bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Clinical Impacts and Attitudes Related to COVID-19 among Residential Substance use Disorder Patients
Authors: Wildberger Jared , Wenzel Kevin , Fishman Marc
Published: February 2022

Background: Individuals with substance use disorder (SUD) may be particularly at risk during the COVID-19 pandemic. The purpose of this study was to examine attitudes to the pandemic among individuals with SUD. Methods: Survey responses from 266 patients entering a residential treatment program were analyzed. Results: Most participants were White or African American men. A third of participants reported that their substance use had increased during the pandemic (38%), and that they had stockpiled substances because of concerns about supply (30%). A majority of participants indicated more depression (60%), anxiety (61%), worry about finances (62%), and feeling worse about their substance use due to COVID-19 (67%). An exploratory factor analysis revealed five factors that measured interest in SUD treatment, psychological symptoms, adherence to health recommendations, perceptions of vulnerability to COVID-19, and substance use during COVID-19. African American participants indicated a greater interest in treatment than Whites, while White participants indicated increased symptoms and substance use during COVID-19 ( p < .05). Further, African Americans were more likely to have known someone who had developed COVID-19 than whites ( p < .05). Older participants indicated adhering to health recommendations more than younger participants, using substances less than younger participants, as well as feeling more vulnerable to COVID-19 ( p < .05). Conclusions: This is the first study to examine patient attitudes and behaviors related to COVID-19 at a residential SUD treatment program. Treatment providers should be aware of patient attitudes and behaviors related to COVID-19 paying special attention to barriers to treatment engagement.
Molecular dynamics simulations of structural and dynamical aspects of DNA hydration water
Authors: Netz Paulo A
Published: February 2022

Water is a remarkable liquid, both because of it is intriguing but also because of its importance. Water plays a key role on the structure and function of biological molecules, but on the other hand also the structure and dynamics of water are deeply influenced by its interactions with biological molecules, specially at low temperatures, where water’s anomalies are enhanced. Here we present extensive molecular dynamics simulations of water hydrating a oligonucleotide down to very low temperatures (supercooled water), comparing four water models and analyzing the water structure and dynamics in different domains: water in the minor groove, water in the major groove and bulk water. We found that the water in the grooves is slowed down by the interactions with the nucleic acid and a hints of a dynamic transition regarding translational and orientational dynamics were found, specially for the water models TIP4P/2005 and TIP4P-Ew, which also showed the closest agreement with available experimental data. The behavior of water in such extreme conditions is relevant for the study of cryopreservation of biological tissues.
Constraints on self-interacting Bose-Einstein condensate dark matter using large-scale observables
Authors: Hartman S.T.H. , Winther H.A. , Mota D.F.
Published: February 2022

Constraints on the cosmic history of self-interacting Bose-Einstein condensed (SIBEC) dark matter (DM) are obtained using the cosmic microwave background (CMB), baryonic acoustic oscillations (BAO), growth factor measurements, and type Ia supernovae (SNIa) distances. Four scenarios are considered, one with purely SIBEC-DM, and three in which SIBEC-DM is the final product of some transition from different initial states, which are either cold, warm, or has a constant equation of state. Using a fluid approximation for the self-interacting scalar field it is found that in the simplest scenario of purely SIBEC-DM the self-interaction necessary for solving the cusp-core problem, with core-radii of low-mass halos of order R
c ≳ 1kpc, is excluded at 2.4σ, or 98.5% confidence. Introducing a transition, however, relaxes this constraint, but the transitions are preferred to be after matter-radiation equality, and the initial phase to be cold.
Scaffold-free approaches for the fabrication of engineered articular cartilage tissue
Authors: Sun Kang , Tao Chao , Wang Dong-An
Published: February 2022

Tissue engineered cartilaginous constructs have meet great advances in the past decades as a treatment for osteoarthritis, a degenerative disease affecting people all over the world as the population ages. Scaffold-free tissue engineered constructs are designed and developed in recent years with only cells and cell-derived matrix involved. Scaffold-free tissue constructs do not require cell adherence on exogenous materials and are superior to scaffold-based constructs in (a) relying on only cells to produce matrix, (b) not interfering cell–cell signaling, cell migration or small molecules diffusion after implantation and (c) introducing no exogenous impurities. In this review, three main scaffold-free methodologies for cartilage tissue engineering, the cell sheet technology, the phase transfer cell culture-living hyaline cartilage graft system and the cell aggregate-based (bottom-up) methods, were reviewed, covering mold fabrication, decellularization and 3D bioprinting. The recent advances, medical applications, superiority and drawbacks were elaborated in detail.
Attractiveness and toxicity of two insecticides to Tetragonula laeviceps (Apidae: Meliponinae)
Authors: Mubin N , Nurulalia L , Dadang
Published: February 2022

Stingless bee, Tetragonula laeviceps, plays a primary role in ecosystem services as a pollinator for coffee, cocoa, and pepper. Attacks of insect pests cause low production of several plantation plants. Farmers commonly use synthetic insecticides to control insect pests. However, improper use of insecticides often adversely affects the ecosystem and human health, including pollinators. In Indonesia, research on the side effects of insecticides on non-target insects such as flower visitor insects (pollinators) is minimal. This study aimed to evaluate the attractiveness and toxicity of two insecticides to T. laeviceps. Stingless bees were obtained from beekeepers at Banten. Y-tube olfactometer test was used to determine the attractiveness of bees to insecticides, and a topical test was used to determine the mortality effect of insecticide on bees. The insecticides used were insecticide A (a.i. alpha-cypermethrin) and insecticide B (a.i. spinetoram) at 100 ppm and 60 ppm, respectively. The results showed that bees were more attracted to insecticide B by 73.3% than insecticide A (26.7%). Insecticide B caused 100% bee mortality after 48 hours after treatment (HAT), while Insecticide A caused 0% bee mortality after 48 HAT. The results indicate that insecticide B attracted stingless bees and has a high mortality level.
The efficacy of single and double tank thermal fogging tool of Bacillus thuringiensis application in oil palm
Authors: Rozziansha T A P , Priwiratama H , Prasetyo A E , Susanto A
Published: February 2022

Many oil palm planters argue that the application of Bacillus thuringiensis through fogging can only be conducted using double-tank fogging equipment. It was believed that the use of single-tank fogging will be resulting in low efficacy. The study aimed to evaluate the efficacy of single and double-tank fogging machines trial of B. thuringiensis against Mahasena corbetti in oil palm plantations. Two doses of application, i.e., 0.5 L/ha and 1 L/ha, were tested using each fogging machine. A plot of mock fogging application was used as a control treatment. The result showed that B. thuringiensis have high efficacy against M. corbetti. More than 90% of larvae mortality was observed at 14 day s after application via a single-tank and a double-tank fogging machine. This result suggests that a single-tank fogging machine could be used for B. thuringiensis application without reducing its efficacy against target pests.
Fertilizer recommendation for pepper based on soil properties and nutrient uptake
Authors: Hartono A , Barus B , Simanihuruk D M P
Published: February 2022

Generally, pepper fertilizer’s application is based on the old recommendation decided by related institutions. Fertilizer application in the SpiceUp project is based on current soil properties and nutrient uptake. This study aimed to compare leaf chlorophyll content and plant growth with fertilization treatment based on soil and nutrient uptake (recommendation) and fertilization treatment based on the old recommendation (conventional). The treatments tested on two varieties of pepper, namely Petaling 1 and Nyelungkup. Measurements of leaf chlorophyll content and plant growth parameters were in a demonstration plot located in Namang District, Central Bangka Regency, Bangka Belitung Islands, from December 2020 to March 2021. The leaf chlorophyll content was expressed by the chlorophyll content index, and plant growth parameters were represented by the number of leaves, number of internodes, number of climbing vines, number of fruit stalks, and plant height. The results showed that the leaf chlorophyll content and plant growth parameters with the recommendation treatment were higher than conventional treatments, in the Petaling 1 and Nyelungkup varieties. The results suggested that recommended treatment of the SpiceUp provided more optimum nutrients for pepper.
Increase of coffee tree susceptibility to stem canker disease mediated by glyphosate application
Authors: Suryaningsih A S , Wiyono S , Sopandie D
Published: February 2022

Stem canker is a major disease of coffee in Indonesia, caused byFusarium solani. Previous studies showed a correlation between stem canker incidence and glyphosate application. The study aimed to determine the effect of glyphosate application on coffee stem canker and the underlying physiological mechanisms. The research used glyphosate treatments with the concentrations of 0, 4, 8, and 16 ml.L−1.In vitroexperiments were carried out by measuring the growth ofF. solanicolony after glyphosate treatment.In planta, tests were conducted by artificial inoculation on glyphosate-treated coffee seedlings. The severity of stem canker was assessed. In a separate test, coffee seedlings were treated with glyphosate without pathogen inoculation. In the second experiment, physiological change was determined by measuring photosynthetic pigments, gas-exchange properties, lipid peroxidation, and activity of ascorbate peroxidase (APX) and catalase (CAT) enzymes.In vitrotests showed that glyphosate had antifungal activity againstF. solani. In planta, the test showed that glyphosate treatment caused higher susceptibility to stem canker in coffee seedlings, indicated by the increase of canker wound depth. Glyphosate treatment on coffee decreased the chlorophyll, carotene contents, and reduced photosynthesis rate, caused oxidative stress depicted by higher lipid peroxidation and increased enzyme APX and CAT activity.
The analysis of labor efficiency on sugarcane cultivation through mechanization application
Authors: Fatah G S A , Supriyadi  , Verona L , Nugraheni S D
Published: February 2022

One of the problems that often arise in people’s sugarcane cultivation is the scarcity of labor and high wages. The application of mechanization is an alternative solution to this problem, especially in people’s sugarcane fields on the island of Java. Land ownership of sugarcane farmers on the island of Java is relatively narrow, with an average land area of less than 0.25 ha. This requires the application of mechanization by the area of the land. This study examines the prospects for the application of tools and machines in sugarcane cultivation by farmers, planters, and companies. Mechanization in sugarcane cultivation can be carried out starting from soil processing, seeding, planting, weed control, and root cutting (pedot oyot) for sugar cane treated with ratoon. The use of mechanization in sugarcane cultivation can increase efficiency by 45.91% and save labor as much as 22 people. The use of mechanization in sugarcane cultivation in Indonesia needs to be encouraged, especially in planting and maintenance activities, to increase farmers’ income and support the country’s sugarcane plantation sustainable development.
Synthesis of polypyrrole-modified Fe3O4/SiO2/TiO2 nanocomposite microspheres and their photocatalytic activity
Authors: Han Kwang-Hyok , Kim Yong-Ho , Mun Myong-Hak , Yu Ju-Hyon , Han Ryong-Huan
Published: February 2022

A polypyrrole-modified Fe3O4/SiO2/TiO2 composite material was successfully synthesized on the FST surface by in situ polymerization of pyrrole. Structural, morphological and magnetic response of Fe3O4/SiO2/TiO2/PPy(FST/PPy) were characterized by transmission electron microscopy, scanning electron microscopy, X-ray diffraction pattern, Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy, etc. Through SEM images, the crystal sizes of the prepared FST/PPy nanoparticles were determined to be about 110 nm. The catalytic activity of FST/PPy was evaluated by the degree of decomposition of rhodamine B under ultraviolet and visible light, respectively. FST/PPy had the photocatalytic activity under the action of the light: the degradation rate of rhodamine B reached 92.8% and 63.5% after 3 h of UV and Vis light irradiation, respectively. Especially, compared with FST, the degradation rate has shown obvious improvement under the action of Vis light. Furthermore, FST/PPy photocatalyst could be easily recycled using a magnet.
Sampling Validation Data to Achieve a Planned Precision of the Bias-Adjusted Estimate of Effect
Authors: Collin Lindsay J , MacLehose Richard F , Ahern Thomas P , Gradus Jaimie L , Getahun Darios , Silverberg Michael J , Goodman Michael , Lash Timothy L
Published: February 2022

Data collected from a validation substudy permit calculation of a bias-adjusted estimate of effect that is expected to equal the estimate that would have been observed had the gold standard measurement been available for the entire study population. In this paper, we develop and apply a framework for adaptive validation to determine when sufficient validation data have been collected to yield a bias-adjusted effect estimate with a prespecified level of precision. Prespecified levels of precision are decided a priori by the investigator, based on the precision of the conventional estimate and allowing for wider confidence intervals that would still be substantively meaningful. We further present an applied example of the use of this method to address exposure misclassification in a study of transmasculine/transfeminine youth and self-harm. Our method provides a novel approach to effective and efficient estimation of classification parameters as validation data accrue, with emphasis on the precision of the bias-adjusted estimate. This method can be applied within the context of any parent epidemiologic study design in which validation data will be collected and modified to meet alternative criteria given specific study or validation study objectives.
SPLDExtraTrees: robust machine learning approach for predicting kinase inhibitor resistance
Authors: Yang Zi-Yi , Ye Zhao-Feng , Xiao Yi-Jia , Hsieh Chang-Yu , Zhang Sheng-Yu
Published: February 2022

Drug resistance is a major threat to the global health and a significant concern throughout the clinical treatment of diseases and drug development. The mutation in proteins that is related to drug binding is a common cause for adaptive drug resistance. Therefore, quantitative estimations of how mutations would affect the interaction between a drug and the target protein would be of vital significance for the drug development and the clinical practice. Computational methods that rely on molecular dynamics simulations, Rosetta protocols, as well as machine learning methods have been proven to be capable of predicting ligand affinity changes upon protein mutation. However, the severely limited sample size and heavy noise induced overfitting and generalization issues have impeded wide adoption of machine learning for studying drug resistance. In this paper, we propose a robust machine learning method, termed SPLDExtraTrees, which can accurately predict ligand binding affinity changes upon protein mutation and identify resistance-causing mutations. Especially, the proposed method ranks training data following a specific scheme that starts with easy-to-learn samples and gradually incorporates harder and diverse samples into the training, and then iterates between sample weight recalculations and model updates. In addition, we calculate additional physics-based structural features to provide the machine learning model with the valuable domain knowledge on proteins for these data-limited predictive tasks. The experiments substantiate the capability of the proposed method for predicting kinase inhibitor resistance under three scenarios and achieve predictive accuracy comparable with that of molecular dynamics and Rosetta methods with much less computational costs.
CRESSP: a comprehensive pipeline for prediction of immunopathogenic SARS-CoV-2 epitopes using structural properties of proteins
Authors: An Hyunsu , Eun Minho , Yi Jawoon , Park Jihwan
Published: February 2022

The development of autoimmune diseases following SARS-CoV-2 infection, including multisystem inflammatory syndrome, has been reported, and several mechanisms have been suggested, including molecular mimicry. We developed a scalable, comparative immunoinformatics pipeline called cross-reactive-epitope-search-using-structural-properties-of-proteins (CRESSP) to identify cross-reactive epitopes between a collection of SARS-CoV-2 proteomes and the human proteome using the structural properties of the proteins. Overall, by searching 4 911 245 proteins from 196 352 SARS-CoV-2 genomes, we identified 133 and 648 human proteins harboring potential cross-reactive B-cell and CD8+ T-cell epitopes, respectively. To demonstrate the robustness of our pipeline, we predicted the cross-reactive epitopes of coronavirus spike proteins, which were recognized by known cross-neutralizing antibodies. Using single-cell expression data, we identified PARP14 as a potential target of intermolecular epitope spreading between the virus and human proteins. Finally, we developed a web application (https://ahs2202.github.io/3M/) to interactively visualize our results. We also made our pipeline available as an open-source CRESSP package (https://pypi.org/project/cressp/), which can analyze any two proteomes of interest to identify potentially cross-reactive epitopes between the proteomes. Overall, our immunoinformatic resources provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune and chronic inflammatory diseases following COVID-19.
An interactive process model of knowledge transfer for social work through university–agency collaboration: Subjective experiences of the agency social workers in Hong Kong
Authors: Xia Lily L L , Ma Joyce L C , Yau-Ng Monica L T , Yiu Cindy Yan-Yee
Published: February 2022

This article reports on the outcome of an exploratory study on a university–agency collaboration in a Chinese context for transferring social work knowledge from academia to the field and beyond. A six-stage process characterised by interactive contributions from the university and the agency in question was identified from the trainees’ narratives of the content, process and their subjective experiences with the three-year collaboration. The two parties co-constructed and adapted knowledge oriented for a specific clientele and agency context, and they implemented the intervention together with underlying theories and ways of thinking. Through interactive practising and coaching, knowledge was indigenised and disseminated into and beyond the agency. The study highlighted the trainees’ active participation, the deep collaboration between the two parties and the trusting relationship within the changing power dynamics, and the comprehensive planning at the organisational level for a fully sustainable transfer of social work knowledge with tacit characteristics. Multiple implications for continuing professional education in social work are drawn.
Spike-timing-dependent plasticity rewards synchrony rather than causality
Authors: Anisimova Margarita , van Bommel Bas , Wang Rui , Mikhaylova Marina , Wiegert Jörn Simon , Oertner Thomas G , Gee Christine E
Published: February 2022

Spike-timing-dependent plasticity (STDP) is a candidate mechanism for information storage in the brain, but the whole-cell recordings required for the experimental induction of STDP are typically limited to 1 h. This mismatch of time scales is a long-standing weakness in synaptic theories of memory. Here we use spectrally separated optogenetic stimulation to fire precisely timed action potentials (spikes) in CA3 and CA1 pyramidal cells. Twenty minutes after optogenetic induction of STDP (oSTDP), we observed timing-dependent depression (tLTD) and timing-dependent potentiation (tLTP), depending on the sequence of spiking. As oSTDP does not require electrodes, we could also assess the strength of these paired connections three days later. At this late time point, late tLTP was observed for both causal (CA3 before CA1) and anticausal (CA1 before CA3) timing, but not for asynchronous activity patterns (Δt = 50 ms). Blocking activity after induction of oSTDP prevented stable potentiation. Our results confirm that neurons wire together if they fire together, but suggest that synaptic depression after anticausal activation (tLTD) is a transient phenomenon.
The performance monitoring system is attuned to others’ actions during dyadic motor interactions
Authors: Moreau Quentin , Tieri Gaetano , Era Vanessa , Aglioti Salvatore Maria , Candidi Matteo
Published: February 2022

Interpersonal motor interactions require the simultaneous monitoring of one’s own and one’s partner’s actions. To characterize how the action monitoring system tracks self and other behavior during synchronous interactions, we combined electroencephalography recordings and immersive virtual reality in two tasks where participants were asked to synchronize their actions with those of a virtual partner (VP). The two tasks differed in the features to be monitored: the Goal task required participants to predict and monitor the VP’s reaching goal; the Spatial task required participants to predict and monitor the VP’s reaching trajectory. In both tasks, the VP performed unexpected movement changes to which the participant needed to adapt. By extracting the neural activity locked to the detection of unexpected changes in the VP’s action (other-monitoring) or to the participants’ action-replanning (self-monitoring), we show that the monitoring system is more attuned to others’ than to one’s own actions. Additionally, distinctive neural responses to VP’s unexpected goals and trajectory corrections were found: goal changes were reflected both in early fronto-central and later posterior neural responses while trajectory deviations were reflected only in later posterior responses. Altogether, our results indicate that the monitoring system adopts an inherent social mode to handle interpersonal motor interactions.
Simplified High Level Parallelism Expression on Heterogeneous Systems through Data Partition Pattern Description
Authors: Wu Shusen , Dong Xiaoshe , Chen Heng , Wang Longxiang , Wang Qiang , Zhu Zhengdong
Published: February 2022

With the development of heterogeneous systems, the demand for high-level programming methods that ease heterogeneous programming and produce portable applications has become more urgent. This paper proposes DACL, the data associated computing language. DACL introduces data partition patterns to achieve architecture-independent parallelism expression. Meanwhile, DACL provides simplified language extensions, as well as programming features such as serialization of the computing process, parameterization of data attributes and modularity, thus reducing the difficulty of heterogeneous programming and improving programming productivity. The operational semantics show that DACL enables different levels of parallelism degree calculation and retains data access patterns, reserving optimization potential. To support cross-platform execution, the currently implemented source-to-source compilers employ OpenMP and OpenCL as the backend. We reconstructed multiple benchmarks selected from the Parboil and Rodinia benchmark suits with DACL and conducted a comparison test on CPU, GPU and MIC platforms. The code size of each rebuilt benchmark is roughly equivalent to that of the serial code, which is only 13%–64% of the benchmark OpenCL code. With the support of the compilation system, the reconstructed code can execute on different processors without modification, yielding a competitive or better performance to that of the manually written benchmark code.
The Role of Schools in Supporting Students Experiencing Homelessness: Perceptions of School Staff
Authors: Wagaman M Alex , Gattis Maurice N , Watts Keith J , Yabar Mauricio P , Blair Dmitri , Haynes Tiffany S , Williams Elaine G
Published: February 2022

Housing instability has a detrimental impact on the academic success of children and youth. Despite having federal policy to direct schools on how to identify and support students experiencing homelessness, many schools still face challenges to developing a systemwide approach that involves school staff in varying positions and addresses the unique needs of disproportionately impacted student populations. This study was conducted using secondary data analysis of a data set collected through participatory action research in a mid-Atlantic state across three school systems. Findings suggest that school staff are largely unaware of their own role in supporting students experiencing homelessness and need further training. Schools need more resources and community connections to support the needs of their students who are facing housing instability. The study suggests that a systems theory approach to understanding and responding to the needs of students experiencing homelessness will equip schools and their staff to be better positioned to effectively provide support that promotes academic achievement and well-being.
Asynchrony in Seasonal Patterns of Taxonomic and Functional Diversity in an Aboveground Ant (Hymenoptera: Formicidae) Community (Florida, USA)
Authors: Ohyama Leo
Published: February 2022

Seasonal dynamics of diversity patterns are a key component to understand when assessing ecological communities across temporal scales given that long-term trends in diversity are often a product of the intricate dynamisms that occur at shorter temporal scales. However, seasonal trends in diversity are usually dependent on local-scale conditions, such as habitat types or the demographic characteristics of a given fauna, thus requiring better data coverage from consistent local-scale sampling. Furthermore, the assessment of seasonal dynamics in the context of functional diversity derived from trait-based data is often lacking in many important taxa such as insects. In this study, I quantify and describe the diversity of a Floridian subtropical aboveground ant community from monthly sampling across seasons using both contemporary taxonomic diversity metrics and functional diversity metrics. Results show differences in the timing of peaks across different diversity metrics. Species richness and abundances peak in months leading up to wet seasons while functional richness and divergence peak near the end of the wet season. This asynchrony is likely a result of species-specific differences in natural histories and demographic dynamics. While clear temporal dynamics are observed across diversity metrics, differences between wet or dry seasons were lacking for all metrics except functional richness. Fine-scale sampling data of seasonal trends in insect communities compiled from studies like this will be essential tools for future assessments and predictions of insect biodiversity.
Vitamin D levels in primary care patients: correlations with clinical, seasonal, and quality-of-life parameters
Authors: Bouloukaki Izolde , Markakis Manolis , Pateli Rodanthi , Lyronis Ioannis , Schiza Sophia , Tsiligianni Ioanna
Published: February 2022

Background

The prevalence of vitamin D deficiency varies across countries and few data exist in the adult population in Greece.

Objectives

To assess vitamin D levels in unselected patients from primary care and to investigate possible correlations with clinical, seasonal, and quality-of-life parameters.

Methods

In this cross-sectional study, 389 consecutive patients were included. They were grouped according to vitamin D status as vitamin D deficient (<20 ng/mL) and vitamin D sufficient groups (≥20 ng/mL). Demographic, Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), Beck Depression Inventory (BDI), and Fatigue Severity Scale (FSS) scores were measured and compared between groups.

Results

Vitamin D deficiency (<20 ng/mL) was observed in 50.4% of the cohort. Female gender (76% vs 66%, P = 0.026), obesity (42% vs 26%, P = 0.005), and hypertension (55% vs 43%, P = 0.023) were higher in the vitamin D deficiency group compared with the group without deficiency. After multiparametric adjustments (for age, gender, obesity, comorbidities, and seasonality), hypertension (odds ratio [OR] = 2.338, 95% confidence interval [CI] = 1.257–4.349, P = 0.007), excessive daytime sleepiness (ESS >10; OR = 3.345, 95% CI = 1.124–9.948, P = 0.029), depressive symptoms (BDI >10; OR = 3.769, 95% CI = 0.984–14.443, P = 0.04), and fatigue (FSS >36; OR = 7.157, 95% CI = 0.855–59.877, P = 0.04) showed significant independent associations with vitamin D deficiency in specific subgroups of patients.

Conclusion

A large proportion of patients in primary care had vitamin D deficiency, independently associated with hypertension, sleepiness, depressive symptoms, and fatigue. Further research is needed in order to determine the role of vitamin D in these patients.
Two ovarian candidate enhancers, identified by time series enhancer RNA analyses, harbor rare genetic variations identified in ovarian insufficiency
Authors: Nakagawa Ryuichi , Takasawa Kei , Gau Maki , Tsuji-Hosokawa Atsumi , Kawaji Hideya , Murakawa Yasuhiro , Takada Shuji , Mikami Masashi , Narumi Satoshi , Fukami Maki , Sreenivasan Rajini , Maruyama Tetsuo , Tucker Elena J , Zhao Liang , Bowles Josephine , Sinclair Andrew , Koopman Peter , Hayashizaki Yoshihide , Morio Tomohiro , Kashimada Kenichi
Published: February 2022

The genetic regulation of ovarian development remains largely unclear. Indeed, in most cases of impaired ovarian development—such as 46,XX disorders of sex development (DSD) without SRY, and premature ovarian insufficiency (POI)—the genetic causes have not been identified, and the vast majority of disease-associated sequence variants could lie within non-coding regulatory sequences. In this study, we aimed to identify enhancers of five ovarian genes known to play key roles in early ovarian development, basing our analysis on the expression of enhancer derived transcripts (eRNAs), which are considered to characterize active enhancers. Temporal expression profile changes in mouse WT1-positive ovarian cells were obtained from cap analysis of gene expression at E13.5, E16.5 and P0. We compared the chronological expression profiles of ovarian-specific eRNA with expression profiles for each of the ovarian-specific genes, yielding two candidate sequences for enhancers of Wnt4 and Rspo1. Both sequences are conserved between mouse and human, and we confirmed their enhancer activities using transient expression assays in murine granulosa cells. Furthermore, by sequencing the region in patients with impaired ovarian development in 24 patients, such as POI, gonadal dysgenesis and 46,XX DSD, we identified rare single nucleotide variants in both sequences. Our results demonstrate that combined analysis of the temporal expression profiles of eRNA and mRNA of target genes presents a powerful tool for locating cis-element enhancers, and a means of identifying disease-associated sequence variants that lie within non-coding regulatory sequences, thus advancing an important unmet need in forward human genetics.
The ciliary transition zone protein TMEM218 synergistically interacts with the NPHP module and its reduced dosage leads to a wide range of syndromic ciliopathies
Authors: Epting Daniel , Decker Eva , Ott Elisabeth , Eisenberger Tobias , Bader Ingrid , Bachmann Nadine , Bergmann Carsten
Published: February 2022

Mutations in genes that lead to dysfunctional cilia can cause a broad spectrum of human disease phenotypes referred to as ciliopathies. Many ciliopathy-associated proteins are localized to the evolutionary conserved ciliary transition zone (TZ) subdomain. We identified biallelic missense and nonsense mutations in the gene encoding the transmembrane protein TMEM218 in unrelated patients with features related to Bardet–Biedl, Joubert and Meckel–Gruber syndrome (MKS) and characterized TMEM218 as a major component of the ciliary TZ module. Co-immunoprecipitation assays resulted in the physical interaction of TMEM218 with the MKS module member TMEM67/Meckelin that was significantly reduced by the TMEM218 missense change harboured by one of our patients. We could further validate its pathogenicity by functional in vivo analysis in zebrafish (Danio rerio) as a well-established vertebrate model for ciliopathies. Notably, ciliopathy-related phenotypes were most prominent by genetic interactions with the NPHP module component Nphp4. Conclusively, we describe TMEM218 as a new disease gene for patients with a wide spectrum of syndromic ciliopathy phenotypes and provide evidence for a synergistic interaction of TMEM218 and the NPHP module crucial for proper ciliary function.
Multisystem involvement, defective lysosomes and impaired autophagy in a novel rat model of nephropathic cystinosis
Authors: Krohn Patrick , Rega Laura Rita , Harvent Marianne , Festa Beatrice Paola , Taranta Anna , Luciani Alessandro , Dewulf Joseph , Cremonesi Alessio , Camassei Francesca Diomedi , Hanson James V M , Gerth-Kahlert Christina , Emma Francesco , Berquez Marine , Devuyst Olivier
Published: February 2022

Recessive mutations in the CTNS gene encoding the lysosomal transporter cystinosin cause cystinosis, a lysosomal storage disease leading to kidney failure and multisystem manifestations. A Ctns knockout mouse model recapitulates features of cystinosis, but the delayed onset of kidney manifestations, phenotype variability and strain effects limit its use for mechanistic and drug development studies. To provide a better model for cystinosis, we generated a Ctns knockout rat model using CRISPR/Cas9 technology. The Ctns−/− rats display progressive cystine accumulation and crystal formation in multiple tissues including kidney, liver and thyroid. They show an early onset and progressive loss of urinary solutes, indicating generalized proximal tubule dysfunction, with development of typical swan-neck lesions, tubulointerstitial fibrosis and kidney failure, and decreased survival. The Ctns−/− rats also present crystals in the cornea, and bone and liver defects, as observed in patients. Mechanistically, the loss of cystinosin induces a phenotype switch associating abnormal proliferation and dedifferentiation, loss of apical receptors and transporters, and defective lysosomal activity and autophagy in the cells. Primary cultures of proximal tubule cells derived from the Ctns−/− rat kidneys confirmed the key changes caused by cystine overload, including reduced endocytic uptake, increased proliferation and defective lysosomal dynamics and autophagy. The novel Ctns−/− rat model and derived proximal tubule cell system provide invaluable tools to investigate the pathogenesis of cystinosis and to accelerate drug discovery.
The Inconsistencies of Age-Related Incapacity Thresholds in International Law: Child Rape Victims at a Disadvantage
Authors: Maravall-Buckwalter Isabel
Published: February 2022

Over the past few decades, the definition of rape has been the focus of widespread attention in international law. However, the circumstance of age-related incapacity in its definition has been left unexplored. While no definition of an age of sexual consent is found in international criminal law, though suggestions have been made in international criminal jurisprudence, other international legal frameworks have included clear and well-defined thresholds in their definitions, i.e. recruitment, trafficking, sale, prostitution, and pornography. This article argues that the vagueness of an undefined threshold in the rape definition, and the existing inconsistencies when compared with the other frameworks, are at odds with the evolving trends in international law on the treatment of consent and child victims. This leaves child rape victims at a comparative disadvantage, especially adolescent girls, who pervasively experience the consequences and harms derived from this vagueness and inconsistency.
Repellency Potential of Tomato Herbivore-Induced Volatiles Against the Greenhouse Whitefly (Trialeurodes vaporariorum) (Hemiptera: Aleyrodidae)
Authors: Deletre Emilie , Matu Francis Kiamba , Murungi Lucy Kananu , Mohamed Samira
Published: February 2022

The greenhouse whitefly, Trialeurode vaporariorum, is among the key pests of tomato (Solanum lycopersicum) in sub-Saharan Africa with Tuta absoluta, spider mite, thrips, and fruitworms. To understand the interaction between the pest and the plant’s herbivory-induced plant volatile (HIPVs), we investigated the repellency of four tomato cultivars (Kilele F1, Assila F1, Red Beauty F1, and Nemonneta F1) upon infestation by Trialeurode vaporariorum. We analyzed the behavioral response of T. vaporariorum to infested and uninfested tomato plants of these cultivars using olfactory bioassays followed by gas chromatography–mass spectrometry (GC–MS) analyses of emitted volatiles. Trialeurode vaporariorum was attracted to uninfested plants of all four tomato cultivars. However, two cultivars Kilele F1 and Red Beauty F1 were no longer attractive to the whitefly when they were already infested by the pest. GC–MS analyses identified 25 compounds, 18 monoterpenes, 3 sesquiterpenes, 2 xylenes, 1 aldehyde, and 1 carboxylic compound in the 4 uninfested and infested cultivars. Based on the insects’ behavioral response, 1,8-cineole, p-cymene, and limonene did not attract T. vaporariorum at varying concentrations when combined with Red Beauty F1, the most attractive tomato cultivar. This repellence behavioral response can be used as a basis for improvement of other vegetable crops for the management of arthropod pests as for odor masking technique.
Cancer Survivorship and Supportive Care Economics Research: Current Challenges and Next Steps
Authors: Nicholas Lauren Hersch , Davidoff Amy J , Howard David H , Keating Nancy L , Ritzwoller Debra P , Robin Yabroff K , Bradley Cathy J
Published: February 2022

Background

Rapid growth in the number of cancer survivors raises numerous questions about health and economic outcomes among survivors along with their families, caregivers, and employers. Health economics theory and methods can contribute to many open questions to improve survivorship.

Methods

In this paper, we review key areas where more research is needed and describe strategies for improving data infrastructure, research funding, and capacity building to strengthen survivorship health economics research.

Conclusions

Health economics has broadened an understanding of key supply- and demand-side factors that promote cancer survivorship. To ensure necessary research in survivorship health economics moving forward, we recommend dedicated funding, inclusion of health economics outcomes in primary data collection, and investments in secondary data sets.
Prediction of the potential mechanism of compound gingerol against liver cancer based on network pharmacology and experimental verification
Authors: Su Min , Wang Xueqin , Cao Gang , Sun Li , Ho Rodney J Y , Han Yanquan , Hong Yan , Wu Deling
Published: February 2022

Objectives

To explore gingerol’s potential mechanism for treating liver cancer using network pharmacology and molecular docking technology and to conduct in-vitro experiments of human liver cancer cell HepG2 to verify important signalling pathways.

Methods

We obtained potential targets of gingerol derivatives (6-gingerol, 8-gingerol and 10-gingerol) from PubChem and SwissTargetPrediction websites and collected related targets for liver cancer with the help of GeneCards. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on key targets using the DAVID data platform and combined with Cytoscape 3.7.1 software to construct a component–target–signal pathway interaction map to study its mechanism of action. Subsequently, the components and key proteins were molecularly docked through Autodock Vina software. Finally, the important signal pathways were verified by HepG2 cell in-vitro experiments.

Key findings

A total of 318 drug targets were screened for gingerol derivatives, and 2509 gene targets related to liver cancer were collected. The Venn diagram showed that there were 104 intersection targets between gingerol derivatives and liver cancer. Module analysis results show that these intersection targets can be divided into 5 modules and 49 nodes. Bioinformatics analysis found that GO obtained 20 important functional items including cancer cell proliferation, protein kinase activity, phosphotransferase activity and kinase activity; KEGG enrichment analysis yielded a total of 20 key signal pathways including the PI3K–Akt signalling pathway. The results of molecular docking show that the binding energy of gingerol derivatives has good binding activity with PI3K and Akt. In-vitro experimental results show that gingerol derivatives and compound gingerol (compound gingerol is composed of 6-gingerol, 8-gingerol and 10-gingerol in a ratio of 7:1.5:1.5) can produce HepG2 cell proliferation inhibition, and each administration group can significantly increase the apoptosis rate of HepG2 cells and the fluorescence intensity of the nucleus and block the cell cycle in the S phase; the results of Western Blot and real-time quantitative PCR show that gingerol derivatives and compound gingerol can down-regulate the expression of Akt and p-Akt and up-regulate the expression of Bax/Bcl-2. And the effect of compound gingerol is more obvious than that of gingerol derivatives.

Conclusions

The results of network pharmacology and experimental validation suggest that gingerol derivatives and compound gingerol can act against liver cancer by acting on the PI3K-Akt signalling pathway.
The production of wax esters in transgenic plants: towards a sustainable source of bio-lubricants
Authors: Domergue Frédéric , Miklaszewska Magdalena
Published: February 2022

Wax esters are high-value compounds used as feedstocks for the production of lubricants, pharmaceuticals, and cosmetics. Currently, they are produced mostly from fossil reserves using chemical synthesis, but this cannot meet increasing demand and has a negative environmental impact. Natural wax esters are also obtained from Simmondsia chinensis (jojoba) but comparably in very low amounts and expensively. Therefore, metabolic engineering of plants, especially of the seed storage lipid metabolism of oil crops, represents an attractive strategy for renewable, sustainable, and environmentally friendly production of wax esters tailored to industrial applications. Utilization of wax ester-synthesizing enzymes with defined specificities and modulation of the acyl-CoA pools by various genetic engineering approaches can lead to obtaining wax esters with desired compositions and properties. However, obtaining high amounts of wax esters is still challenging due to their negative impact on seed germination and yield. In this review, we describe recent progress in establishing non-food-plant platforms for wax ester production and discuss their advantages and limitations as well as future prospects.
A collisional test-particle model of electrons at a comet
Authors: Stephenson Peter , Galand M , Deca J , Henri P , Carnielli G
Published: February 2022

We have developed the first 3D collisional model of electrons at a comet, which we use to examine the impact of electron-neutral collisions in the weakly outgassing regime. The test-particle Monte Carlo model uses electric and magnetic fields from a fully kinetic Particle-in-Cell (PiC) model as an input. In our model, electrons originate from the solar wind or from ionization of the neutral coma, either by electron impact or absorption of an extreme ultraviolet photon. All relevant electron-neutral collision processes are included in the model including elastic scattering, excitation, and ionization. Trajectories of electrons are validated against analytically known drifts and the stochastic energy degradation used in the model is compared to the continuous slowing down approximation. Macroscopic properties of the solar wind and cometary electron populations, such as density and temperature, are validated with simple known cases and via comparison with the collisionless PiC model. We demonstrate that electrons are trapped close to the nucleus by the ambipolar electric field, causing an increase in the efficiency of electron-neutral collisions. Even at a low-outgassing rate (Q = 1026 s−1), electron-neutral collisions are shown to cause significant cooling in the coma. The model also provides a multistep numerical framework that is used to assess the influence of the electron-to-ion mass ratio, enabling access to electron dynamics with a physical electron mass.
Deficiency of ribosomal proteins reshapes the transcriptional and translational landscape in human cells
Authors: Luan Yizhao , Tang Nan , Yang Jiaqi , Liu Shuting , Cheng Chichi , Wang Yan , Chen Congying , Guo Ya-nan , Wang Hongwei , Zhao Wenxue , Zhao Qian , Li Wei , Xiang Mengqing , Ju Rong , Xie Zhi
Published: February 2022

Human ribosomes have long been thought to be uniform factories with little regulatory function. Accumulating evidence emphasizes the heterogeneity of ribosomal protein (RP) expression in specific cellular functions and development. However, a systematic understanding of functional relevance of RPs is lacking. Here, we surveyed translational and transcriptional changes after individual knockdown of 75 RPs, 44 from the large subunit (60S) and 31 from the small subunit (40S), by Ribo-seq and RNA-seq analyses. Deficiency of individual RPs altered specific subsets of genes transcriptionally and translationally. RP genes were under cotranslational regulation upon ribosomal stress, and deficiency of the 60S RPs and the 40S RPs had opposite effects. RP deficiency altered the expression of genes related to eight major functional classes, including the cell cycle, cellular metabolism, signal transduction and development. 60S RP deficiency led to greater inhibitory effects on cell growth than did 40S RP deficiency, through P53 signaling. Particularly, we showed that eS8/RPS8 deficiency stimulated apoptosis while eL13/RPL13 or eL18/RPL18 deficiency promoted senescence. We also validated the phenotypic impacts of uL5/RPL11 and eL15/RPL15 deficiency on retina development and angiogenesis, respectively. Overall, our study provides a valuable resource for and novel insights into ribosome regulation in cellular activities, development and diseases.