bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex Differences in Risk Profile, Stroke Cause and Outcome in Ischemic Stroke Patients With and Without Migraine
Authors: Linstra Katie M. , van Os Hendrikus J. A. , Ruigrok Ynte M. , Nederkoorn Paul J. , van Dijk Ewoud J. , Kappelle L. Jaap , Koudstaal Peter J. , Visser Marieke C. , Ferrari Michel D. , MaassenVanDenBrink Antoinette , Terwindt Gisela M. , Wermer Marieke J. H.
Published: November 2021

Background: An increased risk of stroke in patients with migraine has been primarily found for women. The sex-dependent mechanisms underlying the migraine–stroke association, however, remain unknown. This study aims to explore these sex differences to improve our understanding of pathophysiological mechanisms behind the migraine–stroke association.

Methods: We included 2,492 patients with ischemic stroke from the prospective multicenter Dutch Parelsnoer Institute Initiative study, 425 (17%) of whom had a history of migraine. Cardiovascular risk profile, stroke cause (TOAST classification), and outcome [modified Rankin scale (mRS) at 3 months] were compared with both sexes between patients with and without migraine.

Results: A history of migraine was not associated with sex differences in the prevalence of conventional cardiovascular risk factors. Women with migraine had an increased risk of stroke at young age (onset < 50 years) compared with women without migraine (RR: 1.7; 95% CI: 1.3–2.3). Men with migraine tended to have more often stroke in the TOAST category other determined etiology (RR: 1.7; 95% CI: 1.0–2.7) in comparison with men without migraine, whereas this increase was not found in women with migraine. Stroke outcome was similar for women with or without migraine (mRS ≥ 3 RR 1.1; 95% CI 0.7–1.5), whereas men seemed to have a higher risk of poor outcome compared with their counterparts without migraine (mRS ≥ 3 RR: 1.5; 95% CI: 1.0–2.1).

Conclusion: Our results indicate possible sex differences in the pathophysiology underlying the migraine–stroke association, which are unrelated to conventional cardiovascular risk factors. Further research in larger cohorts is needed to validate these findings.
m5C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Papillary Thyroid Carcinoma
Authors: Li Fei , Deng Qingmei , Pang Xiaoxi , Huang Shan , Zhang Jingmiao , Zhu Xiaxia , Chen Hong , Liu Xiuxia
Published: November 2021

Recently, immune response modulation at the epigenetic level is illustrated in studies, but the possible function of RNA 5-methylcytosine (m5C) modification in cell infiltration within the tumor microenvironment (TME) is still unclear. Three different m5C modification patterns were identified, and high differentiation degree was observed in the cell infiltration features within TME under the above three identified patterns. A low m5C-score, which was reflected in the activated immunity, predicted the relatively favorable prognostic outcome. A small amount of effective immune infiltration was seen in the high m5C-score subtype, indicating the dismal patient survival. Our study constructed a diagnostic model using the 10 signature genes highly related to the m5C-score, discovered that the model exhibited high diagnostic accuracy for PTC, and screened out five potential drugs for PTC based on this m5C-score model. m5C modification exerts an important part in forming the TME complexity and diversity. It is valuable to evaluate the m5C modification patterns in single tumors, so as to enhance our understanding towards the infiltration characterization in TME.
Intracranial Metastases Tend to Be Overt and Predict Poor Prognosis in Children With Neuroblastoma
Authors: Liu Ying , Huo Liang , Zhang Jinhua , Liu Ying
Published: November 2021

Background: Neuroblastoma (NB) is the most common pediatric extracranial solid neoplasm after leukemia. Intracranial metastases (IM) rarely occur in patients with NB. The present study aimed to review the clinical characteristics of NB patients from a single center presenting with IM.

Methods: Two hundred children (aged 3–91 months) with NB admitted to the Fourth Affiliated Hospital of China Medical University between January 2009 and December 2015 were enrolled, and their clinical characteristics were recorded. The patients were divided into two groups based on the presence of IM. Their clinical characteristics, including demographics, clinical features, and laboratory and imaging studies, were retrospectively analyzed.

Results: IM occurred in 22 of 200 (11%) neuroblastoma patients, with a median age of 42.5 months (range, 3–91 months), with a male-to-female ratio of 1.4:1. Seven patients had IM at the initial diagnosis. Among the 15 children who did not have IM at initial presentation, the median interval from presentation to the diagnosis of IM was 17.3 months (range, 1–55 months). Compared with the control group, NB patients with IM tended to be asymptomatic at the time of NB diagnosis, which was made incidentally during routine physical examination (5 of 22, 22.7%, p < 0.05). In addition, this group had more primary intra-abdominal sites (18 of 22, 81.8%, p < 0.001) and worse prognosis (5 of 22, 22.7%, p < 0.05).

Conclusions: NB patients with IM have insidious onset in the early stage and a lower survival rate, especially patients with primary intra-abdominal lesions. Regular neurological monitoring could improve the rate of early diagnosis and prognosis of NB children with IM. Familiarity with the characteristic findings of NB with IM is necessary to avoid misdiagnosis and initiate necessary interventions.
Jinmaitong Alleviates Diabetic Neuropathic Pain Through Modulation of NLRP3 Inflammasome and Gasdermin D in Dorsal Root Ganglia of Diabetic Rats
Authors: Sun Qing , Zhang Rui , Xue Xiaowei , Wu Qunli , Yang Dan , Wang Chao , Yan Bin , Liang Xiaochun
Published: November 2021

Jinmaitong (JMT) is a compound prescription of traditional Chinese medicine that has been used to treat diabetic neuropathic pain (DNP) for many years. Here, we investigated the effects of JMT on the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and pyroptosis in Dorsal root ganglia (DRG) of diabetic rats. Streptozotocin (STZ)-induced diabetic rats were gavaged with JMT (0.88 g/kg/d) or alpha-lipoic acid (ALA, positive control, 0.48 mmol/kg/d) for 12 weeks. Distilled water was administered as a vehicle control to both diabetic and non-affected control rats. Blood glucose levels and body weights were measured. Behavioral changes were tested with mechanical withdrawal threshold (MWT) and tail-flick latency (TFL) tests. Morphological injury associated with DRG was observed with hematoxylin and eosin (H&E) and Nissl’s staining. mRNA and protein levels of NLRP3 inflammasome components (NLRP3, ASC, caspase-1), downstream IL-1β and gasdermin D (GSDMD) were evaluated by immunohistochemistry, quantitative real time-PCR and western blot. The results showed that JMT had no effect on blood glucose levels and body weights, but significantly improved MWT and TFL behavior in diabetic rats, and attenuated morphological damage in the DRG tissues. Importantly, JMT decreased the mRNA and protein levels of components of NLRP3 inflammasome, including NLRP3, ASC and caspase-1. JMT also down-regulated the expression of IL-1β and GSDMD in the DRG of DNP rats. In addition, ALA treatment did not perform better than JMT. In conclusion, JMT effectively relieved DNP by decreasing NLRP3 inflammasome activation and pyroptosis, providing new evidence supporting JMT as an alternative treatment for DNP.
(-)-T-Cadinol—a Sesquiterpene Isolated From Casearia sylvestris (Salicaceae)—Displayed In Vitro Activity and Causes Hyperpolarization of the Membrane Potential of Trypanosoma cruzi
Authors: dos Santos Augusto L. , Amaral Maiara , Hasegawa Flavia Rie , Lago João Henrique G. , Tempone Andre G. , Sartorelli Patricia
Published: November 2021

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects 6–8 million people worldwide, mainly from developing countries. The treatment is limited to two approved nitro-derivatives, nifurtimox and benznidazole, with several side effects and reduced efficacy. Casearia sylvestris has been used in folk medicine as an antiseptic and cicatrizing in skin diseases. In the present work, the hexane phase from the MeOH extract from the leaves of Casearia sylvestris afforded a fraction composed by the sesquiterpene T-cadinol, which was chemically characterized by NMR and HRMS. The activity of T-cadinol was evaluated against T. cruzi, and IC50 values of 18 (trypomastigotes) and 15 (amastigotes) µM were established. The relation between the mammalian toxicity and the antiparasitic activity resulted in a selectivity index >12. Based on this promising activity, the mechanism of action was investigated by different approaches using fluorescent-based techniques such as plasma membrane permeability, plasma membrane electric potential, mitochondrial membrane electric potential, reactive oxygen species, and the intracellular calcium (Ca2+) levels. The obtained results demonstrated that T-cadinol affected neither the parasite plasma membrane nor the electric potential of the membrane. Nevertheless, this compound induced a mitochondrial impairment, resulting in a hyperpolarization of the membrane potential, with decreased levels of reactive oxygen species. No alterations in Ca2+ levels were observed, suggesting that T-cadinol may affect the single mitochondria of the parasite. This is the first report about the occurrence of T-cadinol in C. sylvestris, and our data suggest this sesquiterpene as an interesting hit compound for future optimizations in drug discovery studies for Chagas disease.
Evaluation of Kratom Opioid Derivatives as Potential Treatment Option for Alcohol Use Disorder
Authors: Gutridge Anna M. , Chakraborty Soumen , Varga Balazs R. , Rhoda Elizabeth S. , French Alexander R. , Blaine Arryn T. , Royer Quinten H. , Cui Haoyue , Yuan Jinling , Cassell Robert J. , Szabó Márk , Majumdar Susruta , van Rijn Richard M.
Published: November 2021

Background and Purpose:Mitragyna speciosaextract and kratom alkaloids decrease alcohol consumption in mice at least in part through actions at the δ-opioid receptor (δOR). However, the most potent opioidergic kratom alkaloid, 7-hydroxymitragynine, exhibits rewarding properties and hyperlocomotion presumably due to preferred affinity for the mu opioid receptor (µOR). We hypothesized that opioidergic kratom alkaloids like paynantheine and speciogynine with reduced µOR potency could provide a starting point for developing opioids with an improved therapeutic window to treat alcohol use disorder.

Experimental Approach:We characterized paynantheine, speciociliatine, and four novel kratom-derived analogs for their ability to bind and activate δOR, µOR, and κOR. Select opioids were assessed in behavioral assays in male C57BL/6N WT and δOR knockout mice.

Key Results:Paynantheine (10 mg∙kg−1, i.p.) produced aversion in a limited conditioned place preference (CPP) paradigm but did not produce CPP with additional conditioning sessions. Paynantheine did not produce robust antinociception but did block morphine-induced antinociception and hyperlocomotion. Yet, at 10 and 30 mg∙kg−1doses (i.p.), paynantheine did not counteract morphine CPP. 7-hydroxypaynantheine and 7-hydroxyspeciogynine displayed potency at δOR but limited µOR potency relative to 7-hydroxymitragyninein vitro, and dose-dependently decreased voluntary alcohol consumption in WT but not δOR in KO mice. 7-hydroxyspeciogynine has a maximally tolerated dose of at least 10 mg∙kg−1(s.c.) at which it did not produce significant CPP neither alter general locomotion nor induce noticeable seizures.

Conclusion and Implications:Derivatizing kratom alkaloids with the goal of enhancing δOR potency and reducing off-target effects could provide a pathway to develop novel lead compounds to treat alcohol use disorder with an improved therapeutic window.
Mitochondrial MicroRNAs Contribute to Macrophage Immune Functions Including Differentiation, Polarization, and Activation
Authors: Duroux-Richard Isabelle , Apparailly Florence , Khoury Maroun
Published: November 2021

A subset of microRNA (miRNA) has been shown to play an important role in mitochondrial (mt) functions and are named MitomiR. They are present within or associated with mitochondria. Most of the mitochondrial miRNAs originate from the nucleus, while a very limited number is encoded by mtDNA. Moreover, the miRNA machinery including the Dicer and Argonaute has also been detected within mitochondria. Recent, literature has established a close relationship between miRNAs and inflammation. Indeed, specific miRNA signatures are associated with macrophage differentiation, polarization and functions. Nevertheless, the regulation of macrophage inflammatory pathways governed specifically by MitomiR and their implication in immune-mediated inflammatory disorders remain poorly studied. Here, we propose a hypothesis in which MitomiR play a key role in triggering macrophage differentiation and modulating their downstream activation and immune functions. We sustain this proposition by bioinformatic data obtained from either the human monocytic THP1 cell line or the purified mitochondrial fraction of PMA-induced human macrophages. Interestingly, 22% of the 754 assayed miRNAs were detected in the mitochondrial fraction and are either exclusively or highly enriched cellular miRNA. Furthermore, the in silico analysis performed in this study, identified a specific MitomiR signature associated with macrophage differentiation that was correlated with gene targets within the mitochondria genome or with mitochondrial pathways. Overall, our hypothesis and data suggest a previously unrecognized link between MitomiR and macrophage function and fate. We also suggest that the MitomiR-dependent control could be further enhanced through the transfer of mitochondria from donor to target cells, as a new strategy for MitomiR delivery.
Post-exercise Warm or Cold Water Immersion to Augment the Cardiometabolic Benefits of Exercise Training: A Proof of Concept Trial
Authors: Russell Brooke M. , Chang Courtney R. , Hill Terry , Cotter James D. , Francois Monique E.
Published: November 2021

We investigated whether substituting the final half within 60-min bouts of exercise with passive warm or cold water immersion would provide similar or greater benefits for cardiometabolic health. Thirty healthy participants were randomized to two of three short-term training interventions in a partial crossover (12 sessions over 14–16 days, 4 week washout): (i) EXS: 60 min cycling 70% maximum heart rate (HRmax), (ii) WWI: 30 min cycling then 30 min warm water (38–40°C) immersion, and/or (iii) CWI: 30 min cycling then 30 min cold water (10–12°C) immersion. Before and after, participants completed a 20 min cycle work trial, V.O2max test, and an Oral Glucose Tolerance Test during which indirect calorimetry was used to measure substrate oxidation and metabolic flexibility (slope of fasting to post-prandial carbohydrate oxidation). Data from twenty two participants (25 ± 5 year, BMI 23 ± 3 kg/m2, Female = 11) were analyzed using a fixed-effects linear mixed model. V.O2max increased more in EXS (interaction p = 0.004) than CWI (95% CI: 1.1, 5.3 mL/kg/min, Cohen’s d = 1.35), but not WWI (CI: −0.4, 3.9 mL/kg/min, d = 0.72). Work trial distance and power increased 383 ± 223 m and 20 ± 6 W, respectively, without differences between interventions (interaction both p > 0.68). WWI lowered post-prandial glucose ∼9% (CI −1.9, −0.5 mmol/L; d = 0.63), with no difference between interventions (interaction p = 0.469). Substituting the second half of exercise with WWI provides similar cardiometabolic health benefits to time matched exercise, however, substituting with CWI does not.
The Influence of Physical Education on Self-Efficacy in Overweight Schoolgirls: A 12-Week Training Program
Authors: Latino Francesca , Cataldi Stefania , Bonavolontà Valerio , Carvutto Roberto , De Candia Michele , Fischetti Francesco
Published: November 2021

The purpose of this randomized controlled study was to investigate the impact of a 12-week physical education (PE) program on the self-efficacy of overweight schoolgirls. We randomly assigned 60 overweight schoolgirls (15–17 years) to either an experimental moderate to vigorous aerobic exercise (∼90 min, three times a week) group (n = 30) or a control group (CG) (n = 30) that received non-specific regular PE lessons with activities chosen by the curricular teacher mainly focused on team games and sports skills that aimed to achieve general psycho-physical wellness (∼90 min, three times a week). To assess the starting level of students and significant changes reached, at baseline and after training, a battery of standardized assessment motor tests and a psychometric scale (generalized self-efficacy scale, GES) were administered. At the end of the intervention, the experimental group reported a considerable decrease in body mass index (BMI) and a large improvement in self-efficacy (p < 0.001). No significant changes were found in the CG. The results suggested that the 12-week moderate to a vigorous aerobic exercise program is an effective weight loss intervention and a vehicle to promote a range of outcomes important to the qualitative growth of adolescents. In fact, it could provide a positive and significant impact on the self-efficacy of overweight schoolgirls.
Assessment of the Relationship Between Executive Function and Cardiorespiratory Fitness in Healthy Older Adults
Authors: Predovan David , Berryman Nicolas , Lussier Maxime , Comte Francis , Vu Thien Tuong Minh , Villalpando Juan Manuel , Bherer Louis
Published: November 2021

Associations between cardiorespiratory fitness and brain health in healthy older adults have been reported using a variety of cardiorespiratory fitness estimates (CRFe). Using commonly used methods to determine CRF, we assessed the relationship between CRFe and executive function performance. Healthy older adults (n = 60, mean age 68 years, 77% women), underwent three CRF tests: a Maximal Graded Exercise Test performed on a cycle ergometer, the Rockport Fitness Walking Test, and a Non-Exercise Prediction Equation. Executive function was assessed by a computerized cognitive assessment using an N-Back task (updating cost) and a Stroop task (interference cost, global and local switch cost). Multiple hierarchical regression analyses were conducted to assess the relationship between different CRFe and executive function performance. Regardless of age and education, cardiorespiratory fitness estimated from the Maximal Graded Exercise Test and the Rockport Fitness Walking Test was significantly associated with the global switch cost. All CRFe were associated with the interference cost. No association was observed between CRFe and local switching costs or the updating costs. In the present study, not all subcomponents of executive function were related to CRFe. Interestingly, the executive functions that were associated with CRFe are those that are known to be the most affected by aging.
Understanding the Impact of Face Masks on the Processing of Facial Identity, Emotion, Age, and Gender
Authors: Fitousi Daniel , Rotschild Noa , Pnini Chen , Azizi Omer
Published: November 2021

The COVID-19 pandemic has introduced new challenges for governments and individuals. Unprecedented efforts at reducing virus transmission launched a novel arena for human face recognition in which faces are partially occluded with masks. Previous studies have shown that masks decrease accuracy of face identity and emotion recognition. The current study focuses on the impact of masks on the speed of processing of these and other important social dimensions. Here we provide a systematic assessment of the impact of COVID-19 masks on facial identity, emotion, gender, and age. Four experiments (N = 116) were conducted in which participants categorized faces on a predefined dimension (e.g., emotion). Both speed and accuracy were measured. The results revealed that masks hindered the perception of virtually all tested facial dimensions (i.e., emotion, gender, age, and identity), interfering with normal speed and accuracy of categorization. We also found that the unwarranted effects of masks were not due to holistic processes, because the Face Inversion Effect (FIE) was generally not larger with unmasked compared with masked faces. Moreover, we found that the impact of masks is not automatic and that under some contexts observers can control at least part of their detrimental effects.
The Influence of Face on Online Purchases: Evidence From China
Authors: Sun Gong , Shen Famei , Ma Xinyi
Published: November 2021

This study examines the influence of an indigenous concept – face on online purchases in China. Specifically, we test the mediating role of materialism and the moderating role of price consciousness. We conduct a survey of 315 Chinese consumers. The results demonstrate that consumers tend to make online purchases to satisfy some facets of their materialistic needs and then gain face, especially for those highly conscious of price. The current research can help both scholars and practitioners better understand Chinese consumers and their decision-making processes. Implications, limitations, and directions for future research are also provided.
Methods to Develop an in silico Clinical Trial: Computational Head-to-Head Comparison of Lisdexamfetamine and Methylphenidate
Authors: Gutiérrez-Casares José Ramón , Quintero Javier , Jorba Guillem , Junet Valentin , Martínez Vicente , Pozo-Rubio Tamara , Oliva Baldomero , Daura Xavier , Mas José Manuel , Montoto Carmen
Published: November 2021

Regulatory agencies encourage computer modeling and simulation to reduce the time and cost of clinical trials. Although still not classified in formal guidelines, system biology-based models represent a powerful tool for generating hypotheses with great molecular detail. Herein, we have applied a mechanistic head-to-headin silicoclinical trial (ISCT) between two treatments for attention-deficit/hyperactivity disorder, to wit lisdexamfetamine (LDX) and methylphenidate (MPH). The ISCT was generated through three phases comprising (i) the molecular characterization of drugs and pathologies, (ii) the generation of adult and children virtual populations (vPOPs) totaling 2,600 individuals and the creation of physiologically based pharmacokinetic (PBPK) and quantitative systems pharmacology (QSP) models, and (iii) data analysis with artificial intelligence methods. The characteristics of our vPOPs were in close agreement with real reference populations extracted from clinical trials, as did our PBPK models within vivoparameters. The mechanisms of action of LDX and MPH were obtained from QSP models combining PBPK modeling of dosing schemes and systems biology-based modeling technology, i.e., therapeutic performance mapping system. The step-by-step process described here to undertake a head-to-head ISCT would allow obtaining mechanistic conclusions that could be extrapolated or used for predictions to a certain extent at the clinical level. Altogether, these computational techniques are proven an excellent tool for hypothesis-generation and would help reach a personalized medicine.
Integrated Transportation, Building, and Electricity System Models to Explore Decarbonization Pathways in Regina, Saskatchewan
Authors: Seatle Madeleine , Stanislaw Lauren , Xu Robert , McPherson Madeleine
Published: November 2021

In Canada, the majority of urban energy demand services the transportation or building sectors, primarily with non-renewable energy sources including gasoline and natural gas. As a result, these two sectors account for 70% of urban greenhouse gas (GHG) emissions. The objective of this paper is to explore the potential for co-benefits when simultaneously electrifying transportation and building demand sectors while expanding variable renewable energy (VRE) production. The investigation uses a novel integrated framework of the transportation, building, and electricity sectors to represent the operational implications of demand side flexibility on both the demand and supply side of the energy system. This original approach allows for very fine temporal and spatial resolution within models, while still performing a multi-sector analysis. First, the activity-based transportation model produces passenger travel demand profiles, allowing for investigation of potential electricity demand and demand response from electric vehicles with high spatial and temporal resolution. Second, the archetype-based building model predicts electricity demand of the residential building sector, allowing for investigation into demand-side management strategies such as load-shifting, building retrofits, and changes in appliance technology. Third, the electricity system production cost dispatch model is used to model the operations of Regina's electricity grid and has a spatial resolution capable of assessing individual and connected positive energy districts as well as VRE integration. Through linking of these three models, the effects of consumer flexibility in transportation and building energy demand are explored, especially in the context of introducing much needed flexibility for large-scale VRE integration. A utility-controlled demand response (DR) strategy is explored as means for Regina to reach their renewable target, along with battery storage. Various pathways to Regina's target are considered, based on the various proposed scopes of the target. The results show that Regina can meet their renewable target with large-scale rooftop solar and wind capacity. DR strategies are marginally effective in aiding toward the renewable target, but, when implemented in conjunction with battery storage, is able to get Regina to within 1% of their renewable target.
THE Impact of Disruption on the Relationship Between Exploitation, Exploration, and Organizational Adaptation
Authors: Xiao Yao , Cen Jie , Soberg Peder
Published: November 2021

Firms should deploy exploration and exploitation to foster organizational adaptation. Previous research on exploration and exploitation lacked a focus on disruption implications in different contexts. This study aims to empirically test a moderation model including disruption events, exploration, exploitation, and organizational adaptation and enable a deeper understanding of organizational learning and innovation theory to yield competitive advantage and sustainability of innovative firms. Our results reveal that exploration is more effective during outside disruption events. The results do not support the concept that exploitation is more effective during inside disruptions. Disruptions also moderate the combined effect of exploration and exploitation. Although they are generally complementary in facilitating organizational adaptation, a singular focus on either exploration or exploitation is as effective as is combining exploration and exploitation during inside and outside disruption events. The results of an event study using seven Chinese international firms, including Alibaba, Meituan, Dianping, Baidu, Beibei, TP-link, and Maxio, provided 132 completed and usable questionnaires that supported our hypotheses. Our study contributes to a better understanding of disruption, exploration, exploitation, and related performance implications.
Scoping Out Elements of Sociocultural Adaptation in European Urban Agriculture
Authors: Cavicchi Bianca , Hegnes Atle Wehn
Published: November 2021

This paper explores and sheds light on the elements, complexity, and dynamics of sociocultural adaptation to innovation and climate change in European Urban Agriculture. We use a scoping-exploratory review to search and unveil elements of sociocultural adaptation (SCA) in the existing literature on European urban agriculture. We categorize these elements into three main categories. This categorization can inform and be further explored, operationalized, and developed in new case-study-based research and serve as a starting point to better understand social adaptation to innovation and climate change in urban contexts, and beyond. Key results draw attention to (a) socio-technical and socio-ecological innovations as critical to sociocultural adaptation to innovation and climate change (b) some elements of SCA identified through the scoping review seem more central than others for the adaption process (c) we are left with the question of whether we need to bridge social science with biology sciences, such as human behavioral biology and neurobiology to find the answer to deeper questions about SCA.
“He Who Relies on His Brother's Property Dies Poor”: The Complex Narratives of Livestock Care in Northern Tanzania
Authors: Davis Alicia , Virhia Jennika , Buza Joram , Crump John A. , de Glanville William A. , Halliday Jo E. B. , Lankester Felix , Mappi Tauta , Mnzava Kunda , Swai Emanuel S. , Thomas Kate M. , Toima Mamus , Cleaveland Sarah , Mmbaga Blandina T. , Sharp Jo
Published: November 2021

Background:Endemic zoonoses have important impacts for livestock-dependent households in East Africa. In these communities, people's health and livelihoods are severely affected by livestock disease losses. Understanding how livestock keepers undertake remedial actions for livestock illness has the potential for widespread benefits such as improving health interventions. Yet, studies about livestock and human health behaviours in the global south tend to focus on individual health choices. In reality, health behaviours are complex, and not solely about individualised health experiences. Rather, they are mediated by a range of “upstream” factors (such as unequal provision of services), which are beyond the control of the individual.

Methods:This paper presents qualitative research conducted from 2014 to 2019 for a study focused on the Social, Economic, and Environmental Drivers of Zoonoses in Tanzania (SEEDZ). Qualitative data were collected via focus group discussions, community meetings, informal interviews, formal in-depth interviews, observations and surveys that addressed issues of health, disease, zoonotic disease risks, and routes for treatment across 21 villages. Thematic analysis was carried out on in-depth interviews and focus group discussions. Conceptual analyses and observations were made through application of social science theories of health.

Findings:Livestock keepers undertake a range of health seeking strategies loosely categorised around self and formal treatment. Two key themes emerged that are central to why people make the decisions they do: access to resources and trust in health care providers. These two issues affect individual sense of agency which impacts their ability to act to improve livestock health outcomes. We suggest that individual choice and agency in veterinary health seeking decisions are only beneficial if health systems can offer adequate care and health equity is addressed.

Significance:This study demonstrates the value of in-depth qualitative research which reveals the nuance and complexity of people's decisions around livestock health. Most importantly, it explains why “better” knowledge does not always translate into “better” practise. The paper suggests that acknowledging and addressing these aspects of veterinary health seeking will lead to more effective provision.
Assessing Competitiveness of Fine Fescues (Festuca L. spp.) and Tall Fescue (Schedonorus arundinaceous (Schreb.) Dumort) Established with White Clover (Trifolium repens L., WC), Daisy (Bellis perennis L.) and Yarrow (Achillea millefolium L.)
Authors: Hahn Daniel , Morales Alejandro , Velasco-Cruz Ciro , Leinauer Bernd
Published: November 2021

Regulatory restrictions on herbicide use for managing turfgrass weeds has prompted the search for alternative control strategies. Fescue (Festuca) species were identified for their potential to interfere with growth of annual and perennial weeds. In a study conducted in 2018 and 2019, six fescue cultivars were tested from five different species for interference with the growth of three common turfgrass weeds: white clover (Trifolium repens L., WC), daisy (Bellis perennis L.) and yarrow (Achillea millefolium L.). Fine (Festuca L. spp.) and tall fescues (Schedonorus arundinaceus (Schreb.) Dumort.) were sown and grown in a field trial for 14 days before overseeding with different weeds. vigor and visual quality of grasses, weed cover, and vegetation cover was recorded regularly for 84 days. Differences in mean temperatures and precipitation between the two years of the study resulted in differences in growth of grasses and weeds, as well as in the extent of weed interference of fescue cultivars. Cultivars Musica (F. rubra L. ssp. commutata Gaudin) and Barpearl (F. rubra L. ssp. littoralis) were least affected by weed growth during both years, but there was overlap with other cultivars for the measured parameters. Melyane (tall fescue) was deemed unsuitable for natural weed suppression because growth and vigor declined after first mowing, ultimately leading to unacceptable visual quality. Turfgrass visual scores were moderately negatively correlated to weed cover in both years. Future research should focus on F. rubra L. ssp. rubra Gaudin and F. rubra L. ssp. littoralis subspecies and identify the mechanisms used to interfere with weed growth.
Oxysterols and Retinal Microvascular Dysfunction as Early Risk Markers for Cardiovascular Disease in Normal, Ageing Individuals
Authors: Shokr Hala , Dias Irundika HK , Gherghel Doina
Published: November 2021

The aim of the present paper is to assess the relationship between oxysterol levels and retinal microvascular function in individuals of various age groups, free of clinically evident diseases. Forty-two apparently healthy individuals were included in the present study (group 1: 19–30 years, group 2: 31–50 years, and group 3: 51–70 years). Retinal microvascular function was assessed using the dynamic retinal vessel analyzer (DVA, IMEDOS GmbH, Jena, Germany). Fasting plasma was obtained from all subjects and quantification of monohydroxy and dihydroxy oxysterols assessment was performed using LC-MS/MS following reverse phase chromatography. A Griess assay was used to evaluate the Nitric Oxide (NO) concentration in all individuals. The glutathione redox ratio was also analyzed by means of whole blood glutathione recycling assay. In all participants, the levels of 7-Ketocholesterol, 25-hydroxycholesterol and 7β-hydroxycholesterol correlated significantly and positively with the time to maximum arteriolar dilation. In addition, 25-hydroxycholesterol and 7β-hydroxycholesterol negatively correlated to the percentage of maximum arteriolar dilation. A negative correlation was observed for 27-hydroxycholesterol and 7β-hydroxycholesterol with microvascular arteriolar constriction. These results suggest that, with age, abnormal oxysterol levels correlate with early changes in microvascular bed function. This relationship could signal early risk for cardiovascular diseases (CVDs) in an ageing population.
Effects of Iodonium Analogs on Nadph Oxidase 1 in Human Colon Cancer Cells
Authors: Roy Krishnendu K. , Lu Jiamo , Doroshow James H.
Published: November 2021

Recent studies suggest that of the molecules postulated to function as inhibitors of the NADPH oxidase family of enzymes iodonium analogs known to broadly interfere with flavin dehydrogenase function demonstrate mechanistic validity as NADPH oxidase poisons. In recent work, we have produced a series of novel iodonium compounds as putative inhibitors of these oxidases. To evaluate the potential utility of two novel molecules with favorable chemical properties, NSC 740104 and NSC 751140, we compared effects of these compounds to the two standard inhibitors of this class, diphenyleneiodonium and di-2-thienyliodonium, with respect to antiproliferative, cell cycle, and gene expression effects in human colon cancer cells that require the function of NADPH oxidase 1. Both new agents blocked NADPH oxidase-related reactive oxygen production, inhibited tumor cell proliferation, produced a G1/S block in cell cycle progression, and inhibited NADPH oxidase 1 expression at the mRNA and protein levels at low nM concentrations in a fashion similar to or better than the parent molecules. These studies suggest that NSC 740104 and NSC 751140 should be developed further as mechanistic tools to better understand the role of NADPH oxidase inhibition as an approach to the development of novel therapeutic agents for colon cancer.
A Multi-Feature Ensemble Learning Classification Method for Ship Classification with Space-Based AIS Data
Authors: Wang Yitao , Yang Lei , Song Xin , Chen Quan , Yan Zhenguo
Published: November 2021

AIS (Automatic Identification System) is an effective navigation aid system aimed to realize ship monitoring and collision avoidance. Space-based AIS data, which are received by satellites, have become a popular and promising approach for providing ship information around the world. To recognize the types of ships from the massive space-based AIS data, we propose a multi-feature ensemble learning classification model (MFELCM). The method consists of three steps. Firstly, the static and dynamic information of the original data is preprocessed and features are then extracted in order to obtain static feature samples, dynamic feature distribution samples, time-series samples, and time-series feature samples. Secondly, four base classifiers, namely Random Forest, 1D-CNN (one-dimensional convolutional neural network), Bi-GRU (bidirectional gated recurrent unit), and XGBoost (extreme gradient boosting), are trained by the above four types of samples, respectively. Finally, the base classifiers are integrated by another Random Forest, and the final ship classification is outputted. In this paper, we use the global space-based AIS data of passenger ships, cargo ships, fishing boats, and tankers. The model gets a total accuracy of 0.9010 and an F1 score of 0.9019. The experiments prove that MFELCM is better than the base classifiers. In addition, MFELCM can achieve near real-time online classification, which has important applications in ship behavior anomaly detection and maritime supervision.
Vertical Characteristics of Secondary Aerosols Observed in the Seoul and Busan Metropolitan Areas of Korea during KORUS-AQ and Associations with Meteorological Conditions
Authors: Kim Jong-Min , Lee Hyo-Jung , Jo Hyun-Young , Jo Yu-Jin , Kim Cheol-Hee
Published: November 2021

In this study, the chemical components of aerosols observed at ground level and in upper layers during the Korea–United States Air Quality (KORUS-AQ) campaign were analyzed in two representative metropolitan areas of Korea: the Seoul metropolitan area (SMA) and the Busan-containing southeastern metropolitan area (BMA). First, we characterized emissions using the Clean Air Policy Support System (CAPSS) emission statistics, and compared them with both ground- and aircraft-based measurements obtained during the KORUS-AQ campaign. The emission statistics showed that the SMA had higher NOx levels, whereas BMA had significantly higher SO2 levels. Ground-level observations averaged for the summer season also showed SMA–nitrate and BMA–sulfate relationships, reflecting the CAPSS emission characteristics of both areas. However, organic carbon (OC) was higher in BMA than SMA by a factor of 1.7, despite comparable volatile organic compound (VOC) emissions in the two areas. DC-8 aircraft-based measurements showed that, in most cases, nitrogen-rich localities were found in the SMA, reflecting the emission characteristics of precursors in the two sampling areas, whereas sulfur-rich localities in the BMA were not apparent from either ground-based or aircraft observations. KORUS-AQ measurements were classified according to two synoptic conditions, stagnant (STG) and long-range transport (LRT), and the nitrate-to-sulfate (N/S) ratio in both ground and upper layers was higher in the SMA for both cases. Meanwhile, organic aerosols reflected local emissions characteristics in only the STG case, indicating that this stagnant synoptic condition reflect local aerosol characteristics. The LRT case showed elevated peaks of all species at altitudes of 1.0–3.5 km, indicating the importance of LRT processes for predicting and diagnosing aerosol vertical distributions over Northeast Asia. Other chemical characteristics of aerosols in the two metropolitan areas were also compared.
Air Pollutant Concentration Prediction Based on a CEEMDAN-FE-BiLSTM Model
Authors: Jiang Xuchu , Wei Peiyao , Luo Yiwen , Li Ying
Published: November 2021

The concentration series of PM2.5 (particulate matter ≤ 2.5 μm) is nonlinear, nonstationary, and noisy, making it difficult to predict accurately. This paper presents a new PM2.5 concentration prediction method based on a hybrid model of complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and bi-directional long short-term memory (BiLSTM). The new method was applied to predict the same kind of particulate pollutant PM10 and heterogeneous gas pollutant O3, proving that the prediction method has strong generalization ability. First, CEEMDAN was used to decompose PM2.5 concentrations at different frequencies. Then, the fuzzy entropy (FE) value of each decomposed wave was calculated, and the near waves were combined by K-means clustering to generate the input sequence. Finally, the combined sequences were put into the BiLSTM model with multiple hidden layers for training. We predicted the PM2.5 concentrations of Seoul Station 116 by the hour, with values of the root mean square error (RMSE), the mean absolute error (MAE), and the symmetric mean absolute percentage error (SMAPE) as low as 2.74, 1.90, and 13.59%, respectively, and an R2 value as high as 96.34%. The “CEEMDAN-FE” decomposition-merging technology proposed in this paper can effectively reduce the instability and high volatility of the original data, overcome data noise, and significantly improve the model’s performance in predicting the real-time concentrations of PM2.5.
The Effects of Vitamin D on Immune System and Inflammatory Diseases
Authors: Ao Tomoka , Kikuta Junichi , Ishii Masaru
Published: November 2021

Immune cells, including dendritic cells, macrophages, and T and B cells, express the vitamin D receptor and 1α-hydroxylase. In vitro studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, has an anti-inflammatory effect. Recent epidemiological evidence has indicated a significant association between vitamin D deficiency and an increased incidence, or aggravation, of infectious diseases and inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the impact of vitamin D on treatment and prevention, particularly in infectious diseases such as the 2019 coronavirus disease (COVID-19), remains controversial. Here, we review recent evidence associated with the relationship between vitamin D and inflammatory diseases and describe the underlying immunomodulatory effect of vitamin D.
Advances in Pancreatic Ductal Adenocarcinoma Treatment
Authors: Anderson Eric M. , Thomassian Shant , Gong Jun , Hendifar Andrew , Osipov Arsen
Published: November 2021

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest malignancies among all cancers. Despite curative intent, surgery and the use of standard cytotoxic chemotherapy and radiation therapy, PDAC remains treatment-resistant. In recent years, more contemporary treatment modalities such as immunotherapy via checkpoint inhibition have shown some promise in many other malignancies, yet PDAC still eludes an effective curative treatment. In investigating these phenomena, research has suggested that the significant desmoplastic and adaptive tumor microenvironment (TME) of PDAC promote the proliferation of immunosuppressive cells and act as major obstacles to treatment efficacy. In this review, we explore challenges associated with the treatment of PDAC, including its unique immunosuppressive TME. This review examines the role of surgery in PDAC, recent advances in surgical approaches and surgical optimization. We further focus on advances in immunotherapeutic approaches, including checkpoint inhibition, CD40 agonists, and discuss promising immune-based future strategies, such as therapeutic neoantigen cancer vaccines as means of overcoming the resistance mechanisms which underly the dense stroma and immune milieu of PDAC. We also explore unique signaling, TME and stromal targeting via novel small molecule inhibitors, which target KRAS, FAK, CCR2/CCR5, CXCR4, PARP and cancer-associated fibroblasts. This review also explores the most promising strategy for advancement in treatment of pancreatic cancer by reviewing contemporary combinatorial approaches in efforts to overcome the treatment refractory nature of PDAC.
The BRD9/7 Inhibitor TP-472 Blocks Melanoma Tumor Growth by Suppressing ECM-Mediated Oncogenic Signaling and Inducing Apoptosis
Authors: Mason Lawrence David , Chava Suresh , Reddi Kiran Kumar , Gupta Romi
Published: November 2021

Melanoma accounts for the majority of all skin cancer-related deaths and only 1/3rd of melanoma patients with distal metastasis survive beyond five years. However, current therapies including BRAF/MEK targeted therapies or immunotherapies only benefit a subset of melanoma patients due to the emergence of intrinsic or extrinsic resistance mechanisms. Effective treatment of melanoma will thus require new and more effective therapeutic agents. Towards the goal of identifying new therapeutic agents, we conducted an unbiased, druggable epigenetic drug screen using a library of 32 epigenetic inhibitors obtained from the Structural Genome Consortium that targets proteins encoding for epigenetic regulators. This chemical genetic screening identified TP-472, which targets bromodomain-7/9, as the strongest inhibitor of melanoma growth in both short- and long-term survival assays and in mouse models of melanoma tumor growth. Mechanistically, using a transcriptome-wide mRNA sequencing profile we identified TP-472 treatment downregulates genes encoding various extracellular matrix (ECM) proteins, including integrins, collagens, and fibronectins. Reactome-based functional pathway analyses revealed that many of the ECM proteins are involved in extracellular matrix interactions required for cancer cell growth and proliferation. TP-472 treatment also upregulated several pro-apoptotic genes that can inhibit melanoma growth. Collectively, our results identify BRD7/9 inhibitor TP-472 as a potentially useful therapeutic agent for melanoma therapy.
Gene Expression Signature Associated with Clinical Outcome in ALK-Positive Anaplastic Large Cell Lymphoma
Authors: Daugrois Camille , Bessiere Chloé , Dejean Sébastien , Anton-Leberre Véronique , Commes Thérèse , Pyronnet Stephane , Brousset Pierre , Espinos Estelle , Brugiere Laurence , Meggetto Fabienne , Lamant Laurence
Published: November 2021

Anaplastic large cell lymphomas associated with ALK translocation have a good outcome after CHOP treatment; however, the 2-year relapse rate remains at 30%. Microarray gene-expression profiling of 48 samples obtained at diagnosis was used to identify 47 genes that were differentially expressed between patients with early relapse/progression and no relapse. In the relapsing group, the most significant overrepresented genes were related to the regulation of the immune response and T-cell activation while those in the non-relapsing group were involved in the extracellular matrix. Fluidigm technology gave concordant results for 29 genes, of which FN1, FAM179A, and SLC40A1 had the strongest predictive power after logistic regression and two classification algorithms. In parallel with 39 samples, we used a Kallisto/Sleuth pipeline to analyze RNA sequencing data and identified 20 genes common to the 28 genes validated by Fluidigm technology—notably, the FAM179A and FN1 genes. Interestingly, FN1 also belongs to the gene signature predicting longer survival in diffuse large B-cell lymphomas treated with CHOP. Thus, our molecular signatures indicate that the FN1 gene, a matrix key regulator, might also be involved in the prognosis and the therapeutic response in anaplastic lymphomas.