bluuebunny/crossref_metadata_2025 huggingface dataset:
Beta-2-microglobulin Mutations Are Linked to a Distinct Metastatic Pattern and a Favorable Outcome in Microsatellite-Unstable Stage IV Gastrointestinal Cancers
Authors: Busch Elena , Ahadova Aysel , Kosmalla Kosima , Bohaumilitzky Lena , Pfuderer Pauline L. , Ballhausen Alexej , Witt Johannes , Wittemann Jan-Niklas , Bläker Hendrik , Holinski-Feder Elke , Jäger Dirk , von Knebel Doeberitz Magnus , Haag Georg Martin , Kloor Matthias
Published: June 2021

Immune checkpoint blockade (ICB) shows remarkable clinical effects in patients with metastatic microsatellite-unstable (MSI) cancer. However, markers identifying potential non-responders are missing. We examined the prevalence of Beta-2-microglobulin (B2M) mutations, a common immune evasion mechanism, in stage IV MSI gastrointestinal cancer and its influence on metastatic pattern and patients’ survival under ICB. Twenty-five patients with metastatic, MSI gastrointestinal adenocarcinoma were included. Eighteen patients received ICB with pembrolizumab and one patient with nivolumab/ipilimumab. Sequencing was performed to determine B2M mutation status. B2M mutations and loss of B2M expression were detected in 6 out of 25 stage IV MSI cancers. B2M mutations were strongly associated with exclusively peritoneal/peritoneal and lymph node metastases (p=0.0055). However, no significant differences in therapy response (25% vs. 46.6%, p>0.99) and survival (median PFS: 19.5 vs 33.0 months, p=0.74; median OS 39 months vs. not reached, p>0.99) were observed between B2M-mutant and B2M-wild type tumor patients. Among metastatic MSI GI cancers, B2M-mutant tumors represent a biologically distinct disease with distinct metastatic patterns. To assess ICB response in B2M-mutant MSI cancer patients, future studies need to account for the fact that baseline survival of patients with B2M-mutant MSI cancer may be longer than of patients with B2M-wild type MSI cancer.
US-Based Deep Learning Model for Differentiating Hepatocellular Carcinoma (HCC) From Other Malignancy in Cirrhotic Patients
Authors: Zhou Hang , Jiang Tao , Li Qunying , Zhang Chao , Zhang Cong , Liu Yajing , Cao Jing , Sun Yu , Jin Peile , Luo Jiali , Pan Minqiang , Huang Pintong
Published: June 2021

The aim was to build a predictive model based on ultrasonography (US)-based deep learning model (US-DLM) and clinical features (Clin) for differentiating hepatocellular carcinoma (HCC) from other malignancy (OM) in cirrhotic patients. 112 patients with 120 HCCs and 60 patients with 61 OMs were included. They were randomly divided into training and test cohorts with a 4:1 ratio for developing and evaluating US-DLM model, respectively. Significant Clin predictors of OM in the training cohort were combined with US-DLM to build a nomogram predictive model (US-DLM+Clin). The diagnostic performance of US-DLM and US-DLM+Clin were compared with that of contrast enhanced magnetic resonance imaging (MRI) liver imaging and reporting system category M (MRI LR-M). US-DLM was the best independent predictor for evaluating OMs, followed by clinical information, including high cancer antigen 199 (CA199) level and female. The US-DLM achieved an AUC of 0.74 in the test cohort, which was comparable with that of MRI LR-M (AUC=0.84, p=0.232). The US-DLM+Clin for predicting OMs also had similar AUC value (0.81) compared with that of LR-M+Clin (0.83, p>0.05). US-DLM+Clin obtained a higher specificity, but a lower sensitivity, compared to that of LR-M +Clin (Specificity: 82.6% vs. 73.9%, p=0.007; Sensitivity: 78.6% vs. 92.9%, p=0.006) for evaluating OMs in the test set. The US-DLM+Clin model is valuable in differentiating HCC from OM in the setting of cirrhosis.
Case Report: EGFR-Positive Early-Stage Lung Adenocarcinoma Transforming to Squamous Cell Carcinoma After TKI Treatment
Authors: Liao Jiatao , Li Yuan , Liu Chang , Long Qianqian , Wang Jialei
Published: June 2021

The histological transformation from epidermal growth factor receptor (EGFR)-mutated adenocarcinoma (ADC) to squamous cell carcinoma (SCC) after tyrosine kinase inhibitor (TKI) treatment is rare. We present a case of a patient who transitioned from early-stage primary lung ADC with partial squamous differentiation, EGFR mutation and amplification, to adrenal gland metastasis as SCC with EGFR amplification disappearance 115-months after surgery, during which gefitinib and local radiotherapy were utilized for the metastasis in the right femoral head and mediastinal lymph nodes. This case might indicate a possible mechanism of EGFR inhibition resistance with SCC transition and EGFR amplification loss from the initially well-responding ADC, especially those with SCC or partial squamous differentiation. The optimal post-progression therapy for ADC-SCC patients is challenging and further studies are needed.
Association Between Allergen Sensitization and Anaphylaxis in Patients Visiting a Pediatric Emergency Department
Authors: Lee Won Seok , Cha Lily Myung-Jin , Han Man Yong , Lee Kyung Suk
Published: June 2021

Background and Objectives: Anaphylaxis, a severe allergic disease, can be triggered by various causes. This study investigated the association between allergic sensitization and anaphylactic symptoms and the severity of anaphylaxis in children.

Patients and Methods: A retrospective review of 107 pediatric patients with anaphylaxis was performed between January 1, 2015, and December 31, 2017; 74 patients underwent allergen testing for specific immunoglobulin E. Allergic sensitizations and associations with anaphylactic symptoms and severity were investigated.

Results: Overall, 64 (86.5%) patients were sensitized to food or inhalant allergens. In children under 2 years of age, 90.5% were sensitized to food (P = 0.001); in those over 6 years of age, 84.6% were sensitized to inhalant allergens (P = 0.001). Milk sensitization was significantly associated with severe anaphylaxis (P = 0.036). The following symptoms showed significant associations with certain allergen sensitizations: facial edema with food; wheezing with milk; dyspnea with mite, etc. Certain allergen sensitizations presenting as risk factors for anaphylactic symptoms: wheat (adjusted odds ratio [aOR] = 4.644, P = 0.044) and nuts (aOR=3.614, P = 0.041) for wheezing, nuts (aOR=5.201, P = 0.026) for dyspnea, and milk (aOR=4.712, P = 0.048) for vomiting.

Conclusion: The allergen sensitization status differed according to the age of the children experiencing anaphylaxis. The severity, symptoms, and signs of anaphylaxis differed depending on the allergen sensitization status.
Salidroside Improves Chronic Stress Induced Depressive Symptoms Through Microglial Activation Suppression
Authors: Fan Yang , Bi Yajuan , Chen Haixia
Published: June 2021

Depression is a severe neurological disorder highly associated with chronic mental stress stimulation, which involves chronic inflammation and microglial activation in the central nervous system (CNS). Salidroside (SLDS) has been reported to exhibit anti-neuroinflammatory and protective properties on neurological diseases. However, the mechanism underlying the effect of SLDS on depressive symptoms has not been well elaborated. In the present study, the effects of SLDS on depressive behaviors and microglia activation in mice CNS were investigated. Behavioral tests, including Forced swimming test (FST), Open field test (OFT) and Morris water maze (MWM) revealed that SLDS treatment attenuated the depressive behaviors in stress mice. SLDS treatment significantly reduced the microglial immunoreactivity for both Iba-1 and CD68, characteristic of deleterious M1 phenotype in hippocampus of stress mice. Additionally, SLDS inhibited microglial activation involving the suppression of ERK1/2, P38 MAPK and p65 NF-κB activation and thus reduced the expression and release of neuroinflammatory cytokines in stress mice as well as in lipopolysaccharide (LPS)-induced primary microglia. Also, SLDS changed microglial morphology, attachment and reduced the phagocytic ability in LPS-induced primary microglia. The results demonstrated that SLDS treatment could improve the depressive symptoms caused by unpredictable chronic stress, indicating a potential therapeutic application of SLDS in depression treatment by interfering microglia-mediated neuroinflammation.
Impaired Cerebral Autoregulation After Subarachnoid Hemorrhage: A Quantitative Assessment Using a Mouse Model
Authors: Koide Masayo , Ferris Hannah R. , Nelson Mark T. , Wellman George C.
Published: June 2021

Subarachnoid hemorrhage (SAH) is a common form of hemorrhagic stroke associated with high rates of mortality and severe disability. SAH patients often develop severe neurological deficits days after ictus, events attributed to a phenomenon referred to as delayed cerebral ischemia (DCI). Recent studies indicate that SAH-induced DCI results from a multitude of cerebral circulatory disturbances including cerebral autoregulation malfunction. Cerebral autoregulation incorporates the influence of blood pressure (BP) on arterial diameter in the homeostatic regulation of cerebral blood flow (CBF), which is necessary for maintaining constant brain perfusion during physiological swings in systemic BP. In this study, we quantitatively examined the impact of SAH on cerebral autoregulation using a mouse endovascular perforation model and a newly developed approach combining absolute and relative CBF measurements. This method enables a direct quantitative comparison of cerebral autoregulation between individual animals (e.g., SAH vs. control or sham-operated mice), which cannot be done solely using relative CBF changes by laser Doppler flowmetry. Here, absolute CBF was measured via injection of fluorescent microspheres at a baseline BP. In separate groups of animals, in vivo laser Doppler flowmetry was used to measure relative CBF changes over a range of BP using phlebotomy and the pressor phenylephrine to lower and raise BP, respectively. Absolute CBF measurements from microspheres were then used to calibrate laser Doppler measurements to calculate the relationship between CBF and BP, i.e., “cerebral autoregulation curves.” Un-operated and sham-operated groups exhibited similar cerebral autoregulatory curves, showing comparable levels of relatively constant CBF over a range of BP from ~80 mmHg to ~130 mmHg. In contrast, SAH animals exhibited a narrower autoregulatory range of BP, which was primarily due to a decrease in the upper limit of BP whereby cerebral autoregulation was maintained. Importantly, SAH animals also exhibited a marked decrease in CBF throughout the entire range of BP. In sum, this study provides evidence of the dramatic reduction in cortical CBF and the diminished range of autoregulation after SAH. Furthermore, this novel methodology should pave the way for future studies examining pathological mechanisms and/or therapeutic strategies targeting impaired cerebral autoregulation, a pathology common to many cardiovascular and cerebrovascular disorders.
Genetic Variation for Economically Important Traits in Cupressus lusitanica in New Zealand
Authors: Ismael Ahmed , Klápště Jaroslav , Stovold Grahame T. , Fleet Kane , Dungey Heidi
Published: June 2021

Increasing productivity and tolerance against cypress canker disease is an important goal in the Mexican white cypress breeding program in New Zealand, and screening has been in place since 1983. Cypress canker disease is caused by Seiridium cardinale and Seiridium cupressi, the current study presents the results of two progeny trials within the breeding program in the North Island of New Zealand. The trials were established as open-pollinated progeny tested and were assessed for diameter at breast height, branch size, canker severity score, malformation score, and stem straightness score and acceptability score. Heritability estimates were moderate ranging from 0.21 to 0.41 for diameter at breast height and from 0.14 to 0.31 for canker severity score. Stem form attributes showed heritability from 0.08 (malformation) to 0.38 (straightness). No trait showed any significant G × E interaction between investigated sites. This was supported by the very strong genetic correlations estimated between the traits recorded in Welcome Bay and Matata trials. Unfavourable genetic correlations ranging from 0.25 to 0.46 were found between diameter at breast height and canker severity score, indicating that the continued selection for genotypes with improved diameter at breast height would also increase susceptibility to cypress canker. Additionally, unfavourable genetic correlations ranging from 0.52 to 0.73 were found between branch size and diameter at breast height and should be considered in selection programs. The moderate heritability estimated for canker severity score indicates that breeding values for this trait could be predicted with acceptable accuracy and included in the breeding program for Cupressus lusitanica, enabling the identification of genotypes with tolerance to canker severity to be deployed to locations where cypress canker is present in New Zealand.
Exposure to Literary Fiction Is Associated With Lower Psychological Essentialism
Authors: Castano Emanuele , Paladino Maria Paola , Cadwell Olivia G. , Cuccio Valentina , Perconti Pietro
Published: June 2021

We investigated the impact of exposure to literary and popular fiction on psychological essentialism. Exposure to fiction was measured by using the Author Recognition Test, which allows us to separate exposure to authors of literary and popular fiction. Psychological essentialism was assessed by the discreteness subscale of the psychological essentialism scale in Study 1, and by the three subscales of the same scale (such as discreteness, informativeness, and biological basis) in Study 2 that was pre-registered. Results showed that exposure to literary fiction negatively predicts the three subscales. The results emerged controlling for political ideology, a variable that is commonly associated with psychological essentialism, and level of education.
Development of the Family Togetherness Scale: A Mixed-Methods Validation Study in Kenya
Authors: Puffer Eve S. , Giusto Ali , Rieder Amber D. , Friis-Healy Elsa , Ayuku David , Green Eric P.
Published: June 2021

Family functioning is an important target of clinical intervention and research given its close ties with mental health outcomes of both children and adults. However, we lack family functioning measures validated for use in many low- and middle-income country (LMIC) settings. In this mixed-methods prospective diagnostic accuracy study, we first used formative qualitative data to develop an extensive battery of screening items to measure family functioning in Kenya. We then recruited 30 Kenyan families (N = 44 adults; 30 youth aged 8–17 years) to complete the questionnaires and participate in clinical interviews conducted by local interviewers. Quantitative and qualitative analyses were then conducted to select a subset of screening items that balanced conceptual understanding of family distress with diagnostic efficiency and accuracy to yield a brief but valid scale. The final index test consisting of 30 items correctly identified distressed families in 89% of cases according to adult-report and 76% of cases according to child-report. The optimal cutoffs are associated with estimates of sensitivity/specificity of 0.88/0.90 and 0.75/0.77 for adult-report and child-report measures, respectively. The final measure—the Family Togetherness Scale (FTS)—assesses global family functioning, including items related to family organization, emotional closeness, and communication/problem-solving. In addition to general items, the scale also includes items explicitly assessing family responses to stressors common in LMIC settings. Results establish a strong rationale for larger-scale validation studies.
Development of Young Children’s Time Perception: Effect of Age and Emotional Localization
Authors: Qu Fangbing , Shi Xiaojia , Zhang Aozi , Gu Changwei
Published: June 2021

Time perception is a fundamental aspect of young children’s daily lives and is affected by a number of factors. The present study aimed to investigate the precise developmental course of young children’s time perception from 3 to 5 years old and the effects of emotion localization on their time perception ability. A total of 120 children were tested using an adapted time perception task with black squares (Experiment 1) and emotional facial expressions (Experiment 2). Results suggested that children’s time perception was influenced by stimulus duration and improved gradually with increasing age. Both accuracy and reaction time were affected by the presentation sequence of emotional faces, indicating an effect of emotion localization. To summarize, young children’s time perception showed effects of age, stimulus duration, and emotion localization.
Gray Matter Abnormalities of Orbitofrontal Cortex and Striatum in Drug-Naïve Adult Patients With Obsessive-Compulsive Disorder
Authors: Bowen Zhang , Changlian Tan , Qian Liu , Wanrong Peng , Huihui Yang , Zhaoxia Liu , Feng Li , Jinyu Liu , Xiongzhao Zhu , Mingtian Zhong
Published: June 2021

Objective: This study examined whether obsessive-compulsive disorder (OCD) patients have gray matter abnormalities in regions related to executive function, and whether such abnormalities are associated with impaired executive function.

Methods: Multiple scales were administered to 27 first-episode drug-naïve OCD patients and 29 healthy controls. Comprehensive brain morphometric indicators of orbitofrontal cortex (OFC) and three striatum areas (caudate, putamen, and pallidum) were determined. Hemisphere lateralization index was calculated for each region of interest. Correlations between lateralization index and psychological variables were examined in OCD group.

Results: The OCD group had greater local gyrification index for the right OFC and greater gray matter volumes of the bilateral putamen and left pallidum than healthy controls. They also had weaker left hemisphere superiority for local gyrification index of the OFC and gray matter volume of the putamen, but stronger left hemisphere superiority for gray matter volume of the pallidum. Patients' lateralization index for local gyrification index of the OFC correlated negatively with Yale-Brown Obsessive Compulsive Scale and Dysexecutive Questionnaire scores, respectively.

Conclusion: Structural abnormalities of the bilateral putamen, left pallidum, and right OFC may underlie OCD pathology. Abnormal lateralization in OCD may contribute to the onset of obsessive-compulsive symptoms and impaired executive function.
Applying the Realist Evaluation Approach to the Complex Process of Policy Implementation—The Case of the User Fee Exemption Policy for Cesarean Section in Benin
Authors: Dossou Jean-Paul , Van Belle Sara , Marchal Bruno
Published: June 2021

Realist evaluation is making inroads in the field of health policy and systems research to a large extent because of its good fit with complex issues. Until now, most realist studies focused on evaluating interventions or projects related to health care delivery, organization of health services, education, management, and leadership of health workers in high income countries. With this paper, we apply the realist approach to the study of national health policy implementation in a low resource country. We use the case of the user fee exemption policy for cesarean section in Benin, which we followed up from 2009 to 2018. We report on how realist evaluation can be applied for policy implementation research. We illustrate how we developed the initial programme theory—the starting point of any realist evaluation -, how we designed the study and data collection tools, and how we analyzed the data. For each step, we present current good practices, how we adapted them when needed, the challenges and the lessons learned. We report also on how the dynamic interactions between the central level (the national implementing agency) and the peripheral level (an implementing hospital) shaped the policy implementation. We found that at central level, availability of resources for a given policy is constantly challenged in the competitive national resource allocation arena. Key factors include the political power and the legitimacy of the group supporting the policy. These are influenced by the policy implementation structure, how the actual outputs of the implementation align with promises of the group supporting the policy and consequently how these outputs, the policy and its promoters are perceived by the community. We found that the service providers are key to the implementation, and that they are constrained or influenced by the dependability of the funding, their autonomy, their personal background, and the accountability arrangements. This study can inform the design and implementation of national health policies that involve interactions between central and operational level in other low-income countries.
Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts
Authors: Chu Yuxin , Zhang Cheng , Xie Min
Published: June 2021

One of the characteristics of the failing human heart is a significant alteration in its energy metabolism. Recently, a ketone body, β-hydroxybutyrate (β-OHB) has been implicated in the failing heart’s energy metabolism as an alternative “fuel source.” Utilization of β-OHB in the failing heart increases, and this serves as a “fuel switch” that has been demonstrated to become an adaptive response to stress during the heart failure progression in both diabetic and non-diabetic patients. In addition to serving as an alternative “fuel,” β-OHB represents a signaling molecule that acts as an endogenous histone deacetylase (HDAC) inhibitor. It can increase histone acetylation or lysine acetylation of other signaling molecules. β-OHB has been shown to decrease the production of reactive oxygen species and activate autophagy. Moreover, β-OHB works as an NLR family pyrin domain-containing protein 3 (Nlrp3) inflammasome inhibitor and reduces Nlrp3-mediated inflammatory responses. It has also been reported that β-OHB plays a role in transcriptional or post-translational regulations of various genes’ expression. Increasing β-OHB levels prior to ischemia/reperfusion injury results in a reduced infarct size in rodents, likely due to the signaling function of β-OHB in addition to its role in providing energy. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been shown to exert strong beneficial effects on the cardiovascular system. They are also capable of increasing the production of β-OHB, which may partially explain their clinical efficacy. Despite all of the beneficial effects of β-OHB, some studies have shown detrimental effects of long-term exposure to β-OHB. Furthermore, not all means of increasing β-OHB levels in the heart are equally effective in treating heart failure. The best timing and therapeutic strategies for the delivery of β-OHB to treat heart disease are unknown and yet to be determined. In this review, we focus on the crucial role of ketone bodies, particularly β-OHB, as both an energy source and a signaling molecule in the stressed heart and the overall therapeutic potential of this compound for cardiovascular diseases.
Adrenergic-Angiogenic Crosstalk in Head and Neck Cancer: Mechanisms and Therapeutic Implications
Authors: Vincent-Chong Vui King , Seshadri Mukund
Published: June 2021

Head and neck squamous cell carcinomas (HNSCC) are loco-regionally aggressive tumors that often lead to debilitating changes in appearance, speech, swallowing and respiratory function in patients. It is therefore critical to develop novel targeted treatment strategies that can effectively target multiple components within the tumor microenvironment. In this regard, there has been an increased recognition of the role of neural signaling networks as mediators of disease progression in HNSCC. Here, we summarize the current knowledge on the mechanisms of adrenergic signaling in HNSCC specifically focusing on neurovascular crosstalk and the potential of targeting the adrenergic-angiogenic axis through repurposing of FDA-approved drugs against HNSCC.
New Insights About the Sticking Region in Back Squats: An Analysis of Kinematics, Kinetics, and Myoelectric Activity
Authors: Larsen Stian , Kristiansen Eirik , van den Tillaar Roland
Published: June 2021

The aim of this study was to investigate barbell, joint kinematics, joint kinetics of hip, knee, and ankle in tandem with myoelectric activity around the sticking region in three-repetition maximum (3-RM) back squats among recreationally trained lifters. Unlike previous literature, this study also investigated the event of first-peak deacceleration, which was expected to be the event with the lowest force output. Twenty-five recreationally trained lifters (body mass: 70.8 ± 10.5, age: 24.6 ± 3.4, height: 172 ± 8.5) were tested in 3-RM back squats. A repeated one-way analysis of variance showed that ground reaction force output decreased at first peak deacceleration compared with the other events. Moreover, torso forward lean, hip moment arm, and hip contribution to total moment increased, whereas the knee moment arms and moment contribution to total moment decreased in the sticking region. Also, stable moment arms and moment contributions to total moment were observed for the ankle in the sticking region. Furthermore, the knee extensors together with the soleus muscle decreased myoelectric activity in the post-sticking region, while the gluteus maximus and biceps femoris increased myoelectric activity in the post-sticking region. Our findings suggest that the large hip moment arms and hip contributions to total moment together with a lower myoelectric activity for the hip extensors contribute to a poor biomechanical region for force output and, thereby, to the sticking region among recreationally trained lifters in 3-RM back squats.
Living Labs for Public Sector Innovation: An Integrative Literature Review
Authors: Fuglsang Lars , Hansen Anne Vorre , Mergel Ines , Røhnebæk Maria Taivalsaari
Published: June 2021

The public administration literature and adjacent fields have devoted increasing attention to living labs as environments and structures enabling the co-creation of public sector innovation. However, living labs remain a somewhat elusive concept and phenomenon, and there is a lack of understanding of its versatile nature. To gain a deeper understanding of the multiple dimensions of living labs, this article provides a review assessing how the environments, methods and outcomes of living labs are addressed in the extant research literature. The findings are drawn together in a model synthesizing how living labs link to public sector innovation, followed by an outline of knowledge gaps and future research avenues.
Evolution in Configuration and Productivity of New Zealand Hill Country Sheep and Beef Cattle Systems
Authors: Gobilik Januarius , Morris Stephen Todd , Matthew Cory
Published: June 2021

Metabolic energy budgeting (MEB) was used to evaluate evolution over 30 years (1980–1981 to 2010–2011) in New Zealand southern North Island ‘hill country’ sheep and beef cattle systems. MEB calculates energy required by animals for body weight maintenance, weight gain or loss, pregnancy, and lactation to estimate the system feed demand and thereby provide a basis for calculating feed conversion efficiency. Historic production systems were reconstructed and modeled using averaged data from industry surveys and data from owners’ diaries of three case-study farms and reviewed for patterns of change over time. The modeling indicated that pasture productivity was 11% lower and herbage harvested was 14% lower in 2010–2011 than in the early 1980s. This productivity decline is attributable to warmer, drier summer weather in recent years. However, primarily through increased lambing percentage, feed conversion efficiency based on industry data improved over the study period from 25 to 19 kg feed consumed per kg lamb weaned, while meat production rose from 137 to 147 kg per ha per year. Similar improvements were observed for the three case farms. The New Zealand MEB model was found effective for analysis of tropical beef production systems in Sabah, Malaysia.
Impact of Fungicide Application and Host Genotype on Susceptibility of Brassica napus to Sclerotinia Stem Rot across the South-Western Australian Grain Belt: A Genotype × Environment × Management Study
Authors: Bennett Sarita Jane , Lamichhane Ashmita Rijal , Thomson Linda L. , Lui King Yin , Michael Pippa J.
Published: June 2021

Sclerotinia stem rot (SSR), caused by the necrotroph Sclerotinia sclerotiorum Lib. (de Bary), is a major disease of canola in Australia, greatly reducing yields in high infection years. This study investigated genotype by environment by management interactions at 25 sites across the south-west Australian grainbelt from 2017 to 2020. Up to 10 canola varieties were grown each year with +/− fungicide application at 30% flowering. Disease incidence was low, with less than 20% infection recorded across most sites. Most variation in yield occurred between sites, rather than by management or variety, due to the environmental differences between the sites. Petal assays were found to be a poor indicator of later disease severity, suggesting the winter growing season in south-west Australia does not have reliable conducive conditions for disease development following petal drop in canola. The Additive Main Effects and Multiplicative Interaction model (AMMI) indicated that the open-pollinated varieties were broadly adapted and stable when fungicide was applied but became unstable with no fungicide, indicating SSR has a significant impact on yield when disease incidence is higher. This study highlights that further research is necessary to determine disease thresholds that lead to significant yield loss.
The Freestall Reimagined: Effects on Stall Hygiene and Space Usage in Dairy Cattle
Authors: Beaver Annabelle , Strazhnik Emma , von Keyserlingk Marina A. G. , Weary Daniel M.
Published: June 2021

Modern freestall barns for dairy cattle have been constructed with considerations for dairy cow cleanliness; partitions and other stall features such as neck rails are designed to reduce manure contamination of bedding and decrease farm labor. However, cows prefer to lie in more open spaces, including on bedded packs and pasture. We created an “alternative” housing area by modifying a traditional freestall pen and including flexible partitions to create larger lying areas. We assessed cattle lying behaviour, including lying postures, in this alternative pen (ALT) compared to an open pack (OP) and freestalls (FS) with different stocking densities. We also assessed levels of manure contamination across systems. Cleanliness was highest in FS, but ALT provided substantial improvement compared to OP. Cattle spent more time lying down in OP and ALT compared to FS. There were few differences in postures (such as lying with limbs outstretched) between OP and ALT, but cows in both of these systems more often lay in extended positions compared to when they were housed in FS. Housing in OP and ALT was associated with reduced perching for cows with high body weight; perching has been linked to an increased prevalence of both hoof lesions and lameness. Thus, alternative lying areas can offer a solution for producers seeking to provide cattle with the advantages of a more open lying area, while improving hygiene relative to an open pack.
The Extremophilic Actinobacteria: From Microbes to Medicine
Authors: Hui Martha Lok-Yung , Tan Loh Teng-Hern , Letchumanan Vengadesh , He Ya-Wen , Fang Chee-Mun , Chan Kok-Gan , Law Jodi Woan-Fei , Lee Learn-Han
Published: June 2021

Actinobacteria constitute prolific sources of novel and vital bioactive metabolites for pharmaceutical utilization. In recent years, research has focused on exploring actinobacteria that thrive in extreme conditions to unearth their beneficial bioactive compounds for natural product drug discovery. Natural products have a significant role in resolving public health issues such as antibiotic resistance and cancer. The breakthrough of new technologies has overcome the difficulties in sampling and culturing extremophiles, leading to the outpouring of more studies on actinobacteria from extreme environments. This review focuses on the diversity and bioactive potentials/medically relevant biomolecules of extremophilic actinobacteria found from various unique and extreme niches. Actinobacteria possess an excellent capability to produce various enzymes and secondary metabolites to combat harsh conditions. In particular, a few strains have displayed substantial antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), shedding light on the development of MRSA-sensitive antibiotics. Several strains exhibited other prominent bioactivities such as antifungal, anti-HIV, anticancer, and anti-inflammation. By providing an overview of the recently found extremophilic actinobacteria and their important metabolites, we hope to enhance the understanding of their potential for the medical world.
Prognostic Value of the Time-to-Positivity in Blood Cultures from Septic Shock Patients with Bacteremia Receiving Protocol-Driven Resuscitation Bundle Therapy: A Retrospective Cohort Study
Authors: Bae Hong-Jun , Kim June-sung , Kim Muyeol , Kim Youn-Jung , Kim Won Young
Published: June 2021

Introduction: To evaluate the prognostic value of the time-to-positivity in patients with culture-positive septic shock. Methods: Retrospective study using a prospective data registry was performed at the emergency department of a tertiary hospital. Consecutive adult patients with septic shock (N = 2499) were enrolled between 2014 and 2018. Bacteremia was defined using blood cultures, and viral and fungal pathogens were excluded. The primary outcome was the 28-day mortality. Results: In 803 (46.7%) septic shock patients with bacteremia, median TTP was 10.1 h. The most prevalent isolated bacterial pathogens were Escherichia coli (40.8%) and Klebsiella (23.4%). Although the TTP correlated with a higher sequential organ failure assessment score (Spearman’s rho = −0.12, p < 0.01), it showed no significant difference between the 28-day survivors and non-survivors (10.2 vs. 9.4 days, p = 0.35). In subgroup analysis of the Escherichia coli and Klebsiella bacteremia cases, a shorter TTP showed prognostic value for predicting the 28-day mortality. The optimal TTP cut-off for Escherichia coli and Klebsiella was 10 h and 8 h, respectively. Conclusions: The prognostic value of the TTP in septic shock patients receiving bundle therapy may be limited and its clinical interpretation should only be made on a pathogen-specific basis.
Comparative Analysis of Digital Models of Objects of Cultural Heritage Obtained by the “3D SLS” and “SfM” Methods
Authors: Barszcz Marcin , Montusiewicz Jerzy , Paśnikowska-Łukaszuk Magdalena , Sałamacha Anna
Published: June 2021

In the era of the global pandemic caused by the COVID-19 virus, 3D digitisation of selected museum artefacts is becoming more and more frequent practice, but the vast majority is performed by specialised teams. The paper presents the results of comparative studies of 3D digital models of the same museum artefacts from the Silk Road area generated by two completely different technologies: Structure from Motion (SfM)—a method belonging to the so-called low-cost technologies—and by Structured-light 3D Scanning (3D SLS). Moreover, procedural differences in data acquisition and their processing to generate three-dimensional models are presented. Models built using a point cloud were created from data collected in the Afrasiyab museum in Samarkand (Uzbekistan) during “The 1st Scientific Expedition of the Lublin University of Technology to Central Asia” in 2017. Photos for creating 3D models in SfM technology were taken during a virtual expedition carried out under the “3D Digital Silk Road” program in 2021. The obtained results show that the quality of the 3D models generated with SfM differs from the models from the technology (3D SLS), but they may be placed in the galleries of the vitrual museum. The obtained models from SfM do not have information about their size, which means that they are not fully suitable for archiving purposes of cultural heritage, unlike the models from SLS.
Design of a Semi-Active Prosthetic Knee for Transfemoral Amputees: Gait Symmetry Research by Simulation
Authors: Zhang Zhewen , Yu Hongliu , Cao Wujing , Wang Xiaoming , Meng Qiaoling , Chen Chunjie
Published: June 2021

The key technology of the prosthetic knee is to simulate the torque and angle of the biological knee. In this work, we proposed a novel prosthetic knee operated in semi-active mode. The structure with ball-screw driven by the motor and the passive hydraulic damping cylinder was presented. A four-bar linkage was adapted to track the instantaneous center motion of human knee. The mathematical models of hydraulic cylinder damping and active torque were established to simulate the knee torque and angle. The results show that the knee torque symmetry index is smaller than 10% in the whole gait. The knee angle symmetry index value is 34.7% in stance phase and 11.5% in swing phase. The angle in swing phase is closer to the intact knee. The semi-active prosthetic knee could provide similar torque and angle of the biological knee in the simulation. It has shown good potential in improving the gait symmetry of the transfemoral amputee.
Finger-Actuated Microneedle Array for Sampling Body Fluids
Authors: Sarabi Misagh Rezapour , Ahmadpour Abdollah , Yetisen Ali K. , Tasoglu Savas
Published: June 2021

The application of microneedles (MNs) for minimally invasive biological fluid sampling is rapidly emerging, offering a user-friendly approach with decreased insertion pain and less harm to the tissues compared to conventional needles. Here, a finger-powered microneedle array (MNA) integrated with a microfluidic chip was conceptualized to extract body fluid samples. Actuated by finger pressure, the microfluidic device enables an efficient approach for the user to collect their own body fluids in a simple and fast manner without the requirement for a healthcare worker. The processes for extracting human blood and interstitial fluid (ISF) from the body and the flow across the device, estimating the amount of the extracted fluid, were simulated. The design in this work can be utilized for the minimally invasive personalized medical equipment offering a simple usage procedure.
Development of a Virtual Fit Analysis Method for an Ergonomic Design of Pilot Oxygen Mask
Authors: Lee Wonsup , Jung Daehan , Park Seikwon , Kim Heeeun , You Heecheon
Published: June 2021

In the ergonomic design of wearable products such as an oxygen mask, systematic design methods including the analysis of anthropometric information, evaluation of fit, and product design need to utilize 3D human scan data. The present study intends to develop a virtual fit analysis method that generates an ergonomic shape of an oxygen mask for fighter pilots based on 3D facial scans. The proposed virtual fit analysis method enables iteratively to revise the shape of an oxygen mask until an appropriate level of fit between the mask and a group of pilot faces is achieved. The proposed method of virtual fit analysis and design optimization was applied to find ergonomic shapes of oxygen masks for four size categories (small narrow, medium narrow, medium wide, and large wide) to accommodate 336 pilots of the Republic of Korea Air Force. The virtual fit analysis results in the study showed that the revised oxygen mask shapes achieved significantly higher accommodation percentages (4.8~88.7%) at facial areas (nasal root, nasal side, cheek, and chin) compared to the existing oxygen mask shapes. The proposed method can be applied to develop an ergonomic product design that fits the face and other human body parts.
A Procedure to Prepare Sand–Clay Mixture Samples for Soil–Structure Interface Direct Shear Tests
Authors: Yin Kexin , Liu Jiangxin , Vasilescu Andreea-Roxana , Di Filippo Eugenia , Othmani Khaoula
Published: June 2021

A large number of experimental studies on sand–clay mixtures are well documented in the literature; however, the preparation protocol is rarely clearly detailed or varies a lot according to the authors. Variations in the preparation technique obviously increases the challenge of comparing different test results. As a consequence, sample preparation for sand–clay mixtures should be kept as constant as possible to ensure homogeneity and uniformity of samples and limit result variability. This paper develops a detailed procedure on how to prepare sand–clay samples for interface direct shear tests. Sand–clay mixtures are prepared with Fontainebleau sand, kaolinite clay and distilled water by the S1 (sand–water–clay) protocol. The uniformity of the reconstituted specimens is assessed by measuring the water content and density on three slices from the top to the bottom across the specimens. The repeatability of the samples is checked with oedometer and interface direct shear tests. This sample preparation procedure can be used for preparing sand–clay mixture for interface direct shear tests to investigate the influence of clay content or other effects (e.g., temperature) on the mechanical behavior of soil–structure interface. It has demonstrated great performance in preparing samples with good homogeneity and shape, compared to other traditional reconstitution techniques. With the sample preparation procedure, we can obtain repeatable test results as well.
Presence of Longitudinal Roll Structures during Synoptic Forced Conditions in Complex Terrain
Authors: Payne Cory M. , Passner Jeffrey E. , Dumais Robert E. , Abdelkefi Abdessattar , Hocut Christopher M.
Published: June 2021

To investigate synoptic interactions with the San Andres Mountains in southern New Mexico, the Weather Research and Forecasting (WRF) model was used to simulate several days in the period 2018–2020. The study domain was centered on the U.S. Department of Agriculture (USDA) Agricultural Research Service’s Jornada Experimental Range (JER) and the emphasis was on synoptic conditions that favor strong to moderate winds aloft from the southwest, boundary layer shear, a lack of moisture (cloud coverage), and modest warming of the surface. The WRF simulations on these synoptic days revealed two distinct regimes: lee waves aloft and SW-to-NE oriented Longitudinal Roll Structures (LRS) that have typical length scales of the width of the mountain basin in the horizontal and the height of the boundary layer (BL) in the vertical. Analysis of the transitional periods indicate that the shift from the lee wave to LRS regime occurs when the surface heating and upwind flow characteristics reach a critical threshold. The existence of LRS is confirmed by satellite observations and the longitudinal streak patterns in the soil of the JER that indicate this is a climatologically present BL phenomenon.
A Quantitative Analysis of Point Clouds from Automotive Lidars Exposed to Artificial Rain and Fog
Authors: Montalban Karl , Reymann Christophe , Atchuthan Dinesh , Dupouy Paul-Edouard , Riviere Nicolas , Lacroix Simon
Published: June 2021

Light Detection And Ranging sensors (lidar) are key to autonomous driving, but their data is severely impacted by weather events (rain, fog, snow). To increase the safety and availability of self-driving vehicles, the analysis of the phenomena consequences at stake is necessary. This paper presents experiments performed in a climatic chamber with lidars of different technologies (spinning, Risley prisms, micro-motion and MEMS) that are compared in various artificial rain and fog conditions. A specific target with calibrated reflectance is used to make a first quantitative analysis. We observe different results depending on the sensors, valuable multi-echo information, and unexpected behaviors in the analysis with artificial rain are seen where higher rain rates do not necessarily mean higher degradations on lidar data.
A Comparison of Lithium-Ion Cell Performance across Three Different Cell Formats
Authors: Bridgewater Grace , Capener Matthew J. , Brandon James , Lain Michael J. , Copley Mark , Kendrick Emma
Published: June 2021

To investigate the influence of cell formats during a cell development programme, lithium-ion cells have been prepared in three different formats. Coin cells, single layer pouch cells, and stacked pouch cells gave a range of scales of almost three orders of magnitude. The cells used the same electrode coatings, electrolyte and separator. The performance of the different formats was compared in long term cycling tests and in measurements of resistance and discharge capacities at different rates. Some test results were common to all three formats. However, the stacked pouch cells had higher discharge capacities at higher rates. During cycling tests, there were indications of differences in the predominant degradation mechanism between the stacked cells and the other two cell formats. The stacked cells showed faster resistance increases, whereas the coin cells showed faster capacity loss. The difference in degradation mechanism can be linked to the different thermal and mechanical environments in the three cell formats. The correlation in the electrochemical performance between coin cells, single layer pouch cells, and stacked pouch cells shows that developments within a single cell format are likely to lead to improvements across all cell formats.
Cholesteryl Ester Promotes Mammary Tumor Growth in MMTV-PyMT Mice and Activates Akt-mTOR Pathway in Tumor Cells
Authors: Wei Lengyun , Lu Xuyang , Weng Shengmei , Zhu Shenglong , Chen Yongquan
Published: June 2021

The association between intratumoral cholesteryl ester (CE) and tumor progression has been reported previously. The objective of our study was to investigate a causal effect of CE on mammary tumor progression. Using MMTV-PyMT (MMTV-polyoma virus middle T) transgenic mice and breast tumor cell MCF-7, we show that both exogenous and endogenous CE can increase mammary tumor growth, that CE upregulates the AKT/mTOR pathway, and that CE synthesis blockade suppresses this signaling pathway. Our data suggest that SOAT1, a sterol O-acyltransferase, may be a potential target for the treatment of breast cancer.
Can Antiviral Activity of Licorice Help Fight COVID-19 Infection?
Authors: Diomede Luisa , Beeg Marten , Gamba Alessio , Fumagalli Oscar , Gobbi Marco , Salmona Mario
Published: June 2021

The phytotherapeutic properties of Glycyrrhiza glabra (licorice) extract are mainly attributed to glycyrrhizin (GR) and glycyrrhetinic acid (GA). Among their possible pharmacological actions, the ability to act against viruses belonging to different families, including SARS coronavirus, is particularly important. With the COVID-19 emergency and the urgent need for compounds to counteract the pandemic, the antiviral properties of GR and GA, as pure substances or as components of licorice extract, attracted attention in the last year and supported the launch of two clinical trials. In silico docking studies reported that GR and GA may directly interact with the key players in viral internalization and replication such as angiotensin-converting enzyme 2 (ACE2), spike protein, the host transmembrane serine protease 2, and 3-chymotrypsin-like cysteine protease. In vitro data indicated that GR can interfere with virus entry by directly interacting with ACE2 and spike, with a nonspecific effect on cell and viral membranes. Additional anti-inflammatory and antioxidant effects of GR cannot be excluded. These multiple activities of GR and licorice extract are critically re-assessed in this review, and their possible role against the spread of the SARS-CoV-2 and the features of COVID-19 disease is discussed.