bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tuberculosis in Children Hospitalized in a Low-burden Country
Authors: Cogo Haude , Caseris Marion , Lachaume Noémie , Cointe Aurélie , Faye Albert , Pommelet Virginie 
Published: January 2021

Background:
In high-income countries, few pediatric studies have described the clinical expression of tuberculosis (TB) according to age, and their results are discordant. Patients <2 years of age are usually considered to be at higher risk for severe disease than older children. Our aim was to better describe pediatric TB disease severity in a low-incidence country.

Methods:
All children (<18 years of age) admitted with TB disease to the Robert Debré University Hospital, Paris, between 1992 and 2015 were included. Patients were classified by the severity of TB disease based on the original classification of Wiseman et al. Risk factors associated with severity were analyzed.

Results:
We included 304 patients with a median age of 9.9 years (interquartile range 3.3–13.3) and a male to female ratio of 1.04. Overall, 280/304 (92%) were classified: 168/304 (55%) were classified as showing severe TB and 112/304 (37%) as showing non-severe TB. Central nervous system disease was more frequent among patients <2 years of age than patients 2–17 years of age (5/54; 9% vs. 5/229; 2% P = 0.024). An age of ≥10 years (P = 0.001) and being born abroad (P = 0.011) were both associated with disease severity in univariate analysis. In multivariate analysis, diagnosis through symptom-based screening was independently associated with severity (odds ratio 7.1, 95% confidence interval: 3.9–12.9, P < 0.0001).

Conclusions:
This description of the clinical spectrum of pediatric TB in a low-burden setting demonstrates that adolescents are the group most at risk of experiencing severe TB.
Pharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092
Authors: Owor Maxensia , Tierney Camlin , Ziemba Lauren , Browning Renee , Moye John , Graham Bobbie , Reding Christina , Costello Diane , Norman Jennifer , Wiesner Lubbe , Hughes Emma , Whalen Meghan E. , Purdue Lynette , Mmbaga Blandina Theophil , Kamthunzi Portia , Kawalazira Rachel , Nathoo Kusum , Bradford Sarah , Coletti Anne , Aweeka Francesca. , Musoke Philippa 
Published: January 2021

Background:
Severe acute malnutrition (SAM) may alter the pharmacokinetics (PK), efficacy, and safety of antiretroviral therapy. The phase IV study, IMPAACT P1092, compared PK, safety, and tolerability of zidovudine (ZDV), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) in children with and without SAM.

Materials and methods:
Children living with HIV 6 to <36 months of age with or without World Health Organization (WHO)-defined SAM received ZDV, 3TC, and LPV/r syrup for 48 weeks according to WHO weight band dosing. Intensive PK sampling was performed at weeks 1, 12, and 24. Plasma drug concentrations were measured using liquid chromatography tandem mass spectrometry. Steady-state mean area under the curve (AUC0–12h) and clearance (CL/F) for each drug were compared. Grade ≥3 adverse events were compared between cohorts.

Results:
Fifty-two children were enrolled across 5 sites in Africa with 44% (23/52) female, median age 19 months (Q1, Q3: 13, 25). Twenty-five children had SAM with entry median weight-for-height Z-score (WHZ) −3.4 (IQR −4.0, −3.0) and 27 non-SAM had median WHZ −1.0 (IQR −1.8, −0.1). No significant differences in mean AUC0–12h or CL/F were observed (P ≥ 0.09) except for lower 3TC AUC0–12h (GMR, 0.60; 95% CI, 0.4–1.0; P = 0.047) at week 12, higher ZDV AUC0–12h (GMR, 1.52; 1.2–2.0; P = 0.003) at week 24 in the SAM cohort compared with non-SAM cohort. Treatment-related grade ≥3 events did not differ significantly between cohorts (24.0% vs. 25.9%).

Conclusion:
PK and safety findings for ZDV, 3TC, and LPV/r support current WHO weight band dosing of syrup formulations in children with SAM.
Advances in acute pancreatitis
Authors: Sinonquel Pieter , Laleman Wim , Wilmer Alexander 
Published: January 2021

Purpose of review
With a potentially life-threatening course, acute pancreatitis (AP) is one of the most common gastrointestinal diseases requiring hospitalization and often necessitating intensive care. Based on recent insights and recommendations, this review provides an overview on clinical management of AP patients with a focus on intensive care unit care.

Recent findings
Possible benefits of percutaneous paracentesis and/or drainage on outcome or inflammation have been further explored. Combined opioid and epidural analgesia for pain management might be a valuable alternative for pain management. Very recent international guidelines now agree on a step-up approach for the management of acute necrotizing pancreatitis favoring a minimally invasive approach with either endoscopic or percutaneous drainage first. Studies for the best timing of these interventions are ongoing. In spite of a better understanding of pathophysiological mechanisms mediating AP, specific treatments are still awaited.

Summary
New evidence and recent international consensus direct the current management of AP toward a tailored, multidisciplinary and less invasive therapy with complementary roles for hepatologists, intensivists, radiologists, and surgeons.
Open reduction and internal fixation (ORIF) versus ORIF and primary subtalar arthrodesis for complex displaced intraarticular calcaneus fractures
Authors: Eisenstein Emmanuel David , Kusnezov Nicholas A. , Waterman Brian R. , Orr Justin D. , Blair James A. 
Published: January 2021

Abstract

Objectives:
To determine the optimal patient-oriented treatment between open reduction and internal fixation (ORIF) with or without primary subtalar arthrodesis (PSTA) for patients with displaced intraarticular calcaneus fractures (DIACFs, OTA 82-C3 and C4).

Design:
Expected value decision analysis.

Setting:
Academic military treatment facility

Participants:
One hundred randomly selected volunteers.

Intervention:
Hypothetical clinical scenario involving ORIF versus ORIF with PSTA.

Main outcome measurements:
Decision analysis was used to elucidate the superior treatment option based on expected patient values, composed of: the product of the average outcome probabilities established by previously published studies and the average ascribed patient utility values for each outcome probability. One-way sensitivity analysis was performed to quantify the amount of change required for the inferior treatment to equal or surpass the superior option.

Results:
Expected values for ORIF and ORIF with PSTA were 8.96 and 18.06, respectively, favoring ORIF with PSTA. One-way sensitivity analysis was performed by artificially decreasing the rate of secondary fusion following isolated ORIF thus increasing its overall expected value. Adjusting the rate of secondary fusion to 0%, the expected value of ORIF with PSTA nearly doubled that of ORIF (18.06 vs 9.45). Similarly, when adjusting the moderate and severe complication rates following ORIF with PSTA to 100%, the expected value of ORIF with PSTA still exceeded that of ORIF (15.45 vs 8.96, and 13.52 vs 8.96, respectively).

Conclusion:
Expected value decision analysis favors ORIF with PSTA as the optimal treatment for complex DIACF.
A salvage strategy for heel pad degloving injury
Authors: Cantrell William A. , Lawrenz Joshua M. , Vallier Heather A. 
Published: January 2021

Abstract

Case:
A 50-year-old female experienced a crush injury to the foot resulting in open degloving of her heel pad. This study details a surgical strategy to achieve healing and limb salvage.

Conclusion:
Heel pad injuries with degloving are difficult to salvage and have a poor prognosis. Amputation is often the only therapeutic option, unless part of the blood supply to the heel pad is intact, rendering limb salvage a possibility.
Atrophic nonunion stromal cells form bone and recreate the bone marrow environment in vivo
Authors: Vallim Frederico C. , Guimarães João Antonio Matheus , Dias Rhayra B. , Sartore Rafaela C. , Cavalcanti Amanda dos S. , Leal Ana C. , Duarte Maria Eugenia L. , Bonfim Danielle C. 
Published: January 2021

AbstractIntroduction:Nonunion is a challenging condition in orthopaedics as its etiology is not fully understood. Clinical interventions currently aim to stimulate both the biological and mechanical aspects of the bone healing process by using bone autografts and surgical fixation. However, recent observations showed that atrophic nonunion tissues contain putative osteoprogenitors, raising the hypothesis that its reactivation could be explored to achieve bone repair.Methods:Here we characterized atrophic nonunion stromal cells (NUSC) in vitro, using bone marrow stromal cells (BMSC) and osteoblasts as controls cells of the osteoblastic lineage, and evaluated its ability to form bone in vivo.Results:NUSC had proliferative and senescence rates comparable to BMSC and osteoblasts, and homogeneously expressed the osteolineage markers CD90 and CD73. Regarding CD105 and CD146 expression, NUSC were closely related to osteoblasts, both with an inferior percentage of CD105+/CD146+cells as compared to BMSC. Despite this, NUSC differentiated along the osteogenic and adipogenic lineages in vitro; and when transplanted subcutaneously into immunocompromised mice, new bone formation and hematopoietic marrow were established.Conclusions:This study demonstrates that NUSC are osteogenically competent, supporting the hypothesis that their endogenous reactivation could be a strategy to stimulate the bone formation while reducing the amount of bone autograft requirements.
Adaptive optics enhanced all-optical photoacoustic tomography
Authors: Czuchnowski Jakub , Prevedel Robert 
Published: January 2021

AbstractAll-optical ultrasound detection bears a number of unique advantages for photoacoustic tomography, including the ability for high resolution sampling of the acoustic field and its compatibility with a wide variety of other optical modalities. However, optical schemes based on miniaturized cavities are sensitive to optical aberrations as well as manufacturing-induced cavity imperfections which degrade sensor sensitivity and deteriorate photoacoustic image quality. Here we present an experimental method based on adaptive optics that is capable of enhancing the overall sensitivity of Fabry-Pérot based photoacoustic sensors. We experimentally observe clear improvements in photoacoustic signal detection as well as overall image quality after photoacoustic tomography reconstructions when applied to mammalian tissuesin vivo.
Lower neural value signaling in the prefrontal cortex is related to childhood family income and depressive symptomatology during adolescence
Authors: Palacios-Barrios Esther E. , Hanson Jamie L. , Barry Kelly R. , Albert Dustin , White Stuart F. , Skinner Ann T. , Dodge Kenneth A. , Lansford Jennifer E. 
Published: January 2021

AbstractLower family income during childhood is related to increased rates of adolescent depression, though the specific mechanisms are poorly understood. Evidence suggests that individuals with depression demonstrate hypoactivation in brain regions involved in reward learning and decision-making processes (e.g., portions of the prefrontal cortex). Separately, lower family income has been associated with neural alterations in similar regions. We examined associations between family income, depression, and brain activity during a reward learning and decision-making fMRI task in a sample of adolescents (full n=94; usable n=78; mean age=15.4 years). We identified neural regions representing 1) expected value (EV), the learned subjective value of an object, and 2) prediction error, the difference between EV and the actual outcome received. Regions of interest related to reward learning were examined in connection to childhood family income and parent-reported adolescent depressive symptoms. As hypothesized, lower activity in the subgenual anterior cingulate (sACC) for EV in response to approach stimuli was associated with lower childhood family income, as well as greater symptoms of depression measured one-year after the neuroimaging session. These results are consistent with the hypothesis that lower early family income leads to disruptions in reward and decision-making brain circuitry, which leads to adolescent depression.
Friction is preferred over grasp configuration in precision grip grasping
Authors: Klein Lina K. , Maiello Guido , Fleming Roland W. , Voudouris Dimitris 
Published: January 2021

ABSTRACTHow humans visually select where to grasp an object depends on many factors, including grasp stability and preferred grasp configuration. We examined how endpoints are selected when these two factors are brought into conflict: Do people favor stable grasps or do they prefer their natural grasp configurations? Participants reached to grasp one of three cuboids oriented so that its two corners were either aligned with, or rotated away from, each individual’s natural grasp axis (NGA). All objects were made of brass (mass: 420 g) but the surfaces of their sides were manipulated to alter friction: 1) all-brass, 2) two opposing sides covered with wood, while the other two remained of brass, or 3) two opposing sides covered with sandpaper, and the two remaining brass sides smeared with vaseline. Grasps were evaluated as either clockwise (thumb to the left of finger in frontal plane) or counterclockwise of the NGA. Grasp endpoints depended on both object orientation and surface material. For the all-brass object, grasps were bimodally distributed in the NGA-aligned condition but predominantly clockwise in the NGA-unaligned condition. These data reflected participants’ natural grasp configuration independently of surface material. When grasping objects with different surface materials, endpoint selection changed: Participants sacrificed their usual grasp configuration to choose the more stable object sides. A model in which surface material shifts participants’ preferred grip angle proportionally to the perceived friction of the surfaces accounts for our results. Our findings demonstrate that a stable grasp is more important than a biomechanically comfortable grasp configuration.NEW & NOTEWORTHYWhen grasping an object, humans can place their fingers at several positions on its surface. The selection of these endpoints depends on many factors, with two of the most important being grasp stability and grasp configuration. We put these two factors in conflict and examine which is considered more important. Our results highlight that humans are not reluctant to adopt unusual grasp configurations in order to satisfy grasp stability.
Microglia perform local protein synthesis at perisynaptic and phagocytic structures
Authors: Vasek Michael J. , Deajon-Jackson Jelani D. , Liu Yating , Crosby Haley W. , Yi Jiwon , Dougherty Joseph D. 
Published: January 2021

AbstractRecent studies have illuminated the importance of several key signaling pathways in regulating the dynamic surveillance and phagocytic activity of microglia. Yet little is known about how these signals result in the assembly of phagolysosomal machinery near targets of phagocytosis, especially in processes distal from the microglial soma. Neurons, astrocytes, and oligodendrocytes locally regulate protein translation within distal processes. Therefore, we tested whether there is regulated local translation within peripheral microglia processes (PeMPs). We show that PeMPs contain ribosomes which engage inde novoprotein synthesis, and these associate with a subpool of transcripts involved in pathogen defense, motility, and phagocytosis. Using a live slice preparation, we further show that acute translation blockade impairs the formation of PeMP phagocytic cups, the localization of lysosomal proteins within them, and phagocytosis. Collectively, these data argue for a regulated local translation in PeMPs and indicate a need for new translation to support dynamic microglial function.
New Gene Embedding Learned from Biomedical Literature and Its Application in Identifying Cancer Drivers
Authors: Liang Lifan , Lu Xinghua , Lu Songjian 
Published: January 2021

AbstractTo investigate molecular mechanism of diseases, we need to understand how genes are functionally associated. Computational researchers have tried to capture functional relationships among genes by constructing an embedding space of genes from multiple sources of high-throughput data. However, correlations in high-throughput data does not necessarily imply functional relations. In this study, we generated gene embedding from literature by constructing semantic representation for each gene. This approach enabled us to cover genes less mentioned in literature and revealed novel functional relationships among genes. Evaluation showed that the learned gene embedding was consistent with pathway knowledge and enhanced the search for cancer driver genes. We further applied our gene embedding to identify protein complexes and functional modules from gene networks. Performance in both scenarios was significantly improved with gene embedding.
CRISPR/Cas-9 mediated knock-in by homology dependent repair in the West Nile Virus vectorCulex quinquefasciatusSay
Authors: Purusothaman Deepak-Kumar , Shackleford Lewis , Anderson Michelle A. E. , Harvey-Samuel Tim , Alphey Luke 
Published: January 2021

AbstractCulex quinquefasciatusSay is a brown, medium sized mosquito distributed widely in both tropical and subtropical regions of the world. It is a night-active, opportunistic blood-feeder and is responsible for vectoring many animal and human diseases, including West Nile Virus and avian malaria. Current vector control methods (e.g. physical / chemical) are increasingly ineffective; use of insecticides also imposes some hazards to both human and ecosystem health. Recent advances in genome editing have allowed the development of genetic methods of insect control, which is species-specific and, theoretically, highly effective. CRISPR/Cas9 is a bacteria-derived programmable gene editing tool that has been shown to be functional in a range of species. We demonstrate here, the first successful germline gene knock-in by homology dependent repair inC. quinquefasciatus. Using CRISPR/Cas9, we integrated exogenous sequence comprising a sgRNA expression cassette and marker gene encoding a fluorescent protein fluorophore (Hr5/IE1-DsRed, Cq7SK-sgRNA) into the kynurenine 3-monooxygenase (kmo) gene. We achieved a minimum transformation rate of 2.8% similar to rates achieved in other mosquito species. Precise knock-in at the intended locus was confirmed by sequencing. Insertion homozygotes displayed a white eye phenotype in early-mid stage larvae and a recessive lethal phenotype by pupation. This work shows an alternative and efficient method for genetic engineering ofC. quinquefasciatus, providing a new tool for researchers interested in developing genetic control tools for this vector.
Sleep problems in preschoolers with autism spectrum disorders are associated with sensory sensitivities and thalamocortical overconnectivity
Authors: Linke A.C. , Chen B. , Olson L. , Ibarra C. , Fong C. , Reynolds S. , Apostol M. , Kinnear M.K. , Müller R.-A. , Fishman I. 
Published: January 2021

AbstractProjections between the thalamus and sensory cortices are established early in development and play an important role in sleep regulation as well as in relaying sensory information to cortex. Atypical thalamocortical functional connectivity frequently observed in children with autism spectrum disorders (ASD) might therefore be linked to sensory and sleep problems common in ASD. Here we investigated the relationship between auditory-thalamic functional connectivity measured during natural sleep fMRI, sleep problems, and sound sensitivities in 70 toddlers and preschoolers (1.5 to 5-year-olds) with ASD compared to a matched group of 46 typically developing (TD) children. In children with ASD, sleep problems and sensory sensitivities were positively correlated, and increased sleep latency was associated with overconnectivity between the thalamus and auditory cortex in a subsample with high quality MRI data (n=29). Additionally, auditory cortex BOLD signal amplitude was elevated in children with ASD, potentially reflecting reduced sensory gating or a lack of auditory habituation during natural sleep. These findings indicate that atypical thalamocortical functional connectivity can be detected early in development and may play a crucial role in sleep problems and sensory sensitivities in ASD.
Are cooperatives transitioning from cost minimizers to profit maximizers?
Authors: Clymer Amanda , Bowman Whitney , Yeager Elizabeth A. , Briggeman Brian C. 
Published: January 2021

PurposeThe purpose of this paper is to examine the optimizing behavior of agricultural supply and marketing cooperatives in the US Midwestern states.Design/methodology/approachThis paper uses firm-level data from CoBank, the primary lender to agricultural cooperatives, to evaluate optimizing behavior of 77 Midwestern agricultural marketing and supply cooperatives from 2014 through 2017. The study uses the data envelopment analysis (DEA) and the weak axioms of cost minimization and profit maximization to identify whether or not a cooperative is following a cost minimization and/or profit maximization objective.FindingsIn contrast to previous research, results provide stronger support for profit maximization as the behavioral objective of agricultural cooperatives instead of cost minimization, especially for larger cooperatives.Practical implicationsTraditional firm theory for investor-owned firms states that businesses seek to maximize profits. Agricultural cooperatives however, could aim to maximize profits so as to redistribute profits back to user-owners as patronage refunds. Or, they could minimize costs so as to lower cost of products sold and services provided to their user-owners. Given users-control the cooperative, knowing the primary objective of agricultural cooperatives will allow for better design of research and education programming.Originality/valueGiven recent changes and consolidation in the agricultural industry among farms and agricultural cooperatives, this study reexamines past work that evaluated the optimizing behavior of agricultural cooperatives. Changes in industry and the necessity to remain competitive from an agribusiness standpoint have resulted in an anticipated shift toward a profit maximizing objective. The value of this study is providing an evaluation framework, using a firm-level comprehensive dataset, that represents the cooperative system.