bluuebunny/crossref_metadata_2025 huggingface dataset:
Native and Bioengineered Exosomes for Ischemic Stroke Therapy
Authors: Khan Haroon , Pan Jia-Ji , Li Yongfang , Zhang Zhijun , Yang Guo-Yuan
Published: March 2021

Exosomes are natural cells-derived vesicles, which are at the forefront toward clinical success for various diseases, including cerebral ischemia. Exosomes mediate cell-to-cell communication in different brain cells during both physiological and pathological conditions. Exosomes are an extensively studied type of extracellular vesicle, which are considered to be the best alternative for stem cell–based therapy. They can be secreted by various cell types and have unique biological properties. Even though native exosomes have potential for ischemic stroke therapy, some undesirable features prevent their success in clinical applications, including a short half-life, poor targeting property, low concentration at the target site, rapid clearance from the lesion region, and inefficient payload. In this review, we highlight exosome trafficking and cellular uptake and survey the latest discoveries in the context of exosome research as the best fit for brain targeting owing to its natural brain-homing abilities. Furthermore, we overview the methods by which researchers have bioengineered exosomes (BioEng-Exo) for stroke therapy. Finally, we summarize studies in which exosomes were bioengineered by a third party for stroke recovery. This review provides up-to-date knowledge about the versatile nature of exosomes with a special focus on BioEng-Exo for ischemic stroke. Standard exosome bioengineering techniques are mandatory for the future and will lead exosomes toward clinical success for stroke therapy.
Tet1 Deficiency Leads to Premature Ovarian Failure
Authors: Liu Linlin , Wang Huasong , Xu Guo_Liang , Liu Lin
Published: March 2021

Tet enzymes participate in DNA demethylation and play critical roles in stem cell pluripotency and differentiation. DNA methylation alters with age. We find that Tet1 deficiency reduces fertility and leads to accelerated reproductive failure with age. Noticeably, Tet1-deficient mice at young age exhibit dramatically reduced follicle reserve and the follicle reserve further decreases with age, phenomenon consistent with premature ovarian failure (POF) syndrome. Consequently, Tet1-deficient mice become infertile by reproductive middle age, while age matched wild-type mice still robustly reproduce. Moreover, by single cell transcriptome analysis of oocytes, Tet1 deficiency elevates organelle fission, associated with defects in ubiquitination and declined autophagy, and also upregulates signaling pathways for Alzheimer’s diseases, but down-regulates X-chromosome linked genes, such as Fmr1, which is known to be implicated in POF. Additionally, Line1 is aberrantly upregulated and endogenous retroviruses also are altered in Tet1-deficient oocytes. These molecular changes are consistent with oocyte senescence and follicle atresia and depletion found in premature ovarian failure or insufficiency. Our data suggest that Tet1 enzyme plays roles in maintaining oocyte quality as well as oocyte number and follicle reserve and its deficiency can lead to POF.
Comparative Genomics, Evolutionary and Gene Regulatory Regions Analysis of Casein Gene Family in Bubalus bubalis
Authors: Rehman Saif ur , Feng Tong , Wu Siwen , Luo Xier , Lei An , Luobu Basang , Hassan Faiz-ul , Liu Qingyou
Published: March 2021

Buffalo is a luxurious genetic resource with multiple utilities (as a dairy, draft, and meat animal) and economic significance in the tropical and subtropical regions of the globe. The excellent potential to survive and perform on marginal resources makes buffalo an important source for nutritious products, particularly milk and meat. This study was aimed to investigate the evolutionary relationship, physiochemical properties, and comparative genomic analysis of the casein gene family (CSN1S1, CSN2, CSN1S2, and CSN3) in river and swamp buffalo. Phylogenetic, gene structure, motif, and conserved domain analysis revealed the evolutionarily conserved nature of the casein genes in buffalo and other closely related species. Results indicated that casein proteins were unstable, hydrophilic, and thermostable, although αs1-CN, β-CN, and κ-CN exhibited acidic properties except for αs2-CN, which behaved slightly basic. Comparative analysis of amino acid sequences revealed greater variation in the river buffalo breeds than the swamp buffalo indicating the possible role of these variations in the regulation of milk traits in buffalo. Furthermore, we identified lower transcription activators STATs and higher repressor site YY1 distribution in swamp buffalo, revealing its association with lower expression of casein genes that might subsequently affect milk production. The role of the main motifs in controlling the expression of casein genes necessitates the need for functional studies to evaluate the effect of these elements on the regulation of casein gene function in buffalo.
Identification of NY-ESO-1157–165 Specific Murine T Cell Receptors With Distinct Recognition Pattern for Tumor Immunotherapy
Authors: Zhang Helin , Sun Meng , Wang Jie , Zeng Bin , Cao Xiaoqing , Han Yi , Tan Shuguang , Gao George F.
Published: March 2021

New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target for T-cell receptor-engineered T cell (TCR-T) therapy, and targeting the human leukocyte antigen (HLA)-A2 restricted NY-ESO-1157−165 epitope has yielded remarkable clinical benefits in the treatment of multiple advanced malignancies. Herein, we report the identification of two NY-ESO-1157−165 epitope-specific murine TCRs obtained from HLA-A*0201 transgenic mice. NY-ESO-1157−165 specific TCRs were isolated after vaccinating HLA-A2 transgenic mice with epitope peptides. HZ6 and HZ8 TCRs could specifically bind to NY-ESO-1157−165/HLA-A2 and were capable of cytokine secretion with engineered Jurkat T cells and primary T cells upon recognition with K562 target cells expressing the single-chain trimer (SCT) of NY-ESO-1157−165/HLA-A2. The reactivity profiles of the HZ6 and HZ8 TCRs were found to be distinct from one another when co-cultured with K562 target cells carrying alanine-substituted NY-ESO-1157−165 SCTs. The binding characterization revealed that the recognition pattern of the HZ6 TCR to NY-ESO-1157−165/HLA-A2 was substantially different from the widely used 1G4 TCR. These findings would broaden the understanding of immunogenicity of the NY-ESO-1157−165, and the two identified TCRs may serve as promising candidates for the future development of TCR-T therapy for tumors.
Single-Arm, Multicenter Phase I/II Clinical Trial for the Treatment of Envenomings by Massive Africanized Honey Bee Stings Using the Unique Apilic Antivenom
Authors: Barbosa Alexandre Naime , Ferreira Rui Seabra , de Carvalho Francilene Capel Tavares , Schuelter-Trevisol Fabiana , Mendes Mônica Bannwart , Mendonça Bruna Cavecci , Batista José Nixon , Trevisol Daisson José , Boyer Leslie , Chippaux Jean-Philippe , Medolago Natália Bronzatto , Cassaro Claudia Vilalva , Carneiro Márcia Tonin Rigotto , de Oliveira Ana Paola Piloto , Pimenta Daniel Carvalho , da Cunha Luís Eduardo Ribeiro , Santos Lucilene Delazari dos , Barraviera Benedito
Published: March 2021

We evaluated the safety, optimal dose, and preliminary effectiveness of a new-approach Africanized honeybee (Apis mellifera) Antivenom (AAV) in a phase I/II, multicenter, non-randomized, single-arm clinical trial involving 20 participants with multiple stings. Participants received 2 to 10 vials of AAV depending on the number of stings they suffered, or a predefined adjuvant, symptomatic, and complementary treatment. The primary safety endpoint was the occurrence of early adverse reactions within the first 24 h of treatment. Preliminary efficacy based on clinical evolution, including laboratory findings, was assessed at baseline and at various time points over the four following weeks. ELISA assays and mass spectrometry were used to estimate venom pharmacokinetics before, during, and after treatment. Twenty adult participants, i.e., 13 (65%) men and 7 (35%) women, with a median age of 44 years and a mean body surface area of 1.92 m2 (median = 1.93 m2) were recruited. The number of stings ranged from 7 to > 2,000, with a median of 52.5. Symptoms of envenoming were classified as mild, moderate, or severe in 80% (16), 15% (3), and 5% (1) of patients, respectively; patients with mild, moderate, or severe envenoming received 2, 6, and 10 vials of AAV as per the protocol. None of the patients had late reactions (serum sickness) within 30 d of treatment. There was no discontinuation of the protocol due to adverse events, and there were no serious adverse events. One patient had a moderate adverse event, transient itchy skin, and erythroderma. All participants completed the intravenous antivenom infusion within 2 h, and there was no loss to follow-up after discharge. ELISA assays showed venom (melittin and PLA2) concentrations varying between 0.25 and 1.479 ng/mL prior to treatment. Venom levels decreased in all patients during the hospitalization period. Surprisingly, in nine cases (45%), despite clinical recovery and the absence of symptoms, venom levels increased again during outpatient care 10 d after discharge. Mass spectrometry showed melittin in eight participants, 30 d after treatment. Considering the promising safety results for this investigational product in the treatment of massive Africanized honeybee attack, and its efficacy, reflected in the clinical improvements and corresponding immediate decrease in blood venom levels, the AAV has shown to be safe for human use. Clinical Trial Registration: UTN: U1111-1160-7011, identifier [RBR-3fthf8].
Microbiota Diversity in Pearl Oyster Pinctada fucata martensii Intestine and Its Aquaculture Environment
Authors: Zheng Zhe , Liao Yongshan , Ye Jianming , Yang Chuangye , Adzigbli Linda , Wang Qingheng , Du Xiaodong , Deng Yuewen
Published: March 2021

Environmental microbiota plays a vital role in the intestinal microbiota of aquatic organisms. However, data concerning the association between the intestinal microbiota of pearl oyster Pinctada fucata martensii and the surrounding seawater are limited. The existing bacterial communities in pearl oyster intestine and surrounding water from two sites (D and H, within Liusha Bay in Guangdong, China) were investigated using 16S rRNA-based sequencing to explore the relationship among the two. D located in the inner bay, and H located in the open sea area outside bay. Results revealed the richness and diversity of pearl oyster intestinal microbiota to be less than those of the surrounding water, with 38 phyla and 272 genera observed as a result of the classifiable sequence. The microbiota compositions in the intestine and the surrounding water were diversified at the phylum and genus levels, with the sequencing data being statistically significant. However, the functional prediction of microbiota emphasized the overall similarity in the functional profile of the surrounding seawater and intestinal microbiomes. This profile was associated with metabolism of cofactors and vitamin, carbohydrates metabolism, amino acids metabolism, metabolism of terpenoids, and polyketides, metabolism of other amino acids, lipids metabolism, and energy metabolism. Seven common operational taxonomic units (OTUs), which belonged to phyla Tenericutes, Cyanobacteria, and Planctomycetes, were noted in the intestines of pearl oysters from two different sites. These OTUs may be affiliates to the core microbiome of pearl oyster. Significantly different bacterial taxa in the intestines of pearl oysters from two different sites were found at the phylum and genus levels. This finding suggested that the bacterial communities in pearl oyster intestines may exhibit some plasticity to adapt to changes in the surrounding water-cultured environment. This study generally offers constructive discoveries associated with pearl oyster intestinal microbiota and provides guidance for sustainable aquaculture.
A Meta-Analysis of Endoscopic vs. Microscopic Transsphenoidal Surgery for Non-functioning and Functioning Pituitary Adenomas: Comparisons of Efficacy and Safety
Authors: Guo Shengfu , Wang Zidong , Kang Xiaokui , Xin Wenqiang , Li Xin
Published: March 2021

Background: Although microscopic (MTSS) and endoscopic transsphenoidal surgery (ETSS) are both effective approaches for treating non-functioning pituitary adenomas (NFPA) and functioning pituitary adenomas (FPA), the consensus remains unidentified on whether there are differences in the risk of postoperative complications between the two surgical approaches.

Method: A meta-analysis of the study of MTSS vs. ETSS for NFPA and FPA was conducted by searching the electronic databases of PubMed, Cochrane Library, and EMBASE, from the date of establishment of electronic databases to September 2020 based on the PRISMA guidelines.

Results: In this study, a total of 16 studies were selected, hailing from Belgium, the USA, India, Finland, France, Korea, Spain, China, and Canada. We enrolled 1003 patients in the ETSS and 992 patients in the MTSS group. In patients with NFPA, the ETSS group was related to a higher incidence of post-operative gross-total resection (GTR). (OR = 1.655, 95% CI 1.131–2.421, P = 0.010). In participants with FPA, the results illustrated that the ETSS group had higher rates of visual improvement (OR = 2.461, 95% CI 1.109–5.459) and gross-total resection (OR = 2.033, 95% CI 1.335–3.096), as well as lower meningitis rates (OR = 0.195, 95% CI 0.041–1.923). In participants with acromegaly, no significant difference was shown in the postoperative complications.

Conclusion: Based on current evidence, participants with NFPA treated by endoscopy were related to higher rates of GTR; patients with FPA treated by ETSS were related to higher rates of visual improvement and GTR, as well as a lower rates of meningitis.
Kinematic and Clinical Outcomes to Evaluate the Efficacy of a Multidisciplinary Intervention on Functional Mobility in Parkinson's Disease
Authors: Bouça-Machado Raquel , Branco Diogo , Fonseca Gustavo , Fernandes Raquel , Abreu Daisy , Guerreiro Tiago , Ferreira Joaquim J. ,   The CNS Physiotherapy Study group
Published: March 2021

Introduction: Functional mobility (FM) is a concept that incorporates the capacity of a person to move independently and safely to accomplish tasks. It has been proposed as a Parkinson's disease (PD) functional and global health outcome. In this study, we aimed to identify which kinematic and clinical outcomes changes better predict FM changes when PD patients are submitted to a specialized multidisciplinary program.

Methods: PD patients engaged in a pre-defined specialized multidisciplinary program were assessed at admission and discharge. Change from baseline was calculated for all kinematic and clinical outcomes, and Timed Up and Go (TUG) was defined as the primary outcome for FM. A stepwise multivariate linear regression was performed to identify which outcome measures better predict TUG changes.

Results: Twenty-four patients were included in the study. The changes in TUG Cognitive test, supervised step length, and free-living (FL) step time asymmetry were identified as the best predictors of TUG changes. The supervised step length and FL step time asymmetry were able to detect a small to moderate effect of the intervention (d values ranging from −0.26 to 0.42).

Conclusions: Our results support the use of kinematic outcome measures to evaluate the efficacy of multidisciplinary interventions on PD FM. The TUG Cognitive, step length, and FL step time asymmetry were identified as having the ability to predict TUG changes. More studies are needed to identify the minimal clinically important difference for step length and FL step time asymmetry in response to a multidisciplinary intervention for PD FM.
Effects of Lower Limb Constraint Induced Movement Therapy in People With Stroke: A Systematic Review and Meta-Analysis
Authors: Abdullahi Auwal , Truijen Steven , Umar Naima A. , Useh Ushotanefe , Egwuonwu Victor A. , Van Criekinge Tamaya , Saeys Wim
Published: March 2021

Background: Constraint induced movement therapy (CIMT) is effective at improving upper limb outcomes after stroke.

Aim: The aim of this study was to carry out a systematic review and meta-analysis of the effects of lower limb CIMT studies of any design in people with stroke.

Materials/ Method: PubMED, PEDro, OTSeeker, CENTRAL, and Web of Science were searched from their earliest dates to February 2021. Lower limbs CIMT studies that measured outcomes at baseline and post-intervention were selected. Sample size, mean, and standard deviation on the outcomes of interest and the protocols of both the experimental and control groups were extracted. McMaster Critical Review Form was used to assess the methodological quality of the studies.

Result: Sixteen studies with different designs were included in this review. The result showed that lower limb CIMT improves functional, physiological and person's reported outcomes including motor function, balance, mobility, gait speed, oxygen uptake, exertion before and after commencement of activities, knee extensor spasticity, weight bearing, lower limb kinematics and quality of life in people with stroke post intervention. However, there were only significant differences in quality of life in favor of CIMT post-intervention [mean difference (MD) = 16.20, 95% CI = 3.30–29.10, p = 0.01]; and at follow-up [mean difference (MD) = 14.10, 95% CI = 2.07–26.13, p = 0.02] between CIMT and the control group. Even for the quality of life, there was significant heterogeneity in the studies post intervention (I2 = 84%, p = 0.01).

Conclusion: Lower limb CIMT improves motor function, balance, functional mobility, gait speed, oxygen uptake, weigh bearing, lower limb kinematics, and quality of life. However, it is only superior to the control at improving quality of life after stroke based on the current literature.
Increase in Beta Power Reflects Attentional Top-Down Modulation After Psychosocial Stress Induction
Authors: Palacios-García Ismael , Silva Jaime , Villena-González Mario , Campos-Arteaga Germán , Artigas-Vergara Claudio , Luarte Nicolas , Rodríguez Eugenio , Bosman Conrado A.
Published: March 2021

Selective attention depends on goal-directed and stimulus-driven modulatory factors, each relayed by different brain rhythms. Under certain circumstances, stress-related states can change the balance between goal-directed and stimulus-driven factors. However, the neuronal mechanisms underlying these changes remain unclear. In this study, we explored how psychosocial stress can modulate brain rhythms during an attentional task and a task-free period. We recorded the EEG and ECG activity of 42 healthy participants subjected to either the Trier Social Stress Test (TSST), a controlled procedure to induce stress, or a comparable control protocol (same physical and cognitive effort but without the stress component), flanked by an attentional task, a 90 s of task-free period and a state of anxiety questionnaire. We observed that psychosocial stress induced an increase in heart rate (HR), self-reported anxiety, and alpha power synchronization. Also, psychosocial stress evoked a relative beta power increase during correct trials of the attentional task, which correlates positively with anxiety and heart rate increase, and inversely with attentional accuracy. These results suggest that psychosocial stress affects performance by redirecting attentional resources toward internal threat-related thoughts. An increment of endogenous top-down modulation reflected an increased beta-band activity that may serve as a compensatory mechanism to redirect attentional resources toward the ongoing task. The data obtained here may contribute to designing new ways of clinical management of the human stress response in the future and could help to minimize the damaging effects of persistent stressful experiences.
RIM-Binding Proteins Are Required for Normal Sound-Encoding at Afferent Inner Hair Cell Synapses
Authors: Krinner Stefanie , Predoehl Friederike , Burfeind Dinah , Vogl Christian , Moser Tobias
Published: March 2021

The afferent synapses between inner hair cells (IHC) and spiral ganglion neurons are specialized to faithfully encode sound with sub-millisecond precision over prolonged periods of time. Here, we studied the role of Rab3 interacting molecule-binding proteins (RIM-BP) 1 and 2 – multidomain proteins of the active zone known to directly interact with RIMs, Bassoon and CaV1.3 – in IHC presynaptic function and hearing. Recordings of auditory brainstem responses and otoacoustic emissions revealed that genetic disruption of RIM-BPs 1 and 2 in mice (RIM-BP1/2–/–) causes a synaptopathic hearing impairment exceeding that found in mice lacking RIM-BP2 (RIM-BP2–/–). Patch-clamp recordings from RIM-BP1/2–/– IHCs indicated a subtle impairment of exocytosis from the readily releasable pool of synaptic vesicles that had not been observed in RIM-BP2–/– IHCs. In contrast, the reduction of Ca2+-influx and sustained exocytosis was similar to that in RIMBP2–/– IHCs. We conclude that both RIM-BPs are required for normal sound encoding at the IHC synapse, whereby RIM-BP2 seems to take the leading role.
Using Microdosing to Induct Patients Into a Long-Acting Injectable Buprenorphine Depot Medication in Low Threshold Community Settings: A Case Study
Authors: Tay Wee Teck Joseph , Baldacchino Alexander , Gibson Lauren , Lafferty Con
Published: March 2021

Healthcare innovation has never been more important as it is now when the world is facing up to the unprecedented challenges brought by the COVID-19 pandemic. Within addictions services in Scotland, the priority has been to tackle our rising drug related death rate by maintaining and improving access to treatment while protecting frontline workers and managing operational challenges as a result of the pandemic. We present here a case study of five patients with opioid use disorder whose treatment represents a confluence of three important Medication Assisted Treatment (MAT) service innovations. The first was a low threshold drop in and outreach MAT service to rapidly and safely initiate opiate replacement therapy (ORT). The second was the provision of a microdosing regimen to enable same day induction to oral buprenorphine while minimizing the risk of precipitated opioid withdrawals and/or treatment disengagement. The third was rapid transitioning to an injectable long-acting buprenorphine depot which reduced unnecessary face to face patient contact and treatment non-adherence. This case study of five patients highlights the valuable role that buprenorphine microdosing can play in making induction to long-acting buprenorphine depot feasible to a broader range of patients, including those on a high dose methadone treatment regime.
Theaflavin-3,3′-Digallate Promotes the Formation of Osteoblasts Under Inflammatory Environment and Increases the Bone Mass of Ovariectomized Mice
Authors: Ge Gaoran , Yang Sen , Hou Zhenyang , Gan Minfeng , Tao Huaqiang , Zhang Wei , Li Wenming , Wang Zheng , Hao Yuefeng , Gu Ye , Geng Dechun
Published: March 2021

Postmenopausal osteoporosis is a disease of bone mass reduction and structural changes due to estrogen deficiency, which can eventually lead to increased pain and fracture risk. Chronic inflammatory microenvironment leading to the decreased activation of osteoblasts and inhibition of bone formation is an important pathological factor that leads to osteoporosis. Theaflavin-3,3′-digallate (TFDG) is an extract of black tea, which has potential anti-inflammatory and antiviral effects. In our study, we found that TFDG significantly increased the bone mass of ovariectomized (OVX) mice by micro-CT analysis. Compared with OVX mice, TFDG reduced the release of proinflammatory cytokines and increased the expression of osteogenic markers in vivo. In vitro experiments demonstrated that TFDG could promote the formation of osteoblasts in inflammatory environment and enhance their mineralization ability. In this process, TFDG activated MAPK, Wnt/β-Catenin and BMP/Smad signaling pathways inhibited by TNF-α, and then promoted the transcription of osteogenic related factors including Runx2 and Osterix, promoting the differentiation and maturation of osteoblasts eventually. In general, our study confirmed that TFDG was able to promote osteoblast differentiation under inflammatory environment, enhance its mineralization ability, and ultimately increase bone mass in ovariectomized mice. These results suggested that TFDG might have the potential to be a more effective treatment of postmenopausal osteoporosis.
Symbolic Analysis of the Heart Rate Variability During the Plateau Phase Following Maximal Sprint Exercise
Authors: Storniolo Jorge L. , Cairo Beatrice , Porta Alberto , Cavallari Paolo
Published: March 2021

Cardiac autonomic control is commonly assessed via the analysis of fluctuations of the temporal distance between two consecutive R-waves (RR). Cardiac regulation assessment following high intensity physical exercise is difficult due to RR non-stationarities. The very short epoch following maximal sprint exercise when RR remains close to its lowest value, i.e., the PLATEAU, provides the opportunity to evaluate cardiac regulation from stationary RR sequences. The aim of the study is to evaluate cardiac autonomic control during PLATEAU phase following 60-m maximal sprint and compare the results to those derived from sequences featuring the same length as the PLATEAU and derived from pre-exercise and post-exercise periods. These sequences were referred to as PRE and POST sequences. RR series were recorded in 21 subjects (age: 24.9 ± 5.1 years, 15 men and six women). We applied a symbolic approach due to its ability to deal with very short RR sequences. The symbolic approach classified patterns formed by three RRs according to the sign and number of RR variations. Symbolic markers were compared to more classical time and frequency domain indexes. Comparison was extended to simulated signals to explicitly evaluate the suitability of methods to deal with short variability series. A surrogate test was applied to check the null hypothesis of random fluctuations. Over simulated data symbolic analysis was able to separate dynamics with different spectral profiles provided that the frame length was longer than 10 cardiac beats. Over real data the surrogate test indicated the presence of determinism in PRE, PLATEAU, and POST sequences. We found that the rate of patterns with two variations with unlike sign increased during PLATEAU and in POST sequences and the frequency of patterns with no variations remained unchanged during PLATEAU and decreased in POST compared to PRE sequences. Results indicated a sustained sympathetic control along with an early vagal reactivation during PLATEAU and a shift of the sympathovagal balance toward vagal predominance in POST compared to PRE sequences. Time and frequency domains markers were less powerful because they were dominated by the dramatic decrease of RR variance during PLATEAU.
The Relationship Between College Teachers’ Frustration Tolerance and Academic Performance
Authors: Shi Song , Zhang Zizai , Wang Ying , Yue Huilan , Wang Zede , Qian Songling
Published: March 2021

The purpose of this study was twofold: to validate the College Teachers’ Academic Frustration Tolerance (CTAFT) Questionnaire and the College Teachers’ Academic Performance (CTAP) Questionnaire and to explore the relationship between frustration tolerance and academic performance among college teachers. A total of 25 experts were recruited to modify and validate both questionnaires, and the results showed that the questionnaires had good content validity. Exploratory factor analysis provided further evidence supporting the reliability of the CTAFT and the CTAP, suggesting that the instruments are reliable and valid. Confirmatory factor analysis showed that frustration tolerance affected academic performance, which could best be modeled in the three dimensions of Affect (AF), Preferred Difficulties (PD), and Action (AC). A total of 450 college teachers from each faculty of both universities were then recruited to explore the significant positive correlation between academic frustration tolerance and academic performance. The results from the structural equation model suggested that AC and PD combined significantly predicted academic performance. To our knowledge, this is the first study to explore the relationship between college teachers’ academic frustration tolerance and academic performance in China.
Predicting the Development of Adult Nature Connection Through Nature Activities: Developing the Evaluating Nature Activities for Connection Tool
Authors: Carr Victoria , Hughes Joelene
Published: March 2021

Nature Connection (NC) is considered an important driver of conservation behavior. Consequently, conservation organizations run many activities aiming to increase NC among participants. However, little is known about which activities are most effective at doing this and why. This study developed the Evaluating Nature Activities for Connection Tool (ENACT), to evaluate the effectiveness of activities for increasing participants’ NC and nature-related intentions. ENACT comprises 11 activity aspects identified through two research phases. In Phase 1, a literature search, focus group and interviews identified desired, short-term behavioral outcomes of nature activities, and variables that might promote these. In Phase 2, 241 adults completed a pilot survey immediately post-nature activity, with 1-month follow-up (N= 145), to evaluate the impact of participation on NC, nature-related behavioral intentions and behaviors. ENACT correlated with NC measures and offered incremental validity in predicting nature-related behavioral intentions and self-reported behaviors after 1 month.
Ten Years of Research on Automatic Voice and Speech Analysis of People With Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review Article
Authors: Martínez-Nicolás Israel , Llorente Thide E. , Martínez-Sánchez Francisco , Meilán Juan José G.
Published: March 2021

Background: The field of voice and speech analysis has become increasingly popular over the last 10 years, and articles on its use in detecting neurodegenerative diseases have proliferated. Many studies have identified characteristic speech features that can be used to draw an accurate distinction between healthy aging among older people and those with mild cognitive impairment and Alzheimer's disease. Speech analysis has been singled out as a cost-effective and reliable method for detecting the presence of both conditions. In this research, a systematic review was conducted to determine these features and their diagnostic accuracy.

Methods: Peer-reviewed literature was located across multiple databases, involving studies that apply new procedures of automatic speech analysis to collect behavioral evidence of linguistic impairments along with their diagnostic accuracy on Alzheimer's disease and mild cognitive impairment. The risk of bias was assessed by using JBI and QUADAS-2 checklists.

Results: Thirty-five papers met the inclusion criteria; of these, 11 were descriptive studies that either identified voice features or explored their cognitive correlates, and the rest were diagnostic studies. Overall, the studies were of good quality and presented solid evidence of the usefulness of this technique. The distinctive acoustic and rhythmic features found are gathered. Most studies record a diagnostic accuracy over 88% for Alzheimer's and 80% for mild cognitive impairment.

Conclusion: Automatic speech analysis is a promising tool for diagnosing mild cognitive impairment and Alzheimer's disease. The reported features seem to be indicators of the cognitive changes in older people. The specific features and the cognitive changes involved could be the subject of further research.
Disgust Sensitivity Among Women During the COVID-19 Outbreak
Authors: Miłkowska Karolina , Galbarczyk Andrzej , Mijas Magdalena , Jasienska Grazyna
Published: March 2021

The emotion of disgust is suggested to be an adaptation that evolved to keep us away from sources of infection. Therefore, individuals from populations with greater pathogen stress should have a greater disgust sensitivity. However, current evidence for a positive relationship between disgust sensitivity and the intensity of infectious diseases in the environment is limited. We tested whether disgust and contamination sensitivity changed in response to the COVID-19 pandemic. Disgust was assessed in 984 women in 2017 (before pandemic) and 633 women in 2020 (during pandemic) by a set of photographs depicting sources of infection and Pathogen and Moral of Three-Domain Disgust Scale. Further, contamination sensitivity among participants in two waves was measured by Contamination Obsessions and Washing Compulsions Subscale of Padua Inventory. State anxiety was measured with the Polish adaptation of the State-Trait Anxiety Inventory (STAI) only during the second wave of data collection. Women from the COVID-19 pandemic group assessed the photographs depicting sources of infection as more disgusting, scoring higher on Padua Inventory, but lower on Moral Disgust Domain as compared to women from before the pandemic. In addition, anxiety levels during pandemic positively correlated with scores from Pathogen Disgust Domain, Padua Inventory, and the ratings of the photographs. The participants of the study scored higher in state anxiety than the norms determined for the Polish population. Summarizing, we present evidence for differences in individual levels of disgust sensitivity in relation to pathogen stress, supporting the idea that disgust evolved to serve as protection from pathogens.
Coping With COVID-19: Mindfulness-Based Approaches for Mitigating Mental Health Crisis
Authors: Antonova Elena , Schlosser Karoly , Pandey Rakesh , Kumari Veena
Published: March 2021

The novel coronavirus disease COVID-19 that first emerged in Wuhan, China, in Nov-Dec 2019 has already impacted a significant proportion of the world population. Governments of many countries imposed quarantines and social distancing measures in 2020, many of which remain in place, to mitigate the spread of the SARS-Cov-2 virus causing the COVID-19 disease. The direct impact of COVID-19 on people infected with the virus, their families and the health care workers, as well as the impact of the mitigation measures such as quarantine, social distancing, and self-isolation on the rest of the population have contributed to a global mental health pandemic, including anxiety, depression, panic attacks, posttraumatic stress symptoms, psychosis, addiction, obsessive-compulsive disorder, and suicidality. These effects are present acutely (for example, due to fear of contamination or losing loved ones, effects of quarantine/isolation, withdrawal of community and social services, etc.) and may continue long after the pandemic is over (for example, due to bereavement, unemployment, financial losses, etc). The COVID-19 pandemic has triggered mental health problems in people without previous history of mental illness, as well as worsened the symptoms in those with pre-existing psychiatric diagnosis. Therefore, the global effort is called for to deal with this mental health pandemic secondary to COVID-19 itself to address the emergence of new as well as the exacerbation of the existing mental health issues. Conversely, this global context provides an extraordinary opportunity for studying individual differences in response to and resilience in the face of physical and psychological threat, challenge to “normal” way of life, and long-term uncertainty. In this viewpoint article we outline the particular suitability of mindfulness, its skills and mechanisms, as an approach to the prevention and management of mental health issues, as well as to the promotion of well-being and building the foundations of adaptability and flexibility in dealing with the long-term uncertainty and profound changes to the social, economic, and possibly political systems as this pandemic continues to unfold.
Therapy Processes Associated With Sudden Gains in Cognitive Therapy for Depression: Exploring Therapeutic Changes in the Sessions Surrounding the Gains
Authors: Lemmens Lotte H. J. M. , DeRubeis Robert J. , Tang Tony Z. , Schulte-Strathaus Julia C. C. , Huibers Marcus J. H.
Published: March 2021

Background: The frequency and clinical impact of Sudden Gains—large symptom improvements during a single between-session interval—in psychotherapy for depression have been well established. However, there have been relatively few efforts to identify the processes that lead to sudden gains.

Aim: To explore therapy processes associated with sudden gains in cognitive therapy for depression by examining changes in the sessions surrounding the gains, and the session preceding the gain in particular.

Methods: Using ratings of video-recordings (n = 36), we assessed the content, frequency and magnitude of within-session cognitive-, behavioral-, and interpersonal change, as well as the quality of the therapeutic alliance in the session prior to the gain (pre-gain session), the session after the gain (post-gain session) and a control session. After that, we contrasted scores in the pre-gain session with those in the control session. In addition, we examined changes that occurred between the pre- and post-gain session (between-session changes) and explored patients' attributions of change.

Results: Although not statistically significant, within-session changes were more frequent and stronger in the pre-gain session compared to the control session. The largest difference between the pre-gain and control session was found in the behavioral domain, and reached the level of trend-significance. There were more, and more impactful between-session changes in the interval during which the gain occurred as compared to a control interval. Exploratory analysis of attributions of change revealed eight subcategories, all corresponding with the cognitive-, behavioral- and interpersonal- domain. The quality of the therapeutic alliance was high and almost identical in all sessions.

Conclusion: In spite of its small sample size, our study provides relevant descriptive information about potential precipitants of, themes related to, and attributions given for sudden gains. Furthermore, our study provides clear suggestions for future research. A better understanding of session content in the sessions surrounding sudden gains may provide insight into the mechanisms of change in psychotherapy, hereby suggesting treatment-enhancing strategies. We encourage researchers to conduct research that could clarify the nature of these mechanisms, and believe the methods used in this study could serve as a framework for further work in this area.
Development and Dissemination of a Strengths-Based Indigenous Children's Storybook: “Our Smallest Warriors, Our Strongest Medicine: Overcoming COVID-19”
Authors: O'Keefe Victoria M. , Maudrie Tara L. , Ingalls Allison , Kee Crystal , Masten Kristin L. , Barlow Allison , Haroz Emily E.
Published: March 2021

The traditions, strengths, and resilience of communities have carried Indigenous peoples for generations. However, collective traumatic memories of past infectious diseases and the current impact of the coronavirus disease 2019 (COVID-19) pandemic in many Indigenous communities point to the need for Indigenous strengths-based public health resources. Further, recent data suggest that COVID-19 is escalating mental health and psychosocial health inequities for Indigenous communities. To align with the intergenerational strengths of Indigenous communities in the face of the pandemic, we developed a strengths- and culturally-based public health education and mental health coping resource for Indigenous children and families. Using a community-engaged process, the Johns Hopkins Center for American Indian Health collaborated with 14 Indigenous and allied child development, mental health, health communications experts and public health professionals, as well as a Native American youth artist. Indigenous collaborators and Indigenous Johns Hopkins project team members collectively represented 12 tribes, and reservation-based, off-reservation, and urban geographies. This group shared responsibility for culturally adapting the children's book “My Hero is You: How Kids Can Fight COVID-19!” developed by the Inter-Agency Standing Committee Reference Group on Mental Health and Psychosocial Support in Emergency Settings and developing ancillary materials. Through an iterative process, we produced the storybook titled “Our Smallest Warriors, Our Strongest Medicine: Overcoming COVID-19” with content and illustrations representing Indigenous values, experiences with COVID-19, and strengths to persevere. In addition, parent resource materials, children's activities, and corresponding coloring pages were created. The book has been disseminated online for free, and 42,364 printed copies were distributed to early childhood home visiting and tribal head start programs, Indian Health Service units, tribal health departments, intertribal, and urban Indigenous health organizations, Johns Hopkins Center for American Indian Health project sites in partnering communities, schools, and libraries. The demand for and response to “Our Smallest Warriors, Our Strongest Medicine: Overcoming COVID-19” demonstrates the desire for Indigenous storytelling and the elevation of cultural strengths to maintain physical, mental, emotional, and spiritual health during the COVID-19 pandemic.
The Interconnected Health Initiative: A Smithsonian Framework to Extend One Health Research and Education
Authors: Comizzoli Pierre , Pagenkopp Lohan Katrina M. , Muletz-Wolz Carly , Hassell James , Coyle Brian
Published: March 2021

To better tackle diseases and sustain healthy ecosystems, One Health programs must efficiently bridge health in humans, domestic/livestock species, wild animals and plants, agriculture/aquaculture, and the environment. The Smithsonian Institution proposes to address this by considering ‘health' in a broad sense – the absence of undue pathogens and unnecessary stress for any organisms as well as access to good living conditions in functional environments. Considering the interconnectedness of all life forms, the Smithsonian plans to create a framework that will integrate cultural, social, and educational components into health research on humans, animals, plants, or ecosystems. The objectives of this perspective article are to (1) propose an innovative framework to support an interconnected/integrated approach to health and (2) provide examples fostering impactful collaborations on One Health research and education. Based on the core strengths of the Smithsonian (multidisciplinary research, outreach and education programs, libraries/archives, and collections) and central institutional support, this framework has the potential to extend existing health-related projects, address new needs and situations (e.g., response to pandemics), provide invaluable resources to inform policy and decision makers, and educate all audiences globally.
Pre-Surgery Cognitive Performance and Voxel-Based Lesion-Symptom Mapping in Patients with Left High-Grade Glioma
Authors: Guarracino Ilaria , Ius Tamara , Baiano Cinzia , D’Agostini Serena , Skrap Miran , Tomasino Barbara
Published: March 2021

(1) Background: The literature on the effects of high-grade glioma (HGG) growth on cognition is still scarce. (2) Method: A consecutive series of 85 patients with HGG involving the left hemisphere underwent an extended neuropsychological evaluation prior to surgery. Voxel-based lesion-symptom mapping (VLSM) was used to identify regions related to cognitive performance. (3) Results: The patients’ mean level of pre-surgery accuracy was overall high. They showed the greatest difficulties in language with tasks such as naming (42.1% of patients impaired on nouns and 61.4% on verbs), reading (36.3% on words and 32.7% on pseudo-words), auditory lexical decisions (43.9%) and writing (41.3%) being most frequently impaired. VLSM analysis revealed anatomically separated areas along the temporal cortex and the white matter related to impairments on the different tasks, with voxels commonly shared by all tasks restricted to a small region in the ventral superior and middle temporal gyrus. (4) Conclusions: High-grade glioma affects cognition; nonetheless, lesions do not cause diffuse deficits but selectively impact the different language sub-domains along the ventral stream and the dorsal stream for language processing.
Inverse Optimal Control in State Derivative Space System with Applications in Motor Control
Authors: Lee Feng-Chi , Tseng Yuan-Wei , Wu Rong-Ching , Chen Wen-Chuan , Chen Chin-Sheng
Published: March 2021

This paper mathematically explains how state derivative space (SDS) system form with state derivative related feedback can supplement standard state space system with state related feedback in control designs. Practically, inverse optimal control is attractive because it can construct a stable closed-loop system while optimal control may not have exact solution. Unlike the previous algorithms which mainly applied state feedback, in this paper inverse optimal control are carried out utilizing state derivative alone in SDS system. The effectiveness of proposed algorithms are verified by design examples of DC motor tracking control without tachometer and very challenging control problem of singular system with impulse mode. Feedback of direct measurement of state derivatives without integrations can simplify implementation and reduce cost. In addition, the proposed design methods in SDS system with state derivative feedback are analogous to those in state space system with state feedback. Furthermore, with state derivative feedback control in SDS system, wider range of problems such as singular system control can be handled effectively. These are main advantages of carrying out control designs in SDS system.
Analysis of Multi-Stream Fuel Injector Flow Using Zonal Proper Orthogonal Decomposition
Authors: Butcher Daniel , Spencer Adrian
Published: March 2021

The 3-component velocity distribution of two lean-burn gas turbine fuel injectors are measured at a planar location near and parallel to the injector outlet. The two injectors are nominally the same design, but one features blocked central passages to study the effects of the presence of multi-streams and reveal the single stream characteristics embedded within the multi-stream configuration. Stereoscopic particle image velocimetry is used in an isothermal, non-reacting water analogue flow facility at an engine relevant Reynolds number. The velocity data is analysed using proper orthogonal decomposition (POD) and the work introduces the concept of Zonal POD. This is the splitting of the velocity field into zones prior to the calculation of POD modes to better identify prominent structures and features associated with each zone. Because modes are sorted by the area averaged energy contribution, zoning of a velocity field of interest may change the individual modes and will almost certainly change their order for anything other than trivial flow fields. Analysis of ensemble average and velocity fluctuation profiles reveals a radial shift outboard of the mains flow with the presence of the pilot as well as a general increase in RMS across the intermediate region between the pilot and mains flows. Analysis of POD temporal coefficients in the frequency domain reveals a low-frequency peak is evident in the mains flow region, but which may be affected by the presence of pilot flow. Furthermore, application of the ZPOD technique results in a closer representation of the velocity data for a given number of modes. This shows the behaviour of the unsteady pilot flow and reveals that a significant proportion of the fluctuating energy, RMS, is caused by this characteristic.