bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing the ASPIRE-SSI study: a multicenter, observational, prospective cohort study to assess the incidence and risk factors of surgical site and bloodstream infections caused by Staphylococcus aureus in Europe
Authors: Troeman Darren P.R. , Weber Susanne , Hazard Derek , Wolkewitz Martin , Timbermount Leen , Vilken Tuba , Harbarth Stephan , Ali Omar , Sifakis Frangiscos , Kluytmans Jan A.J.W. 
Published: July 2020

ABSTRACTBackgroundThere is a continuing need for in-depth and updated knowledge about the epidemiology of surgical site infections (SSIs) caused by Staphylococcus aureus to support the development of effective preventive interventions. The ASPIRE-SSI study aims primarily to determine the incidence of S. aureus SSIs and postoperative bloodstream infections (BSIs) in Europe and to assess their association with patient-related, pathogen-related, and contextual risk factors.MethodsASPIRE-SSI is a prospective, multicenter, observational cohort study primarily assessing the incidence of and risk factors for S. aureus SSI and postoperative BSI in Europe. Five thousand adult surgical patients (of which two-thirds will be S. aureus carriers and one-third non-carriers) undergoing several types of surgical procedures in sites located across Europe were enrolled in the study. Data and specimens were collected from these subjects who were followed for up to 90 days following surgery to assess study outcomes.Using advanced survival analyses and regression techniques (including competing risks models), we will determine event-specific and sub-distribution hazards to assess the independent associations of these study outcomes with risk factors. Additionally, a risk prediction model will be derived to quantify the risk of developing SSI or BSI due to S. aureus.DiscussionDespite the challenges, this study will provide important and contemporary information about the epidemiology of SSI and BSI (and other infections) caused by S. aureus in the current surgical population in Europe, thereby supporting the development of effective preventive interventions.Trial registrationclinicaltrial.gov number NCT02935244
A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19)
Authors: Chen Cheng-Pin , Lin Yi-Chun , Chen Tsung-Chia , Tseng Ting-Yu , Wong Hon-Lai , Kuo Cheng-Yu , Lin Wu-Pu , Huang Sz-Rung , Wang Wei-Yao , Liao Jia-Hung , Liao Chung-Shin , Hung Yuan-Pin , Lin Tse-Hung , Chang Tz-Yan , Hsiao Chin-Fu , Huang Yi-Wen , Chung Wei-Sheng , Cheng Chien-Yu , Cheng Shu-Hsing 
Published: July 2020

AbstractObjectiveIn this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study.MethodsSubjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ 400 mg twice for 1 d and HCQ 200 mg twice daily for 6 days were administered. Both study group and controlled group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020.ResultsThere were 33 and 37 cases in the RCT and retrospective study, respctively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1–9 days) and 10 days (95% CI; 2–12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70).ConclusionsNeither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.
Post-lockdown detection of SARS-CoV-2 RNA in the wastewater of Montpellier, France
Authors: Trottier Julie , Darques Regis , Mouheb Nassim Ait , Partiot Emma , Bakhache William , Deffieu Maika S. , Gaudin Raphael 
Published: July 2020

AbstractThe evolution of the COVID-19 pandemic can be monitored through the detection of SARS-CoV-2 RNA in sewage. Here, we measured the amount of SARS-CoV-2 RNA at the inflow point of the main waste water treatment plant (WWTP) of Montpellier, France. We collected samples 4 days before the end of lockdown and up to 45 days post-lockdown. We detected increased amounts of SARS-CoV-2 RNA at the WWTP, which was not correlated with the number of newly diagnosed patients. Future epidemiologic investigations may explain such asynchronous finding.
COVIDPEN: A Novel COVID-19 Detection Model using Chest X-Rays and CT Scans
Authors: Jaiswal Amit Kumar , Tiwari Prayag , Rathi Vipin Kumar , Qian Jia , Pandey Hari Mohan , Albuquerque Victor Hugo C. 
Published: July 2020

AbstractThe trending global pandemic of COVID-19 is the fastest ever impact which caused people worldwide by severe acute respiratory syndrome (SARS)-driven coronavirus. However, several countries suffer from the shortage of test kits and high false negative rate in PCR test. Enhancing the chest X-ray or CT detection rate becomes critical. The patient triage is of utmost importance and the use of machine learning can drive the diagnosis of chest X-ray or CT image by identifying COVID-19 cases. To tackle this problem, we propose COVIDPEN - a transfer learning approach on Pruned EfficientNet-based model for the detection of COVID-19 cases. The proposed model is further interpolated by post-hoc analysis for the explainability of the predictions. The effectiveness of our proposed model is demonstrated on two systematic datasets of chest radiographs and computed tomography scans. Experimental results with several baseline comparisons show that our method is on par and confers clinically explicable instances, which are meant for healthcare providers.
Stimulation of Locus Coeruleus Noradrenergic System Modulates Sensory Processing and Brain State in two Different Time Scales
Authors: Fazlali Zeinab , Ranjbar-Slamloo Yadollah , Zabeh Erfan , Arabzadeh Ehsan 
Published: July 2020

AbstractLocus Coeruleus (LC) noradrenergic system has widespread projections throughout the brain and affects sensory processing. LC modulation of sensory-evoked cortical activity and brain state is documented by electrical micro-stimulation, optogenetic experiments, and the local application of norepinephrine (NE). The temporal profile of the LC modulation of sensory response and brain state is not well characterized. Our goal in this study is to characterize this modulation. Here, we recorded neuronal activity from the barrel cortex (BC) of urethane-anesthetized rats while combining LC micro-stimulation with brief mechanical deflections of the whiskers at 10 different time lags (50-500 ms). We recorded spikes and local field potentials to quantify the neuronal activity and the brain state. LC micro-stimulation exhibited a biphasic effect on spontaneous activity of the BC: a period of suppression followed by a period of excitation. We observed a similar effect on the sensory-evoked response: at 50-ms lag, the evoked response decreased while at 150-ms lag, the early evoked response was facilitated. At 150 to 350-ms time lags, LC micro-stimulation caused a combined facilitation followed by suppression of the evoked response. In contrast to the fast transient effect of LC stimulation on BC spiking activity, brain state modulation started later and lasted longer. LC stimulation suppressed low-frequency activities that are associated with low arousal states. In summary, we found that LC modulation affects cortical processing of sensory inputs and the brain state at different time scales which are likely to involve distinct circuit mechanisms.
HIP1 mediates oncogenic transformation and cancer progression through STAT3 signalling
Authors: Bantval Rao Roheet , Ramos-Montoya Antonio , Scott Helen , Berry Lorraine , Reichelt Stefanie , MacArthur Stewart , Russell Roslin , Neal David E , Evergren Emma , Mills Ian G 
Published: July 2020

AbstractBackgroundHuntingtin-interacting protein 1 (HIP1) is an adaptor protein involved in transcriptional regulation and receptor-mediated endocytosis. Overexpression of HIP1 transforms cell and is associated with, increasing grades of prostate cancer (CaP) and poor patient outcomes. However, the precise mechanism for the role of HIP1 in prostate cancer progression remains unknown.MethodsUsing a phospho-kinase antibody array we identified changes in signalling associated with HIP1 overexpression PNT1 cells. For validation Western blots were used together with knockdown or inhibitor treatments and phenotypic assays for cellular transformation. The cell line was xenografted to assess tumour growth. Gene expression microarray analysis of the cell line was used to identify perturbations in transcript levels.ResultsHere we demonstrate cellular transformation and phenotypic effects of HIP1 overexpression in a benign prostate epithelial cell line to be dependent on STAT3 signalling.In vivoxenografts confirmed the cellular transformation phenotype. Gene expression analysis revealed serum protein GDF15 to be a marker of prostate cancer tumorigenesis in our model. We present a HIP1-STAT3-GDF15 axis in our pre-clinical model that mediates cellular transformation and tumorigenesis.ConclusionOur findings provide a model defining the functional effects of increased HIP1 expression in prostate tumorigenesis and progression. This model implicates increased STAT3 signalling in HIP1-dependent prostate carcinogenesis and identifies GDF15 as a secreted factor supporting this process. The role of HIP1-STAT3-GDF15 signalling may extend to other epithelial cancers shown to overexpress HIP1; such as gliomas, colon and breast cancer where STAT3 is an emerging oncology drug target.
Enthalpy efficiency of the soleus muscle explains improvements in running economy
Authors: Bohm Sebastian , Mersmann Falk , Santuz Alessandro , Arampatzis Adamantios 
Published: July 2020

AbstractDuring human running, the soleus, as the main plantar flexor muscle, generates the majority of the mechanical work through active shortening. The fraction of chemical energy that is converted into muscular work (i.e. the enthalpy efficiency) depends on the muscle shortening velocity. Here, we investigated the soleus muscle fascicle behavior during running with respect to the enthalpy efficiency as a mechanism that could explain previously reported improvements in running economy after exercise-induced increases of plantar flexor strength and Achilles tendon stiffness. Healthy amateur runners were randomly assigned to a control (n=10) or intervention group (n=13), which performed a specific 14-week muscle-tendon training. Significant increases in plantar flexor maximum strength (10%) and Achilles tendon stiffness (31%) yet reduced metabolic cost of running (4%) was found only in the intervention group (p<0.05). Following training, the soleus fascicle velocity profile throughout stance was altered, with the fascicles operating at a higher enthalpy efficiency during the phase of muscle-tendon unit lengthening (15%) and in average over stance (7%, p<0.05). These findings show that the improvements in energetic cost following increases in plantar flexor strength and Achilles tendon stiffness can be attributed to increased enthalpy efficiency of the operating soleus. This provides the first experimental evidence that the soleus enthalpy efficiency is a determinant of human running economy. Furthermore, the current results imply that the soleus energy production in the first part of the stance phase were the muscle-tendon unit is lengthening is crucial for the overall metabolic energy cost of running.
Gut microbiota profiles of treatment-naïve adult acute myeloid leukemia patients with neutropenic fever during intensive chemotherapy
Authors: Rattanathammethee Thanawat , Tuitemwong Pimchanok , Thiennimitr Parameth , Sarichai Phinitphong , Pombejra Sarisa Na , Piriyakhuntorn Pokpong , Hantrakool Sasinee , Chai-Adisaksopha Chatree , Rattarittamrong Ekarat , Tantiworawit Adisak , Norasetthada Lalita 
Published: July 2020

AbstractIntestinal bacterial flora of febrile neutropenic patients had significantly diverse. However, there were scanty reports of microbiota alteration of adult patients with acute myeloid leukemia (AML). Stool samples of each treatment-naïve AML patient were collected at the day before induction chemotherapy initiation (pretreatment), first day of neutropenic fever and first day of bone marrow recovery. Bacterial DNA was extracted from stool and sequenced bacterial 16s ribosomal RNA genes by next-generation sequencing. Relative abundance, overall richness, Shannon’s diversity index and Simpson’s diversity index were calculated. Ten cases of AML patients (4 men and 6 women) were included with median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes were dominated over the period of neutropenic fever and subsequent declined after bone marrow recovery contrast to Bacteroidetes and Proteobacteria.Enterococcuswas more abundant at febrile neutropenia period compared to pretreatment whileBacteroidesandEscherichiawas notably declined during the febrile neutropenia. At the operational taxonomic units (OTUs) level, there was significant higher level of overall richness of pretreatment period than febrile neutropenic episode. Both of the diversity indexes of Shannon and Simpson were considerably decreased at febrile neutropenic period. Adult AML patients with first episode of febrile neutropenia after initial intensive chemotherapy demonstrated the significant decrease of gut microbiota diversity and the level of diversity consistently remained constant despite of bone marrow recovery.
Development of nano-emulsions based onAyapana triplinervisfor the control ofAedes aegyptilarvae
Authors: Rodrigues Alex Bruno Lobato , Lopes Rosany Martins , Rabelo Érica Menezes , Tomazi Rosana , Santos Lizandra Lima , Brandão Lethícia Barreto , Faustino Cleidjane Gomes , Farias Ana Luzia Ferreira , dos Santos Cleydson Breno Rodrigues , de Castro Cantuária Patrick , Galardo Allan Kardec Ribeiro , da Silva de Almeida Sheylla Susan Moreira 
Published: July 2020

AbstractAyapana triplinervisis a plant species used in traditional medicine and in mystical-religious rituals by traditional communities in the Amazon. The aim of this study is to evaluate the larvicidal activity againstA. aegyptiof nano-emulsions containing essential oils fromA. triplinervismorphotypes, and acute oral toxicity in non-target organism. Essential oils were identified and nano-emulsions were prepared using the low energy method. The mortality test ofA. aegyptilarvae was performed according to the protocol recommended by the World Health Organization, and toxicity in non-target mammals was performed according to the OECD. Phytochemical analyses indicated the major compounds (E)-Caryophyllene (45.93%) and Thymohydroquinone Dimethyl Ether (32.93%) in morphotype A, and in morphotype B, Thymohydroquinone Dimethyl Ether (84.53%) was found. Morphotype A essential oil nano-emulsion showed a particle size of 101.400 ± 0.971 nm (PdI = 0.124 ± 0.009 and ZP = −19,300 ± 0.787 mV). Morphotype B essential oil nano-emulsion had a particle size of 104.567 ± 0.416 nm (PdI = 0.168 ± 0.016 and ZP = −27,700 ± 1,307 mV). Histomorphological analyses showed the presence of inflammatory cells in the liver of animals treated with morphotype A essential oil nano-emulsion (MAEON) and morphotype B essential oil nano-emulsion (MBEON). Congestion and the presence of transudate with leukocyte infiltration in the lung of animals treated with MAEON were observed. The nano-emulsions containing essential oils ofA. triplinervismorphotypes showed an effective nanobiotechnological product in the chemical control ofA. aegyptilarvae and safe for non-target mammals.
A rational approach to identifying effective combined anticoronaviral therapies against feline coronavirus
Authors: Cook S.E. , Vogel H. , Castillo D. , Olsen M. , Pedersen N. , Murphy B. G. 
Published: July 2020

AbstractFeline infectious peritonitis (FIP), caused by a genetic mutant of feline enteric coronavirus known as FIPV, is a highly fatal disease of cats with no currently available vaccine or FDA-approved cure. Dissemination of FIPV in affected cats results in a range of clinical signs including cavitary effusions, anorexia, fever and lesions of pyogranulomatous vasculitis and peri-vasculitis with or without central nervous system and/or ocular involvement. There is a critical need for effective and approved antiviral therapies against coronaviruses including FIPV and zoonotic coronaviruses such as SARS-CoV-2, the cause of COVID-19. With regards to SARS-CoV-2, preliminary evidence suggests that there may be potential clinical and pathological overlap with feline coronaviral disease including enteric and neurological involvement in some cases. We have screened 89 putative antiviral compounds and have identified 25 compounds with antiviral activity against FIPV, representing a variety of drug classes and mechanisms of antiviral action. Based upon successful combination treatment strategies for human patients with HIV or hepatitis C virus infections, we have identified combinations of drugs targeting different steps of the FIPV life cycle resulting in synergistic antiviral effect. Translationally, we suggest that a combined anticoronaviral therapy (cACT) with multiple mechanisms of action and penetration of all potential anatomic sites of viral infection should be applied towards other challenging to treat coronaviruses, like SARS-CoV-2.Author summaryWe have screened 89 compoundsin vitrofor antiviral activity against FIPV. The putative antiviral activity of these compounds was either purported to be a direct effect on viral proteins involved in viral replication or an indirect inhibitory effect on normal cellular pathways usurped by FIPV to aid viral replication. Twenty-five of these compounds were found to have significant antiviral activity. Certain combinations of these compounds were determined to be superior to monotherapy alone.
VAMP3 and VAMP8 regulate the development and functionality of parasitophorous vacuoles housingLeishmania amazonensis
Authors: Séguin Olivier , Mai Linh Thuy , Whiteheart Sidney W. , Stäger Simona , Descoteaux Albert 
Published: July 2020

ABSTRACTTo colonize mammalian phagocytic cells, the parasiteLeishmaniaremodels phagosomes into parasitophorous vacuoles that can be either tight-fitting individual or communal. The molecular and cellular bases underlying the biogenesis and functionality of these two types of vacuoles are poorly understood. In this study, we investigated the contribution of host cell Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor proteins in the expansion and functionality of communal vacuoles as well as on the replication of the parasite. The differential recruitment patterns of Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor to communal vacuoles harboringL. amazonensisand to individual vacuoles housingL. majorled us to further investigate the contribution of VAMP3 and VAMP8 in the interaction ofLeishmaniawith its host cell. We show that whereas VAMP8 contributes to optimal expansion of communal vacuoles, VAMP3 negatively regulatesL. amazonensisreplication, vacuole size, as well as antigen cross-presentation. In contrast, neither proteins has an impact on the fate ofL. major. Collectively, our data support a role for both VAMP3 and VAMP8 in the development and functionality ofL. amazonensis-harboring communal parasitophorous vacuoles.
Biomolecular condensates amplify mRNA decapping by coupling protein interactions with conformational changes in Dcp1/Dcp2
Authors: Tibble Ryan W. , Depaix Anaïs , Kowalska Joanna , Jemielity Jacek , Gross John D. 
Published: July 2020

SUMMARYCells organize biochemical processes into biological condensates. P-bodies are cytoplasmic condensates enriched in factors important for mRNA degradation. P-bodies have been identified as sites of both mRNA storage and decay, but how these opposing outcomes may be achieved in condensates is unresolved. A critical step in mRNA degradation is removal of the 5’-7-methylguanosine cap by Dcp1/Dcp2, which is highly enriched in P-bodies. Dcp1/Dcp2 activity is repressed in condensatesin vitroand requires the activator Edc3. Activation of decapping is amplified in condensates relative to the surrounding solution due to stabilization of an autoinhibited state in Dcp1/Dcp2. Edc3 couples a conformational change in the Dcp1/Dcp2 active site with alteration of the protein-protein interactions driving phase separation to activate decapping in condensates. The composition-dependent regulation of enzyme activity in condensates occurs over length scales ranging from microns to Ångstroms and may control the functional state of P-bodies and related phase-separated compartments.HIGHLIGHTSmRNA decapping in droplets is repressedCatalytically inert droplets are activated by a change in condensate compositionA switch in enzymatic activity requires a conformational change in condensatesCondensates amplify enzyme activation compared to surrounding solution
Several complementary methods of plant establishment are required for effective restoration of banksia woodland
Authors: Brundrett Mark , Wisolith Anna , Collins Margaret , Longman Vanda , Clarke Karen 
Published: July 2020

AbstractNew banksia woodland vegetation was established at two sites totalling 50 ha in the Perth region of Western Australia as part of an offset-funded project. Restoration methods included topsoil transfer (16 ha), planting of nursery-raised local provenance seedlings (46,000 seedlings over 39.5 ha) and direct seeding with machinery or by hand (16.5 ha) with treatments overlapped. Six years of rigorous monitoring revealed trends in plant diversity, density and cover and allowed comparison of vegetation structure and composition to reference sites. Of the 162 native plants recorded, 115 originated primarily from the topsoil seed bank and the remainder from planting and seeding. Native plant germination from topsoil peaked at 700,000 stems per ha in year 2, but there was very high attrition during extreme summer drought. By year 5, native perennials averaged 20,000 stems per ha, well above the target of 7,000, but there was high spatial variability in plant density with 1/3 of quadrats below target. Saplings of Banksia spp. (the dominant local trees) plateaued at 150-220 stems per ha due to high summer mortality. Native plant cover reached 20% and perennial weed cover stabilised at under 5% within 5 years. Several complimentary methods were required for successful restoration, since transferred topsoil established most of the plant diversity. However, trees required planting or seeding, due to their canopy stored seed. Direct seeding and planting without respread topsoil led to lower overall diversity and density, but higher tree density. Most completion criteria targets were reached after 5 years. Areas with respread topsoil are trending towards recovery as a banksia woodland, but areas with only planting and seeding are likely to remain a separate vegetation type. Evidence for resilience of restored areas was provided by abundant pollination and seed set and second-generation seedlings. We suggest it may be possible to restore banksia woodland despite major challenges due to unpredictable offset funding, climate, weeds, grazing, recalcitrant species, and seed availability, but long-term monitoring is required to confirm this.