bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between duration of antimicrobial prophylaxis and postoperative outcomes after lumbar spine surgery
Authors: Porter Mary W. , Burdi William , Casavant Jonathan D. , Eastment McKenna C. , Tulloch-Palomino Luis G.
Published: February 2022

Objectives:

To describe the association between duration of antimicrobial prophylaxis (AMP) and 30-day surgical site infection (SSI), 7-day acute kidney injury (AKI), 90-day Clostridioides difficile infection (CDI), prolonged hospitalization, and 30-day reoperation after lumbar spine surgery for noninfectious indications, and to report adherence to current guidelines.

Design:

Survey.

Participants and setting:

The study cohort comprised 6,198 patients who underwent lumbar spine surgery for noninfectious indications across 137 Veterans’ Health Administration surgery centers between 2016 and 2020.

Methods:

Used univariate and multivariate logistic regression to determine the association between type and duration of AMP with 30-day SSI, 7-day AKI, 90-day CDI, prolonged hospitalization, and 30-day reoperation.

Results:

Only 1,160 participants (18.7%) received the recommended duration of AMP. On multivariate analysis, the use of multiple prophylactic antimicrobials was associated with increased odds of 90-day CDI (adjusted odds ratio [aOR], 5.5; 95% confidence interval [CI], 1.1–28.2) and 30-day reoperation (aOR, 2.3; 95% CI, 1.2–4.4). Courses of antimicrobials ≥3 days were associated with increased odds of prolonged hospitalization (aOR,1.8; 95% CI, 1.4–2.3) and 30-day reoperation (aOR, 3.5; 95% CI, 2.2–5.7). In univariate analysis, increasing days of AMP was associated with a trend toward increasing odds of 90-day CDI (cOR, 1.4; 95% CI, 1.0–1.8 per additional day; P = .056).

Conclusions:

Longer courses of AMP after lumbar spine surgery were associated with higher odds of CDI, prolonged hospitalization, and reoperation, but not with lower odds of SSI. However, adherence to the recommended duration of AMP is very low, hinting at a wide evidence-to-practice gap that needs to be addressed by spine surgeons and antimicrobial stewardship programs.
Characterising the mechanics of cell–cell adhesion in plants
Authors: Atakhani Asal , Bogdziewiez Léa , Verger Stéphane
Published: February 2022

Cell–cell adhesion is a fundamental feature of multicellular organisms. To ensure multicellular integrity, adhesion needs to be tightly controlled and maintained. In plants, cell–cell adhesion remains poorly understood. Here, we argue that to be able to understand how cell–cell adhesion works in plants, we need to understand and quantitatively measure the mechanics behind it. We first introduce cell–cell adhesion in the context of multicellularity, briefly explain the notions of adhesion strength, work and energy and present the current knowledge concerning the mechanisms of cell–cell adhesion in plants. Because still relatively little is known in plants, we then turn to animals, but also algae, bacteria, yeast and fungi, and examine how adhesion works and how it can be quantitatively measured in these systems. From this, we explore how the mechanics of cell adhesion could be quantitatively characterised in plants, opening future perspectives for understanding plant multicellularity.
Regional variations in child and mother’s characteristics influencing the use of insecticide treated net in Nigeria
Authors: Adejoh Samuel Ojima , Alabi Tunde A. , Ezechukwu Chidozie
Published: February 2022

Nigeria accounts for a quarter of malaria cases worldwide, which can be prevented with the use of insecticide treated nets (ITN). While studies have documented mother-related characteristics influencing use of ITN, regional variations in the influence of those factors are not well known. This study investigated nine factors (age, place of residence, education, religion, wealth, number of children in the household, sex of child, age of child and previous experience of child mortality) as possible predictors of use of ITN for children and how the associations vary across northern and southern parts of the country. The study utilised the 2015 Nigeria Malaria Indicator Survey, which comprised 6524 mothers (4009 from the north and 2151 from the south) aged 15-49. Bivariate and multivariate logistic regression models were fitted. It was found that, less than half (47.9%) of the respondents reported no access to a mosquito net in the north compared to 70.8% in the south. More than half (51.4%) of the northern respondents used insecticide treated net (ITN) for the child compared to 27.1% of southern mothers. When the variables are fitted together in the same model, place of residence, mother’s age, mother’s education, wealth, religion, number of children in the household and previous experience of child mortality were associated with the use of ITN. Regional variations exist in the influence of mother’s age, number of children in the household and previous experience of child mortality. It was submitted that mother’s characteristics are more important than the child’s factors in the use of ITN, and that, contrary to the theory of poor utilisation of health-related facilities in the north compared to the south, residents in the former have access to and use ITN more than their counterparts from the latter.
Synthetic Options and Implied Volatility for the Corporate Bond Market
Authors: Chen Steven Shu-Hsiu , Doshi Hitesh , Seo Sang Byung
Published: February 2022

We synthetically create option contracts on a corporate bond index using CDX swaptions, overcoming the limitations that stem from the lack of traded corporate bond options. Our approach allows us to estimate forward-looking moments concerning the corporate bond market in a model-free manner. By constructing an aggregate volatility measure and the associated variance risk premium, we examine the role of volatility risk in the corporate bond market. We highlight that the ex ante conditional second and higher moments we estimate from synthetic corporate bond options carry important implications for credit risk models, providing an extra basis for testing their validity.
On the electric field components in the collisionless plasmoid instability
Authors: Shahraki Pour M. , Hosseinpour M.
Published: February 2022

Using two-dimensional particle-in-cell simulations of collsionless plasmoid instability, the spatial and temporal variations of electric field components are investigated. The initial magnetic field is a Harris sheet which is added by a non-uniform perpendicular magnetic field (guide field). The effects of weak and medium guide field on the evolution of plasmoid instability and associated electric field are discussed with the input parameters of the solar corona with the condition

$\omega _{{\rm pe}}/\omega _{{\rm ce}}>1$

. As the current sheet elongates, magnetic reconnection in an X-point transits into the plasmoid instability, in which secondary X-points are formed and the consequent magnetic islands coalesce and form larger islands. During the instability, electric field components show two types of disturbances. (1) Transient waves, being excited very early, propagate mainly perpendicular to the current sheet and become damped as the instability proceeds to the nonlinear stage. Fourier analysis reveals that electromagnetic right- and left-hand polarized modes parallel to the initial magnetic field and also the extraordinary mode perpendicular to the current sheet are excited. Additionally, electron Langmuir and slow magnetosonic waves are observed in both directions. (2) Inside the current sheet, an electric field is generated by the plasmoid-dominated reconnection and grows in amplitude as the plasmoid instability proceeds. Moreover, in our study, the effects of amplitude-varying guide field on the spatial structure of electric field components outside and inside the current sheet are discussed. This study is valuable because understanding the spatial and temporal variation of the electric field is an essential prerequisite for the issue of particle acceleration in plasmoid-dominated magnetic reconnection.
Recommendations for the rehabilitation and release of wild-born, captive-raised cheetahs: the importance of pre- and post-release management for optimizing survival
Authors: Walker Eli H. , Verschueren Stijn , Schmidt-Küntzel Anne , Marker Laurie
Published: February 2022

Large carnivores are frequently released for conservation purposes, but early efforts struggled with inadequate monitoring and reporting, resulting in poor understanding of success. Although managers have improved release practice and monitoring, the use of orphaned, captive-raised large carnivores for release remains controversial because of the potential influence of captivity and the possible lack of natural behaviours in such individuals. Yet, rehabilitating orphaned individuals for release could help mitigate pressures on vulnerable wild populations. We present a case study on the rearing, rehabilitation and release of wild-born cheetahs Acinonyx jubatus that were rescued as orphans in Namibia. Our aim was to develop a methodological framework for cheetah release planning and post-release management based on the outcome of release trials conducted during 2004–2018. Between 2001 and 2012, we rescued 86 orphaned cheetahs from the wild. Of these, 36 (42%) were selected as release candidates. We found high success rates (75–96%) of selected individuals in achieving independence post-release. Additionally, annual survival estimates for rehabilitated individuals that reached independence were comparable to those of wild counterparts described by other studies, and some rehabilitated individuals reproduced with wild conspecifics. Our findings demonstrate the ability of wild-born, captive-raised cheetahs to transition back into the wild with strategic pre- and post-release management directed towards optimizing survival. This includes selecting appropriate release candidates, forming artificial coalitions, balancing habituation levels during captivity, choosing appropriate release sites, and providing strategic support during post-release monitoring. We encourage scientists and managers to implement and refine our protocol for rehabilitation throughout the cheetah's current and historic range.
Dissenting at the United Nations: Interaction orders and Venezuelan contestation practices (2015–16)
Authors: Albaret Mélanie , Brun Élodie
Published: February 2022

The Venezuelan participation in the United Nations Security Council (UNSC) in 2015 and 2016 was expected to be a challenge for the institution, as the Maduro government adopted controversial positions at the General Assembly (UNGA). However, Venezuela contestation line did not appear clearly at the UNSC. Drawing upon an in-depth qualitative study, Erving Goffman's work, and literature on contestation in international organisations (IOs), we interpret this apparent inconsistency from the concept of interaction order. We argue that the UNGA and the UNSC each constitutes a specific interaction order that influences the way contestation practices are channelled. The contestation practices Venezuelan representatives set up at the UNGA hardly work during the UNSC official sessions, where they adapt their practices to its interaction order. Venezuelan representatives also use informal and backstage actions to express their dissent, without avoiding being called into order. Venezuela's moderation at the UNSC results from an invisibilisation of contestation by interaction practices.
Teaching Computational Social Science for All
Authors: Kim Jae Yeon , Ng Yee Man Margaret
Published: February 2022

Computational methods have become an integral part of political science research. However, helping students to acquire these new skills is challenging because programming proficiency is necessary, and most political science students have little coding experience. This article presents pedagogical strategies to make transitioning from Excel, SPSS, orStatatoRor Python for data analytics less challenging and more exciting. First, it discusses two approaches for making computational methods accessible: showing the big picture and walking through the workflow. Second, a step-by-step guide for a typical course is provided using three examples: learning programming fundamentals, wrangling messy data, and communicating data analysis.
Political Budget Cycles in Autocracies: The Role of Religious Seasons and Political Collective Action
Authors: Mohamed Ahmed Ezzeldin
Published: February 2022

For autocrats ruling over religious populations as in many Muslim majority countries, threats of mass collective action and religious mobilization are risky to ignore, being potentially detrimental to authoritarian survival. Religious seasons, such as Ramadan, could raise the seriousness of such threats. Accordingly, incumbents might adopt expansionary fiscal policies to avoid the escalation of political discontent at these times. Focusing on Egypt's fiscal policy between 2006 and 2019, I find that although the religious season of Ramadan is associated with modest increases in government expenditure and welfare spending, this relationship is dependent on the level of political threats facing the regime. Government spending is higher in Ramadan's season when it is preceded by more episodes of anti-regime collective action. This evidence suggests that the interaction between the religious and political contexts could generate political budget cycles outside electoral seasons.
A response to yet another defence of ECT in the absence of robust efficacy and safety evidence
Authors: Read John
Published: February 2022

It is estimated that electroconvulsive therapy is still administered to approximately a million people a year. It involves passing enough electric current through the human brain, eight to twelve times, to cause convulsions, in the hope of somehow alleviating emotional suffering, primarily depression. There have only ever been 11 placebo-controlled studies (where general anaesthesia is administered but the electric shock is withheld), all of which were pre-1986, had very small sample sizes and were seriously methodologically flawed. Five of these studies found no difference between the two groups at the end of treatment, four found ECT produced better outcomes for some patients, and two produced mixed results, including one where psychiatrists' ratings produced a difference, but the ratings of nurses and patients did not. In the 80 years since the first ECT no studies have found any evidence that ECT is better than placebo beyond the end of treatment. Nevertheless, all five meta-analyses relying on these studies have somehow concluded that ECT is more effective than placebo despite the studies' multiple failings. Meanwhile, evidence of persistent or permanent memory loss in 12% to 55% of patients has accumulated. Attempts to highlight this failure of ECT proponents to provide robust evidence that their treatment is effective and safe are routinely dismissed, diminished, denied and denounced. This paper responds to one such attempt, by Drs Meechan, Laws, Young, McLoughlin and Jauhar, to discredit two systematic reviews of the eleven pre-1986 studies, in 2010 and 2019, the latter of which also reviewed five meta-analyses that had ignored the studies' failings. The criticisms and claims of the recent crtiique of the two systematic reviews are examined in detail, by the first author of both reviews, for accuracy, relevance and logic. The critique is found to include multiple errors, misrepresentations, omissions, inconsistencies and logical flaws. It is concluded that Meechan et al. fail to make a fact-based, coherent argument against suspending ECT pending a series of large, carefully designed placebo-controlled studies to establish whether ECT does have any beneficial effects against which to weigh the significant established adverse effects.
Positive Leaders Propagate Slower at Higher Altitudes: Experimental Evidence and Theoretical Explanation
Authors: He Hengxin , Liu Lipeng , Ding Yujian , Luo Bin , Chen Weijiang , Cheng Chen , Yin Yu , Shi Weidong
Published: February 2022

We provide the clearest experimental evidence to date that positive leader velocity decreases with the decline of air density in the troposphere. The experiments are conducted at altitudes of 4,300 m in Tibet and 53 m in Beijing using the long air gap discharge technique. Rigorous comparative studies are performed using synchronized measurement of positive leader velocity and current under different air densities and similar temperature and humidity conditions. The effect of reduced air density on positive leader velocity is analyzed with a detailed thermal‐hydrodynamic model. It is found that the widely used similarity law setting initial leader radius inversely proportional to air density does not hold in estimating positive leader speeds in the troposphere.
Laboratory Study of the Impact of the Surface Solitary Waves Created by the Internal Solitary Waves on Optical Imaging
Authors: Zhang Meng , Wang Jing , Li Zhixin , Liang Keda , Chen Xu
Published: February 2022

The effects of Surface Solitary Waves (SSWs), which are created by Internal Solitary Waves (ISWs), on optical imaging were investigated in this paper. We explored the connection between SSWs and optical images using simulations and experiments with calm water surface conditions. An experimental platform was built in a controlled laboratory environment where optical images and in‐situ wave data could be gathered simultaneously. SSWs created by different ISWs were successfully observed. The optical images revealed inverse bright and dark patterns for different ISW types (depression or elevation type). Based on theories and experimental results, simulation models of the ISWs and SSWs were built in Unigraphics NX. Using the illumination simulation function of Light Tools, the reason underlying the reversed patterns was explained by the irradiance distribution. Both the experiment and simulation indicated that the SSWs created by the ISWs affected the characteristics of optical images. To further explore how SSWs affect imaging, 16 experiments were designed to investigate the effects of ISW type, amplitude, and water density ratio. It is found that the relationship among the SSW amplitude, ISW amplitude, and density ratio was consistent with earlier studies. The relationships between imaging characteristics (grayscale differences and pattern widths) and the two types of SSWs were consistent.
The Role of the Irminger Current in the Irminger Sea Northward Transport Variability
Authors: Fried Nora , de Jong M. Femke
Published: February 2022

The Irminger Current (IC) on the western flank of the Reykjanes Ridge is an important contributor to the northward transport in the Atlantic Meridional Overturning Circulation. Here, we combine 28 years of Copernicus Marine Environment Monitoring Service (CMEMS) ocean reanalysis data with 6 years of mooring data to investigate variability in volume transport of the IC. We found a mean volume transport for the IC of 11.6 Sv between 1993 and 2020 revealing the dominance of the IC in the total Irminger Sea northward volume transport (20.3 Sv). We found a significant decrease (−3.7 Sv) in volume transport of the IC until 2011 followed by a steeper (but shorter, leading to +2.7 Sv) increase until 2020. These changes across the Irminger Sea section are dominated by the IC, which in turn are driven by changes in the density gradient across the Irminger Sea related to convection. On decadal and interannual time scales the IC volume transport is well correlated with the decrease in the sea surface height difference over the basin. In 2019, a temporary intensification of the western IC core led to an exceptionally strong volume transport of the IC with 20 Sv. This was caused by density changes within the IC boundaries due to the presence of mesoscale eddies. Thus, IC transport variability is a superposition of basin‐wide to local processes that influence the velocity field on different time scales.
Magnetic Stop Signs Show Birds the Way Home
Authors: Duncombe Jenessa
Published: February 2022

Just like salmon and sea turtles, these songbirds appear to be sensitive to shifts in the magnetic field.
Integrated microdevice with a windmill-like hole array for the clog-free, efficient, and self-mixing enrichment of circulating tumor cells
Authors: Li Hao , Li Jinze , Zhang Zhiqi , Guo Zhen , Zhang Changsong , Wang Zixu , Guo Qiuquan , Li Chao , Li Chuanyu , Yao Jia , Zheng Anran , Xu Jingyi , Gao Qingxue , Zhang Wei , Zhou Lianqun
Published: February 2022

Circulating tumor cells (CTCs) have tremendous potential to indicate disease progression and monitor therapeutic response using minimally invasive approaches. Considering the limitations of affinity strategies based on their cost, effectiveness, and simplicity, size-based enrichment methods that involve low-cost, label-free, and relatively simple protocols have been further promoted. Nevertheless, the key challenges of these methods are clogging issues and cell aggregation, which reduce the recovery rates and purity. Inspired by the natural phenomenon that the airflow around a windmill is disturbed, in this study, a windmill-like hole array on the SU-8 membrane was designed to perturb the fluid such that cells in a fluid would be able to self-mix and that the pressure acting on cells or the membrane would be dispersed to allow a greater velocity. In addition, based on the advantages of fluid coatings, a lipid coating was used to modify the membrane surface to prevent cell aggregation and clogging of the holes. Under the optimal conditions, recovery rates of 93% and 90% were found for A549 and HeLa cells in a clinical simulation test of our platform with a CTC concentration of 20–100 cells per milliliter of blood. The white blood cell (WBC) depletion rate was 98.7% (n = 15), and the CTC detection limit was less than 10 cells per milliliter of blood (n = 6). Moreover, compared with conventional membrane filtration, the advantages of the proposed device for the rapid (2 mL/min) and efficient enrichment of CTCs without clogging were shown both experimentally and theoretically. Due to its advantages in the efficient, rapid, uniform, and clog-free enrichment of CTCs, our platform offers great potential for metastatic detection and therapy analyses.
Niche partitioning of the ubiquitous and ecologically relevant NS5 marine group
Authors: Priest Taylor , Heins Anneke , Harder Jens , Amann Rudolf , Fuchs Bernhard M
Published: February 2022

Niche concept is a core tenet of ecology that has recently been applied in marine microbial research to describe the partitioning of taxa based either on adaptations to specific conditions across environments or on adaptations to specialised substrates. In this study, we combine spatiotemporal dynamics and predicted substrate utilisation to describe species-level niche partitioning within the NS5 Marine Group. Despite NS5 representing one of the most abundant marine flavobacterial clades from across the world’s oceans, our knowledge on their phylogenetic diversity and ecological functions is limited. Using novel and database-derived 16S rRNA gene and ribosomal protein sequences, we delineate the NS5 into 35 distinct species-level clusters, contained within four novel candidate genera. One candidate species, “Arcticimaribacter forsetii AHE01FL”, includes a novel cultured isolate, for which we provide a complete genome sequence—the first of an NS5—along with morphological insights using transmission electron microscopy. Assessing species’ spatial distribution dynamics across the Tara Oceans dataset, we identify depth as a key influencing factor, with 32 species preferring surface waters, as well as distinct patterns in relation to temperature, oxygen and salinity. Each species harbours a unique substrate-degradation potential along with predicted substrates conserved at the genus-level, e.g. alginate in NS5_F. Successional dynamics were observed for three species in a time-series dataset, likely driven by specialised substrate adaptations. We propose that the ecological niche partitioning of NS5 species is mainly based on specific abiotic factors, which define the niche space, and substrate availability that drive the species-specific temporal dynamics.
Cold atmospheric plasma differentially affects cell renewal and differentiation of stem cells and APC-deficient-derived tumor cells in intestinal organoids
Authors: Hadefi Alia , Leprovots Morgane , Thulliez Max , Bastin Orianne , Lefort Anne , Libert Frédérick , Nonclercq Antoine , Delchambre Alain , Reniers François , Devière Jacques , Garcia Marie-Isabelle
Published: February 2022

Cold atmospheric plasma (CAP) treatment has been proposed as a potentially innovative therapeutic tool in the biomedical field, notably for cancer due to its proposed toxic selectivity on cancer cells versus healthy cells. In the present study, we addressed the relevance of three-dimensional organoid technology to investigate the biological effects of CAP on normal epithelial stem cells and tumor cells isolated from mouse small intestine. CAP treatment exerted dose-dependent cytotoxicity on normal organoids and induced major transcriptomic changes associated with the global response to oxidative stress, fetal-like regeneration reprogramming, and apoptosis-mediated cell death. Moreover, we explored the potential selectivity of CAP on tumor-like Apc-deficient versus normal organoids in the same genetic background. Unexpectedly, tumor organoids exhibited higher resistance to CAP treatment, correlating with higher antioxidant activity at baseline as compared to normal organoids. This pilot study suggests that the ex vivo culture system could be a relevant alternative model to further investigate translational medical applications of CAP technology.
The lncRNA TCONS_00021785/miR-21-5p/Trim33 axis regulates VMP1-mediated zymophagy, reduces the activation of trypsinogen, and promotes acinar cell recovery
Authors: Wang Qiang , Yu Jingjing , Gao Wenqi , Sun Yuanyuan , Liu Xuxu , Lv Zhenyi , Li Long , Xue Dongbo
Published: February 2022

In the early stage of acute pancreatitis, trypsinogen in acinar cells is activated, and the cells clear trypsin through zymophagy to avoid damage. Studies have shown that the substrate of zymophagy is ubiquitinated pancreatin, but the mechanism of pancreatin ubiquitination and the regulatory mechanism of zymophagy are not fully understood. Our results show that Trim33 can enhance cell viability, reduce cell necrosis, and reduce trypsinogen activation. Trim33 is a key E3 ligase enzyme that mediates trypsin ubiquitination. The results showed that overexpression of Trim33 can significantly increase VMP1 mRNA and protein levels. However, knocking down Trim33 produced the opposite effect, which indicates that Trim33, as a transcriptional mediator, affects zymophagy by regulating the expression of VMP1. In addition, we explored the transcriptional regulation mechanism of the Trim33 molecule. Our research shows that lncRNA TCONS_00021785 can competitively bind miR-21-5p to upregulate Trim33, thereby initiating enzyme autophagy and reducing zymogen activation.
Integrated single-cell multiomics analysis reveals novel candidate markers for prognosis in human pancreatic ductal adenocarcinoma
Authors: Fan Xiaoying , Lu Ping , Wang Hongwei , Bian Shuhui , Wu Xinglong , Zhang Yu , Liu Yang , Fu Danqi , Wen Lu , Hao Jihui , Tang Fuchou
Published: February 2022

The epigenomic abnormality of pancreatic ductal adenocarcinoma (PDAC) has rarely been investigated due to its strong heterogeneity. Here, we used single-cell multiomics sequencing to simultaneously analyze the DNA methylome, chromatin accessibility and transcriptome in individual tumor cells of PDAC patients. We identified normal epithelial cells in the tumor lesion, which have euploid genomes, normal patterns of DNA methylation, and chromatin accessibility. Using all these normal epithelial cells as controls, we determined that DNA demethylation in the cancer genome was strongly enriched in heterochromatin regions but depleted in euchromatin regions. There were stronger negative correlations between RNA expression and promoter DNA methylation in cancer cells compared to those in normal epithelial cells. Through in-depth integrated analyses, a set of novel candidate biomarkers were identified, including ZNF667 and ZNF667-AS1, whose expressions were linked to a better prognosis for PDAC patients by affecting the proliferation of cancer cells. Our work systematically revealed the critical epigenomic features of cancer cells in PDAC patients at the single-cell level.
Expanding the mutation and phenotype spectrum of MYH3-associated skeletal disorders
Authors: Zhao Sen , Zhang Yuanqiang , Hallgrimsdottir Sigrun , Zuo Yuzhi , Li Xiaoxin , Batkovskyte Dominyka , Liu Sen , Lindelöf Hillevi , Wang Shengru , Hammarsjö Anna , Yang Yang , Ye Yongyu , Wang Lianlei , Yan Zihui , Lin Jiachen , Yu Chenxi , Chen Zefu , Niu Yuchen , Wang Huizi , Zhao Zhi , Liu Pengfei , Qiu Guixing , Posey Jennifer E. , Wu Zhihong , Lupski James R. , Micule Ieva , Anderlid Britt-Marie , Voss Ulrika , Sulander Dennis , Kuchinskaya Ekaterina , Nordgren Ann , Nilsson Ola ,   Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Zhang Terry Jianguo , Grigelioniene Giedre , Wu Nan
Published: February 2022

Pathogenic variants inMYH3cause distal arthrogryposis type 2A and type 2B3 as well as contractures, pterygia and spondylocarpotarsal fusion syndromes types 1A and 1B. These disorders are ultra-rare and their natural course and phenotypic variability are not well described. In this study, we summarize the clinical features and genetic findings of 17 patients from 10 unrelated families with vertebral malformations caused by dominant or recessive pathogenic variants inMYH3. Twelve novel pathogenic variants inMYH3(NM_002470.4) were identified: three of them werede novoor inherited in autosomal dominant way and nine were inherited in autosomal recessive way. The patients had vertebral segmentation anomalies accompanied with variable joint contractures, short stature and dysmorphic facial features. There was a significant phenotypic overlap between dominant and recessiveMYH3-associated conditions regarding the degree of short stature as well as the number of vertebral fusions. All monoallelic variants caused significantly decreased SMAD3 phosphorylation, which is consistent with the previously proposed pathogenic mechanism of impaired canonical TGF-β signaling. Most of the biallelic variants were predicted to be protein-truncating, while one missense variant c.4244T>G,p.(Leu1415Arg), which was inherited in an autosomal recessive way, was found to alter the phosphorylation level of p38, suggesting an inhibition of the non-canonical pathway of TGF-β signaling. In conclusion, the identification of 12 novel pathogenic variants and overlapping phenotypes in 17 affected individuals from 10 unrelated families expands the mutation and phenotype spectrum ofMYH3-associated skeletal disorders. We show that disturbances of canonical or non-canonical TGF-β signaling pathways are involved in pathogenesis ofMYH3-associated skeletal fusion (MASF) syndrome.
A population study of clinically actionable genetic variation affecting drug response from the Middle East
Authors: Jithesh Puthen Veettil , Abuhaliqa Mohammed , Syed Najeeb , Ahmed Ikhlak , El Anbari Mohammed , Bastaki Kholoud , Sherif Shimaa , Umlai Umm-Kulthum , Jan Zainab , Gandhi Geethanjali , Manickam Chidambaram , Selvaraj Senthil , George Chinnu , Bangarusamy Dhinoth , Abdel-latif Rania , Al-Shafai Mashael , Tatari-Calderone Zohreh , Estivill Xavier , Pirmohamed Munir ,   The Qatar Genome Program Research Consortium, Abdel-latif Rania , Saqri Tariq Abu , Zaid Tariq Abu , Afifi Nahla , Al-Ali Rashid , Al-Khodor Souhaila , Al-Muftah Wadha , Al-Sarraj Yasser , Albagha Omar , Alkhayat Eiman , Alkuwari Fatima , Almabrazi Hakeem , Alshafai Mashael , Althani Asmaa , Alvi Muhammad , Badii Ramin , Badji Radja , Chouchane Lotfi , Darwish Dima , El Khouly Ahmed , Ennaifar Maryem , Estivill Xavier , Fadl Tasnim , Fakhro Khalid , Fethnou Eleni , Hamza Mehshad , Ismail Said I. , Jithesh Puthen V. , Khatib Mohammedhusen , Liu Wei , Lorenz Stephan , Mbarek Hamdi , Mokrab Younes , Pathare Tushar , Poolat Shafeeq , Qafoud Fatima , Vempalli Fazulur Rehaman , Saad Chadi , Suhre Karsten , Syed Najeeb , Tatari Zohreh , Temanni Ramzi , Tomei Sara , Yasin Heba
Published: February 2022

Clinical implementation of pharmacogenomics will help in personalizing drug prescriptions and alleviate the personal and financial burden due to inefficacy and adverse reactions to drugs. However, such implementation is lagging in many parts of the world, including the Middle East, mainly due to the lack of data on the distribution of actionable pharmacogenomic variation in these ethnicities. We analyzed 6,045 whole genomes from the Qatari population for the distribution of allele frequencies of 2,629 variants in 1,026 genes known to affect 559 drugs or classes of drugs. We also performed a focused analysis of genotypes or diplotypes of 15 genes affecting 46 drugs, which have guidelines for clinical implementation and predicted their phenotypic impact. The allele frequencies of 1,320 variants in 703 genes affecting 299 drugs or class of drugs were significantly different between the Qatari population and other world populations. On average, Qataris carry 3.6 actionable genotypes/diplotypes, affecting 13 drugs with guidelines for clinical implementation, and 99.5% of the individuals had at least one clinically actionable genotype/diplotype. Increased risk of simvastatin-induced myopathy could be predicted in ~32% of Qataris from the diplotypes of SLCO1B1, which is higher compared to many other populations, while fewer Qataris may need tacrolimus dosage adjustments for achieving immunosuppression based on the CYP3A5 diplotypes compared to other world populations. Distinct distribution of actionable pharmacogenomic variation was also observed among the Qatari subpopulations. Our comprehensive study of the distribution of actionable genetic variation affecting drugs in a Middle Eastern population has potential implications for preemptive pharmacogenomic implementation in the region and beyond.
A perspective on spaceflight associated neuro-ocular syndrome causation secondary to elevated venous sinus pressure
Authors: Bateman Grant Alexander , Bateman Alexander Robert
Published: February 2022

Spaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. There is controversy regarding SANS being similar to patients with idiopathic intracranial hypertension (IIH). IIH has been shown to be due to an elevation in venous sinus pressure. The literature suggests an increase in jugular vein pressure secondary to a headward shift of fluid occurs in SANS but this may not be enough to significantly alter the intracranial pressure (ICP). The literature regarding cardiac output and cerebral blood flow (CBF) in long-duration spaceflight is contradictory, however, more recent data suggests increased flow. Recent modelling has shown that an increase in CBF can significantly increase sinus pressure. The purpose of the present paper is to review the SANS vascular dynamics literature and through mathematical modelling suggest the possible underlying cause of SANS as an elevation in venous sinus pressure, secondary to the redistribution of fluids towards the head, together with a significant increase in pressure drop across the venous system related to the CBF.
Planning evaluation of a novel volume-based algorithm for personalized optimization of lung dose in VMAT for esophageal cancer
Authors: Hsu Chen-Xiong , Lin Kuan-Heng , Wang Shan-Ying , Tsai Wei-Ta , Chang Chiu-Han , Tien Hui-Ju , Shueng Pei-Wei , Wu Tung-Hsin , Mok Greta S. P.
Published: February 2022

Radiotherapy treatment planning (RTP) is time-consuming and labor-intensive since medical physicists must devise treatment plans carefully to reduce damage to tissues and organs for patients. Previously, we proposed the volume-based algorithm (VBA) method, providing optimal partial arcs (OPA) angle to achieve the low-dose volume of lungs in dynamic arc radiotherapy. This study aimed to implement the VBA for esophageal cancer (EC) patients and compare the lung dose and delivery time between full arcs (FA) without using VBA and OPA angle using VBA in volumetric modulated arc therapy (VMAT) plans. We retrospectively included 30 patients diagnosed with EC. RTP of each patient was replanned to 4 VMAT plans, including FA plans without (FA-C) and with (FA + C) dose constraints of OARs and OPA plans without (OPA-C) and with (OPA + C) dose constraints of OARs. The prescribed dose was 45 Gy. The OARs included the lungs, heart, and spinal cord. The dose distribution, dose-volume histogram, monitor units (MUs), delivery time, and gamma passing rates were analyzed. The results showed that the lung V5 and V10 in OPA + C plans were significantly lower than in FA + C plans (p < 0.05). No significant differences were noted in planning target volume (PTV) coverage, lung V15, lung V20, mean lung dose, heart V30, heart V40, mean heart dose, and maximal spinal cord dose between FA + C and OPA + C plans. The delivery time was significantly longer in FA + C plans than in OPA + C plans (237 vs. 192 s, p < 0.05). There were no significant differences between FA + C and OPA + C plans in gamma passing rates. We successfully applied the OPA angle based on the VBA to clinical EC patients and simplified the arc angle selection in RTP. The VBA could provide a personalized OPA angle for each patient and effectively reduce lung V5, V10, and delivery time in VMAT.
BODIPY nanoparticles functionalized with lactose for cancer-targeted and fluorescence imaging-guided photodynamic therapy
Authors: Mai Duy Khuong , Kim Chanwoo , Lee Joomin , Vales Temmy Pegarro , Badon Isabel Wen , De Koushitak , Cho Sung , Yang Jaesung , Kim Ho-Joong
Published: February 2022

A series of four lactose-modified BODIPY photosensitizers (PSs) with different substituents (-I, -H, -OCH3, and -NO2) in the para-phenyl moiety attached to the meso-position of the BODIPY core were synthesized; the photophysical properties and photodynamic anticancer activities of these sensitizers were investigated, focusing on the electronic properties of the different substituent groups. Compared to parent BODIPY H, iodine substitution (BODIPY I) enhanced the intersystem crossing (ISC) to produce singlet oxygen (1O2) due to the heavy atom effect, and maintained a high fluorescence quantum yield (ΦF) of 0.45. Substitution with the electron-donating methoxy group (BODIPY OMe) results in a significant perturbation of occupied frontier molecular orbitals and consequently achieves higher 1O2 generation capability with a high ΦF of 0.49, while substitution with the electron-withdrawing nitro group (BODIPY NO2) led a perturbation of unoccupied frontier molecular orbitals and induces a forbidden dark S1 state, which is negative for both fluorescence and 1O2 generation efficiencies. The BODIPY PSs formed water-soluble nanoparticles (NPs) functionalized with lactose as liver cancer-targeting ligands. BODIPY I and OMe NPs showed good fluorescence imaging and PDT activity against various tumor cells (HeLa and Huh-7 cells). Collectively, the BODIPY NPs demonstrated high 1O2 generation capability and ΦF may create a new opportunity to develop useful imaging-guided PDT agents for tumor cells.
Home-based, supervised, and mixed exercise intervention on functional capacity and quality of life of colorectal cancer patients: a meta-analysis
Authors: Kraemer Mauricio Beitia , Priolli Denise Gonçalves , Reis Ivan Gustavo Masseli , Pelosi Andrea Corazzi , Garbuio Ana Luíza Paula , Messias Leonardo Henrique Dalcheco
Published: February 2022

This systematic review and meta-analysis of randomized controlled trials tested the effects of home-based, supervised, or mixed exercise interventions on the functional capacity (FC) and quality of life (QoL) in colorectal cancer patients. A literature search was performed using the PubMed, Embase, Cochrane, and Medline databases. Two reviewers screened the literature through March 10, 2021 for studies related to exercise and colorectal cancer. Of the 1161 screened studies in the initial search, 13 studies met the eligibility criteria (home-based = 6 studies; supervised or mixed = 7 studies). Overall, 706 patients were enrolled in the trials, and 372 patients were submitted to home-based, supervised, or mixed exercise intervention. The overall results from the main meta-analysis showed a significant effect regarding supervised or mixed intervention (6 studies; p = 0.002; I2 = 43%; PI 0.41–1.39); however, no significant effect was observed for home-based intervention (5 studies; p = 0.05; I2 = 25%; PI − 0.34–0.76). A sensitivity analysis based on studies with intervention adherence ≥ 80% (home-based = 3 studies; supervised or mixed = 4 studies) revealed that home-based intervention or intervention entirely supervised or with some level of supervision (mixed) are effective in improving the QoL and FC of CRC patients. In summary, this meta-analysis verified that supervised and home-based exercise can modify QoL and FC when intervention adherence ≥ 80%. Regardless of the supervision characteristics, future RCTs are strongly encouraged to provide a detailed description of the exercise variables in physical interventions for CRC prescription. This perspective will allow a refined exercise prescription for patients with CRC, mainly according to their clinical status.
Early heart rate variability evaluation enables to predict ICU patients’ outcome
Authors: Bodenes Laetitia , N’Guyen Quang-Thang , Le Mao Raphaël , Ferrière Nicolas , Pateau Victoire , Lellouche François , L’Her Erwan
Published: February 2022

Heart rate variability (HRV) is a mean to evaluate cardiac effects of autonomic nervous system activity, and a relation between HRV and outcome has been proposed in various types of patients. We attempted to evaluate the best determinants of such variation in survival prediction using a physiological data-warehousing program. Plethysmogram tracings (PPG) were recorded at 75 Hz from the standard monitoring system, for a 2 h period, during the 24 h following ICU admission. Physiological data recording was associated with metadata collection. HRV was derived from PPG in either the temporal and non-linear domains. 540 consecutive patients were recorded. A lower LF/HF, SD2/SD1 ratios and Shannon entropy values on admission were associated with a higher ICU mortality. SpO2/FiO2 ratio and HRV parameters (LF/HF and Shannon entropy) were independent correlated with mortality in the multivariate analysis. Machine-learning using neural network (kNN) enabled to determine a simple decision tree combining the three best determinants (SDNN, Shannon Entropy, SD2/SD1 ratio) of a composite outcome index. HRV measured on admission enables to predict outcome in the ICU or at Day-28, independently of the admission diagnosis, treatment and mechanical ventilation requirement.

Trial registration: ClinicalTrials.gov identifier NCT02893462.
Mechanical and optimization studies of polypropylene hybrid biocomposites
Authors: Adediran Adeolu A. , Akinwande Abayomi A. , Balogun Oluwatosin A. , Bello Oladele S. , Akinbowale Miracle K. , Adesina Olanrewaju S. , Ojo Ayotunde A.
Published: February 2022

Towards developing a polymeric matrix characterized by high strength to cost ratio, polypropylene (PP) was hybridized with low-cost particulate snail shell (PSS) and kenaf fiber (KF) via compression moulding at 180 °C and 0.2 MPa. The developed composites were grouped into three and labeled as mix 2, 4, and 10. Each group entailed the blend of 5, 10, 20, and 30 wt% KF with 2, 4, 10 wt% PSS respectively. From the results, it is observed that the hardness value was enhanced by the blend of 5 to 30 wt% KF and 2, 4, and 10 wt% PSS. However, 2 wt% PSS mix with 5 to 30 wt% KF resulted in progressive improvement in impact, compressive, flexural, and tensile strengths values. The 4 wt% PSS yielded consecutive increase in impact, compressive and flexural strength when combined with 5 and 10 wt% KF. However, it was observed that subsequent addition of 20 and 30 wt% KF led to a marginal reduction in the strength values. The tensile strength attained optimum value when 4 wt% PSS was commixed with 30 wt% KF. Conversely, the combinations of 10 wt% PSS with 5, 10, 20, and 30 wt% KF had no significant improvement to the mechanical properties of PSS/KF-bio-PP composite (except for hardness) siring strength decrease. Taguchi optimization revealed that the collage of 4 wt% PSS and 10 wt% KF presented optimum mix for hybrid bio-PP composite.
An improved farmland fertility algorithm for many-objective optimization problems
Authors: Wang Yanjiao , Gao Peng , Chen Ye
Published: February 2022

Recent studies on many-objective optimization problems (MaOPs) have tended to employ some promising evolutionary algorithms with excellent convergence accuracy and speed. However, difficulties in scalability upon MaOPs including the selection of leaders, etc., are encountered because the most evolutionary algorithms are proposed for single-objective optimization. To further improve the performance of many-objective evolutionary algorithms in solving MaOPs when the number of the objectives increases, this paper proposes a many-objective optimization algorithm based on the improved Farmland Fertility algorithm (MOIFF). In MOIFF, a novel bio-inspired meta heuristic method proposed in 2018, called Farmland Fertility algorithm (FF), is employed to serve as the optimization strategy. In order to handle MaOPs effectively, FF has been tailored from the following aspects. An individual fitness assessment approach based on cumulative ranking value has been proposed to distinguish the quality of each individual; a novel method based on individual cumulative ranking value to constitute and update the global memory and local memory of each individual is proposed, and a hybrid subspace search and full space search method has been designed to update individuals in the stages of soil optimization and soil fusion. In addition, adaptive environmental selection has been proposed. Finally, MOIFF is compared with four state-of-the art many-objective evolutionary algorithms on many test problems with various characteristics, including the DTLZ and WFG test suites. Experimental results demonstrate that the proposed algorithm has competitive convergence and diversity on MaOPs.
Multi-modal 3D imaging of radionuclides using multiple hybrid Compton cameras
Authors: Omata Akihisa , Masubuchi Miho , Koshikawa Nanase , Kataoka Jun , Kato Hiroki , Toyoshima Atsushi , Teramoto Takahiro , Ooe Kazuhiro , Liu Yuwei , Matsunaga Keiko , Kamiya Takashi , Watabe Tadashi , Shimosegawa Eku , Hatazawa Jun
Published: February 2022

For radiological diagnosis and radionuclide therapy, X-ray and gamma-ray imaging technologies are essential. Single-photon emission tomography (SPECT) and positron emission tomography (PET) play essential roles in radiological diagnosis, such as the early detection of tumors. Radionuclide therapy is also rapidly developing with the use of these modalities. Nevertheless, a limited number of radioactive tracers are imaged owing to the limitations of the imaging devices. In a previous study, we developed a hybrid Compton camera that conducts simultaneous Compton and pinhole imaging within a single system. In this study, we developed a system that simultaneously realizes three modalities: Compton, pinhole, and PET imaging in 3D space using multiple hybrid Compton cameras. We achieved the simultaneous imaging of Cs-137 (Compton mode targeting 662 keV), Na-22 (PET mode targeting 511 keV), and Am-241 (pinhole mode targeting 60 keV) within the same field of view. In addition, the imaging of Ga-67 and In-111, which are used in various diagnostic scenarios, was conducted. We also verified that the 3D distribution of the At-211 tracer inside a mouse could be imaged using the pinhole mode.