bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of an electronic pharmacy scoring tool to prioritize clinical pharmacists’ daily workflow at a pediatric institution
Authors: D Brax Amber , Sapko Matthew M , Cole Justin W , Landgrave Lindsay C , Magers Jacqueline K , Pierson Shawn M 
Published: September 2022

Abstract

Purpose
To describe the development and implementation of an electronic pharmacy scoring tool (PST) to prioritize patients requiring clinical pharmacy intervention and assist in workload management in a freestanding pediatric hospital using quality improvement methodology.

Summary
The department of pharmacy at Nationwide Children’s Hospital developed a pediatric-specific PST within the electronic medical record to aid in patient prioritization and ensuring proficient daily workflow and qualifying workload for clinical pharmacists. The PST identifies patients for monitoring of high-risk medications, complex medication regimens, or abnormal laboratory values related to medication management. Application of the scoring tool ensures each patient is reviewed by clinical pharmacy staff each day, with initial efforts focused on patients with significant clinical pharmacy needs. This tool reduces the need for time-intensive manual chart review for identification of patients whose medication use and/or laboratory values afford greater opportunity for pharmacist intervention. Additionally, clinical pharmacist productivity metrics and workloads are considered, with the qualifying of patient care activities and quantification of time spent on patient review.

Conclusion
A PST enhances pediatric patient prioritization for clinical pharmacists by identifying patients most likely to require intervention in real time. The scoring tool enables future assessment of clinical pharmacists’ workload assignments and better quantifies time spent on patient care activities.
Pachymic acid alleviates experimental pancreatic fibrosis through repressing NLRP3 inflammasome activation
Authors: Li Fu , Chen Meng , Ji Jianmei , Tang Rui , Huang Jinxin , Zhang Xiwen , Yu Jinzhong 
Published: September 2022

ABSTRACT
Pachymic acid (PA), a natural triterpenoid, possesses the capacity to repress inflammatory and profibrotic responses. However, the role of PA in pancreatic fibrosis remains unclear. Here the effect of PA on anti-fibrogenic response was investigated using in vivo and in vitro pancreatitis models. We demonstrated that PA treatment repressed TGF-β-induced pancreatic stellate cells (PSCs) activation in vitro, as evidenced by decreased expression of Collagen I, α-smooth muscle actin, and fibronectin. PA decreased Cerulein-induced acinar injury and pancreatic fibrosis in an experimental pancreatitis model. Mechanistically, PA repressed Cerulein or (TGF-β)-induced activation of nuclear factor (NF)-κB signaling and thus decreased NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome activation in PSCs. Pharmacological inhibition of NLRP3 repressed TGF-β-induced activation of PSCs. More important, NLRP3 activator partially attenuated the effect of PA on inhibiting PSCs activation. Collectively, these data demonstrate that PA represses PSCs activation and pancreatic fibrosis through repressing NF-κB/NLRP3 signaling.
LDAformer: predicting lncRNA-disease associations based on topological feature extraction and Transformer encoder
Authors: Zhou Yi , Wang Xinyi , Yao Lin , Zhu Min 
Published: September 2022

AbstractThe identification of long noncoding RNA (lncRNA)-disease associations is of great value for disease diagnosis and treatment, and it is now commonly used to predict potential lncRNA-disease associations with computational methods. However, the existing methods do not sufficiently extract key features during data processing, and the learning model parts are either less powerful or overly complex. Therefore, there is still potential to achieve better predictive performance by improving these two aspects. In this work, we propose a novel lncRNA-disease association prediction method LDAformer based on topological feature extraction and Transformer encoder. We construct the heterogeneous network by integrating the associations between lncRNAs, diseases and micro RNAs (miRNAs). Intra-class similarities and inter-class associations are presented as the lncRNA-disease-miRNA weighted adjacency matrix to unify semantics. Next, we design a topological feature extraction process to further obtain multi-hop topological pathway features latent in the adjacency matrix. Finally, to capture the interdependencies between heterogeneous pathways, a Transformer encoder based on the global self-attention mechanism is employed to predict lncRNA-disease associations. The efficient feature extraction and the intuitive and powerful learning model lead to ideal performance. The results of computational experiments on two datasets show that our method outperforms the state-of-the-art baseline methods. Additionally, case studies further indicate its capability to discover new associations accurately.
Attention-aware contrastive learning for predicting T cell receptor–antigen binding specificity
Authors: Fang Yiming , Liu Xuejun , Liu Hui 
Published: September 2022

Abstract

Motivation
It has been proven that only a small fraction of the neoantigens presented by major histocompatibility complex (MHC) class I molecules on the cell surface can elicit T cells. This restriction can be attributed to the binding specificity of T cell receptor (TCR) and peptide-MHC complex (pMHC). Computational prediction of T cells binding to neoantigens is a challenging and unresolved task.

Results
In this paper, we proposed an attention-aware contrastive learning model, ATMTCR, to infer the TCR–pMHC binding specificity. For each TCR sequence, we used a transformer encoder to transform it to latent representation, and then masked a percentage of amino acids guided by attention weights to generate its contrastive view. Compared to fully-supervised baseline model, we verified that contrastive learning-based pretraining on large-scale TCR sequences significantly improved the prediction performance of downstream tasks. Interestingly, masking a percentage of amino acids with low attention weights yielded best performance compared to other masking strategies. Comparison experiments on two independent datasets demonstrated our method achieved better performance than other existing algorithms. Moreover, we identified important amino acids and their positional preference through attention weights, which indicated the potential interpretability of our proposed model.
Mental Health Problems amongst Left-behind Adolescents in China: Serial Mediation Roles of Parent-Adolescent Communication and School Bullying Victimisation
Authors: Xie Qian-Wen , Zhao Guanlan , Lu Jingjing , Chen Roujia , Xu Jiayao , Wang Menmen , Akezhuoli Hailati , Wang Feng , Zhou Xudong 
Published: September 2022

AbstractBackgroundAdolescent mental health is a global public health concern and parental migration has been identified as a risk factor. However, the effect mechanism remained unclear.MethodsA total of 2,737 participants (mean = 11.93, SD = 1.23) were recruited from twelve schools in migrant-sending areas in Zhejiang and Anhui provinces. The participants responded to items in Child Depression Inventory, Parent–Adolescent Communication Scale, Olweus Bully or Victim Questionnaire and socio-demographic questions. Serial multiple mediation models were analysed using the bootstrapping method.ResultsCurrent and previous left-behind (LB) experience were significantly associated with higher risks of depression, non-suicidal self-injury and suicidal ideation (p &lt; 0.05). Mother–adolescent communication and school bullying victimisation, in serial order, mediated the effect of current LB status on mental health (p &lt; 0.05). In terms of previously LB adolescents, parent–adolescent communication was a standalone mediator (p &lt; 0.01) and the serial mediation effect of parent–adolescent communication and school bullying victimisation was significant.ConclusionsLack of parent–adolescent communication and school bullying victimisation acted as risk factors for the negative effect of LB status or experience on adolescent mental health. The importance of these two interpersonal factors motivates future intervention initiatives to support the mental health of LB adolescents from an integrated perspective.
Twenty years of real-world data to estimate chronic kidney disease prevalence and staging in an unselected population
Authors: Santos-Araújo Carla , Mendonça Luís , Carvalho Daniel Seabra , Bernardo Filipa , Pardal Marisa , Couceiro João , Martinho Hugo , Gavina Cristina , Taveira-Gomes Tiago , Dinis-Oliveira Ricardo Jorge 
Published: September 2022

ABSTRACT
Chronic kidney disease (CKD) represents a global public health burden, but its true prevalence is not fully characterized in the majority of countries. We studied the CKD prevalence in adult users of the primary, secondary and tertiary healthcare units of an integrated health region in northern Portugal (n = 136 993; representing ∼90% of the region’s adult population). Of these, 45 983 (33.6%) had at least two estimated glomerular filtration rate (eGFR) assessments and 30 534 (22.2%) had at least two urinary albumin:creatinine ratio (UACR) assessments separated by at least 3 months. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines as a persistent decrease in eGFR (&lt;60 ml/min/1.73 m2) and/or an increase in UACR (≥30 mg/g). The estimated overall prevalence of CKD was 9.8% and was higher in females (5.5%) than males (4.2%). From these, it was possible to stratify 4.7% according to KDIGO guidelines. The prevalence of CKD was higher in older patients (especially in patients &gt;70 years old) and in patients with comorbidities.
This is the first real-world-based study to characterize CKD prevalence in a large, unselected Portuguese population. It probably provides the nearest estimate of the true CKD prevalence and may help healthcare providers to guide CKD-related policies and strategies focused on prevention and on the improvement of cardiovascular disease and other outcomes.
Factors associated with changing alcohol consumption during the first UK lockdown
Authors: McAloney-Kocaman Kareena , McPherson Kerri E , McGlinchey Emily , Armour Cherie 
Published: September 2022

AbstractBackgroundIn response to COVID-19 there have been lockdowns and restrictions to hospitality services. Drinking behaviours often change in response to traumatic events and changes in the drinking environment, and this is influenced by a range of factors. This study explores self-reported changes in alcohol consumption in the third month of the UK lockdown, associations with socio-demographics factors and with COVID-19-related concerns, and mental health and wellbeing.MethodsThe COVID-19 Psychological Wellbeing Study was a longitudinal, online, three-wave survey of 1958 UK adults. Data were collected during the first UK lockdown; wave 1 launched 23 March 2020, wave 2 was 1 month after and wave 3 2 months after completion of wave 1A hierarchical multinomial regression model was estimated to investigate factors associated with changes in perceived alcohol consumption in the third month of the lockdown.ResultsThe majority of participants reported changes in drinking (62%) with over one-third indicating increased consumption. Student status and worries about the financial implications of COVID-19 were associated with lower odds of decreased alcohol consumption. Those with above average income and those with children in the household had lower odds of increased alcohol consumption, while younger adults had higher odds of increased alcohol consumption.ConclusionsThis study adds to the growing body of research showing changes in alcohol consumption behaviours during the COVID-19 lockdown restrictions, and identifies risk and protective factors which can aid in targeting intervention at those most in need of support.
Viral life strategies in a heavily anthropized tropical lagoon
Authors: Andrianjakarivony Harilanto Felana , Desnues Christelle , Cecchi Philippe , Bettarel Yvan 
Published: September 2022

Abstract
Ecological traits of aquatic microorganisms have been poorly investigated in tropical latitudes, especially in lagoons, which are often subjected to strong anthropogenic influence, conducive to microbial development. In this study, we examined the abundance of both viral and bacterial communities, as well as their interactions (lytic and lysogenic infections) in the water and sediment of seven main stations of the Ebrié Lagoon (Ivory Coast) with contrasting levels of eutrophication. The highest bacterial and viral concentrations in both planktonic and benthic samples were found in the most eutrophicated stations, where viral lytic infections also exhibited their highest values. Conversely, the highest fractions of inducible lysogens were measured in the most oligotrophic stations, suggesting that these two main viral life strategies are mutually exclusive in this lagoon. Our findings also revealed the importance that nutrients (especially ammonium) play as drivers of the interactions between viruses and their bacterial hosts in tropical lagoons.
Phylogenomic analyses and host range prediction of cluster P mycobacteriophages
Authors: Howell Abigail A , Versoza Cyril J , Cerna Gabriella , Johnston Tyler , Kakde Shriya , Karuku Keith , Kowal Maria , Monahan Jasmine , Murray Jillian , Nguyen Teresa , Sanchez Carreon Aurely , Streiff Abigail , Su Blake , Youkhana Faith , Munig Saige , Patel Zeel , So Minerva , Sy Makena , Weiss Sarah , Pfeifer Susanne P 
Published: September 2022

Abstract
Bacteriophages, infecting bacterial hosts in every environment on our planet, are a driver of adaptive evolution in bacterial communities. At the same time, the host range of many bacteriophages—and thus one of the selective pressures acting on complex microbial systems in nature—remains poorly characterized. Here, we computationally inferred the putative host ranges of 40 cluster P mycobacteriophages, including members from 6 subclusters (P1–P6). A series of comparative genomic analyses revealed that mycobacteriophages of subcluster P1 are restricted to the Mycobacterium genus, whereas mycobacteriophages of subclusters P2–P6 are likely also able to infect other genera, several of which are commonly associated with human disease. Further genomic analysis highlighted that the majority of cluster P mycobacteriophages harbor a conserved integration-dependent immunity system, hypothesized to be the ancestral state of a genetic switch that controls the shift between lytic and lysogenic life cycles—a temperate characteristic that impedes their usage in antibacterial applications.
Biologics: how far can they go in Crohn’s disease?
Authors: Dunleavy Katie A , Pardi Darrell S 
Published: September 2022

Abstract
Crohn’s disease is a chronic gastrointestinal inflammatory disorder, characterized by episodes of relapsing and remitting flares. As the disease mechanism becomes better elucidated, there is a significant increase in the number of available biologic therapies. This article summarizes and synthesizes current Food and Drug Administration-approved biological therapy for Crohn’s disease and examines the positioning of medical therapy as emerging biologics break onto the market.
Developmental history modulates adult olfactory behavioral preferences via regulation of chemoreceptor expression in Caenorhabditis
elegans
Authors: Kyani-Rogers Travis , Philbrook Alison , McLachlan Ian G , Flavell Steven W , O’Donnell Michael P , Sengupta Piali 
Published: September 2022

Abstract
Developmental experiences play critical roles in shaping adult physiology and behavior. We and others previously showed that adult Caenorhabditiselegans which transiently experienced dauer arrest during development (postdauer) exhibit distinct gene expression profiles as compared to control adults which bypassed the dauer stage. In particular, the expression patterns of subsets of chemoreceptor genes are markedly altered in postdauer adults. Whether altered chemoreceptor levels drive behavioral plasticity in postdauer adults is unknown. Here, we show that postdauer adults exhibit enhanced attraction to a panel of food-related attractive volatile odorants including the bacterially produced chemical diacetyl. Diacetyl-evoked responses in the AWA olfactory neuron pair are increased in both dauer larvae and postdauer adults, and we find that these increased responses are correlated with upregulation of the diacetyl receptor ODR-10 in AWA likely via both transcriptional and posttranscriptional mechanisms. We show that transcriptional upregulation of odr-10 expression in dauer larvae is in part mediated by the DAF-16 FOXO transcription factor. Via transcriptional profiling of sorted populations of AWA neurons from control and postdauer animals, we further show that the expression of a subset of additional chemoreceptor genes in AWA is regulated similarly to odr-10 in postdauer animals. Our results suggest that developmental experiences may be encoded at the level of olfactory receptor regulation, and provide a simple mechanism by which C. elegans is able to precisely modulate its behavioral preferences as a function of its current and past experiences.
Recognizing Early Childhood Education as a Human Right in International Law
Authors: Fredman Sandra , Donati Georgina , Richter Linda M , Naicker Sara N , Behrman Jere R , Lu Chunling , Cohrssen Caroline , Lopez Boo Florencia , Raghavan Chemba , Devercelli Amanda , Heymann Jody , Stein Alan ,   Harnessing Global Data to Advance Young Children’s Learning and Development Consortium
Published: September 2022

Abstract
There is incontrovertible evidence that early learning opportunities shape long-term development and health. Nevertheless, early childhood care and education (ECCE) is not expressly mentioned as part of the right to education in the Convention on the Rights of the Child, the International Covenant on Economic, Social and Cultural Rights, and the Convention on the Rights of Persons with Disabilities. This paper argues that the right to education can nevertheless be regarded as including ECCE. We examine the treaties, General Comments, and 264 Concluding Observations by relevant UN monitoring bodies, covering 152 countries from 2015 to 2020, to determine whether the right to ECCE is regarded as part of States’ obligations and the content of the duty. These demonstrate consistently that States must provide affordable, accessible, quality, inclusive ECCE, with adequate resources. We argue that monitoring committees should draw these obligations together in one General Comment, thereby improving States’ accountability and guiding the delivery of ECCE.
Infliximab Trough Levels Are Associated With Transmural Sonographic Healing in Inflammatory Bowel Disease
Authors: Vaughan Rose , Murphy Elise , Nalder Michelle , Gibson Robert N , Ardalan Zaid , Boussioutas Alex , Christensen Britt 
Published: September 2022

AbstractBackgroundMucosal healing improves clinical outcomes in patients with inflammatory bowel disease (IBD) and is associated with higher infliximab trough levels (ITLs). Transmural healing, assessed by intestinal ultrasound (IUS), is emerging as an objective target in Crohn’s disease (CD) and ulcerative colitis (UC). This study explores the correlation between maintenance ITLs and sonographic transmural healing.MethodsPatients on maintenance infliximab therapy were prospectively enrolled to undergo paired IUS examination and serum ITL. Infliximab trough levels were compared between patients with and without sonographic markers of inflammation using the Mann-Whitney U test.ResultsA prospective cohort of 103 patients (51% male; 79 CD; 24 UC; median duration of disease 8 years) underwent IUS and serum ITL testing. Forty-one percent of CD and 66% of UC patients demonstrated sonographic healing (bowel wall thickening ≤3 mm with no increase in color Doppler signal). Crohn’s disease patients with sonographic healing had higher median ITL compared with those with sonographic inflammation (4.8 μg/mL vs 3.1 μg/mL; P = .049). Additionally, the presence of hyperemia on Doppler was independently associated with lower ITL compared with those without hyperemia (2.1 μg/mL vs 4.2 μg/mL, respectively; P = .003). There was no significant association between ITL and other sonographic markers of inflammation. In UC, lower ITL was associated with hyperemia on Doppler imaging (P = .04). There was no association between ITL and sonographic healing or any other individual sonographic parameter of inflammation.ConclusionsLower maintenance infliximab levels are associated with sonographic parameters of inflammation in UC and CD. Further studies are needed to determine whether targeting higher infliximab levels can increase sonographic healing.
Resistance Analyses in Highly Treatment-Experienced People With Human Immunodeficiency Virus (HIV) Treated With the Novel Capsid HIV Inhibitor Lenacapavir
Authors: Margot Nicolas A , Naik Vidula , VanderVeen Laurie , Anoshchenko Olena , Singh Renu , Dvory-Sobol Hadas , Rhee Martin S , Callebaut Christian 
Published: September 2022

Abstract

Background
Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function in clinical development for the treatment of heavily treatment-experienced (HTE) people with HIV (PWH) harboring multidrug resistance (MDR) in combination with an optimized background regimen (OBR). Here we describe resistance analyses conducted in the pivotal phase 2/3 CAPELLA study.

Methods
CAPELLA enrolled viremic HTE PWH with resistance to ≥3 of 4 of the main antiretroviral (ARV) classes and resistance to ≥2 ARV drugs per class. Baseline resistance analyses used commercial assays (HIV-1 protease, reverse transcriptase, integrase genotypic/phenotypic tests). Postbaseline resistance was evaluated in participants experiencing virologic failure.

Results
At baseline, 46% of participants had resistance to the 4 main ARV drug classes, with one-third of participants having exhausted all drugs from ≥3 of the 4 main ARV classes. Treatment with LEN + OBR for 26 weeks led to viral suppression in 81% of participants. Postbaseline resistance mutations to lenacapavir occurred in 8 participants (6 with M66I, 1 with K70H, 1 with Q67H + K70R) who were receiving unintended functional LEN monotherapy at the time of resistance selection.

Conclusions
LEN added to OBR led to high efficacy in this HTE patient population with MDR but could select for resistance when used unintentionally as functional monotherapy.