bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and tolerability of baclofen in a U.S. community population with alcohol use disorder: a dose-response, randomized, controlled trial
Authors: Garbutt James C. , Kampov-Polevoy Alexei B. , Pedersen Cort , Stansbury Melissa , Jordan Robyn , Willing Laura , Gallop Robert J. 
Published: June 2021

AbstractIdentification of new medications for alcohol use disorder (AUD) is important for improving treatment options. Baclofen, a GABABagonist, has been identified as a potential pharmacotherapy for AUD. In a 16-week double-blind, randomized, placebo-controlled trial, we investigated 30 and 90 mg/day of baclofen compared to placebo and examined effects of dose, sex, and level of pretreatment drinking. One hundred and twenty participants with DSM-IV alcohol dependence (age 46.1 (sd = 10.1) years, 51.7% male) were randomized after exclusion for unstable medical/psychiatric illness and/or dependence on drugs other than nicotine. Seventy-three participants completed the trial. A main effect of baclofen was found [%HDD (F(2,112) = 4.16,p = 0.018,d = 0.51 95%CI (0.06–0.95), 13.6 fewer HDD) and %ABST (F(2,112) = 3.68,p = 0.028,d = 0.49 95%CI (0.04–0.93), 12.9 more abstinent days)] and was driven by the 90 mg/day dose. A sex × dose interaction effect was present for both %HDD (F(2,110) = 5.48,p = 0.005) and %ABST (F(2,110) = 3.19,p = 0.045). Men showed a marginally positive effect for 90 mg/day compared to PBO (%HDD t(110) = 1.88,p = 0.063,d = 0.36 95%CI (−0.09–0.80), 15.8 fewer HDD days; %ABST t(110) = 1.68 (p = 0.096,d = 0.32 95%CI (−0.12–0.76), 15.7 more ABST)) with no effect for 30 mg/day. Women showed a positive effect for 30 mg/day (%HDD, t(110) = 3.19,p = 0.002,d = 0.61 95%CI (0.16–1.05), 26.3 fewer HDD days; %ABST t(110) = 2.73,p = 0.007,d = 0.52 95%CI (0.07–0.96), 25.4 more ABST days) with marginal effects for 90 mg/day on %ABST (p = 0.06) with drop-outs/dose reduction from sedative side-effects of 59% in women at 90 mg/day compared to 5% for men. These findings support the hypothesis that baclofen has efficacy in AUD and suggest that dose and sex be further explored as potential moderators of baclofen response and tolerability.
Targeting HIF-1 alpha transcriptional activity drives cytotoxic immune effector cells into melanoma and improves combination immunotherapy
Authors: Lequeux Audrey , Noman Muhammad Zaeem , Xiao Malina , Van Moer Kris , Hasmim Meriem , Benoit Alice , Bosseler Manon , Viry Elodie , Arakelian Tsolere , Berchem Guy , Chouaib Salem , Janji Bassam 
Published: June 2021

AbstractHypoxia is a key factor responsible for the failure of therapeutic response in most solid tumors and promotes the acquisition of tumor resistance to various antitumor immune effectors. Reshaping the hypoxic immune suppressive tumor microenvironment to improve cancer immunotherapy is still a relevant challenge. We investigated the impact of inhibiting HIF-1α transcriptional activity on cytotoxic immune cell infiltration into B16-F10 melanoma. We showed that tumors expressing a deleted form of HIF-1α displayed increased levels of NK and CD8+effector T cells in the tumor microenvironment, which was associated with high levels of CCL2 and CCL5 chemokines. We showed that combining acriflavine, reported as a pharmacological agent preventing HIF-1α/HIF-1β dimerization, dramatically improved the benefit of cancer immunotherapy based on TRP-2 peptide vaccination and anti-PD-1 blocking antibody. In melanoma patients, we revealed that tumors exhibiting high CCL5 are less hypoxic, and displayed high NK, CD3+, CD4+and CD8+T cell markers than those having low CCL5. In addition, melanoma patients with high CCL5 in their tumors survive better than those having low CCL5. This study provides the pre-clinical proof of concept for a novel triple combination strategy including blocking HIF-1α transcription activity along vaccination and PD-1 blocking immunotherapy.
Viral lysis modifies seasonal phytoplankton dynamics and carbon flow in the Southern Ocean
Authors: Biggs Tristan E G , Huisman Jef , Brussaard Corina P D 
Published: June 2021

Abstract
Phytoplankton form the base of marine food webs and are a primary means for carbon export in the Southern Ocean, a key area for global pCO2 drawdown. Viral lysis and grazing have very different effects on microbial community dynamics and carbon export, yet, very little is known about the relative magnitude and ecological impact of viral lysis on natural phytoplankton communities, especially in Antarctic waters. Here, we report on the temporal dynamics and relative importance of viral lysis rates, in comparison to grazing, for Antarctic nano- and pico-sized phytoplankton of varied taxonomy and size over a full productive season. Our results show that viral lysis was a major loss factor throughout the season, responsible for roughly half (58%) of seasonal phytoplankton carbon losses. Viral lysis appeared critically important for explaining temporal dynamics and for obtaining a complete seasonal mass balance of Antarctic phytoplankton. Group-specific responses indicated a negative correlation between grazing and viral losses in Phaeocystis and picoeukaryotes, while for other phytoplankton groups losses were more evenly spread throughout the season. Cryptophyte mortality was dominated by viral lysis, whereas small diatoms were mostly grazed. Larger diatoms dominated algal carbon flow and a single ‘lysis event’ directed &gt;100% of daily carbon production away from higher trophic levels. This study highlights the need to consider viral lysis of key Antarctic phytoplankton for a better understanding of microbial community interactions and more accurate predictions of organic matter flux in this climate-sensitive region.
One-step preparation of antimicrobial silicone materials based on PDMS and salicylic acid: insights from spatially and temporally resolved techniques
Authors: Barbieri Luca , Sorzabal Bellido Ioritz , Beckett Alison J. , Prior Ian A. , Fothergill Jo , Diaz Fernandez Yuri A. , Raval Rasmita 
Published: June 2021

AbstractIn this work, we introduce a one-step strategy that is suitable for continuous flow manufacturing of antimicrobial PDMS materials. The process is based on the intrinsic capacity of PDMS to react to certain organic solvents, which enables the incorporation of antimicrobial actives such as salicylic acid (SA), which has been approved for use in humans within pharmaceutical products. By combining different spectroscopic and imaging techniques, we show that the surface properties of PDMS remain unaffected while high doses of the SA are loaded inside the PDMS matrix. The SA can be subsequently released under physiological conditions, delivering a strong antibacterial activity. Furthermore, encapsulation of SA inside the PDMS matrix ensured a diffusion-controlled release that was tracked by spatially resolved Raman spectroscopy, Attenuated Total Reflectance IR (ATR-IR), and UV-Vis spectroscopy. The biological activity of the new material was evaluated directly at the surface and in the planktonic state against model pathogenic bacteria, combining confocal laser scanning microscopy, electron microscopy, and cell viability assays. The results showed complete planktonic inhibition for clinically relevant strains of Staphylococcus aureus and Escherichia coli, and a reduction of up to 4 orders of magnitude for viable sessile cells, demonstrating the efficacy of these surfaces in preventing the initial stages of biofilm formation. Our approach adds a new option to existing strategies for the antimicrobial functionalisation of a wide range of products such as catheters, wound dressings and in-dwelling medical devices based on PDMS.
Stress distribution of different lumbar posterior pedicle screw insertion techniques: a combination study of finite element analysis and biomechanical test
Authors: Song Mingzhi , Sun Kebin , Li Zhonghai , Zong Junwei , Tian Xiliang , Ma Kai , Wang Shouyu 
Published: June 2021

AbstractAt present, the pedicle screw is the most commonly used internal fixation device. However, there are many kinds of common posterior pedicle screw insertion techniques performed to reconstruct the lumbar stability. Therefore, spinal surgeons often face a difficult choice. The stress distribution of internal fixation system is an important index for evaluating safety. Unfortunately, little had been known about the difference of stress distribution of screw-rod systems that established by Roy-Camille, Magerl and Krag insertion techniques. Here, combination of finite element analysis and model measurement research was adopted to evaluate the difference of stress. Following different pedicle screw insertion techniques, three lumbar posterior surgery models were established after modeling and validation of the L1–S1 vertebrae finite element model. By analyzing the data, we found that stress concentration phenomenon was in all the postoperative models. Roy-Camille and Magerl insertion techniques led to the great stress on screw-rod systems. Then, fresh frozen calf spines were selected as a model for subsequent measurements. Fitted with a specially designed test pedicle screw, L5–L6 vertebrae were selected to repeat and verify the results of the finite element analysis. With the aid of universal testing machine and digital torque wrench, models simulated flexion, extension, lateral bending and rotation. Finally, the strain value was captured by the strain gauge and was then calculated as the stress value. Krag and Magerl were found to be the safer choice for pedicle screw insertion. Overall, our combination method obtained the reliable result that Krag insertion technique was the safer approach for pedicle screw implantation due to its relatively dispersive stress. Therefore, without the consideration of screw size, pedicle fill, bone density, and bone structures, we recommend the Krag insertion technique as the first choice to reconstruction of lumbar stability. Additionally, the combination method of finite element analysis and strain gauge measurement can provide a feasible way to study the stress distribution of spinal internal fixation.
Prognostic value of metabolic parameters on 18F-fluorodeoxyglucose positron tomography/computed tomography in classical rectal adenocarcinoma
Authors: Choi Byung Wook , Kang Sungmin , Bae Sung Uk , Jeong Woon Kyung , Baek Seong Kyu , Song Bong-Il , Won Kyoung Sook , Kim Hae Won 
Published: June 2021

AbstractWe aimed to investigate the prognostic value of the metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in classical rectal adenocarcinoma (CRAC). We retrospectively reviewed 149 patients with CRAC who underwent preoperative 18F-FDG PET/CT at initial diagnosis followed by curative surgical resection. 18F-FDG PET/CT metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for disease-free survival (DFS) and overall survival (OS) were evaluated for prognostic significance by univariate and multivariate analyses, along with conventional risk factors including pathologic T (pT) stage, lymph node (LN) metastasis, lymphovascular invasion (LVI), perineural invasion (PNI), and preoperative carcinoembryonic antigen (CEA) level. On univariate analysis, high pT stage, positive LN metastasis, LVI, PNI, MTV, and TLG were significant prognostic factors affecting DFS (all P < 0.05), while CEA level, high pT stage, positive LN metastasis, LVI, PNI, MTV, and TLG affected OS (all P < 0.05). On multivariate analysis, positive LN metastasis, LVI, MTV, and TLG were independent prognostic factors affecting DFS (all P < 0.05), while CEA level, positive LN metastasis, and MTV affected OS (all P < 0.05). Thus, the volume-based metabolic parameters from preoperative 18F-FDG PET/CT scans are independent prognostic factors in patients with CRAC.
A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue
Authors: Eichholz Karsten , Li Alvason Zhenhua , Diem Kurt , Jensen Michael Claus , Zhu Jia , Corey Lawrence 
Published: June 2021

AbstractChimeric antigen receptor (CAR) T cells are engineered cells used in cancer therapy and are studied to treat infectious diseases. Trafficking and persistence of CAR T cells is an important requirement for efficacy to target cancer. Here, we describe a CAR RNA FISH histo-cytometry platform combined with a random reaction seed image analysis algorithm to quantitate spatial distribution and in vivo functional activity of a CAR T cell population at a single cell resolution for preclinical models. In situ, CAR T cell exhibited a heterogenous effector gene expression and this was related to the distance from tumor cells, allowing a quantitative assessment of the potential in vivo effectiveness. The platform offers the potential to study immune functions of genetically engineered cells in situ with their target cells in tissues with high statistical power and thus, can serve as an important tool for preclinical assessment of CAR T cell effectiveness.
Bleeding outcomes and factor utilization after switching to an extended half-life product for prophylaxis in haemophilia A in Austria
Authors: Ay Cihan , Feistritzer Clemens , Rettl Joachim , Schuster Gerhard , Vavrovsky Anna , Perschy Leonard , Pabinger Ingrid 
Published: June 2021

AbstractTo prevent bleeding in severe haemophilia A [SHA, defined as factor VIII (FVIII) activity < 1%] regular prophylactic FVIII replacement therapy is required, and the benefits of factor products with extended half-life (EHL) over traditional standard half-life (SHL) are still being debated. We performed a multi-centre, retrospective cohort study of persons with SHA in Austria aiming to compare clinical outcomes and factor utilization in patients with SHA, who switched from prophylaxis with SHL to an EHL. Data were collected from haemophilia-specific patient diaries and medical records. Twenty male persons with SHA (median age: 32.5 years) were included. The most common reason for switching to the EHL was a high bleeding rate with SHL. Switch to rFVIII-Fc resulted in a significantly decreased annualized bleeding rate (ABR; median difference (IQR): − 0.3 (− 4.5–0); Wilcoxon signed-rank test for matched pairs: Z = − 2.7, p = 0.008) and number of prophylactic infusions per week (− 0.75 (− 1.0–0.0); Z = − 2.7, p = 0.007). Factor utilization was comparable to prior prophylaxis with SHL (0.0 (− 15.8–24.8) IU/kg/week; Z = − 0.4, p = 0.691). In summary, switch to EHL (rFVIII-Fc) was associated with an improved clinical outcome, reflected by ABR reduction, and less frequent infusions, without significantly higher factor usage.
Physical reservoir computing with origami and its application to robotic crawling
Authors: Bhovad Priyanka , Li Suyi 
Published: June 2021

AbstractA new paradigm called physical reservoir computing has recently emerged, where the nonlinear dynamics of high-dimensional and fixed physical systems are harnessed as a computational resource to achieve complex tasks. Via extensive simulations based on a dynamic truss-frame model, this study shows that an origami structure can perform as a dynamic reservoir with sufficient computing power to emulate high-order nonlinear systems, generate stable limit cycles, and modulate outputs according to dynamic inputs. This study also uncovers the linkages between the origami reservoir’s physical designs and its computing power, offering a guideline to optimize the computing performance. Comprehensive parametric studies show that selecting optimal feedback crease distribution and fine-tuning the underlying origami folding designs are the most effective approach to improve computing performance. Furthermore, this study shows how origami’s physical reservoir computing power can apply to soft robotic control problems by a case study of earthworm-like peristaltic crawling without traditional controllers. These results can pave the way for origami-based robots with embodied mechanical intelligence.
The impact of super-spreader cities, highways, and intensive care availability in the early stages of the COVID-19 epidemic in Brazil
Authors: Nicolelis Miguel A. L. , Raimundo Rafael L. G. , Peixoto Pedro S. , Andreazzi Cecilia S. 
Published: June 2021

AbstractAlthough international airports served as main entry points for SARS-CoV-2, the factors driving the uneven geographic spread of COVID-19 cases and deaths in Brazil remain mostly unknown. Here we show that three major factors influenced the early macro-geographical dynamics of COVID-19 in Brazil. Mathematical modeling revealed that the “super-spreading city” of São Paulo initially accounted for more than 85% of the case spread in the entire country. By adding only 16 other spreading cities, we accounted for 98–99% of the cases reported during the first 3 months of the pandemic in Brazil. Moreover, 26 federal highways accounted for about 30% of SARS-CoV-2’s case spread. As cases increased in the Brazilian interior, the distribution of COVID-19 deaths began to correlate with the allocation of the country’s intensive care units (ICUs), which is heavily weighted towards state capitals. Thus, severely ill patients living in the countryside had to be transported to state capitals to access ICU beds, creating a “boomerang effect” that contributed to skew the distribution of COVID-19 deaths. Therefore, if (i) a lockdown had been imposed earlier on in spreader-capitals, (ii) mandatory road traffic restrictions had been enforced, and (iii) a more equitable geographic distribution of ICU beds existed, the impact of COVID-19 in Brazil would be significantly lower.
The effect of COVID19 pandemic restrictions on an urban rodent population
Authors: Bedoya-Pérez Miguel A. , Ward Michael P. , Loomes Max , McGregor Iain S. , Crowther Mathew S. 
Published: June 2021

AbstractShortly after the enactment of restrictions aimed at limiting the spread of COVID-19, various local government and public health authorities around the world reported an increased sighting of rats. Such reports have yet to be empirically validated. Here we combined data from multi-catch rodent stations (providing data on rodent captures), rodent bait stations (providing data on rodent activity) and residents’ complaints to explore the effects of a six week lockdown period on rodent populations within the City of Sydney, Australia. The sampling interval encompassed October 2019 to July 2020 with lockdown defined as the interval from April 1st to May 15th, 2020. Rodent captures and activity (visits to bait stations) were stable prior to lockdown. Captures showed a rapid increase and then decline during the lockdown, while rodent visits to bait stations declined throughout this period. There were no changes in the frequency of complaints during lockdown relative to before and after lockdown. There was a non-directional change in the geographical distribution of indices of rodent abundance suggesting that rodents redistributed in response to resource scarcity. We hypothesize that lockdown measures initially resulted in increased rodent captures due to sudden shortage of human-derived food resources. Rodent visits to bait stations might not show this pattern due to the nature of the binary data collected, namely the presence or absence of a visit. Relocation of bait stations driven by pest management goals may also have affected the detection of any directional spatial effect. We conclude that the onset of COVID-19 may have disrupted commensal rodent populations, with possible implications for the future management of these ubiquitous urban indicator species.
Interaction between genetic predisposition, smoking, and dementia risk: a population-based cohort study
Authors: Zhang Na , Ranson Janice M. , Zheng Zhi-Jie , Hannon Eilis , Zhou Zhenwei , Kong Xuejun , Llewellyn David J. , King Daniel A. , Huang Jie 
Published: June 2021

AbstractWe evaluated whether the association between cigarette smoking and dementia risk is modified by genetic predisposition including apolipoprotein E (APOE) genotype and polygenic risk (excluding the APOE region). We included 193,198 UK Biobank participants aged 60–73 years without dementia at baseline. Of non-APOE-ε4 carriers, 0.89% (95% CI 0.73–1.08%) current smokers developed dementia compared with 0.49% (95% CI 0.44–0.55%) of never smokers (adjusted HR 1.78; 95% CI 1.39–2.29). In contrast, of one APOE-ε4 allele carriers, 1.69% (95% CI 1.31–2.12%) current smokers developed dementia compared with 1.40% (95% CI 1.25–1.55%) of never smokers (adjusted HR 1.06; 95% CI 0.77–1.45); of two APOE-ε4 alleles carriers, 4.90% (95% CI 2.92–7.61%) current smokers developed dementia compared with 3.87% (95% CI 3.11–4.74%) of never smokers (adjusted HR 0.94; 95% CI 0.49–1.79). Of participants with high polygenic risk, 1.77% (95% CI 1.35–2.27%) current smokers developed dementia compared with 1.05% (95% CI 0.91–1.21%) of never smokers (adjusted HR 1.63; 95% CI 1.16–2.28). A significant interaction was found between APOE genotype and smoking status (P = 0.002) while no significant interaction was identified between polygenic risk and smoking status (P = 0.25). APOE genotype but not polygenic risk modified the effect of smoking on dementia risk.
Vinaxanthone inhibits Semaphorin3A induced axonal growth cone collapse in embryonic neurons but fails to block its growth promoting effects on adult neurons
Authors: Ivakhnitskaia Evguenia , Chin Matthew R. , Siegel Dionicio , Guaiquil Victor H. 
Published: June 2021

AbstractSemaphorin3A is considered a classical repellent molecule for developing neurons and a potent inhibitor of regeneration after nervous system trauma. Vinaxanthone and other Sema3A inhibitors are currently being tested as possible therapeutics to promote nervous system regeneration from injury. Our previous study on Sema3A demonstrated a switch in Sema3A’s function toward induction of nerve regeneration in adult murine corneas and in culture of adult peripheral neurons. The aim of the current study is to determine the direct effects of Vinaxanthone on the Sema3A induced adult neuronal growth. We first demonstrate that Vinaxanthone maintains its anti-Sema3A activity in embryonic dorsal root ganglia neurons by inhibiting Sema3A-induced growth cone collapse. However, at concentrations approximating its IC50 Vinaxanthone treatment does not significantly inhibit neurite formation of adult peripheral neurons induced by Sema3A treatment. Furthermore, Vinaxanthone has off target effects when used at concentrations above its IC50, and inhibits neurite growth of adult neurons treated with either Sema3A or NGF. Our results suggest that Vinaxanthone’s pro-regenerative effects seen in multiple in vivo models of neuronal injury in adult animals need further investigation due to the pleiotropic effect of Sema3A on various non-neuronal cell types and the possible effect of Vinaxanthone on other neuroregenerative signals.