bluuebunny/crossref_metadata_2025 huggingface dataset:
Face Perception and Pareidolia Production in Patients With Parkinson's Disease
Authors: Göbel Nicole , Möller Jens Carsten , Hollenstein Nathalie , Binder Andreas , Oechsner Matthias , Ide Jörg , Urwyler Prabitha , Cazzoli Dario , Müri René M.
Published: August 2021

In Parkinson's disease (PD) patients, visual misperceptions are a major problem within the non-motor symptoms. Pareidolia, i.e., the tendency to perceive a specific, meaningful image in an ambiguous visual pattern, is a phenomenon that occurs also in healthy subjects. Literature suggests that the perception of face pareidolia may be increased in patients with neurodegenerative diseases. We aimed to examine, within the same experiment, face perception and the production of face pareidolia in PD patients and healthy controls (HC). Thirty participants (15 PD patients and 15 HC) were presented with 47 naturalistic photographs in which faces were embedded or not. The likelihood to perceive the embedded faces was modified by manipulating their transparency. Participants were asked to decide for each photograph whether a face was embedded or not. We found that PD patients were significantly less likely to recognize embedded faces than controls. However, PD patients also perceived faces significantly more often in locations where none were actually present than controls. Linear regression analyses showed that gender, age, hallucinations, and Multiple-Choice Vocabulary Intelligence Test (MWT) score were significant predictors of face pareidolia production in PD patients. Montreal Cognitive Assessment (MoCA) was a significant predictor for pareidolia production in PD patients in trials in which a face was embedded in another region [F(1, 13) = 24.4, p = <0.001]. We conclude that our new embedded faces paradigm is a useful tool to distinguish face perception performance between HC and PD patients. Furthermore, we speculate that our results observed in PD patients rely on disturbed interactions between the Dorsal (DAN) and Ventral Attention Networks (VAN). In photographs in which a face is present, the VAN may detect this as a behaviourally relevant stimulus. However, due to the deficient communication with the DAN in PD patients, the DAN would not direct attention to the correct location, identifying a face at a location where actually none is present.
Pretreatment Source Location and Functional Connectivity Network Correlated With Therapy Response in Childhood Absence Epilepsy: A Magnetoencephalography Study
Authors: Zhang Ke , Sun Jintao , Sun Yulei , Niu Kai , Wang Pengfei , Wu Caiyun , Chen Qiqi , Wang Xiaoshan
Published: August 2021

Objective: This study aims to investigate the differences between antiepileptic drug (AED) responders and nonresponders among patients with childhood absence epilepsy (CAE) using magnetoencephalography (MEG) and to additionally evaluate whether the neuromagnetic signals of the brain neurons were correlated with the response to therapy.

Methods: Twenty-four drug-naïve patients were subjected to MEG under six frequency bandwidths during ictal periods. The source location and functional connectivity were analyzed using accumulated source imaging and correlation analysis, respectively. All patients were treated with appropriate AED, at least 1 year after their MEG recordings, their outcome was assessed, and they were consequently divided into responders and nonresponders.

Results: The source location of the nonresponders was mainly in the frontal cortex at a frequency range of 8–12 and 30–80 Hz, especially 8–12 Hz, while the source location of the nonresponders was mostly in the medial frontal cortex, which was chosen as the region of interest. The nonresponders showed strong positive local frontal connections and deficient anterior and posterior connections at 80–250 Hz.

Conclusion: The frontal cortex and especially the medial frontal cortex at α band might be relevant to AED-nonresponsive CAE patients. The local frontal positive epileptic network at 80–250 Hz in our study might further reveal underlying cerebral abnormalities even before treatment in CAE patients, which could cause them to be nonresponsive to AED. One single mechanism cannot explain AED resistance; the nonresponders may represent a subgroup of CAE who is refractory to several antiepileptic drugs.
Emerging Role of Carotid MRI for Personalized Ischemic Stroke Risk Prediction in Patients With Carotid Artery Stenosis
Authors: Nies Kelly P. H. , Smits Luc J. M. , Kassem Mohamed , Nederkoorn Paul J. , Oostenbrugge Robert J. van , Kooi M. Eline
Published: August 2021

Rupture of a vulnerable carotid plaque is an important cause of ischemic stroke. Prediction models can support medical decision-making by estimating individual probabilities of future events, while magnetic resonance imaging (MRI) can provide detailed information on plaque vulnerability. In this review, prediction models for medium to long-term (>90 days) prediction of recurrent ischemic stroke among patients on best medical treatment for carotid stenosis are evaluated, and the emerging role of MRI of the carotid plaque for personalized ischemic stroke prediction is discussed. A systematic search identified two models; the European Carotid Surgery Trial (ECST) medical model, and the Symptomatic Carotid Atheroma Inflammation Lumen stenosis (SCAIL) score. We critically appraised these models by means of criteria derived from the CHARMS (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies) and PROBAST (Prediction model Risk Of Bias ASsessment Tool). We found both models to be at high risk of bias. The ECST model, the most widely used model, was derived from data of large but relatively old trials (1980s and 1990s), not reflecting lower risks of ischemic stroke resulting from improvements in drug treatment (e.g., statins and anti-platelet therapy). The SCAIL model, based on the degree of stenosis and positron emission tomography/computed tomography (PET/CT)-based plaque inflammation, was derived and externally validated in limited samples. Clinical implementation of the SCAIL model can be challenging due to high costs and low accessibility of PET/CT. MRI is a more readily available, lower-cost modality that has been extensively validated to visualize all the hallmarks of plaque vulnerability. The MRI methods to identify the different plaque features are described. Intraplaque hemorrhage (IPH), a lipid-rich necrotic core (LRNC), and a thin or ruptured fibrous cap (TRFC) on MRI have shown to strongly predict stroke in meta-analyses. To improve personalized risk prediction, carotid plaque features should be included in prediction models. Prediction of stroke in patients with carotid stenosis needs modernization, and carotid MRI has potential in providing strong predictors for that goal.
Evaluation of a Case Management to Support Families With Children Diagnosed With Spinal Muscular Atrophy—Protocol of a Controlled Mixed-Methods Study
Authors: Willems Jana , Farin-Glattacker Erik , Langer Thorsten
Published: August 2021

Background: Spinal muscular atrophy (SMA) is a rare neuromuscular disease characterized by degeneration of the anterior horn cells in the spinal cord, resulting in muscle atrophy, and proximal muscle weakness. SMA presents with a wide range of symptoms requiring multiple clinical specialists and therapists. Integrating care between disciplines can be challenging due to the dynamic course of the disease, and great distances between specialist centers and local providers. Insufficient care integration can lead to suboptimal quality of care and more difficulties for patients and families. This study aims to improve care integration through a Case Management intervention, and taking a mixed-methods approach, to evaluate its impact.

Methods: An exploratory, controlled, two-armed study with baseline, post- and follow-up measurement and process evaluation is conducted to evaluate our intervention compared to usual care. Through a multi-perspective state analysis, we investigate the experiences of caregivers and healthcare providers concerning the actual healthcare quality of patients with SMA I and II. Semi-structured interviews and care diaries are used. We apply that data to conceive a tailored Case Management intervention supplemented by a digital platform. The intervention's effect is examined in comparison to a control group taking a mixed-methods approach. As primary endpoints, we investigate the caregivers' health-related quality of life and the quality of care integration. Secondary endpoints are the use of healthcare services (patients and caregivers) and costs. We assess the process quality from the perspectives of caregivers and healthcare providers through semi-structured interviews.

Discussion: This is an exploratory, controlled study to assess the impact of a tailored Case Management intervention to improve the care of patients with SMA I and II. After the evaluation, results on feasibility, expected effect sizes, and process quality will be available. On this basis, future randomized controlled trials can be planned. If demonstrated beneficial, the experience gained within this study may also be valuable for care strategies in other regions and other (non-pediatric) patient groups with rare diseases and/or chronic, complex conditions.

Clinical Trial registration:https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018778, identifier: DRKS00018778.
X-Linked Lymphoproliferative Disease Mimicking Multisystem Inflammatory Syndrome in Children—A Case Report
Authors: Prader Seraina , Ritz Nicole , Baleydier Frédéric , Andre Maya C. , Stähli Noémie , Schmid Kevin , Schmid Hanna , Woerner Andreas , Diesch Tamara , Meyer Sauteur Patrick M. , Trück Johannes , Gebistorf Fabienne , Opitz Lennart , Killian Michael P. , Marchetti Tommaso , Vavassori Stefano , Blanchard-Rohner Géraldine , Mc Lin Valerie , Grazioli Serge , Pachlopnik Schmid Jana
Published: August 2021

Most children with a SARS-CoV-2 infection are asymptomatic or exhibit mild symptoms. However, a small number of children develop features of substantial inflammation temporarily related to the COVID-19 also called multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), clinically similar to Kawasaki disease, toxic shock syndrome and hemophagocytic lymphohistiocytosis (HLH). It is well-known that genetic pre-disposition plays an important role in virally-triggered diseases such as Epstein-Barr virus (EBV)-associated HLH, while this has not yet been established for patients with MIS-C. Here we describe a male patient fulfilling the diagnostic criteria of MIS-C, who was initially treated according to current consensus guidelines. Presence of hypofibrinogenemia, normal lymphocyte counts and C-reactive protein, but substantial hyperferritinemia distinguish this patient from others with MIS-C. The clinical course following initial presentation with acute respiratory distress syndrome was marked by fatal liver failure in the context of EBV-associated HLH despite treatment with steroids, intravenous immunoglobulins, interleukin (IL)-1 receptor blockade and eventually HLH-directed treatment. X-linked lymphoproliferative disease type 1 (XLP1), a subtype of primary HLH was diagnosed in this patient post-mortem. This case report highlights the importance of including HLH in the differential diagnosis in MIS-C with severe disease course to allow specific, risk-adapted treatment and genetic counseling.
Effectiveness of Drug Treatments for Lowering Uric Acid on Renal Function in Patients With Chronic Kidney Disease and Hyperuricemia: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Liu Xiang , Qiu Yuxuan , Li Duohui , Tan Jiaxing , Liang Xiuping , Qin Wei
Published: August 2021

Background: Hyperuricemia is very common in patients with chronic kidney disease (CKD); the role of hyperuricemia in the occurrence and progression of kidney disease remains an interesting and unresolved issue for nephrologists, and whether urate-lowering therapy (ULT) is warranted in CKD patients is still in controversy. To summarize and compare the clinical outcomes and adverse events (AEs) of three common ULT drugs, we performed a systematic review and network meta-analysis of randomized clinical trials (RCTs).

Method: PubMed, MEDLINE, Clinical Trials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials electronic databases were searched. The network meta-analysis was performed using the “gemtc 0.8-7” and its dependent packages in R software. The primary outcome was the change of renal function and uric acid; creatinine, proteinuria, blood pressure, and adverse events were assessed as the secondary outcomes.

Results: 16 RCTs involving 1,943 patients were included in the final network analysis. Febuxostat, allopurinol, and benzbromarone were not found to exert superior effects over placebo upon renoprotective effect. With respect to lowering urate, the three drugs showed to be statistically superior to placebo, while febuxostat could better lower urate than allopurinol (MD: −1.547; 95% CrI: −2.473 to −0.626). It is also indicated that febuxostat was superior to placebo at controlling blood pressure, while no differences were observed when allopurinol and benzbromarone were compared to placebo. These results are stable in subgroup analysis.

Conclusion: There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia; febuxostat shows a tendency to be superior to allopurinol on lowering the decline of eGFR and increment of proteinturia, but the difference does not reach a statistical significance. Regarding its urate-lowering effect, febuxostat appears to be a satisfactory alternative to allopurinol and benzbromarone, and can control blood pressure better.
Bivalirudin Attenuates Thrombin-Induced Endothelial Hyperpermeability via S1P/S1PR2 Category: Original Articles
Authors: Ye Haowen , Zhang Yizhi , Huang Yihui , Li Biao , Cao Ruhao , Dai Libing , Huang Bin , Tian Pingge , Li Li , Han Yaling
Published: August 2021

Aims: To explore the role of the Sphingosine 1-Phosphate (S1P)/Receptor2 (S1PR2) pathway in thrombin-induced hyperpermeability (TIP) and to test whether bivalirudin can reverse TIP via the S1P-S1PRs pathway.

Methods and Results: Using western blot, we demonstrated that Human umbilical vein endothelial cells (HUVECs) that were cultured with 2 U/ml thrombin showed significantly increased S1PR2 expression while S1PR1and three kept unchanged. Such increment was attenuated by JTE-013 pretreatment and by presence of bivalirudin. Exposure of 2 U/ml of thrombin brought a higher level of S1P both intracellularly and extracellularly within the HUVECs by using ELISA detecting. Thrombin induced S1P and S1PR2 increment was restored by usage of PF543 and bivalirudin. Bivalirudin alone did not influenced the level of S1P and S1PR1,2, and S1PR3 compare to control group. As a surrogate of cytoskeleton morphology, phalloidin staining and immunofluorescence imaging were used. Blurry cell edges and intercellular vacuoles or spaces were observed along thrombin-exposed HUVECs. Presence of JTE-013 and bivalirudin attenuated such thrombin-induced permeability morphological change and presence of heparin failed to show the protective effect. Transwell chamber assay and probe assay were used to measure and compare endothelial permeability in vitro. An increased TIP was observed in HUVECs cultured with thrombin, and coculture with bivalirudin, but not heparin, alleviated this increase. JTE-013 treatment yielded to similar TIP alleviating effect. In vivo, an Evans blue assay was used to test subcutaneous and organ microvascular permeability after the treatment of saline only, thrombin + saline, thrombin + bivalirudin, thrombin + heparin or thrombin + JTE-013. Increased subcutaneous and organ tissue permeability after thrombin treatment was observed in thrombin + saline and thrombin + heparin groups while treatment of bivalirudin and JTE-013 absent this effect.

Conclusion: S1P/S1PR2 mediates TIP by impairing vascular endothelial barrier function. Unlike heparin, bivalirudin effectively blocked TIP by inhibiting the thrombin-induced S1P increment and S1PR2 expression, suggesting the novel endothelial protective effect of bivalirudin under pathological procoagulant circumstance.
Rarely Recognized Antibody Diversification in Covid-19 Evolution to Counteract Advanced SARS-CoV-2 Evasion Strategies, and Implications for Prophylactic Treatment
Authors: Mueller Siguna
Published: August 2021

The ongoing Covid-19 pandemic underscores the importance of finding effective and safe ways to combat the virus, and to optimally understand the immune response elicited upon natural infection. This likely involves all components of the immune system, both innate and adaptive. The impetus for the rapid development of prophylactic treatment options has led to an intense focus on neutralizing antibodies (Abs), and many novel and specialized platforms have been designed to achieve that goal. B-cell immunity relies on the generation of a diverse repertoire of Abs. Their structural variation is defined in terms of amino acid composition that is encoded in the genome or acquired through somatic mutations. Yet, key examples of frequently neglected antibody diversification mechanisms involving post-translational modifications such as N- or O-linked glycosylation are present in significant portions of the population. During the last few years, these and other beyond gene sequence determined humoral immune response mechanisms have in some specific cases revealed their potent immunomodulatory effects. Nonetheless, such more unusual mechanisms have not received much attention in the context of SARS-CoV-2. Thus, with specific focus on the latter, this paper presents, (1) the rationale for considering beyond sequence determined strategies, (2) evidence for their possible involvement in Covid-19 disease evolution, (3) consequences for vaccine design exemplified by one of the vaccine candidates that is currently undergoing trial, and (4) more general implications. Based on a critical interpretation of published literature, the hypotheses developed in this study point to a crucial role of non-genetic antibody diversification mechanisms in disease evolution to counteract unique immunogenicity determinants of SARS-CoV-2 infection. The involvement of post translational mechanisms may also help explain the widely varied immune response observed, not only among different patient groups, but also in terms of their observed incompatibility with SARS-CoV-2 infection in several human cell types. The article highlights potentials and challenges of these refined humoral immune response mechanisms to most optimally target non-genetic viral evasion strategies.
Non-invasive Oscillometry-Based Estimation of Cardiac Output – Can We Use It in Clinical Practice?
Authors: Reshetnik Alexander , Gjolli Jonida , van der Giet Markus , Compton Friederike
Published: August 2021

While invasive thermodilution techniques remain the reference methods for cardiac output (CO) measurement, there is a currently unmet need for non-invasive techniques to simplify CO determination, reduce complications related to invasive procedures required for indicator dilution CO measurement, and expand the application field toward emergency room, non-intensive care, or outpatient settings. We evaluated the performance of a non-invasive oscillometry-based CO estimation method compared to transpulmonary thermodilution. To assess agreement between the devices, we used Bland–Altman analysis. Four-quadrant plot analysis was used to visualize the ability of Mobil-O-Graph (MG) to track CO changes after a fluid challenge. Trending analysis of CO trajectories was used to compare MG and PiCCO® calibrated pulse wave analysis over time (6 h). We included 40 patients from the medical intensive care unit at the Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin between November 2019 and June 2020. The median age was 73 years. Forty percent of the study population was male; 98% was ventilator-dependent and 75% vasopressor-dependent at study entry. The mean of the observed differences for the cardiac output index (COI) was 0.7 l∗min–1*m–2 and the lower, and upper 95% limits of agreement (LOA) were -1.9 and 3.3 l∗min–1*m–2, respectively. The 95% confidence interval for the LOA was ± 0.26 l∗min–1*m–2, the percentage error 83.6%. We observed concordant changes in CO with MG and PiCCO® in 50% of the measurements after a fluid challenge and over the course of 6 h. Cardiac output calculation with a novel oscillometry-based pulse wave analysis method is feasible and replicable in critically ill patients. However, we did not find clinically applicable agreement between MG and thermodilution or calibrated pulse wave analysis, respectively, assessed with established evaluation routine using the Bland–Altman approach and with trending analysis methods. In summary, we do not recommend the use of this method in critically ill patients at this time. As the basic approach is promising and the CO determination with MG very simple to perform, further studies should be undertaken both in hemodynamically stable patients, and in the critical care setting to allow additional adjustments of the underlying algorithm for CO estimation with MG.
Recent Advances in Fibrosis and Scar Segmentation From Cardiac MRI: A State-of-the-Art Review and Future Perspectives
Authors: Wu Yinzhe , Tang Zeyu , Li Binghuan , Firmin David , Yang Guang
Published: August 2021

Segmentation of cardiac fibrosis and scars is essential for clinical diagnosis and can provide invaluable guidance for the treatment of cardiac diseases. Late Gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been successful in guiding the clinical diagnosis and treatment reliably. For LGE CMR, many methods have demonstrated success in accurately segmenting scarring regions. Co-registration with other non-contrast-agent (non-CA) modalities [e.g., balanced steady-state free precession (bSSFP) cine magnetic resonance imaging (MRI)] can further enhance the efficacy of automated segmentation of cardiac anatomies. Many conventional methods have been proposed to provide automated or semi-automated segmentation of scars. With the development of deep learning in recent years, we can also see more advanced methods that are more efficient in providing more accurate segmentations. This paper conducts a state-of-the-art review of conventional and current state-of-the-art approaches utilizing different modalities for accurate cardiac fibrosis and scar segmentation.
Potential Role of Cannabidiol on Sports Recovery: A Narrative Review
Authors: Rojas-Valverde Daniel
Published: August 2021

The use of cannabidiol (CBD) among athletes is becoming extensive and frequent. This could be due to the elimination of CBD from the list of prohibited substances by federations and international institutions of sport. The legalization and resulting production, and commercialization of CBD, could increase its intake in sports professionals. This commercialization of cannabinoids has fueled a race to study their properties, benefits, and risks for health and performance in athletes. Although there is evidence that suggests some beneficial properties such as anxiolytics, antidepressants, anti-inflammatory, and antioxidants among others, the evidence presented so far is neither clear nor conclusive. There are significant gaps in knowledge of the physiological pathways that explain the role of CBD in sports performance. This mini-review examines evidence suggesting that CBD has the potential to be used as a part of the strategies to recover from fatigue and muscle damage related to physical and cognitive exertion in sports.
Effects of Urea-Ammonium Nitrate Solution on Yield, N2O Emission, and Nitrogen Efficiency of Summer Maize Under Integration of Water and Fertilizer
Authors: Ren Baizhao , Guo Yanqing , Liu Peng , Zhao Bin , Zhang Jiwang
Published: August 2021

In order to clarify the effects of urea-ammonium nitrate solution (UAN) on the yield, nitrogen-use efficiency (NUE), and N2O emissions of summer maize under the condition of water and fertilizer integration, different types of nitrogen fertilizer were selected, namely, ordinary urea (urea) and UAN. Our results showed that the application of UAN was beneficial to improve the dry matter accumulation and the distribution of summer maize. Compared with urea treatment, the total nitrogen accumulation of UAN treatment was increased by 15.8%, and the harvest index was increased by 5.5%. The partial productivity, agronomic use efficiency, and recovery rate of nitrogen for UAN treatment were also increased by 9.1, 19.8, and 31.2%, respectively, compared to those of urea treatment. The soil nitrogen dependence rate treated with UAN was significantly decreased by 13.6%, compared to that of urea treatment. In addition, UAN was beneficial to reduce N2O emissions. The N2O warming potential (GWPN2O) and N2O greenhouse gas intensity (GHGIN2O) of urea treatment were 39.3 and 52.4% higher, compared to those of UAN treatment. The improvement of dry matter accumulation and distribution and nitrogen efficiency for UAN treatment were beneficial to increase the grain yield by 9.1%, compared to that of urea treatment. In conclusion, under the fertigation, the application of UAN favors higher yield and nitrogen uptake, with less soil nitrogen residue, higher NUE, and better environmental effect.
The Contribution of Word-, Sentence-, and Discourse-Level Abilities on Writing Performance: A 3-Year Longitudinal Study
Authors: Carvalhais Lénia , Limpo Teresa , Pereira Luísa Álvares
Published: August 2021

Writing is a foundational skill throughout school grades. This study analyzed the development of different levels of written language (word, sentence, and discourse) and explored the relationship between these levels and writing performance. About 95 Portuguese students from two cohorts—Grades 4–7 (n = 47) 6–9 (n = 48)—were asked to produce a descriptive text two times, with a 3-year interval. The produced texts were used to assess spelling, syntactic correctness and complexity, and descriptive discourse as well as text length and quality. The main results showed that there were improvements from Grades 4 to 7 and 6 to 9 in word- and sentence-level skills, along with increases in some dimensions of the descriptive discourse. Moreover, the older cohort performed better than the younger cohort in terms of spelling, syntactic complexity, and text quality, but not in terms of syntactic correctness, one dimension of the descriptive discourse, and text length. Regression analyses showed that writing performance was predicted by word and sentence levels in the younger cohort only, and by discourse-level variables in both cohorts. Overall, despite indicating a generalized growth in writing skills throughout schooling, this study also highlighted the areas that may need additional attention from teachers, mainly in terms of the descriptive features.
Emerging ASL Distinctions in Sign-Speech Bilinguals' Signs and Co-speech Gestures in Placement Descriptions
Authors: Frederiksen Anne Therese
Published: August 2021

Previous work on placement expressions (e.g., “she put the cup on the table”) has demonstrated cross-linguistic differences in the specificity of placement expressions in the native language (L1), with some languages preferring more general, widely applicable expressions and others preferring more specific expressions based on more fine-grained distinctions. Research on second language (L2) acquisition of an additional spoken language has shown that learning the appropriate L2 placement distinctions poses a challenge for adult learners whose L2 semantic representations can be non-target like and have fuzzy boundaries. Unknown is whether similar effects apply to learners acquiring a L2 in a different sensory-motor modality, e.g., hearing learners of a sign language. Placement verbs in signed languages tend to be highly iconic and to exhibit transparent semantic boundaries. This may facilitate acquisition of signed placement verbs. In addition, little is known about how exposure to different semantic boundaries in placement events in a typologically different language affects lexical semantic meaning in the L1. In this study, we examined placement event descriptions (in American Sign Language (ASL) and English) in hearing L2 learners of ASL who were native speakers of English. L2 signers' ASL placement descriptions looked similar to those of two Deaf, native ASL signer controls, suggesting that the iconicity and transparency of placement distinctions in the visual modality may facilitate L2 acquisition. Nevertheless, L2 signers used a wider range of handshapes in ASL and used them less appropriately, indicating that fuzzy semantic boundaries occur in cross-modal L2 acquisition as well. In addition, while the L2 signers' English verbal expressions were not different from those of a non-signing control group, placement distinctions expressed in co-speech gesture were marginally more ASL-like for L2 signers, suggesting that exposure to different semantic boundaries can cause changes to how placement is conceptualized in the L1 as well.
Spanish Adaptation of the Inventory Brief Child Abuse Potential and the Protective Factors Survey
Authors: Sahagún-Morales Arturo , Ampudia Rueda Amada , Chacón-Moscoso Salvador , Sanduvete-Chaves Susana , Carro Pérez Ennio Héctor , Andrade Palos Patricia
Published: August 2021

Child maltreatment is a public health problem with different consequences depending on the form of abuse. Measuring risk and protective factors has been a fertile ground for research, without involving instruments with sufficient evidence of validity. The aim of the study was to gather evidence of validity and reliability of the Inventory Brief Child Abuse Potential (IBCAP) and Protective Factors Survey (PFS) in the Mexican population. The instruments were translated into Spanish. In a non-probabilistic sample of 200 participants, the 7-factor model for the IBCAP [comparative fit index (CFI) = 0.984; root mean square error of approximation (RMSEA) = 0.067] and the 4-factor model for the PFS (CFI = 0.974; RMSEA = 0.061) were confirmed, showing adequate fit indices. Reliability was estimated and evidence of convergent, divergent, and discriminant validity was collected, controlling for effects of social desirability. We also report interpretability statistics of the scores. We achieved solid progress in the development of instrumentation that allows determining the presence or absence of protective and risk factors for child abuse.
Psychosocial Adjustment and Mental Distress Associated With In-Game Purchases Among Japanese Junior High School Students
Authors: Shinkawa Hiroki , Irie Tomonari , Tanaka Masanori , Yokomitsu Kengo
Published: August 2021

In-game purchases, including microtransactions and loot box spending, are the monetization systems of free-to-play online games. Although some studies have suggested that excessive in-game purchases increase the risk of psychosocial maladjustment and mental distress as well as predict future problematic gaming and gambling practices, empirical studies on problematic behavioral patterns related to in-game purchasing among adolescents are lacking. This study sought to explore whether knowing the style of in-game purchases (non-purchase, planned purchase, or unplanned purchase) could be useful when characterizing maladaptive behavior among adolescents from the perspective of psychosocial adjustment and mental distress. A total of 335 junior high school students (aged 12–15 years) participated in the survey and completed a questionnaire assessing daily online gaming usage, in-game purchases, psychosocial adjustment, and mental distress. The results showed that (1) 30.7% of students had previously made in-game purchases, and at least 14.0% had made unplanned in-game purchases; (2) 19.2% of the users who had made unplanned purchases had spent greater than or equal to their actual monthly allowance within the past month, and (3) unplanned purchase gamers exhibited more behavioral problems and peer problems regarding psychosocial adjustment compared to planned purchase gamers, and more overall difficulties compared to non-purchasers. Meanwhile, more hyperactivity/inattention was seen among in-game purchasers compared to non-purchasers, regardless of whether the purchase was planned or unplanned. These findings support that understanding whether adolescents make unplanned in-game purchases could be a useful approach to describing the characteristics of online gamers with maladaptive tendencies.
The Impact of Financial Incentives on Service Engagement Among Adults Experiencing Homelessness and Mental Illness: A Pragmatic Trial Protocol
Authors: Reid Nadine , Nisenbaum Rosane , Hwang Stephen W. , Durbin Anna , Kozloff Nicole , Wang Ri , Stergiopoulos Vicky
Published: August 2021

Background: People experiencing homelessness and mental illness have poorer service engagement and health-related outcomes compared to the general population. Financial incentives have been associated with increased service engagement, but evidence of effectiveness is limited. This protocol evaluates the acceptability and impact of financial incentives on service engagement among adults experiencing homelessness and mental illness in Toronto, Canada.

Methods: This study protocol uses a pragmatic field trial design and mixed methods (ClinicalTrials.gov Identifier: NCT03770221). Study participants were recruited from a brief multidisciplinary case management program for adults experiencing homelessness and mental illness following hospital discharge, and were randomly assigned to usual care or a financial incentives arm offering $20 for each week they attended meetings with a program provider. The primary outcome of effectiveness is service engagement, measured by the count of participant-provider health-care contacts over the 6-month period post-randomization. Secondary health, health service use, quality of life, and housing outcomes were measured at baseline and at 6-month follow-up. Quantitative data will be analyzed using descriptive statistics and inferential modeling including Poisson regression and generalized estimating equations. A subset of study participants and other key informants participated in interviews, and program staff in focus groups, to explore experiences with and perspectives regarding financial incentives. Qualitative data will be rigorously coded and thematically analyzed.

Conclusions: Findings from this study will contribute high quality evidence to an underdeveloped literature base on the effectiveness and acceptability of financial incentives to improve service engagement and health-related outcomes among adults experiencing homelessness and mental illness.
A Perspective on the Role of Point-of-Care “Immuno-Triaging” to Optimize COVID-19 Vaccination Distribution in a Time of Scarcity
Authors: Zhang Yi , Rogers Angela , Nadeau Kari , Gu Jun , Yang Samuel
Published: August 2021

Vaccine bears hope to bring COVID-19 pandemic under control. With limited supply, vaccines must be utilized efficiently to provide protection to those who need it most. Currently, no practical framework has been proposed to ensure fair vaccine allocation at individual level, which is a recognized problem. We propose here an evidence-based decision-making framework for COVID-19 vaccine appropriation that prioritizes vaccine doses to individuals based on their immunological status, or immuno-triaging. To ensure successful implementation of the proposed framework, point-of-care (POC) immunodiagnostic testing is needed to quickly ramp up the testing capability. Considerations for deploying POC immunodiagnostic testing at such a large scale are discussed. We hope that the proposed immunological decision-making framework for evidence-based COVID-19 vaccine appropriation provides an objective approach to ensure fair and efficient utilization of the scarce vaccine resource at the individual level that also maximizes the collective societal benefit.
Implementation of HIV Self-Testing to Reach Men in Rural uMkhanyakude, KwaZulu-Natal, South Africa. a DO-ART Trial Sub Study
Authors: Sithole Nsika , Shahmanesh Maryam , Koole Olivier , Krows Meighan , Schaafsma Torin , Siedner Mark J. , Celum Connie , Barnabas Ruanne V. , Shapiro Adrienne E.
Published: August 2021

Background: KwaZulu–Natal, South Africa has one of the highest HIV prevalence rates globally. Persons <35 years and men have lower rates of HIV testing. HIV self-testing (HIVST) may overcome many barriers of facility-based HIV testing in order to identify HIV positive young persons and men and link them to care. We investigated whether HIVST distribution was a feasible approach to reach men and assessed the proportion of participants who reported their HIVST results, tested positive and linked to care.

Methods: Teams comprised of a nurse, clinic research assistant, and recruiters distributed HIVST kits in rural uMkhanyakude, KwaZulu-Natal from August—November 2018 with a focus on testing men. Workplaces (farms), social venues, taxi ranks, and homesteads were used as HIVST kit distribution points following community sensitisation through community advisory boards and community leaders. HIVST kits, demonstration of use, and small incentives to report testing outcomes were provided. The Department of Health provided confirmatory testing and HIV care at clinics.

Results: Over 11 weeks in late 2018, we distributed 2,634 HIVST kits of which 2,113 (80%) were distributed to persons aged <35 years, 2,591 (98%) to men and 356 (14%) to first time testers. Of the HIVST distributed, 2,107 (80%) reported their results to the study team, and 157 (7%) tested positive. Of persons who tested positive, 107/130 (82%) reported having a confirmatory test of which 102/107 (95%) were positive and initiated on ART. No emergencies or social harms were reported.

Conclusion: Large scale distribution of HIVST kits targeting men in rural KwaZulu-Natal is feasible and highly effective in reaching men, including those who had not previously tested for HIV. While two-thirds of persons who tested HIV positive initiated ART, additional linkage strategies are needed for those who do not link after HIVST. HIVST should be used as a tool to reach men in order to achieve 95% coverage in the UNAIDS testing and care cascade in KwaZulu-Natal.
Systematic Review and Quality Evaluation of Pharmacoeconomic Studies on Traditional Chinese Medicines
Authors: Yang Nan , Zhang Huihui , Deng Taoyi , Guo Jeff Jianfei , Hu Ming
Published: August 2021

Objectives: This study was aimed to find and appraise the available published pharmacoeconomic research on Traditional Chinese Medicine (TCM), to identify related issues and make suggestions for improvement in future research.

Methods: After developing a search strategy and establishing inclusion and exclusion criteria, pharmacoeconomic studies on TCM were sourced from seven Chinese and English databases from inception to April 2020. Basic information about the studies and key pharmacoeconomic items of each study were extracted. The quality of each study was evaluated by using the British Medical Journal economic submissions checklist for authors and peer reviewers, focusing on factors such as study design, research time horizon, sample size, perspective, and evaluation methods.

Results: A total of 431 published pharmacoeconomic articles with 434 studies on topics including cost-effectiveness, cost-benefit, cost-minimization, cost-utility, or combination analyses were identified and included in this review. Of these, 424 were published in Chinese and 7 in English. These studies conducted economic evaluations of 264 Chinese patent medicines and 70 types of TCM prescriptions for 143 diseases, including those of the central nervous, cardiovascular, respiratory, gynecologyical, and other systems. The studied TCMs included blood-activating agents (such as Xuesaitong tablet, Fufant Danshen tablet, and Danhong Injection), blood circulation promoting agents (such as Shuxuetong injection, Rupixiao tablet, and Fufang Danshen injection), and other therapeutic agents. The overall quality score of the studies was 0.62 (range 0.38 to 0.85). The mean quality score of studies in English was 0.72, which was higher than that of studies in Chinese with 0.62.

Conclusions: The quality of pharmacoeconomic studies on TCM was relatively, generally low. Major concerns included study design, inappropriate pharmacoeconomic evaluation, insufficient sample size, or non-scientific assessment. Enhanced methodological training and cooperation, the development of a targeted pharmacoeconomic evaluation guideline, and proposal of a reasonable health outcome index are warranted to improve quality of future studies.
Endoscope-Assisted Microsurgery in Pediatric Cases With Pineal Region Tumors: A Study of 18 Cases Series
Authors: Cai Yuankun , Xiong Zhongwei , Xin Can , Chen Jincao , Liu Kui
Published: August 2021

Background: An endoscope-assisted technique was recently introduced to microsurgery (MS) and may compensate for the disadvantages of MS for deep-seated lesions. This study was performed to identify the effectiveness and safety of endoscopic-assisted microsurgery (EAM) and share our experience of EAM for pediatric cases with pineal region tumors.

Method: We retrospectively analyzed the clinical data of consecutive pediatric cases with pineal region tumors treated by EAM or MS from January 2016 to June 2020. These data included the patient population, clinical manifestations, preoperative examination findings, surgical approach, pathological results, and clinical outcomes. The clinical outcomes were analyzed in the EAM group and MS group with a focus on the gross total resection (GTR) rate, postoperative hydrocephalus remission rate, and Karnofsky performance score (KPS). Studies on the surgical management of children with pineal region tumors in the last decade were reviewed.

Result: Eighteen children successfully underwent tumor resection via MS (n = 8) or EAM (n = 10). The children's mean age was 11.4 ± 4.7 years, and the male to female ratio was 7:2. Seventeen patients (94.4%) complicated preoperative hydrocephalus, and 16 (88.9%) presented headache with nausea and/or vomiting. The pathological examination revealed germ cell tumors in 11 (61.1%) patients, neuroepithelial tumors in 4 (22.2%) patients, and a pineoblastoma, arachnoid cyst, and atypical teratoid rhabdoid tumor in 1 (5.6%) patient each. GTR was more commonly achieved in the EAM than MS group (80.0 vs. 50.0%, respectively), and the postoperative hydrocephalus remission rate was higher in the EAM than MS group (87.5 vs. 50.0%, respectively). At a mean follow-up time of 23.6 ± 11.5 weeks, the mean improvement of the KPS 6 months postoperatively was greater in the EAM than MS group (24.0 ± 9.7 vs. 17.5 ± 7.1 points, respectively).

Conclusion: EAM combines endoscopic and microsurgical techniques and can be safely and effectively performed to achieve GTR of pineal region tumors in pediatric patients. In children with pineal region tumors who have obstructive hydrocephalus, EAM could improves hydrocephalus remission rates by checking and clearing the midbrain aqueduct under visualization.
Comparative Analysis of Metabolic Differences of Jersey Cattle in Different High-Altitude Areas
Authors: Kong Zhiwei , Li Bin , Zhou Chuanshe , He Qinghua , Zheng Yuzhong , Tan Zhiliang
Published: August 2021

In high-altitude area, hypoxia is a serious stress for humans and other animals, disrupting oxygen homeostasis and thus affecting tissue metabolism. Up to now, there are few reports on the metabolic changes of dairy cows at different altitudes. In this experiment, metabonomics technology and blood biochemical indexes were used to study the metabolic changes of dairy cows in different altitudes. The results showed that the different metabolites were mainly enriched in amino acid metabolism and sphingolipid metabolism, and sphingolipid metabolism showed a negative correlation with increased altitude. The results of this study will enrich the hypoxia-adaptive mechanism of dairy cows in high-altitude areas and provide a theoretical basis for the nutritional regulation of performance and disease treatment of dairy cows in high-altitude areas.
Motion Characteristics of a Clutch Actuator for Heavy-Duty Vehicles with Automated Mechanical Transmission
Authors: Li Yunxia , Wang Zengcai
Published: August 2021

Clutch control has a great effect on the starting quality and shifting quality of heavy-duty vehicles with automated mechanical transmission (AMT). The motion characteristics of a clutch actuator for heavy-duty vehicles with AMT are studied in this paper to investigate the clutch control strategy further. The modeling principle of the automatic clutch system is analyzed, and a simulation analysis is given to prove its validity and rationality. Normalized velocity and velocity modulation percentage are proposed as evaluation parameters for the clutch actuator driven by pulse width modulation (PWM) signals. Based on an AMT test bench, the actuator motion characteristics are analyzed. Experimental results show that the range of normalized velocity and velocity modulation percentage are obtained for the clutch engagement and disengagement processes. By analyzing the experimental data, the engaging velocity and disengaging velocity of the actuator are estimated using the solenoid valves in combination. The research results provide a fundamental basis for precise controlling of the clutch and improving the smoothness of heave-duty vehicles.
Application of Noise Certification Regulations within Conceptual Aircraft Design
Authors: Nöding Michel , Bertsch Lothar
Published: August 2021

ICAO Annex 16 regulations are used to certify the acoustic performance of subsonic transport aircraft. Each aircraft is classified according to the measured EPNL levels at specific certification locations along the approach and departure. By simulating this certification process, it becomes possible to identify all relevant parameters and assess promising measures to reduce the noise certification levels in compliance with the underlying ICAO regulations, i.e., allowable operating conditions of the aircraft. Furthermore, simulation is the only way to enable an assessment of novel technology and non-existing vehicle concepts, which is the main motivation behind the presented research activities. Consequently, the ICAO Annex 16 regulations are integrated into an existing noise simulation framework at DLR, and the virtual noise certification of novel aircraft concepts is realized at the conceptual design phase. The predicted certification levels can be directly selected as design objectives in order to realize an advantageous ICAO noise category for a new aircraft design, i.e., simultaneously accounting for the design and the resulting flight performance. A detailed assessment and identification of operational limits and allowable flight procedures for each conceptual aircraft design under consideration is enabled. Sensitivity studies can be performed for the relevant input parameters that influence the predicted noise certification levels. Specific noise sources with a dominating impact on the certification noise levels can be identified, and promising additional low-noise measures can be applied within the conceptual design phase. The overall simulation process is applied to existing vehicles in order to assess the validity of the simulation resultsfcompared to published data. Thereafter, the process is applied to some DLR low-noise aircraft concepts to evaluate their noise certification levels. These results can then be compared to other standard noise metrics that are typically applied in order to describe aircraft noise, e.g., SEL isocontour areas. It can be demonstrated that certain technologies can significantly reduce the noise impact along most of an approach or departure flight track but have only a limited influence on the noise certification levels and vice versa. Finally, an outlook of the ongoing developments is provided, in order to apply the new simulation process to supersonic aircraft. Newly proposed regulations for such concepts are implemented into the process in order to evaluate these new regulations and enable direct comparison with existing regulations.