bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using interpretable deep learning to model cancer dependencies
Authors: Lin Chih-Hsu , Lichtarge Olivier 
Published: May 2021

AbstractMotivationCancer dependencies provide potential drug targets. Unfortunately, dependencies differ among cancers and even individuals. To this end, visible neural networks (VNNs) are promising due to robust performance and the interpretability required for the biomedical field.ResultsWe design Biological visible neural network (BioVNN) using pathway knowledge to predict cancer dependencies. Despite having fewer parameters, BioVNN marginally outperforms traditional neural networks (NNs) and converges faster. BioVNN also outperforms an NN based on randomized pathways. More importantly, dependency predictions can be explained by correlating with the neuron output states of relevant pathways, which suggest dependency mechanisms. In feature importance analysis, BioVNN recapitulates known reaction partners and proposes new ones. Such robust and interpretable VNNs may facilitate the understanding of cancer dependency and the development of targeted therapies.Availability and implementationCode and data are available at https://github.com/LichtargeLab/BioVNNSupplementary informationSupplementary data are available at Bioinformatics online.
SAMF: a self-adaptive protein modeling framework
Authors: Ding Wenze , Xu Qijiang , Liu Siyuan , Wang Tong , Shao Bin , Gong Haipeng , Liu Tie-Yan 
Published: May 2021

Abstract

Motivation
Gradient descent-based protein modeling is a popular protein structure prediction approach that takes as input the predicted inter-residue distances and other necessary constraints and folds protein structures by minimizing protein-specific energy potentials. The constraints from multiple predicted protein properties provide redundant and sometime conflicting information that can trap the optimization process into local minima and impairs the modeling efficiency.

Results
To address these issues, we developed a self-adaptive protein modeling framework, SAMF. It eliminates redundancy of constraints and resolves conflicts, folds protein structures in an iterative way, and picks up the best structures by a deep quality analysis system. Without a large amount of complicated domain knowledge and numerous patches as barriers, SAMF achieves the state-of-the-art performance by exploiting the power of cutting-edge techniques of deep learning. SAMF has a modular design and can be easily customized and extended. As the quality of input constraints is ever growing, the superiority of SAMF will be amplified over time.

Availability and implementation
The source code and data for reproducing the results is available at https://msracb.blob.core.windows.net/pub/psp/SAMF.zip.

Supplementary information
Supplementary data are available at Bioinformatics online.
Sodium–glucose cotransporter 2 inhibitors: renal outcomes according to baseline albuminuria
Authors: Delanaye Pierre , Wissing Karl Martin , Scheen Andre J 
Published: May 2021

ABSTRACT
Sodium–glucose co-transporter 2 inhibitors (SGLT2is) reduce albuminuria and hard renal outcomes (decline of renal function, renal replacement therapy and renal death) in patients with/without type 2 diabetes at high cardiovascular or renal risk. The question arises whether baseline albuminuria also influences renal outcomes with SGLT2is as reported with renin–angiotensin–aldosterone system inhibitors. Post hoc analyses focusing on albuminuria and renal outcomes of four cardiovascular outcome trials [EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), CANVAS (Canagliflozin Cardiovascular Assessment Study), DECLARE-TIMI 58 (Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events–Thrombolysis in Myocardial Infarction 58) and VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial)] and some renal data from two heart failure trials [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) and EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction)] showed renal protection with SGLT2is without significant interaction (P &gt; 0.10) when comparing renal outcomes according to baseline levels (A1, A2 and A3) of urinary albumin:creatinine ratio (UACR), a finding confirmed in a dedicated meta-analysis. Two trials [CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) and DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease)] specifically recruited patients with CKD and UACRs of 200–5000 mg/g. A post hoc analysis of CREDENCE that distinguished three subgroups according to UACR (300–1000, 1000–3000 and &gt;3000 mg/g) showed a greater relative reduction in UACR in patients with lower baseline albuminuria levels (P for interaction = 0.03). Patients with a UACR &gt;1000 mg/g showed a significantly greater reduction in absolute (P for interaction &lt; 0.001) and a trend in relative (P for interaction = 0.25) risk of renal events versus those with lower UACR levels. In conclusion, baseline UACR levels do not significantly influence the nephroprotection by SGLT2is, yet the greater protection in patients with very high UACRs in CREDENCE deserves confirmation. The underlying mechanisms of renal protection with SGLT2is might be different in patients with or without (high) UACR.
The second warning to humanity: contributions and solutions from conservation physiology
Authors: Madliger Christine L , Franklin Craig E , Chown Steven L , Fuller Andrea , Hultine Kevin R , Costantini David , Hopkins William A , Peck Myron A , Rummer Jodie L , Sack Lawren , Willis Craig K R , Cooke Steven J 
Published: May 2021

AbstractIn 1992, the Union of Concerned Scientists shared their ‘World Scientists’ Warning to Humanity’ with governmental leaders worldwide, calling for immediate action to halt the environmental degradation that threatens the systems that support life on Earth. A follow-up ‘Second Warning’ was released in 2017, with over 15 000 scientists as signatories, describing the lack of progress in adopting the sustainable practices necessary to safeguard the biosphere. In their ‘Second Warning’, Ripple and colleagues provided 13 ‘diverse and effective steps humanity can take to transition to sustainability.’ Here, we discuss how the field of conservation physiology can contribute to six of these goals: (i) prioritizing connected, well-managed reserves; (ii) halting the conversion of native habitats to maintain ecosystem services; (iii) restoring native plant communities; (iv) rewilding regions with native species; (v) developing policy instruments; and (vi) increasing outdoor education, societal engagement and reverence for nature. Throughout, we focus our recommendations on specific aspects of physiological function while acknowledging that the exact traits that will be useful in each context are often still being determined and refined. However, for each goal, we include a short case study to illustrate a specific physiological trait or group of traits that is already being utilized in that context. We conclude with suggestions for how conservation physiologists can broaden the impact of their science aimed at accomplishing the goals of the ‘Second Warning’. Overall, we provide an overview of how conservation physiology can contribute to addressing the grand socio-environmental challenges of our time.
Presynaptic Gαo (GOA-1) signals to depress command neuron excitability and allow stretch-dependent modulation of egg laying in Caenorhabditis elegans
Authors: Ravi Bhavya , Zhao Jian , Chaudhry Sana I , Signorelli Rossana , Bartole Mattingly , Kopchock Richard J , Guijarro Christian , Kaplan Joshua M , Kang Lijun , Collins Kevin M 
Published: May 2021

Abstract
Egg laying in the nematode worm Caenorhabditis elegans is a two-state behavior modulated by internal and external sensory input. We have previously shown that homeostatic feedback of embryo accumulation in the uterus regulates bursting activity of the serotonergic HSN command neurons that sustains the egg-laying active state. How sensory feedback of egg release signals to terminate the egg-laying active state is less understood. We find that Gαo, a conserved Pertussis Toxin-sensitive G protein, signals within HSN to inhibit egg-laying circuit activity and prevent entry into the active state. Gαo signaling hyperpolarizes HSN, reducing HSN Ca2+ activity and input onto the postsynaptic vulval muscles. Loss of inhibitory Gαo signaling uncouples presynaptic HSN activity from a postsynaptic, stretch-dependent homeostat, causing precocious entry into the egg-laying active state when only a few eggs are present in the uterus. Feedback of vulval opening and egg release activates the uv1 neuroendocrine cells which release NLP-7 neuropeptides which signal to inhibit egg laying through Gαo-independent mechanisms in the HSNs and Gαo-dependent mechanisms in cells other than the HSNs. Thus, neuropeptide and inhibitory Gαo signaling maintain a bi-stable state of electrical excitability that dynamically controls circuit activity in response to both external and internal sensory input to drive a two-state behavior output.
The hazard of coseismic gaps: the 2021 Fukushima earthquake
Authors: Kiser Eric , Kehoe Haiyang 
Published: May 2021

SUMMARY
Subduction zones are associated with significant seismic hazards around the world and determining the future locations of large earthquakes within these systems is a perpetual challenge of the Earth sciences. This study presents back-projection results from the 2021 Mw 7.1 Fukushima earthquake which show that the rupture area of this event filled a previously identified coseismic gap within the rupture area of the 2011 Mw 9.1 Tohoku-oki earthquake. These results, combined with observations of a similar coseismic gap from the 2010 Mw 8.8 Maule, Chile earthquake that was subsequently filled by a Mw 7.1 aftershock, demonstrate that future assessments of seismic hazards following giant earthquakes should include the identification of coseismic gaps left within main shock rupture areas.
The Development and Neuronal Complexity of Bipinnaria Larvae of the Sea StarAsterias rubens
Authors: Carter Hugh F , Thompson Jeffrey R , Elphick Maurice R , Oliveri Paola 
Published: May 2021

SynopsisFree-swimming planktonic larvae are a key stage in the development of many marine phyla, and studies of these organisms have contributed to our understanding of major genetic and evolutionary processes. Although transitory, these larvae often attain a remarkable degree of tissue complexity, with well-defined musculature and nervous systems. Among the best studied are larvae belonging to the phylum Echinodermata, but with work largely focused on the pluteus larvae of sea urchins (class Echinoidea). The greatest diversity of larval strategies among echinoderms is found in the class Asteroidea (sea stars), organisms that are rapidly emerging as experimental systems for genetic and developmental studies. However, the bipinnaria larvae of sea stars have only been studied in detail in a small number of species and although they have been relatively well described neuro-anatomically, they are poorly understood neurochemically. Here, we have analyzed embryonic development and bipinnaria larval anatomy in the common North Atlantic sea star Asterias rubens, using a variety of staining methods in combination with confocal microscopy. Importantly, the chemical complexity of the nervous system of bipinnaria larvae was revealed through use of a diverse set of antibodies, with identification of at least three centers of differing neurochemical signature within the previously described nervous system: the anterior apical organ, oral region, and ciliary bands. Furthermore, the anatomy of the musculature and sites of cell division in bipinnaria larvae was analyzed. Comparisons of developmental progression and molecular anatomy across the Echinodermata provided a basis for hypotheses on the shared evolutionary and developmental processes that have shaped this group of animals. We conclude that bipinnaria larvae appear to be remarkably conserved across ∼200 million years of evolutionary time and may represent a strong evolutionary and/or developmental constraint on species utilizing this larval strategy.
Obsessive Compulsive Disorder During Coronavirus Disease 2019 (COVID-19): 2- and 6-Month Follow-Ups in a Clinical Trial
Authors: Carmi Lior , Ben-Arush Oded , Fostick Leah , Cohen Hagit , Zohar Joseph 
Published: May 2021

Abstract

Background
Psychiatric patients are perceived to be especially vulnerable during a pandemic, as it increases stress and uncertainty. Several current publications have considered obsessive-compulsive disorder (OCD) patients to be particularly vulnerable during the coronavirus disease 2019 (COVID-19), and clinicians were advised to adjust treatments accordingly. The purpose of this study was to evaluate the 2- and 6-month impacts of COVID-19 on the symptom severity of OCD patients.

Methods
A cohort of OCD patients actively treated with Exposure and Response Prevention (ERP) combined with pharmacological treatment was evaluated as part of their regular psychiatric assessment twice: 113 patients were evaluated at their 2-month follow-up and 90 patients (from that cohort) were evaluated at their 6-month follow up.

Results
Obsessive-compulsive symptom deterioration was not present in 84% of the patients at the 2-month follow-up and 96% of the patients at the 6-month follow-up. The results were also replicated in the OCD subgroup that included patients with contamination (washers) and illness obsessions, who were believed to be particularly vulnerable considering their obsessional content.

Conclusions
OCD patients (including those with obsessions related to contamination and health) who were under active ERP and pharmacological treatment did not experience exacerbated symptoms during COVID-19 at their 2- and 6-month follow-ups.
The Evaluation of the Containment Efficacy of Semi-Rigid Isolators for Housing Cages of Laboratory Animals Infected With BSL-3 Agents
Authors: DeTolla Louis , Johnson David K , Reynolds Scott D , Sanchez Rigoberto , Weichbrod Robert H , Terzi Matthew C 
Published: May 2021

Abstract
Research animals models infected with Biosafety Level-3 (BSL-3) agents need to be housed in specialized biocontainment caging. Most of these specialized cages have input and exhaust that is high efficiency particulate air filtered and sealed to prevent escape of the BSL-3 agent. An alternative to the use of the above BSL-3 biocontainment caging is the use of a flexible film or modified semi-rigid plastic film isolator that has its own high efficiency particulate air–filtered input and exhaust and is sealed with respect to the animal room environment, thus preventing BSL-3 agent escape. Standard caging can be housed within such an isolator. Computational fluid dynamics was used to evaluate the integrity of modified semi-rigid isolators for containment of aerosolized BSL-3 agents. Three isolators were located inside an animal BSL-3 room to provide an extra tier of protection and to permit different infectious studies within the same room while reducing or eliminating the risk of cross-contamination. The isolators were sized to house caging for rabbits and smaller non-human primates such as marmosets, African greens, and macaques. Multiple case studies of failure scenarios were investigated, including isolator breaches through the plastic membrane seam separation and rips, and exhaust fan failure. Breaching the level of containment provided by the isolators required the improbable simultaneous event of a plastic membrane rip in addition to the rare malfunction of the back-up exhaust fans. Each isolator was equipped with 2 blower motors connected in parallel to a common exhaust plenum and a battery backup. Even with this rare double (simultaneous) event, the animal BSL-3 room air exhaust system was able to contain the few droplets released in the simulated computational fluid dynamics breach. The modified semi-rigid isolators with negative airflow proved safe and effective for aerosol studies using BSL-3 agents, even in the unlikely event of a breach in containment.
Patient data ownership: who owns your health?
Authors: Liddell Kathleen , Simon David A , Lucassen Anneke 
Published: May 2021

Abstract
This article answers two questions from the perspective of United Kingdom law and policy: (i) is health information property? and (ii) should it be? We argue that special features of health information make it unsuitable for conferral of property rights without an extensive system of data-specific rules, like those that govern intellectual property. Additionally, we argue that even if an extensive set of rules were developed, the advantages of a property framework to govern health information would be slight: propertization is unlikely to enhance patient self-determination, increase market efficiency, provide patients a foothold in the data economy, clarify legal uses of information, or encourage data-driven innovation. The better approach is to rely less, not more, on property. We recommend a regulatory model with four signature features: (i) substantial protection for personal health data similar to the GDPR with transparent limits on how, when, and by whom patient data can be accessed, used, and transmitted; (ii) input from relevant stakeholders; (iii) interoperability; and (iv) greater research into a health-data service, rather than goods, model.
The Effects of Person-Centered Social Support Messages on Recipient Distress Over Time within a Conversation
Authors: Rains Stephen A , High Andrew C 
Published: May 2021

Abstract
Although prior research documents the benefits of supportive messages containing higher levels of verbal person centeredness (VPC), the effects of this message property over time within a discussion are not well understood. This project evaluated predictions about the effects of high and low VPC messages over time drawn from the theory of conversationally induced reappraisals and the dual-process model of supportive communication outcomes. Participants (N = 281) completed an interaction with a computerized support provider in which the level of VPC was manipulated. Before and after the interaction and after receiving each of four supportive messages, participants rated their emotional distress, reappraisal, and validation. Participants in the high and low VPC conditions exhibited a significant reduction in emotional distress from before to after their interaction. Receiving subsequent messages with high levels of VPC produced a non-linear trend in distress reduction, whereas receiving subsequent low VPC messages fostered little change.
Axisymmetric model of the sealing cylinder in service: analytical solutions
Authors: Jin Lan , Cheng Yonggui , Zhang Kai , Xue Zhangna , Liu Jianlin 
Published: May 2021

Abstract
The stress state analysis of the sealing cylinder is of great significance for the safe operation of the sealing system. In this study, we probe a sealing system that can be simplified as an axisymmetric problem. In service, the rubber around the central pipe contacts the casing under the action of the axial pressure, and thus the sealing function is realized. The analytical solution of the stress at the sealing interface is derived based on the Love strain function in the axisymmetric configuration. Then, the relationship between the axial pressure and the gap (between the sealing cylinder and the casing) is presented, and the contact pressure at the contact interface is also given. The numerical simulation is performed, which is in agreement with the analytical solutions in the two deformation stages. The obtained results in the current work have also been comprehensively compared with the previous results, to give suggestions for engineering selection. These findings are beneficial to obtain a deep understanding on the mechanism of the sealing process, and provide some inspirations on the new types of sealing tools for mechanical engineering, chemical engineering, petroleum engineering, etc.
Prognostic significance of inflammatory response markers for locally advanced squamous cell carcinoma of the external auditory canal and middle ear
Authors: Makita Kenji , Hamamoto Yasushi , Takata Noriko , Ishikawa Hirofumi , Tsuruoka Shintaro , Uwatsu Kotaro , Hato Naohito , Kido Teruhito 
Published: May 2021

Abstract
We investigated the prognostic significance and treatment outcomes of pretreatment inflammatory response markers for locally advanced squamous cell carcinoma (SCC) of the external auditory canal (EAC) and middle ear (ME). Between July 2003 and July 2019, 21 patients with SCC of the EAC (n = 18) or ME (n = 3) who received radiotherapy with or without surgery or systemic therapy (radiotherapy alone [n = 2], radiotherapy + systemic therapy [n = 6], radiotherapy + surgery [n = 7], radiotherapy + surgery + systemic therapy [n = 6]) were retrospectively examined. The median radiation dose was 66.0 (range, 50.4–70.0) Gy, with daily fractions of 1.8–2.0 Gy. The median follow-up period was 25 months (range, 6–137). The two-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) rates were 61%, 48%, and 55%, respectively. OS, PFS, and LC did not differ significantly according to patient- (age, sex), tumor- (Pittsburgh stage, pretreatment neurological findings), and treatment-related (surgery or systemic therapy, radiation dose, prophylactic neck irradiation) factors. Conversely, there were significant differences in OS, PFS, and LC between patients with high and low pretreatment C-reactive protein-to-albumin ratios (p = 0.002, 0.003, and 0.004, respectively). OS also differed significantly between patients with high and low pretreatment neutrophil-to-lymphocyte ratios (NLR; p = 0.037). Other inflammatory response markers, including platelet-to-lymphocyte ratio (PLR) and albumin-to-globulin ratio (AGR), did not influence OS, PFS, or LC. Our findings suggest that pretreatment C-reactive protein-to-albumin ratio and NLRs have a significant impact on treatment outcomes in patients with locally advanced SCC of the EAC and ME.