bluuebunny/crossref_metadata_2025 huggingface dataset:
Adsorption Potential of Schizophyllum commune White Rot Fungus for Degradation of Reactive Dye and Condition Optimization: A Thermodynamic and Kinetic Study
Authors: Raees Alia , Bhatti Haq Nawaz , Alshehri Sameer , Aslam Farheen , Al-Fawzan Foziah F. , Alissa Siham A. , Iqbal Munawar , Nazir Arif
Published: February 2023

The pollution due to dyes from textile sector is one of the major issues faced worldwide. This study was focused on the removal of the reactive dye, Drimaren Turquoise CL-B using Schizophyllum commune, a white rot fungus (WRF) keeping in mind the current environmental conditions. Different parameters like pH, sources of carbon & nitrogen, temperature, concentration of dye and C/N ratio were used to investigate their effect on the process. Maximum dye removal of 95.45% was obtained at pH 4.5, temperature 35°C, inoculum size 3 mL, veratryl alcohol (mediator), glucose (carbon source) and ammonium nitrate (nitrogen source). The enzyme activity was determined by employing enzyme assay. Laccase and Lignin peroxidase (LiP) activity was low while Manganese peroxidase (MnP) activity was highest. Maximum bio-sorption was achieved at pH 1 and 313 K. The pseudo-2nd-order kinetic model & Freundlich isotherm was best suited for the process of removal of dye. From these data, it is concluded that white rot fungus could possibly be the excellent biomaterial for elimination of synthetic dyes from wastewater.
Texture Feature‐Based Machine Learning Classification on MRI Image for Sepsis‐Associated Encephalopathy Detection: A Pilot Study
Authors: Mo Xiao , Xiong Xin , Wang Yijie , Gu Heyi , Yang Yuhang , He Jianfeng
Published: February 2023

Objective. The objective of this study was to assess the performance of combining MRI‐based texture analysis with machine learning for differentiating sepsis‐associated encephalopathy (SAE) from sepsis alone. Method. Sixty‐six MRI‐T1WI images of an SAE patient and 125 images of patients with sepsis alone were collected. Frontal lobe, brain stem, hippocampus, and amygdala were selected as regions of interest (ROIs). 279 texture features of each ROI were obtained using MaZda software. After the dimension reduction, 30 highly discriminative features of each ROI were adopted to differentiate SAE from sepsis alone using the CatBoost model. Results. The classification models of frontal, brain stem, hippocampus, and amygdala were constructed. The classification accuracy was above 0.83, and the area under the curve (AUC) exceeded 0.90 in the validation set. Conclusion. The texture features differed between SAE patients and patients with sepsis alone in different anatomical locations, suggesting that MRI‐based texture analysis with machine learning might be helpful in differentiating SAE from sepsis alone.
pH-Responsive Delivery of H2 through Ammonia Borane-Loaded Hollow Polydopamine for Intervertebral Disc Degeneration Therapy
Authors: Wang Weiheng , Xiao Bing , Qiu Yuanyuan , Liu Yi , Tang Guoke , Deng Guoying , Xi Yanhai , Xu Guohua , Wang Yeying
Published: February 2023

An imbalance in oxidative and inflammatory regulation is the main contributor to intervertebral disc degeneration (IDD). Hydrogen (H2) therapy is a promising antioxidation and anti-inflammatory approach. However, the key to the treatment is how to maintain the long-term effective H2 concentration in the intervertebral disc (IVD). Therefore, we developed a pH-responsive delivery of H2 through ammonia borane-loaded hollow polydopamine (AB@HPDA) for IDD therapy, which has sufficient capacity to control long-term H2 release in an acid-dependent manner in degenerative IVD. The characterization, toxicity, and pH-responsive H2 release of AB@HPDA was detected in vitro. The metabolization of AB@HPDA in the degenerated IVD was tested by in vivo imaging. The therapeutic effect of AB@HPDA on IDD was tested in vivo by X-ray, MRI, water content of the disc, and histological changes. Nuclear extracellular matrix (ECM) components, oxidative stress, and inflammation were also tested to explore potential therapeutic mechanisms. AB@HPDA has good biocompatibility at concentrations less than 500 μg/mL. The H2 release of AB@HPDA was pH responsive. Therefore, AB@HPDAs can provide efficient hydrogen therapy with controlled H2 release in response to the acidic degenerated IVD microenvironment. The metabolization of AB@HPDA in IVD was slow and lasted up to 11 days. HPDA and AB@HPDA significantly inhibited IDD, as tested by X-ray, MRI, disc water content, and histology (

P
<
0.05

). pH-responsive H2 delivery through AB@HPDAs has the potential to efficiently treat IDD by inhibiting ECM degradation and rebalancing oxidative stress and inflammation in degenerative IVDs.
Molecular Characterization of African Swine Fever Viruses Circulating in Can Tho City, Vietnam
Authors: Duc Hien Nguyen , Trung Hoang Le , My Quyen To , Phuc Khanh Nguyen , Thanh Nguyen Lam
Published: February 2023

African swine fever (ASF) is a highly contagious and deadly viral disease in domestic and feral pigs. Since 2018, the disease has spread and caused large socioeconomic consequences to the pig industry in several Asian countries including China, Vietnam, and South Korea. This study aims to determine the genotype, serotype, and genetic variation of representative ASF viruses (ASFV) responsible for the outbreaks in 2019–2022 in Can Tho city, a central administrative province in the Mekong delta, Vietnam. For outbreak investigation, the presence of causative ASFVs was tested using conventional PCR targeting the B646L gene. Subsequently, the amplification and sequencing of the DNA fragments of the putative B646L gene encoding the major capsid protein p72, EP402R gene encoding the viral hemagglutinin CD2‐like protein (CD2v), and intergenic region (IGR) between the l73R and I329L genes were performed for molecular characterization. Phylogenetic analyses based on B646L and EP402R genes confirmed that all ASFVs detected in Can Tho city belonged to genotype 2 and serotype 8. In addition, this study revealed that at least two variants of ASFVs, namely, IGR II and IGR III, based on the nucleotide variation of the IGR sequence, cocirculated, and caused outbreaks in Can Tho city. The molecular characterization study provides great significance for understanding the evolution of ASFVs and tracing possible sources of infection in Can Tho and Mekong delta.
Dehydrovomifoliol Alleviates Nonalcoholic Fatty Liver Disease via the E2F1/AKT/mTOR Axis: Pharmacophore Modeling and Molecular Docking Study
Authors: Ma Ji , Li Ruya , Xu Fang , Zhu Fang , Xu Xiangwei
Published: February 2023

Objective. Herbal medicine discovery is a complex and time‐consuming process, while pharmacophore modeling and molecular docking methods enable simple and economic studies. The pharmacophore model provides an abstract description of essential intermolecular interactions between chemical structures, and the molecular docking technology can identify novel compounds of therapeutic interests and predict the ligand‐target interaction at the molecular level. This study was based on the two methods to elucidate the mechanism of dehydrovomifoliol, an active ingredient extracted from Artemisia frigida willd, in nonalcoholic fatty liver disease (NAFLD). Methods. Bioinformatics analysis was performed to screen target genes of dehydrovomifoliol in NAFLD treatment, which were thus intersected with NAFLD‐related differentially expressed genes (DEGs) and NAFLD‐related genes. Venn diagram was used to identify candidate DEGs. A pharmacophore model was then generated, and molecular docking was performed. A protein‐protein interaction (PPI) network was constructed to identify core genes, which were evaluated using GO and the KEGG enrichment analyses. Results. Seven target genes of dehydrovomifoliol in NAFLD treatment were screened out, namely E2F1, MERTK, SOX17, MMP9, SULT2A1, VEGFA, and BLVRA. The pharmacophore model and molecular docking of candidate DEGs and dehydrovomifoliol were successfully constructed. E2F1 was identified as a core gene of dehydrovomifoliol in NAFLD treatment. Further enrichment analysis indicated the regulatory role of E2F1 in fat metabolism was associated with the regulation of the AKT/mTOR signaling pathway. Conclusion. Overall, this study illustrates the anti‐NAFLD mechanism of dehydrovomifoliol, which could be a useful compound for developing novel drugs in the treatment of NAFLD.
Modulatory Effects of Ketamine and Lamotrigine on Cognition: Emotion Interaction in the Brain
Authors: Gärtner Matti , Weigand Anne , Keicher Christian , Meiering Marvin Sören , Weigner David , Carstens Luisa , Hertrampf Rita , Beckmann Christian , Mennes Maarten , Wunder Andreas , Grimm Simone
Published: February 2023

Introduction: Cognition and emotion are fundamentally integrated in the brain and mutually contribute to behavior. The relation between working memory (WM) and emotion is particularly suited to investigate cognition-emotion interaction since WM is an essential component of many higher cognitive functions. Ketamine affects not only WM but also has a profound impact on emotional processing. Effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Accordingly, a combination of these approaches should be particularly suited to investigate cognition-emotion interaction. Methods: Seventy five healthy subjects were investigated in a double-blind, placebo-controlled, randomized, single-dose, parallel-group study with three treatment conditions. All subjects underwent two scanning sessions (acute/post 24 h). Results: Compared to placebo, acute ketamine administration induced significant dissociative, psychotomimetic, and cognitive effects, as well as an increase in neural activity during WM for positive stimuli. Inhibition of glutamate release by pretreatment with lamotrigine did not influence ketamine’s subjective effects, but significantly attenuated its impact on emotional WM and associated neural activity. There was no effect on these measures 24 h after ketamine administration. Conclusion: Our results demonstrate differential acute effects of modulated glutamate release and a swift restoration of disturbed neurobehavioral homeostasis in healthy subjects.
Understanding University Students during COVID-19: A Longitudinal Mixed-Methods Analysis of Their Experiences of Online Learning, Mental Health, Academic Engagement, and Academic Self-Efficacy
Authors: Nicholson Morgan , Bennett Joanne M. , Modesto Oscar , Gould Rachael
Published: February 2023

Introduction: Research has consistently demonstrated that the COVID-19 pandemic, and resulting sudden shift to online learning (OL), had detrimental impacts on the motivation and mental health of university students. To date however this research has been cross-sectional and quantitative. Method: This study employed a mixed-methods design to examine the experiences of students at a large national Australian University both at the outset of the pandemic in 2020 (n = 824) and again 6 months later (n = 254) at the conclusion of their academic year. Results: Key findings from this study highlighted that despite quantitative findings suggesting poorer attitudes toward learning during the pandemic, qualitatively students perceived both positives and negatives to studying online. The qualitative results further highlighted that this experience was not the same for all and suggests the need to reconsider the standard approaches to offering support for students. Conclusion: Students reported poor mental health in both time points, but outlined avenues which improved not only their mental health but also their motivation for studying such as increased peer engagement and self-care activities. Students reported that OL negatively impacted on both their engagement with studies and their mental health, highlighting the need for universities to prioritize supporting their students’ mental health as much as their development of academic skills.
Avelumab plus Axitinib for the Treatment of Patients with End-Stage Renal Disease Undergoing Dialysis: A Retrospective Case Series and Literature Review
Authors: Bando Yukari , Furukawa Junya , Hara Takuto , Okamura Yasuyoshi , Terakawa Tomoaki , Nakano Yuzo , Fujisawa Masato
Published: February 2023

Combination therapies of an immune checkpoint inhibitor and a molecular targeted agent are widely accepted as an appropriate initial systemic therapy for metastatic renal cell carcinoma (RCC), but there is little published evidence regarding the efficacy of this approach in patients with end-stage renal disease (ESRD). Here, we report three patients who were undergoing hemodialysis for ESRD whose metastatic RCC was successfully treated using avelumab plus axitinib. The patients were a 67-year-old man with swollen lymph nodes, a 65-year-old man with pleural dissemination, and a 71-year-old man with lung nodules and an infra-diaphragmatic nodule. They were administered a combination of avelumab plus axitinib as their initial systemic therapy following definitive surgical therapy. The best response of three patients was graded as partial response. No severe adverse events were identified. This is the first report of the use of combination therapy consisting of avelumab plus axitinib in patients with ESRD undergoing hemodialysis. We found that this combination was useful in such patients.
Gamma Knife Radiosurgery for SUNCT: A Case Series
Authors: Franzini Andrea , Milani Davide , Attuati Luca , Navarria Pierina , Pessina Federico , Picozzi Piero
Published: February 2023

Background: The treatment of medically refractory patients with chronic short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is challenging. Stereotactic radiosurgery targeting the trigeminal nerve and sphenopalatine ganglion (SPG) has been used as a less-invasive treatment. The outcomes of this procedure have been described in a few case reports. Objectives: The objective of the study was to report on the effect of Gamma Knife radiosurgery (GKRS) in 5 patients with chronic SUNCT. Methods: Retrospective review of our GKRS database identified 5 patients with chronic SUNCT who underwent GKRS targeted to the trigeminal nerve and SPG. A maximum dose of 80–85 Gy and 80 Gy was, respectively, delivered to the trigeminal nerve and SPG. Pain intensity and facial numbness were evaluated using the Barrow Neurological Institute (BNI) scores. Results: These 5 patients were clinically followed for a mean period of 26.2 months. Within a period ranging from 2 days to 9 months, GKRS was successful in reducing pain attacks and autonomic symptoms in all 5 patients. At the last assessments, BNI pain scores of I, II, and IIIa were achieved in 1, 1, and 3 patients, respectively. Two patients developed nonbothersome facial numbness (BNI facial numbness score II). Conclusions: These 5 cases show that GKRS targeted to both the trigeminal nerve and the SPG is effective in reducing pain and autonomic symptoms of patients with SUNCT, although nonbothersome trigeminal sensory disturbances may occur.
Educational Experiences and Personal Attitudes of Dental Students toward Patients with Special Needs in Trinidad and Tobago
Authors: Hector Trevin , Balkaran Ramaa , Marchan Shivaughn M.
Published: February 2023

This study ascertained dental students’ perceived educational experiences and attitudes toward patients with special needs at an English-speaking dental school in the Caribbean. A modified paper-based version of a previously validated survey instrument was used – Dental Students Attitudes’ Towards the Handicapped Scale – on a convenience sample of all clinical students at the dental school. The instrument was composed of three parts. Part 1 collected demographic information detailing age, gender, and year of study. Part 2 collected perceived educational experiences, and part 3 collected information regarding student attitudes. Data were presented descriptively, and likelihood ratios were used on cross-tabulated data to examine attitudes between different year groups at an alpha level of 0.05. Student attitudes were generally good regarding patients with special needs. Only 41% of students felt confident treating special needs patients upon graduation. The curriculum which already includes robust didactic teaching in special needs dentistry should be supplemented with increased clinical exposure to patients with special needs during undergraduate dental education. This can lead to improvements in the attitude of dental students as well as their confidence in treatment. Earlier clinical exposure of students to patients with special needs in the clinical curriculum is required. Students should also be encouraged to comprehensively manage special needs patients, where possible within the framework of the competency-based training model.
Perseverative Cognition and Psychotic-Like Experiences in Young Adults: A Cross-Lagged Panel Model
Authors: Ballesio Andrea , Zagaria Andrea , Lombardo Caterina
Published: February 2023

Psychotic-like experiences (PLEs), including persecutory ideation, bizarre experiences, and perceptual abnormalities, are considered risk factors for psychotic disorders and mental distress in the general population. The cognitive-affective mechanisms associated with PLEs remain under-investigated. We aimed to longitudinally assess the reciprocal associations between perseverative cognition (PC), an emerging transdiagnostic factor of psychopathology, and PLEs facets in young adults. Participants (n = 160) from the general population completed measures of PC and PLEs at baseline and at 2-month follow-up. A two-wave, three-variable, cross-lagged panel model was implemented controlling for well-established correlates of PC and PLEs such as depression, anxiety, and symptoms of sleep disturbance. Both PLEs and PC exhibited substantive rank-order stability (β ranged from 0.359 to 0.657, ps < 0.001). Cross-lagged effects revealed that baseline PC was associated with bizarre experiences at 2-month follow-up (β = 0.317; p < 0.01). This effect overcame the well-established cut-off for practical significance. In contrast, no baseline PLEs were associated with PC at follow-up. Findings suggest the presence of a monodirectional, rather than bidirectional, association between PC and bizarre experiences in young adulthood. Results should be interpreted in light of the relatively small, non-clinical, and convenient sample.
Use of Complementary and Alternative Medicine in Children with Scabies
Authors: Akca Gulfer , Sen Nalan Ortucu , Akca Unal
Published: February 2023

Introduction: Scabies is a highly contagious infestation that is becoming increasingly resistant to treatment. The use of complementary and alternative medicine (CAM) has gradually increased for numerous diseases, and the aim of this study is to investigate the parental use of CAM in the treatment of scabies. Methods: The study was planned as a cross-sectional study involving children who came to the departments of child health and diseases and dermatology departments for any reason and were diagnosed with scabies. Questionnaires were given to parents by physicians during face-to-face interviews, and responses were recorded. Results: 75.9% of the 162 parents participating in the study were mothers, and 40% of the parents reported that their income was below expenses. The mean number of people living in the household was 4 (min 3–max 13), and the proportion of extended family was 34%. The mean duration of symptoms in patients with scabies was 4.8 ± 3.92 weeks (min. 1–max. 27), and scabies was diagnosed on average at the second visit to the doctor. CAM was used by 80.9% of parents for children with scabies. They most commonly used tea tree oil for itching and ice for the rash. Parents working in education and health care were less likely to use CAM (p < 0.001), while more than 90% of housewives used at least one CAM method on their children. Analysis showed that 61.7% of female users had benefited from CAM. Significant differences between parents who used CAM and those who did not were found in education (p = 0.003), monthly income (p = 0.023), number of children (p = 0.022), and living in large families (p = 0.001). The use of CAM was six times higher in parents in large families (OR: 6.143, 95% CI 0.776–21.252). Conclusions: With regard to the treatment of scabies, it is important to strengthen the education of health professionals at all levels, put the treatment of patients on a regular basis, explain the conditions that require special attention, and monitor patients closely. New treatment protocols must also be developed for refractory scabies, including alternative therapies.
Real-Life Data on the Management of Incompletely Excised Basal Cell Carcinoma
Authors: Daviti Maria , Lallas Konstantinos , Dimitriadis Christos , Moutsoudis Andreas , Eleftheriadis Vlasios , Eftychidou Polychronia , Bakirtzi Maria , Stefanou Eleni , Gkentsidi Theodosia , Papadimitriou Ilias , Sotiriou Elena , Vakirlis Efstratios , Ioannides Dimitrios , Lallas Aimilios
Published: February 2023

Background: The histopathologic presence of basal cell carcinoma (BCC) cells at one or more margins of the specimen after surgical excision is considered suggestive of incomplete tumor clearance. The management of incompletely excised BCC might vary in different clinical scenarios from re-excision to application of other treatments or even watchful waiting. Objective: The aims of the study were to report the real-life management of incompletely excised BCC in a tertiary referral center and compare the recurrence rates according to the selected management modality. Methods: A retrospective study was conducted at a tertiary Dermatology Center in Northern Greece. Our electronic database was scanned over a 5-year period to retrieve all BCCs with available histopathologic assay reporting at least one involved margin (lateral or deep). The included patients were divided into 3 groups according to the selected management after incomplete excision: group 1 included those who underwent immediate re-excision (n = 26), group 2 those who were followed up without any additional therapy (n = 40), and group 3 those who were treated with adjuvant/complementary non-surgical treatment (n = 18). Finally, we recorded the presence or absence of residual tumor in the new histopathologic report of those tumors that were selected to be re-excised (group 1). The primary outcome was the appearance of clinical tumor recurrence. Results: Of 1,689 BCCs recorded in our database, 84 met the inclusion criteria and were included in the analysis. Re-excision had been selected in 26 of 84 patients (group 1), watchful waiting in 40 (group 2), and non-surgical treatments in 18 (group 3). The histopathologic reports of the 26 tumors of group 1 that were re-excised revealed residual tumor in 14 (53.8%) cases. Overall, a clinical recurrence occurred in 14 of 84 patients (16.7%) after a mean follow-up of 17 months. The median time to recurrence was 14 months. Of 40 patients without any treatment, recurrence developed in 10 (25%), while only 2 of 18 patients treated with non-surgical treatments recurred (11.1%). Conclusions: Our study suggests that positive histopathologic margins after BCC excision result in a clinical recurrence only in a proportion of patients. This percentage is higher when no further treatment is applied and lower when the area is re-excised or treated with imiquimod alone or combined with cryotherapy.
Clinicopathologic Features and Pathogens of Granulomatous Lobular Mastitis
Authors: Li Yunyuan , Chen Ling , Zhang Chunyan , Wang Yanwen , Hu Jun , Zhou Mengyun , Zhang Xiaoyun
Published: February 2023

Background: Granulomatous lobular mastitis (GLM) is a rare, benign, and complex breast disease that can be easily misdiagnosed as breast cancer. The etiology of GLM is unclear, and optimal treatment has not been established. Methods: Medical records for 333 patients with GLM in recent 5 years at Longhua Hospital, Shanghai, China, were analyzed. Potential pathogens in 33 fresh tissue specimens were also analyzed using 16S rDNA sequencing technology, matrix-assisted laser desorption ionization time of flight mass spectrometry, and bacterial cultures. Results: The median age of patients was 32 years (range 22–47 years). Among 333 patients, 38.7% displayed elevated prolactin, while 23.7% displayed high interleukin-2. In the granulomatous lesion, CD3-positive T lymphocytes were significantly more than CD20-positive B lymphocytes around the vacuoles or microabscesses. Gram-positive organisms were observed in 82 cases, including in 22 cases from fresh tissue specimens. Thirty-three cases yielded associated pathogens and all displayed multiple pathogenic infections, as identified using 16S rDNA sequencing technology. Pathogenic infections were further identified as belonging to 16 main genera and 8 main pathogenic species. Conclusions: GLM displays distinct histological and clinical features similar to those that have been previously reported in the literature. Using 16S rDNA sequencing technology, all of our cases demonstrated multiple pathogenic infections, which provided more useful information for clinical treatment.
The Value of Ultra-High-Frequency Ultrasound for the Differentiation between Superficial Basal Cell Carcinoma and Bowen’s Disease
Authors: Zhang Ya-Qin , Wang Li-Fan , Ni Na , Li Xiao-Long , Zhu An-Qi , Guo Le-Hang , Wang Qiao , Xu Hu-Xiong
Published: February 2023

Background: The similar visual appearance of superficial basal cell carcinoma (sBCC) and Bowen’s disease (BD) may cause confusion for diagnosis. Objective: The aim of the study was to investigate the value of ultra-high-frequency ultrasound (uHFUS) in differentiating sBCC from BD. Materials and Methods: This prospective study included a pilot cohort of 110 patients (73 BDs and 37 sBCCs) from November 2016 to October 2020 and a validation cohort of 42 patients (30 BDs and 12 sBCCs) from July 2021 to December 2021. Clinical and uHFUS features of pathologically confirmed sBCC and BD were assessed. A predictive model was developed based on the uHFUS features of the pilot cohort. Subsequently, the model was validated and compared with clinical diagnosis in the validation cohort. Results: uHFUS features with significant differences between sBCC and BD included lesion surface, skin layer involvement, hyperkeratosis, and hyperechoic spots (all p < 0.05). A prediction model based on the above features was established to identify sBCC and BD in the pilot and validation cohorts with areas under the curve (AUC) of 0.908 and 0.923, sensitivity of 82.3% and 83.3%, specificity of 91.9% and 91.7%, and accuracy of 85.5% and 85.7%, respectively, which were significantly higher than those obtained by clinical diagnosis based on photographic pictures of lesions, with the AUC of 0.692, sensitivity of 63.3%, specificity of 75.3%, and accuracy of 66.7% (all p < 0.05). Conclusion: uHFUS provides detailed internal features of sBCC and BD, which facilitates the differentiation between sBCC and BD, and its diagnostic performance is superior to clinical diagnosis.
Experience of Subcutaneous Levetiracetam in Palliative Care
Authors: Gaviria-Carrillo Mariana , Mora-Muñoz Laura , Diaz-Forero Andres Felipe , Vargas-Osorio Juliana , Torres-Ballesteros Viviana , Estrada Jhonatan , Vélez Van Meerbeke Alberto , Rodríguez Jesús Hernán
Published: February 2023

Background: Seizures are common in palliative care patients and its control is essential in the management of these patients as it helps to reduce suffering at the end of life. Subcutaneous levetiracetam has been used off-license for seizure control in palliative care. Objective: The objective of the study was to describe our experience with subcutaneous levetiracetam in two hospitals in Bogota, Colombia. Methods: We conducted a retrospective review of patients treated with subcutaneous levetiracetam in two hospitals in Colombia during 2019–2021. Data were extracted from medical records, and participants were followed up as outpatients. Results: Twenty-one patients were included into the study. No severe adverse effects or rise in ictal frequency were documented. Twelve patients died during hospitalization and nine continued treatments as outpatients. The principal diagnosis was structural focal epilepsy. The daily dose of levetiracetam ranged from 1,000 mg to 3,000 mg, and the duration of treatment varied among subjects between 1 and 360 days. Conclusion: Subcutaneous levetiracetam was well tolerated and effective in controlling seizures in palliative care when oral administration or intravenous access was not an option. Randomized controlled trials are needed to elucidate the efficacy and tolerability of subcutaneous levetiracetam in clinical practice.
Different effects of sugars and methods to preserve post-thaw functional properties of cryopreserved caprine spermatogonial stem cells
Authors: Quadri Saleema Ahmedi , Singh Shiva Pratap , Kharche Suresh Dinkar , Pathak Juhi , Saxena Atul , Soni Yogesh Kumar , Swain Dilip
Published: February 2023

The present study aimed to identify the effects of sugar and methods [slow freezing (SF) vs fast freezing (FF)] on post-thaw in-vitro functional characteristics of cryopreserved caprine SSCs (cSSCs) and the cells obtained from cryopreserved testis tissue of pre-pubertal Barbari bucks. For this, in experiment-1, cSSCs were isolated and cryopreserved by either SF or FF method with different nonpermeable [sugars; trehalose (140 mM; 140T or 400 mM; 400T), and sucrose (140 mM; 140S or 400 mM; 400S)] or/and permeable [5% ethylene glycol (EG) and DMSO] cryoprotectants. After one-wk of cryopreservation, the cSSCs were thawed and cultured for evaluation of their characteristics. Further, in experiment-2, the effectiveness of sugars [trehalose (140 mM) or sucrose (140 mM)] for cryopreservation of testicular tissues of pre-pubertal Barbari bucks using the SF or FF method was evaluated. After one-wk of cryopreservation, the tissues were thawed and cSSCs were isolated and cultured for 3-wk. In both experiments, cSSCs were evaluated for recovery rate, proliferation, metabolic viability, senescence, and stemness markers expression. The recovery rate was 1.3, 1.3, and 1.1-folds higher in the 140T group compared with EG, 140S, and 400S groups, respectively. Similarly, the expression of stemness markers (PGP9.5 and OCT-4) was relatively higher in 140T group compared with the other groups. In experiment 2, the recovery rate of cells per unit tissue wt. was significantly (P<0.05) higher when cryopreserved using 140 mM trehalose compared with other groups. The results of immunocytochemical analyses imply the expression of pluripotent stem cell markers in cSSCs following cryopreservation. Overall, the outcome of the study demonstrates different effects of sugars and methods on post-thaw functional properties of cSSCs with superiority of 140 mM trehalose using SF method over other treatment groups. These results are important for ex-vivo expansion and differentiation of cSSCs for fertility preservation and their other downstream applications.
Network-Guided Multiomic Mapping of Aortic Valve Calcification
Authors: Blaser Mark C. , Kraler Simon , Lüscher Thomas F. , Aikawa Elena
Published: February 2023

Despite devastating clinical sequelae of calcific aortic valve disease that range from left ventricular remodeling to arrhythmias, heart failure, and early death, the molecular insights into disease initiation and progression are limited and pharmacotherapies remain unavailable. The pathobiology of calcific aortic valve disease is complex and comprehensive studies are challenging valvular calcification is heterogeneous and occurs preferentially on the aortic surface, along a fibrocalcific spectrum. Here, we review efforts to study (epi-)genomic, transcriptomic, proteomic, and metabolomic aspects of aortic valve calcification in combination with network medicine-/systems biology-based strategies to integrate multilayered omics datasets and prioritize druggable targets for experimental validation studies. Ultimately, such holistic approach efforts may open therapeutic avenues that go beyond invasive and costly valve replacement therapy.
Abstract 122: The P2x4 Inhibitor, Paroxetine Dramatically Prevents Not Only Growth Of Unruptured Cerebral Aneurysms But Also Recanalization After Aneurysm Coil Embolization; A Retrospective Clinical Study, Drug For Aneurysm Study
Authors: Fukuda Shunichi , Niwa Youko , Yonemoto Naohiro , Ren Nice , Iihara Koji ,   NHO Drug for aneurysm study group
Published: February 2023

Introduction:
We have suggested that inhibition of P2X4 purinoceptor, which is involved in the endothelial flow sensing mechanism, prevents cerebral aneurysm development and growth in an animal model. Therefore, we retrospectively investigated whether a P2X4 inhibitor, paroxetine used as an antidepressant, has an inhibitory effect on the growth of unruptured cerebral aneurysms and the rate of recanalization after coil embolization.

Methods:
Among the cases registered in the J-ASPECT Study, the Japanese stroke inpatient reimbursement database, from 2010 to 2019, we searched for cases who were taking paroxetine and with registered unruptured cerebral aneurysm or had undergone cerebral aneurysm coil embolization. We then invited medical centers with these cases to participate in the study and enrolled cases that met the selection criteria by referring to the imaging data and patient background of the cases. The inhibitory effect in the paroxetine-treated group was compared with that of the control group in a multivariate analysis after adjustment for age, gender, and known risk factors.

Results:
There were 708 cases at 226 facilities nationwide that were potentially matched in the criteria. Seventy-four facilities participated, of which 74 cases at 45 facilities met the selection criteria. A total of 700 control cases were enrolled from 14 core participating centers. The rate of growth incidence of aneurysms was 0.0318 for paroxetine-treated cases (n=36) and 0.0960 for control cases (397). The significant factors (regression coefficients) were paroxetine (-2.26), specific sites of occurrence (-1.28), shape irregularity (1.63), age (0.11), female (1.54), hypertension (-0.55), statin (0.87), and family history of stroke (0.71). The significant factors (odds ratios) in recanalization after 1 year of coil embolization were paroxetine (0.21), complete embolization (0.26), ruptured aneurysm (3.95), and size (1.14).

Conclusions:
This retrospective study suggests that P2X4 inhibitors including paroxetine may be clinically applicable as agents to inhibit the growth of unruptured cerebral aneurysms and recanalization after 1 year of aneurysm coil embolization. The use of reimbursement information may be useful when collecting very rare cases.
Abstract 15: Single-cell Immune Landscape Of Human Clot Retrieved At Mechanical Thrombectomy. Association With Stroke Origin.
Authors: Renedo Daniela , Sujijantarat Nanthiya , Antonios Joseph , Koo Andrew , Acosta Julian , Falcone Guido J , Hebert Ryan , Sansing Lauren H , Navaratnam Dhasakumar S , Matouk Charles
Published: February 2023

Background:
Mechanical thrombectomy (MT) has significantly improved clinical outcomes in acute ischemic stroke. We used single-cell RNA sequencing (scRNA-seq) to describe the landscape of human clots at single cell resolution seeking to provide greater mechanistic insight into stroke pathophysiology and to uncover an association with stroke origin.

Methods:
scRNA-seq was performed on 14 clots retrieved from 14 patients undergoing MT between October 2020-July 2022. We followed standard molecular biology and bioinformatics workflows for sample processing and data to characterize differences in cellular composition between clots of different stroke origin (atrial fibrillation (AF) and carotid atherosclerosis (CA)).

Results:
Clots revealed a significant heterogeneity of immune cells with major constituents including cells of the mononuclear phagocyte system (MPS) and neutrophils. The cellular populations most enriched in CA clots were B-cells and CD4+ T-cells. The cellular population most enriched in AF clots was red blood cells. When looking at cellular subpopulations of the MPS component, we found that CD16+ monocytes (intermediate and non-classical) were significantly more abundant than CD14+CD16- (classical) monocytes in all clots. Moreover, the proportions of CD16+ monocytes varied with stroke origin: the proportion of non-classical (CD14-CD16+) monocytes was higher in CA clots (p=0.05) whereas the proportion of intermediate monocytes (CD14+CD16+) was higher in FA clots (p=0.03). AF clots had upregulated biomarkers and pathways involved with AF or contractile dysfunction (IFI30, FABP4, PPAR, HOTAIR, ILK, Integrin). CA clots had upregulated biomarkers and pathways associated with cardiovascular diseases and atherogenesis (RNSE1, POLR2J3.1, PLTP, Sirtuin, FAK).
(Figure)

Conclusions:
These results reveal a significant heterogeneity of immune cells and point to important differences in cellular composition associated with stroke etiology.
Abstract 160: Etiologies Of Intracerebral Hemorrhage In Patients With Atrial Fibrillation On Or Off Oral Anticoagulants: The Neuro-Afib Study
Authors: Gurol Edip M , Das Alvin S , Daoud Nader , Abramovitz Avia , Rotschild Ofer , Gokcal Elif , Yaghi Shadi , Smith Eric E ,   On Behalf of the Neuro-AFib Study Investigators
Published: February 2023

Background:
Intracerebral hemorrhage (ICH) is the most feared complication of oral anticoagulants (OAC) used to prevent ischemic strokes (IS) in patients with atrial fibrillation (AF). As different ICH etiologic factors correspond to different ICH risks, we aimed to present the causes of ICH in AF patients who were or were not using OAC, based on data from a multicenter contemporary cohort.

Methods:
The Neuro-AFib study is a multicenter effort to elucidate the current causes and consequences of IS and ICH in AF patients. Detailed clinical, laboratory and multimodal imaging data were collected from consecutive patients with AF admitted to 15 US stroke centers with an IS or ICH between 1/2018-12/2019. Etiologic factors of AF patients who were admitted with ICH on OAC (OAC-ICH) and off OAC (nonOAC-ICH) will be compared.

Results:
A total of 868 patients presented with ICH and had a diagnosis of AF, either previously known (88%) or diagnosed during admission (12%). 571 patients (66%) were on OAC at the time of their ICH of whom 58% were on direct OAC (DOAC), 40% on warfarin and 2% on heparin. OAC-ICH patients were older than nonOAC-ICH (76.6±10 vs 74.4±13, p=0.006) while sex distribution was the same in both groups (43% female). CHA
2
DS
2
-VASC was higher in OAC-ICH (4.3±1.6 vs 3.9±1.9, p=0.001) but HAS-BLED score was the same in both groups (2.7±1.1). Cerebral amyloid angiopathy (CAA) was diagnosed in 42.5% of the ICH patients based on modified Boston criteria while hypertensive cerebral small vessel disease (HTN-cSVD) in 57.5%. HTN-cSVD was the more common ICH etiology among OAC-ICH (65%) compared to nonOAC-ICH (49%). Among OAC-ICHs, DOAC-related ICHs tended to be more commonly of hypertensive etiology when compared to warfarin-ICH (p=0.09).

Conclusions:
Our study is the first to report the etiologic mechanisms of ICH in AF patients on or off OAC. CAA is known to be a major cause of OAC-ICH with exceedingly high recurrence rates. Despite this fact, HTN-cSVD was more common among OAC-ICH (especially DOAC-ICH) patients, supporting the view that the presence/absence of HTN-cSVD risk markers such as deep microbleeds are as important as CAA-markers in determining the optimal stroke prevention method in AF patients (left atrial appendage closure vs lifelong OAC).
Abstract 53: Long-term Treatment Risk Of Hemorrhage In Unruptured Brain Arteriovenous Malformation Patients
Authors: Kim Helen , Nelson Jeffrey , Al-Shahi Salman Rustam , Flemming Kelly , Hess Christopher , Hetts Steven W , Koroknay-Pál Päivi , Laakso Aki , Lanzino Giuseppe S , Lawton Michael , McCulloch Charles , Moayeri Nicole , Mohr Jay P , Morgan Michael , Stefani Marco , Zaroff Jonathan , Zhao Yuanli ,   Multicenter Arteriovenous Malformation Rsch (MARS) Investigators
Published: February 2023

Introduction:
The long-term effects of interventional treatment (with surgery, stereotactic radiosurgery, or endovascular embolization) for unruptured brain arteriovenous malformations (uBAVM) are uncertain. We address this in a large multi-center international cohort study comparing risk of intracranial hemorrhage (ICH) in the treated and untreated course of uBAVM patients.

Methods:
We pooled individual patient data (n=3,291) from 10 cohorts and imputed missing data. Survival analysis was performed from time of uBAVM diagnosis to intracranial hemorrhage (ICH) using Cox models, stratified by cohort, censoring at death or last follow-up, and including BAVM interventional treatment as a time-varying covariate. We tested for an interaction of treatment with follow-up time, then estimated the association of interventional treatment with ICH, adjusting for propensity quintile. Individual treatment propensity scores were calculated using logistic regression with Spetzler-Martin grade, sex, diagnosis age and year, cohort, and presence of presenting symptoms (seizures, headaches, and/or deficits).

Results:
Median cohort age was 36 years, 48% were female, and 77% received ≥1 treatment modality for uBAVM during follow-up. 373 ICH occurred during 32,054 person-years of follow-up (median=6.6y), for an ICH rate of 1.16 per 100 P-Y. Overall, treatment was not associated with risk of ICH (HR=1.12, 95% CI=0.89-1.51, p=0.33). However, we observed a strong interaction between treatment and follow-up time (p<0.001): between 0-1 year, treatment was associated with higher risk of ICH (HR=3.48, 95% CI: 2.26-5.37, p<0.001); between 1-10 years, we found no association between treatment and risk of ICH (HR=1.02, 95% CI: 0.73-1.45, p=0.87); after 10 years, treatment was associated with a lower risk of ICH (HR=0.46, 95% CI: 0.30-0.70, p<0.001). Survival curves for untreated and treated courses crossed around 17 years.

Conclusion:
After accounting for treatment propensity for uBAVM, we found an initial increased risk of ICH in the treated relative to untreated course, which continually declined over time with survival curves crossing around 17 years. These results require confirmation in a randomized controlled trial of uBAVM with long-term follow-up.
Abstract 64: Screening For Psychosocial Health In Pediatric Stroke
Authors: Thompson Vivian , Nederveld Cindy , Barry Megan , Bernard Timothy J , Thornhill Dianne , Wheat Emily ,   Hemophilia and Thrombosis Cntr at the Univof Colorado Anschutz Med Campus, Aurora, CO
Published: February 2023

Introduction:
Impaired psychosocial health after stroke in adults is well established, with high prevalence of post-stroke anxiety and depression. Behavioral health following pediatric stroke is less well described. Early data suggest that pediatric stroke patients may experience higher rates of anxiety, depression, ADHD and PTSD. Early detection and treatment of behavioral health concerns can lead to improved psychosocial outcomes. However, screening measures to assess psychosocial functioning in pediatric stroke patients have not yet been explored.

Methods:
This single-center retrospective cohort study (COMIRB 21-3536) examined behavioral health following pediatric stroke using the Pediatric Symptom Checklist (PSC-17) at an outpatient stroke clinic. The PSC-17 screens for a broad range of behavioral health symptoms including internalizing, externalizing, and attention concerns. This dataset included patients with a diagnosis of ischemic stroke, hemorrhagic stroke, CSVT, or periventricular venous infarction (PVI) between 0-18 years of age. Comparison data included all children seen at general outpatient pediatric appointments. Chi-square goodness of fit tests were performed to compare elevated PSC-17 score proportions in children with stroke to proportions found in the general pediatric population.

Results:
We identified 65 pediatric stroke patients with a parent-reported PSC-17. Global, internalizing, and externalizing scores were higher among pediatric stroke patients compared to the general pediatric population, but there was no statistically significant difference in attention measures.

Conclusions:
The PSC-17 identifies a higher prevalence of psychosocial health concerns among children who have experienced a stroke as compared to the general pediatric population. The PSC-17 may serve as an effective screening tool to identify pediatric stroke patients who may benefit from further psychosocial evaluation.
Abstract 90: Butylphthalide Improves Functional Outcome In Patients With Acute Ischemic Stroke Receiving Intravenous Thrombolysis And/or Endovascular Treatment In Comparison To Placebo
Authors: Wang Anxin , Jia Baixue , Zhang Xuelei , Wang Yilong , Miao Zhongrong ,   BAST Investigators
Published: February 2023

Introduction:
Butylphthalide is a cerebro-protection drug that was originally extracted from seeds of Apium graveolens. Pre-clinical experiments have shown the cerebro-protective effect of Butylphthalide in animal models of ischemia-reperfusion. This study evaluated whether Butylphthalide can improve the functional outcome in acute ischemic stroke patients who receive intravenous recombinant tissue plasminogen activator (rt-PA) and/or endovascular treatment (EVT) compared to placebo.

Methods:
In the randomized, double-blinded, placebo-controlled trial, we enrolled patients with acute ischemic stroke who received intravenous rt-PA and/or EVT in 59 centers. Patients were randomized in a 1:1 ratio to receive either Butylphthalide or placebo daily for 90 days, including 14 days of intravenous injections and 76 days of oral capsules. All trial personnel and patients were masked to treatment allocation. The primary outcome was an adjusted favorable outcome at 90 days after randomization, defined as a score of 0 on the modified Rankin Scale (mRS) in patients with a baseline score of 4-7 on the National Institutes of Health Stroke Scale (NIHSS); an mRS score of 0-1 in patients with a baseline NIHSS score of 8-14; and an mRS score of 0-2 in patients with a baseline NIHSS score of 15-25. Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke and mortality. The analysis was done in the intention-to-treat population and in subgroups of age, sex, baseline NIHSS score, hypertension, and reperfusion treatment methods. This trial is registered with ClinicalTrials.gov, NCT03539445.

Results:
Between July 1, 2018 and 19 February, 2022, 1216 patients were enrolled, with 607 assigned to the butylphthalide group and 609 to the placebo group. The primary outcome of a favorable outcome on day 90 occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (OR, 1.70; 95% CI, 1.35 to 2.14;
P
<0.001). Secondary outcomes were similar between groups. There was no evidence of treatment modification effect in the subgroups.

Conclusions:
In conclusion, Butylphthalide improved favorable clinical outcome compared with placebo in patients with acute ischemic stroke receiving intravenous rt-PA and/or EVT.