bluuebunny/crossref_metadata_2025_split huggingface dataset:
An inductive transfer learning force field (ITLFF) protocol builds protein force fields in seconds
Authors: Han Yanqiang , Wang Zhilong , Chen An , Ali Imran , Cai Junfei , Ye Simin , Li Jinjin 
Published: December 2021

AbstractAccurate simulation of protein folding is a unique challenge in understanding the physical process of protein folding, with important implications for protein design and drug discovery. Molecular dynamics simulation strongly requires advanced force fields with high accuracy to achieve correct folding. However, the current force fields are inaccurate, inapplicable and inefficient. We propose a machine learning protocol, the inductive transfer learning force field (ITLFF), to construct protein force fields in seconds with any level of accuracy from a small dataset. This process is achieved by incorporating an inductive transfer learning algorithm into deep neural networks, which learn knowledge of any high-level calculations from a large dataset of low-level method. Here, we use a double-hybrid density functional theory (DFT) as a case functional, but ITLFF is suitable for any high-precision functional. The performance of the selected 18 proteins indicates that compared with the fragment-based double-hybrid DFT algorithm, the force field constructed by ITLFF achieves considerable accuracy with a mean absolute error of 0.0039 kcal/mol/atom for energy and a root mean square error of 2.57 $\mathrm{kcal}/\mathrm{mol}/{\AA}$ for force, and it is more than 30 000 times faster and obtains more significant efficiency benefits as the system increases. The outstanding performance of ITLFF provides promising prospects for accurate and efficient protein dynamic simulations and makes an important step toward protein folding simulation. Due to the ability of ITLFF to utilize the knowledge acquired in one task to solve related problems, it is also applicable for various problems in biology, chemistry and material science.
SARS-CoV-2 transmissibility compared between variants of concern and vaccination status
Authors: Wang Liang , Didelot Xavier , Bi Yuhai , Gao George F 
Published: December 2021

Abstract
Since the start of the SARS-CoV-2 pandemic in late 2019, several variants of concern (VOC) have been reported to have increased transmissibility. In addition, despite the progress of vaccination against SARS-CoV-2 worldwide, all vaccines currently in used are known to protect only partially from infection and onward transmission. We combined phylogenetic analysis with Bayesian inference under an epidemiological model to infer the reproduction number (Rt) and also trace person-to-person transmission. We examined the impact of phylogenetic uncertainty and sampling bias on the estimation. Our result indicated that lineage B had a significantly higher transmissibility than lineage A and contributed to the global pandemic to a large extent. In addition, although the transmissibility of VOCs is higher than other exponentially growing lineages, this difference is not very high. The probability of detecting onward transmission from patients infected with SARS-CoV-2 VOCs who had received at least one dose of vaccine was approximate 1.06% (3/284), which was slightly lower but not statistically significantly different from a probability of 1.21% (10/828) for unvaccinated individuals. In addition to VOCs, exponentially growing lineages in each country should also be account for when tailoring prevention and control strategies. One dose of vaccination could not efficiently prevent the onward transmission of SARS-CoV-2 VOCs. Consequently, nonpharmaceutical interventions (such as wearing masks and social distancing) should still be implemented in each country during the vaccination period.
GC-Profile 2.0: an extended web server for the prediction and visualization of CpG islands
Authors: Lai Fei-Liao , Gao Feng 
Published: December 2021

Abstract

Summary
Due to the spontaneous deamination of 5′-methylcytosine into thymine, the number of CpG dinucleotides is less than expected in vertebrate genomes. Exceptionally, there are a large number of CpG dinucleotides clustered at certain genomic loci, known as CpG islands (CGIs), where CpG dinucleotides are free from methylation. Identification of CGIs is of great significance in the field of genomics and epigenetics because they can serve as important gene markers or regulatory elements. Here, GC-Profile 2.0 has been presented as a newly extended application for CGIs detection and visualization. Based on a benchmark test of assembled sequences, GC-Profile 2.0 has shown better overall performance compared with other four popular methods. In addition, cumulative CpG profile, a visualization tool of CpG content variation, is also proposed to intuitively display the change trend of CpG content.

Availability and implementation
GC-Profile 2.0 is freely available at http://tubic.org/GC-Profile2.

Supplementary information
Supplementary data are available at Bioinformatics online.
HOMELETTE: a unified interface to homology modelling software
Authors: Junk Philipp , Kiel Christina 
Published: December 2021

AbstractSummaryHomology modelling, the technique of generating models of 3D protein structures based on experimental structures from related proteins, has become increasingly popular over the years. An abundance of different tools for model generation and model evaluation is available from various research groups. We present HOMELETTE, an interface which implements a unified programmatic access to these tools. This allows for the assemble of custom pipelines from pre- or self-implemented building blocks.Availability and implementationHOMELETTE is implemented in Python, compatible with version 3.6 and newer. It is distributed under the MIT license. Documentation and tutorials are available at Read the Docs (https://homelette.readthedocs.io/). The latest version of HOMELETTE is available on PyPI (https://pypi.org/project/homelette/) and GitHub (https://github.com/PhilippJunk/homelette). A full installation of the latest version of HOMELETTE with all dependencies is also available as a Docker container (https://hub.docker.com/r/philippjunk/homelette_template).Supplementary informationSupplementary data are available at Bioinformatics online.
Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice
Authors: Middleton Steven J , Perini Irene , Themistocleous Andreas C , Weir Greg A , McCann Kirsty , Barry Allison M , Marshall Andrew , Lee Michael , Mayo Leah M , Bohic Manon , Baskozos Georgios , Morrison India , Löken Line S , McIntyre Sarah , Nagi Saad S , Staud Roland , Sehlstedt Isac , Johnson Richard D , Wessberg Johan , Wood John N , Woods Christopher G , Moqrich Aziz , Olausson Håkan , Bennett David L 
Published: December 2021

Abstract
Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial electromyography (n = 3 CIP participants and n = 8 healthy controls), we found that these patients also have abnormalities in the encoding of affective touch, which is mediated by the specialized afferents C-low threshold mechanoreceptors (C-LTMRs).
In the mouse, we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient.
Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch.
The oscillating Mucin-type protein DPY-6 has a conserved role in nematode mouth and cuticle formation
Authors: Sun Shuai , Theska Tobias , Witte Hanh , Ragsdale Erik J , Sommer Ralf J 
Published: December 2021

AbstractNematodes show an extraordinary diversity of mouth structures and strikingly different feeding strategies, which has enabled an invasion of all ecosystems. However, nearly nothing is known about the structural and molecular architecture of the nematode mouth (stoma). Pristionchus pacificus is an intensively studied nematode that exhibits unique life history traits, including predation, teeth-like denticle formation, and mouth-form plasticity. Here, we used a large-scale genetic screen to identify genes involved in mouth formation. We identified Ppa-dpy-6 to encode a Mucin-type hydrogel-forming protein that is macroscopically involved in the specification of the cheilostom, the anterior part of the mouth. We used a recently developed protocol for geometric morphometrics of miniature animals to characterize these defects further and found additional defects that affect mouth form, shape, and size resulting in an overall malformation of the mouth. Additionally, Ppa-dpy-6 is shorter than wild-type with a typical Dumpy phenotype, indicating a role in the formation of the external cuticle. This concomitant phenotype of the cheilostom and cuticle provides the first molecular support for the continuity of these structures and for the separation of the cheilostom from the rest of the stoma. In Caenorhabditis elegans, dpy-6 was an early mapping mutant but its molecular identity was only determined during genome-wide RNAi screens and not further investigated. Strikingly, geometric morphometric analysis revealed previously unrecognized cheilostom and gymnostom defects in Cel-dpy-6 mutants. Thus, the Mucin-type protein DPY-6 represents to the best of our knowledge, the first protein involved in nematode mouth formation with a conserved role in cuticle deposition. This study opens new research avenues to characterize the molecular composition of the nematode mouth, which is associated with extreme ecological diversification.
Bioethics and Gerontology: The Value of Thinking Together
Authors: Berlinger Nancy , de Medeiros Kate , Girling Laura 
Published: December 2021

AbstractThe interdisciplinary field of bioethics focuses on what it means to be a person, flourish as a person, and be respected as a person in different conditions of health, illness, or disability. Bioethics and policy research considers normative questions such as how a good society, through its priorities and investments, should demonstrate its commitments to the lives of different populations. Bioethics and humanities scholarship, often known as “health humanities,” shares affinities with age studies and disability studies and with narrative-based approaches to the study of human experience. Gerontology is concerned with the many aspects of life that affect how people age, including social structures and values that influence the experience of growing old. In this article, we briefly explore the evolution of bioethics, from a discourse that emerged in relation to developments in biomedicine, bioscience, and biotechnology; to research ethics; to broader ethical questions emerging from real-world conditions, with attention to how bioethics has considered the experience of aging. Until recently, most age-focused work in bioethics has concerned age-associated illness, particularly end-of-life decision making. Given the reality of population aging and the ethical concerns accompanying the shift in age for most places in the world, the further evolution of bioethics involves greater attention to the support of flourishing in late life and to social justice and health equity in aging societies. We argue that the discourses of bioethics and critical gerontology, in dialogue, can bring a new understanding of privilege and preference, disparity and disadvantage, and reflection and respect for aging individuals.
Voice Hearing in Borderline Personality Disorder Across Perceptual, Subjective, and Neural Dimensions
Authors: Strawson Will H , Wang Hao-Ting , Quadt Lisa , Sherman Maxine , Larsson Dennis E O , Davies Geoff , Mckeown Brontë L A , Silva Marta , Fielding-Smith Sarah , Jones Anna-Marie , Hayward Mark , Smallwood Jonathan , Critchley Hugo D , Garfinkel Sarah N 
Published: December 2021

Abstract

Background
Auditory verbal hallucinations (AVH) commonly occur in the context of borderline personality disorder (BPD) yet remain poorly understood. AVH are often perceived by patients with BPD as originating from inside the head and hence viewed clinically as “pseudohallucinations,” but they nevertheless have a detrimental impact on well-being.

Methods
The current study characterized perceptual, subjective, and neural expressions of AVH by using an auditory detection task, experience sampling and questionnaires, and functional neuroimaging, respectively.

Results
Perceptually, reported AVH correlated with a bias for reporting the presence of a voice in white noise. Subjectively, questionnaire measures indicated that AVH were significantly distressing and persecutory. In addition, AVH intensity, but not perceived origin (i.e., inside vs outside the head), was associated with greater concurrent anxiety. Neurally, fMRI of BPD participants demonstrated that, relative to imagining or listening to voices, periods of reported AVH induced greater blood oxygenation level–dependent activity in anterior cingulate and bilateral temporal cortices (regional substrates for language processing). AVH symptom severity was associated with weaker functional connectivity between anterior cingulate and bilateral insular cortices.

Conclusion
In summary, our results indicate that AVH in participants with BPD are (1) underpinned by aberrant perceptual-cognitive mechanisms for signal detection, (2) experienced subjectively as persecutory and distressing, and (3) associated with distinct patterns of neural activity that inform proximal mechanistic understanding. Our findings are like analogous observations in patients with schizophrenia and validate the clinical significance of the AVH experience in BPD, often dismissed as “pseudohallucinations.” These highlight a need to reconsider this experience as a treatment priority.
On the Convergence Rate of the Chaos Game
Authors: Bárány Balázs , Jurga Natalia , Kolossváry István 
Published: December 2021

Abstract
This paper studies how long it takes the orbit of the chaos game to reach a certain density inside the attractor of a strictly contracting IFS of which we only assume that its lower dimension is positive. We show that the rate of growth of this cover time is determined by the Minkowski dimension of the push-forward of the shift invariant measure with exponential decay of correlations driving the chaos game. Moreover, we bound the expected value of the cover time from above and below with multiplicative logarithmic correction terms. As an application, for Bedford–McMullen carpets, we completely characterise the family of probability vectors that minimise the Minkowski dimension of Bernoulli measures. Interestingly, these vectors have not appeared in any other aspect of Bedford–McMullen carpets before.
Existence and Stability of Smooth Traveling Circular Pairs for the Generalized Surface Quasi-Geostrophic Equation
Authors: Cao Daomin , Qin Guolin , Zhan Weicheng , Zou Changjun 
Published: December 2021

AbstractIn this paper, we construct smooth traveling counter-rotating vortex pairs with circular supports for the generalized surface quasi-geostrophic equation. These vortex pairs are analogues of the Lamb dipoles for the 2D incompressible Euler equation. The solutions are obtained by maximization of the energy over some appropriate classes of admissible functions. We establish the uniqueness of maximizers and compactness of maximizing sequences in our variational setting. Using these facts, we further prove the orbital stability of the circular vortex pairs for the generalized surface quasi-geostrophic equation.
Immune Reconstitution Bone Loss Exacerbates Bone Degeneration Due to Natural Aging in a Mouse Model
Authors: Weitzmann M Neale , Weiss Daiana , Vikulina Tatyana , Roser-Page Susanne , Yu Kanglun , McGee-Lawrence Meghan E , Tu Chia Ling , Chang Wenhan , Ofotokun Ighovwerha 
Published: December 2021

Abstract

Background
Immune reconstitution bone loss (IRBL) is a common side-effect of antiretroviral therapy (ART) in people with human immunodeficiency virus (PWH). Immune reconstitution bone loss acts through CD4+ T-cell/immune reconstitution-induced inflammation and is independent of antiviral regimen. Immune reconstitution bone loss may contribute to the high rate of bone fracture in PWH, a cause of significant morbidity and mortality. Although IRBL is transient, it remains unclear whether bone recovers, or whether it is permanently denuded and further compounds bone loss associated with natural aging.

Methods
We used a validated IRBL mouse model involving T-cell reconstitution of immunocompromised mice. Mice underwent cross-sectional bone phenotyping of femur and/or vertebrae between 6 and 20 months of age by microcomputed tomography (µCT) and quantitative bone histomorphometry. CD4+ T cells were purified at 20 months to quantify osteoclastogenic/inflammatory cytokine expression.

Results
Although cortical IRBL in young animals recovered with time, trabecular bone loss was permanent and exacerbated skeletal decline associated with natural aging. At 20 months of age, reconstituted CD4+ T cells express enhanced osteoclastogenic cytokines including RANKL, interleukin (IL)-1β, IL-17A, and tumor necrosis factor-α, consistent with elevated osteoclast numbers.

Conclusions
Immune reconstitution bone loss in the trabecular compartment is permanent and further exacerbates bone loss due to natural aging. If validated in humans, interventions to limit IRBL may be important to prevent fractures in aging PWH.
Rapid Identification of Peucedanum praeruptorum Dunn and Its Adulterants by Hand-Held Near-Infrared Spectroscopy
Authors: Wang Fang , Jia Bin , Song Xiangwen , Dai Jun , Li Xiaoli , Gao Haidi , Pan Haoyu , Yan Hui , Han Bangxing 
Published: December 2021

Abstract

Background
Peucedanum praeruptorum Dunn (PPD) is a traditional Chinese medical herb of high medical and economic value. However, PPD is often adulterated by inexpensive plants.

Objective
In order to establish an integrated and straightforward methodology to identify adulterated PPD products, hand-held near-infrared spectroscopy (NIRS) combined with chemical pattern recognition techniques was employed.

Method
The standard normal variate (SNV) was used to preprocess the original near-infrared spectra. Principal component analysis (PCA), linear discriminant analysis (LDA), and partial least-squares regression analysis (PLSDA) were used to construct the recognition models.

Results
PCA analysis could not correctly distinguish PPD from non-PPD. However, based on absorbance in the spectral region of 1405–2442 nm and SNV pretreatment, the accuracy of the LDA model was above 90% at identifying genuine PPD. Compared with the LDA method, the PLSDA model is more stable and reliable, and its model prediction accuracy was 93.4%.

Conclusion
The combination of NIRS and chemometric methods based on a hand-held near-infrared spectrometer is an efficient, nondestructive, and reliable method for validating traditional Chinese medicine PPD.

Highlights
The advanced method based on a hand-held near-infrared spectrometer can be used for rapid identification and quality evaluation of PPD in the field, medicinal material markets, and points of sale.
Competing-risk nomogram for predicting survival in patients with advanced (stage III/IV) gallbladder cancer: A SEER population-based study
Authors: Wang Jian , Yang Yi , Pan Junjie , Qiu Yiwen , Shen Shu , Wang Wentao 
Published: December 2021

Abstract

Objective
The primary aim of this study was to assess the cumulative incidence of cause-specific mortality (CSM) and other cause-specific mortality (OCSM) for patients with advanced gallbladder cancer (GBC), and then to develop a nomogram based on competing-risk analysis to forecast CSM.

Methods
We identified the patients with GBC with specific screening criteria and from the Surveillance Epidemiology and End Results (SEER) database. We calculated the cumulative incidence function for CSM and OCSM, and constructed a competing-risk nomogram based on the Fine and Gray’s proportional subdistribution hazard regression model to forecast the probability of CSM of these patients. In addition, the concordance index and calibration plot were performed to validate the novel established model.

Results
A total of 1411 patients were included in this study. The 1-, 2-, and 3-year overall cumulative mortalities were 46.2, 62.2, and 69.6% for CSM, respectively, while they were 6.2, 8.7, and 10.4% for OCSM. Additionally, the 1-, 2-, and 3-year estimates of overall survival were 47.6, 29.1, and 19.9% for above these patients, respectively. We also developed a competing-risk nomogram to estimate the CSM. The concordance index was 0.775 (95% confidence interval (CI): 0.750–0.800) in the training set and that was 0.765 (95% CI: 0.730–0.800) in the internal validation set, which suggests the robustness of the novel established model. Furthermore, the calibration curves and concordance index demonstrated that the nomogram was well-calibrated and demonstrated good discriminative ability.

Conclusions
The ample sample allowed us to develop a reliable model which demonstrated better calibration and discrimination for predicting the probability of CSM of patients with advanced GBC.
Racial Disparities in Access to Prostate Cancer Clinical Trials: A County-Level Analysis
Authors: Wang Wei-Jhih , Ramsey Scott David , Bennette Caroline Savage , Bansal Aasthaa 
Published: December 2021

Abstract

Background
African American men have a higher burden of prostate cancer compared with other populations. We sought to determine if they experience disparities in access to prostate cancer clinical trials.

Methods
We created a database of all US counties by linking prostate cancer clinical trial data with county-level socioeconomic, demographic, and health-care facility data derived from several external data sources. Using this data linkage, we examined 2 potential access barriers. We investigated the relationship between the proportion of African Americans and access to cancer facilities, adjusting for county population size and other characteristics. Additionally, among counties with cancer facilities, we investigated the relationship between the proportion of African Americans and number of available prostate cancer trials per capita per year. We addressed these questions using logistic and negative binomial regression, respectively.

Results
Between 2008 and 2015, 613 prostate cancer trial sites were found among 3145 US counties. Counties with a higher proportion of African Americans were less likely to have cancer facilities (adjusted odds ratio = 0.85, 95% confidence interval = 0.78 to 0.92). Among counties with cancer facilities, those with a higher proportion of African Americans had statistically significantly fewer prostate cancer trials per capita per year (rate ratio per 10% increase in African Americans = 0.90, 95% confidence interval = 0.83 to 0.96).

Conclusions
Counties with higher proportions of African Americans seem less likely to have access to cancer facilities. Among counties with cancer facilities, those with higher proportions of African Americans appear to have fewer prostate cancer trials available per capita per year. Clinical trials in prostate cancer therapy should ensure adequate availability of enrollment sites in regions with high concentrations of African Americans.