bluuebunny/crossref_metadata_2025 huggingface dataset:
Convergent Functional Changes of Default Mode Network in Mild Cognitive Impairment Using Activation Likelihood Estimation
Authors: Yuan Qianqian , Qi Wenzhang , Xue Chen , Ge Honglin , Hu Guanjie , Chen Shanshan , Xu Wenwen , Song Yu , Zhang XuLian , Xiao Chaoyong , Chen Jiu
Published: October 2021

Background: Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia disorders, especially Alzheimer's disease (AD). The disruption of the default mode network (DMN) is often considered to be a potential biomarker for the progression from MCI to AD. The purpose of this study was to assess MRI-specific changes of DMN in MCI patients by elucidating the convergence of brain regions with abnormal DMN function.

Methods: We systematically searched PubMed, Ovid, and Web of science for relevant articles. We identified neuroimaging studies by using amplitude of low frequency fluctuation /fractional amplitude of low frequency fluctuation (ALFF/fALFF), regional homogeneity (ReHo), and functional connectivity (FC) in MCI patients. Based on the activation likelihood estimation (ALE) algorithm, we carried out connectivity modeling of coordination-based meta-analysis and functional meta-analysis.

Results: In total, this meta-analysis includes 39 articles on functional neuroimaging studies. Using computer software analysis, we discovered that DMN changes in patients with MCI mainly occur in bilateral inferior frontal lobe, right medial frontal lobe, left inferior parietal lobe, bilateral precuneus, bilateral temporal lobe, and parahippocampal gyrus (PHG).

Conclusions: Herein, we confirmed the presence of DMN-specific damage in MCI, which is helpful in revealing pathology of MCI and further explore mechanisms of conversion from MCI to AD. Therefore, we provide a new specific target and direction for delaying conversion from MCI to AD.
Admission Hyperglycemia Predicts Long-Term Mortality in Critically Ill Patients With Subarachnoid Hemorrhage: A Retrospective Analysis of the MIMIC-III Database
Authors: Liu Dongliang , Tang Yiyang , Zhang Qian
Published: October 2021

Subarachnoid hemorrhage (SAH) is a severe subtype of stroke with high mortality. Hyperglycemia is a common phenomenon in critically ill patients and associated with poor clinical outcome. However, the predictive value of admission hyperglycemia for 30 and 90-day all-cause mortality in critically ill patients with SAH remains controversial. All SAH patients between 2001 and 2012 were included based on the MIMIC-III database and were further classified according to the tertiles of blood glucose (BG) measured on intensive care unit (ICU) admission. Clinical information including demographic data, comorbidities, and laboratory indicators were exacted and analyzed. The primary outcomes were 30- and 90-day all-cause mortality. A total of 1,298 SAH patients were included. The 30 and 90-day mortality rates were 19.80% and 22.73%, respectively. Subjects in the high glucose tertile were older, were overweight, had higher sequential organ failure assessment (SOFA) and Simplified Acute Physiology Score II (SAPS II) scores, and presented higher mortality rate. Generalized additive model revealed a U-shaped relationship between BG and 30 and 90-day all-cause mortality. Furthermore, Kaplan–Meier (K-M) survival curve also illustrated that subjects with admission hyperglycemia presented lower survival rate and shorter survival time. In Cox analysis, after adjustment for potential confounders, admission hyperglycemia was related to an increase in 30- and 90-day all-cause mortality in SAH patients. In subgroup analysis, the association between admission hyperglycemia and all-cause mortality was consistent. In conclusion, admission hyperglycemia is associated with significantly increased 30- and 90-day all-cause mortality in critically ill patients with SAH.
Dose Effects of Histone Deacetylase Inhibitor Tacedinaline (CI-994) on Antipsychotic Haloperidol-Induced Motor and Memory Side Effects in Aged Mice
Authors: McClarty Bryan , Rodriguez Guadalupe , Dong Hongxin
Published: October 2021

Background: Elderly patients treated with antipsychotic drugs often experience increased severity and frequency of side effects, yet the mechanisms are not well understood. Studies from our group indicate age-related histone modifications at drug targeted receptor gene promoters may contribute to the increased side effects, and histone deacetylase (HDAC) inhibitors entinostat (MS-275) and valproic acid (VPA) could reverse typical antipsychotic haloperidol (HAL) induced motor-side effects. However, whether such effects could be dose dependent and whether HDAC inhibitors could improve memory function in aged mice is unknown.

Methods: We co-treated selective class 1 HDAC inhibitor tacedinaline (CI-994) at different doses (10, 20, and 30 mg/kg) with HAL (0.05 mg/kg) in young (3 months) and aged (21 months) mice for 14 consecutive days, then motor and memory behavioral tests were conducted, followed by biochemical measurements.

Results: CI-994 at doses of 10 and 20 mg/kg could decrease HAL-induced cataleptic episodes but only 20 mg/kg was sufficient to improve motor coordination in aged mice. Additionally, CI-994 at 10 and 20 mg/kg mitigate HAL-induced memory impairment in aged mice. Biochemical analyses showed increased acetylation of histone marks H3K27ac and H3K18ac at the dopamine 2 receptor (D2R) gene (Drd2) promoter and increased expression of the Drd2 mRNA and D2R protein in the striatum of aged mice after administration of CI-994 at 20 mg/kg.

Conclusions: Our results suggest CI-994 can reduce HAL-induced motor and memory side effects in aged mice. These effects may act through an increase of acetylation at the Drd2 promoter, thereby restoring D2R expression and improving antipsychotic drug action.
Metabotropic Glutamate Receptors 1 Regulates Rat Carotid Body Response to Acute Hypoxia via Presynaptic Mechanism
Authors: Li Chaohong , Zhao Baosheng , Zhao Chenlu , Huang Lu , Liu Yuzhen
Published: October 2021

Background: The carotid body (CB) plays a critical role in oxygen sensing; however, the role of glutamatergic signaling in the CB response to hypoxia remains uncertain. We previously found that functional multiple glutamate transporters and inotropic glutamate receptors (iGluRs) are expressed in the CB. The aim of this present research is to investigate the expression of group I metabotropic glutamate receptors (mGluRs) (mGluR1 and 5) in the CB and its physiological function in rat CB response to acute hypoxia.

Methods: RT-PCR and immunostaining were conducted to examine the mRNA and protein expression of group I mGluRs in the human and rat CB. Immunofluorescence staining was performed to examine the cellular localization of mGluR1 in the rat CB. In vitro carotid sinus nerve (CSN) discharge recording was performed to detect the physiological function of mGluR1 in CB response to acute hypoxia.

Results: We found that (1) mRNAs of mGluR1 and 5 were both expressed in the human and rat CB. (2) mGluR1 protein rather than mGluR5 protein was present in rat CB. (3) mGluR1 was distributed in type I cells of rat CB. (4) Activation of mGluR1 inhibited the hypoxia-induced enhancement of CSN activity (CSNA), as well as prolonged the latency time of CB response to hypoxia. (5) The inhibitory effect of mGluR1 activation on rat CB response to hypoxia could be blocked by GABAB receptor antagonist.

Conclusion: Our findings reveal that mGluR1 in CB plays a presynaptic feedback inhibition on rat CB response to hypoxia.
Oligodendroglioma: A Review of Management and Pathways
Authors: Bou Zerdan Maroun , Assi Hazem I.
Published: October 2021

Anaplastic oligodendrogliomas are a type of glioma that occurs primarily in adults but are also found in children. These tumors are genetically defined according to the mutations they harbor. Grade II and grade III tumors can be differentiated most of the times by the presence of anaplastic features. The earliest regimen used for the treatment of these tumors was procarbazine, lomustine, and vincristine. The treatment modalities have shifted over time, and recent studies are considering immunotherapy as an option as well. This review assesses the latest management modalities along with the pathways involved in the pathogenesis of this malignancies.
β-Lapachone Selectively Kills Hepatocellular Carcinoma Cells by Targeting NQO1 to Induce Extensive DNA Damage and PARP1 Hyperactivation
Authors: Zhao Wenxiu , Jiang Lingxiang , Fang Ting , Fang Fei , Liu Yingchun , Zhao Ye , You Yuting , Zhou Hao , Su Xiaolin , Wang Jiangwei , Liu Sheng , Chen Yaomin , Wan Jun , Huang Xiumei
Published: October 2021

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death globally. Currently there is a lack of tumor-selective and efficacious therapies for hepatocellular carcinoma. β-Lapachone (ARQ761 in clinical form) selectively kill NADPH: quinone oxidoreductase 1 (NQO1)-overexpressing cancer cells. However, the effect of β-Lapachone on HCC is virtually unknown. In this study, we found that relatively high NQO1 and low catalase levels were observed in both clinical specimens collected from HCC patients and HCC tumors from the TCGA database. β-Lapachone treatment induced NQO1-selective killing of HCC cells and caused ROS formation and PARP1 hyperactivation, resulting in a significant decrease in NAD+ and ATP levels and a dramatic increase in double-strand break (DSB) lesions over time in vitro. Administration of β-Lapachone significantly inhibited tumor growth and prolonged survival in a mouse xenograft model in vivo. Our data suggest that NQO1 is an ideal potential biomarker, and relatively high NQO1:CAT ratios in HCC tumors but low ratios in normal tissues offer an optimal therapeutic window to use β-Lapachone. This study provides novel preclinical evidence for β-Lapachone as a new promising chemotherapeutic agent for use in NQO1-positive HCC patients.
Disease-Modifying Anti-rheumatic Drug Prescription Baihu-Guizhi Decoction Attenuates Rheumatoid Arthritis via Suppressing Toll-Like Receptor 4-mediated NLRP3 Inflammasome Activation
Authors: Li Weijie , Mao Xia , Wang Xiaoyue , Liu Yudong , Wang Kexin , Li Congchong , Li Taixian , Zhang Yanqiong , Lin Na
Published: October 2021

As a traditional Chinese medicine-originated disease-modifying anti-rheumatic drug prescription, Baihu-Guizhi decoction (BHGZD) is extensively used for the treatment of rheumatoid arthritis (RA) with a satisfying therapeutic efficacy. Mechanically, our previous data indicated that BHGZD may ameliorate RA partially by restoring the balance of the “inflammation-immune” system through regulating theTLR4-c-Fos-IL2-TNF-alphaaxis. Toll-like receptor 4 (TLR4) has been revealed to be involved in the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome complex. Thus, the aim of the current study was to determine the regulatory effects of BHGZD on the TLR4–mediated inflammasome activation during RA progression based on the modified adjuvant-induced arthritis model (AIA-M) and the lipopolysaccharide/adenosine triphosphate (LPS/ATP)–induced pyroptosis cellular models. As a result, oral administration of BHGZD exhibited prominent improvement in the disease severity of AIA-M rats, such as reducing the redness and swelling of joints, arthritis incidence, arthritic scores, and diameter of the limb and increasing pain thresholds. In line with thein vivofindings, BHGZD treatment effectively inhibited the LPS/ATP–induced pyroptosis of both Raw264.7 macrophage and MH7A cellsin vitroby reducing pyroptotic cell death morphology (swollen cells) and decreasing propidium iodide–positive and terminal deoxynucleotidyl transferase–mediated dUTP-fluorescein nick end labeling (TUNEL)–positive cells. Notably, the increased expression levels of TLR4, NLRP3, interleukin 1β, and interleukin 18 proteins and the elevated activities of caspase-1 and lactic dehydrogenase inin vivoandin vitrodisease models were markedly reversed by the treatment with BHGZD. In conclusion, the above findings proved the immunomodulatory and anti-inflammatory activities of BHGZD, especially in pyroptosis, which may be attributed to the activation of TLR4–mediated NLRP3 inflammasome signaling.
Molecular Mechanisms Underlying the Biosynthesis of Melatonin and Its Isomer in Mulberry
Authors: Zheng Sha , Zhu Yingxue , Liu Changying , Zhang Shuai , Yu Maode , Xiang Zhonghuai , Fan Wei , Wang Shuchang , Zhao Aichun
Published: October 2021

Mulberry (Morus alba L.) leaves and fruit are traditional Chinese medicinal materials with anti-inflammatory, immune regulatory, antiviral and anti-diabetic properties. Melatonin performs important roles in the regulation of circadian rhythms and immune activities. We detected, identified and quantitatively analyzed the melatonin contents in leaves and mature fruit from different mulberry varieties. Melatonin and three novel isoforms were found in the Morus plants. Therefore, we conducted an expression analysis of melatonin and its isomer biosynthetic genes and in vitro enzymatic synthesis of melatonin and its isomer to clarify their biosynthetic pathway in mulberry leaves. MaASMT4 and MaASMT20, belonging to class II of the ASMT gene family, were expressed selectively in mulberry leaves, and two recombinant proteins that they expressed catalyzed the conversion of N-acetylserotonin to melatonin and one of three isomers in vitro. Unlike the ASMTs of Arabidopsis and rice, members of the three ASMT gene families in mulberry can catalyze the conversion of N-acetylserotonin to melatonin. This study provides new insights into the molecular mechanisms underlying melatonin and its isomers biosynthesis and expands our knowledge of melatonin isomer biosynthesis.
Belief in a Just World and Moral Personality as Mediating Roles Between Parenting Emotional Warmth and Internet Altruistic Behavior
Authors: Zhang Ye , Chen Liang , Xia Yumeng
Published: October 2021

This study explores the influence of parental emotional warmth (PEW) on college students’ Internet altruistic behavior (IAB), and the mediating roles of personal belief in a just world (PBJW) and positive moral personality traits (PMPT). A total of 893 college students were assessed using questionnaires. Results: (1) PEW, PBJW, PMPT, and IAB are positively correlated with each other; (2) PEW can directly predict the IAB of college students; and (3) PEW can indirectly predict IAB through the mediating effect of PMPT and PBJW-PMPT. PBJW and PMPT account for 22.79% of the total influence of PEW on IAB.
Accuracy of Tempo Judgments in Disk Jockeys Compared to Musicians and Untrained Individuals
Authors: Foster Nicholas E. V. , Beffa Lauriane , Lehmann Alexandre
Published: October 2021

Professional disk jockeys (DJs) are an under-studied population whose performance involves creating new musical experiences by combining existing musical materials with a high level of temporal precision. In contemporary electronic dance music, these materials have a stable tempo and are composed with the expectation for further transformation during performance by a DJ for the audience of dancers. Thus, a fundamental aspect of DJ performance is synchronizing the tempo and phase of multiple pieces of music, so that over seconds or even minutes, they may be layered and transitioned without disrupting the rhythmic pulse. This has been accomplished traditionally by manipulating the speed of individual music pieces “by ear,” without additional technological synchronization aids. However, the cumulative effect of this repeated practice on auditory tempo perception has not yet been evaluated. Well-known phenomena of experience-dependent plasticity in other populations, such as musicians, prompts the question of whether such effects exist in DJs in their domain of expertise. This pilot study examined auditory judgments of tempo in 10 professional DJs with experience mixing by ear, compared to 7 percussionists, 12 melodic instrumental musicians, and 11 untrained controls. Participants heard metronome sequences between 80 and 160 beats per minute (BPM) and estimated the tempo. In their most-trained tempo range, 120–139 BPM, DJs were more accurate (lower absolute percent error) than untrained participants. Within the DJ group, 120–139 BPM exhibited greater accuracy than slower tempos of 80–99 or 100–119 BPM. DJs did not differ in accuracy compared to percussionists or melodic musicians on any BPM range. Percussionists were more accurate than controls for 100–119 and 120–139 BPM. The results affirm the experience-dependent skill of professional DJs in temporal perception, with comparable performance to conventionally trained percussionists and instrumental musicians. Additionally, the pattern of results suggests a tempo-specific aspect to this training effect that may be more pronounced in DJs than percussionists and musicians. As one of the first demonstrations of enhanced auditory perception in this unorthodox music expert population, this work opens the way to testing whether DJs also have enhanced rhythmic production abilities, and investigating the neural substrates of this skill compared to conventional musicians.
Worry and Positive Episodes in the Daily Lives of Individuals With Generalized Anxiety Disorder: An Ecological Momentary Assessment Study
Authors: Vîslă Andreea , Zinbarg Richard , Hilpert Peter , Allemand Mathias , Flückiger Christoph
Published: October 2021

Worry is a central feature of generalized anxiety disorder (GAD). Although worry is related to anxiety and maintained by beliefs that worry is uncontrollable, there is scarce research on how individuals with GAD react to worry episodes in their daily life and how their positive experiences might impact reactions to worry episodes. The current study examined the level and variability of anxiety and controllability during high worry periods and positive experiences in GAD. Moreover, it investigated the influence of worry and positive experiences on later anxiety and perceived controllability within-persons. Finally, it examined change in anxiety level from previous to current episodes depending on previous episodes type. In the current study, 49 individuals with GAD (514 observations) registered their worry and positive episodes (i.e., episodes in which they had positive experiences) and reported on several variables during these episodes (i.e., anxiety and controllability of episodes and episode duration) using smartphone-based ecological momentary assessment for 7days. Results show anxiety and controllability differed by episode type (higher anxiety, lower controllability in worry episodes, and the opposite in positive episodes), and notable within-person variability in anxiety and controllability in both episode types. The time-lagged multilevel models showed episode type did not predict later anxiety during either episode type, although previous anxiety predicted current anxiety in worry episodes (but not positive episodes). Moreover, worry episodes did predict later controllability in worry episodes (but not positive episodes) and previous controllability predicted current controllability in both episode types. Furthermore, we obtained the increase in anxiety from t0−1 to t0 in a current worry episode to be significantly smaller when preceded by a worry (vs. positive) episode. Likewise, the reduction in anxiety from t0−1 to t0 in a current positive episode was significantly larger when preceded by a worry (vs. positive) episode. The novel findings in the current study that perceptions of controllability and anxiety vary within individuals with GAD, that greater controllability is experienced in positive episodes than worry episodes, and that worry may confer a sense of controllability at a later time could be seen as important contributions to the GAD literature.
Tapping to Music Predicts Literacy Skills of First-Grade Children
Authors: Kertész Csaba , Honbolygó Ferenc
Published: October 2021

The ability to synchronise one’s movements to the sound of a regular beat has been found to be associated with children’s language and reading abilities. Sensorimotor synchronisation or tapping performance can among other factors [e.g., working memory and rapid automatized naming (RAN)] predict phonological awareness and word reading accuracy and fluency of first graders. While tapping tasks that use a simple metronome sound are more often used, applying musical stimuli has the potential advantage of being more engaging and motivating for children. In the present study, we investigated whether tapping to a metronome beat or complex musical stimuli would predict phonological awareness and reading outcomes of Hungarian 6-7-year olds (N=37). We also measured participants’ general cognitive abilities (RAN, non-verbal intelligence and verbal working memory). Our results show that phonological awareness, spelling and reading accuracy were associated with the musical tasks while reading fluency was predicted by the metronome trials. Our findings suggest that complex musical tasks should be considered when investigating this age group, as they were, in general, more effective in predicting literacy outcomes.
Long Term Effects of the COVID-19 Pandemic on Social Concerns
Authors: Blanco Esther , Baier Alexandra , Holzmeister Felix , Jaber-Lopez Tarek , Struwe Natalie
Published: October 2021

While some local, temporary past crises have boosted overall charitable donations, there have been concerns about potential substitution effects that the Covid-19 pandemic might have on other social objectives, such as tackling climate change and reducing inequality. We present results from a donation experiment (n= 1, 762), with data collected between April 2020 and January 2021. We combine data from (i) an online donation experiment, (ii) an extended questionnaire including perceptions, actions, and motives on the Covid-19 pandemic, the climate crisis, and poverty, as well as charitable behavior and (iii) epidemiological data. The experimental results show that donations to diverse social concerns are partially substituted by donations to the Covid-19 fund; yet, this substitution does not fully replace all other social concerns. Over time we observe no systematic trend in charitable donations. In regards to the determinants of individual donations, we observe that women donate more, people taking actions against Covid-19 and against poverty donate more, while those fearing risks from poverty donate less. In addition, we observe that the population under consideration is sensitive to the needs of others, enhancing total donations for higher Covid-19 incidence. For donations to each charity, we find that trusting a given charitable organization is the strongest explanatory factor of donations.

JEL:L3, D64, Q54, I3, D9
Review of Emergency Medical Services Vulnerability to High Consequence Infectious Disease in the United States
Authors: Richey Thomas W. , Fowler Raymond L. , Swienton Ray E. , O'Neal James Patrick , Harris Curtis A.
Published: October 2021

Purpose: Emergency medical services (EMS) responders are a group of medically skilled professionals who perform a wide range of essential medical services within a community including emergency response, patient transport, and mobile integrated healthcare. The proper functioning of the EMS system is paramount to the well-being of the medical system and public health. The intent of this paper is to review current EMS standards and practice to determine the danger a high consequence infectious disease (HCID) may pose to these healthcare workers and the community.

Areas Addressed: Through the review of EMS practice several areas were identified as vulnerabilities to the EMS network. These vulnerabilities consisted of the lack of standardized licensing practice, inconsistent medical direction, and the inability to properly implement the use of personal protective equipment (PPE). The compounding of these vulnerabilities allows for HCIDs to pose a serious threat to EMS personnel with the possibility of devastating and crippling the EMS infrastructure within the US.

Discussion: The vulnerabilities identified must be addressed both to protect EMS providers and to enhance the resilience of the US healthcare system. Ways to address the identified vulnerabilities should focus on improving the EMS curriculum and increasing minimum levels of education for first responders. Targeting minimum education and training standards could be the most effect method of reducing the dangers of HCIDs to EMS systems.
Integration of a Network-Based and an Economy-Wide Water Model to Support Decision Making on Water Resources Planning and Management in Northeastern Brazil
Authors: Alcoforado de Moraes Márcia M. G. , Souza da Silva Gerald N. , Cunha Marcelo Pereira da , Dias Nilena B. M. , Cardoso Terezinha F. , Guilhoto Joaquim J. M. , Candido Laíse Alves , Santos Reinan R. S.
Published: October 2021

Allocation of Water Resources at the basin level is a critical issue for economic growth as well as for environmental sustainability. This study integrates network-based optimization with an Input-Output model, made available through a Spatial Decision Support System (HEAL), to support design and evaluation of water allocation policies. The innovative platform was applied to a case study using four-interlinked hydrographic basins in Northeastern of Brazil. The integrated modeling was able to measure broader socioeconomic impacts of decisions on reservoir volumes and water allocations at basin level, through indicators in a sectoral and regional scale, including ones associated with Sustainable Development Goals, such as the Water Use Efficiency (WUE) indicator. Results of the trade-offs between two scenarios, representative of the limits of performance of regulatory water instruments, were generated using the integrated modeling. They were compared with the Reference scenario for the base year (2011) and show that the economic sector most negatively affected by the regulatory instrument use is the industrial sector. Furthermore, the sugar and ethanol industry, main water users in the industrial sector (93.1% of the sector's water use) and less efficient (WUE 1.47 US$/m3 vs. 30.70 US$/m3 average of the sector) in the base year, maintain their percentage share of water use in the sector and even slightly expand it (93.2%), with slight efficiency gains (+2.3%). On the other hand, non-water-intensive industries, have their shares reduced (from 6.9 to 6.8%) and lose efficiency (−9.5%). Results of the same trade-offs by region showed that the largest proportional economic losses occur in the drier areas, damaging the economy, especially in the most industrialized municipalities with the highest GDPs. Integrated economic modeling can expand aspects involved in water security issues, assisting management by introducing socioeconomic impact measures, in a broader scale, associated with allocation decisions. Hydrological allocation criteria cannot distinguish between user efficiency and which economic sectors are using how much water. This results in economic and social losses. In water-scarce regions and with growing transfer needs, such as in the basins studied, adequate incentives, through management instruments designed based on economic theory, are essential to promote sustainable development.
Grand Challenges of Hydrologic Modeling for Food-Energy-Water Nexus Security in High Mountain Asia
Authors: Mishra Shruti K. , Rupper Summer , Kapnick Sarah , Casey Kimberly , Chan Hoi Ga , Ciraci' Enrico , Haritashya Umesh , Hayse John , Kargel Jeffrey S. , Kayastha Rijan B. , Krakauer Nir Y. , Kumar Sujay V. , Lammers Richard B. , Maggioni Viviana , Margulis Steven A. , Olson Mathew , Osmanoglu Batuhan , Qian Yun , McLarty Sasha , Rittger Karl , Rounce David R. , Shean David , Velicogna Isabella , Veselka Thomas D. , Arendt Anthony
Published: October 2021

Climate-influenced changes in hydrology affect water-food-energy security that may impact up to two billion people downstream of the High Mountain Asia (HMA) region. Changes in water supply affect energy, industry, transportation, and ecosystems (agriculture, fisheries) and as a result, also affect the region's social, environmental, and economic fabrics. Sustaining the highly interconnected food-energy-water nexus (FEWN) will be a fundamental and increasing challenge under a changing climate regime. High variability in topography and distribution of glaciated and snow-covered areas in the HMA region, and scarcity of high resolution (in-situ) data make it difficult to model and project climate change impacts on individual watersheds. We lack basic understanding of the spatial and temporal variations in climate, surface impurities in snow and ice such as black carbon and dust that alter surface albedo, and glacier mass balance and dynamics. These knowledge gaps create challenges in predicting where and when the impact of changes in river flow will be the most significant economically and ecologically. In response to these challenges, the United States National Aeronautics and Space Administration (NASA) established the High Mountain Asia Team (HiMAT) in 2016 to conduct research to address knowledge gaps. This paper summarizes some of the advances HiMAT made over the past 5 years, highlights the scientific challenges in improving our understanding of the hydrology of the HMA region, and introduces an integrated assessment framework to assess the impacts of climate changes on the FEWN for the HMA region. The framework, developed under a NASA HMA project, links climate models, hydrology, hydropower, fish biology, and economic analysis. The framework could be applied to develop scientific understanding of spatio-temporal variability in water availability and the resultant downstream impacts on the FEWN to support water resource management under a changing climate regime.
Dietary Phytochemical Screening of Spider Plant (Gynandropsis gynandra (L.) Briq.) Accessions From Africa and Asia to Identify Genotypes for Use in Nutraceutical Breeding
Authors: Chataika Barthlomew Yonas , Akundabweni Levi Shadeya-Mudogo , Houdegbe Aristide Carlos , Achigan-Dako Enoch G. , Sibiya Julia , Masamba Kingsley
Published: October 2021

Increased public awareness of healthy foods and healthy living, coupled with escalating medicinal costs and recent advances in research and technology, has sparked a paradigm shift to nutraceuticals, which guarantee human health and disease prevention. Spider plant (Gynandropsis gynandra) contains dietary phytochemicals with high nutritional and medicinal properties that can contribute to healthy living. A study was conducted to identify spider plant (Gynandropsis gynandra(L.) Briq.) accessions with superior levels of dietary phytochemicals and anti-oxidative activity for use in nutraceutical breeding. Thirty-three accessions of spider plant, representing a wide genetic diversity based on geographic areas of origin (Asia, East Africa, Southern Africa, and West Africa), were used. Total phenolic acids, tannins, and anthocyanins were extracted and quantified using the Folin-Ciocalteau colorimetric, spectrophotometric, and pH differential methods, respectively. Antioxidant activity was determined using phosphomolybdenum method. Results showed significant variation in levels of total phenolic compounds, tannins, anthocyanins, and antioxidant activity (P< 0.05) amongst the spider plant accessions and regions of origin; ODS-15-037 (464 mg TAE/g DW), ODS-15-053 (270 mg GAE/g DW), and BC-02A (127 mg cyanidin-3-glucoside/g DW) had the highest levels of total tannins, phenolic compounds, and anthocyanins, respectively. Antioxidant activity was high in ODS-15-053 (492.2 mg AAE/100 g DW), NAM 2232 (445.3 mg AAE/100 g DW), and NAM-6 (432.5 mg AAE/100 g DW). On average, West African accessions had significantly high tannin concentrations (239 mg TAE/g DW), while Southern Africa accessions contained significantly high anthocyanin content (58.9 mg cyanidin-3-glucoside/g DW). The superior accessions are potential candidates for use in nutraceutical breeding, while the regions of origin could be used as gene pools for specific phytochemicals for improving dietary supplements of nutraceuticals. The strong antioxidant activity exhibited by spider plant accessions suggests the presence of compounds responsible for scavenging free oxygen or nitrogen radicals. Further studies are recommended to identify the chromosomal regions that contain genes controlling the dietary nutraceuticals in the genetic materials and to determine their association with foliage yield and other phenotypes, which can be utilized in spider plant improvement.
Farmers' Knowledge Is the Basis for Local Level Agro-Forestry Management: The Case of Lemo Woreda in Hadiya Zone, Ethiopia
Authors: Horamo Yohannes , Chitakira Munyaradzi , Yessoufou Kowiyou
Published: October 2021

This research was designed to investigate the hypothesis that farmers practising traditional agro-forestry which dates back for centuries have accumulated immense knowledge of agro-forestry, which can be captured and incorporated into formal development programmes to improve it. Farmers' knowledge must be documented, valued and integrated in order to maximise its importance for planning and decision-making. This research aimed to investigate and document farmers' knowledge of managing agro-forestry and the contribution to sustainable management of natural resources. Accordingly, questionnaire surveys were conducted in six villages from three peasant associations. In total, 73 households were selected for interview and the data collected were analysed using SPSS (Statistical Package for Social Science) version 26. The findings revealed tree species that contribute to crop yield improvement and the important role agro-forestry trees play with regard to soil fertility. Farmers' strategies to associate trees and shrubs in their farmlands were revealed. Tree species with a negative effect on crop yields were identified and recorded. Farmers reported and ranked in the order of importance, opportunities and constraints in the management of agro-forestry. Farmers' accumulated knowledge of tree–crop and tree–animal interactions, the role of trees in soil fertility, crop and livestock improvement, revealed in the study can significantly enhance the stainability of agriculture. If local knowledge is not documented, it remains largely inaccessible to development workers seeking solutions to locally defined problems.
Mean Platelet Volume and Platelet Volume Distribution Width in Canine Parvoviral Enteritis
Authors: Engelbrecht Monique , Atkinson Brogan , Goddard Amelia , Pazzi Paolo , McClure Vanessa
Published: October 2021

Bacterial translocation from the damaged intestinal tract, reported in canine parvoviral (CPV) enteritis, is thought to be responsible for the systemic inflammatory response resulting from coliform septicemia, which could ultimately progress to septic shock and death. Alterations in platelet indices, specifically mean platelet volume (MPV), is a consistent finding in critically ill people and dogs with and without sepsis. Increased MPV has been reported to be an indirect indicator of platelet activation and of bone marrow response in people and dogs with sepsis. The study aim was to compare admission MPV and platelet volume distribution width (PVDW) in dogs with CPV enteritis to that of healthy aged-matched control dogs. Forty-eight dogs with CPV enteritis and 18 healthy age matched control dogs were included. CPV infection was confirmed with electron microscopy and concurrent blood-borne infections were excluded using PCR. EDTA whole blood samples were analyzed on an automated cell counter, ADVIA 2120, within 30-60 min from collection. There was no significant difference for platelet count between the groups. The MPV for CPV infected dogs (median: 14.0; IQR: 12.2–15.1) was significantly higher compared to controls (11.3; IQR: 10.3–13.1, P = 0.002). The PVDW for CPV infected dogs (66.9; IQR: 64.2–68.8) was significantly higher compared to controls (63.3; IQR: 60.2–65.1, P < 0.001). These findings suggest that significant platelet activation is present in dogs with CPV enteritis which may play a role in the disease outcome, similar to people with sepsis. Further studies are required to investigate the prognosticating ability of MPV in dogs with CPV enteritis.
Different Non-cage Housing Systems Alter Duodenal and Cecal Microbiota Composition in Shendan Chickens
Authors: Wan Yi , Ma Ruiyu , Zhang Hongyi , Li Ling , Chai Lilong , Qi Renrong , Liu Wei , Li Junying , Li Yan , Zhan Kai
Published: October 2021

Housing systems are among the most important non-genetic factors affecting hen production performance and intestinal microbes. With increased interest in animal welfare, cage-free laying hen housing systems have become common, providing behavioral freedom and health benefits. The present study aimed to compare the effects of plastic net housing system (NRS) and floor litter housing system (LRS) on the composition and function of the duodenal and cecal microbiota in Shendan chicken, one of the most popular laying hen strains in China. The associations between the differential microbiota abundance and production traits and intestinal morphological parameters were determined. Compared with the LRS, the NRS improved the laying rate (p < 0.05) and increased the villus height (VH) of the duodenum (p < 0.05) and the VH-to-crypt depth ratio (VCR) of the cecum (p < 0.05). Alpha diversity analysis showed that LRS chickens had a significantly higher diversity and richness than NRS chickens. Beta diversity analysis demonstrated differences in the microbiota composition based on housing systems. Within the cecum, Proteobacteria and Kiritimatiellaeota were significantly more abundant in the LRS than in the NRS (p < 0.05), while Bacteroidetes were significantly less abundant in the LRS (p < 0.05). Phascolarctobacterium and Ruminococcaceae_UCG-005 were significantly less abundant in the LRS (p < 0.05) compare to the NRS. Within the duodenum, Lactobacillus was significantly less abundant in the LRS (p < 0.05) than in the NRS, while Pseudomonas was significantly more abundant in the LRS (p < 0.05). Cecal Phascolarctobacterium and Ruminococcaceae_UCG-005 were significantly positively correlated with eggshell strength (R = 0.608, p < 0.01) and egg weight (R = 0.526, p < 0.05), respectively. Duodenal Lactobacillus was significantly positively correlated with VH and VCR (R = 0.548 and 0.565, p < 0.05), while Pseudomonas was significantly negatively correlated with the Haugh unit (R = −0.550, p < 0.05). In conclusion, there are differences in the cecal and duodenal microbiota compositions of Shendan laying hens reared in different non-cage housing systems, and the NRS was superior to the LRS in improving the laying performance and intestinal morphology and microecological environment.
Thirty Years of Changes and the Current State of Swedish Animal Welfare Legislation
Authors: Lundmark Hedman Frida , Berg Charlotte , Stéen Margareta
Published: October 2021

Sweden is often seen as a leading country in animal welfare and legislation, but some recent amendments to the legislation are perceived as relaxing animal welfare requirements in order to improve the competitiveness of the relevant industry and of farmers. In this study, we analysed the suggested and actual changes in the Swedish national animal welfare regulations relating to horses, cattle and pigs between 1988 and 2019 and the consequences for the intended animal welfare level. The regulations and amendments, including the proposals, the written motivations, the stakeholders’ written responses to the proposed amendments and the final amendments, were scrutinised in detail. A sample of 77 requirements was then selected to assess whether and how the animal welfare level was affected by these legislative changes. The results indicated that the animal welfare protection level for cattle, pigs and horses increased overall during the 30-year period, but that a number of specific requirements had been relaxed to meet objectives other than animal welfare. It was more difficult to determine whether animal welfare improved in practice during the same period, due to the lack of systematic evaluations of the consequences of amending the regulations. Future evaluations are needed to evaluate the outcome of new legislative requirements and to monitor whether they serve their purpose in practice.
p53 Forms Redox-Dependent Protein–Protein Interactions through Cysteine 277
Authors: Shi Tao , Polderman Paulien E. , Pagès-Gallego Marc , van Es Robert M. , Vos Harmjan R. , Burgering Boudewijn M. T. , Dansen Tobias B.
Published: October 2021

Reversible cysteine oxidation plays an essential role in redox signaling by reversibly altering protein structure and function. Cysteine oxidation may lead to intra- and intermolecular disulfide formation, and the latter can drastically stabilize protein–protein interactions in a more oxidizing milieu. The activity of the tumor suppressor p53 is regulated at multiple levels, including various post-translational modification (PTM) and protein–protein interactions. In the past few decades, p53 has been shown to be a redox-sensitive protein, and undergoes reversible cysteine oxidation both in vitro and in vivo. It is not clear, however, whether p53 also forms intermolecular disulfides with interacting proteins and whether these redox-dependent interactions contribute to the regulation of p53. In the present study, by combining (co-)immunoprecipitation, quantitative mass spectrometry and Western blot we found that p53 forms disulfide-dependent interactions with several proteins under oxidizing conditions. Cysteine 277 is required for most of the disulfide-dependent interactions of p53, including those with 14-3-3θ and 53BP1. These interaction partners may play a role in fine-tuning p53 activity under oxidizing conditions.
Effect of Printing Layer Thickness on the Trueness and Margin Quality of 3D-Printed Interim Dental Crowns
Authors: Çakmak Gülce , Cuellar Alfonso Rodriguez , Donmez Mustafa Borga , Schimmel Martin , Abou-Ayash Samir , Lu Wei-En , Yilmaz Burak
Published: October 2021

The information in the literature on the effect of printing layer thickness on interim 3D-printed crowns is limited. In the present study, the effect of layer thickness on the trueness and margin quality of 3D-printed composite resin crowns was investigated and compared with milled crowns. The crowns were printed in 3 different layer thicknesses (20, 50, and 100 μm) by using a hybrid resin based on acrylic esters with inorganic microfillers or milled from polymethylmethacrylate (PMMA) discs and digitized with an intraoral scanner (test scans). The compare tool of the 3D analysis software was used to superimpose the test scans and the computer-aided design file by using the manual alignment tool and to virtually separate the surfaces. Deviations at different surfaces on crowns were calculated by using root mean square (RMS). Margin quality of crowns was examined under a stereomicroscope and graded. The data were evaluated with one-way ANOVA and Tukey HSD tests. The layer thickness affected the trueness and margin quality of 3D-printed interim crowns. Milled crowns had higher trueness on intaglio and intaglio occlusal surfaces than 100 μm-layer thickness crowns. Milled crowns had the highest margin quality, while 20 μm and 100 μm layer thickness printed crowns had the lowest. The quality varied depending on the location of the margin.
Strains Comparisons of Unbound Base/Subbase Layer Using Three Elasto-Plastic Models under Repeated Loads
Authors: Li Ning , Ma Biao , Wang Hao
Published: October 2021

The constitutive model is the crucial part for the finite element analyses. To study the elasto-plastic properties of unbound granular materials (UGMs) under repeated vehicular loads, an elasto-plastic constitutive model called revised spatially mobilized plane (SMP) was proposed and validated. In this study, the revised SMP model was used for the plastic strain analyses of a typical three-layer pavement structure. To make comparisons, the Mohr-Coulomb and Druck-Prager models were employed for the numerical computation. The results show that plastic tensile and compressive strains in the horizontal and vertical directions appear on the top surface of UGM using the revised SMP model, but no plastic strains are produced by the Mohr-Coulomb and Druck-Prager models. The distribution of plastic strains in the revised SMP model had a good relationship with the actual loading areas under the vehicular loading, which related to the rutting. With the Mohr-Coulomb and Druck-Prage models, a great plastic strain was produced during the first several loading cycles and hardly increased in the following loading cycles, while the plastic strain in the revised SMP model presented an obvious increasing tendency with increased loading cycles. The predicted permanent deformations of the revised SMP, Mohr-Coulomb and Druck-Prage models were 0.557 mm, 0.78 mm and 0.155 mm, respectively. Our work reveals that the Mohr-Coulomb model may over-predict and Druck-Prage model may under-predict the rutting of pavement in early loading stage and the results proved that the revised SMP model had advantages in the description of the plastic strain of UMG under repeated loads.
Piezoelectric Normally Open Microvalve with Multiple Valve Seat Trenches for Medical Applications
Authors: Durasiewicz Claudia Patricia , Güntner Sophia Thekla , Maier Philipp Klaus , Hölzl Wolfgang , Schrag Gabriele
Published: October 2021

Microfluidic systems for medical applications necessitate reliable, wide flow range, and low leakage microvalves for flow path control. High design complexity of microvalves increases the risk of possible malfunction. We present a normally open microvalve based on energy-efficient piezoelectric actuation for high closing forces and micromachined valve seat trenches for reliable valve operation. A comprehensive investigation of influencing parameters is performed by extensive fluidic 3D finite element simulation, derivation of an analytical closed state leakage rate model, as well as fabrication and test of the microvalve. Additional valve seat coating and a high force actuator are introduced for further leakage reduction. The microvalve has a wide-open flow range as well as good sealing abilities in closed state. Extensive fatigue tests of 1 × 106 actuation cycles show that additional coating of the valve seat or increased actuator strength promote sealing performance stability. Analytical calculations of leakage are suitable to estimate experimentally obtained leakage rates and, along with computational fluidic dynamic (CFD) simulations, enable future microvalve design optimization. In conclusion, we demonstrate that the presented normally open microvalve is suitable for the design of safe and reliable microfluidic devices for medical applications.
Causal Models for the Result of Percutaneous Coronary Intervention in Coronary Chronic Total Occlusions
Authors: Ganopoulou Maria , Kangelidis Ioannis , Sianos Georgios , Angelis Lefteris
Published: October 2021

Background: Patients undergoing coronary angiography very frequently exhibit coronary chronic total occlusions (CTOs). Over the last decade, there has been an increasing acceptance of the percutaneous coronary interventions (PCI) in CTOs due to, among else, rising operator experience and advances in technology. This study is an effort to address the problem of identifying important factors related to the success or failure of the PCI. Methods: The analysis is based on the EuroCTO Registry, which is the largest database available worldwide, consisting of 164 variables and 29,995 cases for the period 2008–2018. The aim is to assess the dynamics of causal models and causal discovery, using observational data, in predicting the result of the PCI. Causal models use graph structure to assess the cause–effect relationships between variables. In this study, the constrained-based algorithm PC was employed. The focus was to find the local causal structure around the PCI result and use it as a feature selection tool for building a predictive model. Results: The model developed was compared with other modeling approaches from the literature, and it was found to perform equally well or better. Conclusions: The analysis showcased the potential of employing local causal structure in predictive model development.