bluuebunny/crossref_metadata_2025 huggingface dataset:
ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis
Authors: Yan Qiang , Ni Chenming , Lin Yingying , Sun Xu , Shen Zhenhua , Zhang Minjie , Han Shuwen , Shi Jiemin , Mao Jing , Yang Zhe , Wang Weilin
Published: December 2021

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.
Local Brain-Age: A U-Net Model
Authors: Popescu Sebastian G. , Glocker Ben , Sharp David J. , Cole James H.
Published: December 2021

We propose a new framework for estimating neuroimaging-derived “brain-age” at a local level within the brain, using deep learning. The local approach, contrary to existing global methods, provides spatial information on anatomical patterns of brain ageing. We trained a U-Net model using brain MRI scans from n = 3,463 healthy people (aged 18–90 years) to produce individualised 3D maps of brain-predicted age. When testing on n = 692 healthy people, we found a median (across participant) mean absolute error (within participant) of 9.5 years. Performance was more accurate (MAE around 7 years) in the prefrontal cortex and periventricular areas. We also introduce a new voxelwise method to reduce the age-bias when predicting local brain-age “gaps.” To validate local brain-age predictions, we tested the model in people with mild cognitive impairment or dementia using data from OASIS3 (n = 267). Different local brain-age patterns were evident between healthy controls and people with mild cognitive impairment or dementia, particularly in subcortical regions such as the accumbens, putamen, pallidum, hippocampus, and amygdala. Comparing groups based on mean local brain-age over regions-of-interest resulted in large effects sizes, with Cohen's d values >1.5, for example when comparing people with stable and progressive mild cognitive impairment. Our local brain-age framework has the potential to provide spatial information leading to a more mechanistic understanding of individual differences in patterns of brain ageing in health and disease.
Effects of Virtual Reality-Based Intervention on Cognition, Motor Function, Mood, and Activities of Daily Living in Patients With Chronic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Gao Yong , Ma Lu , Lin Changsheng , Zhu Shizhe , Yao Lingling , Fan Hong , Gong Jianqiu , Yan Xiaobo , Wang Tong
Published: December 2021

Background: The efficacy of virtual reality (VR)-based intervention for improving cognition in patients with the chronic stage of stroke is controversial. The aims of this meta-analysis were to evaluate the effect of VR-based training combined with traditional rehabilitation on cognition, motor function, mood, and activities of daily living (ADL) after chronic stroke.

Methods: The search was performed in the Cochrane Library (CENTRAL), EBSCO, EMBASE, Medline (OVID), Web of Science databases, PubMed, CINAHL Ovid, and Scopus from inception to May 31, 2021. All included studies were randomized controlled trials (RCTs) examining VR-based intervention combined with traditional rehabilitation for chronic stroke. The main outcomes of this study were cognition, including overall cognition (combined with all cognitive measurement results), global cognition (measured by the Montreal Cognitive Assessment, MoCA, and/or Mini-Mental State Examination, MMSE), and attention/execution. The additional outcomes were motor function, mood, and ADL. Subgroup analyses were conducted to verify the potential factors for heterogeneity.

Results: Six RCTs including 209 participants were included for systematic review, and five studies of 177 participants were included in meta-analyses. Main outcome analyses showed large and significant effect size (ES) of VR-based training on overall cognition (g = 0.642; 95% CI = 0.134–1.149; and P = 0.013) and attention/execution (g = 0.695; 95% CI = 0.052–1.339; and P = 0.034). Non-significant result was found for VR-based intervention on global cognition (g = 0.553; 95% CI = −0.273–1.379; and P = 0.189). Additional outcome analyses showed no superiority of VR-based intervention over traditional rehabilitation on motor function and ADL. The ES of VR-based intervention on mood (g = 1.421; 95% CI = 0.448–2.393; and P = 0.004) was large and significant. In the subgroup analysis, large effects for higher daily intensity, higher weekly frequency, or greater dose of VR intervention were found.

Conclusion: Our findings indicate that VR-based intervention combined with traditional rehabilitation showed better outcomes for overall cognition, attention/execution, and depressive mood in individuals with chronic stroke. However, VR-based training combined with traditional rehabilitation showed a non-significant effect for global cognition, motor function, and ADL in individuals with chronic stroke.
Inflammation Mediated Epileptogenesis as Possible Mechanism Underlying Ischemic Post-stroke Epilepsy
Authors: Tröscher Anna Regina , Gruber Joachim , Wagner Judith N. , Böhm Vincent , Wahl Anna-Sophia , von Oertzen Tim J.
Published: December 2021

Post-stroke Epilepsy (PSE) is one of the most common forms of acquired epilepsy, especially in the elderly population. As people get increasingly older, the number of stroke patients is expected to rise and concomitantly the number of people with PSE. Although many patients are affected by post-ischemic epileptogenesis, not much is known about the underlying pathomechanisms resulting in the development of chronic seizures. A common hypothesis is that persistent neuroinflammation and glial scar formation cause aberrant neuronal firing. Here, we summarize the clinical features of PSE and describe in detail the inflammatory changes after an ischemic stroke as well as the chronic changes reported in epilepsy. Moreover, we discuss alterations and disturbances in blood-brain-barrier leakage, astrogliosis, and extracellular matrix changes in both, stroke and epilepsy. In the end, we provide an overview of commonalities of inflammatory reactions and cellular processes in the post-ischemic environment and epileptic brain and discuss how these research questions should be addressed in the future.
Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Stanculescu Dominic , Sepúlveda Nuno , Lim Chin Leong , Bergquist Jonas
Published: December 2021

We here provide an overview of the pathophysiological mechanisms during heat stroke and describe similar mechanisms found in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Both conditions are characterized by disturbed homeostasis in which inflammatory pathways play a central role. Splanchnic vasoconstriction, increased gut permeability, gut-related endotoxemia, systemic inflammatory response, central nervous system dysfunction, blood coagulation disorder, endothelial-cell injury, and mitochondrial dysfunction underlie heat stroke. These mechanisms have also been documented in ME/CFS. Moreover, initial transcriptomic studies suggest that similar gene expressions are altered in both heat stroke and ME/CFS. Finally, some predisposing factors for heat stroke, such as pre-existing inflammation or infection, overlap with those for ME/CFS. Notwithstanding important differences - and despite heat stroke being an acute condition - the overlaps between heat stroke and ME/CFS suggest common pathways in the physiological responses to very different forms of stressors, which are manifested in different clinical outcomes. The human studies and animal models of heat stroke provide an explanation for the self-perpetuation of homeostatic imbalance centered around intestinal wall injury, which could also inform the understanding of ME/CFS. Moreover, the studies of novel therapeutics for heat stroke might provide new avenues for the treatment of ME/CFS. Future research should be conducted to investigate the similarities between heat stroke and ME/CFS to help identify the potential treatments for ME/CFS.
Oligomer-Targeting Prevention of Neurodegenerative Dementia by Intranasal Rifampicin and Resveratrol Combination – A Preclinical Study in Model Mice
Authors: Umeda Tomohiro , Sakai Ayumi , Shigemori Keiko , Yokota Ayumi , Kumagai Toru , Tomiyama Takami
Published: December 2021

Amyloidogenic protein oligomers are thought to play an important role in the pathogenesis of neurodegenerative dementia, including Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies. Previously we demonstrated that oral or intranasal rifampicin improved the cognition of APP-, tau-, and α-synuclein-transgenic mice by reducing the amount of Aβ, tau, and α-synuclein oligomers in the brain. In the present study, to explore more effective and safer medications for dementia, we tested the drug combination of rifampicin and resveratrol, which is a multifunctional natural polyphenol with the potential to antagonize the adverse effects of rifampicin. The mixture was intranasally administered to APP-, tau-, and α-synuclein-transgenic mice, and their memory and oligomer-related pathologies were evaluated. Compared with rifampicin and resveratrol alone, the combinatorial medicine significantly improved mouse cognition, reduced amyloid oligomer accumulation, and recovered synaptophysin levels in the hippocampus. The plasma levels of liver enzymes, which reflect hepatic injury and normally increase by rifampicin treatment, remained normal by the combination treatment. Notably, resveratrol alone and the combinatorial medicine, but not rifampicin alone, enhanced the levels of brain-derived neurotrophic factor (BDNF) and its precursor, pro-BDNF, in the hippocampus. Furthermore, the combination showed a synergistic effect in ameliorating mouse cognition. These results show the advantages of this combinatorial medicine with regards to safety and effectiveness over single-drug rifampicin. Our findings may provide a feasible means for the prevention of neurodegenerative dementia that targets toxic oligomers.
Dynamic Functional Connectivity Better Predicts Disability Than Structural and Static Functional Connectivity in People With Multiple Sclerosis
Authors: Tozlu Ceren , Jamison Keith , Gauthier Susan A. , Kuceyeski Amy
Published: December 2021

Background:Advanced imaging techniques such as diffusion and functional MRI can be used to identify pathology-related changes to the brain's structural and functional connectivity (SC and FC) networks and mapping of these changes to disability and compensatory mechanisms in people with multiple sclerosis (pwMS). No study to date performed a comparison study to investigate which connectivity type (SC, static or dynamic FC) better distinguishes healthy controls (HC) from pwMS and/or classifies pwMS by disability status.

Aims:We aim to compare the performance of SC, static FC, and dynamic FC (dFC) in classifying (a) HC vs. pwMS and (b) pwMS who have no disability vs. with disability. The secondary objective of the study is to identify which brain regions' connectome measures contribute most to the classification tasks.

Materials and Methods:One hundred pwMS and 19 HC were included. Expanded Disability Status Scale (EDSS) was used to assess disability, where 67 pwMS who had EDSS<2 were considered as not having disability. Diffusion and resting-state functional MRI were used to compute the SC and FC matrices, respectively. Logistic regression with ridge regularization was performed, where the models included demographics/clinical information and either pairwise entries or regional summaries from one of the following matrices: SC, FC, and dFC. The performance of the models was assessed using the area under the receiver operating curve (AUC).

Results:In classifying HC vs. pwMS, the regional SC model significantly outperformed others with a median AUC of 0.89 (p<0.05). In classifying pwMS by disability status, the regional dFC and dFC metrics models significantly outperformed others with a median AUC of 0.65 and 0.61 (p< 0.05). Regional SC in the dorsal attention, subcortical and cerebellar networks were the most important variables in the HC vs. pwMS classification task. Increased regional dFC in dorsal attention and visual networks and decreased regional dFC in frontoparietal and cerebellar networks in certain dFC states was associated with being in the group of pwMS with evidence of disability.

Discussion:Damage to SCs is a hallmark of MS and, unsurprisingly, the most accurate connectomic measure in classifying patients and controls. On the other hand, dynamic FC metrics were most important for determining disability level in pwMS, and could represent functional compensation in response to white matter pathology in pwMS.
Sleep in Habitual Adult Video Gamers: A Systematic Review
Authors: Kemp Chadley , Pienaar Paula R. , Rosslee Dominique T. , Lipinska Gosia , Roden Laura C. , Rae Dale E.
Published: December 2021

Video gaming is a popular, globally recognized phenomenon, played recreationally or competitively as esports. Gaming is a typically sedentary nighttime activity; therefore, the potential to impact sleep and health is high. Furthermore, there are limited studies on adult gamers, who represent the majority demographic in esports. This review examines evidence describing sleep in habitual adult gamers to understand the associated risk for cardiometabolic disease or the benefits to gaming performance. Three electronic databases (PubMed, Scopus, ISI Web of Science) were searched for peer-reviewed articles published between January 2000 – April 2020. Twelve studies reporting on sleep in habitual adult gamers were included. A narrative synthesis was employed to report results, owing to high levels of heterogeneity across the included studies. Gamers with higher gaming addiction scores were more likely to have shorter, poorer quality sleep and greater daytime sleepiness and insomnia scores than gamers with lower gaming addiction scores and non-gamers. In addition, high-volume gamers were more likely to have worsened sleep quantity and quality, with delayed sleep timing and increased prevalence of insomnia. Despite limitations in the design of the included studies, excessive gaming is broadly associated with worsened sleep parameters. Noteworthy is the lack of studies investigating cardiometabolic health in gamers. Future work should explore the relative contribution and associated risk that various games, genres, and timing of gaming activities have on sleep, physical and mental health, particularly in vulnerable gaming cohorts engaged with contemporary forms of gaming and esports.
Anti-inflammatory Effects of GTE in Eye Diseases
Authors: Li Jian , Du Lin , He Jing Na , Chu Kai On , Guo Cosmos Liutao , Wong Mandy Oi Man , Pang Chi Pui , Chu Wai Kit
Published: December 2021

Ocular inflammation is a common complication of various eye diseases with wide consequences from irritations to potentially sight-threatening complications. Green tea is a popular beverage throughout the world. One of the proven health benefits of consuming green tea extract (GTE) is anti-inflammation. Catechins are the biologically active constituents of GTE. Inin vitroandin vivostudies, GTE and catechins present inhibition of inflammatory responses in the development of ocular inflammation including infectious, non-infectious or autoimmune, and oxidative-induced complications. Research on the ocular inflammation in animal models has made significant progress in the past decades and several key disease mechanisms have been identified. Here we review the experimental investigations on the effects of GTE and catechins on various ocular inflammation related diseases including glaucoma, age-related macular degeneration, uveitis and ocular surface inflammation. We also review the pharmacokinetics of GTE constituents and safety of green tea consumption. We discuss the insights and perspectives of these experimental results, which would be useful for future development of novel therapeutics in human.
Immunotherapy in Ovarian Cancer: Thinking Beyond PD-1/PD-L1
Authors: Chardin Laure , Leary Alexandra
Published: December 2021

Ovarian cancer (OC) is the most lethal gynecologic malignancy, affecting approximately 1 in 70 women with only 45% surviving 5 years after diagnosis. This disease typically presents at an advanced stage, and optimal debulking with platinum-based chemotherapy remains the cornerstone of management. Although most ovarian cancer patients will respond effectively to current management, 70% of them will eventually develop recurrence and novel therapeutic strategies are needed. There is a rationale for immune-oncological treatments (IO) in the managements of patients with OC. Many OC tumors demonstrate tumor infiltrating lymphocytes (TILs) and the degree of TIL infiltration is strongly and reproducibly correlated with survival. Unfortunately, results to date have been disappointing in relapsed OC. Trials have reported very modest single activity with various antibodies targeting PD-1 or PD-L1 resulting in response rate ranging from 4% to 15%. This may be due to the highly immunosuppressive TME of the disease, a low tumor mutational burden and low PD-L1 expression. There is an urgent need to improve our understanding of the immune microenvironment in OC in order to develop effective therapies. This review will discuss immune subpopulations in OC microenvironment, current immunotherapy modalities targeting these immune subsets and data from clinical trials testing IO treatments in OC and its combination with other therapeutic agents.
Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats
Authors: Tepes Marijan , Gojkovic Slaven , Krezic Ivan , Zizek Helena , Vranes Hrvoje , Madzar Zrinko , Santak Goran , Batelja Lovorka , Milavic Marija , Sikiric Suncana , Kocman Ivica , Simonji Karol , Samara Mariam , Knezevic Mario , Barisic Ivan , Lovric Eva , Strbe Sanja , Kokot Antonio , Sjekavica Ivica , Kolak Toni , Skrtic Anita , Seiwerth Sven , Boban Blagaic Alenka , Sikiric Predrag
Published: December 2021

Recently, the stable gastric pentadecapeptide BPC 157 was shown to counteract major vessel occlusion syndromes, i.e., peripheral and/or central occlusion, while activating particular collateral pathways. We induced abdominal compartment syndrome (intra-abdominal pressure in thiopental-anesthetized rats at 25 mmHg (60 min), 30 mmHg (30 min), 40 mmHg (30 min), and 50 mmHg (15 min) and in esketamine-anesthetized rats (25 mmHg for 120 min)) as a model of multiple occlusion syndrome. By improving the function of the venous system with BPC 157, we reversed the chain of harmful events. Rats with intra-abdominal hypertension (grade III, grade IV) received BPC 157 (10 µg or 10 ng/kg sc) or saline (5 ml) after 10 min. BPC 157 administration recovered the azygos vein via the inferior–superior caval vein rescue pathway. Additionally, intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were reduced, as were the grossly congested stomach and major hemorrhagic lesions, brain swelling, venous and arterial thrombosis, congested inferior caval and superior mesenteric veins, and collapsed azygos vein; thus, the failed collateral pathway was fully recovered. Severe ECG disturbances (i.e., severe bradycardia and ST-elevation until asystole) were also reversed. Microscopically, transmural hyperemia of the gastrointestinal tract, intestinal mucosa villi reduction, crypt reduction with focal denudation of superficial epithelia, and large bowel dilatation were all inhibited. In the liver, BPC 157 reduced congestion and severe sinusoid enlargement. In the lung, a normal presentation was observed, with no alveolar membrane focal thickening and no lung congestion or edema, and severe intra-alveolar hemorrhage was absent. Moreover, severe heart congestion, subendocardial infarction, renal hemorrhage, brain edema, hemorrhage, and neural damage were prevented. In conclusion, BPC 157 cured primary abdominal compartment syndrome.
Real-World Management and Clinical Outcomes of Stroke Survivors With Atrial Fibrillation: A Population-Based Cohort in Spain
Authors: Rodríguez-Bernal Clara L. , Sanchez-Saez Francisco , Bejarano-Quisoboni Daniel , Riera-Arnau Judit , Sanfélix-Gimeno Gabriel , Hurtado Isabel
Published: December 2021

Objective: Despite the continuous update of clinical guidelines, little is known about the real-world management of patients with atrial fibrillation (AF) who survived a stroke. We aimed to assess patterns of therapeutic management of stroke survivors with AF and clinical outcomes using data from routine practice in a large population-based cohort.

Methods: A population-based retrospective cohort study of all patients with AF who survived a stroke, from January 2010 to December 2017 in the Valencia region, Spain (n = 10,986), was carried out. Treatment strategies and mean time to treatment initiation are described. Temporal trends are shown by the management pattern during the study period. Factors associated with each pattern (including no treatment) vs. oral anticoagulant (OAC) treatment were identified using logistic multivariate regression models. Incidence rates of clinical outcomes (mortality, stroke/TIA, GI bleeding, and ACS) were also estimated by the management pattern.

Results: Among stroke survivors with AF, 6% were non-treated, 23% were prescribed antiplatelets (APT), 54% were prescribed OAC, and 17% received OAC + APT at discharge. Time to treatment was 8.0 days (CI 7.6–8.4) for APT, 9.86 (CI 9.52–10.19) for OAC, and 16.47 (CI 15.86–17.09) for OAC + APT. Regarding temporal trends, management with OAC increased by 20%, with a decrease of 50% for APT during the study period. No treatment and OAC + APT remained relatively stable. The strongest predictor of no treatment and APT treatment was having the same management strategy pre-stroke. Those treated with APT had the highest rates of GI bleeding and recurrent stroke/TIA, and untreated patients showed the highest rates of mortality.

Conclusion: In this large population-based cohort using real-world data, nearly 30% of AF patients who suffered a stroke were untreated or treated with APT, which overall is not recommended. Treatment was started within 2 weeks as recommended, except for OAC + APT, which was started later. The strong association of APT treatment or non-treatment with the same treatment strategy before stroke occurrence suggests a strong therapeutic inertia and opposes recommendations. Patients under these two strategies had the highest rates of adverse outcomes. An inadequate prescription poses a great risk on patients with AF and stroke; thus monitoring their management is necessary and should be setting-specific.
Self-Conscious Affect Is Modulated by Rapid Eye Movement Sleep but Not by Targeted Memory Reactivation–A Pilot Study
Authors: Halonen Risto , Kuula Liisa , Makkonen Tommi , Kauramäki Jaakko , Pesonen Anu-Katriina
Published: December 2021

The neurophysiological properties of rapid eye movement sleep (REMS) are believed to tune down stressor-related emotional responses. While prior experimental findings are controversial, evidence suggests that affective habituation is hindered if REMS is fragmented. To elucidate the topic, we evoked self-conscious negative affect in the participants (N = 32) by exposing them to their own out-of-tune singing in the evening. Affective response to the stressor was measured with skin conductance response and subjectively reported embarrassment. To address possible inter-individual variance toward the stressor, we measured the shame-proneness of participants with an established questionnaire. The stressor was paired with a sound cue to pilot a targeted memory reactivation (TMR) protocol during the subsequent night's sleep. The sample was divided into three conditions: control (no TMR), TMR during slow-wave sleep, and TMR during REMS. We found that pre- to post-sleep change in affective response was not influenced by TMR. However, REMS percentage was associated negatively with overnight skin conductance response habituation, especially in those individuals whose REMS was fragmented. Moreover, shame-proneness interacted with REM fragmentation such that the higher the shame-proneness, the more the affective habituation was dependent on non-fragmented REMS. In summary, the potential of REMS in affective processing may depend on the quality of REMS as well as on individual vulnerability toward the stressor type.
Design and Analysis of a Pitch Fatigue Detection System for Adaptive Baseball Learning
Authors: Ma Yi-Wei , Chen Jiann-Liang , Hsu Chia-Chi , Lai Ying-Hsun
Published: December 2021

Owing to the rapid development of information and communication technologies, such as the Internet of Things, artificial intelligence, and computer vision, in recent years, the concept of smart sports has been proposed. A pitch fatigue detection method that includes acquisition, analysis, quantification, aggregation, learning, and public layers for adaptive baseball learning is proposed herein. The learning determines the fatigue index of the pitcher based on the angle of the pitcher's elbow and back as the number of pitches increases. The coach uses this auxiliary information to avoid baseball injuries during baseball learning. Results show a test accuracy rate of 89.1%, indicating that the proposed method effectively provides reference information for adaptive baseball learning.
Smartphone Psychological Therapy During COVID-19: A Study on the Effectiveness of Five Popular Mental Health Apps for Anxiety and Depression
Authors: Marshall Jamie M. , Dunstan Debra A. , Bartik Warren
Published: December 2021

The aims of this study were to examine the effectiveness of a range of smartphone apps for managing symptoms of anxiety and depression and to assess the utility of a single-case research design for enhancing the evidence base for this mode of treatment delivery. The study was serendipitously impacted by the COVID-19 pandemic, which allowed for effectiveness to be additionally observed in the context of significant community distress. A pilot study was initially conducted using theSuperBetter app to evaluate the proposed methodology, which proved successful with the four finishing participants. In the main study, 39 participants commenced (27 females and 12 males,MAge = 34.04 years,SD = 12.20), with 29 finishing the intervention phase and completing post-intervention measures. At 6-month follow-up, a further three participants could not be contacted. This study used a digitally enhanced, multiple baseline across-individuals single-case research design. Participants were randomly assigned to the following apps:SuperBetter (n = 8),Smiling Mind (n = 7),MoodMission (n = 8),MindShift (n = 8), andDestressify (n = 8). Symptomatology and life functioning were measured at five different time points: pre-baseline/screening, baseline, intervention, 3-week post-intervention, and 6-month follow-up. Detailed individual perceptions and subjective ratings of the apps were also obtained from participants following the study’s completion. Data were analyzed using visual inspection, time-series analysis, and methods of statistical and clinical significance. Positive results were observed for all apps. Overall, more favorable outcomes were achieved by younger participants, those concurrently undertaking psychotherapy and/or psychotropic medication, those with anxiety and mixed anxiety and depression rather than stand-alone depression, and those with a shorter history of mental illness. Outcomes were generally maintained at 6-month follow-up. It was concluded that a diverse range of evidence-based therapies offered via apps can be effective in managing mental health and improving life functioning even during times of significant global unrest and, like all psychotherapies, are influenced by client features. Additionally, this single-case research design is a low-cost/high value means of assessing the effectiveness of mental health apps.

Clinical Trial Registration: The study is registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR), which is a primary registry in the World Health Organization Registry Network, registration number ACTRN12619001302145p (http://www.ANZCTR.org.au/ACTRN12619001302145p.aspx).
Reporting the Social Value Generated by European Universities for Stakeholders: Applicability of the Global Reporting Initiative Model
Authors: Gutiérrez-Goiria Jorge , Amiano-Bonatxea Iratxe , Sianes Antonio , Vázquez-De Francisco María José
Published: December 2021

Universities are increasingly being asked to contribute to addressing the significant local and global challenges, such as those identified in the 2030 Agenda. Set in this framework, universities need to account for the social value they generate through their activities, particularly from the perspective of their contribution to different stakeholders. This approach requires, first of all, that the main stakeholders are identified. Relationship and dialogue mechanisms then need to be established which can help guide universities to choose activities which can better meet the needs of their stakeholders. The current paper analyses the potential of integrated reports, and triple bottom line reports, as an instrument for reporting on aspects that go beyond the financial sphere, including economic, social and environmental aspects. Specifically, the paper focuses on studying the viability of the Global Reporting Initiative (GRI) for reporting the value that European universities generate for their stakeholders. The results show, firstly, that the universities in the sample do not sufficiently address these questions in their reports. Internal stakeholders are prominent in their reports, with the interaction between them and the universities being generally unidirectional. References to value generated are limited, and usually refer to the economic value. However, some examples of good practices are identified that could be used to improve standards of reporting, especially in universities committed to integrated reporting initiatives, in order to better reflect the social value.
1H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids?
Authors: Vilca-Melendez Sylvana , Uthaug Malin V. , Griffin Julian L.
Published: December 2021

While psychedelics may have therapeutic potential for treating mental health disorders such as depression, further research is needed to better understand their biological effects and mechanisms of action when considering the development of future novel therapy approaches. Psychedelic research could potentially benefit from the integration of metabonomics by proton nuclear magnetic resonance (1H NMR) spectroscopy which is an analytical chemistry-based approach that can measure the breakdown of drugs into their metabolites and their metabolic consequences from various biofluids. We have performed a systematic review with the primary aim of exploring published literature where 1H NMR analysed psychedelic substances including psilocin, lysergic acid diethylamide (LSD), LSD derivatives, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and bufotenin. The second aim was to assess the benefits and limitations of 1H NMR spectroscopy-based metabolomics as a tool in psychedelic research and the final aim was to explore potential future directions. We found that the most current use of 1H NMR in psychedelic research has been for the structural elucidation and analytical characterisation of psychedelic molecules and that no papers used 1H NMR in the metabolic profiling of biofluids, thus exposing a current research gap and the underuse of 1H NMR. The efficacy of 1H NMR spectroscopy was also compared to mass spectrometry, where both metabonomics techniques have previously shown to be appropriate for biofluid analysis in other applications. Additionally, potential future directions for psychedelic research were identified as real-time NMR, in vivo1H nuclear magnetic resonance spectroscopy (MRS) and 1H NMR studies of the gut microbiome. Further psychedelic studies need to be conducted that incorporate the use of 1H NMR spectroscopy in the analysis of metabolites both in the peripheral biofluids and in vivo to determine whether it will be an effective future approach for clinical and naturalistic research.
Depression Levels of State Functionaries: Empirical Evidence From China
Authors: He Li , Wang Kun , Zhang Zixian , Wang Jiangyin , Li Tianyang , Wang Yuting , Yang Lixingzi , Wu Yuanyang , Zhang Shuo , Zhang Siqing , Yang Hualei
Published: December 2021

This study aimed to explore the depression levels of those serving as state functionaries in China. We used data from the 2016 China Labor-force Dynamics Survey and the ordinary least squares model for the regression analysis. The results found: i) The degree of depression of state functionaries was found to be lower than that of other workers; that is, the overall depression index of state functionaries was 1.010 points lower, and the result was significant at the degree of 1%; ii) state functionaries had a lower degree of depression than workers in all other occupation groups; iii) older state functionaries had lower depression than their younger counterparts; iv) the degree of depression of state functionaries in the provinces involved in China's three major urban agglomerations was higher than that of those in other provinces; and v) the degree of depression of female state functionaries was lower than that their male peers. Thus, there is an association between serving as a state functionary in China and depression. State functionaries have lower levels of depression than other working groups. These levels were generally lower but varied according to age, sex, and province.
The Mediating Role of Depressive Symptoms, Hopelessness, and Perceived Burden on the Association Between Pain Intensity and Late-Life Suicide in Rural China: A Case–Control Psychological Autopsy Study
Authors: Wang Jiali , Xu Jiahuan , Ma Zhenyu , Jia Cunxian , Wang Guojun , Zhou Liang
Published: December 2021

Background: Few studies have investigated the roles of psychosocial factors such as depressive symptoms and hopelessness on the relationship between pain and suicide with inconsistent results. The study aimed to analyze the impact of pain intensity on suicide death and to estimate the degree to which depressive symptoms, hopelessness, and perceived burden may explain the association in Chinese rural elderly.

Methods: Using a 1:1 matched case–control design, we collected data from 242 elderly suicide cases and 242 living community controls by psychological autopsy method in rural China, including sociodemographic characteristics, pain intensity, depression, hopelessness, perceived burden, physical diseases, and social support. Conditional logistic regression was employed to assess the association between pain intensity and completed suicide. Mediation analysis using the KHB method was applied to explore the mediation effects from depressive symptoms, hopelessness, and perceived burden.

Results: The result of multivariable logistic regression showed that unemployment [odds ratio (OR) = 5.06, 95% confidence interval (CI): 1.76–14.49], higher levels of hopelessness (OR = 7.72, 95% CI: 3.49–17.10), depressive symptom (OR = 15.82, 95% CI: 4.53–55.25), and severe pain (OR = 3.46, 95% CI: 1.31–9.13) were significantly associated with elevated suicide risk in older adults in rural China. Depressive symptoms, hopelessness, and perceived burden significantly mediated 43.71% of the pain–suicide association (p = 0.020), with 17.39% due to depressive symptoms, 17.63% due to hopelessness, and 8.69% due to perceived burden.

Conclusions: Regular screening of pain, depressive symptoms, hopelessness, and perceived burden using simple but sensitive questions or scales for older adults with pain is vital for the prevention and early detection of suicide risk in Chinese rural areas. Moreover, the importance of pain management and psychological interventions targeted on depressive symptoms and hopelessness should be emphasized.
Monitoring Weeder Robots and Anticipating Their Functioning by Using Advanced Topological Data Analysis
Authors: Frahi Tarek , Sancarlos Abel , Galle Mathieu , Beaulieu Xavier , Chambard Anne , Falco Antonio , Cueto Elias , Chinesta Francisco
Published: December 2021

The present paper aims at analyzing the topological content of the complex trajectories that weeder-autonomous robots follow in operation. We will prove that the topological descriptors of these trajectories are affected by the robot environment as well as by the robot state, with respect to maintenance operations. Most of existing methodologies enabling efficient diagnosis are based on the data analysis, and in particular on some statistical quantities derived from the data. The present work explores the use of an original approach that instead of analyzing quantities derived from the data, analyzes the “shape” of the data, that is, the time series topology based on the homology persistence. We will prove that this procedure is able to extract valuable patterns able to discriminate the trajectories that the robot follows depending on the particular patch in which it operates, as well as to differentiate the robot behavior before and after undergoing a maintenance operation. Even if it is a preliminary work, and it does not pretend to compare its performances with respect to other existing technologies, this work opens new perspectives in considering quite natural and simple descriptors based on the intrinsic information that data contains, with the aim of performing efficient diagnosis and prognosis.
Radiolabeling of Nanomaterials: Advantages and Challenges
Authors: Dai Wanqin , Zhang Junzhe , Wang Yun , Jiao Chunlei , Song Zhuda , Ma Yuhui , Ding Yayun , Zhang Zhiyong , He Xiao
Published: December 2021

Quantifying the distribution of nanomaterials in complex samples is of great significance to the toxicological research of nanomaterials as well as their clinical applications. Radiotracer technology is a powerful tool for biological and environmental tracing of nanomaterials because it has the advantages of high sensitivity and high reliability, and can be matched with some spatially resolved technologies for non-invasive, real-time detection. However, the radiolabeling operation of nanomaterials is relatively complicated, and fundamental studies on how to optimize the experimental procedures for the best radiolabeling of nanomaterials are still needed. This minireview looks back into the methods of radiolabeling of nanomaterials in previous work, and highlights the superiority of the “last-step” labeling strategy. At the same time, the problems existing in the stability test of radiolabeling and the suggestions for further improvement are also addressed.
Detection and Genetic Characterization of Seoul Virus in Liver Tissue Samples From Rattus norvegicus and Rattus tanezumi in Urban Areas of Southern China
Authors: He Wenqiao , Fu Jiaqi , Wen Yuqi , Cheng Mingji , Mo Yun , Chen Qing
Published: December 2021

Rodents are important hosts of hantaviruses, and lungs and kidneys are known to be the preferred organs of these viruses. Recently, hantaviruses were detected in liver samples from wild rodents in Hungary and the United States, and feeder rats in the Netherlands. However, few studies have detected hantaviruses in the liver of rats from China. In this study, hantaviruses were investigated in liver samples from R. norvegicus and R. tanezumi trapped in urban areas of southern China. A total of 461 R. norvegicus and 64 R. tanezumi were trapped. Using a pan-hantavirus PCR method, hantaviruses were detected in liver, lung, and serum samples from these animals. About 7.43% of liver samples were positive for Seoul virus (SEOV). The detection rate of SEOV in liver samples from R. norvegicus (8.24%) was higher than that from R. tanezumi (1.56%), suggesting the predominant role of R. norvegicus in the transmission of SEOV in urban areas of China. Three R. norvegicus had SEOV RNA in their liver samples but not in their lung samples, suggesting that the liver might be one of the targeted organs of SEOV. The first full SEOV protein-coding sequences (CDS) of the S and M segments, and partial CDS of the L segment from R. tanezumi were amplified. Several full and partial CDS of the S, M, and L segments from R. norvegicus were also obtained. The SEOV sequences obtained from different animals were highly similar, suggesting the cross-species transmission potential of SEOV between R. norvegicus and R. tanezumi.
A Temporal Network Model for Livestock Trade Systems
Authors: Ansari Sara , Heitzig Jobst , Brzoska Laura , Lentz Hartmut H. K. , Mihatsch Jakob , Fritzemeier Jörg , Moosavi Mohammad R.
Published: December 2021

The movements of animals between farms and other livestock holdings for trading activities form a complex livestock trade network. These movements play an important role in the spread of infectious diseases among premises. For studying the disease spreading among animal holdings, it is of great importance to understand the structure and dynamics of the trade system. In this paper, we propose a temporal network model for animal trade systems. Furthermore, a novel measure of node centrality important for disease spreading is introduced. The experimental results show that the model can reasonably well describe these spreading-related properties of the network and it can generate crucial data for research in the field of the livestock trade system.
Molecular and Immunohistochemical Expression of LTA4H and FXR1 in Canine Oral Melanoma
Authors: Nordio Laura , Bazzocchi Chiara , Genova Francesca , Serra Valentina , Longeri Maria , Franzo Giovanni , Rondena Marco , Stefanello Damiano , Giudice Chiara
Published: December 2021

Oral melanoma is a common canine tumor whose prognosis is considered ominous, but poorly predicted by histology alone. In the present study the gene and protein expression of Leukotriene A4 hydrolase (LTA4H) and Fragile-X-mental retardation-related protein1 (FXR1), both reported as related to metastatic potential in different tumors, were investigated in canine oral melanoma. The main aim of the study was to confirm and quantify the presence of LTA4H and FXR1 genes and protein in oral melanomas. A secondary aim was to investigate their association with histologic prognostic criteria (mitotic count, Ki-67 index). Formalin-fixed-paraffin-embedded canine oral melanomas (36) were collected and histopathological evaluation carried out. Immunolabelling for LTA4H and FXR1 and Ki-67 were performed. RT-PCR evaluated LTA4H and FXR1 gene expressions. Histologically, most tumors were epithelioid cell melanomas (19/36) and were amelanotic, mildly or moderately pigmented (5, 12 and 13/36 respectively), only 6 were highly pigmented. Mitotic count ranged 1-106, Ki-67 index ranged 4.5–52.3. Thirty-two (32/32) melanomas immunolabelled for LTA4H and 33/34 for FXR1. RT-PCR values ranged 0.76–5.11 ΔCt for LTA4H and 0.22–6.24 ΔCt for FXR1. Molecular and immunohistochemical expression of both LTA4H and FXR1 did not statically correlate with mitotic count or Ki-67 index. The present study demonstrates LTA4H and FXR1 gene and protein in canine oral melanoma, however their expression is apparently unrelated to histopathologic prognostic criteria. Although LTA4H and FXR1 seem unrelated to tumor behavior, their extensive expression in the present cohort of cases suggest that they may play a role in canine oral melanoma oncogenesis.
The Genetics of Thermoregulation in Pigs: A Review
Authors: Gourdine Jean-Luc , Rauw Wendy Mercedes , Gilbert Hélène , Poullet Nausicaa
Published: December 2021

Heat stress (HS) affects pig performance, health and welfare, resulting in a financial burden to the pig industry. Pigs have a limited number of functional sweat glands and their thermoregulatory mechanisms used to maintain body temperature, are challenged by HS to maintain body temperature. The genetic selection of genotypes tolerant to HS is a promising long-term (adaptation) option that could be combined with other measures at the production system level. This review summarizes the current knowledge on the genetics of thermoregulation in pigs. It also discusses the different phenotypes that can be used in genetic studies, as well as the variability in thermoregulation between pig breeds and the inheritance of traits related to thermoregulation. This review also considers on-going challenges to face for improving heat tolerance in pigs.
What Determines the Parameters of a Propagating Streamer: A Comparison of Outputs of the Streamer Parameter Model and of Hydrodynamic Simulations
Authors: Lehtinen Nikolai G. , Marskar Robert
Published: December 2021

Electric streamer discharges (streamers) in the air are a very important stage of lightning, taking place before formation of the leader discharge, and with which an electric discharge starts from conducting objects which enhance the background electric field, such as airplanes. Despite years of research, it is still not well understood what mechanism determines the values of a streamer’s parameters, such as its radius and propagation velocity. The novel Streamer Parameter Model (SPM) was made to explain this mechanism, and to provide a way to efficiently calculate streamer parameters. Previously, we demonstrated that SPM results compared well with a limited set of experimental data. In this article, we compare SPM predictions to the published hydrodynamic simulation (HDS) results.
Prolonged Exposure to Air Pollution Increases Periodontal Disease Risk: A Nationwide, Population-Based, Cohort Study
Authors: Lin Han-Jie , Tsai Stella Chin-Shaw , Lin Frank Cheau-Feng , Hsu Yi-Chao , Chen Shih-Wei , Chou Ruey-Hwang , Lin Cheng-Li , Hsu Chung Y. , Chang Kuang-Hsi
Published: December 2021

(1) Background: No association between air pollution and periodontitis has yet been shown. Thus, we merged two nationwide databases to evaluate the risk of periodontitis in Taiwanese residents with long-term exposure to air pollution. (2) Methods: We conducted a nationwide retrospective cohort study using the Longitudinal Generation Tracking Database and the Taiwan Air Quality-Monitoring Database. The daily average air pollutant concentrations were categorized into quartiles (Q1, Q2, Q3, and Q4). We carried out Cox proportional hazards models to compute the hazard ratios of periodontitis, with 95% confidence intervals, in Q2–Q4 of the daily average air pollutant concentrations, compared with Q1. (3) Results: the adjusted HR (95 CI%) for periodontitis in Q2–Q4 increased with increased exposure to SO2, CO, NO, NO2, NOX, PM2.5, and PM10 from 1.72 (1.70, 1.76) to 4.86 (4.78–4.94); from 1.89 (1.85–1.93) to 2.64 (2.59–2.70); from 1.04 (1.02–1.06) to 1.52 (1.49–1.55); from 1.61 (1.58–1.64) to 2.51 (2.47–2.56); from 1.48 (1.45–1.51) to 2.11 (2.07–2.15); from 2.02 (1.98–2.06) to 22.9 (22.4–23.4, and from 2.71 (2.66–2.77) to 17.2 (16.8–17.6), respectively, compared to Q1. (4) Conclusions: Residents in Taiwan with long-term exposure to higher levels of air pollutants had a greater risk of periodontitis.