bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 1/1b Studies of UCB0599, an Oral Inhibitor of α‐Synuclein Misfolding, Including a Randomized Study in Parkinson's Disease
Authors: Smit Johan Willem , Basile Peter , Prato Maria Key , Detalle Laurent , Mathy François‐Xavier , Schmidt Astrid , Lalla Marianna , Germani Massimiliano , Domange Coralie , Biere Anja‐Leona , Bani Massimo , Carson Stan , Genius Just
Published: August 2022

Background

Parkinson's disease (PD) and its progression are thought to be caused and driven by misfolding of α‐synuclein (ASYN). UCB0599 is an oral, small‐molecule inhibitor of ASYN misfolding, aimed at slowing disease progression.

Objective

The aim was to investigate safety/tolerability and pharmacokinetics (PK) of single and multiple doses of UCB0599.

Methods

Safety/tolerability and PK of single and multiple doses of UCB0599 and its metabolites were investigated in two phase 1 studies in healthy participants (HPs), where food effect and possible interaction with itraconazole (ITZ) were assessed (UP0030 [randomized, placebo‐controlled, dose‐escalation, crossover study, N = 65] and UP0078 [open‐label study, N = 22]). Safety/tolerability and multi‐dose PK of UCB0599 were subsequently investigated in a phase 1b randomized, double‐blind, placebo‐controlled study of participants with PD (UP0077 [NCT04875962], N = 31).

Results

Across all studies, UCB0599 displayed rapid absorption with linear, time‐independent PK properties; PK of multiple doses of UCB0599 were predictable from single‐dose exposures. No notable food‐effect was observed; co‐administration with ITZ affected UCB0599 disposition (maximum plasma concentration and area under the curve increased ~1.3‐ and ~2 to 3‐fold, respectively) however, this did not impact the safety profile. Hypersensitivity reactions were reported in UP0030 (n = 2) and UP0077 (n = 2). Treatment‐related adverse events occurred in 43% (UCB0599), and 30% (placebo) of participants with PD were predominantly mild‐to‐moderate in intensity and were not dose related.

Conclusions

Seventy‐three HPs and 21 participants with PD received UCB0599 doses; an acceptable safety/tolerability profile and predictable PK support continued development of UCB0599 for the slowing of PD progression. A phase 2 study in early‐stage PD is underway (NCT04658186). © 2022 UCB Pharma. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Assessing Size-Dependent Population-Level Effects of Largemouth Bass Tournament Mortality
Authors: Sylvia Andrea , Weber Michael J.
Published: August 2022

As black bass Micropterus spp. tournaments continue to grow in popularity, so too must evaluations on the population-level effects of live-release angling events. Although factors influencing the tournament mortality of individuals are well studied, assessments at the population level are lacking. We evaluated differences in tournament capture probability and survival of two size-classes of Largemouth Bass M. salmoides (medium: 381–457 mm; large: >457 mm) using a multistate mark–recapture model. Changes in estimated capture and survival rates of medium and large bass were then simulated to assess potential effects on population size structure. Tournament capture probabilities for medium bass were approximately three times higher than those for large bass, and tournament capture probabilities for both size-classes increased with air temperature. Medium bass also experienced higher survival rates than large bass after tournaments, and survival rates of both groups declined with increasing water temperature. Our simulations indicated that both increases in tournament capture probability and reductions in posttournament survival of large bass resulted in some reductions in population size structure. However, increases in tournament capture probability or reductions in tournament survival of medium bass or medium and large bass alone had little to no effect. Our results suggest that under the observed tournament conditions, tournaments have little effect on bass population size structure, but size structure could be reduced with higher capture probabilities and lower posttournament survival; this information is useful for managing the fishery effects of tournament angling. Our modeling approach also provides a framework for understanding population-level effects of tournaments on other populations under alternative conditions.
Caffeine facilitates extinction of auditory fear conditioning in rats
Authors: Ozawa Takaaki , Kaseda Kodai , Ichitani Yukio , Yamada Kazuo
Published: August 2022

Caffeine is the most widely consumed psychostimulant drug which could affect learning and memory acting through central adenosine receptors. Although caffeine has been suggested to impair the acquisition and the expression of auditory fear conditioning, its effect on the extinction has not been elucidated. To address this issue, in the present study, we investigated whether caffeine affects the extinction of conditioned fear in an auditory fear conditioning paradigm. During conditioning, rats received pairings of auditory cues (conditioned stimulus, CS) and foot shocks (unconditioned stimulus). On the next day, the rats were intraperitoneally administrated saline or caffeine (5 or 10 mg/kg) and then subjected to the extinction training, in which CSs were repeatedly presented without the foot shocks. Twenty‐four hours later, the rats were re‐exposed to the presentations of CSs (retrieval test). We found an acute caffeine administration dose‐dependently decreased freezing rates during the presentations of CS in the extinction training. Furthermore, caffeine‐treated animals showed lower conditioned freezing responses in the retrieval test. These findings suggest that caffeine facilitates the extinction of conditioned fear.
Modeling and influence of thrust force torque and delamination during drilling of natural fiber composite
Authors: Murugesan Venkatasudhahar , Thandavamoorthy Raja , Cheruvu Abhimanyu , Vinayagam Mohanavel
Published: August 2022

Natural fiber composites are named sustainable, renewable environmentally friendly materials. Machining the fiber reinforced composite is difficult due to their anisotropic and heterogeneous nature. Computer numerical controlled drilling caused severe delaminating at the entry and exit of the drilled hole. These can be minimized in several ways such as process parameters, fabrication method, and reinforcement arrangements (Orientation/Treatment/Aspect ratio/Fiber volume fraction). Thrust force and torque are caused machining of composites, it can be controlled by spindle speed, feed rate, and cutting velocity. It has been observed that the output responses such as thrust, torque, delamination peel up and push out of composites depend on the diameters of the drill bit (6, 8, 10 mm), cutting speeds (1000, 2000, 3000 rpm), and feeds (10, 20, 30 mm/min). Total 27 numbers of holes were drilled based on Taguchi L‐27 factorial design orthogonal array. Response surface methodology has been employed to compare input drilling parameters and output responses. It is found that a smaller diameter drill bit of 6 mm with a higher speed of 3000 rpm and lesser feed of 10 mm/min produced high‐quality holes.
Effect of tramadol and DOACs with special attention to dabigatran on concomitant use, on the risk of mayor bleeding using BIFAP database in Spain
Authors: Burgos‐Gonzalez Airam de , Huerta Consuelo , Peñalver María José , Sordo Luis , Pulido José , Soriano Lucía Cea
Published: August 2022

Background

Tramadol, a weak opioid, inhibits the reuptake of serotonin, a key feature on vascular homeostasis. A suspected interaction exists between dabigatran and tramadol, which might trigger an excess on risk of bleeding however, there is a gap in knowledge on this topic.

Purpose

To estimate the effects of tramadol, dabigatran and concomitant use on the risk of hospitalized major bleeds (Gastrointestinal bleeding and intra‐extracranial bleeds).

Methods

Among a validated established cohort of new users of oral anticoagulants for non‐valvular atrial fibrillation (NVAF) aged 18 years or older, we identified all hospitalized bleed episodes (GIB and extra/intracranial bleeds) within 2008–2015. A nested case–control analysis was conducted using conditional logistic regression. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated for dabigatran, tramadol, and concomitant use. Several sensitivity analyses were carried out.

Results

aORs (95%CIs) for current use of only dabigatran, only tramadol and concomitant users were 1.73 (1.37–2.18) and 1.38 (1.13–1.67) and 2.04 (0.74–5.67) compared with non‐users of both drugs (>365 days). aORs for current continuers and non‐continuer users of dabigatran were 1.36 (1.00–1.86) and 2.19 (1.61–2.98), respectively. For the latter, non‐continuer users with a short duration of dabigatran cumulated the highest risk (3.36 [1.88–5.99]). There also was an increased risk with concomitant use of tramadol and rivaroxaban (2.24 [1.19–4.21]), or antagonist of vitamin K (1.30 [1.00–1.69]).

Conclusion

There was a trend towards and increased risk of excess bleeds when using concomitantly with dabigatran. The effect decreases with a narrower definition of current use.
Registration of ‘Comrade’ peanut
Authors: Chamberlin Kelly , Bennett Rebecca S. , Isleib Thomas George , Copeland Susan , Dunne Jeffrey C.
Published: August 2022

‘Comrade’ (Reg. no. CV‐149, PI 698820) is a large‐seeded, high‐oleic, virginia‐type peanut (Arachis hypogaea L. subsp. hypogaea var. hypogaea) with enhanced pod size distribution and seed size compared with the virginia‐type cultivar ‘Contender’. Released jointly by the USDA‐ARS and North Carolina State University in 2021, Comrade (tested as N15022olEJ and NCEX17) is a high‐oleic virginia breeding line resulting from a selection made from the cross N06007E/3/X05248(BC1F1:F04), Bailey//X05027 (F01), Bailey/N02060ol. Comrade had an average pod yield of 5,260 kg ha–1, a total sound mature kernel (TSMK) of 69%, a sound mature kernel (SMK) weight of 97 g 100 seed–1, and 62% extra‐large kernels (ELKs), giving it the highest estimated value per hectare among the virginia‐type cultivars tested in Oklahoma for 2018–2020. When entered in the national Uniform Peanut Performance Test, Comrade performed well in all locations, averaging 5,235 kg ha–1, 84% fancy pods, 44% ELKs, an SMK weight of 103 g 100 seed–1, and a TSMK of 68%. Comrade's average super jumbo pod count per kilogram and average pod brightness score were reported at 317 kg–1 (9 per ounce) and 50, respectively, indicating large, bright pods, which are necessary components of any market‐worthy virginia‐type cultivar. Comrade consistently averaged 47–50% super jumbo pods across locations in Oklahoma and nationwide trials. This significant increase in the percentage of super‐jumbo pods compared with currently grown cultivars will increase growers’ profits and enable producers in the southwestern United States to increase participation in the foreign export market.
Investigating general and specific psychopathology factors with nuance‐level personality traits
Authors: Hang Yuzhan , Speyer Lydia Gabriela , Haring Liina , Murray Aja Louise , Mõttus René
Published: August 2022

Mental health disorders share substantial variance, prompting researchers to develop structural models that can capture both generalised psychopathology risk and disorder/symptom‐specific variation. This study investigated the associations of the general and specific psychopathology factors with multiple personality trait hierarchy levels: broad domains, their facets and nuances (N = 1839 Estonian adults). A bi‐factor model with a general ‘p’ factor and specific factors for internalising problems, thought disorders and substance use best represented psychopathology structure. Although traits' predictive accuracy varied across psychopathology factors, nuances (the lowest level personality units) provided higher predictive accuracy and higher discriminant validity than domains. For example, traits related to high vulnerability, depression and immoderation and low friendliness and achievement striving were most strongly associated with the p factor. Nuances may prove useful for predicting and understanding general and specific psychopathology forms.
Functionalization of polyfluorene‐wrapped carbon nanotubes using thermally cleavable side‐chains
Authors: Ritaine Dialia , Adronov Alex
Published: August 2022

The length and nature of side‐chains in conjugated polymer‐wrapped carbon nanotubes can impact their conductivity. We investigate functionalization of polyfluorene‐single‐walled carbon nanotubes (SWNT's) using cleavable side‐chains that are removable post‐processing. The triethylene glycol side‐chains contain a thermally cleavable carbonate linker. Upon heating the films to 170 °C, the conductivity increased, reaching a plateau of (2.0 ± 0.1) × 10−2 S/m after 16 h, compared to (1.0 ± 0.2) × 10−3 S/m for the control sample. UV–Vis–near‐infrared (NIR) and Raman spectroscopy show well‐dispersed SWNT samples and confirm that the heating treatment did not damage the nanotubes. Functionalization using longer polyethylene glycol side‐chains was also investigated. After heating, cleavage of the longer chains resulted in conductivity of (8.2 ± 1.6) × 10−4 S/m compared to (8.1 ± 1.4) × 10−5 S/m for the control. UV–Vis–NIR and Raman spectroscopy showed well‐dispersed SWNT samples and confirmed that the nanotubes were not damaged. Finally, we investigate dispersions in triethylene glycol monomethyl ether and tetraethylene glycol dimethyl ether, generally deemed “green” solvents. Polymer‐SWNT complexes functionalized with shorter side‐chains did not form stable dispersions, resulting in precipitation of the nanotubes upon standing for a few minutes after the removal of tetrahydrofuran, while complexes functionalized with longer side‐chains formed stable dispersions.
Social determinants and health‐related quality of life in a sample of diverse, low socioeconomic status cancer patients
Authors: Lui Florence , Finik Jackie , Leng Jennifer , Gany Francesca
Published: August 2022

Objectives

In the United States, medically underserved populations, such as ethnoracially underrepresented groups, the limited English proficient (LEP), and the unemployed, may be vulnerable to poor functioning in cancer survivorship. The present study examined whether race/ethnicity, LEP status, and unemployment status were associated with poor health‐related quality of life (HRQL) in four domains (physical, social, emotional, and functional well‐being (FWB)) in a diverse, low socioeconomic status (SES) sample of cancer patients.

Methods

The sample included 1592 ethnoracially diverse, low SES, primarily foreign‐born adult oncology patients participating in an enhanced patient navigation program in 11 New York City hospital‐based cancer clinics. This secondary cross‐sectional analysis of program intake data examined bivariate associations between sociodemographic and clinical factors and poor HRQL (Functional Assessment of Cancer Therapy‐General scores ≤70). Factors found to be related to poor HRQL (at p < 0.05) were entered into logistic regressions with overall HRQL and the four HRQL subscales as outcomes. The Benjamini‐Hochberg Procedure controlled for potentially inflated type‐I error rate due to multiple comparisons.

Results

All three predictor variables (race/ethnicity, LEP status, and unemployment status) were significantly associated with increased odds of reporting poor FWB. Specifically, non‐Hispanic White and Hispanic cancer patients had 2.7 and 1.5 times the odds of reporting poor FWB than non‐Hispanic Black patients. The unemployed had 1.4 times the odds of reporting poor FWB than their employed or retired counterparts. Limited EP patients had 1.4 times the odds of reporting poor FWB than EP participants. Non‐Hispanic Black patients evidenced significantly lower odds of reporting poor HRQL across all subscale domains compared with other ethnoracial groups.

Conclusions

LEP and unemployed individuals were more likely to report poor FWB, which may indicate that the most marginalized cancer patients face significant barriers to adequate functioning. Interventions that promote functional abilities (i.e., activities of daily living, self‐care, and work retention) and policies and programs that reduce systemic inequality and address social determinants of health may aid in improving HRQL for these underserved groups in survivorship. Non‐Hispanic Black cancer patients were less likely than other groups to report poor physical, social, emotional, and FWB. Identifying protective factors in this group may aid in efforts to improve HRQL for all patients.
Observer‐based adaptive sliding‐mode control under dynamic event‐triggered scheme with actuator and communication faults
Authors: He Hangfeng , Qi Wenhai , Cao Jinde , Cheng Jun , Shi Kaibo
Published: August 2022

The adaptive technique and sliding‐mode algorithm (SMA) for observer‐based fault tolerant control is discussed with dynamic event‐triggered scheme (DETS) in this article. Both the actuator and communication faults are considered, which implies that the inputs of system and controller are unreliable. Moreover, the switched DETS for controller‐actuator channel is proposed to reduce bandwidth usage and actuator action frequency, which is different from the traditional event‐triggered strategies. To deal with communication faults, which can be described as packet losses, the closed‐loop system is modeled as a stochastic system. The SMA‐based observer is designed to estimate system states, which lays the foundation for the design of control algorithm to mitigate the effects of faults and DETS. Then, a novel observer‐based adaptive sliding‐mode control (SMC) law based on hyperbolic tangent function is proposed to guarantee the stochastic globally uniformly ultimately boundedness and reduce chattering. At last, the proposed DETS and observer‐based adaptive SMC law are applied into a robotic arm to illustrate the validity.
Renewable energy for sustainable development in Asia‐Pacific region: Do foreign direct investment and regulatory quality matter?
Authors: Annamalaisamy Bhuvaneskumar , Vepur Jayaraman Sivakumar
Published: August 2022

Global climate change has already created noticeable ill‐effects on the environmental system and attaining further economic growth without compromising environmental quality is a difficult challenge for every country on this planet. Inspired by United Nation's Sustainable Development Goals (SDGs) core agenda, we investigated the singular, combined, and coupling influence of income growth, foreign direct investment inflows, renewable energy, and regulatory quality (RQ) on climate change under the scale, technique, and composition effects hypothesis. This analysis enables the creation of appropriate policy interventions to mitigate the severity of climate change in the future for the diverse countries in the Asia‐Pacific region. The study adopted the dynamic heterogenous estimation methodology responsible for accounting for the heterogeneity. We estimated 14 empirical models for the panel data from 1996 to 2015 of Asia‐Pacific countries. Empirical results validated the scale, technique, and composition effects and include that the progress in the share of renewable energy consumption in emerging countries by 1% reduces the greenhouse gas emissions by 0.24% (99% Confidence interval [C.I]), whereas 1% increase in the interactive effect of renewable energy and RQ deepens the emissions by 0.35% (99% C.I). The income level and RQ aggravate greenhouse gas emissions; whereas renewable energy diminishes the overall emissions level in emerging and advanced economies. This article's empirical outcomes would facilitate climate change mitigation‐related policy interventions of diverse economies in the Asia‐Pacific region to attain Sustainable Development Goals (SDGs‐ 7 and 13).
Can nuclear energy technology budgets pave the way for a transition toward low‐carbon economy: Insights from the United Kingdom
Authors: Caglar Abdullah Emre
Published: August 2022

The energy resources of the economies play a critical role in reaching the 2030 and 2050 decarbonization targets. In this respect, research and development budgets for nuclear energy (NRD), which constitutes one‐fifth of the current energy resources in the United Kingdom, can be a step in the transition to a low‐carbon economy. However, the current literature neglects the impact of NRD on environmental quality for the United Kingdom. Thus, this paper explores the impact of NRD on CO2 in the United Kingdom by controlling income, trade openness, and financial development from 1974 to 2020 with a non‐linear autoregressive distributed lag (NARDL) approach. Empirical findings confirm the asymmetrical relationship between NRD and CO2. In this context, while positive changes in NRD reduce environmental degradation, negative changes in NRD hinder environmental sustainability. Another finding is that the environmental Kuznets curve (EKC) hypothesis is valid. Furthermore, the results show that while economic growth and trade openness reduce environmental quality, financial development contributes to environmental quality. Considering these findings, financial deepening activities should continue in the United Kingdom. More resources should be allocated to nuclear energy research and development budgets in the transition to a low‐carbon economy.
The determinants and performance outcome of the firm's capacity to maintain customer loyalty
Authors: Ullah Zeeshan
Published: August 2022

This research aims to study the determinants and performance‐outcome of the firm's capacity to maintain a loyal customer base. Therefore, this research investigates the influence of sustainable product development on the firm's capacity to maintain customer loyalty. Furthermore, this research investigates the moderating influence of marketing resource intensity on sustainable product development and the firm's capacity to maintain customer loyalty. Moreover, this research investigates the firm profitability as a performance outcome of the firm's capacity to maintain customer loyalty. This research uses the panel dataset of 433 manufacturing firms from the United States. The findings from fixed‐effect regression analysis confirm the significant positive influence of sustainable product development on the firm's capacity to maintain customer loyalty. The moderation analysis confirms the significant positive influence of marketing resource intensity on sustainable product development and the firm's capacity to maintain customer loyalty. The results also confirm the contribution of the firm's capacity to maintain customer loyalty to firm profitability. This study contributes to the customer loyalty literature stream by theorizing the capacity to maintain customer loyalty construct and empirically studying its performance outcome, the contribution of sustainable product development in the firm's capacity to maintain customer loyalty and the moderating role of marketing resource intensity in this regard, under the resource‐based view. Based on the study findings, this research suggests that managers need to emphasize sustainable product development in the firms to strengthen the firm's capacity to maintain customer loyalty and recognize the interactional role of marketing resource intensity in this regard.
Decentralized trade finance using blockchain and lightning network
Authors: Kumar Shivansh , Amin Ruhul
Published: August 2022

A decentralized trade finance system is urgently needed, as smart contracts and blockchain can make the entire process fast, secure, and efficient while also allowing ordinary people to participate in the global economy. Decentralization will increase trust and transparency, as well as allow smaller businesses to participate in the industry, resulting in more jobs and a boost to the economy. We have also taken a decentralized approach to solving this massive problem with our project. We propose a decentralized trade finance model that is owned by the general public, such as you and me. On the one hand, a community of people like you and me give liquidity to the platform's liquidity pool via a lighting network, while on the other hand, importers and exporters can create profiles and engage in trade finance via the decentralized network. The exporter will use the platform validator to validate their invoice and then apply for trade finance. If everything goes well, the exporter will get monies from the liquidity pool, and the platform will be compensated by the importer after the trade is completed. Everyone involved in the process will receive trade tokens when each successful deal is completed, incentivizing the participants' good behavior.
Experimental study on mechanical properties of steel and steel fiber reinforced concrete beams
Authors: Wu Kai , Zhang Yanjie , Lin Shiqi , Liang Qingqing , Qian Shiyuan
Published: August 2022

According to the construction difficulties in steel reinforced concrete (SRC) structures, rebar cages were discretized into steel fibers to form steel and steel fiber reinforced concrete (SSFRC) structures. The 18 SSFRC beams without rebar cages were tested under bending, and the effect of the steel fiber volume ratio (ρsf), shaped steel ratio (ρss), and shear span ratio (λ) on mechanical properties were investigated. Increasing ρsf could not only turn shearing failure and debonding failure into bending failure, and effectively reduce the sudden decrease of load, but also enhance the bearing capacity, ductility, and damage resistance of specimens to a certain extent. As the ρss ascended, the mechanical properties were obviously improved. However, ρsf should be accordingly increased to avoid adverse effects of excessive ρss. The specimen with small λ had the better bearing and energy dissipation capacity and poor ductility. A large λ meant that ρss and ρsf should be appropriately increased to prevent premature failure of specimens.
High school students' out‐of‐school science participation: A latent class analysis and unique associations with science aspirations and achievement
Authors: Burns Emma C. , Martin Andrew J. , Kennett Roger , Pearson Joel , Munro‐Smith Vera
Published: August 2022

Students' out‐of‐school science participation has been identified as a factor that supports adaptive science outcomes. Researchers have largely investigated students' out‐of‐school science participation in terms of structured science activities (e.g., attending a science camp), with far less consideration of how students' involvement in unstructured out‐of‐school science activities (e.g., using at‐home science kits) may also be associated with students' aspirations and achievement in science. Research in this area has established a conceptual framework by which activities can be categorized by the activity's level of interaction (i.e., whether receptive or active). Although this conceptual framework is useful to understand the types of unstructured activities in which students engage, this research has tended to overlook the fact that students often participate in more than one out‐of‐school unstructured activity. The present investigation addressed this dearth of research by examining the extent to which different typologies of student participation in out‐of‐school receptive and active unstructured activities existed. The study also examined if these profiles were uniquely associated with students' aspirations and achievement in science above and beyond the effects of their current level of in‐school participation. The study employed a latent class analysis of N = 996 Australian high school students (40.60% girls) from six schools serving predominately above average socioeconomic status Australian high school students. Four distinct profiles of out‐of‐school participation in unstructured activities were found: Optimal, Receptive, Active, and Minimal Out‐of‐School Participation (OSP). The Optimal OSP and Receptive OSP profiles were associated with the higher aspirations (beyond students' in‐school participation), and both were significantly higher than the Active OSP and Minimal OSP profiles. Students' in‐school participation was most strongly associated with students' achievement. These findings suggest that encouraging students' participation in unstructured activities, especially receptive unstructured activities, and their in‐school participation may be viable avenues by which to improve students' science aspirations and achievement.
Conference report: Second annual young researcher forum of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine
Authors: Yoshino Tetsuhiro , Yoneda Taichi , Yang Ximeng , Nishihara Masakazu , Ogawa Keiko , Kitamura Masashi , Ando Hirokazu , Nakashima Souichi , Horie Ichiro
Published: August 2022

Five young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan‐yaku) at the second annual young researcher forum entitled “Growing Research Buds by Young Investigators,” held during the annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine 2021. Mr. Yoneda presented exploratory research on new pharmaceutical seed compounds from garlic (Allium sativum). Dr. Yang investigated whether diosgenin promoted proper axonal regeneration in the brain using a mouse model of Alzheimer's disease. Her study clarified the molecular mechanisms of the diosgenin‐driven accurate pathfinding of injured axons. Mr. Nishihara presented his research on promoting the effective utilization of Phellodendron trees in Nara Prefecture. His research team evaluated the possibility of short‐term cultivation, screened for useful components in the leaves. Dr. Ogawa used the Japanese Adverse Drug Event Report (JADER) database, which contains reports of side effects associated with drug treatment, to demonstrate the effectiveness of hokizai in reducing side effects, particularly those of anticancer drugs. Dr. Kitamura reported that Cnidium monnieri (L.) Cusson fruit extract and the isolated active ingredients, osthol and imperatorin, strongly inhibited the activity of furin‐like enzymes. Further screening indicated that root extracts of Paeonia lactiflora Pall. and Scutellaria baicalensis Georgi suppressed cell syncytial formation by the S protein. The event was held online, and we had 86 participants. We can improve this forum in terms of format, frequency, and publicity activities; however, we hope to hold this forum in 2022 and in the future.
Noncoding RNAs in oral cancer
Authors: Balakittnen Jaikrishna , Weeramange Chameera Ekanayake , Wallace Daniel F. , Duijf Pascal H. G. , Cristino Alexandre S. , Kenny Liz , Vasani Sarju , Punyadeera Chamindie
Published: August 2022

Oral cancer (OC) is the most prevalent subtype of cancer arising in the head and neck region. OC risk is mainly attributed to behavioral risk factors such as exposure to tobacco and excessive alcohol consumption, and a lesser extent to viral infections such as human papillomaviruses and Epstein–Barr viruses. In addition to these acquired risk factors, heritable genetic factors have shown to be associated with OC risk. Despite the high incidence, biomarkers for OC diagnosis are lacking and consequently, patients are often diagnosed in advanced stages. This delay in diagnosis is reflected by poor overall outcomes of OC patients, where 5‐year overall survival is around 50%. Among the biomarkers proposed for cancer detection, noncoding RNA (ncRNA) can be considered as one of the most promising categories of biomarkers due to their role in virtually all cellular processes. Similar to other cancer types, changes in expressions of ncRNAs have been reported in OC and a number of ncRNAs have diagnostic, prognostic, and therapeutic potential. Moreover, some ncRNAs are capable of regulating gene expression by various mechanisms. Therefore, elucidating the current literature on the four main types of ncRNAs namely, microRNA, lncRNA, snoRNA, piwi‐RNA, and circular RNA in the context of OC pathogenesis is timely and would enable further improvements and innovations in diagnosis, prognosis, and treatment of OC.

This article is categorized under:

RNA in Disease and Development > RNA in Disease

RNA in Disease and Development > RNA in Development
The Relationship Between Teaching and Research in the Italian University System
Authors: Carillo Maria Rosaria , Sapio Alessandro , Venittelli Tiziana
Published: August 2022

We study the relationship between the quality of research and teaching in the Italian university system, at the study program level. We run a cross-sectional econometric analysis by using a very rich dataset collected by the Italian National Agency for the Evaluation of Universities and Research Institutes on the BA and MA-level degrees of all universities in Italy in the academic year 2016/2017. We find that a positive relationship between teaching quality and research performance emerges if we take account of yardstick competition among study programs belonging to the same department. Indeed, previous theoretical results suggest that, despite the individual trade-off between teaching and research faced by individual academics, in multi-unit universities adopting a budget sharing rule based on both research performance and number of students, the negative relation between teaching and research is reduced or even completely counterbalanced. We find a confirmation of this hypothesis by proxying yardstick competition with the number of study programs activated per department. However, the teaching–research relationship is positive and stronger where study programs are relatively few and immediately comparable by the department managers. Such results emerge more strongly in MA-level degrees, where teaching is more aligned with individual research interests.
Precision neuro-oncology: a pilot analysis of personalized treatment in recurrent glioma
Authors: Lazaridis Lazaros , Schmidt Teresa , Oster Christoph , Blau Tobias , Pierscianek Daniela , Siveke Jens T. , Bauer Sebastian , Schildhaus Hans-Ulrich , Sure Ulrich , Keyvani Kathy , Kleinschnitz Christoph , Stuschke Martin , Herrmann Ken , Deuschl Cornelius , Scheffler Björn , Kebir Sied , Glas Martin
Published: August 2022

Purpose

When brain cancer relapses, treatment options are scarce. The use of molecularly matched targeted therapies may provide a feasible and efficacious way to treat individual patients based on the molecular tumor profile. Since little information is available on this strategy in neuro-oncology, we retrospectively analyzed the clinical course of 41 patients who underwent advanced molecular testing at disease relapse.

Methods

We performed Sanger sequencing, targeted next generation sequencing, and immunohistochemistry for analysis of potential targets, including programmed death ligand 1, cyclin D1, phosphorylated mechanistic target of rapamycin, telomerase reverse transcriptase promoter mutation, cyclin-dependent kinase inhibitor 2A/B deletion, or BRAF-V600E mutation. In selected patients, whole exome sequencing was conducted.

Results

The investigation included 41 patients, of whom 32 had isocitrate dehydrogenase (IDH) wildtype glioblastoma. Molecular analysis revealed actionable targets in 31 of 41 tested patients and 18 patients were treated accordingly (matched therapy group). Twenty-three patients received molecularly unmatched empiric treatment (unmatched therapy group). In both groups, 16 patients were diagnosed with recurrent IDH wildtype glioblastoma. The number of severe adverse events was comparable between the therapy groups. Regarding the IDH wildtype glioblastoma patients, median progression-free survival (mPFS) and median overall survival (mOS) were longer in the matched therapy group (mPFS: 3.8 versus 2.0 months, p = 0.0057; mOS: 13.0 versus 4.3 months, p = 0.0357).

Conclusion

These encouraging data provide a rationale for molecularly matched targeted therapy in glioma patients. For further validation, future study designs need to additionally consider the prevalence and persistence of actionable molecular alterations in patient tissue.
Optical coherence tomography and convolutional neural networks can differentiate colorectal liver metastases from liver parenchyma ex vivo
Authors: Amygdalos Iakovos , Hachgenei Enno , Burkl Luisa , Vargas David , Goßmann Paul , Wolff Laura I. , Druzenko Mariia , Frye Maik , König Niels , Schmitt Robert H. , Chrysos Alexandros , Jöchle Katharina , Ulmer Tom F. , Lambertz Andreas , Knüchel-Clarke Ruth , Neumann Ulf P. , Lang Sven A.
Published: August 2022

Purpose

Optical coherence tomography (OCT) is an imaging technology based on low-coherence interferometry, which provides non-invasive, high-resolution cross-sectional images of biological tissues. A potential clinical application is the intraoperative examination of resection margins, as a real-time adjunct to histological examination. In this ex vivo study, we investigated the ability of OCT to differentiate colorectal liver metastases (CRLM) from healthy liver parenchyma, when combined with convolutional neural networks (CNN).

Methods

Between June and August 2020, consecutive adult patients undergoing elective liver resections for CRLM were included in this study. Fresh resection specimens were scanned ex vivo, before fixation in formalin, using a table-top OCT device at 1310 nm wavelength. Scanned areas were marked and histologically examined. A pre-trained CNN (Xception) was used to match OCT scans to their corresponding histological diagnoses. To validate the results, a stratified k-fold cross-validation (CV) was carried out.

Results

A total of 26 scans (containing approx. 26,500 images in total) were obtained from 15 patients. Of these, 13 were of normal liver parenchyma and 13 of CRLM. The CNN distinguished CRLM from healthy liver parenchyma with an F1-score of 0.93 (0.03), and a sensitivity and specificity of 0.94 (0.04) and 0.93 (0.04), respectively.

Conclusion

Optical coherence tomography combined with CNN can distinguish between healthy liver and CRLM with great accuracy ex vivo. Further studies are needed to improve upon these results and develop in vivo diagnostic technologies, such as intraoperative scanning of resection margins.
A systematic review of the mental health changes of children and young people before and during the COVID-19 pandemic
Authors: Kauhanen Laura , Wan Mohd Yunus Wan Mohd Azam , Lempinen Lotta , Peltonen Kirsi , Gyllenberg David , Mishina Kaisa , Gilbert Sonja , Bastola Kalpana , Brown June S. L. , Sourander Andre
Published: August 2022

There is increasing knowledge that the COVID-19 pandemic has had an impact on mental health of children and young people. However, the global evidence of mental health changes before compared to during the COVID-19 pandemic focusing on children and young people has not been systematically reviewed. This systematic review examined longitudinal and repeated cross-sectional studies comparing before and during COVID-19 pandemic data to determine whether the mental health of children and young people had changed before and during the COVID-19 pandemic. The Web of Science, PubMed, Embase and PsycINFO databases were searched to identify peer-reviewed studies that had been published in English and focused on children and young people between 0 and 24 years of age. This identified 21 studies from 11 countries, covering more than 96,000 subjects from 3 to 24 years of age. Pre-pandemic and pandemic data were compared. Most studies reported longitudinal deterioration in the mental health of adolescents and young people, with increased depression, anxiety and psychological distress after the pandemic started. Other findings included deteriorated negative affect, mental well-being and increased loneliness. Comparing data for pandemic and pre-pandemic periods showed that the COVID-19 pandemic may negatively impact the mental health of children and young people. There is an urgent need for high-quality research to address the impact, risks and protective factors of the pandemic on their mental health, as this will provide a good foundation for dealing with future health emergencies and other crises.
Red blood cell omega-3 fatty acids and attention scores in healthy adolescents
Authors: Pinar-Martí Ariadna , Fernández-Barrés Silvia , Gignac Florence , Persavento Cecilia , Delgado Anna , Romaguera Dora , Lázaro Iolanda , Ros Emilio , López-Vicente Mònica , Salas-Salvadó Jordi , Sala-Vila Aleix , Júlvez Jordi
Published: August 2022

Omega-3 fatty acids are critical for brain function. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. In contrast to the abundant research on the omega-3 docosahexaenoic acid (DHA) in cognition, research on DHA and attention in healthy adolescents is scarce. In addition, the role of alpha-linolenic acid (ALA), the vegetable omega-3 fatty acid, is unexplored. We examined associations between DHA and ALA and attention function among a healthy young population. In this cross-sectional study conducted in 372 adolescents (13.8 ± 0.9 years-old), we determined the red blood cell proportions of DHA and ALA by gas chromatography (objective biomarkers of their long-term dietary intake) and measured attention scores through the Attention Network Test. We constructed multivariable linear regression models to analyze associations, controlling for known confounders. Compared to participants at the lowest DHA tertile (reference), those at the highest DHA tertile showed significantly lower hit reaction time-standard error (higher attentiveness) (28.13 ms, 95% confidence interval [CI] =  – 52.30;  – 3.97), lower hit reaction time ( – 38.30 ms, 95% CI =  – 73.28;  – 3.33) and lower executive conflict response ( – 5.77 ms, 95% CI =  – 11.44;  – 0.09). In contrast, higher values were observed in those at the top tertile of ALA in hit reaction time compared to the lowest one (46.14 ms, 95% CI = 9.90; 82.34). However, a beneficial association was observed for ALA, with decreasing impulsivity index across tertiles. Overall, our results suggest that DHA (reflecting its dietary intake) is associated with attention performance in typically developing adolescents. The role of dietary ALA in attention is less clear, although higher blood levels of ALA appear to result in lower impulsivity. Future intervention studies are needed to determine the causality of these associations and to better shape dietary recommendations for brain health during the adolescence period.
Rangelands in a fragmented grass-dominated landscape are vulnerable to tree invasion from roadsides
Authors: Hogan Katharine F. E. , Fogarty Dillon T. , Ellerman Hugh , Fill Christopher T. , Morales D. , Seguin Baxter , Uden Daniel R. , Allen Craig R.
Published: August 2022

Roadsides can be vectors for tree invasion within rangelands by bisecting landscapes and facilitating propagule spread to interior habitat. Current invasive tree management in North America’s Great Plains focuses on reducing on-site (i.e., interior habitat) vulnerability through on-site prevention and eradication, but invasive tree management of surrounding areas known to serve as invasion vectors, such as roadsides and public rights-of-ways, is sporadic. We surveyed roadsides for invasive tree propagule sources in a central Great Plains grassland landscape to determine how much of the surrounding landscape is potentially vulnerable to roadside invasion, and by which species, and thereby provide insights into the locations and forms of future landcover change. Invasive tree species were widespread in roadsides. Given modest seed dispersal distances of 100–200 m, our results show that roadsides have potential to serve as major sources of rangeland exposure to tree invasion, compromising up to 44% of rangelands in the study area. Under these dispersal distances, funds spent removing trees on rangeland properties may have little impact on the landscape’s overall vulnerability, due to exposure driven by roadside propagule sources. A key implication from this study is that roadsides, while often neglected from management, represent an important component of integrated management strategies for reducing rangeland vulnerability to tree invasion.
The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence
Authors: Iwasaki Masae , Zhao Hailin , Hu Cong , Saito Junichi , Wu Lingzhi , Sherwin Aislinn , Ishikawa Masashi , Sakamoto Atsuhiro , Buggy Donal , Ma Daqing
Published: August 2022

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5 h or propofol (20 μg g−1; ip injection) with or without 4 μg g−1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1β (IL1β), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.
Dimethyl sulfoxide-free cryopreservation solution containing trehalose, dextran 40, and propylene glycol for therapy with human adipose tissue-derived mesenchymal stromal cells
Authors: Fujita Yasutaka , Nishimura Masuhiro , Wada Tamaki , Komori Natsuki , Otoi Takeshige
Published: August 2022

We evaluated a dimethyl sulfoxide (Me2SO)-free cryopreservation solution to freeze human adipose-derived mesenchymal stromal cells (hADSCs). In the first experiment, we compared the combined effects of 3% trehalose (3 T) and 5% dextran (5D) in lactated Ringer’s solution (LR) as a cryopreservation base solution containing 10% propylene glycol (PG). The cell viability of hADSCs immediately after thawing was significantly higher (p < 0.05) in LR supplemented with 3 T (LR-3 T) and with 3 T and 5D (LR-3 T-5D) than in LR. In the second experiment, we compared the cell characteristics of hADSCs freeze-thawed in LR-3 T-5D containing either 10% Me2SO or 10% PG. The cell viability, annexin V-positive ratio, colony-forming capacity, cell proliferation, cell surface antigen positivity, adipogenic differentiation, osteogenic differentiation, and genetic response to cytokine stimulation of hADSCs immediately after thawing were similar between the LR-3 T-5D containing 10% Me2SO and 10% PG. In the third experiment, we examined various concentrations of PG on the cell proliferative capacity of freeze-thawed hADSCs. The cell proliferative capacity of hADSCs frozen with LR-3 T-5D containing 2.5% to 5% PG was significantly higher (p < 0.05) than LR-3 T-5D containing 10% PG. Furthermore, the cell proliferative capacity of hADSCs frozen with LR-3 T-5D containing 4% PG was similar to that of fresh hADSCs. These results indicate that the combination of 3 T-5D in an LR solution as a basic solution is effective for post-thaw cell viability, and that the optimal concentration of PG to maintain the cell characteristics of hADSCs frozen with LR-3 T-5D is 2.5% to 5%, which is promising for cell therapy applications.