bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of gamma ray iradiation on the growth, production and quality of Indigofera zollingeriana to support the development of forage crops
Authors: Hutasoit R , Romjali E , Tarigan A , Sirait J , Ginting S P , Harahap M K
Published: July 2022

Indigofera zollingeriana plant has high production and quality as ruminant feed. Its development is constrained by the availability of land. The alternative is to expand the agricultural area towards marginal lands. This study aims to evaluate the genetic diversity of Indigofera plants through gamma ray irradiation. Indigofera seeds were irradiated at doses: 0, 100, 200, 300, 400, 500, 600, 700, 800, 900, and 1000 grays. Based on the LD50 test, plants with radiation doses of 0 Gy, 100 Gy, 200 Gy, and 300 Gy are the best. The study was continued with a field growth test, in a randomized block design, four radiation dose treatments with 20 replications (plants). The parameters observed were plant growth characteristics, dry matter production and chemical composition. The results showed that the 300 Gy dose was higher and significantly different from other treatments in the parameters of plant height (268 cm), canopy width (195.5 cm) and fiber content (14.81%). The 0 Gy treatment was superior on the number of leaves (2,972), number of flowers 311, and calcium content of 1.76%. It was concluded that the dose of 0 and 300 Gy had advantages on the growth and production of Indigofera plants.
Fecundity profiles and physiological traits of Iraqi Awassi ewes supplemented mulberry leaves powder extract
Authors: Khafaji S S
Published: July 2022

The fecundity efficacy of ewes depends on reproductive hormones, ovarian activity so the current research was designed to improve the fecundity of Iraqi anestrous ewes by mulberry leaves (Morus alba) powder extract supplementation. 30th healthy non-pregnant ewes aged 2-3.5 year outbreeding season were divided into equal three groups, 1st group represent a (control) had fed the standard diet, second and third group represent T1 and T2 supplemented 15 and 30 mg/kg mulberry powder extract, respectively, for 40 day before sponge insertion. At day 28th of beginning supplementation the intra-vaginal sponge were inserted for 12 days. After sponges eliminated, estrous onset reported and blood collected before 20 and after 23 & 40 hrs of VSPR to estimate FSH, LH, progesterone and Estradiol concentration. Also, the fecundity, lambing and prolificacy rates had manifested. The results recorded a significant elevation in FSH, estradiol and LH while progesterone registered significant decreased in T1 &T2 comparing with C at 23 & 40 hr after VSPR. Also the fecundity, lambing rates were significantly higher in T1 &T2 in comparing with C. In concluded, that the mulberry leaves powder extract can augment the fecundity in anestrus Iraqi ewes by enhancing the fecundity profile and prolificacy rate.
A hyperplane restriction theorem and applications to reductions of ideals
Authors: Caviglia Giulio
Published: July 2022

Green’s general hyperplane restriction theorem gives a sharp upper bound for the Hilbert function of a standard graded algebra over an infinite field

K
K

modulo a general linear form. We strengthen Green’s result by showing that the linear forms that do not satisfy such estimate belong to a finite union of proper linear spaces. As an application we give a method to derive variations of the Eakin-Sathaye theorem on reductions. In particular, we recover and extend results by O’Carroll on the Eakin-Sathaye theorem for complete and joint reductions.
The Criminal Justice System in Mexico
Authors: Baron Hannah , Ingram Matthew C.
Published: July 2022

The criminal justice system in Mexico underwent a major constitutional reform to criminal procedure in 2008. The reform, alongside a transition to electoral democracy, followed a long period of authoritarianism in which criminal procedure served basic repressive functions in service to the regime. The reform has had a formal, de jure impact on the justice system, as well as more practical, de facto effects on the implementation of justice. It has also touched on every aspect of the criminal justice system, from police to prisons, and many elements of the reform promised to strengthen criminal justice with the aim of aligning institutional design and practices with principles of democratic governance and the rule of law. However, the reform’s implementation has been uneven and incomplete. Several factors helped implementation, and others continue to hinder it. Some legal practitioners, scholars, and activists pushed for the reform, although, unsurprisingly, it has been challenging to advocate for due process and the rights of the accused among both elites and the public amidst criminal wars and persistently high levels of violence and insecurity. The forward and backward movement of criminal procedure reform is an important part of the liberalizing and “illiberalizing” dynamics of democracy in Mexico. These tensions within the criminal justice system in Mexico resonate with larger literatures in politics, law, and socio-legal studies on due process, procedural justice, judicial empowerment, the causes and consequences of institutional change, and, most broadly, democratization, the quality of democracy, and the rule of law.
The Soviet Legacy in Central Asian Politics and Society
Authors: Artman Vincent
Published: July 2022

To trace the Soviet legacy in Central Asia is to trace the contours of a complex, multifaceted, and in many ways unfinished process. Between the advent of Russian imperial rule in the late 19th century and the collapse of Soviet power in 1991, the dynastic monarchies and nomadic federations of Central Asia were subdued, and the region was refashioned first into a European settler colony and then into industrialized national republics. Everything from political geography and institutions, economic patterns, urban patterns, and normative identities were indelibly shaped by the Soviet experience. Despite the legacies of the Soviet period, however, each of the states of Central Asia has also followed its own distinct trajectory since 1991, complicating the search for a coherent regional narrative. All of the post-Soviet states of Central Asia share certain common political, economic, and cultural “inheritances,” but their divergent histories since 1991 highlight not only the enduring significance of this shared patrimony, but also their remarkably different responses and trajectories since 1991.
Advancements in Social Sciences Applied to Health in Latin America and the Caribbean
Authors: Ianni Aurea Maria Zöllner , Ribeiro Patricia Tavares
Published: July 2022

The second half of the 20th century saw the development of social thought in health in Latin America and the Caribbean in which the social sciences had a central role. Such an innovative development was based on the understanding that health and disease are social processes that require the understanding of different health contexts. The origins of this development dates back to the renewal of medical teaching in Latin America, which had important support from the Pan-American Health Organization. The so-called field of social sciences in health then took shape, especially beginning in the 1970s and 1980s. The social sciences became part of teaching and assistance activities in social medicine and public health in many countries and contributed to consolidating postgraduate programs and networks of professors, researchers, professionals, and government agents who were active in public health actions and policies. Regarding Latin American realities, the issues of inequality in incidences of sickness and death and in the healthcare delivered to populations became relevant during this time. In close dialogue with relevant social groups, these actors have been significant in constructing responses to health problems in the region. Given the profound political, social, economic, environmental, and sanitary changes that took place in the transition from the 20th to the 21st century, social thought has attempted to meet the new empirical as well as theoretical and conceptual challenges to social sciences as applied to health. The analysis of the trajectory of this regional development, its details, advancements, and limits, is an important endeavor that should help to encourage suggestions toward bettering public health as well as fairness in these times of uncertainties and of new risks for humanity, as evidenced in an unprecedented way in the handling of the Covid-19 pandemic.
Impact Crater Densities as a Tool for Dating Planetary Surfaces
Authors: Hartmann William K.
Published: July 2022

The use of impact crater densities to estimate the ages of planetary surfaces began in the 1960s. Some predictive successes have been confirmed with radiometric dating of sites on the Moon and Mars. The method is highly dependent on our understanding of the rate of crater formation on different worlds, and, more importantly, on the history of that rate, starting with intense cratering during planetary formation 4.5 Ga ago. The system is thus calibrated by obtaining radiometric dates from samples of relatively homogeneous geologic units on various worlds.

Crater chronometry is still in its infancy. Future sample-returns and in situ measurements, obtained by missions from collaborating nations to various worlds, will provide ever-increasing improvements in the system in coming decades. Such data can lead to at least two-significant-figure measurements, not only of the ages of broad geologic provinces on solar system worlds, but of the characteristic survival times of various-sized smaller craters. Such data, in turn, clarify the rates of turnover of surface materials and the production rates of gravel-like regolith and megaregolith in the surface layers. Better measurements of the impact rate at various times, in turn, support better modeling of the accretion and fragmentation processes among early planetesimals as well as contemporary asteroids, in various parts of the solar system. Once the crater chronometry system is calibrated for various planetary bodies, important chronological information about those various planetary bodies can be obtained by orbital missions, without the need for expensive sample-return or lander missions on each individual surface.
Rock Art Conservation with a Focus on Southern Africa
Authors: Laue Ghilraen , Dean J. Claire
Published: July 2022

Rock art sites around the world are disappearing due to natural weathering, vandalism, and development. In Africa, conservation problems are compounded by the continent’s colonial legacy. Conservation can no longer just be seen in the narrow sense of conserving only the rock art; rather, there is a need for “consultative conservation” that includes the broader significance of a site and accommodates all stakeholders, including local communities. In this way, we can decolonize practices and work toward ideas for sustainable African conservation. Before embarking on conservation projects, all the values and significance of a site need to be considered. There is no point conserving an object or a site unless people find meaning in that conservation.

The natural deterioration of a site can be due to exposure to the elements, rain, fluctuations in humidity and temperature, biological growth both on the art and in front of it, animal activity, wildfires, and geological and seismic activity. Human activities that degrade a site include scratching or writing of graffiti, repainting or adding details to images, water or other liquids splashed on the paintings to bring out the details, smoke from fires made in the shelters, and target practice. Some of these conservation problems can be mitigated with remedial interventions, but these require the skills of professional conservators that are often expensive and out of reach for many rock art conservation projects. Conservation through the management of sites is far more common and feasible in Africa. In working toward management practices that take all a site’s significance into account, there is a need to acknowledge and work toward undoing injustices, coercions, and exploitation in both conservation practice and legislation. Rather than seeing the conservators’ way of doing things as “best practice” to be implemented from a top-down level, local conservation practices that have worked for centuries need to be considered alongside other conservation measures. Although attempts here are made to be as inclusive as possible the authors’ experience means that the focus and many of the examples given are from southern Africa.
Quality of critical care clinical practice guidelines involving pharmacotherapy recommendations
Authors: Edwards Christopher , Lam Jonathan , Gardiner Jordan , Erstad Brian L
Published: July 2022

Purpose

To assess the quality of critical care clinical practice guidelines (CPGs) involving pharmacotherapy recommendations.

Methods

A systematic electronic search was performed using PubMed, MEDLINE, and Embase for critical care CPGs published between 2012 and 2022 and involving pharmacotherapy recommendations. The Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument was employed to appraise CPG quality through independent assessment by 2 appraisers.

Results

Twenty-one CPGs were evaluated. The number of recommendations in each guideline ranged from 2 to 250, with a total of 1,604 recommendations. The number of strong (vs weak) recommendations in each guideline ranged from 0 to 31, with a total of 116 strong recommendations, or 7.23% of the total number of recommendations. There was at least 1 pharmacist author for 9 (43%) of the guidelines. The AGREE II domains for which mean quality scores of evaluated guidelines were highest were scope and purpose (0.88; 95% CI, 0.85-0.92), rigor of development (0.80; 95% CI, 0.77-0.83), clarity of presentation (0.84; 95% CI, 0.81-0.87), and editorial independence (0.86; 95% CI, 0.79-0.94), while those for which mean scores were lowest were stakeholder involvement (0.69; 95% CI, 0.63-0.75) and applicability (0.49; 95% CI, 0.43-0.55). Involvement of a pharmacist in CPG development was associated with significantly higher scoring for stakeholder involvement (P = 0.0356).

Conclusion

Strong recommendations accounted for less than 10% of the recommendations in the evaluated CPGs. Moreover, there are concerns related to guideline applicability (ie, advice or tools for putting recommendations into practice) and stakeholder involvement (ie, inclusion of individuals from all relevant groups). It is important to involve pharmacists in CPGs with pharmacotherapy recommendations.
Multivariate Base Rates of Low Neuropsychological Test Scores in Cognitively Intact Older Adults with Subjective Cognitive Decline from a Specialist Memory Clinic
Authors: Romero Kristoffer , Coleman Astrid , Heir Arjan , Leach Larry , Proulx Guy B
Published: July 2022

Objective

To avoid misdiagnosing mild cognitive impairment (MCI), knowledge of the multivariate base rates (MVBRs) of low scores on neuropsychological tests is crucial. Base rates have typically been determined from normative population samples, which may differ from clinically referred samples. The current study addresses this limitation by calculating the MVBR of low or high cognitive scores in older adults who presented to a memory clinic experiencing subjective cognitive decline but were not diagnosed with MCI.

Method

We determined the MVBRs on the Kaplan–Baycrest Neurocognitive Assessment for 107 cognitively healthy older adults (M age = 75.81), by calculating the frequency of patients producing n scores below or above different cut-off values (i.e., 1, 1.5, 2.0, 2.5 SD from the mean), stratifying by education and gender.

Results

Performing below or above cut-off was common, with more stringent cut-offs leading to lower base rates (≥1 low scores occurred in 84.1% of older adults at −1 SD, 55.1% at −1.5 SD, and 39.3% at −2 SD below the mean; ≥1 high scores occurred in 80.4% of older adults at +1 SD, 35.5% at +1.5 SD, and 16.8% at +2 SD above the mean). Higher education was associated with varying base rates. Overall, the MVBR of obtaining a low cognitive test score was higher in this clinic sample, compared with prior studies of normative samples.

Conclusions

MVBRs for clinically referred older adults experiencing memory complaints provide a diagnostic benefit, helping to prevent attributing normal variability to cognitive impairment and limiting false positive diagnoses.
Best practice and reproducible science are required to advance artificial intelligence in real-world applications
Authors: Liu Zhichao , Li Ting , Connor Skylar , Thakkar Shraddha , Roberts Ruth , Tong Weida
Published: July 2022

Drug-induced liver injury (DILI) is one of the most significant concerns in medical practice but yet it still cannot be fully recapitulated with existing in vivo, in vitro and in silico approaches. To address this challenge, Chen et al. [ 1] developed a deep learning-based DILI prediction model based on chemical structure information alone. The reported model yielded an outstanding prediction performance (i.e. 0.958, 0.976, 0.935, 0.947, 0.926 and 0.913 for AUC, accuracy, recall, precision, F1-score and specificity, respectively, on a test set), far outperforming all publicly available and similar in silico DILI models. This extraordinary model performance is counter-intuitive to what we know about the underlying biology of DILI and the principles and hypothesis behind this type of in silico approach. In this Letter to the Editor, we raise awareness of several issues concerning data curation, model validation and comparison practices, and data and model reproducibility.
AI for predicting chemical-effect associations at the chemical universe level—deepFPlearn
Authors: Schor Jana , Scheibe Patrick , Bernt Matthias , Busch Wibke , Lai Chih , Hackermüller Jörg
Published: July 2022

Many chemicals are present in our environment, and all living species are exposed to them. However, numerous chemicals pose risks, such as developing severe diseases, if they occur at the wrong time in the wrong place. For the majority of the chemicals, these risks are not known. Chemical risk assessment and subsequent regulation of use require efficient and systematic strategies. Lab-based methods—even if high throughput—are too slow to keep up with the pace of chemical innovation. Existing computational approaches are designed for specific chemical classes or sub-problems but not usable on a large scale. Further, the application range of these approaches is limited by the low amount of available labeled training data. We present the ready-to-use and stand-alone program deepFPlearn that predicts the association between chemical structures and effects on the gene/pathway level using a combined deep learning approach. deepFPlearn uses a deep autoencoder for feature reduction before training a deep feed-forward neural network to predict the target association. We received good prediction qualities and showed that our feature compression preserves relevant chemical structural information. Using a vast chemical inventory (unlabeled data) as input for the autoencoder did not reduce our prediction quality but allowed capturing a much more comprehensive range of chemical structures. We predict meaningful—experimentally verified—associations of chemicals and effects on unseen data. deepFPlearn classifies hundreds of thousands of chemicals in seconds. We provide deepFPlearn as an open-source and flexible tool that can be easily retrained and customized to different application settings at https://github.com/yigbt/deepFPlearn.
Predicting miRNA-disease associations based on graph attention networks and dual Laplacian regularized least squares
Authors: Wang Wengang , Chen Hailin
Published: July 2022

Increasing biomedical evidence has proved that the dysregulation of miRNAs is associated with human complex diseases. Identification of disease-related miRNAs is of great importance for disease prevention, diagnosis and remedy. To reduce the time and cost of biomedical experiments, there is a strong incentive to develop efficient computational methods to infer potential miRNA-disease associations. Although many computational approaches have been proposed to address this issue, the prediction accuracy needs to be further improved. In this study, we present a computational framework MKGAT to predict possible associations between miRNAs and diseases through graph attention networks (GATs) using dual Laplacian regularized least squares. We use GATs to learn embeddings of miRNAs and diseases on each layer from initial input features of known miRNA-disease associations, intra-miRNA similarities and intra-disease similarities. We then calculate kernel matrices of miRNAs and diseases based on Gaussian interaction profile (GIP) with the learned embeddings. We further fuse the kernel matrices of each layer and initial similarities with attention mechanism. Dual Laplacian regularized least squares are finally applied for new miRNA-disease association predictions with the fused miRNA and disease kernels. Compared with six state-of-the-art methods by 5-fold cross-validations, our method MKGAT receives the highest AUROC value of 0.9627 and AUPR value of 0.7372. We use MKGAT to predict related miRNAs for three cancers and discover that all the top 50 predicted results in the three diseases are confirmed by existing databases. The excellent performance indicates that MKGAT would be a useful computational tool for revealing disease-related miRNAs.
m6 Aexpress-BHM: predicting m6A regulation of gene expression in multiple-groups context by a Bayesian hierarchical mixture model
Authors: Zhang Teng , Zhang Shao-wu , Feng Jian , Zhang Bei
Published: July 2022

As the most abundant RNA modification, N6-methyladenosine (m6A) plays an important role in various RNA activities including gene expression and translation. With the rapid application of MeRIP-seq technology, samples of multiple groups, such as the involved multiple viral/ bacterial infection or distinct cell differentiation stages, are extracted from same experimental unit. However, our current knowledge about how the dynamic m6A regulating gene expression and the role in certain biological processes (e.g. immune response in this complex context) is largely elusive due to lack of effective tools. To address this issue, we proposed a Bayesian hierarchical mixture model (called m6Aexpress-BHM) to predict m6A regulation of gene expression (m6A-reg-exp) in multiple groups of MeRIP-seq experiment with limited samples. Comprehensive evaluations of m6Aexpress-BHM on the simulated data demonstrate its high predicting precision and robustness. Applying m6Aexpress-BHM on three real-world datasets (i.e. Flaviviridae infection, infected time-points of bacteria and differentiation stages of dendritic cells), we predicted more m6A-reg-exp genes with positive regulatory mode that significantly participate in innate immune or adaptive immune pathways, revealing the underlying mechanism of the regulatory function of m6A during immune response. In addition, we also found that m6A may influence the expression of PD-1/PD-L1 via regulating its interacted genes. These results demonstrate the power of m6Aexpress-BHM, helping us understand the m6A regulatory function in immune system.
Molormer: a lightweight self-attention-based method focused on spatial structure of molecular graph for drug–drug interactions prediction
Authors: Zhang Xudong , Wang Gan , Meng Xiangyu , Wang Shuang , Zhang Ying , Rodriguez-Paton Alfonso , Wang Jianmin , Wang Xun
Published: July 2022

Multi-drug combinations for the treatment of complex diseases are gradually becoming an important treatment, and this type of treatment can take advantage of the synergistic effects among drugs. However, drug–drug interactions (DDIs) are not just all beneficial. Accurate and rapid identifications of the DDIs are essential to enhance the effectiveness of combination therapy and avoid unintended side effects. Traditional DDIs prediction methods use only drug sequence information or drug graph information, which ignores information about the position of atoms and edges in the spatial structure. In this paper, we propose Molormer, a method based on a lightweight attention mechanism for DDIs prediction. Molormer takes the two-dimension (2D) structures of drugs as input and encodes the molecular graph with spatial information. Besides, Molormer uses lightweight-based attention mechanism and self-attention distilling to process spatially the encoded molecular graph, which not only retains the multi-headed attention mechanism but also reduces the computational and storage costs. Finally, we use the Siamese network architecture to serve as the architecture of Molormer, which can make full use of the limited data to train the model for better performance and also limit the differences to some extent between networks dealing with drug features. Experiments show that our proposed method outperforms state-of-the-art methods in Accuracy, Precision, Recall and F1 on multi-label DDIs dataset. In the case study section, we used Molormer to make predictions of new interactions for the drugs Aliskiren, Selexipag and Vorapaxar and validated parts of the predictions. Code and models are available at https://github.com/IsXudongZhang/Molormer.
Lakes in Hot Water: The Impacts of a Changing Climate on Aquatic Ecosystems
Authors: Woolway R Iestyn , Sharma Sapna , Smol John P
Published: July 2022

Our planet is being subjected to unprecedented climate change, with far-reaching social and ecological repercussions. Below the waterline, aquatic ecosystems are being affected by multiple climate-related and anthropogenic stressors, the combined effects of which are poorly understood and rarely appreciated at the global stage. A striking consequence of climate change on aquatic ecosystems is that many are experiencing shorter periods of ice cover, as well as earlier and longer summer stratified seasons, which often result in a cascade of ecological and environmental consequences, such as warmer summer water temperatures, alterations in lake mixing and water levels, declines in dissolved oxygen, increased likelihood of cyanobacterial algal blooms, and the loss of habitat for native cold-water fisheries. The repercussions of a changing climate include impacts on freshwater supplies, water quality, biodiversity, and the ecosystem benefits that they provide to society.
A controlled effects approach to assessing immune correlates of protection
Authors: Gilbert Peter B , Fong Youyi , Kenny Avi , Carone Marco
Published: July 2022

An immune correlate of risk (CoR) is an immunologic biomarker in vaccine recipients associated with an infectious disease clinical endpoint. An immune correlate of protection (CoP) is a CoR that can be used to reliably predict vaccine efficacy (VE) against the clinical endpoint and hence is accepted as a surrogate endpoint that can be used for accelerated approval or guide use of vaccines. In randomized, placebo-controlled trials, CoR analysis is limited by not assessing a causal vaccine effect. To address this limitation, we construct the controlled risk curve of a biomarker, which provides the causal risk of an endpoint if all participants are assigned vaccine and the biomarker is set to different levels. Furthermore, we propose a causal CoP analysis based on controlled effects, where for the important special case that the biomarker is constant in the placebo arm, we study the controlled vaccine efficacy curve that contrasts the controlled risk curve with placebo arm risk. We provide identification conditions and formulae that account for right censoring of the clinical endpoint and two-phase sampling of the biomarker, and consider G-computation estimation and inference under a semiparametric model such as the Cox model. We add modular approaches to sensitivity analysis that quantify robustness of CoP evidence to unmeasured confounding. We provide an application to two phase 3 trials of a dengue vaccine indicating that controlled risk of dengue strongly varies with 50$\%$ neutralizing antibody titer. Our work introduces controlled effects causal mediation analysis to immune CoP evaluation.
Towards adaptive deep brain stimulation for freezing of gait
Authors: Tan Huiling
Published: July 2022

This scientific commentary refers to ‘Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait’ by Yin et al. (https://doi.org/10.1093/brain/awac121).
Interictal epileptiform discharges show distinct spatiotemporal and morphological patterns across wake and sleep
Authors: Fouad Amal , Azizollahi Hamed , Le Douget Jean-Eudes , Lejeune François-Xavier , Valderrama Mario , Mayor Liliana , Navarro Vincent , Le Van Quyen Michel
Published: July 2022

Presurgical evaluation of mesial temporal and neocortical focal pharmacoresistant epilepsy patients using intracranial EEG recordings has led to the generation of extensive data on interictal epileptiform discharges, located within or remotely from seizure onset zones. In this study, we used this data to investigate how interictal epileptiform discharges are modulated and how their spatial distribution changes during wake and sleep and analysed the relationship between these discharge events and seizure onset zones. Preoperative evaluation data from 11 adult patients with focal pharmacoresistant epilepsy were extracted from the Epilepsiae database. Interictal epileptiform discharges were automatically detected during wakefulness and over several hours of continuous seizure-free sleep (total duration of EEG recordings:106.7 h; mean per patient: 9.7 h), and analysed across four brain areas (mesial temporal, lateral neocortical, basal cortical and the temporal pole). Sleep stages were classified manually from scalp EEG. Discharge events were characterized according to their rate and morphology (amplitude, sharpness and duration). Eight patients had a seizure onset zone over mesial areas and three patients over lateral neocortical areas. Overall, discharge rates varied across brain areas during wakefulness and sleep [wake/sleep stages × brain areas interaction; Wald χ2(df = 6) = 31.1, P < 0.0001]. N2–N3 non-rapid eye movement sleep increased interictal epileptiform discharges in mesial areas compared with wakefulness and rapid eye movement sleep (P < 0.0001), and to other areas (P < 0.0001 for all comparisons). This mesial pattern was observed both within and outside of seizure onset zones. During wakefulness, the rate of interictal epileptiform discharges was significantly higher than during N2–N3 non-rapid eye movement sleep (P = 0.04), and rapid eye movement sleep (P = 0.01) in lateral neocortical areas (referred to as lateral neocortical pattern), a finding that was more pronounced in seizures onset zones (P = 0.004). The morphological characteristics of the discharge events were modulated during wakefulness and sleep stages across brain areas. The effect of seizure onset zones on discharge morphology was conditioned by brain area and was particularly marked in temporal pole areas. Our analysis of discharge patterns in relation to cerebral localization, vigilance state and the anatomical affiliation of seizure onset zones revealed the global and local aspects of the complex relationship between interictal discharges, sleep and seizure onset zones. This novel approach may lead to a better understanding of cognitive decline and responses to therapy, as well as to adaptation of surgical interventions for epileptic patients.
Row, Row, Row Your Boat: How to Not Find Weak Keys in Pilsung
Authors: Chuengsatiansup Chitchanok , Ronen Eyal , Rose Gregory G , Yarom Yuval
Published: July 2022

The Pilsung cipher is part of the North Korean Red Star operating system, which was leaked to the West in 2014. Initial analysis by Kryptos Logic reported a possibility of a class of weak keys due to the use of pseudo-random diffusion. Following this lead, we analyzed the cipher and identified a small class of such weak keys. We developed techniques for searching for a key that belongs to the class. After spending thousands of CPU hours, we found a supposedly weak key for a slightly weaker version of Pilsung, but the key did not behave as we expected. On further investigation we found out a crucial misunderstanding in a critical part of the cipher and that no such class of weak keys exists in Pilsung. Thus, this paper makes two main contributions to the art of cryptanalysis. First, it identifies and shows how to investigate a potential weakness in randomizing diffusion, which although does not exist in Pilsung, may affect future designs. Second, it highlights the need for early verification of results in order to identify errors before expending significant resources.
A BERT-based ensemble learning approach for the BioCreative VII challenges: full-text chemical identification and multi-label classification in PubMed articles
Authors: Lin Sheng-Jie , Yeh Wen-Chao , Chiu Yu-Wen , Chang Yung-Chun , Hsu Min-Huei , Chen Yi-Shin , Hsu Wen-Lian
Published: July 2022

In this research, we explored various state-of-the-art biomedical-specific pre-trained Bidirectional Encoder Representations from Transformers (BERT) models for the National Library of Medicine - Chemistry (NLM CHEM) and LitCovid tracks in the BioCreative VII Challenge, and propose a BERT-based ensemble learning approach to integrate the advantages of various models to improve the system’s performance. The experimental results of the NLM-CHEM track demonstrate that our method can achieve remarkable performance, with F1-scores of 85% and 91.8% in strict and approximate evaluations, respectively. Moreover, the proposed Medical Subject Headings identifier (MeSH ID) normalization algorithm is effective in entity normalization, which achieved a F1-score of about 80% in both strict and approximate evaluations. For the LitCovid track, the proposed method is also effective in detecting topics in the Coronavirus disease 2019 (COVID-19) literature, which outperformed the compared methods and achieve state-of-the-art performance in the LitCovid corpus.

Database URL: https://www.ncbi.nlm.nih.gov/research/coronavirus/.
GeMo: a web-based platform for the visualization and curation of genome ancestry mosaics
Authors: Summo Marilyne , Comte Aurore , Martin Guillaume , Perelle Pierrick , Weitz Eric M , Droc Gaëtan , Rouard Mathieu
Published: July 2022

In silico chromosome painting is a technique by which contributions of distinct genetic groups are represented along chromosomes of hybrid individuals. This type of analysis is used to study the mechanisms by which these individuals were formed. Such techniques are well adapted to identify genetic groups contributing to these individuals as well as hybridization events. It can also be used to follow chromosomal recombinations that occurred naturally or were generated by selective breeding. Here, we present GeMo, a novel interactive web-based and user-oriented interface to visualize in a linear-based fashion results of in silico chromosome painting. To facilitate data input generation, a script to execute analytical commands is provided and an interactive data curation mode is supported to ensure consistency of the automated procedure. GeMo contains preloaded datasets from published studies on crop domestication but can be applied to other purposes, such as breeding programs Although only applied so far on plants, GeMo can handle data from animals as well.

Database URL: https://gemo.southgreen.fr/
Cerebrovascular accidents in paediatric patients supported by the Berlin Heart EXCOR
Authors: Rohde Sofie , Sandica Eugen , Veen Kevin , Miera Oliver , Amodeo Antonio , Napoleone Carlo Pace , Özbaran Mustafa , Sliwka Joanna , Thiruchelvam Timothy , Zimpfer Daniel , Schubert Stephan , Bogers Ad J J C , de By Theo M M H
Published: July 2022

OBJECTIVES

Ventricular assist device support as a bridge to transplant or recovery is a well-established therapy in children on the cardiac transplant waiting list. The goal of this study was to investigate the incidence of and the associated factors for cerebrovascular accidents in paediatric patients supported by a Berlin Heart EXCOR.

METHODS

All patients <19 years of age supported by a Berlin Heart EXCOR between January 2011 and January 2021 from the European Registry for Patients with Mechanical Circulatory Support were included.

RESULTS

In total, 230 patients were included. A total of 140 (60.9%) patients had a diagnosis of dilated cardiomyopathy. 46 patients (20.0%) sustained 55 cerebrovascular accidents, with 70.9% of the episodes within 90 days after the ventricular assist device was implanted. The event rate of cerebrovascular accidents was highest in the first era (0.75). Pump thrombosis and secondary need for a right ventricular assist device were found to be associated with a cerebrovascular accident (hazard ratio 1.998, P = 0.040; hazard ratio 11.300, P = 0.037). At the 1-year follow-up, 44.4% of the patients had received a transplant, 13.1% were weaned after recovery and 24.5% had died. Event rates for mortality showed a significantly decreasing trend.

CONCLUSIONS

Paediatric ventricular assist device support is associated with important adverse events, especially in the early phase after the device is implanted. Pump thrombosis and the need for a secondary right ventricular assist device are associated with cerebrovascular accidents. Furthermore, an encouragingly high rate of recovery in this patient population was shown, and death rates declined. More complete input of data into the registry, especially concerning anticoagulation protocols, would improve the data.
Health literacy and prognosis of heart failure: a prospective propensity-matched study in the community
Authors: Gomez Rocio , Andrey Jose L , Puerto Jose L , Romero Sotero P , Pedrosa Maria J , Rosety-Rodriguez Manuel , Gomez Francisco
Published: July 2022

Aims

Health literacy (HL), the ability to obtain and understand health information, is critical to self-care in chronic disorders. A low HL is common among these patients and has been associated with a worse prognosis. Nevertheless, the relationship between HL and the prognosis of heart failure (HF) with reduced (HFrEF) vs. preserved (HFpEF) ejection fraction remains unsettled. To analyse the relationship between HL and the prognosis of patients with incident HFrEF and HFpEF.

Methods and results

Prospective study over 10 years (2010–19) on 6444 patients diagnosed with incident HF. The main outcomes were mortality, hospitalizations, and visits to emergency services. The independent relationship between HL and the prognosis, stratifying patients for cardiovascular comorbidity after propensity score-matching was analysed.

After matching 5355 HF patients, 1785 with low HL (874 with HFrEF and 911 with HFpEF) vs. 3570 with adequate HL (1748 with HFrEF and 1822 with HFpEF), during a median follow-up of 5.41 years, 3874 patients died (72.3%) and 3699 patients were hospitalized (69.1%). After adjustment for potential confounders, an adequate HL was associated with a lower all-cause and cardiovascular mortality, less hospitalizations, and less 30-day readmissions [relative risk (RR) for HF <0.72 (0.66–0.86), RR for HFrEF <0.69 (0.63–0.95), and RR for HFpEF <0.62 (0.55–0.88), P < 0.001 in all cases], both for patients with HFrEF and HFpEF. Analyses of recurrent hospitalizations gave larger HL effects than time-to-first-event analyses.

Conclusions

In this propensity-matched study, a low HL is associated with a worse prognosis of patients with incident HFrEF and HFpEF.
Trade and traders in Plantation Ulster, c.1600–c.1650
Authors: Roulston William , Scott Brendan
Published: July 2022

The Ulster Plantation of the early seventeenth century introduced to that province not only new markets and marketplaces, but also a new community interested in buying and selling the goods now on offer there. The Ulster port books for 1612–15 not only offer a great deal of information regarding the products being bought and sold in the province, but also provide us with the names and activities of the merchants and the captains entrusted with the transportation of these goods. This essay investigates the traders themselves, their activities and the conditions under which they operated during this unsettled period.
Updated variant curation expert panel criteria and pathogenicity classifications for 251 variants for RYR1-related malignant hyperthermia susceptibility
Authors: Johnston Jennifer J , Dirksen Robert T , Girard Thierry , Hopkins Phil M , Kraeva Natalia , Ognoon Mungunsukh , Radenbaugh K Bailey , Riazi Sheila , Robinson Rachel L , Saddic, III Louis A , Sambuughin Nyamkhishig , Saxena Richa , Shepherd Sarah , Stowell Kathryn , Weber James , Yoo Seeley , Rosenberg Henry , Biesecker Leslie G
Published: July 2022

The ClinGen malignant hyperthermia susceptibility (MHS) variant curation expert panel specified the American College of Medical Genetics and Genomics/Association of Molecular Pathologists (ACMG/AMP) criteria for RYR1-related MHS and a pilot analysis of 84 variants was published. We have now classified an additional 251 variants for RYR1-related MHS according to current ClinGen standards and updated the criteria where necessary. Criterion PS4 was modified such that individuals with multiple RYR1 variants classified as pathogenic (P), likely pathogenic (LP), or variant of uncertain significance (VUS) were not considered as providing evidence for pathogenicity. Criteria PS1 and PM5 were revised to consider LP variants at the same amino-acid residue as providing evidence for pathogenicity at reduced strength. Finally, PM1 was revised such that if PS1 or PM5 are used PM1, if applicable, should be downgraded to supporting. Of the 251 RYR1 variants, 42 were classified as P/LP, 16 as B/LB, and 193 as VUS. The primary driver of 175 VUS classifications was insufficient evidence supporting pathogenicity, rather than evidence against pathogenicity. Functional data supporting PS3/BS3 was identified for only 13 variants. Based on the posterior probabilities of pathogenicity and variant frequencies in gnomAD, we estimated the prevalence of individuals with RYR1-related MHS pathogenic variants to be between 1/300 and 1/1075, considerably higher than current estimates. We have updated ACMG/AMP criteria for RYR1-related MHS and classified 251 variants. We suggest that prioritization of functional studies is needed to resolve the large number of VUS classifications and allow for appropriate risk assessment. RYR1-related MHS pathogenic variants are likely to be more common than currently appreciated.
Immunomodulatory functions of the circ_001678/miRNA-326/ZEB1 axis in non-small cell lung cancer via the regulation of PD-1/PD-L1 pathway
Authors: Tian Qi , Wu Tong , Zhang Xiudi , Xu Ke , Yin Xiaobo , Wang Xiaojie , Shi Shanshan , Wang Ping , Gao Liming , Xu Shufeng , Liu Xinyan
Published: July 2022

High-throughput circular RNA (circRNA) sequencing identified circRNA_001678 (circ_001678) as an upregulated circRNA in non-small cell lung cancer (NSCLC) tissues. Hence, the current study sought to investigate the function and the underlying mechanism of circRNA_001678 in immune escape of NSCLC. Briefly, commercially purchased NSCLC cell lines were adopted for in vitro experiment to evaluate the effects of circ_001678 over-expression or knockdown on cell biological functions, including proliferation, migration and invasive abilities. In addition, the effects of circ_001678 on the in vivo tumorigenicity ability were evaluated for verification. Accordingly, we uncovered that circ_001678 over-expression augmented NSCLC progression in vitro and enhanced tumorigenicity ability in vivo. The interaction between circ_001678 and miR-326 predicted online was verified by means of luciferase and RNA pull-down assays. Furthermore, circ_001678 could sponge miR-326 to up-regulate ZEB1. On the other hand, the tumor-promoting effects of circ_001678 could be inhibited by anti-PD-L1/PD-1 treatment. Mechanistically, circ_001678 led to the activation of the PD-1/PD-L1 pathway to promote CD8+ T cell apoptosis, thereby inducing NSCLC cell immune escape via regulation of the miR-326/ZEB1 axis. To conclude, our findings revealed that circ_001678 sponges miR-326 to up-regulate ZEB1 expression and induce the PD-1/PD-L1 pathway-dependent immune escape, thereby promoting the malignant progression of NSCLC.
Is modularity robust to misfits? A formal test
Authors: Fang Christina , Kim Ji-hyun Jason
Published: July 2022

In this paper, we ask—is the power of modularity robust to a potential misfit between organizations and their underlying technical systems? We design a computational model to systematically explore the role of misfits, building on prior models using the numerical NK paradigm. We find that the impact of misfits is either neutral or even performance-enhancing when the organizations carry out a decentralized search while coordinating and evaluating the alternatives at the organizational level. This is good news for the theoretical efficacy of modularity—the benefits of modular search do not have to be contingent upon a precise understanding of the underlying technical dependencies. The reason is that in decentralized and hierarchical systems, there exists a tension between (i) the exploration and generation of alternatives and (ii) the exercise of restraint and control. The latter is important to implement only those alternatives that have an overall positive impact on the organization, by limiting the downside of radical experiments.
Interpretation of Mendelian randomization using a single measure of an exposure that varies over time
Authors: Morris Tim T , Heron Jon , Sanderson Eleanor C M , Davey Smith George , Didelez Vanessa , Tilling Kate
Published: July 2022

Background

Mendelian randomization (MR) is a powerful tool through which the causal effects of modifiable exposures on outcomes can be estimated from observational data. Most exposures vary throughout the life course, but MR is commonly applied to one measurement of an exposure (e.g. weight measured once between ages 40 and 60 years). It has been argued that MR provides biased causal effect estimates when applied to one measure of an exposure that varies over time.

Methods

We propose an approach that emphasizes the liability that causes the entire exposure trajectory. We demonstrate this approach using simulations and an applied example.

Results

We show that rather than estimating the direct or total causal effect of changing the exposure value at a given time, MR estimates the causal effect of changing the underlying liability for the exposure, scaled to the effect of the liability on the exposure at that time. As such, results from MR conducted at different time points are expected to differ (unless the effect of the liability on exposure is constant over time), as we illustrate by estimating the effect of body mass index measured at different ages on systolic blood pressure.

Conclusion

Univariable MR results should not be interpreted as time-point-specific direct or total causal effects, but as the effect of changing the liability for the exposure. Estimates of how the effects of a genetic variant on an exposure vary over time, together with biological knowledge that provides evidence regarding likely effective exposure periods, are required to interpret time-point-specific causal effects.