bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of salidroside in promoting endogenous neural regeneration after cerebral ischemia/reperfusion involves notch signaling pathway and neurotrophic factors
Authors: Zheng Jiabing , Zhang Jizhou , Han Jing , Zhao Zhichang , Lin Kan 
Published: August 2024

Abstract
Background
Salidroside is the major bioactive and pharmacological active substance in Rhodiola rosea L. It has been reported to have neuroprotective effects on cerebral ischemia/reperfusion (I/R). However, whether salidroside can enhance neural regeneration after cerebral I/R is still unknown. This study investigated the effects of salidroside on the endogenous neural regeneration after cerebral I/R and the related mechanism.

Methods
Focal cerebral I/R was induced in rats by transient middle cerebral artery occlusion/reperfusion (MCAO/R). The rats were intraperitoneally treated salidroside once daily for 7 consecutive days. Neurobehavioral assessments were performed at 3 days and 7 days after the injury. TTC staining was performed to assess cerebral infarct volume. To evaluate the survival of neurons, immunohistochemical staining of Neuronal Nuclei (NeuN) in the ischemic hemisphere were conducted. Also, immunofluorescence double or triple staining of the biomarkers of proliferating neural progenitor cells in Subventricular Zone (SVZ) and striatum of the ischemia hemisphere were performed to investigate the neurogenesis. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of neurotrophic factors (NTFs) brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Expression of Notch1 and its target molecular Hes1 were also analyzed by western-blotting and RT-PCR.

Results
Salidroside treatment ameliorated I/R induced neurobehavioral impairment, and reduced infarct volume. Salidroside also restored NeuN positive cells loss after I/R injury. Cerebral I/R injury significantly increased the expression of 5-Bromo-2’-Deoxyuridine (BrdU) and doublecotin (DCX), elevated the number of BrdU/Nestin/DCX triple-labeled cells in SVZ, and BrdU/Nestin/glial fibrillary acidic protein (GFAP) triple-labeled cells in striatum. Salidroside treatment further promoted the proliferation of BrdU/DCX labeled neuroblasts and BrdU/Nestin/GFAP labeled reactive astrocytes. Furthermore, salidroside elevated the mRNA expression and protein concentration of BDNF and NGF in ischemia periphery area, as well. Mechanistically, salidroside elevated Notch1/Hes1 mRNA expression in SVZ. The protein levels of them were also increased after salidroside administration.

Conclusions
Salidroside enhances the endogenous neural regeneration after cerebral I/R. The mechanism of the effect may involve the regulation of BDNF/NGF and Notch signaling pathway.
Association of microbial community structure with gill disease in marine-stage farmed Atlantic salmon (Salmo salar); a yearlong study
Authors: Clinton Morag , Wyness Adam J. , Martin Samuel A. M. , Brierley Andrew S. , Ferrier David E. K. 
Published: August 2024

Abstract
Background
Understanding the relationship between resident microbiota and disease in cultured fish represents an important and emerging area of study. Marine gill disorders in particular are considered an important challenge to Atlantic salmon (Salmo salar) aquaculture, however relatively little is known regarding the role resident gill microbiota might play in providing protection from or potentiating different gill diseases. Here, 16S rRNA sequencing was used to examine the gill microbiome alongside fish health screening in farmed Atlantic salmon. Results were used to explore the relationship between microbial communities and gill disease.

Results
Microbial community restructuring was observed throughout the sampling period and linked to varied drivers of change, including environmental conditions and severity of gill pathology. Taxa with significantly greater relative abundance on healthier gills included isolates within genus Shewanella, and taxa within family Procabacteriaceae. In contrast, altered abundance of Candidatus Branchiomonas and Rubritalea spp. were associated with damaged gills. Interestingly, more general changes in community richness and diversity were not associated with altered gill health, and thus not apparently deleterious to fish. Gross and histological gill scoring demonstrated seasonal shifts in gill pathology, with increased severity of gill damage in autumn. Specific infectious causes that contributed to observed pathology within the population included the gill disorder amoebic gill disease (AGD), however due to the uncontrolled nature of this study and likely mixed contribution of various causes of gill disease to observed pathology results do not strongly support an association between the microbial community and specific infectious or non-infectious drivers of gill pathology.

Conclusions
Results suggest that the microbial community of farmed Atlantic salmon gills undergo continual restructuring in the marine environment, with mixed influences upon this change including environmental, host, and pathogenic factors. A significant association of specific taxa with different gill health states suggests these taxa might make meaningful indicators of gill health. Further research with more frequent sampling and deliberate manipulation of gills would provide important advancement of knowledge in this area. Overall, although much is still to be learnt regarding what constitutes a healthy or maladapted gill microbial community, the results of this study provide clear advancement of the field, providing new insight into the microbial community structure of gills during an annual production cycle of marine-stage farmed Atlantic salmon.
Sex differences in the diagnostic algorithm of screening for heart failure by symptoms and NT-proBNP in patients with type 2 diabetes
Authors: Hofer-Zeni Sarah , Leutner Michael , Klimek Peter , Bellach Luise , Pavo Noemi , Prausmüller Suriya , Hülsmann Martin , Kautzky-Willer Alexandra 
Published: August 2024

Abstract
Objectives
This study aimed to assess the guideline recommended diagnostic tools NT-proBNP and NYHA classification, with a focus on sex-specific differences.

Background
Patients with Type 2 Diabetes (T2D) face a heart failure (HF) risk up to four times higher than those without T2D, particularly affecting women more than twice as much as men. Despite distinct pathophysiological differences between men and women, there are currently no sex-specific recommendations for the diagnostic algorithm of HF in diabetic patients.

Methods
A total of 2083 patients with T2D were enrolled, and the primary endpoint was heart failure during hospitalization within a 5-year timeframe. The secondary endpoint was all-cause death.

Results
In female patients, frequency of HF diagnosis prior to or during hospitalization and mortality did not differ significantly between NYHA II and III, in contrast to male patients. Additionally, there was no notable difference in mean NT-proBNP levels between NYHA stage II and III only in female patients. The multivariable regression analysis highlighted NYHA classification not to be a predictor of NT-proBNP levels in female but solely in male patients. On multivariable Cox regression NYHA score was also no significant risk factor for occurence of HF in female patients. Furthermore, there was no significant disparity in mortality between men with NT-proBNP levels between 125 and 400 pg/ml and those below 125 pg/ml, whereas in women mortality was significantly higher in the group with NT-proBNP levels between 125 and 400 pg/ml than below 125 pg/ml.

Conclusion
These findings suggest that NYHA classification may not be the most suitable tool for assessing the diagnosis of HF in female patients with T2D. Moreover, the need for consideration of a more symptom-independent screening for HF in female patients with T2D and re-evaluation of current guidelines especially regarding sex-specific aspects is highlighted.
Malaria community case management usage and quality of malaria care in a moderate Plasmodium falciparum burden region of Chadiza District, Zambia
Authors: Wallender Erika , Kabamba Bupe , Rutagwera Marie-Reine I. , Kangale Chabu , Miller John M. , Porter Travis , Musunse Maximillian , Gallalee Sarah , Bennett Adam , Psychas Paul , Gutman Julie R. , Hamainza Busiku , Thwing Julie 
Published: August 2024

Abstract
Background
Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia.

Methods
Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking.

Results
Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5–14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p < 0.001). Reported malaria treatment was similar by provider, and 85.9% of those with a reported positive malaria test reported getting malaria treatment; 66.9% of the subset with prior fever and a positive survey RDT reported malaria treatment. Age under 5 years, monthly or more frequent CHW home visits, and greater wealth were associated with increased odds of receiving healthcare.

Conclusions
Chadiza District had high CHW coverage among individuals who sought care for fever. Further interventions are needed to increase the proportion of febrile individuals who receive healthcare. Strategies to decrease barriers to healthcare, such as CHW home visits, particularly targeting those of all ages in lower wealth strata, could maximize the benefits of CHW programmes.
Periareolar minimally invasive approach for cardiac surgery: a case series and description of technique with a review of literature
Authors: Mortada Hatan , Alsuhaim Abdulaziz , Alkhamees Nasser , Neel Omar Fouda 
Published: August 2024

Abstract
Background
Minimally invasive cardiac surgery (MICS) has garnered significant attention for its potential benefits, including decreased surgical trauma, accelerated recovery, and improved aesthetic outcomes. This case series aims to elucidate the technical aspects and assess the aesthetic, functional, and quality of life outcomes associated with the utilization of a periareolar incision approach in female patients undergoing cardiac surgery.

Methods
The periareolar MICS technique, performed with or without high-definition (HD) 3D endoscopic visualization, limited rib-spreading, and a periareolar incision spanning the 3 to 9 o’clock positions, was employed. We present a case series encompassing five female patients who underwent various cardiac procedures for different pathologies using this approach.

Results
No intraoperative complications occurred, and all patients experienced uneventful postoperative recoveries. The periareolar approach resulted in well-healed incisions with minimal scaring, preserving breast contour and yielding satisfactory cosmetic outcomes. Patients reported negligible pain levels and expressed contentment with the scar appearance.

Conclusion
The periareolar incision technique in MICS represents an efficacious approach characterized by favorable aesthetic outcomes and enhanced patient experience. Further investigations are warranted to compare different MICS approaches with respect to pain management and their impact on quality-of-life domains.
Association of postoperative delirium with hypotension in critically ill patients after cardiac surgery: a prospective observational study
Authors: Othman Saleh Mohammed Alhaj , Aziz Mohammed Ali Ali , Al-Mushiki Gaber Musaed Ali , Sriwayyapram Chanyanud , okubai Tecleab , Al-Muwaffaq Gamil , Xu Qin , Alqudaimi Mohammed 
Published: August 2024

Abstract
Background
Postoperative delirium (POD), an acute and variable disturbance in cognitive function, is an intricate and elusive phenomenon that occurs after cardiac surgery. Despite progress in surgical techniques and perioperative management, POD remains a formidable challenge, imposing a significant burden on patients, caregivers, and healthcare systems.

Methods
This prospective observational study involved 307 patients who underwent cardiac surgery. Data on the occurrence of delirium, clinical parameters, and postoperative characteristics were collected. A multivariate analysis was performed to assess the relationship between POH and POD.

Results
Sixty-one patients (21%) developed delirium, with an average onset of approximately 5 days postoperatively and a duration of approximately 6 days. On multivariate analysis, POH was significantly associated with POD, and the adjusted odds ratios indicated that patients with POH were more likely to develop delirium (OR, 5.61; p = 0.006). Advanced age (OR, 1.11; p = 0.002), emergency surgery (OR, 8.31; p = 0.001), and on-pump coronary artery bypass grafting were identified as risk factors of POD. Patients who developed delirium were typically older, more likely to be male, and had higher morbidity rates than those who did not.

Conclusion
POH is significantly associated with delirium in critically ill patients after cardiac surgery. Surgical complexity and advanced age contribute to the risk of developing POD and poor postoperative outcomes.
Antidepressant treatment initiation among children and adolescents with acute versus long COVID: a large retrospective cohort study
Authors: Tran Phuong TM , Amill-Rosario Alejandro , dosReis Susan 
Published: August 2024

Abstract
Background
Child and adolescent antidepressant use increased post-pandemic, but it is unknown if this disproportionally affected those who develop post-acute sequelae of coronavirus disease 2019 (COVID) or long COVID. This study compared the risk of antidepressant initiation among children and adolescents with long COVID with those who had COVID but did not have evidence of long COVID.

Methods
Our retrospective cohort study of children and adolescents aged 3–17 years at the first evidence of COVID or long COVID from October 1, 2021 through April 4, 2022 was conducted within Komodo’s Healthcare Map™ database. The index date was the earliest date of a medical claim associated with a COVID (COVID comparators) or long COVID diagnosis (long COVID cases). The baseline period was six months before the index date. The outcome was antidepressant initiation within twelve months after the index date. Due to the large number of COVID relative to long COVID cases, COVID comparators were randomly selected with a ratio of 2 COVID to 1 long COVID. We used propensity score matching to control for confounding due to imbalances in the baseline covariates. Log-binomial models estimated the relative risk (RR) of antidepressant initiation in the propensity score matched sample. We conducted several sensitivity analyses to test the robustness of our findings to several assumptions.

Results
Our child and adolescent sample included 18 274 with COVID and 9137 with long COVID. Compared with those with COVID, a larger proportion of long COVID children and adolescents had psychiatric disorders, psychotropic use, medical comorbidities, were previously hospitalized, or visited the emergency department. In the propensity score-adjusted analysis, the long COVID group had a statistically significant higher risk of antidepressant initiation relative to the COVID comparator (adjusted-RR: 1.40, 95% CI = 1.20, 1.62). Our findings were robust across sensitivity analyses.

Conclusions
The increased risk of antidepressant initiation following long COVID warrants further study to better understand the underlying reasons for this higher risk. Emerging evidence of long COVID’s impact on child mental health has important implications for prevention and early interventions.
Association between treatment with sacubitril/valsartan and the risk of Alzheimer’s disease: a clinical update
Authors: Garnier-Crussard Antoine 
Published: August 2024

AbstractSince 2014, sacubitril/valsartan (Entresto®) is widely prescribed for heart failure. Despite neprilysin inhibition’s benefits in heart failure, concerns about potential amyloid-beta (Aβ) accumulation and Alzheimer’s disease (AD) risk have persisted. This narrative review, a decade post-approval, evaluates the risk of amyloid pathology and neurocognitive disorders in long-term sacubitril/valsartan use. Clinical trials, real-world studies, and pharmacovigilance data do not indicate an increased risk of cognitive decline. In patients treated with sacubitril/valsartan blood-based amyloid biomarkers show perturbations, while neuroimaging biomarkers reveal no significant increase in amyloid load. Despite a theoretical risk of amyloid accumulation and AD under treatment with sacubitril/valsartan, current clinical data appears reassuring, and there is no signal indicating an increased risk of cognitive decline, but a perturbation of amyloid blood-based biomarkers, which implies great caution when interpreting biomarkers in this context.
Scalable isolation of surface-engineered extracellular vesicles and separation of free proteins via tangential flow filtration and size exclusion chromatography (TFF-SEC)
Authors: Kawai-Harada Yuki , Nimmagadda Vasudha , Harada Masako 
Published: August 2024

Abstract
Background
Extracellular vesicles (EVs) represent small lipid bilayer structures pivotal in mediating intercellular communication via biomolecular transfer. Their inherent characteristics, including packaging, non-immunogenicity, and biofluid stability, position EVs as promising drug delivery vectors. However, developing clinical quality EVs requires multifaceted technological advancement.

Methods
In this study, a method is introduced for engineering extracellular vesicles (eEVs) from cultured cells and their subsequent isolation using lab-scale tangential flow filtration (TFF). This is the first study to evaluate DNA loading efficacy into EVs isolated by TFF, marking a significant milestone in the field of targeted drug delivery. Initially, cells are transfected with EV-display constructs to facilitate the secretion of eEVs bearing the desired coding molecules. Following brief centrifugation, the cell culture media undergoes filtration using hollow fiber filters. TFF, by applying a constant flow, effectively segregates molecules based on designated molecular weight cut-off (MWCO), enriching particles between 50 and 650 nm.

Results
Compared to conventional methods like ultracentrifugation, TFF demonstrates higher efficiency in removing undesired molecules/aggregates while exerting less stress on EVs. Characterization of eEVs through various assays confirms TFF’s superiority in isolating pure EV populations. Additionally, the necessity of size-exclusion chromatography (SEC) after tangential flow filtration (TFF) becomes evident for effectively removing unbound protein contaminants.

Conclusion
In conclusion, TFF-SEC emerges as a scalable and superior approach for eEV isolation, promising significant advancements in clinical applications.
Association Between Prior Antipsychotic Adherence and Adherence Three Years After Clozapine Initiation: A Real-World Observational Study
Authors: Brodeur Sébastien , Courteau Josiane , Vanasse Alain , Roy Marc-André , Courteau Mireille 
Published: August 2024

AimsOur previous findings challenged the widely held view among a large proportion of psychiatrists (41% to 82%) that previous non-adherence to antipsychotics is a major barrier to the introduction of clozapine (Brodeur et al. 2022 BJPsych). Indeed, our previous work showed that most patients, even those with the poorest adherence profiles, remained on their treatment after clozapine initiation (>68% for clozapine and >84% for all antipsychotics combined) after one year of follow-up. Because of this, the study extended the follow-up period to three years to assess whether patterns of adherence were sustained over time. Therefore, this study aimed to determine whether poor adherence prior to initiating clozapine predicted poor adherence to clozapine or any other antipsychotic (including clozapine) three years after initiation.MethodsThis cohort study included 2,258 patients living in Quebec (Canada) with a diagnosis of SCZ who initiated oral clozapine between 2009 and 2016 (index date). Adherence to AP was measured by the medication possession ratio (MPR) over a 1-year period before and a 3-year period after the index date. Five groups of patients were formed based on their prior MPR level (independent variable), and two dependent variables were defined after clozapine initiation (good adherence (MPR ≥ 0.8) to any APs and to clozapine only). In addition to multiple logistic regression, state sequence analysis was used to visualise the trajectories of AP use over time, before and after clozapine initiation, for each group.ResultsThe graphical representation of the SSA immediately showed that AP adherence was significantly improved in all groups, regardless of the level of previous adherence to AP treatment. On the other hand, logistic regression showed that poorer adherence to APs before the index date was significantly associated with an increased risk of poor adherence to any AP treatment 3 years after the index date (adjusted ORs ranging from 2.2 to 3.0). However, the majority of patients (ranging from 80.8% to 92.4%) had good adherence to any APs and to oral clozapine (ranging from 57.7% to 73.8%), regardless of previous adherence level.ConclusionThese results add to previous findings and demonstrate that initiation of clozapine leads to improved adherence over a 3-year period. Although widely recognised by clinicians as a barrier to clozapine use, previous poor adherence does not appear to justify avoiding clozapine treatment in patients who would otherwise be considered eligible.