bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delta Neutrophil Index for the Prediction of the Development of Sepsis-Induced Acute Kidney Injury in the Emergency Department
Authors: Kim Ji Hoon , Park Yoo Seok , Yoon Chang-Yun , Lee Hye Sun , Kim Sinae , Lee Jong Wook , Kong Taeyoung , You Je Sung , Park Jong Woo , Chung Sung Phil 
Published: March 2019

ABSTRACT

Background and Purpose:
The early prediction of acute kidney injury (AKI) in sepsis and provision of timely treatment may improve outcomes. We investigated the efficacy of the delta neutrophil index (DNI)—which reflects the fraction of immature granulocytes—in predicting sepsis-induced AKI and 30-day mortality in cases of severe sepsis or septic shock.

Methods:
This retrospective, observational cohort study was performed with patients prospectively integrated in a critical pathway of early-goal-directed therapy /SEPSIS. We analyzed adult sepsis patients admitted to the emergency department with normal kidney function or stage 1 disease, based on the Acute Kidney Injury Network classification, between January 1, 2014 and September 30, 2017. The outcomes were the development of sepsis-induced severe AKI within 7 days and 30-day mortality.

Results:
A total of 346 patients were enrolled. An increase in the DNI values at Time-0 (odds ratio [OR], 1.060; P < 0.001) and Time-12 (OR, 1.086; P < 0.001) were strong independent predictors of severe AKI development. The increasing predictability of AKI was closely associated with a DNI ≥14.0% at Time-0 (OR, 7.238; P < 0.001) and ≥13.3% at Time-12 (OR, 18.089; P < 0.001). The development of severe AKI was an independent predictor of 30-day mortality (hazard ratio: 25.2, P < 0.001).

Conclusion:
Higher DNI values are independent predictors of severe AKI development and 30-day mortality in sepsis. Physicians can use the DNI to quickly determine the severity of sepsis and initial treatment strategies without additional costs and effort.
Treatment of Congenital Gastric Outlet Obstruction due to a Web: A Retrospective Single-center Review
Authors: Gehwolf Philipp , Hechenleitner Paul , Sanal Murat , Profanter Christoph , Häussler Beatrice , Härter Bettina 
Published: March 2019

Background:
Congenital gastric antral web and congenital pyloric atresia are rare reasons of congenital gastric outlet obstruction (CGOO). Depending on the different forms, the symptoms vary from unspecific epigastric pain to nonbilious “projectile” vomiting, ileus and failure to thrive. Throughout the years, many different treatment options are described, like simple surgical dilatation, incision or excision of the membrane, possibly combined with a pyloroplasty.

Patients and Methods:
In this retrospective single-center observation study, we present 9 cases with different kinds of webs leading to CGOO. In a time period of 45 years (1970 to 2015) different treatment strategies and limitations of minimal invasive endoscopic treatment on the basis of complications and outcome are discussed.

Results:
Six patients had an incomplete antrum web. One patient suffered from a complete antrum web. In addition, in 2 patients a complete pyloric web, as well as an incomplete pyloric web was found. During the past 45 years, the treatment options for CGOO due to webs changed, and with the development of smaller and more flexible video endoscopes an endoscopic treatment has become feasible. The treatment strategy and follow-up examination was specific to every patient.

Conclusion:
On the basis of our review, minimal endoscopic procedures in small newborns and toddlers require a high level of experience. They are technically challenging and need suitable equipment. Overall, endoscopists and pediatric surgeons should equally be prepared for all possible complications in every treatment step. The endoscopic approach to managing this unusual disease may require multiple interventions and is associated with a risk of perforation. Therefore, we are convinced that centers undertaking this treatment modality should be equipped with the proper instrumentation, prepared to perform multiple endoscopic interventions, and supported with an ability to emergently convert to surgery if required.
Dynamics of acute respiratory distress syndrome development due to smoke inhalation injury: Implications for prolonged field care
Authors: Batchinsky Andriy I. , Wyckoff Ruth , Choi Jae-Hyek , Burmeister David , Jordan Bryan S. , Necsoiu Corina , Burkett Samuel E. , Morris Michael J. , Chung Kevin K. , Cancio Leopoldo C. 
Published: March 2019

BACKGROUND
Smoke inhalation injury (SII) causes 30% to 40% mortality and will increase as a cause of death during prolonged field care. We used a combat relevant model of acute respiratory distress syndrome due to SII to study temporal changes in ventilation-perfusion (V/Q) matching, computed tomography (CT) scan data, and histopathology and hypothesized that SII leads to increase in shunt (Qshunt), V/Q mismatch, lung consolidation, and diffuse alveolar damage.

METHODS
Swine received severe SII and airway pressure release ventilation (APRV, n = 6), or conventional ARDSNet mechanical ventilation (MV) (CMV, n = 8). A control group without injury received volume controlled MV (CTRL, n = 6), The multiple inert gas elimination technique and CT were performed at baseline (BL), 0.5 hours, 1 hours, 2 hours, 24 hours, and 48 hours after injury. Diffuse alveolar damage scoring was performed post mortem. Significance at p less than 0.05: APRV versus CTRL‡; CMV versus CTRL†; APRV versus CMV*; & denotes changes versus BL.

RESULTS
(1) SII caused increases in Qshunt more so in APRV than CMV group. Qshunt did not change in CTRL. (2) Pao
2-to-FIO2 ratio (PFR) was lower in APRV versus CTRL at 2 hours (375 ± 62‡ vs. 549 ± 40) and 24 hours (126 ± 34‡*& vs. 445 ± 5) and 48 hours (120 ± 41‡& vs. 430 ± 13). In CMV animals, PFR was lower versus CTRL and BL at 24 hours (238 ± 33†&) and 48 hours (98 ± 27†&). Qshunt correlated with PFR (r = 0.75, p < 0.0001, APRV and (r = 0.65, p < 0.0001, CMV). CT showed decrease in normally aerated lung, while poorly and nonaerated lung increased.

CONCLUSION
Smoke inhalation injury leads to early development of shunt, V/Q mismatch, lung consolidation, and diffuse alveolar damage. These data substantiate the need for new point of injury interventions in the prolonged field care setting.

LEVEL OF EVIDENCE
Animal research.
Low-value clinical practices in injury care: A scoping review and expert consultation survey
Authors: Moore Lynne , Lauzier François , Tardif Pier-Alexandre , Boukar Khadidja Malloum , Farhat Imen , Archambault Patrick , Mercier Éric , Lamontagne François , Chassé Michael , Stelfox Henry T. , Berthelot Simon , Gabbe Belinda , Lecky Fiona , Yanchar Natalie , Champion Howard , Kortbeek John , Cameron Peter , Bonaventure Paule Lessard , Paquet Jérôme , Truchon Catherine , Turgeon Alexis F. 
Published: March 2019

BACKGROUND
Tests and treatments that are not supported by evidence and could expose patients to unnecessary harm, referred to here as low-value clinical practices, consume up to 30% of health care resources. Choosing Wisely and other organizations have published lists of clinical practices to be avoided. However, few apply to injury and most are based uniquely on expert consensus. We aimed to identify low-value clinical practices in acute injury care.

METHODS
We conducted a scoping review targeting articles, reviews and guidelines that identified low-value clinical practices specific to injury populations. Thirty-six experts rated clinical practices on a five-point Likert scale from clearly low value to clearly beneficial. Clinical practices reported as low value by at least one level I, II, or III study and considered clearly or potentially low-value by at least 75% of experts were retained as candidates for low-value injury care.

RESULTS
Of 50,695 citations, 815 studies were included and led to the identification of 150 clinical practices. Of these, 63 were considered candidates for low-value injury care; 33 in the emergency room, 9 in trauma surgery, 15 in the intensive care unit, and 5 in orthopedics. We also identified 87 “gray zone” practices, which did not meet our criteria for low-value care.

CONCLUSION
We identified 63 low-value clinical practices in acute injury care that are supported by empirical evidence and expert opinion. Conditional on future research, they represent potential targets for guidelines, overuse metrics and de-implementation interventions. We also identified 87 “gray zone” practices, which may be interesting targets for value-based decision-making. Our study represents an important step toward the deimplementation of low-value clinical practices in injury care.

LEVEL OF EVIDENCE
Systematic Review, Level IV.
Transient non-integrative nuclear reprogramming promotes multifaceted reversal of aging in human cells
Authors: Sarkar Tapash Jay , Quarta Marco , Mukherjee Shravani , Colville Alex , Paine Patrick , Doan Linda , Tran Christopher M. , Chu Constance R. , Horvath Steve , Bhutani Nidhi , Rando Thomas A. , Sebastiano Vittorio 
Published: March 2019

SummaryAging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels1-3. At the chromatin level, aging is associated with the progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis3. The technology of nuclear reprogramming to pluripotency, through over-expression of a small number of transcription factors, can revert both the age and the identity of any cell to that of an embryonic cell by driving epigenetic reprogramming2,4,5. Recent evidence has shown that transient transgenic reprogramming can ameliorate age-associated hallmarks and extend lifespan in progeroid mice6. However, it is unknown how this form of ‘epigenetic rejuvenation’ would apply to physiologically aged cells and, importantly, how it might translate to human cells. Here we show that transient reprogramming, mediated by transient expression of mRNAs, promotes a rapid reversal of both cellular aging and of epigenetic clock in human fibroblasts and endothelial cells, reduces the inflammatory profile in human chondrocytes, and restores youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity. Our method, that we named Epigenetic Reprogramming of Aging (ERA), paves the way to a novel, potentially translatable strategy for ex vivo cell rejuvenation treatment. In addition, ERA holds promise for in vivo tissue rejuvenation therapies to reverse the physiological manifestations of aging and the risk for the development of age-related diseases.
Pan-GWAS of Streptococcus agalactiae highlights lineage-specific genes associated with virulence and niche adaptation
Authors: Gori Andrea , Harrison Odile , Mlia Ethwako , Nishihara Yo , Chinkwita-Phiri Jacquline , Mallewa Macpherson , Dube Queen , Swarthout Todd D , Nobbs Angela H , Maiden Martin , French Neil , Heyderman Robert S 
Published: March 2019

ABSTRACTStreptococcus agalactiae (Group B streptococcus, GBS) is a coloniser of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterised by Clonal Complexes (CCs) with different invasive potentials. CC17 for example, is a hypervirulent lineage commonly associated with neonatal sepsis and meningitis, while CC1 is less invasive in neonates and more commonly causes invasive disease in adults with co-morbidities. The genetic basis of GBS virulence and to what extent different CCs have adapted to different host environments remain uncertain. We have therefore applied a pan-genome wide association study approach to 1988 GBS strains isolated from different hosts and countries. Our analysis identified 279 CC-specific genes associated with virulence, disease, metabolism and regulation of cellular mechanisms that may explain the differential virulence potential of particular CCs. In CC17 and CC23 for example, we have identified genes encoding for pilus, quorum sensing proteins, and proteins for the uptake of ions and micronutrients which are absent in less invasive lineages. Moreover, in CC17, carriage and disease strains were distinguished by the allelic variants of 21 of these CC-specific genes. Together our data highlight the lineage-specific basis of GBS niche adaptation and virulence, and suggest that human-associated GBS CCs have largely evolved in animal hosts before crossing to the humans and then spreading clonally.
Growth Mode and Carbon Source Impact the Surfaceome Dynamics ofLactobacillus rhamnosusGG
Authors: Savijoki Kirsi , Nyman Tuula A. , Kainulainen Veera , Miettinen Ilkka , Siljamäki Pia , Fallarero Adyary , Sandholm Jouko , Satokari Reetta , Varmanen Pekka 
Published: March 2019

AbstractBacterial biofilms have clear implications in disease and in food applications involving probiotics. Here, we show that switching the carbohydrate source from glucose to fructose increased the biofilm formation and the total surface-antigenicity of a well-known probiotic,Lactobacillus rhamnosusGG. Surfaceomes (all cell surface-associated proteins) of GG cells grown with glucose and fructose in planktonic and biofilm cultures were identified and compared, which indicated carbohydrate source-dependent variations, especially during biofilm growth. The most distinctive differences under these conditions were detected with several surface adhesins (e.g., MBF, SpaC/A pilus and penicillin-binding proteins), enzymes (glycoside hydrolases, PrsA, PrtP, PrtR and HtrA) and moonlighting proteins (glycolytic, transcription/translation and stress-associated proteins, r-proteins, tRNA synthetases, Clp family proteins, PepC, PepN and PepA). The abundance of several known adhesins and novel moonlighters, including enzymes acting on casein-derived peptides (ClpP, PepC and PepN), increased in the biofilm cells grown on fructose, from which the surface-associated aminopeptidase activity mediated by PepC and PepN was further confirmed by an enzymatic assay. The classical surface adhesins were predicted to be more abundant on planktonic cells growing either on fructose (MBF and SpaA) or glucose (SpaC). An additional indirect ELISA indicated both growth mode- and carbohydrate-dependent differences in abundance of SpaC, whereas the overall adherence of GG assessed with porcine mucus indicated that the carbon source and the growth mode affected mucus adhesion. The adherence of GG cells to mucus was almost completely inhibited by anti-SpaC antibodies regardless of growth mode and/or carbohydrate source, indicating the key role of the SpaCBA pilus in adherence under the tested conditions. Altogether, our results suggest that carbon source and growth mode coordinate classical and nonclassical protein export in GG, which ensures the presence of an integral and coordinated system that contributes to resistance, nutrient acquisition and cell-cell interactions under different conditions. In conclusion, the present study shows that different growth regimes and conditions can have a profound impact on the adherent and antigenic features of GG, thereby providing new information on how to gain additional benefits from this probiotic.
Exceptional subgenome stability and functional divergence in allotetraploid teff, the primary cereal crop in Ethiopia
Authors: VanBuren Robert , Wai Ching Man , Pardo Jeremy , Yocca Alan E. , Wang Xuewen , Wang Hao , Chaluvadi Srinivasa R. , Bryant Doug , Edger Patrick P. , Bennetzen Jeffrey L. , Mockler Todd C. , Michael Todd P. 
Published: March 2019

AbstractTeff (Eragrostis tef) is a cornerstone of food security in the Horn of Africa, where it is prized for stress resilience, grain nutrition, and market value. Despite its overall importance to small-scale farmers and communities in Africa, teff suffers from low production compared to other cereals because of limited intensive selection and molecular breeding. Here we report a chromosome-scale genome assembly of allotetraploid teff (variety ‘Dabbi’) and patterns of subgenome dynamics. The teff genome contains two complete sets of homoeologous chromosomes, with most genes maintained as syntenic gene pairs. Through analyzing the history of transposable element activity, we estimate the teff polyploidy event occurred ∼1.1 million years ago (mya) and the two subgenomes diverged ∼5.0 mya. Despite this divergence, we detected no large-scale structural rearrangements, homoeologous exchanges, or bias gene loss, contrasting most other allopolyploid plant systems. The exceptional subgenome stability observed in teff may enable the ubiquitous and recurrent polyploidy within Chloridoideae, possibly contributing to the increased resilience and diversification of these grasses. The two teff subgenomes have partitioned their ancestral functions based on divergent expression patterns among homoeologous gene pairs across a diverse expression atlas. The most striking differences in homoeolog expression bias are observed during seed development and under abiotic stress, and thus may be related to agronomic traits. Together these genomic resources will be useful for accelerating breeding efforts of this underutilized grain crop and for acquiring fundamental insights into polyploid genome evolution.
Bacterial endosymbionts influence fungal transcriptional profiles with implications for host response in the human fungal pathogensRhizopus microsporusandRhizopus delemar
Authors: Sephton-Clark Poppy , Muñoz José F , Itabangi Herbert , Voelz Kerstin , Cuomo Christina A , Ballou Elizabeth R 
Published: March 2019

AbstractMucorales spores, the causative agents of mucormycosis, interact with the innate immune system to cause acute, chronic, or resolving infection. Understanding the factors that influence disease initiation and progression is key to understanding mucormycosis and developing new treatments. Complicating this, mucormycosis can be caused by a number of species that span the Mucorales order and may be host to bacterial endosymbionts. This study sets out to examine the differences between two species in the Mucorales order by characterising their differential interactions with the innate immune system, and their interactions with environmental bacterial endosymbionts. Through a holistic approach, this study examines the transcriptional responses ofRhizopus delemarandRhizopus microsporus, two of the most commonly diagnosed species, to innate immune cells. This study also examines the immune cell response and assesses the variation in these responses, given the presence or absence of bacterial endosymbionts within the fungi. We see that the fungal response is driven by interaction with innate immune cells. Moreover, the effect of the bacterial endosymbiont on the fungus is species-specific and strongly influences fungal transcription during phagocyte stress. The macrophage response varies depending on the infecting fungal species, and depending on endosymbiont status. Macrophages are better able to survive when germination is inhibited, or upon a pro-inflammatory response. This work reveals species-specific host responses to related Mucorales spores and shows that bacterial endosymbionts have an important role to play by impacting both innate immune cell response, and fungal response when under stress.
ZapA stabilizes FtsZ filament bundles without slowing down treadmilling dynamics
Authors: Caldas Paulo , López-Pelegrín Mar , Pearce Daniel J.G. , Budanur Nazmi B. , Brugués Jan , Loose Martin 
Published: March 2019

AbstractFor bacterial cell division, treadmilling filaments of FtsZ organize into a ring-like structure at the center of the cell. What governs the architecture and stability of this dynamic Z-ring is currently unknown, but FtsZ-associated proteins have been suggested to play an important role. Here, we used anin vitroreconstitution approach combined with fluorescence microscopy to study the influence of the well-conserved protein ZapA on the organization and dynamics of FtsZ filaments recruited to a supported membrane. We found that ZapA increases the spatial order and stabilizes the steady-state architecture of the FtsZ filament network in a highly cooperative manner. Despite its strong influence on their large-scale organization, ZapA binds only transiently to FtsZ filaments and has no effect on their treadmilling velocity. Together, our data explains how FtsZ-associated proteins can contribute to the precision and stability of the Z-ring without compromising treadmilling dynamics.
Analysis of Genetically Regulated Gene Expression identifies a trauma type specific PTSD gene, SNRNP35
Authors: Huckins Laura M , Breen Michael S , Chatzinakos Chris , Hartmann Jakob , Klengel Torsten , da Silva Almeida Ana C , Dobbyn Amanda , Girdhar Kiran , Hoffman Gabriel E , Klengel Claudia , Logue Mark W , Lori Adriana , Morrison Filomene G , Nguyen Hoang T , Park Yongjin , Ruderfer Douglas , Sloofman Laura G , van Rooij Sanne JH ,   PTSD Working Group of Psychiatric Genomics Consortium, Baker Dewleen G , Chen Chia-Yen , Cox Nancy , Duncan Laramie E , Geyer Mark A , Glatt Stephen J. , Im Hae Kyung , Maihofer Adam X , Risbrough Victoria B , Smoller Jordan W , Stein Dan J , Yehuda Rachel , Liberzon Israel , Koenen Karestan C , Jovanovic Tanja , Kellis Manolis , Miller Mark W , Bacanu Silviu-Alin , Nievergelt Caroline M , Buxbaum Joseph D , Sklar Pamela , Ressler Kerry J , Stahl Eli A , Daskalakis Nikolaos P 
Published: March 2019

SUMMARYPTSD has significant genetic heritability; however, it is unclear how genetic risk influences tissue-specific gene expression. We used brain and non-brain transcriptomic imputation models to impute genetically regulated gene expression (GReX) in 9,087 PTSD-cases and 23,811 controls and identified thirteen significant GReX-PTSD associations. The results suggest substantial genetic heterogeneity between civilian and military PTSD cohorts. The top study-wide significant PTSD-association was with predicted downregulation of the Small Nuclear Ribonucleoprotein U11/U12 Subunit 35 (SNRNP35) in the BA9 region of the prefrontal cortex (PFC) in military cohorts. In peripheral leukocytes from 175 U.S. Marines, the observed PTSD differential gene expression correlated with the predicted blood GReX differences for these individuals, and deployment stress downregulatedSNRNP35expression, primarily in Marines with post-deployment PTSD. SNRNP35 is a subunit of the minor spliceosome complex andSNRNP35knockdown in cells validated its functional importance in U12-intron splicing. Finally, mimicking acute activation of the endogenous stress axis in mice downregulated PFCSnrnp35expression.