bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound-mediated blood–brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer’s disease
Authors: Mehta Rashi I. , Carpenter Jeffrey S. , Mehta Rupal I. , Haut Marc W. , Wang Peng , Ranjan Manish , Najib Umer , D’Haese Pierre-François , Rezai Ali R. 
Published: June 2023

Abstract
Background
Focused ultrasound (FUS)-mediated blood–brain barrier (BBB) opening is under investigation as a therapeutic modality for neurodegeneration, yet its effects in humans are incompletely understood. Here, we assessed physiologic responses to FUS administered in multifocal brain sites of persons with Alzheimer’s disease (AD).

Methods
At a tertiary neuroscience institute, eight participants with AD (mean age 65, 38% F) enrolled in a phase 2 clinical trial underwent three successive targeted BBB opening procedures at 2 week intervals using a 220 kHz FUS transducer in combination with systemically administered microbubbles. In all, 77 treatment sites were evaluated and encompassed hippocampal, frontal, and parietal brain regions. Post-FUS imaging changes, including susceptibility effects and spatiotemporal gadolinium-based contrast agent enhancement patterns, were analyzed using serial 3.0-Tesla MRI.

Results
Post-FUS MRI revealed expected intraparenchymal contrast extravasation due to BBB opening at all targeted brain sites. Immediately upon BBB opening, hyperconcentration of intravenously-administered contrast tracer was consistently observed around intracerebral veins. Following BBB closure, within 24–48 h of FUS intervention, permeabilization of intraparenchymal veins was observed and persisted for up to one week. Notably, extraparenchymal meningeal venous permeabilization and associated CSF effusions were also elicited and persisted up to 11 days post FUS treatment, prior to complete spontaneous resolution in all participants. Mild susceptibility effects were detected, however no overt intracranial hemorrhage or other serious adverse effects occurred in any participant.

Conclusions
FUS-mediated BBB opening is safely and reproducibly achieved in multifocal brain regions of persons with AD. Post-FUS tracer enhancement phenomena suggest the existence of a brain-wide perivenous fluid efflux pathway in humans and demonstrate reactive physiological changes involving these conduit spaces in the delayed, subacute phase following BBB disruption. The delayed reactive venous and perivenous changes are consistent with a dynamic, zonal exudative response to upstream capillary manipulation. Further preclinical and clinical investigations of these FUS-related imaging phenomena and of intracerebral perivenous compartment changes are needed to elucidate physiology of this pathway as well as biological effects of FUS administered with and without adjuvant neurotherapeutics.
Trial registration: ClinicalTrials.gov identifier: NCT03671889, registered 9/14/2018
Acceptability of donated breast milk among pregnant women in selected hospitals in central Uganda: a cross-sectional study
Authors: Namuddu Mary Gorreth , Kiguli Juliet , Nakibuuka Victoria , Nantale Ritah , Mukunya David 
Published: June 2023

Abstract
Background
Donated breast milk is considered beneficial to vulnerable infants. Thus, Uganda launched its first human milk bank in November 2021 to provide breast milk to preterm, low birthweight and sick babies. However, there is a scarcity of information on the acceptability of donated breast milk in Uganda. The study sought to assess the acceptability of using donated breast milk and associated factors among pregnant women at a private and a public hospital in central Uganda.

Methods
This cross-sectional study enrolled pregnant women attending antenatal care at the selected hospitals between July and October 2020. All pregnant women recruited had already given birth to at least one child. Data were collected using a semi-structured questionnaire, and we recruited participants through systematic sampling. Used frequencies, percentages and means with standard deviations to summarize variables. Assessed the association between the acceptability of donated milk and selected factors by comparing their arithmetic means using a generalized linear model to allow for clustering at the health facility level. Used a normal distribution and an identity link and calculated the adjusted mean differences together with 95% CIs [generated using robust variance estimators to correct for model misspecification].

Results
A total of 244 pregnant women with a mean age of 30 (± 5.25) years were enrolled. Sixty-one-point 5% (150/244) of the women reported that they would accept donated breast milk. Higher education (adjusted mean difference, technical versus primary level: 1.33; 95% CI 0.64, 2.02), being Muslim (adjusted mean difference, Muslim versus Christian: 1.24; 95% CI 0.77, 1.70), having heard of donated breast milk banking (adjusted mean difference, ever versus never: 0.62; 95% CI 0.18, 1.06) and presence of a serious medical condition (adjusted mean difference, preference of donated milk versus other feeds in a serious medical condition: 3.96; 95% CI, 3.28, 4.64) were associated with acceptability of donated breast milk.

Conclusions
The acceptability of using donated breast milk for infant feeding was high among pregnant women. Public sensitization and education campaigns are indispensable for the acceptability of donated milk. These programs should be designed to include women with lower education levels.
GAU-PED study for early diagnosis of Gaucher disease in children with splenomegaly and cytopenia
Authors: Pession Andrea , Di Rocco Maja , Venturelli Francesco , Tappino Barbara , Morello William , Santoro Nicola , Giordano Paola , Filippini Beatrice , Rinieri Simona , Russo Giovanna , Girardi Katia , Ruggiero Antonio , Galea Eulalia , Antonucci Roberto , Tovaglieri Nicola , Porta Fulvio , Tartaglione Immacolata , Giona Fiorina , Fagioli Franca , Burlina Alberto ,   Pediatric Gaucher Study Group, Mura Rosamaria , Russo Bambina , Tornesello Assunta , Menna Giuseppe , Russo Delia , Caniglia Maurizio , Schettini Sergio , Onofrillo Daniela , Ladogana Saverio , Civino Adele 
Published: June 2023

Abstract
Background
Gaucher disease (GD) diagnosis can be delayed due to non-specific symptoms and lack of awareness, leading to unnecessary procedures and irreversible complications. GAU-PED study aims to assess GD prevalence in a high-risk pediatric population and the presence, if any, of novel clinical or biochemical markers associated with GD.

Materials and methods
DBS samples were collected and tested for β-glucocerebrosidase enzyme activity for 154 patients selected through the algorithm proposed by Di Rocco et al. Patients showing β-glucocerebrosidase activity below normal values were recalled to confirm the enzyme deficiency with the gold standard essay on cellular homogenate. Patients tested positive at the gold standard analysis were evaluated through GBA1 gene sequencing.

Results
14 out of 154 patients were diagnosed with GD, with a prevalence of 9.09% (5.06–14.78%, CI 95%). Hepatomegaly, thrombocytopenia, anemia, growth delay/deceleration, elevated serum ferritin, elevated Lyso-Gb1 and chitotriosidase were significantly associated with GD.

Conclusions
GD prevalence in a pediatric population at high-risk appeared to be higher compared to high-risk adults. Lyso-Gb1 was associated with GD diagnosis. The algorithm proposed by Di Rocco et al. can potentially improve the diagnostic accuracy of pediatric GD, allowing the prompt start of therapy, aiming to reduce irreversible complications.
Prevalence and risk factors for laminitis within the Norwegian pony breed Nordlandshest/Lyngshest
Authors: Lykkjen Sigrid , Stenbakk Linda Koldal , Holmøy Ingrid Hunter 
Published: June 2023

Abstract
Background
Laminitis is a systemic condition resulting in debilitating pain and structural changes within the feet, and hence has major welfare implications. Causes include endocrine and systemic inflammatory conditions. Ponies are frequently affected, and observations in the field suggest that occurrence of laminitis is also common in Norwegian breeds. The aim of this study was to estimate the prevalence and risk factors for laminitis within the Norwegian pony breed Nordlandshest/Lyngshest.

Results
The study was a cross-sectional study based on questionnaires sent to members of the Norwegian Nordlandshest/Lyngshest breed association. Questionnaires were received for 504 animals, of which 464 records were eligible and included in analyses. The population comprised 71 stallions, 156 geldings, and 237 mares, with an age between 1 and 40 years (median and interquartile ranges: 12 (6–18) years). The estimated 3-year period prevalence of laminitis was 8.4% (95% confidence interval (CI95): 6.0–11.3%), whereas lifetime prevalence was 12.5% (CI95: 9.6–15.9%). Mares had a significantly higher period- and lifetime prevalence of laminitis than male horses, and horses 10 years and older had a significantly higher prevalence than younger horses. The lifetime prevalence of laminitis was 3.2% in horses 9 years and younger, whereas from 17.3–20.5% in older horses. Multivariable logistic regression analysis identified age, sex, and regional adiposity as significantly (P < 0.05) associated with the 3-year period outcome of laminitis: Horses older than 9 years had a three-fold increase in the likelihood of having laminitis compared to the younger horses (Odds Ratio (OR)10–14 years = 3.37 (CI95 = 1.19–9.50), OR15-19 years = 3.06 (CI95 = 1.04–9.05), and OR>20 years = 2.70 (CI95 = 0.90–8.02). Mares were more than twice as likely (OR = 2.44 (CI95 = 1.17–5.12) to have laminitis compared to male horses, and horses with regional adiposity had increased odds (OR = 2.35 (CI95 = 1.15–4.82) of laminitis compared to horses without regional adiposity.

Conclusions
Laminitis appears to be a considerable welfare issue in the Norwegian pony breed Nordlandshest/Lyngshest. The identified risk factors age, sex, and regional adiposity highlight the need for improved owner education and awareness of strategies to reduce laminitis risk.
Towards measuring effective coverage: critical bottlenecks in quality- and user-adjusted coverage for major depressive disorder in São Paulo metropolitan area, Brazil
Authors: Henriques Franca Mariane , Bharat Chrianna , Novello Ercole , Hwang Irving , Medina-Mora Maria Elena , Benjet Corina , Andrade Laura Helena , Vigo Daniel V. , Viana Maria Carmen 
Published: June 2023

Abstract
Background
Major depressive disorder (MDD) contributes to a significant proportion of disease burden, disability, economic losses, and impact on need of treatment and health care in Brazil, but systematic information about its treatment coverage is scarce. This paper aims to estimate the gap in treatment coverage for MDD and identify key bottlenecks in obtaining adequate treatment among adult residents in the São Paulo Metropolitan area, Brazil.

Methods
A representative face-to-face household survey was conducted among 2942 respondents aged 18+ years to assess 12-month MDD, characteristics of 12-month treatment received, and bottlenecks to deliver care through the World Mental Health Composite International Diagnostic Interview.

Results
Among those with MDD (n = 491), 164 (33.3% [SE, 1.9]) were seen in health services, with an overall 66.7% treatment gap, and only 25.2% [SE, 4.2] received effective treatment coverage, which represents 8.5% of those in need, with a 91.5% gap in adequate care (66.4% due to lack of utilization and 25.1% due to inadequate quality and adherence). Critical service bottlenecks identified were: use of psychotropic medication (12.2 percentage points drop), use of antidepressants (6.5), adequate medication control (6.8), receiving psychotherapy (19.8).

Conclusions
This is the first study demonstrating the huge treatment gaps for MDD in Brazil, considering not only overall coverage, but also identifying specific quality- and user-adjusted bottlenecks in delivering pharmacological and psychotherapeutic care. These results call for urgent combined actions focused in reducing effective treatment gaps within services utilization, as well as in reducing gaps in availability and accessibility of services, and acceptability of care for those in need.
Impact of COVID-19 on the lives of people with severe mental illness—front-line community psychiatry workers observation from a provincial survey of assertive community treatment teams in Ontario, Canada
Authors: Kassam Aly , Beder Michaela , Sediqzadah Saadia , Levy Matthew , Ritts Madeleine , Maher John , Kirwan Nicole , Law Samuel 
Published: June 2023

AbstractUsing an online survey distributed to members of the provincial organization that represents the 88 Assertive Community Treatment (ACT) and Flexible ACT teams in Ontario, Canada, this descriptive study relied on the unique vantage points and observations of the front-line community psychiatry workers who maintained contact with patients through outreach and telecommunication during the height of COVID-19. The patients who suffer from serious mental illness (SMI) were uniquely affected by COVID-19 due to the changes, reduction or shut down of many essential clinical and community support services. Thematic and quantitative analyses of the workers’ observations highlighted 6 main areas of note, including significant social isolation and loneliness, clinical course deterioration and life disruption, increased hospital and ER use, police and legal contacts, and substance abuse and related deaths. There were also encouraging signs of positive adaptations in terms of independence and resilience. Reflections of these impacts and potential ameliorating approaches are further discussed.
Cervical collar use following anterior cervical hybrid surgery: protocol for a prospective randomized, time-controlled trial
Authors: He Junbo , Liu Qingyu , Yang Zijiao , Liu Hao , Wu Tingkui , Ding Chen , Huang Kangkang , Wang Beiyu 
Published: June 2023

Abstract

Introduction
Cervical hybrid surgery (HS) combines anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) to establish an individualized surgical plan for patients with multiple cervical disc degenerative diseases. In order to maintain the stability of the spine after HS, an external cervical collar is often used. However, there is still controversy regarding the importance of a cervical collar following surgery. This study aims to determine whether the cervical collar is effective and how long it should be worn after surgery.

Methods
This is a randomized, single-center, prospective, parallel-controlled trial. Eligible participants will be selected according to the inclusion and exclusion criteria. The primary outcome is the neck disability index, which will be evaluated before surgery and at one week, 3 weeks, 6 weeks, 3 months, 6 months, and 12 months following surgery. The secondary outcomes consist of the Japanese Orthopedic Association Scores, MOS 36-item short-form health survey (SF-36), visual analog scale, Pittsburgh Sleep Quality Index (PSQI), Bazaz dysphagia scoring system, Falls Efficacy Scale, cervical collar satisfaction score, neck soft tissue assessment, and Braden Scale, as well as radiologic assessments for cervical lordosis, disc height of the operative levels, fusion rate, range of motion (ROM), and complications including anterior bone loss, prosthesis migration, and heterotopic ossification. The clinical and radiologic examinations were performed by investigators with no therapeutic relationship with the individual patient. All radiographs were examined by one independent radiologist.

Ethics and dissemination
The results of this study will be published in peer-reviewed journals and presented at conferences. Upon completion of this trial, our findings could provide an appropriate cervical collar-wearing guideline for patients receiving HS.

Trial registration
ChiCTR.org.cn ChiCTR2000033002. Registered on 2020–05-17.
Design, synthesis, molecular docking and biological evaluation of new carbazole derivatives as anticancer, and antioxidant agents
Authors: Çapan İrfan , Hawash Mohammed , Jaradat Nidal , Sert Yusuf , Servi Refik , Koca İrfan 
Published: June 2023

AbstractBackgroundThe carbazole skeleton is an important structural motif occurring naturally or synthesized chemically and has antihistaminic, antioxidant, antitumor, antimicrobial, and anti-inflammatory activities.ObjectivesThis study aimed to design and synthesize a novel series of carbazole derivatives and evaluate their antiproliferative and antioxidant activities.MethodsThe synthesized compounds were characterized utilizing HRMS,1H-, and13CAPT-NMR, and assessed for their anticancer, antifibrotic, and antioxidant effects utilizing reference biomedical procedures. In addition, the AutoDock Vina application was used to perform in-silico docking computations.ResultsA series of carbazole derivatives were synthesized and characterized in the current study. Compounds10and11were found to have a stronger antiproliferative effect than compounds2–5against HepG2, HeLa, and MCF7 cancer cell lines with IC50values of 7.68, 10.09, and 6.44 µM, respectively. Moreover, compound 9 showed potent antiproliferative activity against HeLa cancer cell lines with an IC50value of 7.59 µM. However, except for compound5, all of the synthesized compounds showed moderate antiproliferative activities against CaCo-2 with IC50values in the range of 43.7–187.23 µM. All of these values were compared with the positive control anticancer drug 5-Fluorouracil (5-FU). In addition, compound9showed the most potent anti-fibrotic compound, and the cellular viability of LX-2 was found 57.96% at 1 µM concentration in comparison with the positive control 5-FU. Moreover, 4 and 9 compounds showed potent antioxidant activities with IC50values of 1.05 ± 0.77 and 5.15 ± 1.01 µM, respectively.ConclusionMost of the synthesized carbazole derivatives showed promising antiproliferative, antioxidant, and antifibrotic biological effects, and further in-vivo investigations are needed to approve or disapprove these results.
The first facile optical density-dependent approach for the analysis of doxorubicin, an oncogenic agent accompanied with the co-prescribed drug; paclitaxel
Authors: Hamad Ahmed Abdulhafez 
Published: June 2023

AbstractDoxorubicin (DRB) is an anthracycline oncogenic drug extracted from cultures of Streptomyces peucetius var. caesius. It is frequently recommended as an anti-neoplastic agent for the treatment of diverse malignancies. It exerts its antineoplastic effect either via inhibiting the enzyme topoisomerase II and/or via intercalation to DNA or reactive oxygen species generation. In the present article, the direct, simple, one-pot, somewhat eco-safe, and non-extractive spectrophotometric system was executed to track doxorubicin, a chemotherapeutic remedy, in the presence of paclitaxel, a naturally occurring Taxan antineoplastic radical, through the greenness rated method. DRB’s optical density was studied in various mediums and solvents to develop the current approach. An acidic ethanolic solution was found to increase the optical density of the sample significantly. At 480 nm., the most remarkable optical density was obtained. Various experimental factors, including intrinsic media, solvent, pH, and stability time, were investigated and controlled. The current approach achieved linearity within the 0.6–40.0 µg mL-1 range, accompanied by a limit of both detection and quantification (LOD and LOQ) of 0.18 and 0.55 µg mL-1, correspondingly. The approach was validated under the ICH guidelines (Quality Guidelines). The system’s greenness and enhancement degree were estimated.
Characterization of miR-335-5p and miR-335-3p in human osteoarthritic tissues
Authors: Wilson Thomas G. , Baghel Madhu , Kaur Navdeep , Moutzouros Vasilios , Davis Jason , Ali Shabana Amanda 
Published: June 2023

Abstract
Objective
We aimed to characterize the expression patterns, gene targets, and functional effects of miR-335-5p and miR-335-3p among seven primary human knee and hip osteoarthritic tissue types.

Methods
We collected synovial fluid, subchondral bone, articular cartilage, synovium, meniscus/labrum, infrapatellar/acetabular fat, anterior cruciate ligament/ligamentum teres, and vastus medialis oblique/quadratus femoris muscle (n = 7–20) from surgical patients with early- or late-stage osteoarthritis (OA) and quantified miR-335-5p and miR-335-3p expression by real-time PCR. Predicted gene targets were measured in knee OA infrapatellar fat following miRNA inhibitor transfection (n = 3), and prioritized gene targets were validated following miRNA inhibitor and mimic transfection (n = 6). Following pathway analyses, we performed Oil-Red-O staining to assess changes in total lipid content in infrapatellar fat.

Results
Showing a 227-fold increase in knee OA infrapatellar fat (the highest expressing tissue) versus meniscus (the lowest expressing tissue), miR-335-5p was more abundant than miR-335-3p (92-fold increase). MiR-335-5p showed higher expression across knee tissues versus hip tissues, and in late-stage versus early-stage knee OA fat. Exploring candidate genes, VCAM1 and MMP13 were identified as putative direct targets of miR-335-5p and miR-335-3p, respectively, showing downregulation with miRNA mimic transfection. Exploring candidate pathways, predicted miR-335-5p gene targets were enriched in a canonical adipogenesis network (p = 2.1e − 5). Modulation of miR-335-5p in late-stage knee OA fat showed an inverse relationship to total lipid content.

Conclusion
Our data suggest both miR-335-5p and miR-335-3p regulate gene targets in late-stage knee OA infrapatellar fat, though miR-335-5p appears to be more prominent, with tissue-, joint-, and stage-specific effects.
Bacterial endocarditis following COVID-19 infection: two case reports
Authors: Barahimi Elham , Defaee Sahar , Shokraei Rahele , Sheybani-Arani MohammadHosein , Salimi Asl Ali , Ghaem Hossein Montazer 
Published: June 2023

Abstract
Background
COVID-19, an emerging disease raised as a pandemic, urgently needed treatment choices. Some options have been confirmed as lifesaving treatments, but long-term complications must be clearly illustrated. Bacterial endocarditis is a less frequent disease among patients infected with SARS_COV_2 compared to other cardiac comorbidities in these patients. This case report discusses bacterial endocarditis as a potential adverse effect after administering tocilizumab, corticosteroids, and COVID-19 infection.

Case presentation
In the first case, a 51-year-old Iranian female housewife was admitted to the hospital with fever, weakness, and monoarthritis symptoms. The second case is a 63-year-old Iranian woman who is a housewife admitted with weakness, shortness of breath, and extreme sweating. Both cases tested positive for Polymerase chain reaction (PCR) less than one month ago and were treated with tocilizumab and corticosteroid. Both patients were suspected of infective endocarditis. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the blood cultures of both patients. The diagnosis of endocarditis is confirmed for both cases. Cases are subjected to open-heart surgery, a mechanical valve is placed, and they are treated with medication. In subsequent visits, their condition was reported to be improving.

Conclusion
Adjacent to cardiovascular inclusion as COVID-19 disease complications, secondary infection taken after the organisation of immunocompromising specialists can result in basic maladies and conditions counting infective endocarditis.