bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resolution of organ dysfunction as a predictor of long-term survival in necrotizing soft tissue infections: Analysis of the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections trial and a retrospective claims database-linked chart study
Authors: Brakenridge Scott C. , Wilfret David A. , Maislin Greg , Andrade Katherine E. , Walker Valery , May Addison K. , Dankner Wayne M. , Bulger Eileen M. 
Published: April 2021

BACKGROUND
Necrotizing soft tissue infections (NSTIs) are an acute surgical condition with high morbidity and mortality. Timely identification, resuscitation, and aggressive surgical management have significantly decreased inpatient mortality. However, reduced inpatient mortality has shifted the burden of disease to long-term mortality associated with persistent organ dysfunction.

METHODS
We performed a combined analysis of NSTI patients from the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections randomized-controlled interventional trial (ATB-202) and comprehensive administrative database (ATB-204) to determine the association of persistent organ dysfunction on inpatient and long-term outcomes. Persistent organ dysfunction was defined as a modified Sequential Organ Failure Assessment (mSOFA) score of 2 or greater at Day 14 (D14) after NSTI diagnosis, and resolution of organ dysfunction defined as mSOFA score of 1 or less.

RESULTS
The analysis included 506 hospitalized NSTI patients requiring surgical debridement, including 247 from ATB-202, and 259 from ATB-204. In both study cohorts, age and comorbidity burden were higher in the D14 mSOFA ≥2 group. Patients with D14 mSOFA score of 1 or less had significantly lower 90-day mortality than those with mSOFA score of 2 or higher in both ATB-202 (2.4% vs. 21.5%; p < 0.001) and ATB-204 (6% vs. 16%: p = 0.008) studies. In addition, in an adjusted covariate analysis of the combined study data sets D14 mSOFA score of 1 or lesss was an independent predictor of lower 90-day mortality (odds ratio, 0.26; 95% confidence interval, 0.13–0.53; p = 0.001). In both studies, D14 mSOFA score of 1 or less was associated with more favorable discharge status and decreased resource utilization.

CONCLUSION
For patients with NSTI undergoing surgical management, persistent organ dysfunction at 14 days, strongly predicts higher resource utilization, poor discharge disposition, and higher long-term mortality. Promoting the resolution of acute organ dysfunction after NSTI should be considered as a target for investigational therapies to improve long-term outcomes after NSTI.

LEVEL OF EVIDENCE
Prognostic/epidemiology study, level III
Development of a computed tomography perfusion protocol to support large animal resuscitation research
Authors: Abdou Hossam , Elansary Noha , Poliner David , Patel Neerav , Edwards Joseph , Richmond Michael , Rasmussen Todd , Ptak Thomas , Scalea Thomas M. , Morrison Jonathan J. 
Published: April 2021

BACKGROUND
Adequate cerebral perfusion is crucial for a positive neurological outcome in trauma; however, it is difficult to characterize in the acute setting with noninvasive methods. Intra-arterial computed tomography perfusion may offer a solution. The aim of this study was to develop an intra-arterial computed tomography perfusion protocol for resuscitation research.

METHODS
The study examined intra-arterial contrast administration for computed tomography perfusion (CTP) acquisition. It consisted of three phases: intra-arterial contrast dose finding, evaluation of reproducibility, and evaluation during hypotension. Blood pressure and laser Doppler flow data were collected. In phase 1, animals underwent CTPs using several intra-arterial contrast injection protocols. In phase 2, animals underwent two CTPs 7 hours apart using the 2.5 mL/s for 3-second protocol. In phase 3, animals underwent CTPs at several pressures following a computer-controlled bleed including euvolemia and at systolic pressures of 60, 40, and 20 mm Hg. Phase 1 CTPs were evaluated for contrast-to-noise ratio. In phase 2, CTPs were compared within each animal and with laser Doppler flow using linear regression. Phase 3 CTPs were graphed against systolic pressure and fitted with a nonlinear fit.

RESULTS
The protocol using 2.5mL/s for 3 seconds was optimal, demonstrating a contrast-to-noise ratio of 40.1 and a superior arterial input function curve compared with the 1 mL/s bolus. Cerebral blood flow demonstrated high concordance between baseline and end of study CTPs (R2 = 0.82, p < 0.001). Cerebral blood flow also compared moderately well against laser Doppler flow during 8 (R2 = 0.53, p = 0.03); however, laser Doppler flow did not perform well during hypovolemia, and the favorable concordance was not maintained (R2 = 0.45, p = 0.06). Cerebral blood flow was graphed against systolic blood pressure and fitted with a nonlinear fit (R2 = 0.95, p = 0.003).

CONCLUSION
Computed tomography perfusion using intra-arterial contrast injection may offer a novel alternative to traditional CTP protocols that could prove a useful additional tool in the setting of resuscitation research.
Does shock index, pediatric age-adjusted predict mortality by trauma center type?
Authors: Austin John R. , Ye Chaonan , Lee Moon O. , Chao Stephanie D. 
Published: April 2021

BACKGROUND
Pediatric trauma patients are treated at adult trauma centers (ATCs), mixed pediatric and ATCs (MTC), or pediatric trauma centers (PTCs). Shock index, pediatric age-adjusted (SIPA) can prospectively identify severely injured children. This study characterized the differences in mortality and hospital length of stay (LOS) among pediatric trauma patients with elevated SIPA (eSIPA) at different trauma centers types.

METHODS
Pediatric patients (1–14 years) were queried from the 2013 to 2016 National Trauma Data Bank. Patients with eSIPA were included for analysis. The primary outcome was mortality. Secondary outcomes included rates of splenectomy, computed tomography chest scans, laparotomy, and hospital LOS. Unadjusted frequencies and multivariable regression analyses were performed. An alpha level of 0.01 was used to determine significance.

RESULTS
Out of 189,003 pediatric trauma patients, 15,832 were included for analysis. After controlling for age, race, sex, payment method, Injury Severity Score, Glasgow Coma Scale score, hospital teaching status, and number of hospital beds, there was no significant difference in mortality among eSIPA patients at ATCs (odds ratio [OR], 0.753; p = 0.078) and MTCs (OR, 1.051; p = 0.776) when compared with PTCs. This remained true even among the most severely injured eSIPA patients (Injury Severity Score > 25). Splenectomy rates were higher at ATCs (OR, 3.234; p = 0.005), as were computed tomography chest scan rates (ATC OR, 4.423; p < 0.001; MTC OR, 6.070; p < 0.001) than at PTCs. There was a trend toward higher splenectomy rates at MTCs (OR, 2.910; p = 0.030) compared with PTCs, but this did not reach statistical significance. Laparotomy rates and hospital LOS were not significantly different.

CONCLUSION
Among eSIPA pediatric trauma patients, there was no difference in mortality between trauma center types. However, other secondary findings indicate that specialty care at PTCs may help optimize the care of pediatric trauma patients.

LEVEL OF EVIDENCE
Retrospective cohort study, level IV.
The Effects of Ibuprofen Consumption on the Incidence of Postpartum Depression
Authors: Kapulsky Leonid , Christos Paul , Ilagan John , Kocsis James 
Published: April 2021

ObjectivesPostpartum depression (PPD) is a common and debilitating psychiatric condition whose etiology is yet to be fully elucidated. Anti-inflammatory medications have been shown to be effective in the treatment of major depressive disorder but there have only been a few trials examining whether anti-inflammatory medications can serve as effective prophylactic agents against the development of major depressive disorder. Prophylaxis against PPD with anti-inflammatory agents has never been studied.Materials and MethodsWe performed a prospective observational trial examining whether consumption of higher doses of the nonsteroidal anti-inflammatory drug ibuprofen is associated with a lower incidence of PPD. We recruited high-risk women and collected data on Edinburgh Postnatal Depression Scale, Patient-Reported Outcome Measurement Information System pain scale and clinical assessment of PPD at postpartum weeks 0, 3, and 6. Subjects were instructed to keep a log of medication consumed.ResultsWhen looking at the total sample, we found that higher consumption of ibuprofen was associated with lower incidence of PPD, although this result was nonsignificant (P= 0.26). When we stratified by concurrent psychotropic medication, we found that among women not taking psychotropic medications, higher consumption of ibuprofen at week 3 was significantly associated with a lower likelihood of having PPD at week 3 (P= 0.03).DiscussionWe found that ibuprofen consumption was significantly associated with a reduced risk of development of PPD at week 3 among high-risk women not taking psychotropic medications.
Low-Dose Aripiprazole-Induced Nocturnal Enuresis in a 9-Year-Old Boy: A Case Report and the Possible Underlying Mechanism
Authors: Özdemir Yahya Esad , Tanir Yaşar 
Published: April 2021

Abstract
Aripiprazole is an atypical antipsychotic commonly used in the treatment of psychiatric disorders, such as schizophrenia, bipolar disorder, and irritability associated with autism spectrum disorder. Common adverse effects associated with aripiprazole usage in children and adolescents are nausea, vomiting, extrapyramidal adverse effects, akathisia, sedation, tremor, and increased appetite. Enuresis is one of the least expected adverse effects during aripiprazole use. The pathophysiology of aripiprazole-induced enuresis has not been fully clarified. To our knowledge, our report presents enuresis related to aripiprazole use at the lowest dose in the literature. In this report, we present the case of a 9-year-old boy who developed nocturnal enuresis after the beginning of low-dose aripiprazole treatment.
Lithium-Induced Treatment-Resistant Akathisia: A Case Report and Literature Overview
Authors: Demir Bahadir , Sancaktar Muhammet , Altindag Abdurrahman 
Published: April 2021

Objective
A case of lithium-induced akathisia is presented, a side effect that has only rarely been reported in the literature.

Case
A 49-year-old married woman was hospitalized 4 weeks before her presentation to our outpatient clinic due to a manic episode with psychotic features. Lithium carbonate (600 mg/d) was started for mood stabilization and soon, thereafter, she developed akathisia, which did not respond to reducing the dose of risperidone and addition of propranolol and lorazepam. The akathisia resolved when lithium was discontinued and replaced with valproic acid for mood stabilization.

Discussion
Akathisia is commonly overlooked or misdiagnosed by physicians. This case report is presented to alert physicians to the possible emergence of akathisia when the lithium ion is prescribed for mood stabilization.
Quantitative Proteomics Identifies PTP1B as Modulator of B Cell Antigen Receptor Signaling
Authors: Schwarz Jennifer J. , Grundmann Lorenz , Kokot Thomas , Kläsener Kathrin , Fotteler Sandra , Medgyesi David , Köhn Maja , Reth Michael , Warscheid Bettina 
Published: April 2021

ABSTRACTB cell antigen receptor (BCR) signaling is initiated by protein kinases and limited by counteracting phosphatases that currently are less well studied in their regulation of BCR signaling. We here used the B cell line Ramos to identify and quantify human B cell signaling components. Specifically, a protein tyrosine phosphatase profiling revealed a high expression of the protein tyrosine phosphatase 1B (PTP1B) in Ramos and human naïve B cells. The loss of PTP1B leads to increased B cell activation. Through substrate trapping in combination with quantitative mass spectrometry, we identified 22 putative substrates or interactors of PTP1B. We validated Igα, CD22, PLCγ1/2, CBL, BCAP and APLP2 as specific substrates of PTP1B in Ramos B cells. The tyrosine kinase BTK and the two adaptor proteins GRB2 and VAV1 were identified as direct binding partners and potential substrates of PTP1B. We showed that PTP1B dephosphorylates the inhibitory receptor protein CD22 at phosphotyrosine 807. We conclude that PTP1B negatively modulates BCR signaling by dephosphorylating distinct phosphotyrosines in B cell specific receptor proteins and various downstream signaling components.
Microglia complement signaling promotes neuronal elimination and normal brain functional connectivity
Authors: Deivasigamani Senthilkumar , Miteva Mariya Timotey , Natale Silvia , Gutierrez-Barragan Daniel , Basilico Bernadette , Di Angelantonio Silvia , Pape Constantin , Bolasco Giulia , Galbusera Alberto , Gozzi Alessandro , Ragozzino Davide , Gross Cornelius T. 
Published: April 2021

AbstractComplement signaling is thought to serve as an opsonization signal to promote the phagocytosis of synapses by microglia. However, while its role in synaptic remodeling has been demonstrated in the retino-thalamic system, it remains unclear whether complement signaling mediates synaptic pruning in the brain more generally. Here we show that mice lacking the complement 3 receptor (C3r), the major microglia complement receptor, fail to show a deficit in either synaptic pruning or axon elimination in the developing mouse cortex. Instead, mice lacking C3r show a deficit in the perinatal elimination of neurons, both in the retina as well as in the cortex, a deficit that is associated with increased cortical thickness and enhanced functional connectivity in these regions in adulthood. These data demonstrate a preferential role for complement in promoting neuronal elimination in the developing brain and argue for a reconsideration of the role of complement in synaptic pruning.
Staying in touch: how highly specialised moth pollinators track host plant phenology in unpredictable climates
Authors: Finch Jonathan T. D. , Power Sally A. , Welbergen Justin A. , Cook James M. 
Published: April 2021

AbstractFor pollinating insects that visit just a single flowering species, the co-occurrence of flowers and insects in time is likely to have critical implications for both plant and pollinator. Insects often utilise diapause to persist through periods in which resources are unavailable, timing their re-emergence by responding to the same environmental cues as their host plants. The obligate pollination mutualisms (OPMs) betweenEpicephalamoths (Gracillariidae) and their leaf flower host plants are some of the most specialised interactions between plants and insects. However, to date there have been very few studies ofEpicephalamoth lifecycles and none of how they synchronise their activity with the flowering of their host plants.Breynia oblongifolia(Phyllanthaceae) is known to be exclusively pollinated by two highly specific species ofEpicephalamoth (Gracillariidae). We surveyed populations of both the host plant and it’s pollinators over multiple years to determine their annual phenology and then modelled the climatic factors that drive their activity. Using our newly gained knowledge of moth and host plant phenology, we then looked for evidence of diapause at both the egg and pre-pupal stages. Our phenology surveys showed that although female flowers were present throughout the entire year, the abundance of flowers and fruits was highly variable between sites and strongly associated with local rainfall and photoperiod. Fruit abundance, but not flower abundance, was a significant predictor of adultEpicephalaactivity, suggesting that eggs or early instar larvae diapause within dormant flowers and emerge as fruits mature. Searches of overwintering flowers confirmed this, with many containing evidence of pollen and diapausing pollinators. We also observed the behaviour of adultEpicephalaprior to pupation and found that ~10% of the Autumn emergingEpicephalaenter diapause, eclosing to adulthood after 38-56 weeks. The remaining 90% of autumn emerging adults pupate directly with no diapause, suggesting a bet hedging strategy for adult emergence. As such,Epicephalamoths appear to utilise diapause at multiple stages in their lifecycle, and possibly bet hedging, in order to deal with variable flowering phenology and climatic unpredictability.
Simulations of fluorescence imaging in the oral cavity
Authors: Lyu Zheng , Jiang Haomiao , Xiao Feng , Rong Jian , Zhang Tingcheng , Wandell Brian , Farrell Joyce 
Published: April 2021

AbstractWe describe an end-to-end image systems simulation that models a device capable of measuring fluorescence in the oral cavity. Our software includes a 3D model of the oral cavity and excitation-emission matrices of endogenous fluorophores that predict the spectral radiance of oral mucosal tissue. The predicted radiance is transformed by a model of the optics and image sensor to generate expected sensor image values. We compare simulated and real camera data from tongues in healthy individuals and show that the camera sensor chromaticity values can be used to quantify the fluorescence from porphyrins relative to the bulk fluorescence from multiple fluorophores (elastin, NADH, FAD, and collagen). Validation of the simulations supports the use of soft-prototyping in guiding system design for fluorescence imaging.© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
Alcohol Cues Elicit Different Abnormalities in Brain Networks of Abstinent Men and Women with Alcohol Use Disorders
Authors: Sawyer Kayle S. , Oscar-Berman Marlene , Ruiz Susan Mosher , Marinkovic Ksenija , Valmas Mary M. , Harris Gordon J. 
Published: April 2021

AbstractWe employed fMRI in 84 men and women with and without a history of alcohol use disorders (ALC and NC, respectively), to explore how gender interacts with alcoholism as reflected in brain activity elicited by alcohol cues. Brain activation was measured in a working memory task (delayed matching-to-sample) with emotional faces as the sample and match cues. During the delay period, intervening distractors were either reward-salient cues (alcoholic beverages) or neutral cues (nonalcoholic beverages or scrambled pictures). ALC women (ALCw) had higher accuracy than ALC men (ALCm). Analyses of scans during the viewing of distractor images revealed significant group-by-gender interactions. Compared to NC men, ALCm evidenced lower activation contrast between reward-salient cues and neutral cues in default mode network regions (including superior prefrontal and precuneus areas), while ALCw had more activation than NC women. Similar interactions were observed for task-regions (including superior parietal, lateral occipital, and prefrontal areas). Region of interest analyses showed that the ALC group had significantly higher levels of activation throughout reward-related circuitry during alcohol distractor interference than during scrambled picture interference. These results suggest that abstinent ALCm and ALCw differ in processing reward-salient cues, which can impact treatment and recovery.HighlightsBrain reward regions activate highly when individuals with a history of alcohol use disorders view alcoholic beverages.The brain regions identified subserve vision, memory, and judgement.Opposite abnormalities in activation patterns appeared for alcoholic men and women.
Envelope analysis of the human alpha rhythm reveals EEG Gaussianity
Authors: Hidalgo Víctor Manuel , Díaz Javier , Mpodozis Jorge , Letelier Juan-Carlos 
Published: April 2021

AbstractThe origin of the human alpha rhythm has been a matter of debate since Lord Adrian attributed it to synchronous neural populations in the occipital cortex. Although some authors have pointed out the Gaussian characteristics of the alpha rhythm, their results have been repeatedly disregarded in favor of Adrian’s interpretation; even though the first EEG Gaussianity reports can be traced back to the origins of the field. Here we revisit this problem using the envelope analysis — a method that relies on the fact that the coefficient of variation of the envelope (CVE) for continuous-time zero-mean Gaussian noise (as well as for any filtered sub-band) is equal to, thus making the CVE a fingerprint for Gaussianity. As a consequence, any significant deviation fromis linked to synchronous neural dynamics. We analyzed occipital EEG and iEEG data from massive public databases. Our results showed the human alpha rhythm can be characterized either as a synchronous or as a Gaussian signal based on the value of its CVE. Furthermore, Fourier analysis showed the canonical spectral peak at ≈ 10[Hz] is present in both the synchronous and Gaussian cases, thus demonstrating this same peak can be produced by different underlying neural dynamics. This study confirms the original interpretation of Adrian regarding the origin of the alpha rhythm but also opens the door for the study of Gaussianity in brain dynamics. These results suggest a broader interpretation for event-related synchronization/desynchronization (ERS/ERD) may be needed. Envelope analysis constitutes a novel complement to Fourier-based methods for neural signal analysis relating amplitude modulation patterns (CVE) to signal energy.
Respiratory coupling between prefrontal cortex and hippocampus of rats anesthetized with urethane in theta and non-theta states
Authors: Mofleh Rola , Kocsis Bernat 
Published: April 2021

AbstractRespiratory modulation of forebrain activity, long considered hard to reliably separate from breathing artifacts, has been firmly established in recent years using a variety of advanced techniques. Respiratory related oscillation (RRO) is derived from rhythmic nasal airflow in the olfactory bulb (OB) and is conveyed to higher order brain networks, including the prefrontal cortex (PFC) and hippocampus (HC), where it may potentially contribute to communication between these structures by synchronizing their activities at the respiratory rate. RRO was shown to change with sleep-wake states, it is strongest in quiet waking, somewhat less in active waking, characterized with theta activity in the HC, and absent in sleep. The goal of this study was to test RRO synchronization between PFC and HC under urethane anesthesia where theta and non-theta states spontaneously alternate. We found that in theta states, PFC-HC coherences significantly correlated with OB-HC but not with OB-PFC, even though RRO was stronger in PFC than in HC. In non-theta states, PFC-HC synchrony correlated with coherences connecting OB to either PFC or HC. Thus, similar to freely behaving rats, PFC-HC synchrony at RRO was primarily dependent on the response of HC to the common rhythmic drive, but only in theta state. The findings help outlining the value and the limits of applications in which urethane-anesthetized rats can be used for modeling the neural mechanisms of RRO in behaving animals.