bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing and piloting a self-assessment tool for medication review competence of practicing pharmacists based on nationally set competence criteria
Authors: Lias Noora , Lindholm Tanja , Pohjanoksa-Mäntylä Marika , Westerholm Aleksi , Airaksinen Marja 
Published: November 2021

Abstract
Background
New competence requirements have emerged for pharmacists as a result of changing societal needs towards more patient-centred practices. Today, medication review competence can be considered as basic pharmaceutical competence. Medication review specific competence criteria and tools for self-assessing the competence are essential in building competences and a shared understanding of medication reviews as a collaborative practice. The aim of this study was to develop and pilot a self-assessment tool for medication review competence among practicing pharmacists in Finland.

Methods
The development of the self-assessment tool was based on the national medication review competence criteria for pharmacists established in Finland in 2017 and piloting the tool among practicing pharmacists in a national online survey in October 2018. The pharmacists self-assessed their medication review competence with a five-point Likert scale ranging from 1 for “very poor/not at all” to 5 for “very good”.

Results
The internal consistency of the self-assessment tool was high as the range of the competence areas’ Cronbach’s alpha was 0.953–0.973. The competence areas consisted of prescription review competence (20 items, Cronbach’s alpha 0.953), additional statements for medication review competence (11 additional items, Cronbach’s alpha 0.963) and medication review as a whole, including both the statements of prescription review and medication review competence (31 items, Cronbach’s alpha 0.973). Competence items closely related to routine dispensing were most commonly self-estimated to be mastered by the practicing pharmacists who responded (n = 344), while the more clinical and patient-centred competence items had the lowest self-estimates. This indicates that the self-assessment tool works logically and differentiates pharmacists according to competence. The self-assessed medication review competence was at a very good or good level among more than half (55%) of the respondents (n = 344).

Conclusion
A self-assessment tool for medication review competence was developed and validated. The piloted self-assessment tool can be used for regular evaluation of practicing pharmacists’ medication review competence which is becoming an increasingly important basis for their contribution to patient care and society.
Telehealth for opioid use disorder treatment in low-barrier clinic settings: an exploration of clinician and staff perspectives
Authors: Aronowitz Shoshana V. , Engel-Rebitzer Eden , Dolan Abby , Oyekanmi Kehinde , Mandell David , Meisel Zachary , South Eugenia , Lowenstein Margaret 
Published: November 2021

Abstract
Background
The majority of individuals with opioid use disorder (OUD) face access barriers to evidence-based treatment, and the COVID-19 pandemic has exacerbated the United States (US) opioid overdose crisis. However, the pandemic has also ushered in rapid transitions to telehealth in the USA, including for substance use disorder treatment with buprenorphine. These changes have the potential to mitigate barriers to care or to exacerbate pre-existing treatment inequities. The objective of this study was to qualitatively explore Philadelphia-based low-barrier, harm-reduction oriented, opioid use disorder (OUD) treatment provider perspectives about and experiences with telehealth during the COVID-19 pandemic, and to assess their desire to offer telehealth to patients at their programs in the future.

Methods
We interviewed 22 OUD treatment prescribers and staff working outpatient programs offering OUD treatment with buprenorphine in Philadelphia during July and August 2020. All participants worked at low-barrier treatment programs that provide buprenorphine using a harm reduction-oriented approach and without mandating counseling or other requirements as a condition of treatment. We analyzed the data using thematic content analysis.

Results
Our analysis yielded three themes: 1/ Easier access for some: telehealth facilitates care for many patients who have difficulty attending in-person appointments due to logistical and psychological barriers; 2/ A layered digital divide: engagement with telehealth can be seriously limited by patients’ access to and comfort with technology; and 3/ Clinician control: despite some clinic staff beliefs that patients should have the freedom to choose their treatment modality, patients’ access to treatment via telehealth may hinge on clinician perceptions of patient “stability” rather than patient preferences.

Conclusions
Telehealth may address many access issues, however, barriers to implementation remain, including patient ability and desire to attend healthcare appointments virtually. In addition, the potential for telehealth models to extend OUD care to patients currently underserved by in-person models may partially depend on clinician comfort treating patients deemed “unstable” via this modality. The ability of telehealth to expand access to OUD care for individuals who have previously struggled to engage with in-person care will likely be limited if these patients are not given the opportunity to receive treatment via telehealth.
Upregulation of TRPC5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout IL-10 mice
Authors: Huo Shiji , Ren Jiling , Ma Yunqing , Ozathaley Ahsawle , Yuan Wenjian , Ni Hong , Li Dong , Liu Zhaowei 
Published: November 2021

AbstractBackgroundMembers of the transient receptor potential canonical (TRPC) protein family are widely distributed in the hippocampus of mammals and exert respective and cooperative influences on the functions of neurons. The relationship between specific TRPC subtypes and neuroinflammation is receiving increasing attention.MethodsUsing Cx3cr1CreERIL-10−/−transgenic mice and their littermates to study the relationship between TRPC channels and memory impairment.ResultsWe demonstrated that Cx3cr1CreERIL-10−/−mice displayed spatial memory deficits in object location recognition (OLR) and Morris water maze (MWM) tasks. The decreased levels of TRPC4 and TRPC5 in the hippocampal regions were verified via reverse transcription polymerase chain reaction, western blotting, and immunofluorescence tests. The expression of postsynaptic density protein 95 (PSD95) and synaptophysin in the hippocampus decreased with an imbalance in the local inflammatory environment in the hippocampus. The number of cells positive for ionized calcium-binding adaptor molecule 1 (Iba1), a glial fibrillary acidic protein (GFAP), increased with the high expression of interleukin 6 (IL-6) in Cx3cr1CreERIL-10−/−mice. The nod-like receptor protein 3 (NLRP3) inflammasome was also involved in this process, and the cytokines IL-1β and IL-18 activated by NLRP3 were also elevated by western blotting. The co-localization of TRPC5 and calmodulin-dependent protein kinase IIα (CaMKIIα) significantly decreased TRPC5 expression in excitatory neurons. AAV9-CaMKIIα-TRPC5 was used to upregulate TRPC5 in excitatory neurons in the hippocampus.ConclusionsThe results showed that the upregulation of TRPC5 improved the memory performance of Cx3cr1CreERIL-10−/−mice related to inhibiting NLRP3 inflammasome-associated neuroinflammation.Graphical Abstract
Early upregulation of cytosolic phospholipase A2α in motor neurons is induced by misfolded SOD1 in a mouse model of amyotrophic lateral sclerosis
Authors: Malada Edelstein Yafa Fetfet , Solomonov Yulia , Hadad Nurit , Alfahel Leenor , Israelson Adrian , Levy Rachel 
Published: November 2021

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a fatal multifactorial neurodegenerative disease characterized by the selective death of motor neurons. Cytosolic phospholipase A2 alpha (cPLA2α) upregulation and activation in the spinal cord of ALS patients has been reported. We have previously shown that cPLA2α upregulation in the spinal cord of mutant SOD1 transgenic mice (SOD1G93A) was detected long before the development of the disease, and inhibition of cPLA2α upregulation delayed the disease’s onset. The aim of the present study was to determine the mechanism for cPLA2α upregulation.

Methods
Immunofluorescence analysis and western blot analysis of misfolded SOD1, cPLA2α and inflammatory markers were performed in the spinal cord sections of SOD1G93A transgenic mice and in primary motor neurons. Over expression of mutant SOD1 was performed by induction or transfection in primary motor neurons and in differentiated NSC34 motor neuron like cells.

Results
Misfolded SOD1 was detected in the spinal cord of 3 weeks old mutant SOD1G93A mice before cPLA2α upregulation. Elevated expression of both misfolded SOD1 and cPLA2α was specifically detected in the motor neurons at 6 weeks with a high correlation between them. Elevated TNFα levels were detected in the spinal cord lysates of 6 weeks old mutant SOD1G93A mice. Elevated TNFα was specifically detected in the motor neurons and its expression was highly correlated with cPLA2α expression at 6 weeks. Induction of mutant SOD1 in primary motor neurons induced cPLA2α and TNFα upregulation. Over expression of mutant SOD1 in NSC34 cells caused cPLA2α upregulation which was prevented by antibodies against TNFα. The addition of TNFα to NSC34 cells caused cPLA2α upregulation in a dose dependent manner.

Conclusions
Motor neurons expressing elevated cPLA2α and TNFα are in an inflammatory state as early as at 6 weeks old mutant SOD1G93A mice long before the development of the disease. Accumulated misfolded SOD1 in the motor neurons induced cPLA2α upregulation via induction of TNFα.
Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: a propensity score-based analysis
Authors: Duarte Mateus Bringel Oliveira , Leal Frederico , Argenton Juliana Luz Passos , Carvalheira José Barreto Campello 
Published: November 2021

AbstractBackgroundPrevious studies hypothesized that androgen deprivation therapy (ADT) may reduce severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infectivity. However, it is unknown whether there is an association between ADT and a higher survival in prostate cancer patients with COVID-19.MethodsWe performed a retrospective analysis of prostate cancer (PC) patients hospitalized to treat COVID-19 in Brazil’s public health system. We compared patients with the active use of ADT versus those with non-active ADT, past use. We constructed propensity score models of patients in active versus non-active use of ADT. All variables were used to derive propensity score estimation in both models. In the first model we performed a pair-matched propensity score model between those under active and non-active use of ADT. To the second model we initially performed a multivariate backward elimination process to select variables to a final inverse-weight adjusted with double robust estimation model.ResultsWe analyzed 199 PC patients with COVID-19 that received ADT. In total, 52.3% (95/199) of our patients were less than 75 years old, 78.4% (156/199) were on active ADT, and most were using a GnRH analog (80.1%; 125/156). Most of patients were in palliative treatment (89.9%; 179/199). Also, 63.3% of our cohort died from COVID-19. Forty-eight patients under active ADT were pair matched against 48 controls (non-active ADT). All patients (199) were analyzed in the double robust model. ADT active use were not protective factor in both inverse-weight based propensity score (OR 0.70, 95% CI 0.38–1.31,P = 0.263), and pair-matched propensity score (OR 0.67, 95% CI 0.27–1.63,P = 0.374) models. We noticed a significant imbalance in the propensity score of patients in active and those in non-active ADT, with important reductions in the differences after the adjustments.ConclusionsThe active use of ADT was not associated with a reduced risk of death in patients with COVID-19.
Multimodal brain imaging effect of “Adjust Zang-fu and Arouse Spirit” electroacupuncture on diabetic cognitive impairment: study protocol of a randomized, sham-controlled pilot trial
Authors: Yao Lin , Li Mengyuan , Sun Shunan , Xu Ming , Yu Shuo , Zhang Ziyang , Zhang Liying , Zheng Haizhu , Zhong Zhen , Ma Shiqi , Huang Haipeng , Wang Hongfeng 
Published: November 2021

Abstract
Background
Diabetic cognitive impairment (DCI) is a serious chronic complication caused by diabetes. The pathogenesis of DCI is complex, but brain nerve injury and brain nerve cell apoptosis are important pathological changes. Multimodal brain imaging is one of the most important techniques to study the neural mechanism of the brain. For the clinical treatment of DCI, there is no effective targeted Western medicine and a lack of clear drug intervention methods. Therefore, there is an urgent need to find effective complementary and alternative methods and clarify their mechanism. This research seeks to explore the multimodal brain imaging effect of “Adjust Zang-fu and Arouse Spirit” electroacupuncture for DCI.

Methods
This clinical research will be a randomized, sham-controlled pilot trial. Eligible participants will be randomly assigned to the intervention group (n = 60) and the control group (n = 30). The intervention group will be divided into the “Adjust Zang-fu and Arouse Spirit” electroacupuncture group (n = 30) and sham electroacupuncture group (n = 30). All participants will continue to receive routine hypoglycemic therapy. The treatment period is the same in both groups. The primary outcomes include functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), Montreal Cognitive Assessment Scale (MoCA), and Clinical Dementia Rating (CDR). The secondary outcomes include blood glucose and blood lipid tests, Instrumental Activities of Daily Living Scale (IADL), Hachinski Ischemic Scale (HIS), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). Outcomes will be assessed at baseline and before and after treatment, and adverse events will be examined. Inter- and intragroup analyses will be performed.

Discussion
This randomized controlled study, combined with multimodal brain imaging techniques and a clinical evaluation scale, was designed to explore the mechanism of “Adjust Zang-fu and Arouse Spirit” electroacupuncture in improving the central nervous system in DCI.

Trial registration
Chinese Clinical Trial Registration ChiCTR2000040268. Registered on 26 November 2020
Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes
Authors: Ghodke-Puranik Yogita , Jin Zhongbo , Zimmerman Kip D. , Ainsworth Hannah C. , Fan Wei , Jensen Mark A. , Dorschner Jessica M. , Vsetecka Danielle M. , Amin Shreyasee , Makol Ashima , Ernste Floranne , Osborn Thomas , Moder Kevin , Chowdhary Vaidehi , Langefeld Carl D. , Niewold Timothy B. 
Published: November 2021

Abstract
Background
We performed expression quantitative trait locus (eQTL) analysis in single classical (CL) and non-classical (NCL) monocytes from patients with systemic lupus erythematosus (SLE) to quantify the impact of well-established genetic risk alleles on transcription at single-cell resolution.

Methods
Single-cell gene expression was quantified using qPCR in purified monocyte subpopulations (CD14++CD16− CL and CD14dimCD16+ NCL) from SLE patients. Novel analysis methods were used to control for the within-person correlations observed, and eQTLs were compared between cell types and risk alleles.

Results
The SLE-risk alleles demonstrated significantly more eQTLs in NCLs as compared to CLs (p = 0.0004). There were 18 eQTLs exclusive to NCL cells, 5 eQTLs exclusive to CL cells, and only one shared eQTL, supporting large differences in the impact of the risk alleles between these monocyte subsets. The SPP1 and TNFAIP3 loci were associated with the greatest number of transcripts. Patterns of shared influence in which different SNPs impacted the same transcript also differed between monocyte subsets, with greater evidence for synergy in NCL cells. IRF1 expression demonstrated an on/off pattern, in which expression was zero in all of the monocytes studied from some individuals, and this pattern was associated with a number of SLE risk alleles. We observed corroborating evidence of this IRF1 expression pattern in public data sets.

Conclusions
We document multiple SLE-risk allele eQTLs in single monocytes which differ greatly between CL and NCL subsets. These data support the importance of the SPP1 and TNFAIP3 risk variants and the IRF1 transcript in SLE patient monocyte function.
Affective temperaments of Lebanese patients with schizophrenia: comparison by gender and severity of psychosis
Authors: Dib Joseph E. , Nehme Ilige , Haddad Chadia , Azar Jocelyne , Hallit Souheil , Obeid Sahar 
Published: November 2021

Abstract
Objectives
Our aim in this study was to identify affective temperament differences utilizing the TEMPS-A in a large sample size of Lebanese patients with schizophrenia and compare them to healthy controls. Gender differences, demographic factors and degree of psychotic symptoms were also considered. A cross‐sectional study was conducted at the Psychiatric Hospital of the Cross (PHC) from March to June 2019. Two-hundred fifty chronic patients with schizophrenia were compared to 250 healthy controls randomly chosen from the general population.

Results
Patients with schizophrenia significantly had higher mean depressive, cyclothymic, irritable and anxious temperament scores compared to healthy controls. Healthy controls significantly had a higher mean hyperthymic temperament score compared to patients with schizophrenia. In the group of patients with schizophrenia exclusively, females scored higher in terms of depressive, cyclothymic and anxious temperaments compared to males. In the group of healthy controls, males scored higher in terms of hyperthymic and irritable temperaments compared to females, whereas a higher mean depressive and anxious temperament scores were significantly found in females compared to males. In addition, higher PANSS total scores, as well as higher positive, negative and general subscales scores were significantly associated with higher depressive, cyclothymic, irritable and anxious temperament scores.
Predicted transmembrane proteins with homology to Mef(A) are not responsible for complementing mef(A) deletion in the mef(A)–msr(D) macrolide efflux system in Streptococcus pneumoniae
Authors: Fox Valeria , Santoro Francesco , Pozzi Gianni , Iannelli Francesco 
Published: November 2021

Abstract
Objectives
In streptococci, the type M resistance to macrolides is due to the mef(A)–msr(D) efflux transport system of the ATP-Binding cassette (ABC) superfamily, where it is proposed that mef(A) codes for the transmembrane channel and msr(D) for the two ATP-binding domains. Phage ϕ1207.3 of Streptococcus pyogenes, carrying the mef(A)–msr(D) gene pair, is able to transfer the macrolide efflux phenotype to Streptococcus pneumoniae. Deletion of mef(A) in pneumococcal ϕ1207.3-carrying strains did not affect erythromycin efflux. In order to identify candidate genes likely involved in complementation of mef(A) deletion, the Mef(A) amino acid sequence was used as probe for database searching.

Results
In silico analysis identified 3 putative candidates in the S. pneumoniae R6 genome, namely spr0971, spr1023 and spr1932. Isogenic deletion mutants of each candidate gene were constructed and used in erythromycin sensitivity assays to investigate their contribution to mef(A) complementation. Since no change in erythromycin sensitivity was observed compared to the parental strain, we produced double and triple mutants to assess the potential synergic activity of the selected genes. Also these mutants did not complement the mef(A) function.
Dementia in Southeast Asia: influence of onset-type, education, and cerebrovascular disease
Authors: Vipin Ashwati , Satish Vaynii , Saffari Seyed Ehsan , Koh Wilbur , Lim Levinia , Silva Eveline , Nyu Mei Mei , Choong Tanya-Marie , Chua Esther , Lim Linda , Ng Adeline Su Lyn , Chiew Hui Jin , Ng Kok Pin , Kandiah Nagaendran 
Published: November 2021

AbstractBackgroundSoutheast Asia represents 10% of the global population, yet little is known about regional clinical characteristics of dementia and risk factors for dementia progression. This study aims to describe the clinico-demographic profiles of dementia in Southeast Asia and investigate the association of onset-type, education, and cerebrovascular disease (CVD) on dementia progression in a real-world clinic setting.MethodsIn this longitudinal study, participants were consecutive series of 1606 patients with dementia from 2010 to 2019 from a tertiary memory clinic from Singapore. The frequency of dementia subtypes stratified into young-onset (YOD; <65 years age-at-onset) and late-onset dementia (LOD; ≥65 years age-at-onset) was studied. Association of onset-type (YOD or LOD), years of lifespan education, and CVD on the trajectory of cognition was evaluated using linear mixed models. The time to significant cognitive decline was investigated using Kaplan-Meier analysis.ResultsDementia of the Alzheimer’s type (DAT) was the most common diagnosis (59.8%), followed by vascular dementia (14.9%) and frontotemporal dementia (11.1%). YOD patients accounted for 28.5% of all dementia patients. Patients with higher lifespan education had a steeper decline in global cognition (p<0.001), with this finding being more pronounced in YOD (p=0.0006). Older patients with a moderate-to-severe burden of CVD demonstrated a trend for a faster decline in global cognition compared to those with a mild burden.ConclusionsThere is a high frequency of YOD with DAT being most common in our Southeast Asian memory clinic cohort. YOD patients with higher lifespan education and LOD patients with moderate-to-severe CVD experience a steep decline in cognition.