bluuebunny/crossref_metadata_2025 huggingface dataset:
Radioligand therapy using [177Lu]Lu-PSMA-617 in mCRPC: a pre-VISION single-center analysis
Authors: Seifert Robert , Kessel Katharina , Schlack Katrin , Weckesser Matthias , Bögemann Martin , Rahbar Kambiz
Published: February 2020

Background

Radioligand therapy with [177Lu]Lu-PSMA-617 is efficacious for the treatment of patients with metastasized castration-resistant prostate cancer (mCRPC). Various studies have evaluated the efficacy and safety of [177Lu]Lu-PSMA-617 using a dose of 6.0 GBq and an 8-week therapy interval. However, the first prospective phase III trial (VISION) plans to use an elevated cumulative dose by applying 7.5 GBq in a 6-week interval. The aim of the present study was to compare safety and efficacy of the two aforementioned [177Lu]Lu-PSMA-617 therapy regimes (7.5 GBq every 6 weeks vs. 6.0 GBq every 8 weeks).

Methods

A total number of 78 consecutive patients with mCRPC and a history of first-line chemotherapy were included in this retrospective analysis. The outcome of patients treated with 6.0 GBq [177Lu]Lu-PSMA-617 per cycle (n = 37) were compared with those treated with 7.5 GBq (n = 41) per cycle. The median therapy intervals were 8.4 weeks (6.0 GBq group) vs. 6.5 (7.5 GBq group). PSA response, PSA progression-free survival (PSA-PFS), overall survival, and adverse events were evaluated and compared between both groups. Chi-squared test, Kaplan Meier estimates, Cox regression, and log-rank test were used. The highest decline from pretherapeutic PSA levels was measured as percentage (best PSA response) and compared between groups by Wilcoxon test.

Results

There was no significant difference comparing the rate of > 50% PSA decline or best PSA response between the 6.0 GBq and 7.5 GBq group (35% vs. 54%, p = 0.065; and − 40.2% vs. − 57.8%, p = 0.329). The median estimated survival and PSA-PFS did not significantly differ between the 6.0 GBq and 7.5 GBq groups as well (11.3 vs. 12.7 months, p = 0.384; and 9.5 vs. 12.3 months, p = 0.258). There was no significant difference regarding the change of kidney, liver, and blood cell parameters under therapy between the treatment groups.

Conclusion

Higher cumulated doses of [177Lu]Lu-PSMA-617 were well tolerated and caused no significantly increased rate of adverse reactions. Moreover, 7.5 GBq of [177Lu]Lu-PSMA-617 every 6 weeks causes slightly higher, though not statistically significant, response rates and seems therefore to be the preferable treatment regime. However, future studies are needed to elucidate the dose-related efficacy of [177Lu]Lu-PSMA-617 as a way to personalized medicine.
Evaluation of a new suture material (Duramesh™) by measuring suture tension in small and large bites techniques for laparotomy closure in a porcine model
Authors: Yurtkap Y. , den Hartog F. P. J. , van Weteringen W. , Jeekel J. , Kleinrensink G. J. , Lange J. F.
Published: February 2020

Purpose

After closure of laparotomies, sutures may pull through tissue due to too high intra-abdominal pressure or suture tension, resulting in burst abdomen and incisional hernia. The objective of this study was to measure the suture tension in small and large bites with a new suture material.

Methods

Closure of thelinea albawas performed with small bites (i.e., 5 mm between two consecutive stitches and 5 mm distance from the incision) and large bites (i.e., 10 mm × 10 mm) with Duramesh™ size 0 (2 mm) and PDS II 2-0 in 24 experiments on six porcine abdominal walls. The abdominal wall was fixated on an artificial computer-controlled insufflatable abdomen, known as the ‘AbdoMan’. A custom-made suture tension sensor was placed in the middle of the incision.

Results

The suture tension was significantly lower with the small bites technique and Duramesh™ when compared with large bites (small bites 0.12 N (IQR 0.07–0.19) vs. large bites 0.57 N (IQR 0.23–0.92),p < 0.025). This significant difference was also found in favour of the small bites with PDS II 2-0 (p < 0.038). No macroscopic tissue failure was seen during or after the experiments.

Conclusion

Closure of the abdominal wall with the small bites technique and Duramesh™was more efficient in dividing suture tension across the incision when compared to large bites. However, suture tension compared to a conventional suture material was not significantly different, contradicting an advantage of the new suture material in the prevention of burst abdomen and incisional hernia during the acute, postoperative phase.
The influence of environmental pollution with fluorine compounds on the level of fluoride in soil, feed and eggs of laying hens in Central Pomerania, Poland
Authors: Bombik Elżbieta , Bombik Antoni , Rymuza Katarzyna
Published: February 2020

The present study was aimed at evaluating fluorine contamination of the eggs of free-ranging laying hens in Northern Poland, in the Central Pomerania region, in relation to the distance from the emission sources. Fluorine levels in the soil, feed, and the shells, and contents of the eggs were assayed with the potentiometric method using an ion-selective electrode from ORION Ion Meter. The sampled eggs were subjected to pressure microwave digestion with the use of a Milestone MLS-1200 microwave. All the samples were digested in 5 ml of supra-pure grade concentrated HNO3 from Merck. The mean level of fluorine in the studied soils ranged from 3.79 mg kg−1 of DM in typical river alluvial soil to 126.19 mg kg−1 of DM in lessive soil. The study revealed an average fluorine content in the feeds administered to the hens on the farms in zone 1 (17.29 mg kg−1 of DM), it being 3.5 times higher than the corresponding content in zone 2 (4.92 mg kg−1 of DM). A statistically significantly higher mean fluorine level was identified in the eggshells of hens on zone 1 farms, located closer to the pollution emission sources (17.52 mg kg−1 of DM), the value being more than 3-fold higher than that in zone 2 (5.47 mg kg−1 of DM). The present study revealed an almost twice as high fluorine mean content in the hen eggs collected on farms in zone 1 (1.488 mg kg−1 of DM) compared with the hen egg contents in the experimental zone 2 (0.640 mg kg−1 of DM), the difference being statistically significant.
The Role of Mast Cells in IgE-Independent Lung Diseases
Authors: Komi Daniel Elieh Ali , Mortaz Esmaeil , Amani Saeede , Tiotiu Angelica , Folkerts Gert , Adcock Ian M
Published: February 2020

Mast cells (MCs) are granular cells of the innate immune system which develop from CD34+/CD117+ progenitors and play a role in orchestrating adaptive immune responses. They have a well-known role in allergic reactions following immunoglobulin (Ig)E-mediated activation of the cell-surface expressed IgE high-affinity receptor (FcεRI). MCs can also respond to various other stimuli due to the expression of a variety of receptors including toll-like receptors (TLRs), immunoglobulin (IgG) receptors (FcγR), complement receptors such as C5a (CD88) expressed by skin MCs, neuropeptides receptors including nerve growth factor receptor, (NGFR), cytokines receptors such as (IL)-1R and IL-3R, and chemokines receptors including CCR-1 and CCR-3. MCs release three groups of mediators upon degranulation differentiated according to their chemical composition, storage, and time to release. These include preformed mediators (mainly histamine, tryptase, and chymase), de novo synthesized mediators such as prostaglandin (PG)D2, leukotriene (LT)B4 and LTD4, and cytokines including IL-1β, IL-3, tumor necrosis factor (TNF)α, and transforming growth factor(TGF)-β. Emerging evidence indicates a role for IgE-independent MC activation in the late-stage asthmatic response as well as in non-allergic airway diseases including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. MC infiltration/activation has been reported in some, but not all, studies of lung cancer. MC-derived TNF-α possesses tumor-suppressive activity while IL-1β supports tumor progression and metastasis. In IPF lungs, an increase in density of tryptase- and chymase-positive MCs (MCTC) and overexpression of TGF-β support the fibrosis progression. MC-derived chymase activates latent TGF-β that induces the differentiation of fibroblasts to matrix-producing myofibroblasts. In summary, increasing evidence highlights a critical role of MCs in non-allergic diseases that may indicate new approaches for therapy.
Syphilis in Pregnancy
Authors: Pradhan Mandakini , Jain Shruti
Published: February 2020

Syphilis is a sexually transmitted bacterial disease relevant to pregnancy because it has the potential to cause congenital syphilis if it occurs at any time during pregnancy. An upsurge in cases of syphilis in women and hence congenital syphilis has been reported worldwide recently. 40% of cases can result in spontaneous miscarriages, stillbirth, non-immune hydrops, fetal growth restriction and perinatal death, as well as serious sequelae in liveborn infected children. Pregnancy complications can be avoided by early detection and treatment in the antenatal period. All antenatal women should be screened for syphilis at the first antenatal visit. There is no gold standard for diagnostic test of syphilis. A combination of serological tests consisting of treponemal and a non treponemal test are used for diagnosis. Screening with non-treponemal tests such as rapid plasma reagin or venereal disease research laboratory test combined with confirmation of reactive individuals with treponemal tests such as the fluorescent treponemal antibody absorption assay is the usual cost effective approach. Those at risk should be retested in the third trimester. Treatment during pregnancy should be with penicillin depending upon the stage of the maternal infection. All neonates born to mothers who have reactive nontreponemal and treponemal test results should be evaluated.
Bentonite/Magnetite Composite for Removal of Nitrofurazone
Authors: Alekseeva Olga V. , Rodionova Anna N. , Noskov Andrew V. , Agafonov Alexander V.
Published: February 2020

The presence of pharmaceutical pollutants in the environment is one of the most pressing environmental problems. Adsorption from solution is an effective way to remove pharmaceuticals from liquid media, but the problem then is to separate the adsorbent from the liquids. The objective of the present study was to remove nitrofurazone from aqueous solutions using a bentonite/magnetite composite, prepared by co-precipitation of magnetite with bentonite, which could then be collected by magnetic separation. The bentonite/magnetite composite was characterized using diverse techniques, such as X-ray diffraction, scanning electron microscopy, low-temperature N2 adsorption/desorption, laser diffraction, and magnetization measurements. The particle size of the composite material did not exceed 50 μm and the particle size distribution was mono-modal with a maximum at 3.2 μm. The strong hysteresis in the magnetization curve revealed that the bentonite/magnetite particles were ferromagnetic. Adsorption of nitrofurazone by the bentonite/magnetite composite from aqueous solutions was measured and the amount of nitrofurazone adsorbed was 3.2×10–2 mmol/g. The adsorption kinetics of nitrofurazone to the bentonite/magnetite composite followed a pseudo-second-order kinetics equation. Upon adsorption, hydrogen bonds were formed between the amide groups of nitrofurazone and oxygen groups in bentonite.
Independent Association of Erectile Dysfunction and Low Testosterone Levels with Life Dissatisfaction in Men with Chronic Spinal Cord Injury
Authors: D'Andrea Settimio , Minaldi Elisa , Castellini Chiara , Cavallo Francesca , Felzani Giorgio , Francavilla Sandro , Francavilla Felice , Barbonetti Arcangelo
Published: February 2020

Background

The loss of global functional independence, along with bladder, bowel, and sexual dysfunctions, may contribute to psychological distress and life dissatisfaction after spinal cord injury (SCI).

Aim

To explore the relationship of erectile function and androgenic status with life satisfaction, independently from confounders recognizable in spinal cord–injured men.

Methods

100 consecutive men (49 ± 17 years) admitted to a rehabilitation program because of chronic SCI (≥1 year) underwent clinical/biochemical evaluations, including the assessment of life and sexual satisfaction using the Life-Satisfaction Questionnaire-9 (LiSat-9), erectile function using the International Index of Erectile Function-5 (IIEF-5), global and bowel-bladder functional independence using the Spinal Cord Independence Measure (SCIM) and measurement of total testosterone (TT) levels. The free testosterone level was calculated using the Vermeulen formula.

Outcomes

The outcomes include the relationship between sexual health and life satisfaction in men with SCI.

Results

A LiSat-9 score <4, suggestive for life dissatisfaction, was exhibited by 49% of men. When compared with the life-satisfied group, a significantly higher percentage of them had sexual dissatisfaction and erectile dysfunction (ED); they also exhibited significantly lower levels of TT and calculated free testosterone (cFT) and a more severe impairment of bowel-bladder function. The life satisfaction degree correlated with sexual satisfaction degree, IIEF-5 score, TT, cFT, and bowel-bladder function degree. At the logistic regression model, including sexual LiSat-9 subscore and bowel-bladder SCIM subscore, only the former exhibited a significant negative association with life dissatisfaction. In a further logistic regression model, including the putative key determinants of sexual satisfaction, erectile function, and cFT levels, a higher odd of life dissatisfaction was independently associated both with a lower IIEF-5 score (OR: 0.93; 95% CI: 0.88, 0.98) and lower cFT levels (OR: 0.98; 95% CI: 0.98, 0.99).

Clinical Implications

In men with chronic SCI, assessment of erectile function and testosterone levels can help to predict life satisfaction.

Strengths & Limitations

This is the first demonstration of the independent association of androgen deficiency and ED with life satisfaction in men with SCI. Prospective studies are warranted to clarify the cause-effect relationships.

Conclusions

In men with SCI, ED and low testosterone levels exhibit a significant independent association with life dissatisfaction; longitudinal intervention studies could explore possible effects of their treatment in improving sexual and life satisfaction in this population.
Effects of Ca, Cu concentration on degradation behavior of Zn alloys in Hank’s solution
Authors: SathishKumar G. , Parameswaran P. , Vijayan V. , Yokeswaran R.
Published: February 2020

In tissue engineering scaffolds and bone implants, the impact of magnesium (Mg) and its alloys were studied for the past 2 decades. The problem with Mg was that it is prone to be attacked by corrosion due to body fluids. In order to find way to make better material, scientist have turned towards the development of zinc (Zn) alloys for its uniform and better corrosion resistance when compared to Mg. The Zn alloy was developed through powder metallurgy route (ball milling for 10 hours). The hardness of the sample was higher when compared to other Zn alloys due to the incorporation of copper (Cu) and calcium (Ca) nutrient elements in the matrix. The immersion test was carried out in the conical flask and the result was revealed. The corrosion rate was satisfactory due to the higher corrosion resistance offered by the alloy along with uniform corrosion in simulated body fluid (SBF)/Hank’s solution in potentiometer. The microstructure and the phases formed was examined through SEM and XRD with EDS.
Contemporary International Business in the Asia-Pacific Region
Authors: Verbeke Alain , Roberts Robin E. , Delaney Deborah , Zámborský Peter , Enderwick Peter , Nagar Swati
Published: February 2020

The increasing dominance of the Asia–Pacific region as a source of international business growth has created a dynamic and complex business environment. For this reason, a sound understanding of regional economies, communities and operational challenges is critical for any international business manager working in a global context. With an emphasis on 'doing business in Asia', Contemporary International Business in the Asia–Pacific Region addresses topics that are driving international business today. Providing content and research that is accessible to local and international students, this text introduces core business concepts and comprehensively covers a range of key areas, including trade and economic development, dimensions of culture, business planning and strategy development, research and marketing, and employee development in cross-cultural contexts. Written by authors with industry experience and academic expertise, Contemporary International Business in the Asia–Pacific Region is an essential resource for students of business and management.
Investigating controls on sea ice algal production using E3SMv1.1-BGC
Authors: Jeffery Nicole , Maltrud Mathew E. , Hunke Elizabeth C. , Wang Shanlin , Wolfe Jon , Turner Adrian K. , Burrows Susannah M. , Shi Xiaoying , Lipscomb William H. , Maslowski Wieslaw , Calvin Kate V.
Published: February 2020

We present the analysis of global sympagic primary production (PP) from 300 years of pre-industrial and historical simulations of the E3SMv1.1-BGC model. The model includes a novel, eight-element sea ice biogeochemical component, MPAS-Seaice zbgc, which is resolved in three spatial dimensions and uses a vertical transport scheme based on internal brine dynamics. Modeled ice algal chlorophyll-a concentrations and column-integrated values are broadly consistent with observations, though chl-a profile fractions indicate that upper ice communities of the Southern Ocean are underestimated. Simulations of polar integrated sea ice PP support the lower bound in published estimates for both polar regions with mean Arctic values of 7.5 and 15.5 TgC/a in the Southern Ocean. However, comparisons of the polar climate state with observations, using a maximal bound for ice algal growth rates, suggest that the Arctic lower bound is a significant underestimation driven by biases in ocean surface nitrate, and that correction of these biases supports as much as 60.7 TgC/a of net Arctic PP. Simulated Southern Ocean sympagic PP is predominantly light-limited, and regional patterns, particularly in the coastal high production band, are found to be negatively correlated with snow thickness.
On the Plastic Strain Accumulation in Notched Bars During High-Temperature Creep Dwell
Authors: Barbera Daniele , Chen Haofeng
Published: February 2020

Structural integrity plays an important role in any industrial activity, due to its capability of assessing complex systems against sudden and unpredicted failures. The work here presented investigates an unexpected new mechanism occurring in structures subjected to monotonic and cyclic loading at high temperature creep condition. An unexpected accumulation of plastic strain is observed to occur, within the high-temperature creep dwell. This phenomenon has been observed during several full inelastic finite element analyses. In order to understand which parameters make possible such behaviour, an extensive numerical study has been undertaken on two different notched bars. The notched bar has been selected due to its capability of representing a multiaxial stress state, which is a practical situation in real components. Two numerical examples consisting of an axisymmetric v-notch bar and a semi-circular notched bar are considered, in order to investigate different notches severity. Two material models have been considered for the plastic response, which is modelled by both Elastic-Perfectly Plastic and Armstrong-Frederick kinematic hardening material models. The high-temperature creep behaviour is introduced using the time hardening law. To study the problem several results are presented, as the effect of the material model on the plastic strain accumulation, the effect of the notch severity and the mesh element type and sensitivity. All the findings further confirm that the phenomenon observed is not an artefact but a real mechanism, which needs to be considered when assessing off-design condition. Moreover, it might be extremely dangerous if the cyclic loading condition occurs at such a high loading level.
Redistribution and the Quality of Government: Evidence from Central and Eastern Europe
Authors: Petrova Bilyana
Published: February 2020

The welfare state literature has largely ignored the impact of a country's quality of government on its levels of redistribution. Using cross-sectional time-series analysis of twenty-one Central and Eastern European countries, this article shows that environments characterized by higher levels of corruption, rampant bureaucratic inefficiency and ineffective enforcement of the rule of law are associated with lower levels of redistribution. Poor government directly affects the supply side of the redistribution process by hindering countries’ ability to allocate funds to redistribution and deliver them to their beneficiaries. Contrary to existing demand-oriented perspectives, the proposed causal mechanism does not blame lower redistribution on the lack of public support for the welfare state. Rather, it focuses on the capacity of states to adopt and implement inequality-reducing policies. The results are robust to numerous extensions and model specifications.
Vowel change across time, space, and conversational topic: the use of localized features in former mining communities
Authors: Devlin Thomas , French Peter , Llamas Carmen
Published: February 2020

This study focuses on speakers who continue to use forms that are recessive in a community, and the phonological and conversational contexts in which recessive forms persist. Use of a local, recessive form is explored across males from four ex-mining communities in Northeast England. Older speakers, who lived in the area when the mines were open, frequently produce the localized variant of themouthvowel, especially in speech produced during conversation about the locally resonant topic of mining, and, most frequently, in communities closest to the location with which the form is associated. Conversely, speakers born since the loss of mining and with little connection to the industry hardly produce the local form in any community or conversational topic. Exploring conversational topic provides evidence for the connections between shifting social contexts and sound change, specifically that speakers retain otherwise recessive features in speech concerning topics which are locally resonant to them.
Comparative efficacy of teat sealants given prepartum for prevention of intramammary infections and clinical mastitis: a systematic review and network meta-analysis
Authors: Winder C. B. , Sargeant J. M. , Hu D. , Wang C. , Kelton D. F. , Leblanc S. J. , Duffield T. F. , Glanville J. , Wood H. , Churchill K. J. , Dunn J. , Bergevin M. D. , Dawkins K. , Meadows S. , Deb B. , Reist M. , Moody C. , O'Connor A. M.
Published: February 2020

A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25–0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.
Access Compromised? The Impact of Healthcare Reforms under Austerity in Lithuania and Spain
Authors: Doblytė Sigita , Guillén Ana M.
Published: February 2020

Using an interpretative comparison in search for cross-case similarities and differences, we examine the evolution of equity of access to healthcare during the economic crisis in two potentially vulnerable Eastern and Southern European countries – Lithuania and Spain. While the type of healthcare system may have shown higher resilience, i.e. equity of access to care during the crisis should have been affected more in Lithuania – a relatively immature health insurance system – than in Spain – a consolidated national health service, the intensity and length of the crisis and types of adjustment measures undertaken may have led, in turn, to different results in terms of equity of access. The analysis focuses on the respective institutional designs and healthcare reforms under austerity as well as subjective and objective indicators of access to care. We conclude that the Lithuanian healthcare system, despite potential comparative disadvantage, has shown greater performance than the Spanish one during the crisis.
Marine Heatwaves in China's Marginal Seas and Adjacent Offshore Waters: Past, Present, and Future
Authors: Yao Yulong , Wang Junjie , Yin Jianjun , Zou Xinqing
Published: February 2020

Under the combined impacts of natural changes and human activities, the past, current, and future marine heatwaves (MHWs) in China's marginal seas and adjacent offshore waters (CMSOW) need a comprehensive understanding. This study provides a systematic analysis of the spatiotemporal variations using daily sea surface temperature data and simulates the future trend using 12 climate models. During 1982–2018, the mean annual total days, duration, frequency, and mean intensity of the MHWs in the CMSOW increased by 20–30 days/decade, 5–9 days/decade, 1–2 decade−1, and 0.1–0.3°C/decade, respectively (p <0.01). The maximum sea surface temperature anomalies in the Bohai Sea was over 6–8°C, and the MHW's frequency, duration, and mean intensity were higher than twice the global average, which could have impacted fishery resources and occurrence of harmful algal blooms. The variations of the MHWs in the CMSOW result from the robust ocean surface warming, which is caused by increased solar radiation due to reduced cloud cover, reduced ocean heat loss from weaker wind speed, weakening but warmer Kuroshio, and strong El Niño. In the future, the areas with longer total days and duration will increase; the spatial pattern of frequency has a negative relationship with that of duration while that of mean intensity is mostly unchanged. Year 2040 is a key node for the future changes of MHW under different Representative Concentration Pathways. The trend of total days increases from fast to slow, and frequency shows an opposite trend; the duration and mean intensity rise faster after 2040.
Olivine‐Carbonate Mineralogy of the Jezero Crater Region
Authors: Brown A. J. , Viviano C. E. , Goudge T. A.
Published: February 2020

A well‐preserved, ancient delta deposit, in combination with ample exposures of carbonate outcrops, makes Jezero Crater in Nili Fossae a compelling astrobiological site. We use Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) observations to characterize the surface mineralogy of the crater and surrounding watershed. Previous studies have documented the occurrence of olivine and carbonates in the Nili Fossae region. We focus on correlations between these two well‐studied lithologies in the Jezero crater watershed. We map the position and shape of the olivine 1 μm absorption band and find that carbonates are found in association with olivine which displays a 1 μm band shifted to long wavelengths. We then use Thermal Emission Imaging Spectrometer (THEMIS) coverage of Nili Fossae and perform tests to investigate whether the long wavelength shifted (redshifted) olivine signature is correlated with high thermal inertia outcrops. We find that there is no consistent correlation between thermal inertia and the unique olivine signature. We discuss a range of formation scenarios for the olivine and carbonate associations, including the possibility that these lithologies are products of serpentinization reactions on early Mars. These lithologies provide an opportunity for deepening our understanding of early Mars and, given their antiquity, may provide a framework to study the timing of valley networks and the thermal history of the Martian crust and interior from the early Noachian to today.
The effects of 10,000 voluntary contractions over 8 weeks on the strength of very weak muscles in people with spinal cord injury: a randomised controlled trial
Authors: Chen Lydia W. , Glinsky Joanne V. , Islam Md. Shofiqul , Hossain Muzaffor , Boswell-Ruys Claire L. , Kataria Chitra , Redhead Jason , Xiong Yuan , Gollan Emilie , Costa Punam D. , Denis Sophie , Ben Marsha , Chaudhary Lovely , Wang Jun , Hasnat Md. Abu Khayer , Yeomans Jayne , Gandevia Simon C. , Harvey Lisa A.
Published: February 2020

Study design

A multi-centred, single-blinded randomised controlled trial.

Objectives

To determine the effect of 10,000 voluntary contractions over 8 weeks on the strength of very weak muscles in people with spinal cord injury (SCI).

Settings

Seven hospitals in Australia and Asia.

Methods

One hundred and twenty people with recent SCI undergoing inpatient rehabilitation were randomised to either a Treatment or Control Group. One major muscle group from an upper or lower limb was selected if the muscle had grade 1 or grade 2 strength on a standard six-point manual muscle test. Participants allocated to the Treatment Group performed 10,000 isolated contractions of the selected muscle group, as well as usual care in 48 sessions over 8 weeks. Participants allocated to the Control Group received usual care alone. Participants were assessed at baseline and 8 weeks by a blinded assessor. The primary outcome was voluntary muscle strength on a 13-point manual muscle test. There were three secondary outcomes capturing therapists’ and participants’ perceptions of strength and function.

Results

The mean between-group difference of voluntary strength at 8 weeks was 0.4/13 points (95% confidence interval −0.5 to 1.4) in favour of the Treatment Group. There were no notable between-group differences on any secondary outcome.

Conclusion

Ten thousand isolated contractions of very weak muscles in people with SCI over 8 weeks has either no or a very small effect on voluntary strength.
Convergence of pathway analysis and pattern recognition predicts sensitization to latest generation TRAIL therapeutics by IAP antagonism
Authors: Vetma Vesna , Guttà Cristiano , Peters Nathalie , Praetorius Christian , Hutt Meike , Seifert Oliver , Meier Friedegund , Kontermann Roland , Kulms Dagmar , Rehm Markus
Published: February 2020

Second generation TRAIL-based therapeutics, combined with sensitising co-treatments, have recently entered clinical trials. However, reliable response predictors for optimal patient selection are not yet available. Here, we demonstrate that a novel and translationally relevant hexavalent TRAIL receptor agonist, IZI1551, in combination with Birinapant, a clinically tested IAP antagonist, efficiently induces cell death in various melanoma models, and that responsiveness can be predicted by combining pathway analysis, data-driven modelling and pattern recognition. Across a panel of 16 melanoma cell lines, responsiveness to IZI1551/Birinapant was heterogeneous, with complete resistance and pronounced synergies observed. Expression patterns of TRAIL pathway regulators allowed us to develop a combinatorial marker that predicts potent cell killing with high accuracy. IZI1551/Birinapant responsiveness could be predicted not only for cell lines, but also for 3D tumour cell spheroids and for cells directly isolated from patient melanoma metastases (80–100% prediction accuracies). Mathematical parameter reduction identified 11 proteins crucial to ensure prediction accuracy, with x-linked inhibitor of apoptosis protein (XIAP) and procaspase-3 scoring highest, and Bcl-2 family members strongly represented. Applied to expression data of a cohort ofn = 365 metastatic melanoma patients in a proof of concept in silico trial, the predictor suggested that IZI1551/Birinapant responsiveness could be expected for up to 30% of patient tumours. Overall, response frequencies in melanoma models were very encouraging, and the capability to predict melanoma sensitivity to combinations of latest generation TRAIL-based therapeutics and IAP antagonists can address the need for patient selection strategies in clinical trials based on these novel drugs.
Preferential gene retention increases the robustness of cold regulation in Brassicaceae and other plants after polyploidization
Authors: Song Xiao-Ming , Wang Jin-Peng , Sun Peng-Chuan , Ma Xiao , Yang Qi-Hang , Hu Jing-Jing , Sun Sang-Rong , Li Yu-Xian , Yu Ji-Gao , Feng Shu-Yan , Pei Qiao-Ying , Yu Tong , Yang Nan-Shan , Liu Yin-Zhe , Li Xiu-Qing , Paterson Andrew H. , Wang Xi-Yin
Published: February 2020

Cold stress profoundly affects plant growth and development and is a key factor affecting the geographic distribution and evolution of plants. Plants have evolved adaptive mechanisms to cope with cold stress. Here, through the genomic analysis of Arabidopsis, threeBrassicaspecies and 17 other representative species, we found that both cold-related genes (CRGs) and their collinearity were preferentially retained after polyploidization followed by genome instability, while genome-wide gene sets exhibited a variety of other expansion mechanisms. The cold-related regulatory network was increased inBrassicaceaegenomes, which were recursively affected by polyploidization. By combining our findings regarding the selective retention ofCRGsfrom this ecological genomics study with the available knowledge of cold-induced chromosome doubling, we hypothesize that cold stress may have contributed to the success of polyploid plants through both increasing polyploidization and selectively maintainingCRGsduring evolution. This hypothesis requires further biological and ecological exploration to obtain solid supporting evidence, which will potentially contribute to understanding the generation of polyploids and to the field of ecological genomics.
MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response
Authors: Qiu Huan , Jin Bang-Ming , Wang Zhan-Feng , Xu Bin , Zheng Qi-Fan , Zhang Li , Zhu Ling-Yu , Shi Shuang , Yuan Jun-Bo , Lin Xiao , Gao Shu-Bin , Jin Guang-Hui
Published: February 2020

The MEN1 gene, a tumor suppressor gene that encodes the protein menin, is mutated at high frequencies in neuroendocrine (NE) tumors; however, the biological importance of this gene in NE-type lung cancer in vivo remains unclear. Here, we established an ATII-specific KrasG12D/+/Men1−/− driven genetically engineered mouse model and show that deficiency of menin results in the accumulation of DNA damage and antagonizes oncogenic Kras-induced senescence and the epithelial-to-mesenchymal transition during lung tumorigenesis. The loss of menin expression in certain human primary lung cancers correlates with elevated NE profiles and reduced overall survival.
Author Correction: Influence of microstructure on superconductivity in KxFe2−ySe2 and evidence for a new parent phase K2Fe7Se8
Authors: Ding Xiaxin , Fang Delong , Wang Zhenyu , Yang Huan , Liu Jianzhong , Deng Qiang , Ma Guobin , Meng Chong , Hu Yuhui , Wen Hai-Hu
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Role of astroglia in Down’s syndrome revealed by patient-derived human-induced pluripotent stem cells
Authors: Chen Chen , Jiang Peng , Xue Haipeng , Peterson Suzanne E. , Tran Ha T. , McCann Anna E. , Parast Mana M. , Li Shenglan , Pleasure David E. , Laurent Louise C. , Loring Jeanne F. , Liu Ying , Deng Wenbin
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Comparative structural investigations of nuclear waste glass alteration layers and sol-gel synthesized aerogels
Authors: Reiser Joelle T. , Ryan Joseph V. , Weber Marc H. , Ilavsky Jan , Olszta Matthew J. , Schreiber Daniel K. , Wall Nathalie A.
Published: February 2020

While various glass alteration layer formation mechanisms have been debated in recent years, the glass alteration community generally agrees that more information on physical properties of the alteration layers is needed to further the understanding of their impacts on overall glass alteration. In this work, pore volumes and solid structures of glass (International Simple Glass, ISG) alteration layers formed in solutions of various pH conditions in initially dilute conditions at 90 °C are evaluated with positron annihilation spectroscopy, small-angle X-ray scattering, and scanning transmission electron microscopy. Pore volumes of alteration layers formed at pH 9 were found to be at their lowest near the surfaces of the alteration layers. Solid structures of alteration layers are compared with those of synthetic aerogels of comparable compositions produced under various pH conditions. Alteration layers formed at pH 11 on ISG were shown to contain large structures (>10 nm) similar to synthetic aerogels created under neutral and basic conditions whereas alteration layers formed at pH 9 did not. Available dissolved silica species defined by silica solubility were proposed to have the greatest impact on alteration layer structure.
Matching STR and SNP genotyping to discriminate between wild boar, domestic pigs and their recent hybrids for forensic purposes
Authors: Lorenzini Rita , Fanelli Rita , Tancredi Francesco , Siclari Antonino , Garofalo Luisa
Published: February 2020

The genetic discrimination between phylogenetically close taxa can be challenging if their gene pools are not differentiated and there are many shared polymorphisms. The gene flow between wild boar (Sus scrofa) and domestic pig (S. s. domesticus) has never been interrupted from domestication onwards, due to non-stop natural and human-mediated crossbreeding. To date there are no individual genetic markers that are able to distinguish between the two forms, nor even to identify effectively their hybrids. We developed a combined molecular protocol based on multiplex porcine-specific STR-profiling system and new real time PCR-based assays of single polymorphisms in the NR6A1 and MC1R genes to gain high diagnostic power in the differentiation of wild boar, pig and hybrids for forensic purposes. The combined approach correctly assigned individuals to one or the other parental gene pool and identified admixed genotypes. Evidence was found for substantial reduction of false negative results by using multiple marker systems jointly, compared to their use individually. Our protocol is a powerful and cost-effective diagnostic tool that can easily be adopted by most forensic laboratories to assist authorities contrast food adulteration, assure veterinary public health and fight against wildlife crimes, like poaching and illegal detention of wild animals.
Factors associated with platelet reactivity during dual antiplatelet therapy in patients with diabetes after acute coronary syndrome
Authors: Tatarunas Vacis , Kupstyte-Kristapone Nora , Zvikas Vaidotas , Jakstas Valdas , Zaliunas Remigijus , Lesauskaite Vaiva
Published: February 2020

Antiplatelet drugs are prescribed without considering the diabetic status of the patient. The objective of the current investigation was to determine the impact of clinical factors, CYP4F2 enzyme and 20-hydroxyeicosatetraenoic acid (20-HETE) concentrations on high on-treatment platelet reactivity in patients with diabetes treated with antiplatelet drugs following acute coronary syndromes. A total of 667 patients were included in the study. Dual antiplatelet drug loading dosages with aspirin (300 mg) and ticagrelor (180 mg) or clopidogrel (600 mg) were prescribed to all the studied patients. Testing of platelet aggregation was performed the day after loading antiplatelet drug dosages. Platelet aggregation test was done according to the classical Born method. Multivariate binary regression analysis demonstrated that insulin use and higher 20-HETE concentration increased the odds of high on-treatment platelet reactivity during the initiation of antiplatelet drug therapy (OR: 3.968, 95% CI: 1.478–10.656, p = 0.006 and OR: 1.139, 95% CI: 1.073–1.210, respectively, p < 0.001). Ticagrelor use decreased the odds of developing high on-treatment platelet reactivity (OR: 0.238, 95% CI: 0.097–0.585, p = 0.002). Data from this study revealed that high on-treatment platelet reactivity during dual antiplatelet therapy in patients with diabetes may depend on such factors as insulin prescription and 20-HETE concentration.
The outcomes of bariatric surgery on rheumatoid arthritis disease activity: a prospective cohort study
Authors: Xu Fang , Yu Chao , Li De-Guan , Yan Qiang , Zhang Shang-Xin , Yang Xiao-Dong , Zhang Zhen
Published: February 2020

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the joints. Overweight and obesity can aggravate disease activity and clinical outcome in patients with RA. However, the role of bariatric surgery in inducing weight loss in the treatment of RA has not been confirmed. In this 12-month prospective cohort study, RA patients with obesity who were referred to our hospital were included. Thirty-two patients were classified into the bariatric surgery group according to the patient’s decision after a comprehensive assessment of surgery indications, and 33 patients received only pharmacotherapy for RA. At the 12-month follow-up, the response rates of ACR20, ACR50 and ACR70 were 75.0% vs. 51.5%, 53.1% vs. 39.4% and 31.3% vs. 21.2% in the bariatric surgery and non-surgery groups, respectively (all p < 0.05); the mean DAS28-ESR, DAS28-CRP and cDAI scores were 1.5 ± 0.9 vs. 2.4 ± 1.4, 1.2 ± 0.9 vs. 2.2 ± 1.7 and 9.5 ± 6.8 vs. 15.8 ± 12.5, respectively, in surgical patients compared to non-surgical patients (all p < 0.05). Compared to baseline, after 12 months, a significant reduction was observed in the use of leflunomide, biological agents, combination treatments, and NSAIDs in both groups (p < 0.05 or p < 0.01). However, there was no difference in medication use between the 2 groups either at baseline or at the 12-month follow-up (all p > 0.05). Compared to non-surgical patients, in RA patients with obesity, weight loss after bariatric surgery was associated with lower disease activity. Medication tapering for RA in patients who underwent bariatric surgery was not superior to that in non-surgical patients.
Bees increase crop yield in an alleged pollinator-independent almond variety
Authors: Sáez Agustin , Aizen Marcelo A. , Medici Sandra , Viel Matias , Villalobos Ethel , Negri Pedro
Published: February 2020

Wild pollinators are declining and the number of managed honey bee colonies is growing slower than agricultural demands for pollination. Because of these contrasting trends in pollinator demand and availability, breeding programs for many pollinator-dependent crops have focused on reducing the need for pollinators. Although numerous crop varieties are now available in the market with the label of pollinator-independent, the real dependence of these varieties on pollinators is mostly unknown. We evaluated the hypothesis of pollinator independence in the Independence almond variety, the fastest growing variety in California that is the main almond production region in the world. In this presumed pollinator-independent variety, we measured the effect of honey bees on fruit set, yield, and kernel nutritional quality at tree level. Fruit set was 60% higher in bee-pollinated than bee-isolated trees, which translated into a 20% increase in kernel yield. Despite its effect on almond production, there was no evidence that bee visitation affected almond nutritional quality. Based on these results, we recommend the use of bees, whether they are wild or managed, to maximize yield even in self-fertile almond varieties.
Memorization of daily routines by children with Down syndrome assisted by a playful virtual environment
Authors: da Cruz Netto Ovidio Lopes , Rodrigues Silvia Cristina Martini , de Castro Marcus Vasconcelos , da Silva Diego Pereira , da Silva Robson Rodrigues , de Souza Richard Ribeiro Brancato , de Souza Adriana A. Ferreira , Bissaco Marcia Aparecida Silva
Published: February 2020

A child with Down syndrome, like any other child, may benefit from interacting with memory stimuli, but needs additional support and help. The use of special teaching methods, which add playfulness and use of the computer, can enhance the memory processes of these children. In this work, we present the virtual environment “Nossa Vida (Our Life)”, which was developed to assist children with Down syndrome to memorize action sequences of their daily routine. A daily routine memorization test (DRMT), consisting of a weekly reminder of typical daily routines completed by the children and parents, was performed before (pre-test) and after (post-test) the intervention. The work involved a multidisciplinary team and assessed the effectiveness of the test performed by 30 children with Down syndrome from APAE, a special education school for children with intellectual disabilities in São Paulo, Brazil. The children were separated into two groups (Experimental - GE and Control - GC) with homogeneity and normality of the data. Two hypotheses were tested in this study: H0 and H1, where: H0 = There is no statistical difference between memorizing daily tasks between individuals with Down syndrome who used our ludic virtual environment and those who used the conventional memory method.H1 = There is a difference between the group of subjects with Down Syndrome who used our virtual game environment and the group that did not use it in relation to memorizing the daily task. This produces t = -14.98 and p <0.0001, with H1 being accepted. The results showed that the EG presented significance in relation to the CG and the evolution mean of the children in the EG was 81.82% higher. According to experts (psychologist and pedagogue) from APAE and parents, the playful activities implemented in this virtual environment have been of great interest to children, who had fun, tested hypotheses and questioned them about the sequences of actions performed in their routine daily.