bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol alters mitophagy by impairing optineurin recruitment and lysosomal clearance in Alzheimer’s disease
Authors: Roca-Agujetas Vicente , Barbero-Camps Elisabet , de Dios Cristina , Podlesniy Petar , Abadin Xenia , Morales Albert , Marí Montserrat , Trullàs Ramon , Colell Anna 
Published: March 2021

Abstract
Background
Emerging evidence indicates that impaired mitophagy-mediated clearance of defective mitochondria is a critical event in Alzheimer’s disease (AD) pathogenesis. Amyloid-beta (Aβ) metabolism and the microtubule-associated protein tau have been reported to regulate key components of the mitophagy machinery. However, the mechanisms that lead to mitophagy dysfunction in AD are not fully deciphered. We have previously shown that intraneuronal cholesterol accumulation can disrupt the autophagy flux, resulting in low Aβ clearance. In this study, we examine the impact of neuronal cholesterol changes on mitochondrial removal by autophagy.

Methods
Regulation of PINK1-parkin-mediated mitophagy was investigated in conditions of acute (in vitro) and chronic (in vivo) high cholesterol loading using cholesterol-enriched SH-SY5Y cells, cultured primary neurons from transgenic mice overexpressing active SREBF2 (sterol regulatory element binding factor 2), and mice of increasing age that express the amyloid precursor protein with the familial Alzheimer Swedish mutation (Mo/HuAPP695swe) and mutant presenilin 1 (PS1-dE9) together with active SREBF2.

Results
In cholesterol-enriched SH-SY5Y cells and cultured primary neurons, high intracellular cholesterol levels stimulated mitochondrial PINK1 accumulation and mitophagosomes formation triggered by Aβ while impairing lysosomal-mediated clearance. Antioxidant recovery of cholesterol-induced mitochondrial glutathione (GSH) depletion prevented mitophagosomes formation indicating mitochondrial ROS involvement. Interestingly, when brain cholesterol accumulated chronically in aged APP-PSEN1-SREBF2 mice the mitophagy flux was affected at the early steps of the pathway, with defective recruitment of the key autophagy receptor optineurin (OPTN). Sustained cholesterol-induced alterations in APP-PSEN1-SREBF2 mice promoted an age-dependent accumulation of OPTN into HDAC6-positive aggresomes, which disappeared after in vivo treatment with GSH ethyl ester (GSHee). The analyses in post-mortem brain tissues from individuals with AD confirmed these findings, showing OPTN in aggresome-like structures that correlated with high mitochondrial cholesterol levels in late AD stages.

Conclusions
Our data demonstrate that accumulation of intracellular cholesterol reduces the clearance of defective mitochondria and suggest recovery of the cholesterol homeostasis and the mitochondrial scavenging of ROS as potential therapeutic targets for AD.
Philadelphia chromosome positive chronic myeloid leukemia with 5q deletion at diagnosis
Authors: Haidary Ahmed Maseh , Ahmed Zeeshan Ansar , Abdul-Ghafar Jamshid , Rahmani Soma , Noor Sarah , Erfani Farahnaz , Ahmad Maryam , Lakanwall Naeem , Malakzai Haider Ali , Ibrahimkhil Abdul Sami , Esmat Esmatullah , Haidari Mujtaba , Yousufzai Nimattullah , Sharif Samuel , Saqib Abdul Hadi 
Published: March 2021

Abstract
Background
Although, molecular genetic analyses became more and more important to guide therapy decisions in leukemia, banding cytogenetic analysis has retained its vital role in diagnosis and monitoring of chronic myeloid leukemia (CML), by quick and easy enabling identification of pathognomonic Philadelphia chromosome (Ph).

Case presentation
A 45 year old female presented with characteristic hematological features of CML in chronic phase; cytogenetic studies revealed the presence of the typical Ph and a deletion of almost entire long arm of a chromosome 5.

Conclusion
5q deletions have rarely been reported in CML. Those seen yet were either associated with tyrosine kinase inhibitor therapy or detected post allogeneic stem cell transplantation. To our knowledge, this is the first case of Ph positive CML accompanied by a 5q deletion.
cAMP activates calcium signalling via phospholipase C to regulate cellulase production in the filamentous fungus Trichoderma reesei
Authors: Chen Yumeng , Fan Xingjia , Zhao Xinqing , Shen Yaling , Xu Xiangyang , Wei Liujing , Wang Wei , Wei Dongzhi 
Published: March 2021

Abstract
Background
The filamentous fungus Trichoderma reesei is one of the best producers of cellulase and has been widely studied for the production of cellulosic ethanol and bio-based products. We previously reported that Mn2+ and N,N-dimethylformamide (DMF) can stimulate cellulase overexpression via Ca2+ bursts and calcium signalling in T. reesei under cellulase-inducing conditions. To further understand the regulatory networks involved in cellulase overexpression in T. reesei, we characterised the Mn2+/DMF-induced calcium signalling pathway involved in the stimulation of cellulase overexpression.

Results
We found that Mn2+/DMF stimulation significantly increased the intracellular levels of cAMP in an adenylate cyclase (ACY1)-dependent manner. Deletion of acy1 confirmed that cAMP is crucial for the Mn2+/DMF-stimulated cellulase overexpression in T. reesei. We further revealed that cAMP elevation induces a cytosolic Ca2+ burst, thereby initiating the Ca2+ signal transduction pathway in T. reesei, and that cAMP signalling causes the Ca2+ signalling pathway to regulate cellulase production in T. reesei. Furthermore, using a phospholipase C encoding gene plc-e deletion strain, we showed that the plc-e gene is vital for cellulase overexpression in response to stimulation by both Mn2+ and DMF, and that cAMP induces a Ca2+ burst through PLC-E.

Conclusions
The findings of this study reveal the presence of a signal transduction pathway in which Mn2+/DMF stimulation produces cAMP. Increase in the levels of cAMP activates the calcium signalling pathway via phospholipase C to regulate cellulase overexpression under cellulase-inducing conditions. These findings provide insights into the molecular mechanism of the cAMP–PLC–calcium signalling pathway underlying cellulase expression in T. reesei and highlight the potential applications of signal transduction in the regulation of gene expression in fungi.
Sex and nest type influence avian blood parasite prevalence in a high-elevation bird community
Authors: Rodriguez Marina D. , Doherty Paul F. , Piaggio Antoinette J. , Huyvaert Kathryn P. 
Published: March 2021

Abstract
Background
The prevalence of avian haemosporidian parasites and the factors influencing infection in the Colorado Rocky Mountains are largely unknown. With climate change expected to promote the expansion of vector and avian blood parasite distributions, baseline knowledge and continued monitoring of the prevalence and diversity of these parasites is needed.

Methods
Using an occupancy modeling framework, we conducted a survey of haemosporidian parasite species infecting an avian community in the Colorado Rocky Mountains in order to estimate the prevalence and diversity of blood parasites and to investigate species-level and individual-level characteristics that may influence infection.

Results
We estimated the prevalence and diversity of avian Haemosporidia across 24 bird species, detecting 39 parasite haplotypes. We found that open-cup nesters have higher Haemoproteus prevalence than cavity or ground nesters. Additionally, we found that male Ruby-crowned Kinglets, White-crowned Sparrows, and Wilson’s Warblers have higher Haemoproteus prevalence compared to other host species. Plasmodium prevalence was relatively low (5%), consistent with the idea that competent vectors may be rare at high altitudes.

Conclusions
Our study presents baseline knowledge of haemosporidian parasite presence, prevalence, and diversity among avian species in the Colorado Rocky Mountains and adds to our knowledge of host–parasite relationships of blood parasites and their avian hosts.

Graphical Abstract
High prevalence, intensity, and genetic diversity of Trichinella spp. in wolverine (Gulo gulo) from Yukon, Canada
Authors: Sharma Rajnish , Harms N. Jane , Kukka Piia M. , Jung Thomas S. , Parker Sarah E. , Ross Sasha , Thompson Peter , Rosenthal Benjamin , Hoberg Eric P. , Jenkins Emily J. 
Published: March 2021

Abstract
Background
Species of Trichinella are globally important foodborne parasites infecting a number of domestic and wild vertebrates, including humans. Free-ranging carnivores can act as sentinel species for detection of Trichinella spp. Knowledge of the epidemiology of these parasites may help prevent Trichinella spp. infections in northern Canadian animals and people. Previous research on Trichinella spp. in wildlife from Yukon did not identify risk factors associated with infection, or the diversity and identity of species of Trichinella in regional circulation, based on geographically extensive sampling with large sample sizes.

Methods
In a cross-sectional study, we determined the prevalence, infection intensity, risk factors, and species or genotypes of Trichinella in wolverine (Gulo gulo) in two regions of Yukon, Canada, from 2013–2017. A double separatory funnel digestion method followed by mutiplex PCR and PCR-RFLP were used to recover and identify species of Trichinella, respectively.

Results
We found larvae of Trichinella in the tongues of 78% (95% CI 73–82) of 338 wolverine sampled. The odds of adult (≥ 2 years) and yearling (1 year) wolverine being Trichinella spp.-positive were four and two times higher, respectively, compared to juveniles (<1 year). The odds of Trichinella spp. presence were three times higher in wolverine from southeast than northwest Yukon. The mean intensity of infection was 22.6 ± 39 (SD, range 0.1–295) larvae per gram. Trichinella T6 was the predominant genotype (76%), followed by T. nativa (8%); mixed infections with Trichinella T6 and T. nativa (12%) were observed. In addition, T. spiralis was detected in one wolverine. Out of 22 isolates initially identified as T. nativa in multiplex PCR, 14 were analyzed by PCR-RFLP to distinguish them from T. chanchalensis, a recently discovered cryptic species, which cannot be distinguished from the T. nativa on multiplex PCR. Ten isolates were identified either as T. chanchalensis alone (n = 7), or mixed infection with T. chanchalensis and T. nativa (n = 2) or T. chanchalensis and Trichinella T6 (n = 1)].

Conclusions
Wolverine hosted high prevalence, high larval intensity, and multiple species of Trichinella, likely due to their scavenging habits, apex position in the food chain, and wide home range. Wolverine (especially adult males) should be considered as a sentinel species for surveys for Trichinella spp. across their distributional range.

Graphical Abstract
Regular swimming exercise improves metabolic syndrome risk factors: a quasi-experimental study
Authors: Omar Jamal Shaker , Jaradat Nidal , Qadoumi Mohammad , Qadoumi Abdel Naser 
Published: March 2021

Abstract
Background
In the past few decades, swimming became one of the most important physical activities within the health system and is considered a practical nonpharmacological approach to managing of type 2 diabetes (T2DM), hyperlipidemia, hypertension (HTN), and obesity. The current study aimed to assess the effect of long-term swimming sessions on glycemic and lipidemic parameters, hemodynamic responses, body fat percent, and body mass index for patients with metabolic risk factors from Palestine.

Methods
Forty participants from both genders with T2DM and HTN (aged 52.4 ± 5.5 yrs) agreed to participate in this quasi-experimental study and were divided into two groups. The first group included the participants who performed long-term swimming sessions and the second group served as the control. The first group exercised for 2 h, 3 times/week in 29–33 °C swimming pool temperature for 16 weeks. Simultaneously, the control group did not participate in any exercise and advised them to keep on with their everyday lifestyle. All the obtained metabolic syndrome risk factors data were analyzed using a two-way ANOVA analysis of variance (2*2) which was applied to determine the differences according group, time, and interaction.

Results
The results showed that there were statistically significant differences at p < 0.05 in the variables of Total Cholesterol (TC), High Density of Lipoprotein (HDL), Low Density of Lipoprotein (LDL), Triglycerides (TG), Blood Glucose (BG), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Body Mass Index (BMI), and body fat percent according to group, time, and interaction for the experimental group.

Conclusions
The findings of the current study suggested that the regular 16 weeks of swimming sessions could be considered nonpharmacological approaches in managing T2DM and HTN.
The effectiveness of manual therapy applied to craniomandibular structures in the treatment of temporomandibular disorders: protocol for a systematic review
Authors: Asquini Giacomo , Rushton Alison , Pitance Laurent , Heneghan Nicola , Falla Deborah 
Published: March 2021

Abstract
Background
The term temporomandibular disorder (TMD) includes disorders of the temporomandibular joints (TMJ), masticatory muscles and adjacent tissues. Several studies have examined the effectiveness of manual therapy (MT) for TMDs by evaluating changes in pain and maximum mouth opening (MMO). Nevertheless, the effectiveness of MT exclusively applied to the craniomandibular structures (craniomandibular manual therapy (CMMT)) on pain and TMJ range of motion remains unclear. This review aims to evaluate the effectiveness of CMMT on pain and TMJ range of motion in people with TMDs.

Methods
This protocol is reported in line with the preferred reporting items for systematic reviews and meta-analysis protocols (PRISMA-P). Databases including MEDLINE, Embase, CINAHL, ZETOC, Web of Science, SCOPUS, PEDro, PubMed, Cochrane Library and Best Evidence, EBM reviews–Cochrane Central Register of Controlled Trials, Index to Chiropractic Literature ChiroAccess and Google Scholar will be searched from inception as well as key journals and grey literature. Randomised controlled trials involving adults with TMD that compare the effect of any type of CMMT (e.g. mobilisation) on pain and range of motion with a placebo intervention, controlled care intervention or other types of treatment will be included. Two reviewers will independently screen articles for inclusion, extract data, assess risk of bias (revised Cochrane risk of bias tool) for included studies and evaluate overall quality of evidence (Grading of Recommendations Assessment, Development and Evaluation). A meta-analysis will be conducted if possible. If not, a narrative synthesis will be conducted reporting the effectiveness of CMMT according to disorder type (TMJ disorders, masticatory muscle disorders and mixed disorders).

Discussion
In this review, the effectiveness of MT applied to craniomandibular structures for the treatment of TMD will be evaluated. Results will be submitted for publication in a peer-reviewed journal and presented at conferences. We expect our findings will facilitate treatment planning for manual therapists managing patients with TMD and provide future clinical research implications.

Systematic review registration
PROSPERO CRD42019160213
Ecological connectivity in fragmented agricultural landscapes and the importance of scattered trees and small patches
Authors: Tiang Darrel Chin Fung , Morris Andrew , Bell Mathew , Gibbins Christopher N. , Azhar Badrul , Lechner Alex M. 
Published: March 2021

Abstract
Background
Fragmentation and habitat loss can restrict species movement and reduce connectivity, negatively impacting biodiversity. Characterising the overall connectivity of an area can inform better management of human modified landscapes. Contemporary connectivity modelling methods seldom incorporate fine-scale movement patterns associated with movement between fine-scaled structural connectivity elements such as scattered trees, roadside corridors and small patches of habitat. This study aims to characterise connectivity within the Karuah-Myall catchments, a typical woodland ecosystem that is fragmented by agriculture, using least-cost path analysis and a graph-theoretic approach; it focuses on how fine-scaled vegetation such as scattered trees support connectivity. We mapped scattered (and paddock) trees within this agricultural landscape where the main human modified land use was pasture. We modelled connectivity for a general representative woodland species using an interpatch dispersal distance and gap crossing threshold, and resistance from different land cover types. The gap crossing distance threshold was used to model movement between fine-scaled vegetation features. We compared the least-cost paths modelled with and without scattered trees.

Results
Our results show that by excluding scattered trees, least-cost paths across the cleared pasture landscape did not reflect the types of movement patterns typically observed from field studies, such as those associated with a foray-search strategy used by small and medium mammals and birds. The modelling also shows that the Karuah-Myall catchments are well connected and provide value to biodiversity beyond the catchment borders, by connecting coastal vegetation to the Great Eastern Ranges national wildlife corridor initiative.

Conclusion
Connectivity models that exclude fine-scale landscape features such as scattered trees and small, linear patches risk misrepresenting connectivity patterns. Models of regional-scale connectivity can be influenced by the presence or absence of even the smallest features, such as scattered trees.
An old weapon with a new function: PIWI-interacting RNAs in neurodegenerative diseases
Authors: Huang Xiaobing , Wong Garry 
Published: March 2021

AbstractPIWI-interacting RNAs (piRNAs) are small non-coding transcripts that are highly conserved across species and regulate gene expression through pre- and post-transcriptional processes. piRNAs were originally discovered in germline cells and protect against transposable element expression to promote and maintain genome stability. In the recent decade, emerging roles of piRNAs have been revealed, including the roles in sterility, tumorigenesis, metabolic homeostasis, neurodevelopment, and neurodegenerative diseases. In this review, we summarize piRNA biogenesis in C. elegans, Drosophila, and mice, and further elaborate upon how piRNAs mitigate the harmful effects of transposons. Lastly, the most recent findings on piRNA participation in neurological diseases are highlighted. We speculate on the mechanisms of piRNA action in the development and progression of neurodegenerative diseases. Understanding the roles of piRNAs in neurological diseases may facilitate their applications in diagnostic and therapeutic practice.
The application of social innovation in healthcare: a scoping review
Authors: van Niekerk Lindi , Manderson Lenore , Balabanova Dina 
Published: March 2021

Abstract
Background
Social innovation has been applied increasingly to achieve social goals, including improved healthcare delivery, despite a lack of conceptual clarity and consensus on its definition. Beyond its tangible artefacts to address societal and structural needs, social innovation can best be understood as innovation in social relations, in power dynamics and in governance transformations, and may include institutional and systems transformations.

Methods
A scoping review was conducted of empirical studies published in the past 10 years, to identify how social innovation in healthcare has been applied, the enablers and barriers affecting its operation, and gaps in the current literature. A number of disciplinary databases were searched between April and June 2020, including Academic Source Complete, CIHAHL, Business Source Complete Psych INFO, PubMed and Global Health. A 10-year publication time frame was selected and articles limited to English text. Studies for final inclusion was based on a pre-defined criteria.

Results
Of the 27 studies included in this review, the majority adopted a case research methodology. Half of these were from authors outside the health sector working in high-income countries (HIC). Social innovation was seen to provide creative solutions to address barriers associated with access and cost of care in both low- and middle-income countries and HIC settings in a variety of disease focus areas. Compared to studies in other disciplines, health researchers applied social innovation mainly from an instrumental and technocratic standpoint to foster greater patient and beneficiary participation in health programmes. No empirical evidence was presented on whether this process leads to empowerment, and social innovation was not presented as transformative. The studies provided practical insights on how implementing social innovation in health systems and practice can be enhanced.

Conclusions
Based on theoretical literature, social innovation has the potential to mobilise institutional and systems change, yet research in health has not yet fully explored this dimension. Thus far, social innovation has been applied to extend population and financial coverage, principles inherent in universal health coverage and central to SDG 3.8. However, limitations exist in conceptualising social innovation and applying its theoretical and multidisciplinary underpinnings in health research.

Graphic abstract
The Maudsley model of anorexia nervosa treatment for adolescents and young adults (MANTRa): a study protocol for a multi-center cohort study
Authors: Wittek Tanja , Truttmann Stefanie , Zeiler Michael , Philipp Julia , Auer-Welsbach Ellen , Koubek Doris , Ohmann Susanne , Werneck-Rohrer Sonja , Sackl-Pammer Petra , Schöfbeck Gabriele , Mairhofer Dunja , Kahlenberg Leonie , Schmidt Ulrike , Karwautz Andreas F. K. , Wagner Gudrun 
Published: March 2021

Abstract
Background
The treatment of anorexia nervosa (AN) is often challenging due to medical complications as well as high relapse and mortality rates. Studies about effective treatment options for people with AN are particularly scarce in the adolescent population. This paper is a study protocol for a multi-center cohort study assessing the feasibility, acceptability and efficacy of a new, manualized treatment program, the “Maudsley Model of Anorexia Nervosa Treatment for Adolescents and Young Adults” (MANTRa) compared to psychotherapeutic treatment as usual (TAU).

Methods/design
One hundred patients between 13 and 21 years who meet the inclusion criteria will receive 24 to 34 individual weekly MANTRa therapy sessions or weekly TAU sessions. Primary outcome variables will be BMI and eating disorder psychopathology 12 months after baseline. Further changes in central coherence, cognitive flexibility, emotion recognition, comorbid psychopathology (e.g. depression, obsessive-compulsive and anxiety disorders, non-suicidal self-injury), personality factors and therapeutic alliance will be assessed.

Discussion
This multi-center study will examine the utility of the treatment program MANTRa for adolescents with AN and, therefore enhances the current knowledge about potential treatments for this patient group.

Trial registration
ClinicalTrials.gov Identifier: NCT03535714. Registered: 24/05/2018 (retrospectively registered, still recruiting).