bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-reflection and screening mental health on Canadian campuses: validation of the mental health continuum model
Authors: Chen Shu-Ping , Chang Wen-Pin , Stuart Heather 
Published: July 2020

Abstract
Background
This study describes the psychometric testing of the Mental Health Continuum (MHC) model the Canadian Department of National Defense developed initially, among undergraduates of three Canadian universities. The MHC is a tool that consists of 6 items to guide students the way to attend to, or monitor, signs and behavior indicators of their mental health status and suggest appropriate actions to improve their mental health.

Methods
Online survey data were collected from 4206 undergraduate students in three universities in two Canadian provinces during the spring of 2015 and winter of 2016. Participants completed an online survey questionnaire that consisted of the MHC questionnaire, the Kessler Psychological Distress Scale (K-10), and demographic information, including age, gender, and year of study.

Results
Factor analysis using the principal components method followed by a two-step internal replication analysis showed that the MHC tool was two-dimensional and that all six domains assessed were crucial. The construct (convergent) validity of the MHC tool was tested against the K-10, and the correlation analysis results were strong overall, as well as within subgroups defined by gender, year of study, and university.

Conclusions
The MHC is a useful tool that helps college students reflect on and enhance their mental health.
Phosphorylated Aβ peptides in human Down syndrome brain and different Alzheimer’s-like mouse models
Authors: Kumar Sathish , Lemere Cynthia A. , Walter Jochen 
Published: July 2020

AbstractThe deposition of neurotoxic amyloid-β (Aβ) peptides in extracellular plaques in the brain parenchyma is one of the most prominent neuropathological features of Alzheimer’s disease (AD), and considered to be closely related to the pathogenesis of this disease. A number of recent studies demonstrate the heterogeneity in the composition of Aβ deposits in AD brains, due to the occurrence of elongated, truncated and post-translationally modified Aβ peptides that have peculiar characteristics in aggregation behavior and biostability. Importantly, the detection of modified Aβ species has been explored to characterize distinct stages of AD, with phosphorylated Aβ being present in the clinical phase of AD. People with Down syndrome (DS) develop AD pathology by 40 years of age likely due to the overproduction of Aβ caused by the additional copy of the gene encoding the amyloid precursor protein on chromosome 21. In the current study, we analysed the deposition of phosphorylated and non-phosphorylated Aβ species in human DS, AD, and control brains. In addition, deposition of these Aβ species was analysed in brains of a series of established transgenic AD mouse models using phosphorylation-state specific Aβ antibodies. Significant amounts of Aβ phosphorylated at serine residue 8 (pSer8Aβ) and unmodified Aβ were detected in the brains of DS and AD cases. The brains of different transgenic mouse models with either only human mutant amyloid precursor protein (APP), or combinations of human mutant APP, Presenilin (PS), and tau transgenes showed distinct age-dependent and spatiotemporal deposition of pSer8Aβ in extracellular plaques and within the vasculature. Together, these results demonstrate the deposition of phosphorylated Aβ species in DS brains, further supporting the similarity of Aβ deposition in AD and DS. Thus, the detection of phosphorylated and other modified Aβ species could contribute to the understanding and dissection of the complexity in the age-related and spatiotemporal deposition of Aβ variants in AD and DS as well as in distinct mouse models.
BCAS1-positive immature oligodendrocytes are affected by the α-synuclein-induced pathology of multiple system atrophy
Authors: Kaji Seiji , Maki Takakuni , Ueda Jun , Ishimoto Tomoyuki , Inoue Yutaka , Yasuda Ken , Sawamura Masanori , Hikawa Rie , Ayaki Takashi , Yamakado Hodaka , Takahashi Ryosuke 
Published: July 2020

AbstractMultiple system atrophy (MSA) is pathologically characterized by the presence of fibrillar α-synuclein-immunoreactive inclusions in oligodendrocytes. Although the myelinating process of oligodendrocytes can be observed in adult human brains, little is known regarding the presence of α-synuclein pathology in immature oligodendrocytes and how their maturation and myelination are affected in MSA brains. Recently, breast carcinoma amplified sequence 1 (BCAS1) has been found to be specifically expressed in immature oligodendrocytes undergoing maturation and myelination. Here, we analyzed the altered dynamics of oligodendroglial maturation in both MSA brains and primary oligodendroglial cell cultures which were incubated with α-synuclein pre-formed fibrils. The numbers of BCAS1-expressing oligodendrocytes that displayed a matured morphology negatively correlated with the density of pathological inclusions in MSA brains but not with that in Parkinson’s disease and diffuse Lewy body disease. In addition, a portion of the BCAS1-expressing oligodendrocyte population showed cytoplasmic inclusions, which were labeled with antibodies against phosphorylated α-synuclein and cleaved caspase-9. Further in vitro examination indicated that the α-synuclein pre-formed fibrils induced cytoplasmic inclusions in the majority of BCAS1-expressing oligodendrocytes. In contrast, the majority of BCAS1-non-expressing mature oligodendrocytes did not develop inclusions on day 4 after maturation induction. Furthermore, exposure of α-synuclein pre-formed fibrils in the BCAS1-positive phase caused a reduction in oligodendroglial cell viability. Our results indicated that oligodendroglial maturation and myelination are impaired in the BCAS1-positive phase of MSA brains, which may lead to the insufficient replacement of defective oligodendrocytes. In vitro, the high susceptibility of BCAS1-expressing primary oligodendrocytes to the extracellular α-synuclein pre-formed fibrils suggests the involvement of insufficient oligodendroglial maturation in MSA disease progression and support the hypothesis that the BCAS1-positive oligodendrocyte lineage cells are prone to take up aggregated α-synuclein in vivo.
CytoSorb removes MDMA in vitro, but is it an effective therapy in vivo?
Authors: Honore Patrick M. , Redant Sebastien , Datzmann Thomas 
Published: July 2020

Abstract
Background
3,4-Methylenedioxymethamphetamine intoxication can result in potentially lethal multi-organ failure, for which the current treatment is largely supportive. Recently, a report of the use of the CytoSorb device as a part of the successful treatment of a patient with 3,4-methylenedioxymethamphetamine intoxication and multi-organ failure has been described.

Main body
While 3,4-methylenedioxymethamphetamine was very effectively removed by CytoSorb in vitro, the degree of removal in the clinical setting described may have been minimal. Indeed, the therapy was started relatively late in this case, and, as the therapy is concentration dependent, the removal of 3,4-methylenedioxymethamphetamine is likely to have been limited. On the other hand, in this case, CytoSorb hemoadsorption was very effective to treat rhabdomyolysis and hyperinflammation.

Conclusion
The in vitro experimentation demonstrates that 3,4-methylenedioxymethamphetamine is effectively removed by CytoSorb. However, it is debatable whether the case report confirms the possibility of in vivo removal of 3,4-methylenedioxymethamphetamine by CytoSorb. Nevertheless, the potential of the CytoSorb device to contribute to the treatment of many critically ill patients has yet to be fully explored, and further studies are warranted.
Splenic sarcoid reaction mimicking metachronous metastasis in patients after distal gastrectomy for gastric cancer: a case report and literature review
Authors: Okada Haruhiko , Ouchi Kazutomo , Saito Tetsuya , Takahashi Yuka , Yamada Masaki , Negami Naoki , Ishido Yasunori , Yamazaki Sanae , Sato Masahiko 
Published: July 2020

Abstract
Background
The occurrence of sarcoid reactions has been recognized in various cancers. The common location for observing these granulomas is mainly the lymph nodes, but a rare occurrence in the spleen has been reported.
Almost all splenic sarcoid reactions associated with gastric cancer have been resected synchronously and diagnosed accidentally, and a rare metachronous occurrence of a sarcoid reaction in the spleen after distal gastrectomy can mimic cancer metastasis. We describe a rare case of a splenic sarcoid reaction recognized in a patient with gastric cancer 6 months after distal gastrectomy.

Case presentation
An 82-year-old man underwent laparoscopic distal gastrectomy for gastric cancer (T3N0M0, stage IIA). Six months after gastrectomy, CT and 18F-fluorodeoxyglucose (FDG)-PET/CT showed the appearance of a splenic mass. We diagnosed solitary splenic metastasis from gastric cancer and performed laparoscopic-assisted splenectomy. His splenic tumor was diagnosed as a sarcoid reaction by histopathological examination.

Conclusion
To our knowledge, this is the first report of a splenic sarcoid reaction recognized 6 months after distal gastrectomy for gastric cancer without any chemotherapy. The splenic sarcoid reaction and cancer metastasis to the spleen were undistinguishable from the CT and FDG-PET/CT findings. The present case and literature review showed that cases of splenic sarcoid reactions associated with gastric cancer can also be accompanied by the occurrence of these granulomas in lymph nodes. When the appearance of a solitary mass is observed in the spleen after resection of primary cancer, it is necessary to consider not only cancer metastasis but also sarcoid reactions. Retrospective histopathological confirmation of the existence of sarcoid reactions in lymph nodes from resected specimens might possibly avoid incorrect diagnosis and intervention.
In-situ simulations for COVID-19: a safety II approach towards resilient performance
Authors: Lakissian Zavi , Sabouneh Rami , Zeineddine Rida , Fayad Joe , Banat Rim , Sharara-Chami Rana 
Published: July 2020

AbstractBackgroundCOVID-19 has taken the world by surprise; even the most sophisticated healthcare systems have been unable to cope with the volume of patients and lack of resources. Yet the gradual spread of the virus in Lebanon has allowed healthcare facilities critical time to prepare. Simulation is the most practical avenue not only for preparing the staff but also for troubleshooting system’s latent safety threats (LSTs) and for understanding these challenges via Hollnagel’s safety I–II approaches.MethodsThis is a quality improvement initiative: daily in situ simulations were conducted across various departments at the American University of Beirut Medical Center (AUBMC), a tertiary medical care center in Beirut, Lebanon. These simulations took place in the hospital with native multidisciplinary teams of 3–5 members followed by debriefing with good judgment using the modified PEARLS (Promoting Excellence and Reflective Learning in Simulation) for systems integration. All participants completed the simulation effectiveness tool (SET-M) to assess the simulation. Debriefings were analyzed qualitatively for content based on the Safety Model and LST identification, and the SET-Ms were analyzed quantitatively.ResultsTwenty-two simulations have been conducted with 131 participants. SET-M results showed that the majority (78–87%) strongly agreed to the effectiveness of the intervention. We were able to glean several clinical and human factor safety I–II components and LSTs such as overall lack of preparedness and awareness of donning/doffing of personal protective equipment (PPE), delayed response time, lack of experience in rapid sequence intubation, inability to timely and effectively assign roles, and lack of situational awareness. On the other hand, teams quickly recognized the patient’s clinical status and often communicated effectively.ConclusionThis intervention allowed us to detect previously unrecognized LSTs, prepare our personnel, and offer crucial practical hands-on experience for an unprecedented healthcare crisis.
Automated [18F]PSMA-1007 production by a single use cassette-type synthesizer for clinical examination
Authors: Naka Sadahiro , Watabe Tadashi , Kurimoto Kenta , Uemura Motohide , Soeda Fumihiko , Neels Oliver C. , Kopka Klaus , Tatsumi Mitsuaki , Kato Hiroki , Nonomura Norio , Shimosegawa Eku , Cardinale Jens , Giesel Frederik L. , Hatazawa Jun 
Published: July 2020

Abstract
Background
[18F]PSMA-1007, a positron emission tomography (PET) tracer, specifically targets prostate-specific membrane antigen (PSMA), which is highly expressed in prostate cancer. PSMA-PET is effective especially for regional detection of biochemical recurrence, which significantly affects patient management. Herein, we established and optimized a one-step radiolabeling protocol to separate and purify [18F]PSMA-1007 with a CFN-MPS200 synthesizer for clinical application.

Results
A dedicated single use cassette and synthesis program for [18F]PSMA-1007 was generated using a single-step method for direct precursor radiolabeling. In the cassette, three tube types (fluoro-elastomer, PharMed® BPT, silicone) and two different precursor salts (trifluoroacetic acid or acetic acid) were compared for optimization. Furthermore, three-lot tests were performed under optimized conditions for quality confirmation. Activity yields and mean radiochemical purity of [18F]PSMA-1007 were > 5000 MBq and 95%, respectively, at the end of synthesis, and the decay-corrected mean radiochemical yield from all three cassettes was approximately 40% using a trifluoroacetic acid salt precursor. Fluoro-elastomer tubings significantly increased the amount of non-radioactive PSMA-1007 (8.5 ± 3.1 μg/mL) compared to those with other tubings (0.3 μg/mL). This reduced the molar activity of [18F]PSMA-1007 synthesized in the cassette assembled by fluoro-elastomer tubings (46 GBq/μmol) compared to that with PharMed® BPT and silicone tubings (1184 and 1411 GBq/μmol, respectively). Residual tetrabutylammonium, acetonitrile, and dimethyl sulfoxide levels were <  2.6 μg/mL, < 8 ppm, and <  11 ppm, respectively, and ethanol content was 8.0–8.1% in all three cassettes and two different salts. Higher activity yields, radiochemical purities, and decay-corrected radiochemical yields were obtained using an acetic acid salt precursor rather than a trifluoroacetic acid salt precursor (7906 ± 1216 MBq, 97% ± 0%, and 56% ± 4%). In the three-lot tests under conditions optimized with silicone cassettes and acetic acid salt precursor, all quality items passed the specifications required for human use.

Conclusions
We successfully automated the production of [18F]PSMA-1007 for clinical use and optimized synthesis procedures with a CFN-MPS200 synthesizer using a silicone cassette and acetic acid salt precursor. Cassette availability will facilitate a wide spread use of [18F]PSMA-1007-PET, leading to an effective prostate cancer management.
Targeting fibroblast activation protein (FAP): next generation PET radiotracers using squaramide coupled bifunctional DOTA and DATA5m chelators
Authors: Moon Euy Sung , Elvas Filipe , Vliegen Gwendolyn , De Lombaerde Stef , Vangestel Christel , De Bruycker Sven , Bracke An , Eppard Elisabeth , Greifenstein Lukas , Klasen Benedikt , Kramer Vasko , Staelens Steven , De Meester Ingrid , Van der Veken Pieter , Rösch Frank 
Published: July 2020

Abstract
Background
Fibroblast activation protein (FAP) is a proline selective serine protease that is overexpressed in tumor stroma and in lesions of many other diseases that are characterized by tissue remodeling. In 2014, a most potent FAP-inhibitor (referred to as UAMC1110) with low nanomolar FAP-affinity and high selectivity toward related enzymes such as prolyl oligopeptidase (PREP) and the dipeptidyl-peptidases (DPPs): DPP4, DPP8/9 and DPP2 were developed. This inhibitor has been adopted recently by other groups to create radiopharmaceuticals by coupling bifunctional chelator-linker systems. Here, we report squaric acid (SA) containing bifunctional DATA5m and DOTA chelators based on UAMC1110 as pharmacophor. The novel radiopharmaceuticals DOTA.SA.FAPi and DATA5m.SA.FAPi with their non-radioactive derivatives were characterized for in vitro inhibitory efficiency to FAP and PREP, respectively and radiochemical investigated with gallium-68. Further, first proof-of-concept in vivo animal study followed by ex vivo biodistribution were determined with [68Ga]Ga-DOTA.SA.FAPi.

Results
[68Ga]Ga-DOTA.SA.FAPi and [68Ga]Ga-DATA5m.SA.FAPi showed high complexation > 97% radiochemical yields after already 10 min and high stability over a period of 2 h. Affinity to FAP of DOTA.SA.FAPi and DATA5m.SA.FAPi and its natGa and natLu-labeled derivatives were excellent resulting in low nanomolar IC50 values of 0.7–1.4 nM. Additionally, all five compounds showed low affinity for the related protease PREP (high IC50 with 1.7–8.7 μM). First proof-of-principle in vivo PET-imaging animal studies of the [68Ga]Ga-DOTA.SA.FAPi precursor in a HT-29 human colorectal cancer xenograft mouse model indicated promising results with high accumulation in tumor (SUVmean of 0.75) and low background signal. Ex vivo biodistribution showed highest uptake in tumor (5.2%ID/g) at 60 min post injection with overall low uptake in healthy tissues.

Conclusion
In this work, novel PET radiotracers targeting fibroblast activation protein were synthesized and biochemically investigated. Critical substructures of the novel compounds are a squaramide linker unit derived from the basic motif of squaric acid, DOTA and DATA5m bifunctional chelators and a FAP-targeting moiety. In conclusion, these new FAP-ligands appear promising, both for further research and development as well as for first human application.
Targeting the cholinergic anti-inflammatory pathway with vagus nerve stimulation in patients with Covid-19?
Authors: Bonaz Bruno , Sinniger Valérie , Pellissier Sonia 
Published: July 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), at the origin of the worldwide COVID-19 pandemic, is characterized by a dramatic cytokine storm in some critical patients with COVID-19. This storm is due to the release of high levels of pro-inflammatory cytokines such as interleukin (IL)-1 β, IL-6, tumor necrosis factor (TNF), and chemokines by respiratory epithelial and dendritic cells, and macrophages. We hypothesize that this cytokine storm and the worsening of patients’ health status can be dampened or even prevented by specifically targeting the vagal-driven cholinergic anti-inflammatory pathway (CAP). The CAP is a concept that involves an anti-inflammatory effect of vagal efferents by the release of acetylcholine (ACh). Nicotinic acetylcholine receptor alpha7 subunit (α7nAChRs) is required for ACh inhibition of macrophage-TNF release and cytokine modulation. Hence, targeting the α7nAChRs through vagus nerve stimulation (VNS) could be of interest in the management of patients with SARS-CoV-2 infection. Indeed, through the wide innervation of the organism by the vagus nerve, especially the lungs and gastrointestinal tract, VNS appears as a serious candidate for a few side effect treatment that could dampen or prevent the cytokine storm observed in COVID-19 patients with severe symptoms. Finally, a continuous vagal tone monitoring in patients with COVID-19 could be used as a predictive marker of COVID-19 illness course but also as a predictive marker of response to COVID-19 treatment such as VNS or others.
Government-mandated warnings on cannabis legally sold for recreational use
Authors: Malouff John M. , Schutte-Malouff Ben P. 
Published: July 2020

Abstract
Background
Frequent cannabis use can pose risks to health and safety. Multiple governments have legalized the sale of cannabis for recreational use and mandated health and safety warnings for recreational cannabis packages or signs at sales locations. The purposes of this study were to identify common themes across warnings and to compare the actual warnings with those previously recommended by cannabis experts and cannabis users.

Methods
We searched Google and Google Scholar for online lists of governments that allow or will soon allow the sale of cannabis for recreational use. Using the online lists we found, we searched for laws mandating the warnings, using the search terms “mandated warnings for recreational use marijuana” in addition to the name of the jurisdiction under review. We evaluated the content of the warnings and compared them with warnings recommended by cannabis experts and by users of recreational cannabis.

Results
Each search led to millions of results. Within the top results of each of the searches there were website links to official legislative websites, databases and documents of the jurisdiction under review. We used these official documents. The search revealed that 11 U.S. states and two countries allow the recreational use of cannabis and that 10 U.S. states and Canada mandate warnings on legally sold recreational cannabis. The mandated warnings can be categorized as focusing on one of nine risks: (1) negative health effects on the user, (2) harm to children or fetuses, (3) risks related to driving or operating machinery, (4) risks of habit formation leading to over-use, (5) risks relating to over-use on a single occasion, especially with regard to edible cannabis, (6) developmental risks for young people, (7) harm caused by secondary smoke, (8) risks of effects lasting several hours, and (9) risks specific to using cannabis topicals. The warnings include no graphic images and no phone number to call for help quitting.

Conclusions
The warnings, as a group, parallel most warnings recommended by cannabis experts and a sample of recreational users of cannabis. The effects of the warnings are unknown, but prior research findings on warnings for cannabis and for other substances suggest potential for positive effects in raising awareness of risks and decreasing the risks. The warnings could be used in public health campaigns. Public health professionals may find it possible through research to help improve the warnings, either in presentation or in content. Cannabis researchers can use the list to identify additional risks suitable for inclusion in mandated warnings.
Transient carriage and low-level colonization of orally administrated lytic and temperate phages in the gut of mice
Authors: Bao Hongduo , Zhang Hui , Zhou Yan , Zhu Shujiao , Pang Maoda , Shahin Khashayar , Olaniran Ademola , Schmidt Stefan , Wang Ran 
Published: July 2020

Abstract
Many studies have shown the efficacy of phage therapy in reducing gastrointestinal pathogens. However, it is unclear whether phages can successfully colonize the gut when administered in an adequate amount for a long time. About 1 × 108 PFU/mL of purified lytic phage PA13076 or temperate phage BP96115 were fed daily to mice via drinking water over 31 days, to elucidate the distribution of phages in the gastrointestinal tract. At day 16 and 31, six different segments of the gastrointestinal tract with their contents, including stomach, duodenum, jejunum, ileum, cecum, colon, and fresh feces, were aseptically collected. The phage titers were determined using the double-layered plate method with S. Enteritidis ATCC 13076 or S. Pullorum SPu-109 used as host cells. The results indicated that a small portion of administered phages survived exposure to gastric acid and entered the intestinal tract. The prevalence of phages in the gastrointestinal tract was lower than 1% of the primary phage count. Highest phage titers were detected in the cecum with 104 ~ 105 PFU/g, and most of the phages were eliminated from the body via feces with 106 PFU/g. On day 16 and day 31, the same level of phage titers in different segments of the gastrointestinal tract indicated that the colonization of phages had reached saturation at day 16. These results demonstrate transient phage carriage and low-level colonization of orally administrated lytic and temperate gut phages in mice.

Graphical abstract