bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Recovery Protocols Reduce Mortality Across Eight Surgical Specialties at Academic and University-affiliated Community Hospitals
Authors: Esper Stephen A. , Holder-Murray Jennifer , Subramaniam Kathirvel , Boisen Michael , Kenkre Tanya S. , Meister Katie , Foos Steve , Wong Hesper , Howard-Quijano Kimberly , Mahajan Aman 
Published: November 2020

Objective:
To determine if implementation of a simplified ERP across multiple surgical specialties in different hospitals is associated with improved short and long-term mortality. Secondary aims were to examine ERP effect on length of stay, 30-day readmission, discharge disposition, and complications.

Summary Background Data:
Enhanced recovery after surgery and various derivative ERPs have been successfully implemented. These protocols typically include elaborate sets of multimodal and multidisciplinary approaches, which can make implementation challenging or are variable across different specialties. Few studies have shown if a simplified version of ERP implemented across multiple surgical specialties can improve clinical outcomes.

Methods:
A simplified ERP with 7 key domains (minimally invasive surgical approach when feasible, pre-/intra-operative multimodal analgesia, postoperative multimodal analgesia, postoperative nausea and vomiting prophylaxis, early diet advancement, early ambulation, and early removal of urinary catheter) was implemented in 5 academic and community hospitals within a single health system. Patients who underwent nonemergent, major orthopedic or abdominal surgery including hip/knee replacement, hepatobiliary, colorectal, gynecology oncology, bariatric, general, and urological surgery were included. Propensity-matched, retrospective case-control analysis was performed on all eligible surgical patients between 2014 and 2017 after ERP implementation or in the 12 months preceding ERP implementation (control population).

Results:
A total of 9492 patients (5185 ERP and 4307 controls) underwent ERP eligible surgery during the study period. Three thousand three hundred sixty-seven ERP patients were matched by surgical specialty and hospital site to control non-ERP patients. Short and long-term mortality was improved in ERP patients: 30 day: ERP 0.2% versus control 0.6% (P = 0.002); 1-year: ERP 3.9% versus control 5.1% (P < 0.0001); 2-year: ERP 6.2% versus control 9.0% (P < 0.0001). Length of stay was significantly lower in ERP patients (ERP: 3.9 ± 3.8 days; control: 4.8 ± 5.0 days, P < 0.0001). ERP patients were also less likely to be discharged to a facility (ERP: 11.3%; control: 14.8%, P < 0.0001). There was no significant difference for 30-day readmission. All complications except venous thromboembolism were significantly reduced in the ERP population (P < 0.02).

Conclusions:
A simplified ERP can uniformly be implemented across multiple surgical specialties and hospital types. ERPs improve short and long-term mortality, clinical outcomes, length of stay, and discharge disposition to home.
Distinct immunologic endotypes are associated with clinical trajectory after severe blunt trauma and hemorrhagic shock
Authors: Brakenridge Scott C. , Wang Zhongkai , Cox Michael , Raymond Steven , Hawkins Russell , Darden Dijoia , Ghita Gabriela , Brumback Babette , Cuschieri Joseph , Maier Ronald V. , Moore Frederick A. , Mohr Alicia M. , Efron Philip A. , Moldawer Lyle L. 
Published: November 2020

BACKGROUND
The genomic/cytokine “storm” after severe trauma is well described. However, the differing composition, magnitude and resolution of this response, and its relationship to clinical outcomes remain unclear.

METHODS
This is a secondary analysis of a prospective longitudinal cohort study of severely injured trauma patients in hemorrhagic shock. Peripheral blood sampling was performed at 0.5, 1, 4, 7, 14, and 28 days after injury for measurement of circulating immune biomarkers. K-means clustering using overall mean and trajectory slope of selected immunologic biomarkers were used to identify distinct temporal immunologic endotypes. Endotypes were compared with known clinical trajectories defined as early death (<14 days), chronic critical illness (CCI) (ICU length of stay of ≥14 days with persistent organ dysfunction), and rapid recovery (RAP) (ICU length of stay of <14 days with organ recovery).

RESULTS
The cohort included 102 subjects enrolled across 2 level 1 trauma centers. We identified three distinct immunologic endotypes (iA, iB, and iC), each with unique associations to clinical trajectory. Endotype iA (n = 47) exhibited a moderate initial proinflammatory response followed by a return to immunologic homeostasis, with a primary clinical trajectory of RAP (n = 44, 93.6%). Endotype iB (n = 44) exhibited an early hyperinflammatory response with persistent inflammation and immunosuppression, with the highest incidence of CCI (n = 10, 22.7%). Endotype iC (n = 11) exhibited a similar hyperinflammatory response, but with rapid return to immunologic homeostasis and a predominant trajectory of RAP (n = 9, 81.8%). Patients with endotype iB had the highest severity/duration of organ dysfunction and highest incidence of nosocomial infections (50%, p = 0.001), and endotype iB was the predominant endotype of patients who developed CCI (10 of 13 patients, 76.9%; p = 0.002).

CONCLUSION
We identified three distinct immunologic endotypes after severe injury differing the magnitude and duration of the early response. The clinical trajectory of CCI is characterized by an endotype (iB) defined by persistent alteration in inflammation/immunosuppression and is associated with poor clinical outcomes.

LEVEL OF EVIDENCE
Prognostic, level III.
Two independent introductions of SARS-CoV-2 into the Iranian outbreak
Authors: Fattahi Zohreh , Mohseni Marzieh , Jalalvand Khadijeh , Moghadam Fatemeh Aghakhani , Ghaziasadi Azam , Keshavarzi Fatemeh , Yavarian Jila , Jafarpour Ali , Mortazavi Seyedeh elham , Ghodratpour Fatemeh , Behravan Hanieh , Khazeni Mohammad , Momeni Seyed Amir , Jahanzad Issa , Moradi Abdolvahab , Tabarraei Alijan , Azimi Sadegh Ali , Kord Ebrahim , Hashemi-Shahri Seyed Mohammad , Azaran Azarakhsh , Yousefi Farid , Mokhames Zakiye , Soleimani Alireza , Ghafari Shokouh , Ziaee Masood , Habibzadeh Shahram , Jeddi Farhad , Hadadi Azar , Abdollahi Alireza , Kaydani Gholam Abbas , Soltani Saber , Mokhtari-Azad Talat , Najafipour Reza , Malekzadeh Reza , Kahrizi Kimia , Jazayeri Seyed Mohammad , Najmabadi Hossein 
Published: November 2020

AbstractThe SARS-CoV-2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence, with now more than one million deaths around the world. While Iran was among the first countries confronted with rapid spread of virus in February, no real-time SARS-CoV-2 whole-genome tracking is performed in the country.To address this issue, we provided 50 whole-genome sequences of viral isolates ascertained from different geographical locations in Iran during March-July 2020. The corresponding analysis on origins, transmission dynamics and genetic diversity, represented at least two introductions of the virus into the country, constructing two major clusters defined as B.4 and B.1*. The first entry of the virus occurred around 26 December 2019, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission, led to dominancy of B.4 lineage in early epidemic till the end of June. Gradually, reduction in dominancy of B.4 occurred possibly as a result of other entries of the virus, followed by surge of B.1.* lineages, as of mid-May.Remarkably, variation tracking of the virus indicated the increase in frequency of D614G mutation, along with B.1* lineages, which showed continuity till October 2020.According to possible role of D614G in increased infectivity and transmission of the virus, and considering the current high prevalence of the disease, dominancy of this lineage may push the country into a critical health situation. Therefore, current data warns for considering stronger prohibition strategies preventing the incidence of larger crisis in future.
Divergence in a stress regulatory network underlies differential growth control
Authors: Sun Ying , Oh Dong-Ha , Duan Lina , Ramachandran Prashanth , Ramirez Andrea , Bartlett Anna , Dassanayake Maheshi , Dinneny José R. 
Published: November 2020

AbstractThe phytohormone abscisic acid (ABA) is a central regulator of acclimation during environmental stress. While some plants exhibit tremendous stress resilience, it has been unclear whether differences in ABA response underlie such adaptations. Here we establish a cross-species gene regulatory network (GRN) for ABA to identify broadly conserved, core components of the ABA signaling network and peripheral pathways exhibiting species-specific connectivity. Genes that are broadly conserved in the network share promoter architecture and patterns of gene expression. Networks associated with growth hormones exhibited highly divergent wiring of their ABA network leading to changes in the physiological outcome of signaling. Together our study provides a model for understanding how GRN subcircuits deploy different growth regulatory states across ecologically diverse species.One Sentence SummaryComparative studies reveal core and peripheral stress-mediated gene networks driving divergent growth control in plants.
Massive occurrence of benthic plastic debris at the abyssal seafloor beneath the Kuroshio Extension, the North West Pacific
Authors: Nakajima Ryota , Tsuchiya Masashi , Yabuki Akinori , Masuda Shuhei , Kitahashi Tomo , Nagano Yuriko , Ikuta Tetsuro , Isobe Noriyuki , Nakata Haruhiko , Ritchie Heather , Oguri Kazumasa , Osafune Satoshi , Kawamura Kiichiro , Suzukawa Maki , Yamauchi Takuya , Iijima Koichi , Yoshida Takao , Chiba Sanae , Fujikura Katsunori 
Published: November 2020

AbstractThe deep-sea is considered to be an ultimate sink for marine plastic debris. The abyssal (3500-6500 m) covers the bulk of the deep ocean floor yet little is known about the extent of plastic debris on the abyssal seafloor. We undertook a quantitative assessment of debris presents on the abyssal seafloor (5700-5800 m depth) beneath the Kuroshio Extension current system in the Northwest Pacific, which is one of the major transit points for massive amounts of debris sourced from Asia that are entering the North Pacific Ocean. The dominant type of debris was single-use plastics-mainly bags and food packaging. The density of plastic debris (average 4561 items km−2) in the abyssal zone was the highest recorded for an abyssal plain, suggesting that the deep-sea basin of the Northwest Pacific is a significant reservoir of plastic debris.
Entropy, complexity, and maturity in children’s neural responses during naturalistic mathematics learning
Authors: Amalric Marie , Cantlon Jessica F. 
Published: November 2020

AbstractA major goal of human neuroscience is to understand how the brain functions in the real world, and to measure neural processes under naturalistic conditions that are more ecologically valid than traditional laboratory tasks. A critical step toward this goal is understanding how neural activity during real world naturalistic tasks relates to neural activity in more traditional laboratory tasks. In the present study, we used intersubject correlations to locate reliable stimulus-driven neural processes among children and adults in naturalistic and laboratory versions of a mathematics task that shared the same content. We show that relative to a control condition with grammatical content, naturalistic and simplified mathematics tasks evoked overlapping activation within brain regions previously associated with math semantics. We further examined the temporal properties of children’s neural responses during the naturalistic and laboratory tasks to determine whether temporal patterns of neural activity change over development, or dissociate based on semantic or task content. We introduce a rather novel measure, not yet used in fMRI studies of child learning: neural multiscale entropy. In addition to showing new evidence of naturalistic mathematics processing in the developing brain, we show that neural maturity and neural entropy are two independent but complementary markers of functional brain development. We discuss the implications of these results for the development of neural complexity in children.
Inferring parameters of cancer evolution from sequencing and clinical data
Authors: Lee Nathan , Bozic Ivana 
Published: November 2020

AbstractAs a cancer develops, its cells accrue new mutations, resulting in a heterogeneous, complex genomic profile. We make use of this heterogeneity to derive simple, analytic estimates of parameters driving carcinogenesis and reconstruct the timeline of selective events following initiation of an individual cancer. Using stochastic computer simulations of cancer growth, we show that we can accurately estimate mutation rate, time before and after a driver event occurred, and growth rates of both initiated cancer cells and subsequently appearing subclones. We demonstrate that in order to obtain accurate estimates of mutation rate and timing of events, observed mutation counts should be corrected to account for clonal mutations that occurred after the founding of the tumor, as well as sequencing coverage. We apply our methodology to reconstruct the individual evolutionary histories of chronic lymphocytic leukemia patients, finding that the parental leukemic clone typically appears within the first fifteen years of life.
Bivariate genomic prediction of phenotypes by selecting epistatic interactions across years
Authors: Vojgani Elaheh , Pook Torsten , Hölker Armin C. , Mayer Manfred , Schön Chris-Carolin , Simianer Henner 
Published: November 2020

AbstractThe importance of accurate genomic prediction of phenotypes in plant breeding is undeniable, as higher prediction accuracy can increase selection responses. In this study, we investigated the ability of three models to improve prediction accuracy by including phenotypic information from the last growing season. This was done by considering a single biological trait in two growing seasons (2017 and 2018) as separate traits in a multi-trait model. Thus, bivariate variants of the Genomic Best Linear Unbiased Prediction (GBLUP) as an additive model, Epistatic Random Regression BLUP (ERRBLUP) and selective Epistatic Random Regression BLUP (sERRBLUP) as epistasis models were compared with respect to their prediction accuracies for the second year. The results indicate that bivariate ERRBLUP is slightly superior to bivariate GBLUP in predication accuracy, while bivariate sERRBLUP has the highest prediction accuracy in most cases. The average relative increase in prediction accuracy from bivariate GBLUP to maximum bivariate sERRBLUP across eight phenotypic traits and studied dataset from 471/402 doubled haploid lines in the European maize landrace Kemater Landmais Gelb/Petkuser Ferdinand Rot, were 7.61 and 3.47 percent, respectively. We further investigated the genomic correlation, phenotypic correlation and trait heritability as the factors affecting the bivariate model’s predication accuracy, with genetic correlation between growing seasons being the most important one. For all three considered model architectures results were far worse when using a univariate version of the model, e.g. with an average reduction in prediction accuracy of 0.23/0.14 for Kemater/Petkuser when using univariate GBLUP.Key MassageBivariate models based on selected subsets of pairwise SNP interactions can increase the prediction accuracy by utilizing phenotypic data across years under the assumption of high genomic correlation across years.
Coiled-coil and RPW8-type immune receptors function at the plasma membrane in a phospholipid dependent manner
Authors: Saile Svenja C. , Ackermann Frank M. , Sunil Sruthi , Bayless Adam , Stöbbe Eva , Bonardi Vera , Wan Li , Doumane Mehdi , Jaillais Yvon , Caillaud Marie-Cécile , Dangl Jeffery L. , Nishimura Marc T. , El Kasmi Farid 
Published: November 2020

AbstractActivation of intracellular nucleotide-binding leucine-rich repeat receptors (NLRs) results in immunity and a localized cell death response of infected cells. Cell death activity of many NLRs requires oligomerization and in some cases plasma membrane (PM) localization. However, the exact mechanisms underlying PM localization of NLRs lacking recognizable N- or C-terminal lipidation motifs or predicted transmembrane domains remains elusive. Here we show that the PM localization and stability of members of the RPW8-like coiled-coil (CCR) domain NLRs (RNLs) and a CC-type NLR (CNL) depend on the interaction with PM phospholipids. Depletion of phosphatidylinositol-4-phosphate (PI4P) from the PM led to a mislocalization of the analyzed NLRs and consequently inhibited their cell death activity. We further demonstrate activation-dependent self-association of cell death inducing RNLs. Our results provide new insights into the molecular mechanism of NLR PM localization and defines an important role of phospholipids for CNL and RNL activity during immunity.
A Proteomic Platform to Identify Off-Target Proteins Associated with Therapeutic Modalities that Induce Protein Degradation or Gene Silencing
Authors: Liu Xin , Zhang Ye , Ward Lucas D. , Yan Qinghong , Bohnuud Tanggis , Hernandez Rocio , Lao Socheata , Yuan Jing , Fan Fan 
Published: November 2020

ABSTRACTNovel modalities such as Proteolysis Targeting Chimera (PROTAC) and RNA interference (RNAi) have a mechanism of action-based potential to alter the abundance of off-target proteins. The currentin vitrosecondary pharmacology assays, which evaluate off-target binding or activity of small molecules, do not fully assess the off-target effects of PROTAC and are not applicable to RNAi. To address this gap, we developed a proteomics-based platform to comprehensively evaluated abundance of off-target proteins. The first part of the manuscript describes the rationale and process through which the off-target proteins and cell lines were selected. The off-target proteins were selected from the entire human proteome based on genetics and pharmacology data (Deatonet al., 2018). The selection yielded 2,813 proteins, forming the nexus of a panel that we refer to as the “selected off-target proteome” (SOTP). An algorithm was then used to identify appropriate cell lines. Four human cell lines out of 932 were selected that, collectively, expressed ~ 80% of the SOTP based on transcriptome data. The second part of the manuscript describes the LC-MS/MS experimentation to quantify the intracellular and extracellular proteins of interest in the 4 selected cell lines. Among over 10,000 quantifiable proteins identified, 1,828 were part of the predefined SOTP. The SOTP was designed to be easily modified or expanded, owing rationale selection process developed and the label free LC-MS/MS approach chosen. This versatility inherent to our platform is essential to design fit-for-purpose studies that can address the dynamic questions faced in investigative toxicology.
A scalable method for identifying recombinants from unaligned sequences
Authors: Feng Qian , Tiedje Kathryn , Ruybal-Pesántez Shazia , Tonkin-Hill Gerry , Duffy Michael , Day Karen , Shim Heejung , Chan Yao-ban 
Published: November 2020

AbstractRecombination is a fundamental process in molecular evolution, and the identification of recombinant sequences is of major interest for biologists. However, current methods for detecting recombinants only work for aligned sequences, often require a reference panel, and do not scale well to large datasets. Thus they are not suitable for the analyses of highly diverse genes, such as thevargenes of the malaria parasitePlasmodium falciparum,which are known to diversify primarily through recombination.We introduce an algorithm to detect recombinant sequences from an unaligned dataset. Our approach can effectively handle thousands of sequences without the need of an alignment or a reference panel, offering a general tool suitable for the analysis of many different types of sequences. We demonstrate the effectiveness of our algorithm through extensive numerical simulations; in particular, it maintains its accuracy in the presence of insertions and deletions.We apply our algorithm to a dataset of 17,335 DBLαtypes invargenes from Ghana, enabling the comparison between recombinant and non-recombinant types for the first time. We observe that sequences belonging to the same ups type or DBLαsubclass recombine amongst themselves more frequently, and that non-recombinant DBLαtypes are more conserved than recombinant ones.Author summaryRecombination is a fundamental process in molecular evolution where two genes exchange genetic material, diversifying the genes. It is important to properly model this process when reconstructing evolutionary history, and to do so we need to be able to identify recombinant genes. In this manuscript, we develop a method for this which can be applied to scenarios where current methods often fail, such as where genes are very diverse.We specifically focus on detecting recombinants in thevargenes of the malaria parasitePlasmodium falciparum. These genes influence the length and severity of malaria infection, and therefore their study is critical to the treatment and prevention of malaria. They are also highly diverse, primarily because of recombination. Our analysis of genes from a cross-sectional study in Ghana study show fundamental relations between the patterns and prevalence of recombination in these genes and other important biological categorisations.
Motor sequence learning deficits in idiopathic Parkinson’s disease are associated with increased substantia nigra activity
Authors: Tzvi Elinor , Bey Richard , Nitschke Matthias , Brüggemann Norbert , Classen Joseph , Münte Thomas F. , Krämer Ulrike M. , Rumpf Jost-Julian 
Published: November 2020

AbstractPrevious studies have shown that persons with Parkinson’s disease (pwPD) share specific deficits in learning new sequential movements, but the neural substrates of this impairment remain unclear. In addition, the degree to which striatal dopaminergic denervation in PD affects the cortico-striato-cerebellar motor learning network remains unknown. We aimed to answer these questions using fMRI in 16 pwPD and 16 healthy age-matched control subjects while they performed an implicit motor sequence learning task. While learning was absent in both pwPD and controls assessed with reaction time differences between sequential and random trials, larger error-rates during the latter suggest that at least some of the complex sequence was encoded. Moreover, we found that while healthy controls could improve general task performance indexed by decreased reaction times across both sequence and random blocks, pwPD could not, suggesting disease-specific deficits in learning of stimulus-response associations. Using fMRI, we found that this effect in pwPD was correlated with decreased activity in the hippocampus over time. Importantly, activity in the substantia nigra (SN) and adjacent bilateral midbrain was specifically increased during sequence learning in pwPD compared to healthy controls, and significantly correlated with sequence-specific learning deficits. As increased SN activity was also associated (on trend) with higher doses of dopaminergic medication as well as disease duration, the results suggest that learning deficits in PD are associated with disease progression, indexing an increased drive to recruit dopaminergic neurons in the SN, however unsuccessfully. Finally, we found no differences between pwPD and controls in task modulation of the cortico-striato-cerebellar network. Notably, in both groups Bayesian model selection revealed cortico-cerebellar connections modulated by the task, suggesting that despite behavioral and activation differences, the same cortico-cerebellar circuitry is recruited for implementing the motor task.