bluuebunny/crossref_metadata_2025 huggingface dataset:
TCS-Fall: Cross-individual fall detection system based on channel state information and time-continuous stack method
Authors: Zhou Ziyu , Liu Zhaoqing , Liu Yujie , Zhao Yan , Wang Jiarui , Zhang Bowen , Xia Youbing , Zhang Xiao , Li Shuyan
Published: June 2024

Background

Falls pose a serious health risk for the elderly, particular for those who are living alone. The utilization of WiFi-based fall detection, employing Channel State Information (CSI), emerges as a promising solution due to its non-intrusive nature and privacy preservation. Despite these advantages, the challenge lies in optimizing cross-individual performance for CSI-based methods.

Objective

This study aimed to develop a resilient real-time fall detection system across individuals utilizing CSI, named TCS-Fall. This method was designed to offer continuous monitoring of activities over an extended timeframe, ensuring accurate and prompt detection of falls.

Methods

Extensive CSI data on 1800 falls and 2400 daily activities was collected from 20 volunteers. The grouped coefficient of variation of CSI amplitudes were utilized as input features. These features capture signal fluctuations and are input to a convolutional neural network classifier. Cross-individual performance was extensively evaluated using various train/test participant splits. Additionally, a user-friendly CSI data collection and detection tool was developed using PyQT. To achieve real-time performance, data parsing and pre-processing computations were optimized using Numba's just-in-time compilation.

Results

The proposed TCS-Fall method achieved excellent performance in cross-individual fall detection. On the test set, AUC reached 0.999, no error warning ratio score reached 0. 955 and correct warning ratio score reached of 0.975 when trained with data from only two volunteers. Performance can be further improved to 1.00 when 10 volunteers were included in training data. The optimized data parsing/pre-processing achieved over 20× speedup compared to previous method. The PyQT tool parsed and detected the fall within 100 ms.

Conclusions

TCS-Fall method enables excellent real-time cross-individual fall detection utilizing WiFi CSI, promising swift alerts and timely assistance to elderly. Additionally, the optimized data processing led to a significant speedup. These results highlight the potential of our approach in enhancing real-time fall detection systems.
Comparisons of three different modes of digital mirror therapy for post-stroke rehabilitation: Preliminary results of randomized controlled trial
Authors: Lee Meng-Ta , Chen Chih-Chi , Lu Hsuan-Lun , Hsieh Yu-Wei
Published: June 2024

Objective

Technologically adapted mirror therapy shows promising results in improving motor function for stroke survivors. The treatment effects of a newly developed multi-mode stroke rehabilitation system offering multiple training modes in digital mirror therapy remain unknown. This study aimed to examine the effects of unilateral mirror visual feedback (MVF) with unimanual training (UM-UT), unilateral MVF with bimanual training (UM-BT), and bilateral MVF with bimanual training (BM-BT) on clinical outcomes in stroke survivors, compared to classical mirror therapy (CMT).

Methods

Thirty-five participants were randomly assigned to one of four groups receiving fifteen 60-minute training sessions for 3–4 weeks. The Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Chedoke Arm and Hand Activity Inventory (CAHAI), Revised Nottingham Sensory Assessment (rNSA), Motor Activity Log (MAL), and EQ-5D-5L were administered at pre- and post-intervention and at 1-month follow-up.

Results

After intervention and follow-up, significant within-group treatment efficacies were found on most primary outcomes of the FMA-UE and CAHAI scores in all four groups. Significant within-group improvements in the secondary outcomes were found on the MAL and EQ-5D-5L index in the UM-BT group, and the rNSA tactile sensation and MAL quality of movement subscales in the BM-BT group. No significant between-group treatment efficacies were found.

Conclusions

UM-UT, UM-BT, BM-BT, and CMT led to similar clinical effects on the FMA-UE and can be considered effective alternative interventions for post-stroke upper-limb motor rehabilitation. UM-BT and BM-BT showed within-group improvements in functional performance in the patients’ affected upper limbs in real-life activities.
The evolution of augmented reality to augment physical therapy: A scoping review
Authors: Hsu Po-Yao , Singer Jonas , Keysor Julie J
Published: June 2024

Augmented reality is increasingly used in health care, yet little is known about how AR is being used in physical therapy practice and what clinical outcomes could occur with technology use. In this scoping review, a broad literature review was conducted to gain an understanding of current knowledge of AR use and outcomes in physical therapy practice. A structured literature search of articles published between 2000 to September 2023 that examined the use of AR in a physical therapy context was conducted. Reference lists of articles for full review were searched for additional studies. Data from articles meeting inclusion criteria were extracted and synthesized across studies. 549 articles were identified; 40 articles met criteria for full review. Gait and balance of neurological and older adult populations were most frequently targeted, with more recent studies including orthopedic and other populations. Approximately half were pilot or observational studies and half are experimental. Many studies found within group improvements. Of studies reporting between group differences, AR interventions were more effective in improving function almost half of the time, with 20%, 27% and 28% showing efficacy in disability, balance, and gait outcomes. AR in physical therapy holds promise; however, efficacy outcomes are unclear.
Relations Between Behavioral Inhibition/Activation Systems and Self-Esteem: Two Multiple Mediation Models With Social Relationships
Authors: Jiang Dan , Yin Jinrong , Zhai Shuyi , He Jie
Published: June 2024

Personality driven by Behavioral Inhibition/Activation Systems (BIS/BAS) can significantly influence self-esteem. Humans form self-esteem during social interactions; thus, social relationships may be a critical mediator. This study aims to systematically explore the role of social relationships in these relations among emerging adults. The essential social relationships of emerging adults, including mother-child, father-child, and peer relationships, were examined. Participants ( N = 967, M age = 19.16, 420 females) completed self-reported measures for BIS/BAS, social relationships, and self-esteem. The results demonstrate the mediating effect of social relationships: BIS was negatively related to all social relationships, which were further related to lower self-esteem; BAS was positively related to mother-child and peer relationships, which were further related to higher self-esteem. Moreover, the mother-child relationship emerged as a mediator linking BIS/BAS and father-child and peer relationships in the two models, indicating the unique contribution of mother-child interactions in Chinese emerging adults.
Cross-Cultural Adaptation, Translation, and Validation of the Victorian Institute of Sport Assessment-Achilles Questionnaire (VISA-A) for Use With Arabic-Speaking Patients With Achilles Tendinopathy
Authors: Alshewaier Shady A. , Alotaibi Raed M. , Alshabanat Abdulrahman S. , Alkathiry Abdulaziz A.
Published: June 2024

Background:

The Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire is a validated instrument for assessing symptoms of Achilles tendinopathy (AT). However, there is a need to validate the Arabic version of the VISA-A (VISA-A-AR) in Arabic-speaking patients with AT.

Purpose:

To validate the VISA-A-AR in Arabic patients with AT and evaluate its reliability and validity.

Study Design:

Cohort study (diagnosis); Level of evidence, 3.

Methods:

The translation and cultural adaptation of the VISA-A questionnaire into Arabic followed international guidelines. A total of 81 participants were recruited, including 45 patients diagnosed with AT and 36 healthy individuals. The AT group comprised male and female native Arabic speakers aged ≥18 years who were diagnosed with and had symptoms of AT. The inclusion criteria for the healthy group were the same, except that they must not have had AT at the time of the study or previously. The exclusion criteria were individuals with a partial or complete Achilles tendon rupture or prior Achilles tendon surgery. The internal consistency of the VISA-A-AR was assessed using the Cronbach α coefficient. Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC[3,1]). Construct validity was assessed through correlation analysis between VISA-A-AR scores and the Arabic versions of the Short Form-36 Health Survey (SF-36-AR) and the Numeric Pain Rating Scale (ANPRS). Differences in VISA-A-AR scores between patients with AT and healthy controls were analyzed using appropriate statistical tests.

Results:

The VISA-A-AR demonstrated a high level of internal consistency (Cronbach α = 0.935) and excellent test-retest reliability (ICC[3,1] = 0.985). Significant positive correlations were observed between VISA-A-AR scores and SF-36-AR ( r(43) = 0.838, P < .001), indicating good construct validity. In addition, VISA-A-AR scores showed a significant negative correlation with ANPRS ( rS(43) = -0.835, P < .001). Furthermore, VISA-A-AR scores exhibited a significant difference between patients with AT (mean, 45.82 ± 16.65) and healthy controls (mean, 99.94 ± 0.33) ( P < .001).

Conclusion:

The findings of this study validate the VISA-A-AR as a reliable and valid tool for assessing symptoms of AT in Arabic-speaking patients.
In-situ Audiometry Compared to Conventional Audiometry for Hearing Aid Fitting
Authors: Van Eeckhoutte Maaike , Jasper Bettina Skjold , Kjærbøl Erik Finn , Jordell David Harbo , Dau Torsten
Published: June 2024

The use of in-situ audiometry for hearing aid fitting is appealing due to its reduced resource and equipment requirements compared to standard approaches employing conventional audiometry alongside real-ear measures. However, its validity has been a subject of debate, as previous studies noted differences between hearing thresholds measured using conventional and in-situ audiometry. The differences were particularly notable for open-fit hearing aids, attributed to low-frequency leakage caused by the vent. Here, in-situ audiometry was investigated for six receiver-in-canal hearing aids from different manufacturers through three experiments. In Experiment I, the hearing aid gain was measured to investigate whether corrections were implemented to the prescribed target gain. In Experiment II, the in-situ stimuli were recorded to investigate if corrections were directly incorporated to the delivered in-situ stimulus. Finally, in Experiment III, hearing thresholds using in-situ and conventional audiometry were measured with real patients wearing open-fit hearing aids. Results indicated that (1) the hearing aid gain remained unaffected when measured with in-situ or conventional audiometry for all open-fit measurements, (2) the in-situ stimuli were adjusted for up to 30 dB at frequencies below 1000 Hz for all open-fit hearing aids except one, which also recommends the use of closed domes for all in-situ measurements, and (3) the mean interparticipant threshold difference fell within 5 dB for frequencies between 250 and 6000 Hz. The results clearly indicated that modern measured in-situ thresholds align (within 5 dB) with conventional thresholds measured, indicating the potential of in-situ audiometry for remote hearing care.
Epidemiology and impact of chronic disease multimorbidity in India: a systematic review and meta-analysis
Authors: Varanasi Roja , Sinha Abhinav , Bhatia Meenakshi , Nayak Debadatta , Manchanda Raj K , Janardhanan Rajiv , Lee John Tayu , Tandon Simran , Pati Sanghamitra
Published: June 2024

Objectives

This is the first systematic review and meta-analysis of the prevalence of multimorbidity, its risk factors including socioeconomic factors, and the consequences of multimorbidity on health systems and broader society in India.

Methods

A systematic review of both published and grey literature from five databases (Medline, Embase, EBSCO, Scopus, and ProQuest) was conducted including original studies documenting prevalence or patient outcomes associated with multimorbidity among adults in India. We excluded studies that did not explicitly mention multimorbidity. Three independent reviewers did primary screening based on titles and abstracts followed by full-text review for potential eligibility. The risk of bias was independently assessed by two reviewers following the Appraisal Tool for Cross-Sectional Studies. We presented both qualitative and quantitative (through meta-analysis) summaries of the evidence. The protocol for this study was prospectively registered with PROSPERO (CRD42021257281).

Results

The review identified 5442 articles out of which 35 articles were finally included in this study. Twenty-three studies were based on the primary data while 12 used secondary data. Eleven studies were conducted in hospital/primary care setting while 24 were community-based. The pooled prevalence of multimorbidity based on (n=19) studies included for meta-analysis was 20% (95% CI: 19% to 20%). The most frequent outcomes were increased healthcare utilization, reduced health-related quality of life, physical and mental functioning.

Conclusion

We identified a wide variance in the magnitude of multimorbidity across age groups and regions with most of the studies from eastern India. Nation-wide studies, studies on vulnerable populations and interventions are warranted.
Systemic failures in New Zealand's child-welfare and Family Court proceedings underlie and perpetuate child offending
Authors: Reil Jerome , Lambie Ian , Allen Ruth
Published: June 2024

Early childhood offending onset (before age 14 years) is associated with increased risk of lifecourse offending and poor life outcomes. The vast majority of children who offend in Aotearoa New Zealand (N.Z.) have had involvement with the child-welfare system prior to offending. Why does this engagement with statutory systems not prevent the trajectory into offending, nor its persistence into the youth-justice system (aged 14–18)? This study interviewed 33 key stakeholders (including family members, lawyers, police officers, social workers, psychologists, school and cultural leaders) on the systemic issues they had experienced with children who had offended and their families. Interviews were transcribed and analysed by the authors. Barriers to effectively responding to offending (and, more importantly, prevention of offending in the first place) included child-welfare engagement that was delayed and ineffective; deficit-focused engagement with families and children; under-resourced Family Court systems that delayed court proceedings and further hindered effective child-welfare intervention; and systemic shortfalls that continued once a child had offended, with widespread uncertainty as to how best to respond or access appropriate resources. Earlier and more effective intervention with children and families with child-welfare concerns is needed to prevent and reduce offending and victimisation of and by children.
Shaping the techno-social landscape of corrections: How values, technology, and culture influence the design of correctional service delivery applications
Authors: Ross Stuart , Wood Mark A , Baird Ron , Lundberg Kajsa
Published: June 2024

Over the past decade, a variety of digital platforms have emerged to deliver core correctional services. Understanding the challenges and drivers of correctional agencies’ digitalisation helps us to understand the processes that shape these technologies and their impact on correctional environments and practices. To bridge this gap, we conducted interviews with 26 software developers and other stakeholders involved in the digitalisation of corrections, aiming to explore the challenges encountered in designing and implementing digital service delivery technologies for correctional services. Our findings shed light on some key challenges faced by software developers and other stakeholders involved in the design process, including institutional culture, justice system bureaucracy, and public perceptions. These challenges significantly influence design processes and the availability of digital products for end users. They shape the techno-social landscape of correctional agencies and contribute to the dominance or absence of certain digital platforms or artefacts.
Contrasting mathematics educational values: An in-depth case study of primary and secondary teachers in Hong Kong
Authors: Zhang Qiaoping , Lam Chung-yin
Published: June 2024

Using an in-depth case study approach, this study explored the mathematics educational values held by two in-service teachers at the primary and secondary levels in Hong Kong through lesson observations and deep structured interviews. The findings revealed that the primary teacher emphasized fun, flexibility, critical thinking, and coherence, while the secondary teacher prioritized achievement, control, higher-order thinking, and progression. Using Seah and Bishop's five complementary pairs framework, the primary teacher aligned with an activist, relational, relevance, and accessibility perspective, contrasting sharply with the secondary teacher. This reflected a shift in values in response to students’ educational stages, revealing the challenges of balancing social expectations and nurturing future science, technology, engineering, and mathematics talent. We discussed the implications for local education reforms, including modernizing assessment methods and curricula, reshaping the social climate, and updating professional development to address these tensions.
Examining the problem-posing performances of seventh-grade students in relation to response order
Authors: Kar Tuğrul , Öçal Mehmet Fatih , Bişgin Büşra , Arslan Melike
Published: June 2024

In this study, 176 Turkish seventh-grade students were asked to pose three problems for each of the swimming and purchasing tasks to examine how the solvability and complexity of the problems changed depending on the order of responses. The purchasing task required to pose a problem to derive a specific answer before posing new problems, whereas the swimming task required to pose problems based on existing data. The findings indicated that students performed poorly in terms of posing solvable problems in both tasks. The majority of solvable responses in the purchasing task were at the high complexity level, but most in the swimming task were at the low complexity level. No evidence of a relationship between the order of the responses and any of the analysis units (solvability and complexity) was found. Furthermore, when comparing the groups that posed and did not pose solvable problems for the specific answer in the purchasing task, the former group had a stronger tendency to maintain the complexity points in their other responses compared to their first response.
Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange
Authors: Kühne Lucas , Knöbl Paul , Eller Kathrin , Thaler Johannes , Sperr Wolfgang R. , Gleixner Karoline , Osterholt Thomas , Kaufeld Jessica , Menne Jan , Buxhofer-Ausch Veronika , Mühlfeld Anja , Seelow Evelyn , Schreiber Adrian , Todorova Polina , Cukoski Sadrija , Jabs Wolfram J. , Özcan Fedai , Gäckler Anja , Schönfelder Kristina , Seibert Felix S. , Westhoff Timm , Schwenger Vedat , Eichenauer Dennis A. , Völker Linus A. , Brinkkoetter Paul T.
Published: June 2024

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency. Caplacizumab, an anti–von Willebrand factor nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet count recovery and survival. We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased after the first caplacizumab dose. Baseline characteristics and patient outcomes were compared with a control group of 59 patients with iTTP receiving frontline treatment with TPE, caplacizumab, and immunosuppression. The main outcome was the time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, iTTP-related deaths, and the time to platelet count doubling. The median time to platelet count normalization was similar between the 2 cohorts (3 and 4 days; P = .31). There were no significant differences in clinical response, exacerbations, refractoriness, iTTP-related deaths, or time to platelet count doubling, reflecting the short-term treatment response. Four patients did not respond to the first caplacizumab dose, and TPE was subsequently initiated. Cytomegalovirus infection, HIV/hepatitis B virus coinfection, an ovarian teratoma with associated antiplatelet antibodies, and multiple platelet transfusions before the correct diagnosis may have impeded the immediate treatment response in these patients. In conclusion, caplacizumab and immunosuppression alone, without TPE, rapidly controlled thrombotic microangiopathy and achieved a sustained clinical response in iTTP. Our study provides a basis for TPE-free iTTP management in experienced centers via shared decision-making between patients and treating physicians.
Affimer reagents as tool molecules to modulate platelet GPVI-ligand interactions and specifically bind GPVI dimer
Authors: Xu Rui-Gang , Tiede Christian , Calabrese Antonio N. , Cheah Lih T. , Adams Thomas L. , Gauer Julia S. , Hindle Matthew S. , Webb Beth A. , Yates Daisie M. , Slater Alexandre , Duval Cédric , Naseem Khalid M. , Herr Andrew B. , Tomlinson Darren C. , Watson Steve P. , Ariëns Robert A. S.
Published: June 2024

Glycoprotein VI (GPVI) plays a key role in collagen-induced platelet aggregation. Affimers are engineered binding protein alternatives to antibodies. We screened and characterized GPVI-binding Affimers as novel tools to probe GPVI function. Among the positive clones, M17, D22, and D18 bound GPVI with the highest affinities (dissociation constant (KD) in the nanomolar range). These Affimers inhibited GPVI-collagen-related peptide (CRP)-XL/collagen interactions, CRP-XL/collagen-induced platelet aggregation, and D22 also inhibited in vitro thrombus formation on a collagen surface under flow. D18 bound GPVI dimer but not monomer. GPVI binding was increased for D18 but not M17/D22 upon platelet activation by CRP-XL and adenosine 5′-diphosphate. D22 but not M17/D18 displaced nanobody 2 (Nb2) binding to GPVI, indicating similar epitopes for D22 with Nb2 but not for M17/D18. Mapping of binding sites revealed that D22 binds a site that overlaps with Nb2 on the D1 domain, whereas M17 targets a site on the D2 domain, overlapping in part with the glenzocimab binding site, a humanized GPVI antibody fragment antigen-binding fragment. D18 targets a new region on the D2 domain. We found that D18 is a stable noncovalent dimer and forms a stable complex with dimeric GPVI with 1:1 stoichiometry. Taken together, our data demonstrate that Affimers modulate GPVI-ligand interactions and bind different sites on GPVI D1/D2 domains. D18 is dimer-specific and could be used as a tool to detect GPVI dimerization or clustering in platelets. A dimeric epitope regulating ligand binding was identified on the GPVI D2 domain, which could be used for the development of novel bivalent antithrombotic agents selectively targeting GPVI dimer on platelets.
Deletion of pyruvate dehydrogenase kinases reduces susceptibility to deep vein thrombosis in mice
Authors: Flora Gagan D. , Ghatge Madankumar , Nayak Manasa K. , Barbhuyan Tarun , Kumskova Mariia , Chauhan Anil K.
Published: June 2024

Neutrophils contribute to deep vein thrombosis (DVT) by releasing prothrombotic neutrophil extracellular traps (NETs). NET formation (known as NETosis) is an energy-intensive process that requires an increased rate of aerobic glycolysis. The metabolic enzymes pyruvate dehydrogenase kinases (PDKs) inhibit the pyruvate dehydrogenase complex to divert the pyruvate flux from oxidative phosphorylation toward aerobic glycolysis. Herein, we identified that the combined deletion of PDK2 and PDK4 (PDK2/4–/–) renders mice less susceptible to DVT (measured by thrombus incidence, weight, and length) in the inferior vena cava–stenosis model at day 2 after surgery. Compared with wild-type (WT) mice, the venous thrombus obtained from PDK2/4–/– mice exhibited reduced citrullinated histone content, a known marker of NETs. In line with in vivo observations, phorbol 12-myristate 13-acetate (PMA)–stimulated PDK2/4–/– neutrophils displayed reduced NETosis and secretion of cathepsin G and elastase compared with PMA-stimulated WT neutrophils. The formation of platelet aggregates mediated by PMA-stimulated PDK2/4–/– neutrophils were significantly reduced compared with PMA-stimulated WT neutrophils. Finally, PDK2/4–/– neutrophils exhibited reduced levels of intracellular Ca2+ concentration, extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and glycolytic proton efflux rate (a measure of aerobic glycolysis), known to facilitate NETosis. Together, these findings elucidate, to our knowledge, for the first time, the fundamental role of PDK2/4 in regulating NETosis and acute DVT.
Clonal hematopoiesis of indeterminate potential as a prognostic factor: a systematic review and meta-analysis
Authors: Singh Jasmine , Li Nancy , Ashrafi Elham , Thao Le Thi Phuong , Curtis David J. , Wood Erica M. , McQuilten Zoe K.
Published: June 2024

With advances in sequencing, individuals with clonal hematopoiesis of indeterminate potential (CHIP) are increasingly being identified, making it essential to understand its prognostic implications. We conducted a systematic review of studies comparing the risk of clinical outcomes in individuals with and without CHIP. We searched MEDLINE and EMBASE and included original research reporting an outcome risk measure in individuals with CHIP, adjusted for the effect of age. From the 3305 studies screened, we included 88 studies with 45 to 470 960 participants. Most studies had a low-to-moderate risk of bias in all domains of the Quality in Prognostic Factor Studies tool. Random-effects meta-analyses were performed for outcomes reported in at least 3 studies. CHIP conferred an increased risk of all-cause mortality (hazard ratio [HR], 1.34; 95% confidence interval, 1.19-1.50), cancer mortality (HR, 1.46; 1.13-1.88), composite cardiovascular events (HR, 1.40; 1.19-1.65), coronary heart disease (HR, 1.76; 1.27-2.44), stroke (HR, 1.16; 1.05-1.28), heart failure (HR, 1.27; 1.15-1.41), hematologic malignancy (HR, 4.28; 2.29-7.98), lung cancer (HR, 1.40; 1.27-1.54), renal impairment (HR, 1.25; 1.18-1.33) and severe COVID-19 (odds ratio [OR], 1.46; 1.18-1.80). CHIP was not associated with cardiovascular mortality (HR, 1.09; 0.97-1.22), except in the subgroup analysis restricted to larger clones (HR, 1.31; 1.12-1.54). Isolated DNMT3A mutations did not increase the risk of myeloid malignancy, all-cause mortality, or renal impairment. The reasons for heterogeneity between studies included differences in definitions and measurements of CHIP and the outcomes, and populations studied. In summary, CHIP is associated with diverse clinical outcomes, with clone size, specific gene, and inherent patient characteristics important mediators of risk.
Icariin improves oxidative stress injury during ischemic stroke via inhibiting mPTP opening
Authors: Zhou Zhiyong , Li Weili , Ni Lu , Wang Tianlun , Huang Yan , Yu Yuanqi , Hu Mingxin , Liu Yinling , Wang Jin’e , Huang Xiaofei , Wang Yanyan
Published: June 2024

Background

Ischemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear.

Methods

PC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting.

Results

In vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32–40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA.

Conclusions

ICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke.

Graphical Abstract
Genetic evidence for the causal relationships between migraine, dementia, and longitudinal brain atrophy
Authors: Zhao Lei , Tang Yilan , Tu Yiheng , Cao Jin
Published: June 2024

Background

Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR).

Methods

We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer’s disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis.

Results

The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10− 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10− 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10− 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10− 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10− 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect.

Discussion

This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients.
Whole-genome sequencing reveals genomic diversity and selection signatures in Xia’nan cattle
Authors: Song Xingya , Yao Zhi , Zhang Zijing , Lyu Shijie , Chen Ningbo , Qi Xingshan , Liu Xian , Ma Weidong , Wang Wusheng , Lei Chuzhao , Jiang Yu , Wang Eryao , Huang Yongzhen
Published: June 2024

Background

The crossbreeding of specialized beef cattle breeds with Chinese indigenous cattle is a common method of genetic improvement. Xia’nan cattle, a crossbreed of Charolais and Nanyang cattle, is China’s first specialized beef cattle breed with independent intellectual property rights. After more than two decades of selective breeding, Xia’nan cattle exhibit a robust physique, good environmental adaptability, good tolerance to coarse feed, and high meat production rates. This study analyzed the population genetic structure, genetic diversity, and genomic variations of Xia’nan cattle using whole-genome sequencing data from 30 Xia’nan cattle and 178 published cattle genomic data.

Result

The ancestry estimating composition analysis showed that the ancestry proportions for Xia’nan cattle were mainly Charolais with a small amount of Nanyang cattle. Through the genetic diversity studies (nucleotide diversity and linkage disequilibrium decay), we found that the genomic diversity of Xia’nan cattle is higher than that of specialized beef cattle breeds in Europe but lower than that of Chinese native cattle. Then, we used four methods to detect genome candidate regions influencing the excellent traits of Xia’nan cattle. Among the detected results, 42 genes (θπ and CLR) and 131 genes (FST and XP-EHH) were detected by two different detection strategies. In addition, we found a region in BTA8 with strong selection signals. Finally, we conducted functional annotation on the detected genes and found that these genes may influence body development (NR6A1), meat quality traits (MCCC1), growth traits (WSCD1, TMEM68, MFN1, NCKAP5), and immunity (IL11RA, CNTFR, CCL27, SLAMF1, SLAMF7, NAA35, and GOLM1).

Conclusion

We elucidated the genomic features and population structure of Xia’nan cattle and detected some selection signals in genomic regions potentially associated with crucial economic traits in Xia’nan cattle. This research provided a basis for further breeding improvements in Xia’nan cattle and served as a reference for genetic enhancements in other crossbreed cattle.
The draft genome of Nitzschia closterium f. minutissima and transcriptome analysis reveals novel insights into diatom biosilicification
Authors: Li Yajun , He Jinman , Zhang Xiuxia , Deng Xiaodong
Published: June 2024

Background

Nitzschia closterium f. minutissima is a commonly available diatom that plays important roles in marine aquaculture. It was originally classified as Nitzschia (Bacillariaceae, Bacillariophyta) but is currently regarded as a heterotypic synonym of Phaeodactylum tricornutum. The aim of this study was to obtain the draft genome of the marine microalga N. closterium f. minutissima to understand its phylogenetic placement and evolutionary specialization. Given that the ornate hierarchical silicified cell walls (frustules) of diatoms have immense applications in nanotechnology for biomedical fields, biosensors and optoelectric devices, transcriptomic data were generated by using reference genome-based read mapping to identify significantly differentially expressed genes and elucidate the molecular processes involved in diatom biosilicification.

Results

In this study, we generated 13.81 Gb of pass reads from the PromethION sequencer. The draft genome of N. closterium f. minutissima has a total length of 29.28 Mb, and contains 28 contigs with an N50 value of 1.23 Mb. The GC content was 48.55%, and approximately 18.36% of the genome assembly contained repeat sequences. Gene annotation revealed 9,132 protein-coding genes. The results of comparative genomic analysis showed that N. closterium f. minutissima was clustered as a sister lineage of Phaeodactylum tricornutum and the divergence time between them was estimated to be approximately 17.2 million years ago (Mya). CAFF analysis demonstrated that 220 gene families that significantly changed were unique to N. closterium f. minutissima and that 154 were specific to P. tricornutum, moreover, only 26 gene families overlapped between these two species. A total of 818 DEGs in response to silicon were identified in N. closterium f. minutissima through RNA sequencing, these genes are involved in various molecular processes such as transcription regulator activity. Several genes encoding proteins, including silicon transporters, heat shock factors, methyltransferases, ankyrin repeat domains, cGMP-mediated signaling pathways-related proteins, cytoskeleton-associated proteins, polyamines, glycoproteins and saturated fatty acids may contribute to the formation of frustules in N. closterium f. minutissima.

Conclusions

Here, we described a draft genome of N. closterium f. minutissima and compared it with those of eight other diatoms, which provided new insight into its evolutionary features. Transcriptome analysis to identify DEGs in response to silicon will help to elucidate the underlying molecular mechanism of diatom biosilicification in N. closterium f. minutissima.
Real-time procedure information sharing as a means to reduce perioperative anxiety in families of children undergoing elective surgery - a randomized controlled study
Authors: Yun Linjun , Li Yuanhong , Yin Lu
Published: June 2024

Objective

To investigate whether the surgical process information sharing system could alleviate the parental anxiety during a pediatric selective operation.

Design

Randomized controlled trial.

Methods

A questionnaire survey was conducted one day before surgery for the enrolled participants. Family members assigned to the intervention group received real-time process information sharing through service reminders during the surgical period, while the control group received standard perioperative education. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality during the perioperative period, and the State of Cohesion-13 Scale (SOC-13) and Self-rating Anxiety Scale (SAS) were used to assess anxiety levels. Satisfaction levels during the perioperative period were assessed through a follow-up survey conducted one day after surgery.

Results

The intervention group showed better scores in terms of PSQI, SOC-13, SAS, and postoperative satisfaction levels at various time points compared to the control group, with statistically significant differences observed (P < 0.05).

Conclusion

Real-time process information sharing is effective in reducing perioperative sleep disorders and anxiety among family members of pediatric patients, as well as improving satisfaction levels. This approach not only establishes a process and mechanism for effective doctor-patient communication but also helps implement continuous perioperative care, thereby optimizing internet healthcare services.
Isoflurane-induced neuroinflammation and NKCC1/KCC2 dysregulation result in long-term cognitive disorder in neonatal mice
Authors: Xu Dongni , Liu Jiayi , Meng Shiyu , Sun Meixian , Chen Yuqing , Hong Yu
Published: June 2024

Background

The inhalational anesthetic isoflurane is commonly utilized in clinical practice, particularly in the field of pediatric anesthesia. Research has demonstrated its capacity to induce neuroinflammation and long-term behavioral disorders; however, the underlying mechanism remains unclear [1]. The cation-chloride cotransporters Na+–K+–2Cl−–1 (NKCC1) and K+–2Cl−–2 (KCC2) play a pivotal role in regulating neuronal responses to gamma-aminobutyric acid (GABA) [2]. Imbalances in NKCC1/KCC2 can disrupt GABA neurotransmission, potentially leading to neural circuit hyperexcitability and reduced inhibition following neonatal exposure to anesthesia [3]. Therefore, this study postulates that anesthetics have the potential to dysregulate NKCC1 and/or KCC2 during brain development.

Methods

We administered 1.5% isoflurane anesthesia to neonatal rats for a duration of 4 h at postnatal day 7 (PND7). Anxiety levels were assessed using the open field test at PND28, while cognitive function was evaluated using the Morris water maze test between PND31 and PND34. Protein levels of NKCC1, KCC2, BDNF, and phosphorylated ERK (P-ERK) in the hippocampus were measured through Western blotting analysis. Pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were quantified using ELISA.

Results

We observed a decrease in locomotion trajectories within the central region and a significantly shorter total distance in the ISO group compared to CON pups, indicating that isoflurane induces anxiety-like behavior. In the Morris water maze (MWM) test, rats exposed to isoflurane exhibited prolonged escape latency onto the platform. Additionally, isoflurane administration resulted in reduced time spent crossing in the MWM experiment at PND34, suggesting long-term impairment of memory function. Furthermore, we found that isoflurane triggered activation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; downregulated KCC2/BDNF/P-ERK expression; and increased the NKCC1/KCC2 ratio in the hippocampus of PND7 rats. Bumetadine (NKCC1 specific inhibitors) reversed cognitive damage and effective disorder induced by isoflurane in neonatal rats by inhibiting TNF-α activation, normalizing IL-6 and IL-1β levels, restoring KCC2 expression levels as well as BDNF and ERK signaling pathways. Based on these findings, it can be speculated that BDNF, P-ERK, IL-1β, IL-6 and TNF - α may act downstream of the NKCC1/KCC2 pathway.

Conclusions

Our findings provide evidence that isoflurane administration in neonatal rats leads to persistent cognitive deficits through dysregulation of the Cation-Chloride Cotransporters NKCC1 and KCC2, BDNF, p-ERK proteins, as well as neuroinflammatory processes.
Comment on “Does the 5-2-1 criteria identify patients with advanced Parkinson’s disease? Real-world screening accuracy and burden of 5-2-1-positive patients in 7 countries”
Authors: Moes Harmen R. , Buskens Erik , van Laar Teus
Published: June 2024

The 5-2-1 criteria are intended to help general neurologists identify patients with advanced Parkinson’s disease who may benefit from treatment optimisation, such as with a device-aided therapy. Although the 5-2-1 criteria claim to address an unmet need, we urge readers to cautiously interpret the results of this validation study.
Application of modified Yamane technique in intrascleral intraocular lens fixation combined with or without iris reconstruction
Authors: Wang Xiaofang , Su Mengru , Li Yushan , Xie Hairong , Sun Xinghong , Jiang Feng
Published: June 2024

Aims

To explore the application and long-term clinical effects of modified Yamane technique in intrascleral intraocular lens (IOL) fixation combined with or without iris reconstruction.

Settings and design

The data of patients receiving IOL fixation with modified Yamane technique in an ophthalmology department between December 2021 and August 2023 were analyzed retrospectively. The longest follow-up duration was > 12 months.

Methods and material

The trailing haptic was fixed with the needle before the leading haptic. The silicone haptic stoppers were used to stabilize the IOL when iris reconstruction was combined. Preoperative and postoperative best-corrected visual acuity (BCVA), corneal endothelial cells (CECs), postoperative intraocular pressure (IOP), surgical indications and methods, and postoperative complications were recorded. Anterior segment optical coherence tomography (OCT) was used to evaluate IOL decentration and tilt. The paired sample t-test or Wilcoxon rank sum test were used to compare the results of the same index before and after the operation.

Results

Twelve patients (12 eyes) were included in this cohort. There were 1 case of IOL dislocation, eight cases of lens dislocation or subluxation, and three cases of aphakia. Traumatic lens dislocation was the main cause of aphakia. Primary lens extraction was performed in previous surgeries, and all three were combined with pars plana vitrectomy (PPV). Four of 12 patients underwent IOL fixation and iris reconstruction. The mean age of participants was 63 ± 10.61 years. The mean BCVA increased from 0.89 ± 0.72 logMAR to 0.39 ± 0.56 logMAR at the last visit (p < 0.05). The postoperative relative refractive error was − 0.13 ± 0.42 D (–0.60 D to + 0.57 D). The OCT showed that the IOLs were well centered, with a mean decentration of 0.20 ± 0.13 mm and a mean tilt of 2.31°±0.93°. Ten patients did not experience any complications.

Conclusions

The modified Yamane technique in IOL fixation surgery, especially combined with iris reconstruction, reduces operation difficulty, increases operational stability and safety, and improves postoperative visual acuity without serious intra- or postoperative complications. The long-term improvement effect was remarkable.
The relationship between mental health and risky decision-making in children and adolescents: a scoping review
Authors: Bentivegna Francesca , Papachristou Efstathios , Flouri Eirini
Published: June 2024

Background

Evidence from studies on adult participants and clinical samples of children suggest an association between risky decision-making and mental health problems. However, the extent and nature of this association in the general youth population remains unknown. Therefore, this scoping review explores the current evidence on the relationship between mental health (internalising and externalising symptoms) and risky decision-making in the general youth population.

Methods

A three-step search strategy was followed and applied to four databases. Selection criteria included participants < 18 years representative of the general population, and information on both risky decision-making (assessed using gambling tasks) and internalising /externalising symptoms. Data were extracted and synthesised for study and participant characteristics, aspects and measures for the main variables, and key findings.

Results

Following screening, twenty-one studies were retrieved. Non-significant associations were more frequent than significant associations for both internalising and externalising symptoms, particularly for social difficulties and broad externalising symptoms. Among the significant associations, hyperactivity/inattention and conduct problems appeared to be positively associated with risk-taking and negatively associated with quality of decision-making. However, patterns were less clear for links between risky decision-making and internalising symptoms, especially between risk-taking and anxiety symptoms.

Conclusions

The present review suggests predominantly a lack of relationship between risky decision-making and mental health problems, and outlines several possible reasons for it. However, when specificity is considered carefully there seems to be a link between risk-taking and specific externalising problems. Future research should employ study designs aimed at disentangling the direction of this relationship and identifying specific aspects of mental health and risky decision-making that could be eventually addressed by tailored interventions.