bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSICalc: a novel approach to identifying and ranking critical non-proximal interdependencies within the overall protein structure
Authors: Townsley Thomas D , Wilson James T , Akers Harrison , Bryant Timothy , Cordova Salvador , Wallace T L , Durston Kirk K , Deweese Joseph E 
Published: August 2022

Abstract

Motivation
AlphaFold has been a major advance in predicting protein structure, but still leaves the problem of determining which sub-molecular components of a protein are essential for it to carry out its function within the cell. Direct coupling analysis predicts two- and three-amino acid contacts, but there may be essential interdependencies that are not proximal within the 3D structure. The problem to be addressed is to design a computational method that locates and ranks essential non-proximal interdependencies within a protein involving five or more amino acids, using large, multiple sequence alignments (MSAs) for both globular and intrinsically unstructured proteins.

Results
We developed PSICalc (Protein Subdomain Interdependency Calculator), a laptop-friendly, pattern-discovery, bioinformatics software tool that analyzes large MSAs for both structured and unstructured proteins, locates both proximal and non-proximal inter-dependent sites, and clusters them into pairwise (second order), third-order and higher-order clusters using a k-modes approach, and provides ranked results within minutes. To aid in visualizing these interdependencies, we developed a graphical user interface that displays these subdomain relationships as a polytree graph. To demonstrate, we provide examples of both proximal and non-proximal interdependencies documented for eukaryotic topoisomerase II including between the unstructured C-terminal domain and the N-terminal domain.

Availability and implementation
https://github.com/jdeweeselab/psicalc-package

Supplementary information
Supplementary data are available at Bioinformatics Advances online.
Design of Analytical Method Validation Protocol Evaluating Environmental Monitoring of AND Contamination on Surfaces Based on Cleaning Validation Procedures: A Multi Component RP-UHPLC Method
Authors: Demircan Yildirim Fatma , Ekmekci Ismail 
Published: August 2022

Abstract
Environmental monitoring of anti-neoplastic drug (AND) residues in workplaces is crucial to limit exposure to workers who handle with them. Although wipe sampling is the most appropriate methodology to evaluate the risk, conflicting results are also reported due to the lack of standardized and validated procedures. In this study, procedures for surface contamination of ANDs in workplaces are presented, with a focus on sampling, sample preparation and instrumentation. The analytical method validation parameters are designed to comply with requirements of The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q7 Good Manufacturing Practice (GMP) for active pharmaceutical ingredients. Additionally, the study provides a simple, specific, rapid and multi-component analytical method to evaluate seven ANDs that are Gefitinib, Imatinib, Dasatinib, Axitinib, Erlotinib, Nilotinib and Sorafenib at very low concentration levels, simultaneously. Quantitative, precise and reproducible results obtained from the study show that environmental monitoring procedure and analytical method validation protocol presented in the study can be used to reduce and monitor occupational exposure risk to ANDs in wokplaces.
Large-bore arterial access closure after transcatheter aortic valve replacement: a systematic review and network meta-analysis
Authors: Montalto Claudio , Munafò Andrea Raffaele , Arzuffi Luca , Soriano Francesco , Mangieri Antonio , Nava Stefano , De Maria Giovanni Luigi , Burzotta Francesco , D’Ascenzo Fabrizio , Colombo Antonio , Latib Azeem , Oreglia Jacopo Andrea , Banning Adrian P , Porto Italo , Crimi Gabriele 
Published: August 2022

AbstractAimsAs the indications to transcatheter aortic valve replacement (TAVR) expand to patients at increasingly lower risk, procedure-related vascular and bleeding complications events must be minimized. We aimed to evaluate the impact of different large-bore arterial access closure devices on clinical outcomes after TAVR.Methods and resultsWe searched for papers that reported outcomes according to the type of vascular closure device/technique used after TAVR and performed a Bayesian network meta-analysis (NMA). Fifteen studies involving 9259 patients who underwent access site closure using PROSTAR™ XL percutaneous vascular surgical system (Abbott Vascular, Santa Clara, CA, USA), Perclose ProGlide™ suture-mediated closure system (Abbott), or MANTATM vascular closure device (Teleflex, Morrisville, NC, USA) were included. NMA showed MANTA to have the highest likelihood of reducing a primary composite endpoint of intra-hospital death, major vascular complications, and major or life-threatening bleedings [surface under the cumulative ranking curve analysis (SUCRA) 94.8%], but this was mitigated when only randomized clinical trials and propensity-matched cohorts were included (SUCRA 56.1%). The ProGlide showed the highest likelihood to reduce major or life-threatening bleedings, especially with increasing procedural complexity, and the MANTA device to reduce major and minor vascular complications. The ProStar XL device performed poorly in all explored endpoints.ConclusionAvailable evidence summarized through a NMA shows that ProGlide and MANTA devices appear to be both valid vascular closure devices globally and to be the best options to minimize vascular complications and reduce bleeding in patients undergoing TAVR, respectively.
The improved genome of the nematode Parapristionchus giblindavisi provides insights into lineage-specific gene family evolution
Authors: Röseler Waltraud , Collenberg Maximilian , Yoshida Kohta , Lanz Christa , Sommer Ralf J , Rödelsperger Christian 
Published: August 2022

Abstract
Nematodes such as Caenorhabditis elegans and Pristionchus pacificus are extremely successful model organisms for comparative biology. Several studies have shown that phenotypic novelty but also conserved processes are controlled by taxon-restricted genes. To trace back the evolution of such new or rapidly evolving genes, a robust phylogenomic framework is indispensable. Here, we present an improved version of the genome of Parapristionchus giblindavisi which is the only known member of the sister group of Pristionchus. Relative to the previous short-read assembly, the new genome is based on long reads and displays higher levels of contiguity, completeness, and correctness. Specifically, the number of contigs dropped from over 7,303 to 735 resulting in an N50 increase from 112 to 791 kb. We made use of the new genome to revisit the evolution of multiple gene families. This revealed Pristionchus-specific expansions of several environmentally responsive gene families and a Pristionchus-specific loss of the de novo purine biosynthesis pathway. Focusing on the evolution of sulfatases and sulfotransferases, which control the mouth form plasticity in P. pacificus, reveals differences in copy number and genomic configurations between the genera Pristionchus and Parapristionchus. Altogether, this demonstrates the utility of the P. giblindavisi genome to date and polarizes lineage-specific patterns.
De-risking clinical trial failure through mechanistic simulation
Authors: Brown Liam V , Wagg Jonathan , Darley Rachel , van Hateren Andy , Elliott Tim , Gaffney Eamonn A , Coles Mark C 
Published: August 2022

AbstractDrug development typically comprises a combination of pre-clinical experimentation, clinical trials, and statistical data-driven analyses. Therapeutic failure in late-stage clinical development costs the pharmaceutical industry billions of USD per year. Clinical trial simulation represents a key derisking strategy and combining them with mechanistic models allows one to test hypotheses for mechanisms of failure and to improve trial designs. This is illustrated with a T-cell activation model, used to simulate the clinical trials of IMA901, a short-peptide cancer vaccine. Simulation results were consistent with observed outcomes and predicted that responses are limited by peptide off-rates, peptide competition for dendritic cell (DC) binding, and DC migration times. These insights were used to hypothesise alternate trial designs predicted to improve efficacy outcomes. This framework illustrates how mechanistic models can complement clinical, experimental, and data-driven studies to understand, test, and improve trial designs, and how results may differ between humans and mice.
Digital twins to enable better precision and personalized dementia care
Authors: Wickramasinghe Nilmini , Ulapane Nalika , Andargoli Amir , Ossai Chinedu , Shuakat Nadeem , Nguyen Tuan , Zelcer John 
Published: August 2022

Abstract
In this perspective paper, we want to highlight the potential benefits of incorporating digital twins to support better dementia care. In particular, we assert that, by doing so, it is possible to ensure greater precision regarding dementia care while simultaneously enhancing personalization. Digital twins have been used successfully in manufacturing to enable better prediction and tailoring of solutions to meet required needs, and thereby have enabled more effective and efficient deployment of resources. We develop a model for digital twin in the healthcare domain as a clinical decision support tool by extrapolating its current uses from the manufacturing domain. We illustrate the power of the developed model in the context of dementia. Given the rapid rise of chronic conditions and the pressures on healthcare delivery to provide high quality, cost-effective care anywhere and anytime, we assert that such an approach is consistent with a value-based healthcare philosophy and thus important as the numbers of people with dementia continues to grow exponentially and this pressing healthcare issue is yet to be optimally addressed. Further research and development in this rapidly evolving domain is a strategic priority for ensuring the delivery of superior dementia care.
Osteogenesis Imperfecta Diagnosed in an Active Duty Female Due to CREB3L1 Heterozygosity
Authors: DeMasters David P , Paulus Andrew O , Scott Joshua N 
Published: August 2022

ABSTRACT

Introduction
Osteogenesis imperfecta (OI) is a heritable, collagen-related disorder with varying degrees of disease severity and systemic involvement. The hallmark of OI is bone matrix fragility, but diverse effects related to structural integrity and impaired development of connective tissue can account for hearing loss, blue sclera, dentinogenesis imperfecta, frequent fractures, joint hypermobility, and cardiac valve or vessel fragility in some cases. There is emerging recognition of unique genetic mutations leading to OI including CREB3L1, which codes for an important transcription factor for differentiation of osteoblasts.

Case Presentation
We present a case of OI diagnosed in an active duty female with multiple prior fractures and heterozygous CREB3L1, a rare cause of OI.

Conclusion
This case highlights the importance of consideration of the variable phenotypes of OI and careful assessment of fracture history during evaluation at the Military Entrance Processing Station and subsequent encounters at military treatment facilities to improve readiness.
METTL14 Regulates Osteogenesis of Bone Marrow Mesenchymal Stem Cells via Inducing Autophagy Through m6A/IGF2BPs/Beclin-1 Signal Axis
Authors: He Mingyu , Lei Hong , He Xiaoqi , Liu Ying , Wang Ao , Ren Zijing , Liu Xiaoyan , Yan Gege , Wang Wenbo , Wang Yang , Li Guanghui , Wang Tong , Pu Jiaying , Shen Zhihua , Wang Yanquan , Xie Jiajie , Du Weijie , Yuan Ye , Yang Lei 
Published: August 2022

Abstract
The development of osteoporosis is often accompanied by autophagy disturbance, which also causes new osteoblast defects from bone marrow mesenchymal stem cells (BMSCs). However, the underlying molecular mechanisms are still not fully understood. Methyltransferase-like 14 (METTL14) is the main enzyme for N6-methyladenosine (m6A), the most prevalent internal modification in mammalian mRNAs, and it has been implicated in many bioprocesses. Herein, we demonstrate that METTL14 plays a critical role in autophagy induction and hinders osteoporosis process whose expression is decreased both in human osteoporosis bone tissue and ovariectomy (OVX) mice. In vivo, METTL14+/− knockdown mice exhibit elevated bone loss and impaired autophagy similar to the OVX mice, while overexpression of METTL14 significantly promotes bone formation and inhibits the progression of osteoporosis caused by OVX surgery. In vitro, METTL14 overexpression significantly enhances the osteogenic differentiation ability of BMSCs through regulating the expression of beclin-1 depending on m6A modification and inducing autophagy; the opposite is true with METTL14 silencing. Subsequently, m6A-binding proteins IGF2BP1/2/3 recognize m6A-methylated beclin-1 mRNA and promote its translation via mediating RNA stabilization. Furthermore, METTL14 negatively regulates osteoclast differentiation. Collectively, our study reveals the METTL14/IGF2BPs/beclin-1 signal axis in BMSCs osteogenic differentiation and highlights the critical roles of METTL14-mediated m6A modification in osteoporosis.
Taxation of Offshore Trusts and the Rule of Law: The Case of Australia and China
Authors: Fazal Zaif Hassan 
Published: August 2022

Abstract
There is an increasing trend among policy makers and tax administrators to do whatever it takes to tax offshore trusts. This article discusses how this approach may lead to the violation of the rule of law in the case of Australia and China. In Australia, several complex rules are enacted to close the ‘gaps’ in the law. While in China, there are insufficient rules to elaborate the vague laws surrounding taxation of offshore trusts. This article will dissect what a trust is and how the rules work in practice to determine whether the rule of law is violated in these jurisdictions.
Neurons in inferior temporal cortex are sensitive to motion trajectory during degraded object recognition
Authors: Burk Diana C , Sheinberg David L 
Published: August 2022

Abstract
Our brains continuously acquire sensory information and make judgments even when visual information is limited. In some circumstances, an ambiguous object can be recognized from how it moves, such as an animal hopping or a plane flying overhead. Yet it remains unclear how movement is processed by brain areas involved in visual object recognition. Here we investigate whether inferior temporal (IT) cortex, an area known for its relevance in visual form processing, has access to motion information during recognition. We developed a matching task that required monkeys to recognize moving shapes with variable levels of shape degradation. Neural recordings in area IT showed that, surprisingly, some IT neurons responded stronger to degraded shapes than clear ones. Furthermore, neurons exhibited motion sensitivity at different times during the presentation of the blurry target. Population decoding analyses showed that motion patterns could be decoded from IT neuron pseudo-populations. Contrary to previous findings, these results suggest that neurons in IT can integrate visual motion and shape information, particularly when shape information is degraded, in a way that has been previously overlooked. Our results highlight the importance of using challenging multifeature recognition tasks to understand the role of area IT in naturalistic visual object recognition.
Anomalous and heterogeneous characteristics of the BOLD hemodynamic response function in white matter
Authors: Schilling Kurt G , Li Muwei , Rheault Francois , Ding Zhaohua , Anderson Adam W , Kang Hakmook , Landman Bennett A , Gore John C 
Published: August 2022

Abstract
Detailed knowledge of the BOLD hemodynamic response function (HRF) is crucial for accurate analyses and interpretation of functional MRI data. Considerable efforts have been made to characterize the HRF in gray matter (GM), but much less attention has been paid to BOLD effects in white matter (WM). However, several recent reports have demonstrated reliable detection and analyses of WM BOLD signals both after stimulation and in a resting state. WM and GM differ in composition, energy requirements, and blood flow, so their neurovascular couplings also may well be different. We aimed to derive a comprehensive characterization of the HRF in WM across a population, including accurate measurements of its shape and its variation along and between WM pathways, using resting-state fMRI acquisitions. Our results show that the HRF is significantly different between WM and GM. Features of the HRF, such as a prominent initial dip, show strong relationships with features of the tissue microstructure derived from diffusion imaging, and these relationships differ between WM and GM, consistent with BOLD signal fluctuations reflecting different energy demands and neurovascular couplings in tissues of different composition and function. We also show that the HRF varies in shape significantly along WM pathways and is different between different WM pathways, suggesting the temporal evolution of BOLD signals after an event vary in different parts of the WM. These features of the HRF in WM are especially relevant for interpretation of the biophysical basis of BOLD effects in WM.
Disentangling the role of poultry farms and wild birds in the spread of highly pathogenic avian influenza virus in Europe
Authors: Guinat Claire , Valenzuela Agüí Cecilia , Vaughan Timothy G , Scire Jérémie , Pohlmann Anne , Staubach Christoph , King Jacqueline , Świętoń Edyta , Dán Ádám , Černíková Lenka , Ducatez Mariette F , Stadler Tanja 
Published: August 2022

Abstract
In winter 2016–7, Europe was severely hit by an unprecedented epidemic of highly pathogenic avian influenza viruses (HPAIVs), causing a significant impact on animal health, wildlife conservation, and livestock economic sustainability. By applying phylodynamic tools to virus sequences collected during the epidemic, we investigated when the first infections occurred, how many infections were unreported, which factors influenced virus spread, and how many spillover events occurred. HPAIV was likely introduced into poultry farms during the autumn, in line with the timing of wild birds’ migration. In Germany, Hungary, and Poland, the epidemic was dominated by farm-to-farm transmission, showing that understanding of how farms are connected would greatly help control efforts. In the Czech Republic, the epidemic was dominated by wild bird-to-farm transmission, implying that more sustainable prevention strategies should be developed to reduce HPAIV exposure from wild birds. Inferred transmission parameters will be useful to parameterize predictive models of HPAIV spread. None of the predictors related to live poultry trade, poultry census, and geographic proximity were identified as supportive predictors of HPAIV spread between farms across borders. These results are crucial to better understand HPAIV transmission dynamics at the domestic–wildlife interface with the view to reduce the impact of future epidemics.
Dendrobium officinale polysaccharide inhibits vascular calcification via anti‐inflammatory and anti‐apoptotic effects in chronic kidney disease
Authors: Jiang Wangsheng , Ruan Wenfeng , Wang Zhengqiang 
Published: August 2022

AbstractVascular calcification is very common in patients with chronic kidney disease (CKD), but so far, there is no effective treatment. Dendrobium officinale polysaccharide (DOP), a natural component of Chinese herbal medicine, has been shown to exert anti‐inflammatory and anti‐apoptotic activity. Inflammation and apoptosis play an essential role in the progression of vascular calcification. However, the exact role and molecular mechanisms of DOP in vascular calcification remain unclear. In this study, we investigated the effects of DOP on vascular calcification using vascular smooth muscle cells (VSMCs), arterial rings, and CKD rats. Alizarin red staining and gene expression analysis revealed that DOP inhibited calcification and osteogenic differentiation of rat VSMCs in a dose‐dependent manner. Similarly, ex vivo studies revealed that DOP inhibited the calcification of rat arterial rings. Furthermore, the administration of DOP alleviated vascular calcification in CKD rats. Moreover, DOP treatment suppressed VSMC inflammation and apoptosis. Finally, DOP treatment upregulated mRNA and protein levels of heme oxygenase‐1 (HMOX‐1); both pharmacological inhibition of HMOX‐1 by the HMOX‐1 inhibitor zinc protoporphyrin‐9ZnPP9 and knockdown of HMOX‐1 by siRNA markedly abrogated the suppression of inflammation and osteogenic differentiation of VSMCs by DOP. Collectively, these results suggest that DOP alleviates vascular calcification in CKD by suppressing apoptosis and inflammation via HMOX‐1 activation. These results may provide a promising treatment for vascular calcification in CKD.
A Modern Day Timeline for In-Hospital Monitoring in Perfused, Pulseless Pediatric Supracondylar Humerus Fractures
Authors: Heyer Jessica H. , Mitchell Stuart L. , Garcia Samantha , Flynn John M. , Anari Jason B. 
Published: August 2022

Background:
The perfused, pulseless supracondylar humerus fracture (ppSCHF) remains a consistent topic of discussion in the literature. Inpatient observation of these patients postoperatively for worsening vascular exam or compartment syndrome is frequently recommended but not well studied. The purpose of this study was to evaluate the postoperative complications in a cohort of ppSCHF patients and their timeline to discharge.

Methods:
This study is a retrospective review of a prospectively maintained database of all operatively treated supracondylar humerus fractures from a tertiary pediatric hospital from 2013 to 2019. All patients without a palpable pulse were included. We excluded patients with <4 weeks follow-up. Demographic, operative, and postoperative data were collected, including time from presentation to operating room (OR), time from OR to discharge, and incidence of postoperative complications, including return to OR, compartment syndrome, new neurovascular deficits, and Volkmann contractures. The descriptive statistics were used to summarize the data.

Results:
Among 1371 operatively treated supracondylar humerus fractures, 39 (2.8%) presented with a ppSCHF. Five (15%) had a signal on doppler ultrasound, whereas 34 (85%) had no signal. Thirty-seven (95%) patients had a Gartland type III fracture and 2 (5%) had type IV fractures. Twenty-two (56%) patients had a neurological deficit, of which 14 had an anterior interosseous nerve deficit. The average time to OR was 6.9 (range 2.2 to 15) hours; 6 (15%) required open reduction. At the time of discharge, 85% of patients had a palpable pulse and 13% had a dopplerable signal. Postoperatively, no patients were returned to the OR for any secondary procedures. The average length of stay after the operation was 25 (range 8.5 to 40) hours, with 92% of patients being discharged by 36 hours postoperatively. No patients developed compartment syndrome, new neurological deficits, or Volkmann contractures at a mean follow-up of 112 (range 34 to 310) days.

Conclusions:
In our study of 39 patients presenting with ppSCHF, no patient required an unexpected return to the OR, or developed post-treatment compartment syndrome, neurological deficits, or Volkmann contractures. The average time from OR to discharge for ppSCHF was 25 hours.

Level of Evidence:
Level II.