bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single Layers of Attention Suffice to Predict Protein Contacts
Authors: Bhattacharya Nicholas , Thomas Neil , Rao Roshan , Dauparas Justas , Koo Peter K. , Baker David , Song Yun S. , Ovchinnikov Sergey 
Published: December 2020

AbstractThe established approach to unsupervised protein contact prediction estimates co-evolving positions using undirected graphical models. This approach trains a Potts model on a Multiple Sequence Alignment, then predicts that the edges with highest weight correspond to contacts in the 3D structure. On the other hand, increasingly large Transformers are being pretrained on protein sequence databases but have demonstrated mixed results for downstream tasks, including contact prediction. This has sparked discussion about the role of scale and attention-based models in unsupervised protein representation learning. We argue that attention is a principled model of protein interactions, grounded in real properties of protein family data. We introduce a simplified attention layer,factored attention, and show that it achieves comparable performance to Potts models, while sharing parameters both within and across families. Further, we extract contacts from the attention maps of a pretrained Transformer and show they perform competitively with the other two approaches. This provides evidence that large-scale pretraining can learn meaningful protein features when presented with unlabeled and unaligned data. We contrast factored attention with the Transformer to indicate that the Transformer leverages hierarchical signal in protein family databases not captured by our single-layer models. This raises the exciting possibility for the development of powerful structured models of protein family databases.1
Listeria monocytogenesMenI encodes a DHNA-CoA thioesterase necessary for menaquinone biosynthesis, cytosolic survival, and virulence
Authors: Smith Hans B. , Li Tin Lok , Liao Man Kit , Chen Grischa Y. , Guo Zhihong , Sauer John-Demian 
Published: December 2020

ABSTRACTListeria monocytogenesis a Gram-positive intracellular pathogen that is highly adapted to invade and replicate in the cytosol of eukaryotic cells. Intermediate metabolites in the menaquinone biosynthesis pathway are essential for the cytosolic survival and virulence ofL. monocytogenes, independent of the production of MK and aerobic respiration. Determining which specific intermediate metabolite(s) are essential for cytosolic survival and virulence has been hindered by the lack of an identified DHNA-CoA thioesterase essential for converting DHNA-CoA to DHNA in the MK synthesis pathway. Using the recently identifiedEscherichia coliDHNA-CoA thioesterase as a query, homology sequence analysis revealed a single homolog inL. monocytogenes, LMRG_02730. Genetic deletion of LMRG_02730 resulted in an ablated membrane potential, indicative of a non-functional electron transport chain (ETC) and an inability to aerobically respire. Biochemical kinetic analysis of LMRG_02730 revealed strong activity towards DHNA-CoA, similar to itsE. colihomolog, further demonstrating that LMRG_02730 is a DHNA-CoA thioesterase. Functional analysesin vitro,ex vivo, andin vivousing mutants directly downstream and upstream of LMRG_02730 revealed that DHNA-CoA is sufficient to facilitatein vitrogrowth in minimal media, intracellular replication, and plaque formation in fibroblasts. In contrast, protection against bacteriolysis in the cytosol of macrophages and tissue specific virulencein vivorequires the production of DHNA. Taken together, these data implicate LMRG_02730 (renamed MenI) as a DHNA-CoA thioesterase and suggest that while DHNA protects the bacteria from killing in the macrophage cytosol, DHNA-CoA is necessary for intracellular bacterial replication.
Bumblebees develop more efficient traplines than honey bees
Authors: Buatois Alexis , Dubois Thibault , Lihoreau Mathieu 
Published: December 2020

AbstractCentral place foraging pollinators, such as bees, tend to learn multi-destination routes (traplines) to efficiently visit known feeding locations and return to their nest. To what extent these routing behaviours are shared across species is unknown. Here we ran laboratory experiments to compare trapline formation and efficiency by foragers of two social bee species that differ in their collective foraging strategies: the solo foraging bumblebeeBombus terrestrisand the mass foraging honey beeApis mellifera. In a simple routing task with four artificial flowers, both bumblebees and honey bees developed a stable route, although honey bees were slower and less efficient to do so. In a more complex routing task with six flowers, only bumblebees developed a stable route. Honey bees took a longer time to discover all flowers and never integrated them in a single route. Simulations of a model of trapline formation show that these inter-specific differences can be replicated by adjusting the strength of a single learning parameter. Comparing bumblebees and honey bees in the same experimental conditions thus revealed key differences in their spatial foraging strategies, potentially driven by social constraints.
Provision of health care for prisoners during the COVID-19 pandemic: an ethical analysis of challenges and summary of select best practices
Authors: Brelje Andrea Berkemeier , Pinals Debra A. 
Published: December 2020

Purpose
This paper aims to analyze the COVID-19 pandemic response in prisons, focusing on the USA, which imprisons a higher percentage of its population than any other country in the world.

Design/methodology/approach
This paper evaluates the current pandemic response in prisons based on legal and ethical imperatives for providing health care to prisoners.

Findings
Themes of best practices identified include increasing rapid detection of new cases, reducing transmission and advocating for both short- and long-term ethical health care policies. Halting progress now could risk dire consequences and is unacceptable on legal, ethical and public health grounds.

Research limitations/implications
This paper does not involve primary research with prisoners; rather it focuses on reviewing the pandemic response in prisons. Although it may be possible to translate findings in this study to similar environments (e.g. jails and detainment centers), there are unique characteristics pertaining to each that deserve separate, focused analyses.

Originality/value
Outbreaks that occur within prisons are likely to spread to the community and vice versa. Analyses based on ethics, law and public health point to the same conclusion: preventing significant outbreaks within prisons will benefit not only prisoners but also the general public. Furthermore, even though the scientific understanding of the pandemic may change with future research, the ethical and legal principles highlighted in this paper will continue to be foundational when considering just care for prisoners.
Application of LC‐HRMS identified marker peptides in an LC‐MS/MS method for detection and quantification of heat‐resistant proteolytic activity in raw milk
Authors: Verhegghe Marijke , De Block Jan , Heyndrickx Marc , Van Coillie Els , Van Poucke Christof , Duquenne Barbara 
Published: December 2020

For the dairy industry, it would be useful to be able to determine the heat‐resistant proteolytic activity of the raw milk upon arrival at the plant, preferably before processing (within 24 h of arrival). This would allow producers to choose the most optimal processing of the raw milk and hence its fate, together with a more accurate prediction of shelf‐life. A liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method for the detection and quantification of Pseudomonas‐derived heat‐resistant proteolytic activity in raw milk based on three new marker peptides, identified using liquid chromatography coupled to high‐resolution mass spectrometry (LC‐HRMS), was developed. This method involved a sample preparation where existing peptides are removed from the milk sample, after which the heat‐resistant protease‐containing fraction is mixed with a casein substrate. After incubation, the increase of the peptide markers is determined using an LC‐MS/MS method. The limit of detection (LOD) and limit of quantification (LOQ) of this method were determined using synthetically produced peptides (with an average LOD between 0.1 and 5 ng/mL and an average LOQ between 0.1 and 10 ng/mL).
Genetic diagnosis of infantile‐onset epilepsy in the clinic: Application of whole‐exome sequencing following epilepsy gene panel testing
Authors: Kim Soo Yeon , Jang Se Song , Kim Hunmin , Hwang Hee , Choi Ji Eun , Chae Jong‐Hee , Kim Ki Joong , Lim Byung Chan 
Published: December 2020

AbstractThis study aimed to evaluate the clinical utility of whole‐exome sequencing in a group of infantile‐onset epilepsy patients who tested negative for epilepsy using a gene panel test. Whole‐exome sequencing was performed on 59 patients who tested negative on customized epilepsy gene panel testing. We identified eight pathogenic or likely pathogenic sequence variants in eight different genes (FARS2, YWHAG, KCNC1, DYRK1A, SMC1A, PIGA, OGT, and FGF12), one pathogenic structural variant (8.6 Mb‐sized deletion on chromosome X [140 994 419–149 630 805]), and three putative low‐frequency mosaic variants from three different genes (GABBR2, MTOR, and CUX1). Subsequent whole‐exome sequencing revealed an additional 8% of diagnostic yield with genetic confirmation of epilepsy in 55.4% (62/112) of our cohort. Three genes (YWHAG, KCNC1, and FGF12) were identified as epilepsy‐causing genes after the original gene panel was designed. The others were initially linked with mitochondrial encephalopathy or different neurodevelopmental disorders, although an epilepsy phenotype was listed as one of the clinical features. Application of whole‐exome sequencing following epilepsy gene panel testing provided 8% of additional diagnostic yield in an infantile‐onset epilepsy cohort. Whole‐exome sequencing could provide an opportunity to reanalyze newly recognized epilepsy‐linked genes without updating the gene panel design.
Effect of multiple freeze‐thaw cycles on protein and lipid oxidation in rabbit meat
Authors: Wang Zefu , He Zhifei , Zhang Dong , Chen Xiaosi , Li Hongjun 
Published: December 2020

SummaryFrozen storage is chosen to be the preferred method in meat preservation. However, multiple freeze‐thaw (F‐T) cycles will occur during the transfers or distribution processes under poor cold‐chain conditions. This study investigated the effects of multiple freeze‐thaw (F‐T) cycles on water mobility, microstructure damage, protein oxidation and lipid oxidation in rabbit meat during seven F‐T cycles through 56 days. Scanning electron microscopy results indicated that the increase of F‐T cycles induced the rupture of endomysia and the increase of gaps between fibres. Low‐field nuclear magnetic resonance (LF‐NMR) results showed that the peak area of T21 and T22 decreased with increasing number of repeated F‐T cycles, indicating that immobile water shifted to free water, and free water mobility increased. During repeated freeze‐thaw process, the peroxide value, thiobarbituric acid‐reactive substances, non‐haem iron content and carbonyl groups of rabbit meat gradually increased, whereas haem content, haem iron content and sulfhydryl content of rabbit meat gradually decreased. In addition, the results of Fourier transform infrared, sodium dodecyl sulphate polyacrylamide gel electrophoresis, and intrinsic fluorescence spectroscopy indirectly proved that multiple F‐T cycles could cause α‐helix structure disruption, protein aggregation and degradation, and tryptophan oxidation of rabbit meat myofibrillar protein (MP). Overall, multiple repeated F‐T cycles changed moisture migration, damaged microstructure and promoted lipid and protein oxidation of rabbit meat.
Patients’ experiences of recovery: Beyond the intensive care unit and into the community
Authors: Calkins Kelly , Kako Peninnah , Guttormson Jill 
Published: December 2020

AbstractAimsTo understand barriers and facilitators of recovery for critical illness survivors’, who are discharged home from the hospital and do not have access to dedicated outpatient care.DesignMulti‐site descriptive study guided by interpretive phenomenology using semi‐structured interviews.MethodsInterviews were conducted between December 2017 ‐July 2018. Eighteen participants were included. Data were collected from interview recordings, transcripts, field notes, and a retrospective chart review for sample demographics. Analysis was completed using Interpretive Phenomenological Analysis which provided a unique view of recovery through the survivors’ personal experiences and perception of those experiences.ResultsParticipants encountered several barriers to their recovery; however, they were resilient and initiated ways to overcome these barriers and assist with their recovery. Facilitators of recovery experienced by survivors included seeking support from family and friends, lifestyle adaptations, and creative management of their multiple medical needs. Barriers included unmet needs experienced by survivors such as mental health issues, coordination of care, and spiritual needs. These unmet needs left participants feeling unsupported from healthcare providers during their recovery.ConclusionThis study highlights important barriers and facilitators experienced by critical illness survivors during recovery that need be addressed by healthcare providers. New ways to support critical illness survivors, that can reach a broader population, must be developed and evaluated to support survivors during their recovery in the community.ImpactThis study addressed ICU survivors’ barriers and facilitators to recovery. Participants encountered several barriers to recovery at home, such as physical, cognitive, psychosocial, financial, and transportation barriers, however, these survivors were also resilient and resourceful in the development of strategies to try to manage their recovery at home. These results will help healthcare providers develop interventions to better support ICU survivors in the community.
Place of death of children and young adults with a life-limiting condition in England: a retrospective cohort study
Authors: Gibson-Smith Deborah , Jarvis Stuart William , Fraser Lorna K 
Published: December 2020

ObjectiveTo assess trends in place of death for children with a life-limiting condition and the factors associated with death at home or hospice rather than hospital.DesignObservational cohort study using linked routinely collected data.SettingEngland.PatientsChildren aged 0–25 years who died between 2003 and 2017.Main outcome measuresPlace of death: hospital, hospice, home. Multivariable multinomial logistic regression models.Results39 349 children died: 73% occurred in hospital, 6% in hospice and 16% at home. In the multivariable models compared with dying in a hospital: neonates were less likely, and those aged 1–10 years more likely, than those aged 28 days to <1 year to die in hospice. Children from all ethnic minority groups were significantly less likely to die in hospice, as were those in the most deprived group (RR 0.8, 95% CI 0.7 to 0.9). Those who died from 2008 were more likely than those who died earlier to die in a hospice.Children with cancer (RR 4.4, 95% CI 3.8 to 5.1), neurological (RR 2.0, 95% CI 1.7 to 2.3) or metabolic (RR 3.7, 95% CI 3.0 to 4.6) diagnoses were more likely than those with a congenital diagnosis to die in a hospice.Similar patterns were seen for clinical/demographic factors associated with home versus hospital deaths.ConclusionsMost children with a life-limiting condition continue to die in the hospital setting. Further research on preferences for place of death is needed especially in children with conditions other than cancer. Paediatric palliative care services should be funded adequately to enable equal access across all settings, diagnostic groups and geographical regions.
Primary acquired melanosis/melanoma: utility of conjunctival map biopsy
Authors: Soto Hansell , Bowen Randy C , Raval Vishal , Yeaney Gabrielle , Singh Arun 
Published: December 2020

AimTo assess the role of map biopsy in patients with conjunctival primary acquired melanosis (PAM)/melanoma.MethodsRetrospective case series of 400 conjunctival biopsy samples of 51 unique patients in a tertiary referral centre.ResultsEach patient underwent one diagnostic biopsy and several additional map biopsies (range 2–7) providing a total of 400 samples for the analysis (55 diagnostic biopsies, 345 map biopsies). The median age was 63 years old (range 20–88) with women representing 67% of the cases. Histopathological findings were graded as negative for melanosis/normal (grade 0), melanosis without atypia (grade 1), melanosis with mild atypia (grade 2), melanosis with severe atypia (grade 3) or invasive melanoma (grade 4). Clinicopathologic concordance was observed in the majority of the map biopsies (313, 91%) (positive: clinical+/path+ (57,17%), negative: clinical−/path− (256, 74%)). Three discordant samples (clinical−/path+) represented PAM sine pigmento. The histopathological spectrum of atypia was absent (40, 73%) or limited (11, 20%) in the majority of cases with tendency to cluster as low-grade or high-grade atypia. Map biopsy led to the identification of six patients (11%) with severe atypia, requiring topical mitomycin (MMC). Similarly, in 29 cases, periodic observation without topical MMC was recommended. One case of invasive melanoma transformation occurred in the MMC-treated group.ConclusionsMap biopsy enhances overall assessment of the anatomic and pathologic extent, impacting use of adjuvant topical chemotherapy. In absence of map biopsy, it would be impossible to diagnose PAM sine pigmento. Additional corroborative work is needed to validate our observations.
Development and validation of a deep learning system to screen vision-threatening conditions in high myopia using optical coherence tomography images
Authors: Li Yonghao , Feng Weibo , Zhao Xiujuan , Liu Bingqian , Zhang Yan , Chi Wei , Lu Mingzhi , Lin Jierong , Wei Yantao , Li Jun , Zhang Qi , Zhu Yi , Chen Chuan , Lu Lin , Zhao Lanqin , Lin Haotian 
Published: December 2020

Background/aimsTo apply deep learning technology to develop an artificial intelligence (AI) system that can identify vision-threatening conditions in high myopia patients based on optical coherence tomography (OCT) macular images.MethodsIn this cross-sectional, prospective study, a total of 5505 qualified OCT macular images obtained from 1048 high myopia patients admitted to Zhongshan Ophthalmic Centre (ZOC) from 2012 to 2017 were selected for the development of the AI system. The independent test dataset included 412 images obtained from 91 high myopia patients recruited at ZOC from January 2019 to May 2019. We adopted the InceptionResnetV2 architecture to train four independent convolutional neural network (CNN) models to identify the following four vision-threatening conditions in high myopia: retinoschisis, macular hole, retinal detachment and pathological myopic choroidal neovascularisation. Focal Loss was used to address class imbalance, and optimal operating thresholds were determined according to the Youden Index.ResultsIn the independent test dataset, the areas under the receiver operating characteristic curves were high for all conditions (0.961 to 0.999). Our AI system achieved sensitivities equal to or even better than those of retina specialists as well as high specificities (greater than 90%). Moreover, our AI system provided a transparent and interpretable diagnosis with heatmaps.ConclusionsWe used OCT macular images for the development of CNN models to identify vision-threatening conditions in high myopia patients. Our models achieved reliable sensitivities and high specificities, comparable to those of retina specialists and may be applied for large-scale high myopia screening and patient follow-up.
Remote Rainfall of Typhoon Khanun (2017): Monsoon Mode and Topographic Mode
Authors: Lin Yi-Hsuan , Wu Chun-Chieh 
Published: December 2020

AbstractRemote rainfall related to tropical cyclones (TCs) can be attributed to interaction between the northeasterly monsoon and TC circulation (hereafter monsoon mode), and topographic blocking and lifting effects (hereafter topographic mode). Typhoon Khanun (2017) is a case in point affected by both modes. The objective of this study is to understand the key factors leading to uncertainty in the TC-induced remote rainfall. Ensemble simulations are conducted, with the ensemble members related to the monsoon mode classified into subtypes based on the geographic location of the precipitation maxima. The results demonstrate that frontogenesis and terrain-induced uplifting are the main mechanisms leading to the heavy precipitation in northeastern Taiwan, while the orographic lifting and the interaction between the TC circulation and the topographically blocked northeasterlies result in the heavy rainfall in southeastern Taiwan. For the topographic mode, at a larger rainfall threshold, strong relation is found between the inflow angle of the TC circulation and the cumulative frequency of the rainfall, while at a smaller rainfall threshold, rainfall cumulative frequency is related to the ensemble track directions. Sensitivity experiments with TC-related moisture reduced (MR) and the terrain of Taiwan removed (TR) show that the average of the 3-day accumulated rainfall is reduced by 40% and more than 90% over the mountainous area in MR and TR, respectively. Overall, this study highlights the fact that multiple mechanisms contribute to remote rainfall processes in Khanun, particularly the orographic forcing, thus providing better insights into the predictability of TC remote rainfall.
Does the Degree of Platelet Adenosine Diphosphate and Arachidonic Acid Receptor Inhibition Correlate With the Severity of Injury in Non-Brain-Injured Trauma Patients?
Authors: Woodruff Grant , Price Dustin , Sodhi Aparna , Kerwin Andrew , Crandall Marie 
Published: December 2020

Background Direct correlations between platelet adenosine diphosphate (ADP) and arachidonic acid (AA) receptor inhibition have been described in the traumatic brain injury (TBI) population. Our goal was to evaluate the percent inhibition of ADP receptor inhibition (ADPri) and AA receptor inhibition (AAri) receptors in non-TBI patients and correlate injury severity and outcomes. Methods We performed a retrospective review of non-TBI patients admitted to our trauma center, who received thromboelastography with platelet mapping prior to blood transfusion. Exclusion criteria included patients younger than 18 years, current antiplatelet therapy, or history of renal failure. Univariate descriptive statistics and bivariate comparisons were performed on patient demographic and outcomes. Multivariable linear regression models were constructed to quantify any association between ADPri and AAri with injury outcomes. High ADP inhibition was defined >20% and high AA inhibition >7%. Results 117 patients met inclusion criteria. Mean age was 53 years with 61% male. Mean ADPri was 64% and AAri 42%. On bivariate analysis, no statistically significant differences with respect to injury severity measures or outcomes were identified. On multivariable linear regression, AAri was associated with longer hospital length of stay. Discussion There was a high degree of platelet dysfunction in this cohort of severely injured patients without TBI. Despite this, the only correlation identified between injury severity and outcomes was AAri correlating with hospital length of stay. Irrespective of injury severity or outcomes, these patients’ results were far from reported “normal” values. Further, research is needed to determine the significance and clinical implications of thromboelastography with platelet mapping use in trauma care.