bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pharmacogenetics of Statin Therapy on Clinical Events: No Evidence that Genetic Variation Affects Statin Response on Myocardial Infarction
Authors: Trompet Stella , Postmus Iris , Warren Helen R. , Noordam Raymond , Smit Roelof A. J. , Theusch Elizabeth , Li Xiaohui , Arsenault Benoit , Chasman Daniel I. , Hitman Graham A. , Munroe Patricia B. , Rotter Jerome I. , Psaty Bruce M. , Caulfield Mark J. , Krauss Ron M. , Cupples Adrienne L. , Jukema Wouter J.
Published: January 2022

Background: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction.

Methods: The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI. For imputed single nucleotide polymorphisms (SNPs), regression analysis was performed on expected allelic dosage and meta-analysed with a fixed-effects model, inverse variance weighted meta-analysis. All SNPs with p-values <5.0 × 10−4 in stage 1 GWAS meta-analysis were selected for further investigation in stage-2. As a secondary analysis, we extracted SNPs from the Stage-1 GWAS meta-analysis results based on predefined hypotheses to possibly modifying the effect of statin therapy on MI.

Results: In stage-1 meta-analysis (eight studies, n = 10,769, 4,212 cases), we observed no genome-wide significant results (p < 5.0 × 10−8). A total of 144 genetic variants were followed-up in the second stage (three studies, n = 1,525, 180 cases). In the combined meta-analysis, no genome-wide significant hits were identified. Moreover, none of the look-ups of SNPs known to be associated with either CHD or with statin response to cholesterol levels reached Bonferroni level of significance within our stage-1 meta-analysis.

Conclusion: This GWAS analysis did not provide evidence that genetic variation affects statin response on cardiovascular risk reduction. It does not appear likely that genetic testing for predicting effects of statins on clinical events will become a useful tool in clinical practice.
Integration Analysis of Pharmacokinetics and Metabolomics to Predict Metabolic Phenotype and Drug Exposure of Remdesivir
Authors: Du Ping , Wang Guoyong , Hu Ting , Li Han , An Zhuoling
Published: January 2022

Remdesivir has displayed pharmacological activity against SARS-CoV-2. However, no pharmacometabolomics (PM) or correlation analysis with pharmacokinetics (PK) was revealed. Rats were intravenously administered remdesivir, and a series of blood samples were collected before and after treatment. Comprehensive metabolomics profile and PK were investigated and quantitated simultaneously using our previous reliable HPLC-MS/MS method. Both longitudinal and transversal metabolic analyses were conducted, and the correlation between PM and PK parameters was evaluated using Pearson’s correlation analysis and the PLS model. Multivariate statistical analysis was employed for discovering candidate biomarkers which predicted drug exposure or toxicity of remdesivir. The prominent metabolic profile variation was observed between pre- and posttreatment, and significant changes were found in 65 metabolites. A total of 15 metabolites—12 carnitines, one N-acetyl-D-glucosamine, one allantoin, and one corticosterone—were significantly correlated with the concentration of Nuc (active metabolite of remdesivir). Adenosine, spermine, guanosine, sn-glycero-3-phosphocholine, and l-homoserine may be considered potential biomarkers for predicting drug exposure or toxicity. This study is the first attempt to apply PM and PK to study remdesivir response/toxicity, and the identified candidate biomarkers might be used to predict the AUC and Cmax, indicating capability of discriminating good or poor responders. Currently, this study originally offers considerable evidence to metabolite reprogramming of remdesivir and sheds light on precision therapy development in fighting COVID-19.
In Silico Prediction and Insights Into the Structural Basis of Drug Induced Nephrotoxicity
Authors: Shi Yinping , Hua Yuqing , Wang Baobao , Zhang Ruiqiu , Li Xiao
Published: January 2022

Drug induced nephrotoxicity is a major clinical challenge, and it is always associated with higher costs for the pharmaceutical industry and due to detection during the late stages of drug development. It is desirable for improving the health outcomes for patients to distinguish nephrotoxic structures at an early stage of drug development. In this study, we focused on in silico prediction and insights into the structural basis of drug induced nephrotoxicity, based on reliable data on human nephrotoxicity. We collected 565 diverse chemical structures, including 287 nephrotoxic drugs on humans in the real world, and 278 non-nephrotoxic approved drugs. Several different machine learning and deep learning algorithms were employed for in silico model building. Then, a consensus model was developed based on three best individual models (RFR_QNPR, XGBOOST_QNPR, and CNF). The consensus model performed much better than individual models on internal validation and it achieved prediction accuracy of 86.24% external validation. The results of analysis of molecular properties differences between nephrotoxic and non-nephrotoxic structures indicated that several key molecular properties differ significantly, including molecular weight (MW), molecular polar surface area (MPSA), AlogP, number of hydrogen bond acceptors (nHBA), molecular solubility (LogS), the number of rotatable bonds (nRotB), and the number of aromatic rings (nAR). These molecular properties may be able to play an important part in the identification of nephrotoxic chemicals. Finally, 87 structural alerts for chemical nephrotoxicity were mined with f-score and positive rate analysis of substructures from Klekota-Roth fingerprint (KRFP). These structural alerts can well identify nephrotoxic drug structures in the data set. The in silico models and the structural alerts could be freely accessed via https://ochem.eu/article/140251 and http://www.sapredictor.cn, respectively. We hope the results should provide useful tools for early nephrotoxicity estimation in drug development.
USP14: Structure, Function, and Target Inhibition
Authors: Wang Feng , Ning Shuo , Yu Beiming , Wang Yanfeng
Published: January 2022

Ubiquitin-specific protease 14 (USP14), a deubiquitinating enzyme (DUB), is associated with proteasomes and exerts a dual function in regulating protein degradation. USP14 protects protein substrates from degradation by removing ubiquitin chains from proteasome-bound substrates, whereas promotes protein degradation by activating the proteasome. Increasing evidence have shown that USP14 is involved in several canonical signaling pathways, correlating with cancer, neurodegenerative diseases, autophagy, immune responses, and viral infections. The activity of USP14 is tightly regulated to ensure its function in various cellular processes. Structural studies have demonstrated that free USP14 exists in an autoinhibited state with two surface loops, BL1 and BL2, partially hovering above and blocking the active site cleft binding to the C-terminus of ubiquitin. Hence, both proteasome-bound and phosphorylated forms of USP14 require the induction of conformational changes in the BL2 loop to activate its deubiquitinating function. Due to its intriguing roles in the stabilization of disease-causing proteins and oncology targets, USP14 has garnered widespread interest as a therapeutic target. In recent years, significant progress has been made on identifying inhibitors targeting USP14, despite the complexity and challenges in improving their selectivity and affinity for USP14. In particular, the crystal structures of USP14 complexed with IU1-series inhibitors revealed the underlying allosteric regulatory mechanism and enabled the further design of potent inhibitors. In this review, we summarize the current knowledge regarding the structure, regulation, pathophysiological function, and selective inhibition of USP14, including disease associations and inhibitor development.
Heavy Metals and Probabilistic Risk Assessment via Pheretima (a Traditional Chinese Medicine) Consumption in China
Authors: Xu Xiaohui , Li Limin , Zhou Heng , Hu Qing , Wang Lingling , Cai Qiang , Zhu Yin , Ji Shen
Published: January 2022

Earthworms are known to accumulate inorganic contaminants from the soil; they are also used as a traditional Chinese medicine (TCM) called Pheretima, which might cause safety problems with long-term exposure. Here, this study was conducted to determine and analyze the level of heavy metal contamination such as arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), manganese (Mn), nickel (Ni), and lead (Pb) in Pheretima and then explore the probabilistic health risks caused by 8 heavy metals in 98 batches of Pheretima using Monte Carlo simulation. A risk assessment strategy was conducted to assess heavy metal–associated health risk of Pheretima based on consumption data. For random consumption sampling, the results found that the non-carcinogenic risk of As is higher than the acceptable level, and the carcinogenic risk levels of As and Cr exceeded the acceptable risk recommended by the USEPA. Cr and As were regarded as the priority metals for risk control in the present study. Finally, it was recommended that the dosing frequency should be less than 24 d/y. In general, this study conducted a probabilistic risk assessment of heavy metals in Pheretima, which would be of significance for policy makers to take effective strategies to improve the quality and safety of Pheretima.
An Identical Twin Study on Human Achilles Tendon Adaptation: Regular Recreational Exercise at Comparatively Low Intensities Can Increase Tendon Stiffness
Authors: Sichting Freddy , Kram Nicolai C. , Legerlotz Kirsten
Published: January 2022

Achilles tendon adaptation is a key aspect of exercise performance and injury risk prevention. However, much debate exists about the adaptation of the Achilles tendon in response to exercise activities. Most published research is currently limited to elite athletes and selected exercise activities. Also, existing studies on tendon adaptation do not control for genetic variation. Our explorative cross-sectional study investigated the effects of regular recreational exercise activities on Achilles tendon mechanical properties in 40 identical twin pairs. Using a handheld oscillation device to determine Achilles tendon mechanical properties, we found that the Achilles tendon appears to adapt to regular recreational exercise at comparatively low intensities by increasing its stiffness. Active twins showed a 28% greater Achilles tendon stiffness than their inactive twin (p < 0.05). Further, our research extends existing ideas on sport-specific adaptation by showing that tendon stiffness seemed to respond more to exercise activities that included an aerial phase such as running and jumping. Interestingly, the comparison of twin pairs revealed a high variation of Achilles tendon stiffness (305.4–889.8 N/m), and tendon adaptation was only revealed when we controlled for genetic variance. Those results offer new insights into the impact of genetic variation on individual Achilles tendon stiffness, which should be addressed more closely in future studies.
Development of a Robust, Simple, and Affordable Human Gait Analysis System Using Bottom-Up Pose Estimation With a Smartphone Camera
Authors: Viswakumar Aditya , Rajagopalan Venkateswaran , Ray Tathagata , Gottipati Pranitha , Parimi Chandu
Published: January 2022

Gait analysis is used in many fields such as Medical Diagnostics, Osteopathic medicine, Comparative and Sports-related biomechanics, etc. The most commonly used system for capturing gait is the advanced video camera-based passive marker system such as VICON. However, such systems are expensive, and reflective markers on subjects can be intrusive and time-consuming. Moreover, the setup of markers for certain rehabilitation patients, such as people with stroke or spinal cord injuries, could be difficult. Recently, some markerless systems were introduced to overcome the challenges of marker-based systems. However, current markerless systems have low accuracy and pose other challenges in gait analysis with people in long clothing, hiding the gait kinematics. The present work attempts to make an affordable, easy-to-use, accurate gait analysis system while addressing all the mentioned issues. The system in this study uses images from a video taken with a smartphone camera (800 × 600 pixels at an average rate of 30 frames per second). The system uses OpenPose, a 2D real-time multi-person keypoint detection technique. The system learns to associate body parts with individuals in the image using Convolutional Neural Networks (CNNs). This bottom-up system achieves high accuracy and real-time performance, regardless of the number of people in the image. The proposed system is called the “OpenPose based Markerless Gait Analysis System” (OMGait). Ankle, knee, and hip flexion/extension angle values were measured using OMGait in 16 healthy volunteers under different lighting and clothing conditions. The measured kinematic values were compared with a standard video camera based normative dataset and data from a markerless MS Kinect system. The mean absolute error value of the joint angles from the proposed system was less than 90for different lighting conditions and less than 110for different clothing conditions compared to the normative dataset. The proposed system is adequate in measuring the kinematic values of the ankle, knee, and hip. It also performs better than the markerless systems like MS Kinect that fail to measure the kinematics of ankle, knee, and hip joints under dark and bright light conditions and in subjects with long robe clothing.
Building a Barrier: The Influence of Different Wax Fractions on the Water Transpiration Barrier of Leaf Cuticles
Authors: Seufert Pascal , Staiger Simona , Arand Katja , Bueno Amauri , Burghardt Markus , Riederer Markus
Published: January 2022

Waxes are critical in limiting non-stomatal water loss in higher terrestrial plants by making up the limiting barrier for water diffusion across cuticles. Using a differential extraction protocol, we investigated the influence of various wax fractions on the cuticular transpiration barrier. Triterpenoids (TRPs) and very long-chain aliphatics (VLCAs) were selectively extracted from isolated adaxial leaf cuticles using methanol (MeOH) followed by chloroform (TCM). The water permeabilities of the native and the solvent-treated cuticles were measured gravimetrically. Seven plant species (Camellia sinensis, Ficus elastica, Hedera helix, Ilex aquifolium, Nerium oleander, Vinca minor, and Zamioculcas zamiifolia) with highly varying wax compositions ranging from nearly pure VLCA- to TRP-dominated waxes were selected. After TRP removal with MeOH, water permeability did not or only slightly increase. The subsequent VLCA extraction with TCM led to increases in cuticular water permeabilities by up to two orders of magnitude. These effects were consistent across all species investigated, providing direct evidence that the cuticular transpiration barrier is mainly composed of VLCA. In contrast, TRPs play no or only a minor role in controlling water loss.
Environmental Factors Driving Seed Hydration Status of Soil Seed Banks and the Implications for Post-fire Recruitment
Authors: Tangney Ryan , Merritt David J. , Miller Ben P.
Published: January 2022

Changes in fire regimes due to climate change and fire management practices are affecting the timing, length, and distribution of vegetation fires throughout the year. Plant species responses and tolerances to fire differ from season to season and are influenced by species-specific phenological processes. The ability of seeds to tolerate extreme temperatures associated with fire is one of these processes, with survival linked to seed moisture content at the time of exposure. As fire is more often occurring outside historic dry fire seasons, the probability of fire occurring when seeds are hydrated may also be increasing. In this study, we set out to understand the seasonal dynamics of seed hydration for seeds of Banksia woodland species, and how certain seed traits interact with environmental conditions to influence survival of high temperatures associated with fire. We measured the moisture content of seeds buried to 2 cm in the soil seed bank for four common native species and one invasive species on a weekly basis throughout 2017, along with soil moisture content and environmental correlates. We determined water sorption isotherms at 20°C for seeds of each species and used these functions to model weekly variation in seed water activity and predict when seeds are most sensitive to soil heating. Using Generalised additive models (GAMs), we were able to describe approximately 67% of the weekly variance in seed water activity and explored differences in seed hydration dynamics between species. Seed water activity was sufficiently high (i.e., ≥ 0.85 aw) so as to have created an increased risk of mortality if a fire had occurred during an almost continuous period between May and November in the study period (i.e., 2017). There were brief windows when seeds may have been in a dry state during early winter and late spring, and also when they may have been in a wet state during summer and late autumn. These data, and the associated analyses, provide an opportunity to develop approaches to minimize seed mortality during fire and maximize the seed bank response.
Identification of Heat Tolerant Cotton Lines Showing Genetic Variation in Cell Membrane Thermostability, Stomata, and Trichome Size and Its Effect on Yield and Fiber Quality Traits
Authors: Abro Saifullah , Rizwan Muhammad , Deho Zaheer Ahmed , Abro Shafiq Ahmed , Sial Mahboob Ali
Published: January 2022

Heat stress in cotton reduces its productivity. The development of heat-tolerant cotton varieties having resilience against changing climate is feasible. The purpose of this study was to probe the genetic variability in upland cotton for heat tolerance, the association of cell membrane thermostability (CMT), stomata, and trichome size with cotton adaptation to high temperature and effective breeding strategy to advance the valued traits. Relative cell injury percentage (RCI%) in studied genotypes ranged from 39 to 86%. Seventeen genotypes were found heat tolerant on the basis of low RCI%, heat susceptibility index (HSI<1), higher number of boll/plant, and seed cotton yield (SCY). Scanning electron microscopy (SEM) of heat-tolerant genotypes revealed the presence of different size of stomata (21.57 to 105.04 μm2) and trichomes (177 to 782.6 μm) on leaves of selected genotypes. The regression analysis showed a strong and negative association of RCI% and stomata size with SCY. However, no association was observed between the trichome size, yield, and fiber traits. On the overall location basis, a significant genotype × environment interaction was observed. All selected genotypes produced a higher SCY as compared with check varieties. But the stability analysis showed that the high yielding genotypes NIA-M-30, NIA-80, NIA-83, and CRIS-342 were also wide adaptive with unit regression (bi∼1) and non-significant deviation from the regression line (S2d∼0). The ability for the combination of some heat-tolerant genotypes was estimated by using the line × tester method among nine hybrids along with their 3 testers (i.e., male) and 3 lines (i.e., females). Genotypes, CRIS-342 and NIA-Perkh, were observed as best general combiners for SCY with a negative general combining ability effects for RCI%. Five hybrids showed a positive specific combining ability and heterotic effects for studied traits and also found lowest for HSI. RCI% and SCY/plant displayed higher estimates of heritability and genetic advance, indicating the heritability due to additive gene effects and chances of effective selection. The identified heat-tolerant and wide adaptive germplasm can be further advanced and utilized in cotton breeding programs for developing heat-tolerant cultivars. Selection criteria involving CMT and stomata size concluded to be an effective strategy for the screening of heat-tolerant cotton.
Analysis of Genetic Regions Related to Field Grain Number per Spike From Chinese Wheat Founder Parent Linfen 5064
Authors: Qiao Ling , Li Hanlin , Wang Jie , Zhao Jiajia , Zheng Xingwei , Wu Bangbang , Du Weijun , Wang Juanling , Zheng Jun
Published: January 2022

Wheat founder parents have been important in the development of new wheat cultivars. Understanding the effects of specific genome regions on yield-related traits in founder variety derivatives can enable more efficient use of these genetic resources through molecular breeding. In this study, the genetic regions related to field grain number per spike (GNS) from the founder parent Linfen 5064 were analyzed using a doubled haploid (DH) population developed from a cross between Linfen 5064 and Nongda 3338. Quantitative trait loci (QTL) for five spike-related traits over nine experimental locations/years were identified, namely, total spikelet number per spike (TSS), base sterile spikelet number per spike (BSSS), top sterile spikelet number per spike (TSSS), fertile spikelet number per spike (FSS), and GNS. A total of 13 stable QTL explaining 3.91–19.51% of the phenotypic variation were found. The effect of six of these QTL, Qtss.saw-2B.1, Qtss.saw-2B.2, Qtss.saw-3B, Qfss.saw-2B.2, Qbsss.saw-5A.1, and Qgns.saw-1A, were verified by another DH population (Linfen 5064/Jinmai 47), which showed extreme significance (P < 0.05) in more than three environments. No homologs of reported grain number-related from grass species were found in the physical regions of Qtss.saw-2B.1 and Qtss.saw-3B, that indicating both of them are novel QTL, or possess novel-related genes. The positive alleles of Qtss.saw-2B.2 from Linfen 5064 have the larger effect on TSS (3.30%, 0.62) and have 66.89% in Chinese cultivars under long-term artificial selection. This study revealed three key regions for GNS in Linfen 5064 and provides insights into molecular marker-assisted breeding.
Wellbeing and Resilience in Tourism: A Systematic Literature Review During COVID-19
Authors: Pocinho Margarida , Garcês Soraia , de Jesus Saúl Neves
Published: January 2022

The United Nations World Tourism Organization (UWTO) has acknowledged 2020 as the worst year in tourism history due to the worldwide pandemic COVID-19. Destinations, tourists, local communities, stakeholders, and residents, and their daily activities were affected. Thus, wellbeing and resilience are two crucial variables to help the industry and the people recover. This research aims to analyze early positive approaches and attitudes to respond to the negative impact of COVID-19 in tourism everyday activities that have at its core wellbeing and resilience, the two main variables of the Positive Psychology field of studies. A systematic literature review was conducted, following PRISMA guidelines to achieve this aim. The research was done using the Online Knowledge Library (B-on) and all the available databases. The research led to 32 articles that were screened using the inclusion and exclusion criteria. A total of 18 scientific articles met all criteria. Overall, results show that a positive and resilient approach to deal with the adverse outcomes of the pandemic is a concern for stakeholders and the future of the organizations in the tourism and hospitality sector, as is tourists’ wellbeing. However, less research has been done on wellbeing and a clear lack of research regarding residents’ wellbeing and resilience is evident. A deeper study of wellbeing and resilience in tourism is needed, and actual practices and interventions to ensure that all tourism actors have the resources to overcome the pandemic and restart the industry’s daily lives feeling well and safe.
Effects of Daytime Electric Light Exposure on Human Alertness and Higher Cognitive Functions: A Systematic Review
Authors: Siraji Mushfiqul Anwar , Kalavally Vineetha , Schaefer Alexandre , Haque Shamsul
Published: January 2022

This paper reports the results of a systematic review conducted on articles examining the effects of daytime electric light exposure on alertness and higher cognitive functions. For this, we selected 59 quantitative research articles from 11 online databases. The review protocol was registered with PROSPERO (CRD42020157603). The results showed that both short-wavelength dominant light exposure and higher intensity white light exposure induced alertness. However, those influences depended on factors like the participants’ homeostatic sleep drive and the time of day the participants received the light exposure. The relationship between light exposure and higher cognitive functions was not as straightforward as the alerting effect. The optimal light property for higher cognitive functions was reported dependent on other factors, such as task complexity and properties of control light. Among the studies with short-wavelength dominant light exposure, ten studies (morning: 3; afternoon: 7) reported beneficial effects on simple task performances (reaction time), and four studies (morning: 3; afternoon: 1) on complex task performances. Four studies with higher intensity white light exposure (morning: 3; afternoon: 1) reported beneficial effects on simple task performance and nine studies (morning: 5; afternoon: 4) on complex task performance. Short-wavelength dominant light exposure with higher light intensity induced a beneficial effect on alertness and simple task performances. However, those effects did not hold for complex task performances. The results indicate the need for further studies to understand the influence of short-wavelength dominant light exposure with higher illuminance on alertness and higher cognitive functions.
The Emergence of 5-Year-Olds’ Behavioral Difficulties: Analyzing Risk and Protective Pathways in the United Kingdom and Germany
Authors: Huang Wei , Weinert Sabine , Wareham Helen , Law James , Attig Manja , von Maurice Jutta , Roßbach Hans-Günther
Published: January 2022

This study aimed to advance our understanding of 5-year-olds’ behavioral difficulties by modeling and testing both mediational protective and risk pathways simultaneously. Drawing on two national samples from different Western European countries—the United Kingdom (13,053) and Germany (2,022), the proposed model considered observed sensitive parental interactive behaviors and tested child vocabulary as protective pathways connecting parental education with children’s behavioral outcomes; the risk pathways focused on negative parental disciplinary practices linking (low) parental education, parental distress, and children’s difficult temperament to children’s behavioral difficulties. Further, the tested model controlled for families’ income as well as children’s sex and formal child care attendance. Children with comparatively higher educated parents experienced more sensitive interactive behavior, had more advanced vocabulary, and exhibited fewer behavioral difficulties. Children with a comparatively higher level of difficult temperament or with parents who suffered from distress tended to experience more negative disciplinary behavior and exhibited more behavioral difficulties. Additionally, children’s vocabulary skills served as a mechanism mediating the association between parental education and children’s behavioral difficulties. Overall, we found similar patterns of results across the United Kingdom and Germany with both protective and risk pathways contributing simultaneously to children’s behavioral development. The findings suggest that promoting parents’ sensitive interactive behaviors, favorable disciplinary practices, and child’s vocabulary skills have potential for preventing early behavioral difficulties.
Hong Kong Women Project a Larger Body When Speaking to Attractive Men
Authors: Lee Albert , Ng Eva
Published: January 2022

In this pilot study we investigated the vocal strategies of Cantonese women when addressing an attractive vs. unattractive male. We recruited 19 young female native speakers of Hong Kong Cantonese who completed an attractiveness rating task, followed by a speech production task where they were presented a subset of the same faces. By comparing the rating results and corresponding acoustic data of the facial stimuli, we found that when young Cantonese women spoke to an attractive male, they were less breathy, lower in fundamental frequency, and with denser formants, all of which are considered to project a larger body. Participants who were more satisfied with their own height used these vocal strategies more actively. These results are discussed in terms of the body size projection principle.
The Work Gratitude Scale: Development and Evaluation of a Multidimensional Measure
Authors: Youssef-Morgan Carolyn M. , van Zyl Llewellyn E. , Ahrens Barbara L.
Published: January 2022

This study explores gratitude as a multidimensional and work-specific construct. Utilizing a sample of 625 employees from a variety of positions in a medium-sized school district in the United States, we developed and evaluated a new measure, namely the Work Gratitude Scale (WGS), which encompasses recognized conative (intentional), cognitive, affective, and social aspects of gratitude. A systematic, six-phased approach through structural equation modeling (SEM) was used to explore and confirm the factorial structure, internal consistency, measurement invariance, concurrent, convergent, and discriminant validity of the WGS. The results supported a 10-item measure with three dimensions: “grateful appraisals” (three items), “gratitude toward others” (four items), and “intentional attitude of gratitude” (three items). Thereafter, first-order, second-order, and bifactor confirmatory models were estimated and compared. Work gratitude was found to be best described by a second-order construct with three underlying first-order dimensions. Measurement invariance was supported in relation to gender. Concurrent validity was supported in relation to two existing dispositional gratitude scales, namely the Gratitude Questionnaire and the Gratitude, Resentment, and Appreciation Scale (GRAT). Convergent validity was supported in relation to the Core Self-Evaluations Scale (CSES) and the Psychological Capital Questionnaire. Discriminant validity was supported in relation to various demographic factors such as age, gender, occupation, and tenure. The findings support the WGS as a multidimensional measure that can be used in practice to measure overall work-related gratitude and to track the effectiveness of gratitude-related workplace interventions.
Dosing Cariprazine Within and Beyond Clinical Trials: Recommendations for the Treatment of Schizophrenia
Authors: Rancans Elmars , Dombi Zsófia Borbála , Barabássy Ágota
Published: January 2022

Although the optimal dosing of an antipsychotic medication is known to be essential in the long-term management of schizophrenia, in case of novel drugs such as cariprazine, determining the right dosing strategy is not that simple. Without decades of experience with a particular compound, evidence regarding dosing and titration comes primarily from double-blind, placebo controlled clinical trials that are not necessarily mirroring the real-life experiences of doctors. Via summarizing data from both clinical data (n = 3275) and real-world evidence (observational study n = 116, case studies n = 29), this perspective paper aims to shed a light on the appropriate dosing strategies of cariprazine from treatment initiation through switching strategies to concomitant medications.
Analysis of Tracheobronchial Diverticula Based on Semantic Segmentation of CT Images via the Dual-Channel Attention Network
Authors: Zhang Maoyi , Ding Changqing , Guo Shuli
Published: January 2022

Tracheobronchial diverticula (TD) is a common cystic lesion that can be easily neglected; hence accurate and rapid identification is critical for later diagnosis. There is a strong need to automate this diagnostic process because traditional manual observations are time-consuming and laborious. However, most studies have only focused on the case report or listed the relationship between the disease and other physiological indicators, but a few have adopted advanced technologies such as deep learning for automated identification and diagnosis. To fill this gap, this study interpreted TD recognition as semantic segmentation and proposed a novel attention-based network for TD semantic segmentation. Since the area of TD lesion is small and similar to surrounding organs, we designed the atrous spatial pyramid pooling (ASPP) and attention mechanisms, which can efficiently complete the segmentation of TD with robust results. The proposed attention model can selectively gather features from different branches according to the amount of information they contain. Besides, to the best of our knowledge, no public research data is available yet. For efficient network training, we constructed a data set containing 218 TD and related ground truth (GT). We evaluated different models based on the proposed data set, among which the highest MIOU can reach 0.92. The experiments show that our model can outperform state-of-the-art methods, indicating that the deep learning method has great potential for TD recognition.
Co-Inference of Data Mislabelings Reveals Improved Models in Genomics and Breast Cancer Diagnostics
Authors: Gerber Susanne , Pospisil Lukas , Sys Stanislav , Hewel Charlotte , Torkamani Ali , Horenko Illia
Published: January 2022

Mislabeling of cases as well as controls in case–control studies is a frequent source of strong bias in prognostic and diagnostic tests and algorithms. Common data processing methods available to the researchers in the biomedical community do not allow for consistent and robust treatment of labeled data in the situations where both, the case and the control groups, contain a non-negligible proportion of mislabeled data instances. This is an especially prominent issue in studies regarding late-onset conditions, where individuals who may convert to cases may populate the control group, and for screening studies that often have high false-positive/-negative rates. To address this problem, we propose a method for a simultaneous robust inference of Lasso reduced discriminative models and of latent group-specific mislabeling risks, not requiring any exactly labeled data. We apply it to a standard breast cancer imaging dataset and infer the mislabeling probabilities (being rates of false-negative and false-positive core-needle biopsies) together with a small set of simple diagnostic rules, outperforming the state-of-the-art BI-RADS diagnostics on these data. The inferred mislabeling rates for breast cancer biopsies agree with the published purely empirical studies. Applying the method to human genomic data from a healthy-ageing cohort reveals a previously unreported compact combination of single-nucleotide polymorphisms that are strongly associated with a healthy-ageing phenotype for Caucasians. It determines that 7.5% of Caucasians in the 1000 Genomes dataset (selected as a control group) carry a pattern characteristic of healthy ageing.
Consolidating and Upscaling Molecular Research Capacity in Nigeria: On Who's Account?
Authors: Chukwudi Chinwe Uzoma
Published: January 2022

Molecular research and researchers engage in studies that seek to understand the structures, functions, and interactions of biomolecules as the basis for cellular and systemic effects in living organisms. This research approach was made possible by considerable technological advancements that equip researchers with tools to view biomolecules. Although molecular research holds great promises for improving lives and living, the technological requirements and equipment to undertake molecular research are quite expensive, often requiring a heavy start-up capital or investment. In developing countries such as Nigeria, where the majority of the population lives below the poverty line and research funding is abysmally low, such heavy investments into research that do not provide immediate solutions to societal problems are difficult. This is mostly due to limited resources available to tackle many urgent and pressing needs, and limited perspective and understanding of policymakers, leading to infrastructural and skilled personnel deficit to support molecular research. Despite all these, the field of molecular research continues to grow exponentially globally, hence, funding and investments into this critical life science research area have become imperative. With the rich biodiversity of humans, animals, and plants in Nigeria, and the huge burden of infectious diseases in the country or region, global advances in genomics and proteomics studies will be incomplete without adequate contribution from Nigeria and sub-Saharan Africa region. This paper examines the progression and challenges of undertaking molecular research in Nigeria, and how Nigerian molecular research scientists are tackling these issues, with recommendations for improved molecular research capacity and output in the country or region.
Parrots, Cockroaches, Octopuses: Are They Conscious?
Authors: Jablonka Eva , Ginsburg Simona , Zeligowski Anat
Published: January 2022

Which living organisms are conscious, feeling creatures, and which are more like sophisticated robots that can only respond to stimuli and solve simple problems? There are many different and hotly debated answers to this question. We used biology to come up with a new approach for determining which organisms are conscious. We propose that organisms that can learn in a specific, flexible manner are conscious. Using this criterion, it is likely that consciousness first appeared about 540 million years ago and can now be found in many animal species. If our ideas are accepted, this means that we must change our attitude toward non-human animals and do a better job of protecting them from pain and suffering.
Seafood in Food Security: A Call for Bridging the Terrestrial-Aquatic Divide
Authors: Stetkiewicz Stacia , Norman Rachel A. , Allison Edward Hugh , Andrew Neil L. , Ara Gulshan , Banner-Stevens Gill , Belton Ben , Beveridge Malcolm , Bogard Jessica R. , Bush Simon R. , Coffee Pete , Crumlish Margaret , Edwards Peter , Eltholth Mahmoud , Falconer Lynne , Ferreira Joao G. , Garrett Angus , Gatward Iain , Islam Faruk U. , Kaminski Alexander M. , Kjellevold Marian , Kruijssen Froukje , Leschen William , Mamun Abdullah-Al , McAdam Bruce , Newton Richard , Krogh-Poulsen Birgitte , Pounds Alexandra , Richardson Belinda , Roos Nanna , Röös Elin , Schapper Andrea , Spence-McConnell Tori , Suri Sharon K. , Thilsted Shakuntala Haraksingh , Thompson Kim D. , Tlusty Michael F. , Troell Max Fredrik , Vignola Raffaele , Young James A. , Zhang Wenbo , Little David C.
Published: January 2022

The contribution of seafood to global food security is being increasingly highlighted in policy. However, the extent to which such claims are supported in the current food security literature is unclear. This review assesses the extent to which seafood is represented in the recent food security literature, both individually and from a food systems perspective, in combination with terrestrially-based production systems. The results demonstrate that seafood remains under-researched compared to the role of terrestrial animal and plant production in food security. Furthermore, seafood and terrestrial production remain siloed, with very few papers addressing the combined contribution or relations between terrestrial and aquatic systems. We conclude that far more attention is needed to the specific and relative role of seafood in global food security and call for the integration of seafood in a wider interdisciplinary approach to global food system research.
Localization of the Serotonin Transporter in the Dog Intestine and Comparison to the Rat and Human Intestines
Authors: Chiocchetti Roberto , Galiazzo Giorgia , Giancola Fiorella , Tagliavia Claudio , Bernardini Chiara , Forni Monica , Pietra Marco
Published: January 2022

Serotonin is crucial in gastrointestinal functions, including motility, sensitivity, secretion, and the inflammatory response. The serotonin transporter (SERT), responsible for serotonin reuptake and signaling termination, plays a prominent role in gastrointestinal physiology, representing a promising therapeutic target in digestive disorders. Serotonin transporter expression has been poorly investigated in veterinary medicine, under both healthy and pathological conditions, including canine chronic enteropathy, in which the serotonin metabolism seems to be altered. The aim of the present study was to determine the distribution of SERT immunoreactivity (SERT-IR) in the dog intestine and to compare the findings with those obtained in the rat and human intestines. Serotonin transporter-IR was observed in canine enterocytes, enteric neurons, lamina propria cells and the tunica muscularis. Data obtained in dogs were consistent with those obtained in rats and humans. Since the majority of the serotonin produced by the body is synthesized in the gastrointestinal tract, SERT-expressing cells may exert a role in the mechanism of serotonin reuptake.
Initial Home Dialysis Is Increased for Rural Patients by Accessing Urban Facilities
Authors: Adler Joel T. , Husain S. Ali , Xiang Lingwei , Rodrigue James R. , Waikar Sushrut S.
Published: January 2022

Key Points

Despite having access to fewer facilities that offer home dialysis, rural patients with ESKD are more likely to be on home dialysis.

There remains a significant mortality gap between urban and rural patients with ESKD, even when accessing home dialysis.

Background

The 240,000 rural patients with end stage kidney disease in the United States have less access to nephrology care and higher mortality than those in urban settings. The Advancing American Kidney Health initiative aims to increase the use of home renal replacement therapy. Little is known about how rural patients access home dialysis and the availability and quality of rural dialysis facilities.

Methods

Incident dialysis patients in 2017 and their facilities were identified in the United States Renal Data System. Facility quality and service availability were analyzed with descriptive statistics. We assessed the availability of home dialysis methods, depending on rural versus urban counties, and then we used multivariate logistic regression to identify the likelihood of rural patients with home dialysis as their initial modality and the likelihood of rural patients changing to home dialysis within 90 days. Finally, we assessed mortality after dialysis initiation on the basis of patient home location.

Results

Of the 97,930 dialysis initiates, 15,310 (16%) were rural. Rural dialysis facilities were less likely to offer home dialysis (51% versus 54%, P<0.001). Although a greater proportion of rural patients (9% versus 8%, P<0.001) were on home dialysis, this was achieved by traveling to urban facilities to obtain home dialysis (OR=2.74, P<0.001). After adjusting for patient and facility factors, rural patients had a higher risk of mortality (HR=1.06, P=0.004).

Conclusions

Despite having fewer facilities that offer home dialysis, rural patients were more often on home dialysis methods because they traveled to urban facilities, representing an access gap. Even if rural patients accessed home dialysis at urban facilities, rural patients still suffered worse mortality. Future dialysis policy should address this access gap to improve care and overall mortality for rural patients.
Potenciais complicações do uso inadequado de medicamentos contínuos em pacientes com problemas de longa duração / Complicaciones potenciales de uso inadecuado de medicamentos continuos en pacientes con problemas a largo plazo
Authors: Da Mata Tamara Nicoletti , Barros Lizandra Alvares Félix , Oshiro Maria de Lourdes
Published: January 2022

Com o envelhecimento, algumas pessoas podem necessitar de cuidados em variados graus de dependência, e por isso, alguns idosos são internados em instituições não hospitalares de longa permanência. O objetivo do presente estudo foi analisar o uso de medicamentos em idosos internados em uma instituição não hospitalar, de longa permanência, com atenção ao perfil de uso e demais fatores associados à terapia medicamentosa. Realizou-se um estudo quantitativo, descritivo e de corte transversal, a partir da avaliação de prontuários de pacientes idosos, que residem na instituição de longa permanência. Foram analisados 70 prontuários. Cada idoso utiliza em média 9,8 medicamentos, sendo que 8,1 fármacos são administrados no mesmo horário por idoso. Considerando a importância da assistência multidisciplinar na terapia medicamentosa e no cuidado à pessoa idosa, os profissionais devem possuir amplo conhecimento sobre os medicamentos, além de zelar para que o processo seja seguro e eficiente.
Estágio optativo em otorrinolaringologia e sua importância: relato de experiência
Authors: Vargas Larissa Jardim , Duarte Bianca Sousa , Pimenta Raissa de Sousa Marinho , Vaz Gleiciane Ramos , Oliveira Andressa Viana , Braga Stephanie Oliveira , de Lucena Talytta Marinho , Manari Adria Luiza Silva , Pires Maria Eugênia de Paula , Rabelo Kamylla Paulla Saldanha
Published: January 2022

Introdução: O estágio vem se mostrando cada vez mais importante para a formação do acadêmico de medicina e a consolidação do seu conhecimento, bem como oportunidade de experiências valiosas para o aprendizado prático. Assim, vivências proporcionadas por estágios voluntários contribuem para a formação de habilidades necessárias de um médico generalista, com capacidade de resolutividade, reflexão e integração do conhecimento. Objetivo: Relatar a experiência de um estágio voluntário em otorrinolaringologia e a sua importância para a formação do estudante de medicina como generalista. Relato de experiência: O relato conta com experiências vividas por um discente no estágio obrigatório e optativo durante o período de 18 de fevereiro de 2019 a 08 de abril de 2019, com carga horaria de 40 horas semanais, pelo Instituto de Otorrino Dr. Aureo C. Cangussu, na cidade de Imperatriz-MA. O estágio optativo é um elo entre o mercado de trabalho e a rotina estudantil, como uma forma de apresentação do estudante a sua rotina profissional. Assim, é permitido desfrutar de diversas áreas de aprendizagem, bem como acompanhar a rotina ambulatorial e ainda do centro cirúrgico, aumentando assim a possibilidade de novas experiências. Conclusão: Nesse sentido, conclui-se que o estágio traz ao acadêmico de medicina grandes possibilidades referentes a aplicabilidade do conteúdo teórico aprendido durante a sua formação nas atividades que são propostas durante esse período, além de permitir uma formação generalista com maior qualidade devido as experiências que são desenvolvidas no estágio.
DIRECT SALE AS ONE OF THE ORGANIZATIONAL FORMS OF LOCAL FOOD SYSTEMS. THE SPATIAL CONCENTRATION OF DIRECT SALE ENTITIES IN POLAND
Authors: Bareja-Wawryszuk Ola , Pajewski Tomasz
Published: January 2022

Direct selling is one of the most common local activities in the agri-food sector. Contemporary trends in the production and consumption of food indicate a duality of food systems, in which the concept of industrialization of the agri-food sector is simultaneously developing together with a concept of local food systems. In this article, it was noticed that the direct sale of agri-food products is in a line with the contemporary trends in the agri-food sector, and that it is important to analyze its spatial patterns. Taking into account the spatial concentration of direct selling entities, it has been proved that their distribution is random and does not show clustering patterns.