination in the CP. The histone methyltransferase Disruptor of Telomeric Silencing 1-like (DOT1L) is necessary for proper CP development and layer distribution of glutamatergic neurons. However, its specific role on cortical interneuron development has not yet been explored. Here, we demonstrate that DOT1L affects interneuron development in a cell autonomous manner. Deletion of Dot1l in Nkx2.1-expressing interneuron precursor cells results in an overall reduction and altered distribution of GABAergic interneurons in the CP from postnatal day 0 onwards. We observed an altered proportion of GABAergic interneurons in the cortex, with a significant decrease in parvalbumin-expressing interneurons. Moreover, a decreased number of mitotic cells at the embryonic day E14.5 was observed upon Dot1l deletion. Altogether, our results indicate that reduced numbers of cortical interneurons upon DOT1L deletion result from premature cell cycle exit, but effects on postmitotic differentiation, maturation, and migration are likely at play as well.
Fixation-related fMRI analysis reveals the neural basis of natural reading of unspaced and spaced Chinese sentences
Authors: Zhou Wei , Wang Sile , Yan Ming 
Published: August 2023

Abstract
Although there are many eye-movement studies focusing on natural sentence reading and functional magnetic resonance imaging research on reading with serial visual presentation paradigms, there is a scarcity of investigations into the neural mechanism of natural sentence reading. The present study recruited 33 adults to read unspaced and spaced Chinese sentences with the eye tracking and functional magnetic resonance imaging data recorded simultaneously. By using fixation-related functional magnetic resonance imaging analysis, this study showed that natural reading of Chinese sentences produced activations in ventral visual, dorsal attention, and semantic brain regions, which were modulated by the properties of words such as word length and word frequency. The multivoxel pattern analysis showed that the activity pattern in the left middle temporal gyrus could significantly predict the visual layout categories (i.e. unspaced vs. spaced conditions). Dynamic causal modeling analysis showed that there were bidirectional brain connections between the left middle temporal gyrus and the left inferior occipital cortex in the unspaced Chinese sentence reading but not in the spaced reading. These results provide a neural mechanism for the natural reading of Chinese sentences from the perspective of word segmentation.
Brain network flexibility as a predictor of skilled musical performance
Authors: Uehara Kazumasa , Yasuhara Masaki , Koguchi Junya , Oku Takanori , Shiotani Sachiko , Morise Masanori , Furuya Shinichi 
Published: August 2023

AbstractInteractions between the body and the environment are dynamically modulated by upcoming sensory information and motor execution. To adapt to this behavioral state-shift, brain activity must also be flexible and possess a large repertoire of brain networks so as to switch them flexibly. Recently, flexible internal brain communications, i.e. brain network flexibility, have come to be recognized as playing a vital role in integrating various sensorimotor information. Therefore, brain network flexibility is one of the key factors that define sensorimotor skill. However, little is known about how flexible communications within the brain characterize the interindividual variation of sensorimotor skill and trial-by-trial variability within individuals. To address this, we recruited skilled musical performers and used a novel approach that combined multichannel-scalp electroencephalography, behavioral measurements of musical performance, and mathematical approaches to extract brain network flexibility. We found that brain network flexibility immediately before initiating the musical performance predicted interindividual differences in the precision of tone timbre when required for feedback control, but not for feedforward control. Furthermore, brain network flexibility in broad cortical regions predicted skilled musical performance. Our results provide novel evidence that brain network flexibility plays an important role in building skilled sensorimotor performance.
The long-term benefits of early intensive therapy in chronic diseases—the legacy effect
Authors: Zoccali Carmine , Mallamaci Francesca , Tripepi Giovanni , Fu Edouard L , Stel Vianda S , Dekker Friedo W , Jager Kitty J 
Published: August 2023

ABSTRACT
The ‘legacy effect’ refers to the long-term benefits of intensive therapy that are observed long after the end of clinical trials and trial interventions in chronic diseases such as diabetes, hyperlipidaemia and hypertension. It emphasizes the importance of intensive treatment to prevent long-term complications and mortality. In chronic kidney disease (CKD), the legacy effect is evident in various studies. Long-term nephroprotection in diabetes is well documented in major studies in the early stages of diabetes, such as Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC), UK Prospective Diabetes Study (UKPDS) and Intensified Multifactorial Intervention in Patients with Type 2 Diabetes and Microalbuminuria (STENO-2). These studies highlight the importance of intensive glycaemic control in reducing microvascular complications, including nephropathy, in patients with recently diagnosed type 1 and type 2 diabetes. However, the legacy effect is less evident in patients with long-term, established diabetes. In chronic glomerulonephritis, studies on immunoglobulin A nephropathy showed that early immunosuppressive treatment could have long-term beneficial effects on kidney function in children and adults with CKD. The Frequent Hemodialysis (FH) and the EXerCise Introduction To Enhance Performance in Dialysis (EXCITE) trials indicated that frequent haemodialysis and a personalized walking exercise program could improve clinical outcomes and reduce the long-term risk of death and hospitalization. The legacy effect concept underscores the importance of intensive intervention in chronic diseases, including CKD. This concept has significant implications for public health and warrants in-depth basic and clinical research to be better understood and exploited in clinical practice. However, its limitations should be considered when interpreting long-term observational data collected after a clinical trial. Appropriate study designs are necessary to investigate an unbiased legacy effect.
CCIDB: a manually curated cell–cell interaction database with cell context information
Authors: Noh Jin Young , Lee Hae In , Choi Ji-Hye , Cho Seong-Ho , Yi Yoon Hui , Lim Ji Hyun , Myung Eun Been , Shin Ye Ju , Shin Hyo Jin , Woo Hyun Goo 
Published: August 2023

Abstract
Cell–cell interaction (CCI) is a crucial event in the development and function of multicellular organisms. The development of CCI databases is beneficial for researchers who want to analyze single-cell sequencing data or study CCI through molecular experiments. CCIs are known to act differently according to cellular and biological contexts such as cell types, gene mutations or disease status; however, previous CCI databases do not completely provide this contextual information pertaining to CCIs. We constructed a cell-cell interaction database (CCIDB) containing the biological and clinical contexts involved in each interaction. To build a database of cellular and tissue contexts, we collected 38 types of context features, which were categorized into seven categories, including ‘interaction’, ‘cell type’, ‘cofactor’, ‘effector’, ‘phenotype’, ‘pathology’ and ‘reference’. CCIs were manually retrieved from 272 studies published recently (less than 6 years ago). In the current version of CCIDB, 520 CCIs and their 38 context features have been manually collected and curated by biodata engineers. We suggest that CCIDB is a manually curated CCI resource that is highly useful, especially for analyzing context-dependent alterations in CCIs.
Database URL https://ccidb.sysmed.kr/