bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains
Authors: Rhodes Roy H. , Love Gordon L. , Da Silva Lameira Fernanda , Sadough Shahmirzadi Maryam , Fox Sharon E. , Vander Heide Richard S. 
Published: February 2024

Abstract
Background
Hypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evidence of direct SARS-CoV-2 brain infection in COVID-19 patients.

Methods
Brain histopathology of 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied along with findings from contemporary and pre-pandemic historical control groups. Immunostaining for serum and blood cell proteins and for complement components was employed. Microcirculatory wall complement deposition in the COVID-19 cohort was compared to historical control cases. Comparisons also included other relevant clinicopathological and microcirculatory findings in the COVID-19 cohort and control groups.

Results
The COVID-19 cohort and both the contemporary and historical control groups had the same rate of hypertension, diabetes mellitus, and obesity. The COVID-19 cohort had varying amounts of acute neutrophilic vasculitis with leukocytoclasia in the microcirculation of the brain in all cases. Prominent vascular neutrophilic transmural migration was found in several cases and 25 cases had acute perivasculitis. Paravascular microhemorrhages and petechial hemorrhages (small brain parenchymal hemorrhages) had a slight tendency to be more numerous in cohort cases that displayed less acute neutrophilic vasculitis. Tissue burden of acute neutrophilic vasculitis with leukocytoclasia was the same in control cases as a group, while it was significantly higher in COVID-19 cases. Both the tissue burden of acute neutrophilic vasculitis and the activation of complement components, including membrane attack complex, were significantly higher in microcirculatory channels in COVID-19 cohort brains than in historical controls.

Conclusions
Acute neutrophilic vasculitis with leukocytoclasia, acute perivasculitis, and associated paravascular blood extravasation into brain parenchyma constitute the first phase of an immune-related, acute small-vessel inflammatory condition often termed type 3 hypersensitivity vasculitis or leukocytoclastic vasculitis. There is a higher tissue burden of acute neutrophilic vasculitis and an increased level of activated complement components in microcirculatory walls in COVID-19 cases than in pre-pandemic control cases. These findings are consistent with a more extensive small-vessel immune-related vasculitis in COVID-19 cases than in control cases. The pathway(s) and mechanism for these findings are speculative.
Natural products in osteoarthritis treatment: bridging basic research to clinical applications
Authors: Fang Shunzheng , Zhang Bin , Xiang Wei , Zheng Liujie , Wang Xiaodong , Li Song , Zhang Tongyi , Feng Daibo , Gong Yunquan , Wu Jinhui , Yuan Jing , Wu Yaran , Zhu Yizhen , Liu Enli , Ni Zhenhong 
Published: February 2024

AbstractOsteoarthritis (OA) is the most prevalent degenerative musculoskeletal disease, severely impacting the function of patients and potentially leading to disability, especially among the elderly population. Natural products (NPs), obtained from components or metabolites of plants, animals, microorganisms etc., have gained significant attention as important conservative treatments for various diseases. Recently, NPs have been well studied in preclinical and clinical researches, showing promising potential in the treatment of OA. In this review, we summed up the main signaling pathways affected by NPs in OA treatment, including NF-κB, MAPKs, PI3K/AKT, SIRT1, and other pathways, which are related to inflammation, anabolism and catabolism, and cell death. In addition, we described the therapeutic effects of NPs in different OA animal models and the current clinical studies in OA patients. At last, we discussed the potential research directions including in-depth analysis of the mechanisms and new application strategies of NPs for the OA treatment, so as to promote the basic research and clinical transformation in the future. We hope that this review may allow us to get a better understanding about the potential bioeffects and mechanisms of NPs in OA therapy, and ultimately improve the effectiveness of NPs-based clinical conservative treatment for OA patients.
Psychotic illness in people with Prader–Willi syndrome: a systematic review of clinical presentation, course and phenomenology
Authors: Aman Lucie C. S. , Lester Suzannah D. , Holland Anthony J. , Fletcher Paul C. 
Published: February 2024

Abstract
Background
Prader–Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder resulting from absent paternal expression of maternally imprinted genes at chromosomal locus 15q11-13. This absence of expression occurs as a consequence of a deletion on the chromosome 15 of paternal origin (ca. 70%), a chromosome 15 maternal uniparental disomy (mUPD; ca. 25%), or an imprinting centre defect (IC; ca. 1–3%). At birth, individuals with PWS are severely hypotonic and fail to thrive. Hyperphagia and characteristic physical and neuropsychiatric phenotypes become apparent during childhood. The risk for the development of a co-morbid psychotic illness increases during the teenage years, specifically in those with PWS due to the presence of an mUPD. The primary aim of this literature review is to inform clinical practice. To achieve this, we have undertaken a systematic analysis of the clinical research literature on prevalence, presentation, course, characteristics, diagnosis and treatment of psychotic illness in people with PWS. The secondary aim is to identify clinical aspects of psychotic illness in PWS in need of further investigation.

Methods and findings
A systematic literature review on psychosis in PWS was conducted on the databases Web of Knowledge, PubMed and Scopus, using the terms “((Prader–Willi syndrome) OR (Prader Willi Syndrome)) AND ((psychosis) OR (psychotic illness))”. All articles written in English and reporting original human research were reviewed. In all but three of the 16 cohort studies in which the genetic types were known, the authors reported higher rates of psychosis in people with PWS resulting from an mUPD, compared to those with the deletion subtype of PWS. When psychosis was present the presentation was psychosis similar regardless of genetic type and was usually characterised by an acute onset of hallucinations and delusions accompanied by confusion, anxiety and motor symptoms.

Conclusions
The onset of confusion, an affective cyclical pattern with the presence of abnormal mental beliefs and experiences, usually of rapid onset is suggestive of the development of psychotic illness. Phenomenologically, this psychosis in people with PWS is atypical in comparison to schizophrenia and bipolar disorder in the general population. The relationship to psychosis in the general population and the optimum treatments remain uncertain.
Transcriptional profiling of peripheral blood mononuclear cells identifies inflammatory phenotypes in Ataxia Telangiectasia
Authors: Michki Nigel S. , Singer Benjamin D. , Perez Javier V. , Thomas Aaron J. , Natale Valerie , Helmin Kathryn A. , Wright Jennifer , Cheng Leon , Young Lisa R. , Lederman Howard M. , McGrath-Morrow Sharon A. 
Published: February 2024

Abstract
Introduction
Ataxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disease with widespread systemic manifestations and marked variability in clinical phenotypes. In this study, we sought to determine whether transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) defines subsets of individuals with A-T beyond mild and classic phenotypes, enabling identification of novel features for disease classification and treatment response to therapy.

Methods
Participants with classic A-T (n = 77), mild A-T (n = 13), and unaffected controls (n = 15) were recruited from two outpatient clinics. PBMCs were isolated and bulk RNAseq was performed. Plasma was also isolated in a subset of individuals. Affected individuals were designated mild or classic based on ATM mutations and clinical and laboratory features.

Results
People with classic A-T were more likely to be younger and IgA deficient and to have higher alpha-fetoprotein levels and lower % forced vital capacity compared to individuals with mild A-T. In classic A-T, the expression of genes required for V(D)J recombination was lower, and the expression of genes required for inflammatory activity was higher. We assigned inflammatory scores to study participants and found that inflammatory scores were highly variable among people with classic A-T and that higher scores were associated with lower ATM mRNA levels. Using a cell type deconvolution approach, we inferred that CD4 + T cells and CD8 + T cells were lower in number in people with classic A-T. Finally, we showed that individuals with classic A-T exhibit higher SERPINE1 (PAI-1) mRNA and plasma protein levels, irrespective of age, and higher FLT4 (VEGFR3) and IL6ST (GP130) plasma protein levels compared with mild A-T and controls.

Conclusion
Using a transcriptomic approach, we identified novel features and developed an inflammatory score to identify subsets of individuals with different inflammatory phenotypes in A-T. Findings from this study could be used to help direct treatment and to track treatment response to therapy.
Rare neurodevelopmental conditions and parents’ mental health – how and when does genetic diagnosis matter?
Authors: Chi Zhaotian , Devine Rory T. , Wolstencroft Jeanne , Skuse David , Hughes Claire , Baker Kate ,   IMAGINE-ID consortium
Published: February 2024

Abstract
Background
Parents of individuals with rare neurodevelopmental conditions and intellectual disabilities (ID) are vulnerable to mental health difficulties, which vary between parents and within parents over time. The underlying cause of a child’s condition can influence parents’ mental health, via uncertain pathways and within unknown time-windows.

Results
We analysed baseline data from the IMAGINE-ID cohort, comprising 2655 parents of children and young people with ID of known genetic origin. First, we conducted a factor analysis of the SDQ Impact scale to isolate specific pathways from genetic aetiology to parents’ mental health. This suggested a two-factor structure for the SDQ Impact scale, with a “home & distress” dimension and a “participation” dimension. Second, we tested via structural equation modelling (SEM) whether genetic diagnosis affects Impact and mental health directly, or indirectly via children’s characteristics. This analysis identified an indirect pathway linking genetic aetiology to parents’ mental health, serially through child characteristics (physical disabilities, emotional and behavioural difficulties) and Impact: home & distress. Third, we conducted moderation analysis to explore the influence of time elapsed since genetic diagnosis. This showed that the serial mediation model was moderated by time since diagnosis, with strongest mediating effects among recently diagnosed cases.

Conclusions
There are multiple steps on the pathway from ID-associated genetic diagnoses to parents’ mental health. Pathway links are strongest within 5 years of receiving a genetic diagnosis, highlighting opportunities for better post-diagnostic support. Recognition and enhanced support for children’s physical and behavioural needs might reduce impact on family life, ameliorating parents’ vulnerabilities to mental health difficulties.
Assessing support for mental health policies among policy influencers and the general public in Alberta and Manitoba, Canada
Authors: Nykiforuk Candace I. J. , Thomson Mathew , Curtin Kimberley D. , Colman Ian , Wild T. Cameron , Hyshka Elaine 
Published: February 2024

Abstract
Background
There is a need to improve mental health policy in Canada to address the growing population burden of mental illness. Understanding support for policy options is critical for advocacy efforts to improve mental health policy. Our purpose was to describe support for population-level healthy public policies to improve mental health among policy influencers and the general public in Alberta and Manitoba; and, identify associations between levels of support and sociodemographic variables and relative to the Nuffield Bioethics Intervention Ladder framework.

Methods
We used data from the 2019 Chronic Disease Prevention Survey, which recruited a representative sample of the general public in Alberta (n = 1792) and Manitoba (n = 1909) and policy influencers in each province (Alberta n = 291, Manitoba n = 129). Level of support was described for 16 policy options using a Likert-style scale for mental health policy options by province, sample type, and sociodemographic variables using ordinal regression modelling. Policy options were coded using the Nuffield Council on Bioethics Intervention Ladder to classify support for policy options by level of intrusiveness.

Results
Policy options were categorized as ‘Provide Information’ and ‘Enable Choice’ according to the Nuffield Intervention Ladder. There was high support for all policy options, and few differences between samples or provinces. Strong support was more common among women and among those who were more politically left (versus center). Immigrants were more likely to strongly support most of the policies. Those who were politically right leaning (versus center) were less likely to support any of the mental health policies. Mental health status, education, and Indigenous identity were also associated with support for some policy options.

Conclusions
There is strong support for mental health policy in Western Canada. Results demonstrate a gap between support and implementation of mental health policy and provide evidence for advocates and policy makers looking to improve the policy landscape in Canada.
Mapping mental health care services for children and youth population in Colombia’s Pacific: potential for boundary spanning between community and formal services
Authors: Weber Sanne , Carranza Francy , Rengifo Juan Roberto , Romero Camilo , Arrieta Sergio , Martínez Karina , Pinilla-Roncancio Mónica , Fenton Sarah-Jane , Casas Germán , Jackson Paul , Aranguren Juan Pablo 
Published: February 2024

Abstract
Background
Conflict and violence can impact on the mental health of children and young people, who are in a crucial stage of their personal growth. Not much is known about the provision of mental health care to young people in conflict-affected areas. Community-based care can be essential, as state-led services are often scarce in conflict contexts, like Colombia’s Pacific region where this research was conducted. According to the WHO, such care is ideally provided in the form of a network of interconnected services, offered by different actors beyond the formal health sector. This article describes the relationship between the formal and community mental health systems in Colombia’s Pacific region, and identifies ways of improving their interaction.

Methods
Qualitative data were collected through 98 semi-structured interviews with community organisations, schools, international organisations and state institutions. These interviews aimed to identify the strategies used to promote young people’s mental health and the interactions between the different providers. Boundary spanning theory was used to analyse how different actors and forms of mental health care provision could coordinate better.

Results
Community organisations and schools use a wide array of strategies to attend to the mental health of children and young people, often of a collective and psychosocial nature. State institutions offer more clinically focused strategies, which are however limited in terms of accessibility and continuity. International organisations aim to strengthen state capacity, but often struggle due to high staff turnover. Although mental health care pathways exist, their effectiveness is limited due to ineffective coordination between actors.

Conclusions
To make sure that the variety of strategies to improve young people’s mental health effectively reach their beneficiaries, better coordination is needed between the different actors. Mental health care pathways should therefore integrate community organisations, while community connectors can help to manage the coordination between different actors and forms of clinical and psychosocial support.
Advanced biomanufacturing and evaluation of adeno-associated virus
Authors: Chen Kai , Kim Seulhee , Yang Siying , Varadkar Tanvi , Zhou Zhuoxin Zora , Zhang Jiashuai , Zhou Lufang , Liu Xiaoguang Margaret 
Published: February 2024

AbstractRecombinant adeno-associated virus (rAAV) has been developed as a safe and effective gene delivery vehicle to treat rare genetic diseases. This study aimed to establish a novel biomanufacturing process to achieve high production and purification of various AAV serotypes (AAV2, 5, DJ, DJ8). First, a robust suspensive production process was developed and optimized using Gibco Viral Production Cell 2.0 in 30–60 mL shaker flask cultures by evaluating host cells, cell density at the time of transfection and plasmid amount, adapted to 60–100 mL spinner flask production, and scaled up to 1.2–2.0-L stirred-tank bioreactor production at 37 °C, pH 7.0, 210 rpm and DO 40%. The optimal process generated AAV titer of 7.52–8.14 × 1010 vg/mL. Second, a new AAV purification using liquid chromatography was developed and optimized to reach recovery rate of 85–95% of all four serotypes. Post-purification desalting and concentration procedures were also investigated. Then the generated AAVs were evaluated in vitro using Western blotting, transmission electron microscope, confocal microscope and bioluminescence detection. Finally, the in vivo infection and functional gene expression of AAV were confirmed in tumor xenografted mouse model. In conclusion, this study reported a robust, scalable, and universal biomanufacturing platform of AAV production, clarification and purification.
Identification of CD160-TM as a tumor target on triple negative breast cancers: possible therapeutic applications
Authors: Scheffges Claire , Devy Jérôme , Giustiniani Jérôme , Francois Stessy , Cartier Lucille , Merrouche Yacine , Foussat Arnaud , Potteaux Stéphane , Bensussan Armand , Marie-Cardine Anne 
Published: February 2024

Abstract
Background
Despite major therapeutic advances, triple-negative breast cancer (TNBC) still presents a worth prognosis than hormone receptors-positive breast cancers. One major issue relies in the molecular and mutational heterogeneity of TNBC subtypes that is reinforced by the absence of reliable tumor-antigen that could serve as a specific target to further promote efficient tumor cell recognition and depletion. CD160 is a receptor mainly expressed by NK lymphocytes and presenting two isoforms, namely the GPI-anchored form (CD160-GPI) and the transmembrane isoform (CD160-TM). While CD160-GPI is constitutively expressed on resting cells and involved in the generation of NK cells' cytotoxic activity, CD160-TM is neo-synthesized upon activation and promotes the amplification of NK cells' killing ability.

Methods
CD160 expression was assessed by immunohistochemistry (IHC) and flow cytometry on TNBC patient biopsies or cell lines, respectively. Antibody (Ab)-mediated tumor depletion was tested in vitro by performing antibody-dependent cell cytotoxicity (ADCC) and phagocytosis (ADCP) assays, and in vivo on a TNBC mouse model.

Results
Preliminary data obtained by IHC on TNBC patients' tumor biopsies revealed an unconventional expression of CD160 by TNBC tumor cells. By using a specific but conformation-dependent anti-CD160-TM Ab, we established that CD160-TM, but not CD160-GPI, was expressed by TNBC tumor cells. A conformation-independent anti-CD160-TM mAb (22B12; muIgG2a isotype) was generated and selected according to pre-defined specificity and functional criterions. In vitro functional assays demonstrated that ADCC and ADCP could be induced in the presence of 22B12, resulting in TNBC cell line apoptosis. The ability of 22B12 to exert an in vivo anti-tumor activity was also demonstrated on a TNBC murine model.

Conclusions
Our data identify CD160-TM as a tumor marker for TNBC and provide a rational for the use of anti-CD160-TM antibodies as therapeutic tools in this tumor context.
Continuous combined oral contraceptive use versus vitamin E in the treatment of menstrual migraine: rationale and protocol of a randomized controlled trial (WHAT!)
Authors: van der Arend Britt W. H. , van Casteren Daphne S. , Verhagen Iris E. , MaassenVanDenBrink Antoinette , Terwindt Gisela M. 
Published: February 2024

Abstract
Background
Currently, there is no evidence-based hormonal treatment for migraine in women. Several small studies suggest a beneficial effect of combined oral contraceptives, but no large randomized controlled trial has been performed. As proof of efficacy is lacking and usage may be accompanied by potentially severe side effects, there is a great need for clarity on this topic.

Methods
Women with menstrual migraine (n = 180) are randomly assigned (1:1) to ethinylestradiol/levonorgestrel 30/150 μg or vitamin E 400 IU. Participants start with a baseline period of 4 weeks, which is followed by a 12-week treatment period. During the study period, a E-headache diary will be used, which is time-locked and includes an automated algorithm differentiating headache and migraine days.

Results
The primary outcome will be change in monthly migraine days (MMD) from baseline (weeks − 4 to 0) to the last 4 weeks of treatment (weeks 9 to 12). Secondary outcomes will be change in monthly headache days (MHD) and 50% responder rates of MMD and MHD.

Conclusions
The WHAT! trial aims to investigate effectivity and safety of continuous combined oral contraceptive treatment for menstrual migraine. Immediate implementation of results in clinical practice is possible.

Trial registration
Clinical trials.gov NCT04007874. Registered 28 June 2019.