bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum amyloid A is a positive acute phase protein in Russian sturgeon challenged with Aeromonas hydrophila
Authors: Castellano Mauricio , Silva-Álvarez Valeria , Aversa-Marnai Marcio , Lamas-Bervejillo María , Quartiani Ignacio , Perretta Alejandro , Villarino Andrea , Ferreira Ana María 
Published: December 2020

AbstractThe immune system of sturgeons, one of the most ancient and economically valuable fish worldwide, is poorly understood. The lack of molecular tools and data about infection biomarkers hinders the possibility to monitor sturgeon health during farming and detect infection outbreaks. To tackle this issue, we mined publicly available transcriptomic datasets and identified putative positive acute-phase proteins (APPs) of Russian sturgeons that could be induced by a bacterial infection and monitored using non-invasive methods. Teleost literature compelled us to focus on five promising candidates: hepcidin, a warm acclimation associated hemopexin, intelectin, serum amyloid A protein (SAA) and serotransferrin. Among them, SAA was the most upregulated protein at the mRNA level in the liver of sturgeons challenged with heat-inactivated or liveAeromonas hydrophila. To assess whether this upregulation yielded increasing SAA levels in circulation, we developed an in-house ELISA to quantify SAA levels in sturgeon serum. Circulating SAA rose upon bacterial challenge and positively correlated with hepaticsaaexpression. This is the first time serum SAA has been quantified in an Actinopterygii fish. Since APPs vary across different fish species, our work sheds light on sturgeon acute-phase response, revealing that SAA is a positive APP with potential value as infection biomarker.
Population pharmacokinetic analysis of doripenem for Japanese patients in intensive care unit
Authors: Nonoshita Ko , Suzuki Yosuke , Tanaka Ryota , Kaneko Tetsuya , Ohchi Yoshifumi , Sato Yuhki , Yasuda Norihisa , Goto Koji , Kitano Takaaki , Itoh Hiroki 
Published: December 2020

AbstractWe aimed to construct a novel population pharmacokinetics (PPK) model of doripenem (DRPM) for Japanese patients in intensive care unit, incorporating the clearance of DRPM by continuous renal replacement therapy (CRRT). Twenty-one patients treated with DRPM (0.25 or 0.5 g) by intravenous infusion over 1 h were included in the study. Nine of the 21 patients were receiving CRRT. Plasma samples were obtained before and 1, 2, 4, 6 and 8 h after the first DRPM administration. PPK analysis was conducted by nonlinear mixed effects modeling using a two-compartment model. Total clearance (CLtotal) in the model was divided into CRRT clearance (CLCRRT) and body clearance (CLbody). The final model was: CLtotal (L h−1) = CLbody(non-CRRT) = 3.65 × (Ccr/62.25)0.64 in the absence of CRRT, or = CLbody(CRRT) + CLCRRT = 2.49 × (Ccr/52.75)0.42 + CLCRRT in the presence of CRRT; CLCRRT = QE × 0.919 (0.919 represents non-protein binding rate of DRPM); V1 (L) = 10.04; V2 (L) = 8.13; and Q (L h−1) = 3.53. Using this model, CLtotal was lower and the distribution volumes (V1 and V2) tended to be higher compared to previous reports. Also, Ccr was selected as a significant covariate for CLbody. Furthermore, the contribution rate of CLCRRT to CLtotal was 30–40%, suggesting the importance of drug removal by CRRT. The population analysis model used in this study is a useful tool for planning DRPM regimen and administration. Our novel model may contribute greatly to proper use of DRPM in patients requiring intensive care.
Selenization of S. cerevisiae increases its protective potential in experimental autoimmune encephalomyelitis by triggering an intestinal immunomodulatory loop
Authors: de Campos Fraga-Silva Thais Fernanda , Mimura Luiza Ayumi Nishiyama , de Oliveira Larissa Ragozo Cardoso , dos Santos Toledo Juliana Helena , Borim Patrícia Aparecida , Zorzella-Pezavento Sofia Fernanda Gonçalvez , Alonso Diego Peres , Ribolla Paulo Eduardo Martins , de Oliveira Carlos Alberto Ferreira , da Fonseca Denise Morais , Villablanca Eduardo J. , Sartori Alexandrina 
Published: December 2020

AbstractMultiple sclerosis is an autoimmune disease that affects the myelinated central nervous system (CNS) neurons and triggers physical and cognitive disabilities. Conventional therapy is based on disease-modifying drugs that control disease severity but can also be deleterious. Complementary medicines have been adopted and evidence indicates that yeast supplements can improve symptoms mainly by modulating the immune response. In this investigation, we evaluated the therapeutic potential of Saccharomyces cerevisiae and its selenized derivative (Selemax) in experimental autoimmune encephalomyelitis (EAE). Female C57BL/6 mice submitted to EAE induction were orally supplemented with these yeasts by gavage from day 0 to day 14 after EAE induction. Both supplements determined significant reduction in clinical signs concomitantly with diminished Th1 immune response in CNS, increased proportion of Foxp3+ lymphocytes in inguinal and mesenteric lymph nodes and increased microbiota diversity. However, Selemax was more effective clinically and immunologically; it reduced disease prevalence more sharply, increased the proportion of CD103+ dendritic cells expressing high levels of PD-L1 in mesenteric lymph nodes and reduced the intestinal inflammatory process more strongly than S. cerevisiae. These results suggest a clear gut-brain axis modulation by selenized S. cerevisiae and suggest their inclusion in clinical trials.
DNA damage in human glomerular endothelial cells induces nodular glomerulosclerosis via an ATR and ANXA2 pathway
Authors: Fujii Ai , Sunatani Yumi , Furuichi Kengo , Fujimoto Keiji , Adachi Hiroki , Iwabuchi Kuniyoshi , Yokoyama Hitoshi 
Published: December 2020

AbstractCollagen type VI (COL6) deposition occurs in various glomerular diseases, causing serious pathological damage like nodular lesions. However, the mechanisms underlying the deposition of COL6 remain unclear. In renal biopsy samples, immunohistochemical analyses revealed that COL6 and phosphorylated histone H2AX (γ-H2AX), a DNA damage marker, were detected mainly in diabetic nodular glomerulosclerosis, in which the γ-H2AX-positive area was identified as the independent factor significantly associated with the COL6-positive area (β: 0.539, t = 2.668). In in vitro studies, COL6 secretion from human renal glomerular endothelial cells (HRGECs) was assessed by measuring the decrease in the cytoplasmic COL6-positive cells and an increase in the amount of COL6 in the culture medium. Mitomycin C (MMc) treatment of HRGECs increased the number of γ-H2AX-positive cells and COL6 secretion, which were suppressed by a specific inhibitor of ataxia telangiectasia and Rad3-related (ATR). MMc-induced COL6 secretion was also suppressed by Annexin A2 (ANXA2) siRNA transfection. Moreover, the inhibition of ATR activity did not induce any extra suppression in the MMc-induced COL6 secretion by ANXA2 siRNA transfected cells. These results confirm that nodular glomerulosclerosis partially results from DNA damage in the glomerulus and that DNA damage-induced COL6 secretion from HRGECs occurs through an ATR and ANXA2-mediated pathway.
Long-term memory guides resource allocation in working memory
Authors: Bruning Allison L. , Lewis-Peacock Jarrod A. 
Published: December 2020

AbstractWorking memory capacity is incredibly limited and thus it is important to use this resource wisely. Prior knowledge in long-term memory can aid in efficient encoding of information by allowing for the prioritization of novel stimuli over familiar ones. Here we used a full-report procedure in a visual working memory paradigm, where participants reported the location of six colored circles in any order, to examine the influence of prior information on resource allocation in working memory. Participants learned that one of the items appeared in a restricted range of locations, whereas the remaining items could appear in any location. We found that participants’ memory performance benefited from learning this prior information. Specifically, response precision increased for all items when prior information was available for one of the items. Responses for both familiar and novel items were systematically ordered from highest to lowest precision. Participants tended to report the familiar item in the second half of the six responses and did so with greater precision than for novel items. Moreover, novel items that appeared near the center of the prior location were reported with worse precision than novel items that appeared elsewhere. This shows that people strategically allocated working memory resources by ignoring information that appeared in predictable locations and prioritizing the encoding of information that appeared in unpredictable locations. Together these findings demonstrate that people rely on long-term memory not only for remembering familiar items, but also for the strategic allocation of their limited capacity working memory resources.
Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models
Authors: Horiai Machi , Otsuka Ayano , Hidema Shizu , Hiraoka Yuichi , Hayashi Ryotaro , Miyazaki Shinji , Furuse Tamio , Mizukami Hiroaki , Teruyama Ryoichi , Tamura Masaru , Bito Haruhiko , Maejima Yuko , Shimomura Kenju , Nishimori Katsuhiko 
Published: December 2020

AbstractAutism spectrum disorder (ASD) is a continuum of neurodevelopmental disorders and needs new therapeutic approaches. Recently, oxytocin (OXT) showed potential as the first anti-ASD drug. Many reports have described the efficacy of intranasal OXT therapy to improve the core symptoms of patients with ASD; however, the underlying neurobiological mechanism remains unknown. The OXT/oxytocin receptor (OXTR) system, through the lateral septum (LS), contributes to social behavior, which is disrupted in ASD. Therefore, we selectively express hM3Dq in OXTR-expressing (OXTR+) neurons in the LS to investigate this effect in ASD mouse models developed by environmental and genetic cues. In mice that received valproic acid (environmental cue), we demonstrated successful recovery of impaired social memory with three-chamber test after OXTR+ neuron activation in the LS. Application of a similar strategy to Nl3R451C knock-in mice (genetic cue) also caused successful recovery of impaired social memory in single field test. OXTR+ neurons in the LS, which are activated by social stimuli, are projected to the CA1 region of the hippocampus. This study identified a candidate mechanism for improving core symptoms of ASD by artificial activation of DREADDs, as a simulation of OXT administration to activate OXTR+ neurons in the LS.
Dynamic survival prediction in intensive care units from heterogeneous time series without the need for variable selection or curation
Authors: Deasy Jacob , Liò Pietro , Ercole Ari 
Published: December 2020

AbstractExtensive monitoring in intensive care units (ICUs) generates large quantities of data which contain numerous trends that are difficult for clinicians to systematically evaluate. Current approaches to such heterogeneity in electronic health records (EHRs) discard pertinent information. We present a deep learning pipeline that uses all uncurated chart, lab, and output events for prediction of in-hospital mortality without variable selection. Over 21,000 ICU patients and tens of thousands of variables derived from the MIMIC-III database were used to train and validate our model. Recordings in the first few hours of a patient’s stay were found to be strongly predictive of mortality, outperforming models using SAPS II and OASIS scores, AUROC 0.72 and 0.76 at 24 h respectively, within just 12 h of ICU admission. Our model achieves a very strong predictive performance of AUROC 0.85 (95% CI 0.83–0.86) after 48 h. Predictive performance increases over the first 48 h, but suffers from diminishing returns, providing rationale for time-limited trials of critical care and suggesting that the timing of decision making can be optimised and individualised.
Low oxygen levels caused by Noctiluca scintillans bloom kills corals in Gulf of Mannar, India
Authors: Raj K. Diraviya , Mathews G. , Obura David O. , Laju R. L. , Bharath M. Selva , Kumar P. Dinesh , Arasamuthu A. , Kumar T. K. Ashok , Edward J. K. Patterson 
Published: December 2020

AbstractCoral reefs around the world are undergoing severe decline in the past few decades. Mass coral mortalities have predominantly been reported to be caused by coral bleaching or disease outbreaks. Temporary hypoxic conditions caused by algal blooms can trigger mass coral mortalities though are reported rarely. In this study in Gulf of Mannar (GoM), southeast India, we report a significant coral mortality caused by a bloom of the ciguatoxic dinoflagellate Noctiluca scintillans during September–October 2019. Dissolved oxygen levels declined below 2 mg l−1 during the bloom causing temporary hypoxia and mortality (up to 71.23%) in the fast growing coral genera Acropora, Montipora and Pocillopora. Due to global climate change, more frequent and larger algal blooms are likely in the future. Hence, it is likely that shallow water coral reefs will be affected more frequently by episodic hypoxic conditions driven by algal blooms. More studies are, however, required to understand the mechanism of coral mortality due to algal blooms, impacts on community composition and the potential for subsequent recovery.
Unrepaired decompressive craniectomy worsens motor performance in a rat traumatic brain injury model
Authors: Andrews Brian T. , Barbay Scott , Townsend Jakob , Detamore Michael , Harris Janna , Tuchek Chad , Nudo Randolph J. 
Published: December 2020

AbstractDecompressive craniectomy (DC) is often required to manage rising intracranial pressure after traumatic brain injury (TBI). Syndrome of the trephine (SoT) is a reversible neurologic condition that often occurs following DC as a result of the unrepaired skull. The purpose of the present study is to characterize neurological impairment following TBI in rats with an unrepaired craniectomy versus rats with a closed cranium. Long Evans male rats received a controlled cortical impact (CCI) over the caudal forelimb area (CFA) of the motor cortex. Immediately after CCI, rats received either a hemi-craniectomy (TBI Open Skull Group) or an immediate acrylic cranioplasty restoring cranial anatomy (TBI Closed Skull Group). Motor performance was assessed on a skilled reaching task on post-CCI weeks 1—4, 8, 12, and 16. Three weeks after the CCI injury, the TBI Closed Skull Group demonstrated improved motor performance compared to TBI Open Skull Group. The TBI Closed Skull Group continued to perform better than the TBI Open Skull Group throughout weeks 4, 8, 12 and 16. The protracted recovery of CFA motor performance demonstrated in rats with unrepaired skulls following TBI suggests this model may be beneficial for testing new therapeutic approaches to prevent SoT.
Experimental evidence for yawn contagion in orangutans (Pongo pygmaeus)
Authors: van Berlo Evy , Díaz-Loyo Alejandra P. , Juárez-Mora Oscar E. , Kret Mariska E. , Massen Jorg J. M. 
Published: December 2020

AbstractYawning is highly contagious, yet both its proximate mechanism(s) and its ultimate causation remain poorly understood. Scholars have suggested a link between contagious yawning (CY) and sociality due to its appearance in mostly social species. Nevertheless, as findings are inconsistent, CY’s function and evolution remains heavily debated. One way to understand the evolution of CY is by studying it in hominids. Although CY has been found in chimpanzees and bonobos, but is absent in gorillas, data on orangutans are missing despite them being the least social hominid. Orangutans are thus interesting for understanding CY’s phylogeny. Here, we experimentally tested whether orangutans yawn contagiously in response to videos of conspecifics yawning. Furthermore, we investigated whether CY was affected by familiarity with the yawning individual (i.e. a familiar or unfamiliar conspecific and a 3D orangutan avatar). In 700 trials across 8 individuals, we found that orangutans are more likely to yawn in response to yawn videos compared to control videos of conspecifics, but not to yawn videos of the avatar. Interestingly, CY occurred regardless of whether a conspecific was familiar or unfamiliar. We conclude that CY was likely already present in the last common ancestor of humans and great apes, though more converging evidence is needed.
Improved cyber-physical system captured post-flowering high night temperature impact on yield and quality of field grown wheat
Authors: Hein Nathan T. , Bheemanahalli Raju , Wagner Dan , Vennapusa Amaranatha R. , Bustamante Carlos , Ostmeyer Troy , Pokharel Meghnath , Chiluwal Anuj , Fu Jianming , Srikanthan Dhanush S. , Neilsen Mitchell L. , Jagadish S. V. Krishna 
Published: December 2020

AbstractWinter wheat (Triticum aestivum L.) is essential to maintain food security for a large proportion of the world’s population. With increased risk from abiotic stresses due to climate variability, it is imperative to understand and minimize the negative impact of these stressors, including high night temperature (HNT). Both globally and at regional scales, a differential rate of increase in day and night temperature is observed, wherein night temperatures are increasing at a higher pace and the trend is projected to continue into the future. Previous studies using controlled environment facilities and small field-based removable chambers have shown that post-anthesis HNT stress can induce a significant reduction in wheat grain yield. A prototype was previously developed by utilizing field-based tents allowing for simultaneous phenotyping of popular winter wheat varieties from US Midwest and advanced breeding lines. Hence, the objectives of the study were to (i) design and build a new field-based infrastructure and test and validate the uniformity of HNT stress application on a scaled-up version of the prototype (ii) improve and develop a more sophisticated cyber-physical system to sense and impose post-anthesis HNT stress uniformly through physiological maturity within the scaled-up tents; and (iii) determine the impact of HNT stress during grain filling on the agronomic and grain quality parameters including starch and protein concentration. The system imposed a consistent post-anthesis HNT stress of + 3.8 °C until maturity and maintained uniform distribution of stress which was confirmed by (i) 0.23 °C temperature differential between an array of sensors within the tents and (ii) statistically similar performance of a common check replicated multiple times in each tent. On average, a reduction in grain-filling duration by 3.33 days, kernel weight by 1.25% per °C, grain number by 2.36% per °C and yield by 3.58% per °C increase in night temperature was documented. HNT stress induced a significant reduction in starch concentration indicating disturbed carbon balance. The pilot field-based facility integrated with a robust cyber-physical system provides a timely breakthrough for evaluating HNT stress impact on large diversity panels to enhance HNT stress tolerance across field crops. The flexibility of the cyber-physical system and movement capabilities of the field-based infrastructure allows this methodology to be adaptable to different crops.
Two high-rate pentose-phosphate pathways in cancer cells
Authors: Cossu Vanessa , Bonanomi Marcella , Bauckneht Matteo , Ravera Silvia , Righi Nicole , Miceli Alberto , Morbelli Silvia , Orengo Anna Maria , Piccioli Patrizia , Bruno Silvia , Gaglio Daniela , Sambuceti Gianmario , Marini Cecilia 
Published: December 2020

AbstractThe relevant role of pentose phosphate pathway (PPP) in cancer metabolic reprogramming has been usually outlined by studying glucose-6-phosphate dehydrogenase (G6PD). However, recent evidence suggests an unexpected role for a less characterized PPP, triggered by hexose-6-phosphate dehydrogenase (H6PD) within the endoplasmic reticulum (ER). Studying H6PD biological role in breast and lung cancer, here we show that gene silencing of this reticular enzyme decreases cell content of PPP intermediates and d-ribose, to a similar extent as G6PD silencing. Decrease in overall NADPH content and increase in cell oxidative status are also comparable. Finally, either gene silencing impairs at a similar degree cell proliferating activity. This unexpected response occurs despite the absence of any cross-interference between the expression of both G6PD and H6PD. Thus, overall cancer PPP reflects the contribution of two different pathways located in the cytosol and ER, respectively. Disregarding the reticular pathway might hamper our comprehension of PPP role in cancer cell biology.
Nuclear factor kappa B activation in cardiomyocytes by serum of children with obstructive sleep apnea syndrome
Authors: Goldbart Aviv D. , Gannot Meital , Haddad Hen , Gopas Jacob 
Published: December 2020

AbstractObstructive sleep apnea syndrome (OSA) is associated with cardiovascular morbidity in adults and children. NFκB activity is enhanced in circulating monocytes of adults with OSA, that decreases following positive pressure therapy. OSA children’s serum activates NFκB in a cell line. We hypothesized that OSA children’s serum can activate NFκB in cardiomyocytes (CM) and effect their viability. In order to explore the role played by NFκB in OSA cardiovascular pathophysiology, rat, mouse and human immortalized CM were exposed to human serum drawn from OSA children and matched controls. Increased expression of NFκB classical subunits p65/p50 as well as major morphological changes occurred in cardiomyocytes following OSA’s serum exposure. OSA children’s serum induced NFκB activity as measured by p65 nuclear translocation in immortalized human CM and rat cardiomyocytes as well as dense immunostaining of the nucleus. Trypan blue and XTT assays showed that OSA sera induced CM apoptosis. We conclude that NFκB is systemically activated in cardiomyocytes, who also demonstrate decreased viability and contractility following exposure to OSA serum. It supports the hypothesis NFκB plays a role in the evolution of cardiovascular morbidity in OSA. It may support the search for new therapeutic interventions controlling NFκB activation in OSA.
Mesalazine allergy and an attempt at desensitization therapy in patients with inflammatory bowel disease
Authors: Matsumoto Satohiro , Mashima Hirosato 
Published: December 2020

AbstractMesalazine is a key drug used for remission induction and maintenance therapy in inflammatory bowel disease (IBD). We sometimes encounter patients who develop allergic reactions to the drug and inevitably discontinue treatment. Of 692 patients who received mesalazine for IBD between 2014 and March 2020, 33 diagnosed with mesalazine allergy (43 episodes) were included, and their clinical manifestations were evaluated. For ten patients undergoing desensitization therapy, therapeutic outcomes were evaluated. The incidence of mesalazine allergy was 4.8%. The time from the start of oral medication to allergy onset was 10 ± 5 days for the first allergic attack and 2 ± 1 days for the second and subsequent allergic attacks. The observed clinical symptoms included fever (93%), diarrhea (26%), abdominal pain (23%), and bloody stool (12%). Drug-induced lymphocyte stimulation test was performed in 85% of the patients (28/33), and the sensitivity was 51%. Desensitization therapy with a time-dependent mesalazine granule formulation was successful in nine of the ten patients (90%), allowing them to receive 2000 mg or more of the drug. Fever was a common allergic symptom, and its presence appeared to be useful for distinguishing mesalazine allergy from exacerbation of the primary disease. Desensitization therapy was useful in patients with mesalazine allergy.