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This study aims to present an easily scalable, cost-efficient process of dECM extraction from porcine meniscus, dedicated to bioink preparation and 3D bioprinting. Due to its cartilage like structure and mechanical robustness, the meniscus is an exceptionally demanding tissue for extraction and decellularisation of its ECM. Its processing poses a great difficulty and renders the methods previously developed for soft tissues useless. A process, combining homogenisation, hydrolysis, supercritical CO2 (scCO2) extraction and lyophilisation, was developed to meet this challenge. This protocol allows for retaining its native compounds and biocompatibility while offering good printability and providing a stimulatory environment for cell proliferation and differentiation towards a meniscus-like phenotype. Also, this process is economically and ecologically friendly since it doesn't require the use of high amounts of solvents, detergents or expensive enzymes (DNase). The decellularisation process has been meticulously studied, demonstrating a substantial reduction in DNA content but still exceeding accepted thresholds. The study further explores the biocompatibility of the dECM, demonstrating no detrimental effects of remnant DNA on cell survival during extended in vitro culture, indicating excellent biocompatibility. These findings challenge the current definition of decellularisation effectiveness based solely on DNA content, proposing a broader assessment of biological effects.

Digitization in Indonesia has been on the rise since the Covid-19 pandemic, reshaping the lifestyle of the population with a shift from conventional to online shopping. E-commerce transactions, especially through smartphones, offer speed and convenience, making e-commerce the primary intermediary between businesses and consumers. For instance, Traveloka, despite the tourism industry's impact in 2021, remains a key developer, facing the staycation trend for continued transaction growth amid competition. Established in 2012, Traveloka Holding Ltd has successfully secured the top position in the Top Brand Awards. This study, conducted with 111 respondents in the Bekasi Regency, one of the largest metropolis city in the Indonesian capital region, aims to examine the impact of Traveloka's co-creation, currency, communal activation, and conversation on customer loyalty. Customer journey serves as a mediator, while the user interface does not significantly moderate the relationship. The results indicate that each element of the 4C Mix Marketing 4.0 directly contributes to enhancing user loyalty to Traveloka, although the mediating role of the customer journey tends to be low.

Background Multiple randomized trials could not establish the noninferiority of endovascular thrombectomy (EVT) alone without preceding intravenous thrombolysis (IVT) or superiority of IVT followed by EVT in anterior circulation large‐vessel occlusion stroke. The role of prior IVT in posterior circulation large‐vessel occlusion remains controversial. Methods In this multicenter, retrospective study, patients with stroke with large‐vessel occlusion in the posterior circulation who received EVT alone or with IVT were selected from the stroke thrombectomy and aneurysm registry between 2013 and 2022. Effects of IVT followed by thrombectomy on favorable functional outcome (defined as modified Rankin scale≤3 at 90 days) and safety were investigated using multivariable logistic and linear regression models. Results Of the 588 included patients, 67% (n = 394) were treated with EVT alone and 29% (n = 170) with EVT after IVT, and 4% (n = 24) have missing values on this variable. Controlling for multiple confounding factors, IVT was not associated with a higher likelihood of favorable functional outcome at 90 days (odds ratio, 1.04 [95% CI, 0.52–2.09; P = 0.901). Thrombectomy alone did not show any safety advantages compared with those receiving IVT. Conclusion Similar functional outcomes and complication rates were seen in patients with posterior circulation large‐vessel occlusion treated with EVT alone versus EVT after IVT. Further prospective studies are required to determine the utility of IVT in posterior circulation stroke, especially in patients being directly admitted to thrombectomy centers.

With the rapid urbanization in Malaysia, human activities have caused damage to many waterfront areas. Efforts are being made to restore the connection between the community and river waterfronts while creating attractive urban spaces. However, the implementation of modern design development strategies without sufficient consideration of cultural aspects and societal visual preferences has raised a number of questions with regard to the public’s acceptance and appreciation of the newly implemented urban facades. This study aims to comprehensively examine the relationship between cultural elements and visual preferences in the context of urban waterfront walkways in Malaysia. This study implemented a photo survey to assess the visual preferences of the study’s respondents. The results indicated a significant correlation between subjects’ visual preferences and their cultural backgrounds. Additionally, the analysis of the collected data highlights a strong correlation between the presence of green elements and what the respondents perceived as part of the Malaysian culture. Additionally, the historical character of the study area, as represented by historical buildings, significantly influences the preferences of Malaysian respondents. Furthermore, certain elements, such as food carts, high-rise buildings, and water, are among the least preferred compared to other elements. Ultimately, incorporating these elements in the early design stages can contribute to the creation of culturally connected and visually appealing urban waterfront spaces in Malaysia.

We present the NAIL Accelerator Interface Layer, a framework for offloading accelerated computations to Field Programmable Gate Arrays served across the network. NAIL has been specifically optimised for latency sensitive applications and has been deployed and sustained for a variety of high-scale operational workloads. It allows compute acceleration benefits of Field Programmable Gate Arrays (FPGAs) to be more easily exploited through a flexible host communication layer. Multiple accelerators with independent streams are supported with demonstrated scalability to large numbers of concurrent tasks. Virtualisation and management is incorporated into the hardware to do away with the typical overheads and design complexities of software-managed offload frameworks. As a result, it achieves very low latencies of 4 microseconds for inline requests to below 10 microseconds for larger request sizes. NAIL has been developed and deployed in a challenging industrial setting and is now released to the wider community as open source.

Background and Purpose Outcomes following mechanical thrombectomy (MT) are strongly correlated with successful recanalization, traditionally defined as modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b. This retrospective cohort study aimed to compare the outcomes of patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS; 2–5) who achieved mTICI 2b versus those who achieved mTICI 2c/3 after MT. Methods This study utilized data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combined databases from 32 thrombectomy-capable stroke centers between 2013 and 2023. The study included only patients with low ASPECTS who achieved mTICI 2b, 2c, or 3 after MT for internal carotid artery or middle cerebral artery (M1) stroke. Results Of the 10,229 patients who underwent MT, 234 met the inclusion criteria. Of those, 98 (41.9%) achieved mTICI 2b, and 136 (58.1%) achieved mTICI 2c/3. There were no significant differences in baseline characteristics between the two groups. The 90-day favorable outcome (modified Rankin Scale score: 0–3) was significantly better in the mTICI 2c/3 group than in the mTICI 2b group (adjusted odds ratio 2.35; 95% confidence interval [CI] 1.18–4.81; P=0.02). Binomial logistic regression revealed that achieving mTICI 2c/3 was significantly associated with higher odds of a favorable 90-day outcome (odds ratio 2.14; 95% CI 1.07–4.41; P=0.04). Conclusion In patients with low ASPECTS, achieving an mTICI 2c/3 score after MT is associated with a more favorable 90-day outcome. These findings suggest that mTICI 2c/3 is a better target for MT than mTICI 2b in patients with low ASPECTS.

Abstract Background Despite clear evidence of nonlinear interactions in the molecular architecture of polygenic diseases, linear models have so far appeared optimal in genotype-to-phenotype modeling. A key bottleneck for such modeling is that genetic data intrinsically suffers from underdetermination ( $$p \gg n$$ p ≫ n ). Millions of variants are present in each individual while the collection of large, homogeneous cohorts is hindered by phenotype incidence, sequencing cost, and batch effects. Results We demonstrate that when we provide enough training data and control the complexity of nonlinear models, a neural network outperforms additive approaches in whole exome sequencing-based inflammatory bowel disease case–control prediction. To do so, we propose a biologically meaningful sparsified neural network architecture, providing empirical evidence for positive and negative epistatic effects present in the inflammatory bowel disease pathogenesis. Conclusions In this paper, we show that underdetermination is likely a major driver for the apparent optimality of additive modeling in clinical genetics today.

Mathematics is a subject taught at every level of education and has a vital role in everyday life. However, in reality, student mathematics learning achievement tends to be low. One of the reasons is the monotonous learning model or strategy and uninteresting learning media. The learning process is only one-way, making students imitate and record how to answer the questions given by the teacher without understanding the concept correctly. In addition, the learning media used is monotonous and tends to be traditional. Namely, only the whiteboard and several times using an LCD projector, making students bored and passive. So, innovative learning strategies and media are needed to overcome these problems. This study aims to determine the improvement of student mathematics learning achievement in statistics material in grade 10 through implementing Problem-based Learning integrated with Flipped Classroom assisted by Google Sites. The research method used is Classroom Action Research with the Kemmis and McTaggart model, which consists of four stages: Planning, Action, Observation, and Reflection. The results showed increased student mathematics learning achievement in statistics material in grade 10 through implementing Problem-based Learning integrated with Flipped Classroom, assisted by Google Sites. The percentage of classical learning completeness in each cycle is Pre-Cycle 56% with an average of 69.3, Cycle I 72% with an average of 75.7, and Cycle II 89% with an average of 84.7. So, Problem-based Learning integrated with Flipped Classroom, assisted by Google Sites, successfully improves student learning achievement and is recommended to be implemented in the classroom.

Place attachment is often seen as a resource for coping with health recovery, especially in the post-pandemic period. The purpose of this review was to systematically review the variables, research frameworks, and interactions related to place attachment and recovery perceptions. This paper reviewed 53 papers from 2020 to 2023 on place attachment and recovery perception using ATLAS.ti. Existing research confirms that there are differences in the degree of attachment and recovery in different types of urban environments. This paper encourages the integration of information between different disciplines, such as urban planning specialists, environmental psychologists, and public health experts, to further improve the urban environment.

Abstract Introduction Despite the increasing popularity of social media, little research has been conducted on its impact on lifestyle behaviors and health outcomes among adults. This study aimed to investigate whether more frequent social media screen time use is associated with poorer lifestyle behaviors, overweight or obesity, and depressive symptoms. Additionally, this study examined the potential use of social media to positively influence health. Methods An anonymous one‐time survey was conducted among English‐speaking social media users aged 18–34 in Southern California. Self‐reported height and weight were used to calculate body mass index (BMI), and the Patient Health Questionnaire‐9 (PHQ‐9) was used to estimate the severity of depressive symptoms. A cumulative risk score for lifestyle behaviors was also tallied. Three focus groups were held with a subset of the survey population to gain insights on social media, lifestyle behaviors, and health. A mixed method analysis was used to analyze the data. Results The survey data of 86 complete cases showed a positive correlation (r = 0.421; p

Background As the number of thrombectomy passes increases during endovascular therapy (EVT) for acute stroke, neurointerventionalists must weigh the risks of potential complications against the risk of failing to recanalize the affected vessel. Thus, we investigated the effectiveness and safety of EVT for patients with acute stroke in which ≥5 EVT passes were performed. Methods This retrospective cohort study from January 2013 to December 2022 included 31 thrombectomy‐capable centers. Patients in whom ≥5 EVT passes were made were included in the analysis. The patients with successful recanalization defined as modified Thrombolysis in Cerebral Infarction ≥2b at 5, 6, 7, or more passes were compared with unsuccessful recanalization. We also compared procedure time, separated by 30 minutes. Primary outcome was a favorable 90‐day outcome (modified Rankin scale score of 0–2). Secondary outcomes were intracranial hemorrhage and death. Results A total of 407 patients met the inclusion criteria, of which 175 were women (43.1%); the mean age was 67.3 years. In 265 (65.1%) patients, successful recanalization was achieved: 134 patients with 5 passes, 67 patients with 6 passes, and 64 with ≥7 passes. Intravenous recombinant tissue plasminogen activator administration was more common in the unsuccessful recanalization group (successful recanalization with 5, 6, and ≥7 EVT passes and unsuccessful recanalization: 35.3%, 30.3%, 18.8%, and 45.4%, respectively). Successful recanalization with 5, 6, and ≥7 EVT passes was associated with favorable outcome compared with unsuccessful recanalization group (adjusted odds ratio successful recanalization with 5, 6, and ≥7 EVT passes to unsuccessful recanalization [95% CIs]: 8.29 [2.13–32.3]; 14.0 [3.27–60.3]; and 5.26 [1.12–24.8], respectively). However, symptomatic intracranial hemorrhage was not significantly different between the groups. Regarding procedure time, favorable outcome was not significantly different in each group, while symptomatic intracranial hemorrhage occurred more frequently in the 60 to 89 minutes group compared with the

In a drug discovery setting, pharmaceutical companies own substantial but confidential datasets. The MELLODDY project developed a privacy-preserving federated machine learning solution and deployed it at an unprecedented scale. Each partner built models for their own private assays that benefitted from a shared representation. Established predictive performance metrics such as AUC ROC or AUC PR are constrained to unseen labeled chemical space and cannot gage performance gains in unlabeled chemical space. Federated learning indirectly extends labeled space, but in a privacy-preserving context, a partner cannot use this label extension for performance assessment. Metrics that estimate uncertainty on a prediction can be calculated even where no label is known. Practically, the chemical space covered with predictions above an uncertainty threshold, reflects the applicability domain of a model. After establishing a link to established performance metrics, we propose the efficiency from the conformal prediction framework (‘conformal efficiency’) as a proxy to the applicability domain size. A documented extension of the applicability domain would qualify as a tangible benefit from federated learning. In interim assessments, MELLODDY partners reported a median increase in conformal efficiency of the federated over the single-partner model of 5.5% (with increases up to 9.7%). Subject to distributional conditions, that efficiency increase can be directly interpreted as the expected increase in conformal i.e. low uncertainty predictions. In conclusion, we present the first indication that privacy-preserving federated machine learning across massive drug-discovery datasets from ten pharma partners indeed extends the applicability domain of property prediction models.

Introduction Transradial access (TRA) has become increasingly utilized among neurointerventionalists. There is evidence of reduced complications and higher patient satisfaction compared to transfemoral access (TFA), but more data directly comparing the safety and efficacy of the two approaches is needed. To assess the proportion of technical success and complications with TRA versus TFA in patients who underwent neuroendovascular diagnostic and therapeutic procedures. Methods PRISMA guidelines were used to conduct a systematic review of the literature with PubMed/Medline, Scopus, Embase, and Cochrane databases up to February 2023. Randomized clinical trials (RCT) and observational studies that compared TRA and TFA were included. Studies reporting results of patients who underwent diagnostic angiograms, endovascular management of acute stroke, aneurysm repair, and carotid or vertebral stenting were included. Our primary outcome was technical success, defined as successful arterial access and completion of the intended procedure without crossover. Secondary safety outcomes were rate of complications including access site and non‐access site related, and other efficacy measures such as procedure duration, fluoroscopy time, and radiation exposure. Random effects model was used to perform a meta‐analysis. The Mantel‐Haenszel method was used to calculate risk ratio (RR) and 95% confidence intervals (CI) for each outcome. Heterogeneity was evaluated using I2 and considered high if over 70%. Results Twenty‐nine studies comprising 14,523 patients met inclusion criteria. TRA was attempted in 5,865 (40.38%) patients and TFA in 8,658 (59.62%). Baseline characteristics were similar between groups. The rate of technical success was 95.46% (95% CI: 93.59 – 96.81; p < 0.01) in the TRA group compared with 98.43% (95% CI: 97.60 – 98.97; p = 0.02) in the TFA group. Patients who underwent a diagnostic or therapeutic angiogram via TRA had a slightly lower chance of achieving technical success (RR = 0.98; 95% CI: 0.96 – 0.99; p < 0.01) compared to TFA, with substantial heterogeneity (I2 = 68%). Major access site complications were non‐significantly lower in the TRA group (RR = 0.64; 95% CI: 0.29 – 1.41; p = 0.81) with null heterogenicity (I2 = 0%) between groups. Minor access site complications were significantly lower in the TRA group (RR = 0.43; 95% CI 0.28 – 0.67; p < 0.01), with moderate heterogeneity (I2 = 57%). Non‐access site related complications (including mortality) were lower in the TRA group (RR = 0.69; 95% CI 0.51 – 0.94; p = 0.14) with low heterogeneity (I2 = 26%) between groups; for this outcome, the TRA approach shows a protective but not statistically significant result. Conclusion Our study suggests TRA is feasible and safe for diagnostic and therapeutic neuroendovascular procedures with low certainty of evidence. Minor complications were lower in the TRA group. RCTs directly comparing TRA vs TFA for these procedures are needed to confirm these results.

Abstract Articular cartilage and meniscus injuries are prevalent disorders with insufficient regeneration responses offered by available treatment methods. In this regard, 3D bioprinting has emerged as one of the most promising new technologies, offering novel treatment options. Additionally, the latest achievements from the fields of biomaterials and tissue engineering research identified constituents facilitating the creation of biocompatible scaffolds. In this study, we looked closer at hyaluronic acid and multi-walled carbon nanotubes as bioink additives. Firstly, we assessed the minimal concentrations that stimulate cell viability, and decrease reactive oxygen species and apoptosis levels in 2D cell cultures of normal human knee articular chondrocytes (NHAC) and human adipose-derived mesenchymal stem cells (hMSC-AT). In this regard, 0.25 mg/ml of hyaluronic acid and 0.0625 mg/ml of carbon nanotubes were selected as the most optimal concentrations. In addition, we investigated the protective influence of 2-phospho-L-ascorbic acid in samples with carbon nanotubes. Tests conducted on 3D bioprinted constructs revealed that only a combination of components positively impacted cell viability throughout the whole experiment. Gene expression analysis of COL1A1, COL6A1, HIF1A, COMP, RUNX2, and POU5F1 showed significant changes in the expression of all analyzed genes with a progressive overall loss of transcriptional activity in most of them.

Background Mechanical thrombectomy of middle cerebral artery M2 segment occlusion of the middle cerebral artery has reported safety and efficacy in recent post‐hoc and observational studies. However, there is no known benefit of mechanical thrombectomy for patients with M2 segment occlusions in the delayed time window (>6 hours). Methods The Stroke Thrombectomy and Aneurysm Registry (STAR) is a prospective, multicenter, nonrandomized observational study registry for acute ischemic stroke thrombectomy and aneurysm treatment. We analyzed all patients who underwent mechanical thrombectomy within the late time window (>6 hours from symptom onset) involving isolated M2 occlusions. We used propensity score matching to select a comparison group of patients who underwent mechanical thrombectomy for M1 occlusion in the same time window. Results Of 1083 consecutive patients analyzed, propensity matching yielded 180 well matched M1 and M2 pairs. Baseline demographics were well balanced between the groups (M1 and M2). Alberta stroke program early CT score (7.6±1.7 versus 8.3±1.5; P

In the Western Hemisphere, bat-associated rabies viruses (RABVs) have established independent transmission cycles in multiple mammal hosts, forming genetically distinct lineages. In New Mexico, USA, skunks, bats, and gray foxes are rabies reservoir hosts and represent a public health risk because of encounters with humans. During 2015 and 2019, two previously undescribed RABVs were detected in 2 gray foxes (Urocyon cinereoargenteus) in Lincoln County, New Mexico. Phylogenetic analysis of the nucleoprotein gene indicated that the isolates are a novel RABV variant. These 2 cases probably represent repeated spillover events from an unknown bat reservoir to gray foxes. Molecular analysis of rabies cases across New Mexico identified that other cross-species transmission events were the result of viral variants previously known to be enzootic to New Mexico. Despite a robust rabies public health surveillance system in the United States, advances in testing and surveillance techniques continue to identify previously unrecognized zoonotic pathogens.

Abstract Background From 2012 to 2015, a health promotion intervention (under a project called HADP) aiming to improve children’s well-being was implemented in Horowpathana, Sri Lanka. The donor organization reports positive results regarding children’s well-being and behaviour changes, but mixed results regarding its sustainability. A need for a complementary evaluation was therefore identified. The current study intended to provide a complementary evaluation at four months after the programme closure and to assess the sustainability of the HP intervention from the perspective of mothers who participated in the HADP. Ethical approval for this study was obtained from the ethics review subcommittee of Faculty of Applied Sciences, RUSL. Methods A descriptive qualitative study was carried out using in-depth, semi-structured interviews with a convenient sample of 15 mothers who previously participated in HADP. Data analysis was done using the content analysis method. Results Mothers attributed diverse perceptions in line with the theme of “health literacy”. Two sub-themes emerged: transformation for betterment and sustainability. The sub-theme of transformation for betterment consists of three categories: individual-level transformation, family-level transformation and social/community-level transformation. Sub-theme sustainability consists of two categories: (1) drivers/adaptations for continuation and (2) determinants that hinder the continuation. Conclusions The mothers’ perspectives were strongly related to the definition of health literacy, which emphasizes people’s ability to use health information to make “well-informed” decisions that incorporate a public health perspective. They also acknowledged the responsibility of social organizations to address health literacy. From a health promotion perspective, the findings of our study indicate that people and organizations can use their health literacy skills to improve the health and well-being of their community and its members. Further research is necessary to explore the factors that affect the sustainability of health promotion interventions in the long run.

The integration of artificial neuromorphic devices with biological systems plays a fundamental role for future brain-machine interfaces, prosthetics, and intelligent soft robotics. Harikesh et al. demonstrate all-printed organic electrochemical neurons on Venus flytrap that is controlled to open and close.

The team of the Institute of Archaeological Sciences of the Eötvös Loránd University conducted a rescue excavation in the Baradla Cave in 2019. The work concentrated in a passage leading to a less-researched branch of the cave (the so-called Róka-ág [Fox Branch]) and one of the lesser rooms named Biológiai labor (Biological Laboratory). The passage towards the low and narrow Róka-ág was used for millennia, as attested by the objects from various historical periods and the stakeholes, probably related to former wooden walkways, discovered there. We unearthed an intact Neolithic culture layer preserved by a travertine (calc-sinter) deposit in Biológiai labor, while the metal detector survey carried out in the cave simultaneously with the excavations yielded Late Bronze and Early Iron Age, as well as medieval metal objects. The most significant discovery of our metal detector specialists was a Middle Bronze Age depot of decorative bronze clothing accessories. The recovered findings and observed features confirmed that the internal spaces of the Baradla Cave served as venues for ritual activity in the Neolithic and the Bronze Age.

In 2020, the spread of Coronavirus (COVID-19) had a global impact on normal daily life. The Government of Malaysia officially declared the Movement Control Order (MCO), an official national lockdown, to reduce the virus’s spread. In the face of the unprecedented global health pandemic, Malaysia had struggled to protect its citizens’ welfare and livelihoods, particularly in the hardest-hit rural areas. Therefore, this study uses the sustainable livelihood approach (SLA) focusing on the aspect of financial assets and government intervention to enhance understanding on the vulnerability in rural area’s livelihood. Pasir Puteh, Kelantan was identified as the rural area for this study. The analysis was performed on a questionnaire survey based on convenience sampling of 62 respondents. Cross table analysis and a correlation test were used to examine the livelihood of the rural area concerning the financial assets, government intervention and vulnerability. The findings indicated that the MCO had a substantial impact on the rural area regarding the vulnerability toward the financial assets, such as employment status, job loss, increasing living costs, and an insufficient response to rural economic challenges. At the same time, there is no substantial government intervention in the welfare of rural areas. According to the results, the study concluded that the government should set up training courses to assist in the long-term recovery of rural areas due to the enforced lockdown, which has adversely affected rural livelihoods.

Abstract Background Many mental health problems emerge in late childhood and contribute significantly to the global burden of disease. Adverse outcomes can extend into adulthood if left untreated. This impact is exacerbated in low- and middle-income countries where significant treatment gaps persist. Improving mental health literacy may offer an effective strategy for early intervention but remains underexplored in these contexts. Methods An intervention was co-developed with children and young people (CYP) by undertaking a needs analysis combined with stakeholder consensus activities. A systematic review of mental health literacy interventions in South-East Asia was undertaken in addition to semi-structured interviews with 43 children and young people (19 with and 24 without experience of anxiety and depression), 19 parents of children with experience of mental health problems and 25 education and health professionals. A focus group was also held with 8 key stakeholders immersed nationally in policy and practice. Interview schedules explored participants’ experiences of mental health, unmet needs and priorities for intervention. Data were synthesised and presented at a 3-day co-production workshop. Attendees included 13 CYP, 6 parents/guardians, 2 teachers, 8 health professionals, 2 academics and 3 game designers. Consensus exercises were utilised to identify the preferred format, content and delivery of the intervention. A smaller group of patient and public involvement contributors worked with designers to further iterate the intervention. Results An immersive storyline digital application was co-developed for young people aged 11–15 with the primary aim of improving mental health literacy and self-management. The intervention comprises two chapters; one depression focussed, and the other anxiety focussed. The storyline format is interspersed with interactive games and exercises to promote engagement and encourage self-management. CYP also take part in group sessions delivered by trained facilitators before and after intervention use to discuss outcomes of and issues raised during the game. Conclusion The IMPeTUs intervention has been co-designed for CYP aged 11–15 to improve mental health literacy and enhance self-management abilities. To the best of our knowledge, this is the first Indonesian digital intervention to improve mental health literacy and self-management for this population. Implementation, acceptability, and impact are currently being explored in a multi-site case study evaluation.

Background Mechanical thrombectomy has become the first‐line treatment strategy for patients with large‐vessel occlusion strokes. Often >1 thrombectomy maneuver is necessary to achieve reperfusion. A first‐pass (FP) effect with improved functional outcomes after mechanical thrombectomy has been described. Aim of the present study is to investigate the FP effect in a large, international, multicenter stroke database. Methods Patients who underwent mechanical thrombectomy for large‐vessel occlusion stroke in the anterior cerebral circulation between January 2014 and January 2021 and achieved complete reperfusion were identified from the STAR (Stroke Thrombectomy and Aneurysm Registry). We compared functional outcomes of patients with FP (defined as modified treatment in cerebral ischemia score 3 after a single thrombectomy maneuver) versus multiple‐pass complete reperfusion (defined as modified treatment in cerebral ischemia 3 after ≥1 thrombectomy maneuver). Results A total of 1481 patients with anterior circulation large‐vessel occlusion stroke and successful recanalization were included in the analysis. FP complete recanalization was achieved in 778 patients versus 703 patients with multiple‐pass complete reperfusion. Patients with FP complete recanalization had higher Alberta Stroke Programme Early CT [Computed Tomography] Score at baseline (9 [7–10] versus 8 [7–10]; P=0.002), were less likely to be men (47% versus 51%; P=0.078) and to have intracranial internal carotid artery occlusions (14% versus 27%), as well as more likely to have M1/M2 occlusions (86% versus 73%; P

Background In cases of failed recanalization despite modern mechanical thrombectomy (MT) techniques, intracranial rescue stenting (RS) may be beneficial. However, outcomes and complications of RS relative to the natural history of ongoing emergent large vessel occlusion are unknown. To evaluate whether RS for ongoing emergent large vessel occlusion after failed MT achieves superior outcomes to the natural history of persistent emergent large vessel occlusion. Methods Patients from the Stroke Thrombectomy and Aneurysm Registry who underwent RS after failed MT from 2014 to 2019 were analyzed. For outcome comparisons, patients were screened for inclusion/exclusion criteria of 3 major randomized, controlled MT trials. Results Over 5 years, 2827 patients underwent thrombectomy, of which 120 required RS for failed revascularization. RS resulted in reperfusion (Thrombolysis in Cerebral Infarction≥2B) in 85.8%. Good 90‐day clinical outcomes (modified Rankin scale 0–2) were achieved in 33.9% of patients. Inclusion/exclusion criteria was met in 50 patients for MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), 64 patients for ESCAPE (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), and 45 patients for DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake‐Up and Late Presenting Strokes Undergoing Neurointervention). Of patients meeting trial criteria, 40.8% of the RS cohort achieved modified Rankin scale 0–2 versus 19% in the MR CLEAN medical arm (P

Plants are able to sense and respond to a myriad of external stimuli, using different signal transduction pathways, including electrical signaling. The ability to monitor plant responses is essential not only for fundamental plant science, but also to gain knowledge on how to interface plants with technology. Still, the field of plant electrophysiology remains rather unexplored when compared to its animal counterpart. Indeed, most studies continue to rely on invasive techniques or on bulky inorganic electrodes that oftentimes are not ideal for stable integration with plant tissues. On the other hand, few studies have proposed novel approaches to monitor plant signals, based on non-invasive conformable electrodes or even organic transistors. Organic electrochemical transistors (OECTs) are particularly promising for electrophysiology as they are inherently amplification devices, they operate at low voltages, can be miniaturized, and be fabricated in flexible and conformable substrates. Thus, in this study, we characterize OECTs as viable tools to measure plant electrical signals, comparing them to the performance of the current standard, Ag/AgCl electrodes. For that, we focused on two widely studied plant signals: the Venus flytrap (VFT) action potentials elicited by mechanical stimulation of its sensitive trigger hairs, and the wound response of Arabidopsis thaliana. We found that OECTs are able to record these signals without distortion and with the same resolution as Ag/AgCl electrodes and that they offer a major advantage in terms of signal noise, which allow them to be used in field conditions. This work establishes these organic bioelectronic devices as non-invasive tools to monitor plant signaling that can provide insight into plant processes in their natural environment.

In vitro non-cellular permeability models such as the parallel artificial membrane permeability assay (PAMPA) are widely applied tools for early-phase drug candidate screening. In addition to the commonly used porcine brain polar lipid extract for modeling the blood–brain barrier’s permeability, the total and polar fractions of bovine heart and liver lipid extracts were investigated in the PAMPA model by measuring the permeability of 32 diverse drugs. The zeta potential of the lipid extracts and the net charge of their glycerophospholipid components were also determined. Physicochemical parameters of the 32 compounds were calculated using three independent forms of software (Marvin Sketch, RDKit, and ACD/Percepta). The relationship between the lipid-specific permeabilities and the physicochemical descriptors of the compounds was investigated using linear correlation, Spearman correlation, and PCA analysis. While the results showed only subtle differences between total and polar lipids, permeability through liver lipids highly differed from that of the heart or brain lipid-based models. Correlations between the in silico descriptors (e.g., number of amide bonds, heteroatoms, and aromatic heterocycles, accessible surface area, and H-bond acceptor–donor balance) of drug molecules and permeability values were also found, which provides support for understanding tissue-specific permeability.

Background. The aim of this study was to determine the long-term efficacy and safety of tacrolimus (Tac) and cyclosporine immunosuppression in pediatric liver transplantation (LTx). Methods. One hundred fifty-six patients who had taken part in a multicenter, randomized, open, parallel study of Tac and corticosteroids versus cyclosporine A microemulsion (CyA-ME), corticosteroids, and azathioprine. Patients were assessed at regular intervals up to 14 y after LTx. Analysis was conducted descriptively. Results. In a long-term follow-up, there was a similar incidence of acute rejection (Tac versus CyA-ME, 5 versus 8) and graft loss (5 versus 10). There were 11 deaths in the cohort, which were from infectious complications/malignancy in the Tac group (n = 2/5) and from chronic rejection/liver failure in the CyA-ME group (n = 3/6). A similar incidence of Epstein-Barr virus and posttransplant lymphoproliferative disease was observed (8 versus 8, 3 versus 3). However, there was a greater incidence of cosmetic adverse events in the CyA-ME cohort, with higher incidences of hypertrichosis (8 versus 27) and gum hyperplasia (20 versus 6). Growth improved equally in both groups. Overall, 81% of patients randomized to Tac remained on Tac therapy at study end, compared with 31% of patients randomized to CyA-ME. Common reasons for switching from CyA-ME included steroid-resistant/acute rejection (n = 12/8) and cosmetic changes (n = 8). Conclusions. This study is the first prospective, observational follow-up study of pediatric patients randomized to Tac and CyA-ME to evaluate long-term outcomes. Our analysis was limited by the degree of switchover between the cohorts; however, there were fewer deaths from chronic rejection/liver failure and reduced adverse events with Tac. Long-term use of Tac and Tac combination therapy appears to be safe and effective immunosuppression for pediatric LTx recipients.

Objective: The objective of this study was to describe the clinical course of a newborn who developed dilated cardiomyopathy (DCM) after COVID-19 infection.Methods: We retrospectively assessed the clinical notes of a pediatric patient with decompensated heart failure and who was previously positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Results: A 23-day-old newborn presented with diarrhea, hypoactivity, tachypnea, and lethargy. The infant progressed to develop respiratory failure and required orotracheal intubation due to apnea. A nasopharyngeal swab tested positive for SARS-COV-2. An echocardiogram (ECHO) demonstrated severe left ventricular dysfunction. The patient was discharged after 18 days with furosemide and angiotensin-converting enzyme inhibitors. During the follow-up period, the infant had two episodes of decompensated heart failure, with evidence of DCM. Investigations for known causes of secondary DCM were negative. The infant was promptly referred for heart transplantation.Conclusion: Although rare, we have observed a case of DCM in a newborn following COVID-19 disease. DCM may be a complication following COVID-19 disease in newborns.

Scurvy is a disorder of vitamin C deficiency which leads to vascular fragility and multisystemic complications. The paper presents a case of scurvy resulting in cardiac tamponade in addition to its classic manifestations. Life-threatening tamponade is an extreme presentation of scurvy and has not been reported in modern publications to the best of the present authors’ knowledge. (Level of Difficulty: Beginner.)

Abstract Background Despite evidence for the harms of waterpipe tobacco smoking (WTS), its use is increasing amongst college and university students worldwide. This systematic review aims to assess the knowledge of, attitudes towards and perceptions of WTS among college or university students. Methods We electronically searched MEDLINE, EMBASE, CINAHL, PSYCHINFO and ISI the Web of Science in October 2018, restricting our search to studies published since January 1990. We included studies among university or college students that used qualitative or quantitative methods, and addressed either knowledge, attitudes, or perceptions towards WTS. We excluded studies where WTS could not be distinguished from other forms of tobacco use and studies reported as abstracts where the full text could not be identified. Data were synthesised qualitatively and analysed data by region (global north/ south), and by reasons for use, knowledge of health hazards, how knowledge influences use, perceptions towards dependence, and policy knowledge. Results Eighty-six studies were included; 45 from the global north and 41 from the global south. Socio-cultural and peer influences were major contributing factors that encouraged students to initiate WTS. Furthermore, WTS dependence had two components: psychological and social. This was compounded by the general perception that WTS is a less harmful, less addictive and more sociable alternative to cigarette smoking. Knowledge of WTS harms failed to correlate with a reduced risk of WTS use, and some students reported symptoms of WTS addiction. A large proportion of students believed that quitting WTS was easy, yet few were able to do so successfully. Finally, students believed current public health campaigns to educate on WTS harms were inadequate and, particularly in the global north, were not required. Conclusion Reasons for WTS amongst university students are multi-faceted. Overall, interventions at both the individual and community level, but also policy measures to portray a message of increased harm amongst students, are required. Additional studies are necessitated to understand temporal changes in students’ beliefs, thus allowing for better targeted interventions.

Promoting well-being is one of the main goals to improve health in the world. We examined the well-being and quality of life over the course of one year in a sample that participated in an Indigenous Shipibo healing program where traditional healers work in a series of ayahuasca ceremonies. We also explored the role of decentering as a mediator of psychological well-being. Participants who attended the program responded to an online survey that included a Psychological Well-Being Scale; Oxford Happiness Questionnaire; The World Health Organization Quality of Life Spirituality, Religiousness, and Personal Beliefs scale; the WHO Quality of Life-BREF scale; and Decentering scale. Baseline (T0) and postassessment (T1) were completed by 200 individuals. Of these, 101 completed the follow-up assessment at three months (T2), 91 at 6 months (T3), and 94 at 12 months follow-up (T4) after leaving the center. ANOVA test was performed in a representative subsample to control the passing of time two months before attending the program (T-1). Pearson’s test was performed to examine the relationship between psychological well-being and decentering during the period of T0 and T1. A significant increase was observed in all the scales at all time points (p ≤ 0.01). The subgroup analysis performed in a representative subsample allowed us to infer that the significant differences in outcomes are due to the effect of their stay at the center and not the passing of time. We found a relationship between decentering and the improvement of psychological well-being (r = 0.57; p < 0.01). Our results suggest that the Indigenous Shipibo healing work with ayahuasca has value to improve long-term well-being and quality of life for Westerners.

Excitotoxicity is a phenomenon that describes the toxic actions of excitatory neurotransmitters, primarily glutamate, where the exacerbated or prolonged activation of glutamate receptors starts a cascade of neurotoxicity that ultimately leads to the loss of neuronal function and cell death. In this process, the shift between normal physiological function and excitotoxicity is largely controlled by astrocytes since they can control the levels of glutamate on the synaptic cleft. This control is achieved through glutamate clearance from the synaptic cleft and its underlying recycling through the glutamate-glutamine cycle. The molecular mechanism that triggers excitotoxicity involves alterations in glutamate and calcium metabolism, dysfunction of glutamate transporters, and malfunction of glutamate receptors, particularly N-methyl-D-aspartic acid receptors (NMDAR). On the other hand, excitotoxicity can be regarded as a consequence of other cellular phenomena, such as mitochondrial dysfunction, physical neuronal damage, and oxidative stress. Regardless, it is known that the excessive activation of NMDAR results in the sustained influx of calcium into neurons and leads to several deleterious consequences, including mitochondrial dysfunction, reactive oxygen species (ROS) overproduction, impairment of calcium buffering, the release of pro-apoptotic factors, among others, that inevitably contribute to neuronal loss. A large body of evidence implicates NMDAR-mediated excitotoxicity as a central mechanism in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and epilepsy. In this review article, we explore different causes and consequences of excitotoxicity, discuss the involvement of NMDAR-mediated excitotoxicity and its downstream effects on several neurodegenerative disorders, and identify possible strategies to study new aspects of these diseases that may lead to the discovery of new therapeutic approaches. With the understanding that excitotoxicity is a common denominator in neurodegenerative diseases and other disorders, a new perspective on therapy can be considered, where the targets are not specific symptoms, but the underlying cellular phenomena of the disease.

The long atmospheric residence time of CO2 creates an urgent need to add atmospheric carbon drawdown to CO2 regulatory strategies. Synthetic and systems biology (SSB), which enables manipulation of cellular phenotypes, offers a powerful approach to amplifying and adding new possibilities to current land management practices aimed at reducing atmospheric carbon. The participants (in attendance: Christina Agapakis, George Annas, Adam Arkin, George Church, Robert Cook-Deegan, Charles DeLisi, Dan Drell, Sheldon Glashow, Steve Hamburg, Henry Jacoby, Henry Kelly, Mark Kon, Todd Kuiken, Mary Lidstrom, Mike MacCracken, June Medford, Jerry Melillo, Ron Milo, Pilar Ossorio, Ari Patrinos, Keith Paustian, Kristala Jones Prather, Kent Redford, David Resnik, John Reilly, Richard J. Roberts, Daniel Segre, Susan Solomon, Elizabeth Strychalski, Chris Voigt, Dominic Woolf, Stan Wullschleger, and Xiaohan Yang) identified a range of possibilities by which SSB might help reduce greenhouse gas concentrations and which might also contribute to environmental sustainability and adaptation. These include, among other possibilities, engineering plants to convert CO2 produced by respiration into a stable carbonate, designing plants with an increased root-to-shoot ratio, and creating plants with the ability to self-fertilize. A number of serious ecological and societal challenges must, however, be confronted and resolved before any such application can be fully assessed, realized, and deployed.

Introduction. South Asians in the United States have a high prevalence of obesity and an elevated risk for cardiometabolic diseases. Yet, little is known about how aspects of neighborhood environment influence cardiometabolic risk factors such as body mass index (BMI) in this rapidly growing population. We aimed to investigate the association between perceived neighborhood social cohesion and BMI among South Asians. Methods. We utilized cross-sectional data from the MASALA study, a prospective community-based cohort of 906 South Asian men and women from the San Francisco Bay area and the greater Chicago area. Multivariable linear regression models, stratified by sex, were used to examine the association between perceived level of neighborhood social cohesion and individual BMI after adjusting for sociodemographics. Results. Participants were 54% male, with an average age of 55 years, 88% had at least a bachelor’s degree, and the average BMI was 26.0 kg/m2. South Asian women living in neighborhoods with the lowest social cohesion had a significantly higher BMI than women living in neighborhoods with the highest cohesion (β coefficient = 1.48, 95% CI 0.46–2.51, p=0.02); however, the association was not statistically significant after adjusting for sociodemographic factors (β coefficient = 1.06, 95% CI −0.01–2.13, p=0.05). There was no association between level of neighborhood social cohesion and BMI in South Asian men. Conclusion. Perceived neighborhood social cohesion was not significantly associated with BMI among South Asians in our study sample. Further research is recommended to explore whether other neighborhood characteristics may be associated with BMI and other health outcomes in South Asians and the mechanisms through which neighborhood may influence health.

Orthopaedic training in the United Kingdom has changed little from the Halstedian apprenticeship model of graduated responsibility, with the mantra “see one, do one, teach one”. Whilst still relevant in surgical teaching, the current and ongoing disruption to surgical training secondary to the coronavirus disease 2019 (COVID-19) outbreak highlights the need for alternative methods of experiential surgical learning, which allow for the development of the knowledge, skills, and attitudes of orthopaedic surgeons, to be sought.

Modernist practice, the modernist way of conservation and restoration, is against historicism, against reconstruction. The main rule is: deceit, forgery, falsification is forbidden. Despite this, some reconstructions were undertaken in Hungary, and recently the pressure for reconstructions has become even greater. Unfortunately, the categories of listed buildings, open-air museums and Disneyland are sometimes mixed up by the public and even by decision makers.

Background Recent randomized controlled clinical trials have provided solid evidence that mechanical thrombectomy (MT) coupled with best medical therapy (BMT) improve functional outcomes of acute ischemic stroke patients with large vessel occlusion compared with BMT alone. However, they provided inconclusive evidence on the benefit of MT on mortality. Methods and Results We evaluated the association of MT+BMT compared with BMT with the risk of 3‐month mortality using aggregate data from all available randomized controlled clinical trials. We also sought to identify potential predictors on the mortality risk and performed univariate meta‐regression analyses. Our literature search identified 11 eligible randomized controlled clinical trials, including a total of 2460 patients. The pooled rates of 3‐month mortality were 15% (95% CI:12%–19%) and 19% (95% CI:16%–23%), respectively, in the MT+BMT and BMT groups. In the overall analysis MT+BMT was associated with a significantly lower risk for 3‐month mortality compared with BMT (risk ratio=0.83, 95% CI:0.69–0.99; P=0.04), without heterogeneity across included studies (I2=3%, P for Cochran Q=0.41). No evidence of publication bias was present in funnel plot inspection and Egger statistical test (P=0.762). In meta‐regression analyses no moderating effect on the aforementioned association was detected with patient age (P=0.254), sex (P=0.702), admission systolic blood pressure (P=0.601), admission glucose (P=0.277), onset‐to‐groin puncture time (P=0.985), administration of intravenous alteplase before MT (P=0.804), MT under general anesthesia (P=0.735), and successful reperfusion following MT (P=0.663). Conclusions Our meta‐analysis provides evidence that MT+BMT reduces the risk of 3‐month mortality compared with BMT alone. This association appears not to be moderated by individual patient or procedural characteristics.