bluuebunny/crossref_metadata_2025 huggingface dataset:
Community-Based ART Service Delivery for Key Populations in Sub-Saharan Africa: Scoping Review of Outcomes Along the Continuum of HIV Care
Authors: Ibiloye Olujuwon , Masquillier Caroline , Jwanle Plang , Van Belle Sara , van Olmen Josefien , Lynen Lut , Decroo Tom
Published: January 2022

HIV positive key population (KP) often face health system and social barriers to HIV care. KP include sex workers, men who have sex with men, persons who inject drugs, transgender people, and people in prisons and other closed settings. Community-based ART service delivery (CBART) has the potential to increase access to antiretroviral treatment (ART) and enhance retention in care. This scoping review summarized the evidence on the effect of CBART along the continuum of HIV care among KP in sub-Saharan Africa. We searched Pubmed, Web of Science, Google scholar, and NGO websites for articles published between 2010 and April 2020. We synthesized the involvement of KP community members or lay providers in medical task provision, and outcomes along the continuum of HIV care. Of 3,330 records identified, 66 were eligible for full test screening, out of which 12 were included in the review. CBART for KP was provided through: (a) community drop-in-centres, (b) community drop-in-centres plus mobile team, or (c) community-based health centres. KP were engaged as peer educators and they provided services such as community mobilisation activities for HIV testing and ART, ART adherence counselling, and referral for ART initiation. Across the KP-CBART studies, outcomes in terms of ART uptake, adherence to ART, retention in care and viral suppression were at least as good as those obtained for KP attending facility-based care. KP-CBART was as effective as facility-based care. To achieve the UNAIDS 95–95–95 target in sub-Saharan Africa, national programmes should scale-up KP-CBART to complement facility-based care.
Bayesian Deep Learning for Spatial Interpolation in the Presence of Auxiliary Information
Authors: Kirkwood Charlie , Economou Theo , Pugeault Nicolas , Odbert Henry
Published: January 2022

Earth scientists increasingly deal with ‘big data’. For spatial interpolation tasks, variants of kriging have long been regarded as the established geostatistical methods. However, kriging and its variants (such as regression kriging, in which auxiliary variables or derivatives of these are included as covariates) are relatively restrictive models and lack capabilities provided by deep neural networks. Principal among these is feature learning: the ability to learn filters to recognise task-relevant patterns in gridded data such as images. Here, we demonstrate the power of feature learning in a geostatistical context by showing how deep neural networks can automatically learn the complex high-order patterns by which point-sampled target variables relate to gridded auxiliary variables (such as those provided by remote sensing) and in doing so produce detailed maps. In order to cater for the needs of decision makers who require well-calibrated probabilities, we also demonstrate how both aleatoric and epistemic uncertainty can be quantified in our deep learning approach via a Bayesian approximation known as Monte Carlo dropout. In our example, we produce a national-scale probabilistic geochemical map from point-sampled observations with auxiliary data provided by a terrain elevation grid. By combining location information with automatically learned terrain derivatives, our deep learning approach achieves an excellent coefficient of determination ($$R^{2} = 0.74$$

R
2

=
0.74

) and near-perfect probabilistic calibration on held-out test data. Our results indicate the suitability of Bayesian deep learning and its feature-learning capabilities for large-scale geostatistical applications where uncertainty matters.

Graphic Abstract
Strong spatial structuring of clonal genetic diversity within blackthorn (Prunus spinosa) hedgerows and woodlands
Authors: Brown James A. , Montgomery W. Ian , Provan Jim
Published: January 2022

Hedgerows are an important component of agricultural landscapes, but in recent years have increasingly faced threats such as habitat loss, land use change, climate change, invasive species, pests and plant pathogens. Given the potential importance of genetic diversity in countering these threats, and the spatial distribution of such diversity within and across natural populations, we analyzed levels and patterns of diversity in blackthorn (Prunus spinosa), a key component of many hedgerows. Twenty-one populations of blackthorn from a mixture of hedgerows and woodlands were genotyped for four nuclear and five chloroplast microsatellites. Three hundred twenty-one unique clonal genotypes were identified from 558 individuals analyzed, 207 of which were found in a single individual. With the exception of a single population that appears to have been planted recently from seed (Peatlands Park), all populations exhibited evidence of vegetative reproduction via suckering. Multi-ramet clones were highly spatially structured within populations, and ranged in size from < 1 to 258 m. These findings indicate that asexual reproduction is widespread in the populations of blackthorn studied. Although levels of clonality varied across study sites, there was clear spatial structuring of clones in each case. Such clonal organization should be taken into account in hedge management or where planting or replanting of hedgerows becomes necessary. Knowledge of the patterns and extent of spatial structuring of genotypes within potential source populations will allow the selection of genetically divergent material, rather than selection of clonal replicates of the same genotype.
A spatiotemporal analysis of cattle herd movement in relation to drinking-water sources: implications for Cryptosporidium control in rural Kenya
Authors: Floyd Jessica R. , Kwoba Emmah , Mwangi Thumbi , Okotto-Okotto Joseph , Wanza Peggy , Wardrop Nicola , Yu Weiyu , Wright Jim A.
Published: January 2022

Given the increasing evidence that domestic contact with livestock is a risk factor for child diarrhoea in low- and middle-income countries, there have been calls for greater quantification of human-livestock contact in such countries. This study aimed to quantify seasonality in cattle proximity to domestic water sources and household compounds and develop a preliminary landscape model of faecal deposition by cattle. A total of 120 cattle in smallholder herds in the Asembo area of Siaya County, Kenya, were tracked over 1 week in April 2018 to July 2018 and November 2018 to February 2019 using GPS tracking devices. Dung deposition and behaviour were observed among 33 cattle from these herds over 185.4 hours. Mean cattle home ranges were small at 3.78 km2 and 5.85 km2 in the wet and dry seasons, respectively. There were significant differences between seasons in home range size, distance travelled from the household, and time spent tethered, but not in the time spent at domestic water sources or home range overlap with other herds. On average, 0.76 dung deposition events/hour were observed, with higher frequency in bulls. Variation in cattle proximity to household compounds and water sources did not account for seasonal variation in child diarrhoea in this population. The preliminary landscape model of faecal deposition by cattle could be further developed to inform interventions for safe separation of livestock and people, such as fencing and separate water troughs.
Noch legitime Religionspraxis oder bereits problematisch?
Authors: Figlestahler Carmen , Schau Katja
Published: January 2022

Der Beitrag stellt besondere Herausforderungen im Umgang mit Ungewissheiten in der (sozial-)pädagogischen Präventions- und Distanzierungsarbeit im Bereich des islamistischen Extremismus dar. Fachkräfte müssen mit komplexen Problemlagen zwischen Radikalisierung und antimuslimischen Ausgrenzungen umgehen, ergebnisoffene Entwicklungen in der Jugendphase ihrer Adressat_innen abschätzen und wirkmächtige Kategorisierungen reflektieren. Auch in der Kooperation mit muslimischen Trägern wird die Ungewissheit, mit geeigneten Partnern zusammen zu arbeiten, durch polarisierte gesellschaftliche Debatten und insbesondere die sogenannte Kontaktschuld erschwert.
On a numerical bifurcation analysis of a particle reaction-diffusion model for a motion of two self-propelled disks
Authors: Yasugahira Yusuke , Nagayama Masaharu
Published: January 2022

Theoretical analysis using mathematical models is often used to understand a mechanism of collective motion in a self-propelled system. In the experimental system using camphor disks, several kinds of characteristic motions have been observed due to the interaction of two camphor disks. In this paper, we understand the emergence mechanism of the motions caused by the interaction of two self-propelled bodies by analyzing the global bifurcation structure using the numerical bifurcation method for a mathematical model. Finally, it is also shown that the irregular motion, which is one of the characteristic motions, is chaotic motion and that it arises from periodic bifurcation phenomena and quasi-periodic motions due to torus bifurcation.
Dynamic whole-body FDG-PET imaging for oncology studies
Authors: Tamaki Nagara , Kotani Tomoya , Nishimura Motoki , Kaji Tomohito
Published: January 2022

Introduction

Recent PET/CT systems have improved sensitivity and spatial resolution by smaller PET detectors and improved reconstruction software. In addition, continuous-bed-motion mode is now available in some PET systems for whole-body PET imaging. In this review, we describe the advantages of dynamic whole-body FDG-PET in oncology studies.

Methods

PET–CT imaging was obtained at 60 min after FDG administration. Dynamic whole-body imaging with continuous bed motion in 3 min each with flow motion was obtained over 400 oncology cases. For routine image analysis, these dynamic phases (usually four phases) were summed as early FDG imaging. The image quality of each serial dynamic imaging was visually evaluated. In addition, changes in FDG uptake were analyzed in consecutive dynamic imaging and also in early delayed (90 min after FDG administration) time point imaging (dual-time-point imaging; DTPI). Image interpretation was performed by consensus of two nuclear medicine physicians.

Result

All consecutive dynamic whole-body PET images of 3 min duration had acceptable image quality. Many of the areas with physiologically high FDG uptake had altered uptake on serial images. On the other hand, most of the benign and malignant lesions did not show visual changes on serial images. In the study of 60 patients with suspected colorectal cancer, unchanged uptake was noted in almost all regions with pathologically proved FDG uptake, indicating high sensitivity with high negative predictive value on both serial dynamic imaging and on DTPI. We proposed another application of serial dynamic imaging for minimizing motion artifacts for patients who may be likely to move during PET studies.

Discussion

Dynamic whole-body imaging has several advantages over the static imaging. Serial assessment of changes in FDG uptake over a short period of time is useful for distinguishing pathological from physiological uptake, especially in the abdominal regions. These dynamic PET studies may minimize the need for DPTI. In addition, continuous dynamic imaging has the potential to reduce motion artifacts in patients who are likely to move during PET imaging. Furthermore, kinetic analysis of the FDG distribution in tumor areas has a potential for precise tissue characterization.

Conclusion

Dynamic whole-body FDG-PET imaging permits assessment of serial FDG uptake change which is particularly useful for differentiation of pathological uptake from physiological uptake with high diagnostic accuracy. This imaging can be applied for minimizing motion artifacts. Wide clinical applications of such serial, dynamic whole-body PET imaging is expected in oncological studies in the near future.
Potential of Seaweed Extract on Growth, Physiological, Cytological and Biochemical Parameters of Wheat (Triticum aestivum L.) Seedlings
Authors: Hamouda Marwa M. , Saad-Allah Khalil M. , Gad Dina
Published: January 2022

Synthetic fertilizers are widely employed in agriculture relative to biofertilizers. Long-term use affects soil fertility, plant vigor, human and livestock health, and the soil microbial community. Seaweeds were employed as biofertilizers in sustainable agriculture to overcome this issue and boost the agricultural productivity. Therefore, the current study investigates the effect of wheat seeds priming with the aqueous extracts of Ulva linza or Corallina officinalis seaweeds at various concentrations (5, 10, 15, 20, and 30%). Wheat grains were primed with seaweed extracts and grown in petri dishes, and the germination rate, growth attributes, physiological parameters, cytological traits, and molecular analyses were evaluated. The physico-chemical characterization revealed that U. linza possessed higher levels of ash, soluble proteins, and sugars, as well as essential macronutrients and amino acids, than C. officinalis. Seedling growth parameters, physiological characteristics, and mitotic index all showed a substantial increase in low concentrations of both extracts when compared to the control. Higher concentrations, on the other hand, exhibited an inhibitory effect as well as certain chromosomal abnormalities. In the treated seedlings, new proteins were expressed, which could be owing to the activity of bioactive components in the extracts. As compared to untreated seedlings, PCR-RAPD analysis utilizing five markers revealed that both seaweed extracts triggered low and high molecular weight DNA fragments, as well as fragments specific to each extract. Seaweed extracts could be employed as an environmentally friendly and soil-safe alternative to typical chemical fertilizers.
Outcomes and antibiotic use in patients with coronavirus disease 2019 (COVID-19) admitted to an intensive care unit
Authors: Petteys Megan M. , Medaris Leigh Ann , Williamson Julie E. , Soman Rohit S. , Denmeade Travis A. , Anderson William E. , Leonard Michael K. , Polk Christopher M.
Published: January 2022

Antibiotic overuse is high in patients hospitalized with coronavirus disease 2019 (COVID-19) despite a low documented prevalence of bacterial infections in many studies. In this study evaluating 65 COVID-19 patients in the intensive care unit, empiric broad-spectrum antibiotics were often overutilized with an inertia to de-escalate despite negative culture results.
Barriers and solutions to developing and maintaining research networks during a pandemic: An example from the iELEVATE perinatal network
Authors: Santillan Donna A. , Brandt Debra S. , Sinkey Rachel , Scheib Sheila , Peterson Susan , LeDuke Rachel , Dimperio Lisa , Cherek Cindy , Varsho Angela , Granza Melissa , Logan Kim , Hunter Stephen K. , Knosp Boyd M. , Davis Heather A. , Spring Joseph C. , Piehl Debra , Makkapati Rani , Doering Thomas , Harris Stacy , Day Lyndsey , Eder Milton , Winokur Patricia , Santillan Mark K.
Published: January 2022

Introduction:

To improve maternal health outcomes, increased diversity is needed among pregnant people in research studies and community surveillance. To expand the pool, we sought to develop a network encompassing academic and community obstetrics clinics. Typical challenges in developing a network include site identification, contracting, onboarding sites, staff engagement, participant recruitment, funding, and institutional review board approvals. While not insurmountable, these challenges became magnified as we built a research network during a global pandemic. Our objective is to describe the framework utilized to resolve pandemic-related issues.

Methods:

We developed a framework for site-specific adaptation of the generalized study protocol. Twice monthly video meetings were held between the lead academic sites to identify local challenges and to generate ideas for solutions. We identified site and participant recruitment challenges and then implemented solutions tailored to the local workflow. These solutions included the use of an electronic consent and videoconferences with local clinic leadership and staff. The processes for network development and maintenance changed to address issues related to the COVID-19 pandemic. However, aspects of the sample processing/storage and data collection elements were held constant between sites.

Results:

Adapting our consenting approach enabled maintaining study enrollment during the pandemic. The pandemic amplified issues related to contracting, onboarding, and IRB approval. Maintaining continuity in sample management and clinical data collection allowed for pooling of information between sites.

Conclusions:

Adaptability is key to maintaining network sites. Rapidly changing guidelines for beginning and continuing research during the pandemic required frequent intra- and inter-institutional communication to navigate.
INITIAL HUMAN COLONIZATION OF THE AMERICAS, REDUX
Authors: Fiedel Stuart J
Published: January 2022

The study of the peopling of the Americas has been transformed in the past decade by astonishing progress in paleogenomic research. Ancient genomes now show that Native American ancestors were formed in Siberia or the Amur region by admixture of ca. 15–30% Ancient North Eurasian genes with those of East Asians. The Anzick infant, buried with Clovis bifaces at 12,900 cal BP, belonged to a group that was ancestral to later Native Central and South Americans. Fishtail points, derived from Clovis, mark the arrival and rapid expansion of Clovis-descended Paleoindians across South America, also evident in the sharp increase of radiocarbon dates, continent-wide, at 13,000–12,500 cal BP. In both North and South America, extinction of most genera of megafauna was virtually simultaneous with Paleoindian expansion. Human hunting must have been involved, perhaps in concert with other indirect impacts. Contrary to the alternative bolide impact theory, there is no evidence of a dramatic human population decline after 12,800 cal BP. Ancient genomes show that divergent lithic traditions after 13,000 cal BP need not be attributed to a separate Pacific Rim migration stream. Several recent finds raise the possibility that pre-Clovis people might have reached the Americas before 20,000 cal BP, but these precursors must have either failed to thrive, or were ultimately replaced by proto-Clovis or Clovis people. Consilient paleogenomic and archaeological data indicate that initial colonization by Paleoindian ancestors of living Native Americans occurred after 14,500 cal BP.
Trump and the Shifting Meaning of “Conservative”: Using Activists’ Pairwise Comparisons to Measure Politicians’ Perceived Ideologies
Authors: HOPKINS DANIEL J. , NOEL HANS
Published: January 2022

Although prior scholarship has made considerable progress in measuring politicians’ positions, it has only rarely considered voters’ or activists’perceptionsof those positions. Here, we present a novel measure of U.S. senators’ perceived ideologies derived from 9,030 pairwise comparisons elicited from party activists in three 2016 YouGov surveys. By focusing on activists, we study a most-likely case for perceiving within-party ideological distinctions. We also gain empirical leverage from Donald Trump’s nomination and heterodox positions on some issues. Our measure of perceived ideology is correlated withnominatebut differs in informative ways: senators with very conservative voting records were sometimes perceived as less conservative if they did not support Trump. A confirmatory test shows these trends extended into 2021. Even among activists, perceived ideology appears to be anchored by prominent people as well as policy positions.
NONPARAMETRIC ESTIMATION OF GENERALIZED TRANSFORMATION MODELS WITH FIXED EFFECTS
Authors: Chen Songnian , Lu Xun , Wang Xi
Published: January 2022

This paper considers a generalized panel data transformation model with fixed effects where the structural function is assumed to be additive. In our model, no parametric assumptions are imposed on the transformation function, the structural function, or the distribution of the idiosyncratic error term. The model is widely applicable and includes many popular panel data models as special cases. We propose a kernel-based nonparametric estimator for the structural function. The estimator has a closed-form solution and is easy to implement. We study the asymptotic properties of our estimator and show that it is asymptotically normally distributed. The Monte Carlo simulations demonstrate that our new estimator performs well in finite samples.
Improving parenting, child attachment, and externalizing behaviors: Meta-analysis of the first 25 randomized controlled trials on the effects of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline
Authors: van IJzendoorn Marinus H. , Schuengel Carlo , Wang Qiang , Bakermans-Kranenburg Marian J.
Published: January 2022

Improving parenting, child attachment, and externalizing behaviors: Meta-analysis of the first 25 randomized controlled trials on the effects of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD). VIPP-SD combines support of parental sensitive responsiveness with coaching parents in sensitive limit setting. Here, we present meta-analyses of 25 RCTs conducted with more than 2,000 parents and caregivers. Parents or children had various risks. We examined its effectiveness in promoting parental cognitions and behavior regarding sensitive parenting and limit setting, in promoting secure child–parent attachment, and reducing externalizing child behavior. Web of Science, MEDLINE, PubMed, and recent reviews were searched for relevant trials (until May 10, 2021). Multilevel meta-analysis with META, METAFOR, and DMETAR in R took account of the 3-level structure of the datasets (studies, participants, measures). The meta-analyses showed substantial combined effect sizes for parenting behavior (r = .18) and attitudes (r = .16), and for child attachment security (r = .23), but not for child externalizing behavior (r = .07). In the subset of studies examining effects on both parenting and attachment, the association between effect sizes for parenting and for attachment amounted to r = .48. We consider the way in which VIPP-SD uses video-feedback an active intervention component. Whether VIPP-SD indeed stimulates secure attachment through enhanced positive parenting remains an outstanding question for further experimental study and individual participant data meta-analysis.
Interpretation of the Altitudinal Variation in the Martian Ionosphere Longitudinal Wave‐3 Structure
Authors: Wan Weixing , Zhou Xu , Yue Xinan , Wei Yong , Ding Feng , Ren Zhipeng
Published: January 2022

Using the electron density profiles from Mars Global Surveyor Radio Occultation observations, the ionospheric longitudinal wave‐3 (WN3) structure with different frequencies is investigated. The semidiurnal component is the dominant component for the entire Mars ionosphere profile at northern high latitudes. Both diurnal and semidiurnal components manifest double peaks in altitudinal variations in amplitude, which are 5–15 km lower than the ionospheric M1 and M2 peaks. The phase generally increases with altitude and shows a rapid rate of increase around the M2 peak. To interpret the altitudinal variation in amplitude and phase, we then derive the tidal coupling equation to elucidate the impact of atmospheric tides on the Mars ionosphere. Under the assumption of photochemical equilibrium, the tidal coupling equation indicates that the log density gradient of electrons () critically modulates the ionospheric response to atmospheric tides. In the observations, a positive correlation between the profile and the amplitude of the WN3 structure at altitude is found. The solar longitude variation in the peaks also agrees with the vertical movement of the amplitude peaks of the WN3 structure along the solar longitude. The rapid phase increase corresponds to the abrupt decrease in around the M2 peak. These observational results agree with the tidal coupling equation prediction, thereby supporting that the interpretation of in modulating the altitudinal variation in the WN3 structure is reasonable.
ArchKalmag14k: A Kalman‐Filter Based Global Geomagnetic Model for the Holocene
Authors: Schanner M. , Korte M. , Holschneider M.
Published: January 2022

We propose a global geomagnetic field model for the last 14 thousand years, based on thermoremanent records. We call the model ArchKalmag14k. ArchKalmag14k is constructed by modifying recently proposed algorithms, based on space‐time correlations. Due to the amount of data and complexity of the model, the full Bayesian posterior is numerically intractable. To tackle this, we sequentialize the inversion by implementing a Kalman‐filter with a fixed time step. Every step consists of a prediction, based on a degree dependent temporal covariance, and a correction via Gaussian process regression. Dating errors are treated via a noisy input formulation. Cross correlations are reintroduced by a smoothing algorithm and model parameters are inferred from the data. Due to the specific statistical nature of the proposed algorithms, the model comes with space and time‐dependent uncertainty estimates. The new model ArchKalmag14k shows less variation in the large‐scale degrees than comparable models. Local predictions represent the underlying data and agree with comparable models, if the location is sampled well. Uncertainties are bigger for earlier times and in regions of sparse data coverage. We also use ArchKalmag14k to analyze the appearance and evolution of the South Atlantic anomaly together with reverse flux patches at the core‐mantle boundary, considering the model uncertainties. While we find good agreement with earlier models for recent times, our model suggests a different evolution of intensity minima prior to 1650 CE. In general, our results suggest that prior to 6000 BCE the data is not sufficient to support global models.
GOSML: A Global Ocean Surface Mixed Layer Statistical Monthly Climatology: Means, Percentiles, Skewness, and Kurtosis
Authors: Johnson Gregory C. , Lyman John M.
Published: January 2022

Here we discuss a global ocean surface mixed layer statistical monthly climatology (GOSML) of depth, temperature, and salinity that includes means; variances; 5th, 50th, and 95th percentiles; as well as skewness and kurtosis. Ocean surface mixed layer properties are influenced by gravity and a wide variety of factors that operate over a wide variety of time scales. Mixed layer depths can shoal very quickly as a result of surface heating, precipitation, or “slumping” of horizontal density gradients. However, deepening the mixed layer in the presence of a strong pycnocline requires substantial buoyancy loss or strong wind mixing, which often takes more time. This pattern is clear in the annual cycle monthly mixed layer depth values, with deepening in the fall much slower than shoaling in the spring. The 95th percentile values are chosen as a reasonable indicator of ventilation depth, robust to extreme outliers. Mean mixed layer depths are on average 0.56 of 95th percentile mixed layer depths, with only 1% of values below 0.31% and 1% above 0.81. Over 71% of mixed layer depth distributions are skewed positive, usually when there are more shallow mixed layer depths than not and deep mixed layer tails are strong. Comparing 95th percentile depth conditions to mean values shows in late winter temperatures are generally lower in the subtropics and salinities generally higher in the subpolar regions, consistent with the importance of temperature in the midlatitudes and salinity in the higher latitudes in setting stratification.
Bonding formation and gas absorption using Au/Pt/Ti layers for vacuum packaging
Authors: Kariya Shingo , Matsumae Takashi , Kurashima Yuichi , Takagi Hideki , Hayase Masanori , Higurashi Eiji
Published: January 2022

In this study, we developed a metal multilayer that can provide hermetic sealing after degassing the assemblies and absorbing the residual gases in the package. A package without a leak path was obtained by the direct bonding of the Au/Pt/Ti layers. After packaging, annealing at 450 °C caused thermal diffusion of the Ti underlayer atoms to the inner surface, which led to absorption of the residual gas molecules. These results indicated that a wafer coated with a Au/Pt/Ti layer can provide hermetic sealing and absorb residual gases, which can simplify vacuum packaging processes in the electronics industry.
Real-world evidence of patients with metastatic castration-resistant prostate cancer treated with cabazitaxel: comparison with the randomized clinical study CARD
Authors: de Wit Ronald , Freedland Stephen J. , Oudard Stephane , Marinov Georgi , Capart Philippe , Combest Austin J. , Peterson Ryan , Ozatilgan Ayse , Morgans Alicia K.
Published: January 2022

Background

The CARD study demonstrated superiority of cabazitaxel over abiraterone/enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who received prior docetaxel and progressed ≤12 months on the alternative androgen-receptor-targeted agent (ARTA). The objective was to compare characteristics and treatment patterns of patients from a real-world dataset with the CARD population.

Methods

Real-world data were collected from Medimix Live TrackerTM, a retrospective, global oncology database of healthcare professional-reported electronic patient medical forms (2001–2019), with data from patients from Europe, USA, Brazil and Japan. The database contained patient, tumor and treatment information for 12,140 patients who received ≥1 line of treatment for mCRPC. A CARD-like cohort included patients treated with docetaxel, prior abiraterone/enzalutamide and cabazitaxel.

Results

A large proportion of patients received ≥2 lines of ARTA (35.1%) with 42% of patients who received a first-line ARTA receiving another ARTA in second line. Of the total patients, 452 were eligible for the CARD-like cohort. Median age of the CARD-like cohort was comparable to CARD (73 vs 70 years). The CARD-like cohort had unfavorable disease characteristics vs CARD: ECOG PS ≥ 2 (45% vs 4.7%); metastasis at diagnosis (46% vs 38%) and Gleason 8–10 (65% vs 57%). More patients in the CARD-like cohort received ARTA before docetaxel (48% vs 39%) and received the first ARTA for >12 months (30% vs 17%) compared with CARD. Despite more patients in the CARD-like cohort receiving the lower 20 mg/m2 dose of cabazitaxel (55% vs 21%), cabazitaxel treatment duration was similar (21.9 vs 22.0 weeks).

Conclusions

Sequential use of ARTA was frequent. Results indicate the CARD population is reflective of routine clinical practice and duration of response to cabazitaxel was similar in a real-world population.
European LeukemiaNet-defined primary refractory acute myeloid leukemia: the value of allogeneic hematopoietic stem cell transplant and overall response
Authors: Begna K. H. , Kittur J. , Gangat N. , Alkhateeb H. , Patnaik M. S. , Al-Kali A. , Elliott M. A. , Hogan W. J. , Litzow M. R. , Pardanani A. , Hanson C. A. , Ketterling R. P. , Tefferi A.
Published: January 2022

We sought to appraise the value of overall response and salvage chemotherapy, inclusive of allogeneic hematopoietic stem cell transplant (AHSCT), in primary refractory acute myeloid leukemia (prAML). For establishing consistency in clinical practice, the 2017 European LeukemiaNet (ELN) defines prAML as failure to attain CR after at least 2 courses of intensive induction chemotherapy. Among 60 consecutive patients (median age 63 years) correspondent with ELN-criteria for prAML, salvage was documented in 48 cases, 30/48 (63%) being administered intensive chemotherapy regimens and 2/48 consolidated with AHSCT as first line salvage. 13/48 (27%) attained response: CR, 7/13 (54%), CRi, 2/13 (15%), MLFS, 4/13 (31%). The CR/CRi rate was 9/48 (19%), with CR rate of 7/48 (15%). On univariate analysis, intermediate-risk karyotype was the only predictor of response (44% vs 17% in unfavorable karyotype; P = 0.04). Administration of any higher-dose (>1 g/m2) cytarabine intensive induction (P = 0.50), intensive salvage chemotherapy (P = 0.72), targeted salvage (FLT3 or IDH inhibitors) (P = 0.42), greater than 1 salvage regimen (P = 0.89), age < 60 years (P = 0.30), and de novo AML (P = 0.10) did not enhance response achievement, nor a survival advantage. AHSCT was performed in 12 patients with (n = 8) or without (n = 4) CR/CRi/MLFS. 1/2/5-year overall survival (OS) rates were 63%/38%/33% in patients who received AHSCT (n = 12) vs 27%/0%/0% in those who achieved CR/CRi/MLFS but were not transplanted (n = 5), vs 14%/0%/0% who were neither transplanted nor achieved CR/CRi/MLFS (n = 43; P < 0.001); the median OS was 18.6, 12.6 and 5.6 months, respectively. Although CR/CRi/MLFS bridged to AHSCT (n = 8), appeared to manifest a longer median OS (20 months), vs (13.4 months) for those with no response consolidated with AHSCT (n = 4), the difference was not significant P = 0.47. We conclude AHSCT as indispensable for securing long-term survival in prAML (p = 0.03 on multivariate analysis), irrespective of response achievement.
Changes in body composition in patients with malignant pleural mesothelioma and the relationship with activity levels and dietary intake
Authors: Jeffery Emily , Lee Y. C. Gary , Newton Robert U. , Lyons-Wall Philippa , McVeigh Joanne , Fitzgerald Deirdre B. , Straker Leon , Peddle-McIntyre Carolyn J.
Published: January 2022

Background

Skeletal muscle loss is common in advanced cancer and is associated with negative outcomes. In malignant pleural mesothelioma (MPM), no study has reported body composition changes or factors associated with these changes. This study aimed to describe changes in body composition over time and its relationship with activity levels, dietary intake and survival.

Methods

The study was a secondary analysis of data collected from a longitudinal observational study of patients with MPM. Participants completed 3-month assessments for up to 18 months. Participants with two dual-energy x-ray absorptiometry (DXA) scans were included. Changes in appendicular skeletal muscle mass (ASM) and total fat mass were used to categorise participants into phenotypes. Activity levels were measured with an ActiGraph GT3X+ accelerometer and energy and protein intake was measured with a 3-day food record and 24-h recall.

Results

Eighteen participants were included (89% men, mean age 68.9 ± 7.1 years). Median time between DXA was 91 [IQR 84–118] days. Compared to participants with ASM maintenance (n = 9), fewer participants with ASM loss (n = 9) survived ≥12 months from follow-up (p = 0.002). Participants with ASM loss increased sedentary time (p = 0.028) and decreased light activity (p = 0.028) and step count (p = 0.008). Activity levels did not change in participants with ASM maintenance (p > 0.05). Energy and protein intake did not change in either group (p > 0.05).

Conclusions

Muscle loss was associated with poorer survival and decreased activity levels. Interventions that improve physical activity or muscle mass could benefit patients with MPM.
Analysis of NIA and GSNOR family genes and nitric oxide homeostasis in response to wheat-leaf rust interaction
Authors: Hurali Deepak T. , Bhurta Ramesh , Tyagi Sandhya , Sathee Lekshmy , Sandeep Adavi B. , Singh Dalveer , Mallick Niharika , Vinod  , Jha Shailendra K.
Published: January 2022

Nitric oxide (NO) modulates plant response to biotic and abiotic stresses by S-nitrosylation-mediated protein post-translational modification. Nitrate reductase (NR) and S-nitrosoglutathione reductase (GSNOR) enzymes are essential for NO synthesis and the maintenance of Nitric oxide/S-nitroso glutathione (NO/GSNO) homeostasis, respectively. S-nitrosoglutathione, formed by the S-nitrosylation reaction of NO with glutathione, plays a significant physiological role as the mobile reservoir of NO. The genome-wide analysis identified nine NR(NIA) and three GSNOR genes in the wheat genome. Phylogenic analysis revealed that the nine NIA genes +were clustered into four groups and the 3 GSNORs into two groups. qRT-PCR expression profiling of NIAs and GSNORs was done in Chinese spring (CS), a leaf rust susceptible wheat line showing compatible interaction, and Transfer (TR), leaf rust-resistant wheat line showing incompatible interaction, post-inoculation with leaf rust pathotype 77–5 (121-R-63). All the NIA genes showed upregulation during incompatible interaction in comparison with the compatible reaction. The GSNOR genes showed a variable pattern of expression: the TaGSNOR1 showed little change, whereas TaGSNOR2 showed higher expression during the incompatible response. TaGSNOR3 showed a rise of expression both in compatible and incompatible reactions. Before inoculation and after 72 h of pathogen inoculation, NO localization was studied in both compatible and incompatible reactions. The S-nitrosothiol accumulation, NR, and glutathione reductase activity showed a consistent increase in the incompatible interactions. The results demonstrate that both NR and GSNOR plays significant role in defence against the leaf rust pathogen in wheat by modulating NO homeostasis or signalling.
Quadriceps physiological response during the 1-min sit-to-stand test in people with severe COPD and healthy controls
Authors: Gephine Sarah , Mucci Patrick , Bielmann Mathieu , Martin Mickael , Bouyer Laurent , Saey Didier , Maltais François
Published: January 2022

We compared quadriceps oxygenation and surface electromyography (sEMG) responses during the 1-min sit-to-stand (1STS) in 14 people with severe COPD and 12 controls, in whom cardiorespiratory response, near-infrared spectroscopy signals (oxy [Hb-Mb], deoxy [Hb-Mb], total [Hb-Mb], and SmO2) and sEMG signals of the quadriceps were recorded. Time duration of each sit-to-stand cycle and the total work performed during the 1STS were measured. The quadriceps oxygenation parameters were normalized by reporting their values according to the total work during 1STS. The rate of sit-to-stand maneuvers decelerated in people with COPD leading to smaller total work compared with controls. The pattern of quadriceps oxygenation response during 1STS was similar between groups. However, in COPD, the recovery after 1STS was characterized by larger overshoots in oxy [Hb-Mb], total [Hb-Mb], and SmO2. When corrected for the cumulative total work, the increase in muscle O2 extraction (deoxy [Hb-Mb]) during the first 30 s of recovery was greater in people with COPD compared to controls. Quadriceps sEMG changes suggestive of a fatiguing contraction pattern was observed only in people with COPD. All together, these results highlighted physiological misadaptation of people with severe COPD to the 1STS.
Essential oil from Lavandula angustifolia elicits expression of three SbWRKY transcription factors and defense-related genes against sorghum damping-off
Authors: Rashad Younes M. , Abdel Razik Elsayed S. , Darwish Doaa B.
Published: January 2022

Sorghum damping-off, caused byFusarium solani(Mart.) Sacc., is a serious disease which causes economic loss in sorghum production. In this study, antagonistic activity of lavender essential oil (EO) at 0.5, 0.75, 1.0, 1.25, 1.5, and 1.6% againstF. solaniwas studied in vitro. Their effects on regulation of threeSbWRKYtranscription factors, the response factorJERF3and eight defense-related genes, which mediate different signaling pathways, in sorghum were investigated. Effects of application under greenhouse conditions were also evaluated. The results showed that lavender EO possesses potent antifungal activity againstF. solani. A complete inhibition in the fungal growth was recorded for lavender EO at 1.6%. Gas chromatography–mass spectrometric analysis revealed that EO antifungal activity is most likely attributed to linalyl anthranilate, α-terpineol, eucalyptol, α-Pinene, and limonene. Observations using transmission electron microscopy revealed many abnormalities in the ultrastructures of the fungal mycelium as a response to treating with lavender EO, indicating that multi-mechanisms contributed to their antagonistic behavior. Results obtained from Real-time PCR investigations demonstrated that the genes studied were overexpressed, to varying extents in response to lavender EO. However,SbWRKY1was the highest differentially expressed gene followed byJERF3, which suggest they play primary role(s) in synchronously organizing the transcription-regulatory-networks enhancing the plant resistance. Under greenhouse conditions, treating of sorghum grains with lavender EO at 1.5% prior to infection significantly reduced disease severity. Moreover, the growth parameters evaluated, the activities of antioxidant enzymes, and total phenolic and flavonoid contents were all enhanced. In contrast, lipid peroxidation was highly reduced. Results obtained from this study support the possibility of using lavender EO for control of sorghum damping-off. However, field evaluation is highly needed prior to any usage recommendation.
A data-driven ultrasound approach discriminates pathological high grade prostate cancer
Authors: Akatsuka Jun , Numata Yasushi , Morikawa Hiromu , Sekine Tetsuro , Kayama Shigenori , Mikami Hikaru , Yanagi Masato , Endo Yuki , Takeda Hayato , Toyama Yuka , Yamaguchi Ruri , Kimura Go , Kondo Yukihiro , Yamamoto Yoichiro
Published: January 2022

Accurate prostate cancer screening is imperative for reducing the risk of cancer death. Ultrasound imaging, although easy, tends to have low resolution and high inter-observer variability. Here, we show that our integrated machine learning approach enabled the detection of pathological high-grade cancer by the ultrasound procedure. Our study included 772 consecutive patients and 2899 prostate ultrasound images obtained at the Nippon Medical School Hospital. We applied machine learning analyses using ultrasound imaging data and clinical data to detect high-grade prostate cancer. The area under the curve (AUC) using clinical data was 0.691. On the other hand, the AUC when using clinical data and ultrasound imaging data was 0.835 (p = 0.007). Our data-driven ultrasound approach offers an efficient tool to triage patients with high-grade prostate cancers and expands the possibility of ultrasound imaging for the prostate cancer detection pathway.
RBL2/DREAM-mediated repression of the Aurora kinase A/B pathway determines therapy responsiveness and outcome in p53 WT NSCLC
Authors: Duan Lei , Perez Ricardo E. , Calhoun Sarah , Maki Carl G.
Published: January 2022

Wild-type p53 is a stress-responsive transcription factor and potent tumor suppressor. P53 activates or represses genes involved in cell cycle progression or apoptosis in order to arrest the cell cycle or induce cell death. Transcription repression by p53 is indirect and requires repressive members of the RB-family (RB1, RBL1, RBL2) and formation of repressor complexes of RB1-E2F and RBL1/RBL2-DREAM. Many aurora kinase A/B (AURKA/B) pathway genes are repressed in a p53-DREAM-dependent manner. We found heightened expression of RBL2 and reduced expression of AURKA/B pathway genes is associated with improved outcomes in p53 wild-type but not p53 mutant non-small cell lung cancer (NSCLC) patients. Knockdown of p53, RBL2, or the DREAM component LIN37 increased AURKA/B pathway gene expression and reduced paclitaxel and radiation toxicity in NSCLC cells. In contrast, pharmacologic inhibition of AURKA/B or knockdown of AURKA/B pathway components increased paclitaxel and IR sensitivity. The results support a model in which p53-RBL2-DREAM-mediated repression of the AURKA/B pathway contributes to tumor suppression, improved tumor therapy responses, and better outcomes in p53 wild-type NSCLCs.
Statistical estimation of deltoid subcutaneous fat pad thickness: implications for needle length for vaccination
Authors: Sebro Ronnie
Published: January 2022

Current US Centers for Disease Control and Prevention intramuscular injection needle length guidelines for injection fo the deltoid muscle are based on weight and gender. The aims of this study are (1) to evaluate whether other biometric data (age, gender, height, weight and body mass index (BMI)) are better predictors of the thickness of the deltoid subcutaneous fat pad (DSFP) than weight and gender and (2) to evaluate the performance of the CDC weight-based needle length guidelines. This was a retrospective single center cohort study of 386 patients who underwent surveillance PET/CT between 01/01/2020 and 04/01/2021. Patient age, gender, height, weight, BMI and CT measurements of the DSFP were evaluated. DSFP was positively correlated with weight and BMI in men (r = 0.67, P < 0.001; r = 0.74, P < 0.001) and women (r = 0.69, P < 0.001; r = 0.75, P < 0.001) respectively. DSFP was negatively correlated with age in women (r =  − 0.19, P = 0.013). Age and BMI were better predictors of DSFP than weight. The best model to predict the DSFP is: $$DSFP in mm= 6.267199 -2.711159*Male + 0.228407*BMI + 0.012295*{BMI}^{2} -0.294211*BMI*Male -0.110063*Age + 0.085589*Age*Male$$

D
S
F
P
i
n
m
m
=
6.267199
-
2.711159

∗
M
a
l
e
+
0.228407

∗
B
M
I
+
0.012295

∗

BMI

2

-
0.294211

∗
B
M
I

∗
M
a
l
e
-
0.110063

∗
A
g
e
+
0.085589

∗
A
g
e

∗
M
a
l
e

A 1-inch needle is expected to reach the deltoid in 85.3% of women less than 200 pounds, and 98.6% of men less than 260 pounds. This rate differed between genders (P < 0.001, odds ratio (OR) 0.08, 95% CI (0.02, 0.29)). A 1.5-inch needle is expected to reach the deltoid in 76.7% of women greater than 200 pounds, and 75.0% of men greater than 260 pounds. Current CDC deltoid intramuscular injection needle length guidelines result in women and obese individuals being more likely to receive subcutaneous injections. Age and BMI based guidelines for needle length selection are more accurate.
Feeder-supported in vitro exercise model using human satellite cells from patients with sporadic inclusion body myositis
Authors: Li Yuqing , Chen Weijian , Ogawa Kazumi , Koide Masashi , Takahashi Tadahisa , Hagiwara Yoshihiro , Itoi Eiji , Aizawa Toshimi , Tsuchiya Masahiro , Izumi Rumiko , Suzuki Naoki , Aoki Masashi , Kanzaki Makoto
Published: January 2022

Contractile activity is a fundamental property of skeletal muscles. We describe the establishment of a “feeder-supported in vitro exercise model” using human-origin primary satellite cells, allowing highly-developed contractile myotubes to readily be generated by applying electrical pulse stimulation (EPS). The use of murine fibroblasts as the feeder cells allows biological responses to EPS in contractile human myotubes to be selectively evaluated with species-specific analyses such as RT-PCR. We successfully applied this feeder-supported co-culture system to myotubes derived from primary satellite cells obtained from sporadic inclusion body myositis (sIBM) patients who are incapable of strenuous exercise testing. Our results demonstrated that sIBM myotubes possess essentially normal muscle functions, including contractility development, de novo sarcomere formation, and contraction-dependent myokine upregulation, upon EPS treatment. However, we found that some of sIBM myotubes, but not healthy control myotubes, often exhibit abnormal cytoplasmic TDP-43 accumulation upon EPS-evoked contraction, suggesting potential pathogenic involvement of the contraction-inducible TDP-43 distribution peculiar to sIBM. Thus, our “feeder-supported in vitro exercise model” enables us to obtain contractile human-origin myotubes, potentially utilizable for evaluating exercise-dependent intrinsic and pathogenic properties of patient muscle cells. Our approach, using feeder layers, further expands the usefulness of the “in vitro exercise model”.